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S. title: Hypercapnia Alters Expression of Immune Response, Nucleosome Assembly and Lipid Metabolism Genes in Differentiated Human Bronchial Epithelial Cells date: 2018-09-10 journal: Sci Rep DOI: 10.1038/s41598-018-32008-x sha: doc_id: 3196 cord_uid: fdb6az0v file: cache/cord-000402-unr44dvp.json key: cord-000402-unr44dvp authors: Yoo, Hyun Jung; Yoon, Sung Soo; Park, Seon Yang; Lee, Eun Young; Lee, Eun Bong; Kim, Ju Han; Song, Yeong Wook title: Gene Expression Profile during Chondrogenesis in Human Bone Marrow derived Mesenchymal Stem Cells using a cDNA Microarray date: 2011-06-20 journal: J Korean Med Sci DOI: 10.3346/jkms.2011.26.7.851 sha: doc_id: 402 cord_uid: unr44dvp file: cache/cord-001858-nmi39n6h.json key: cord-001858-nmi39n6h authors: Petriccione, Milena; Mastrobuoni, Francesco; Zampella, Luigi; Scortichini, Marco title: Reference gene selection for normalization of RT-qPCR gene expression data from Actinidia deliciosa leaves infected with Pseudomonas syringae pv. actinidiae date: 2015-11-19 journal: Sci Rep DOI: 10.1038/srep16961 sha: doc_id: 1858 cord_uid: nmi39n6h file: cache/cord-001921-73esrper.json key: cord-001921-73esrper authors: Lin, Cheng-Yung; Chiang, Cheng-Yi; Tsai, Huai-Jen title: Zebrafish and Medaka: new model organisms for modern biomedical research date: 2016-01-28 journal: J Biomed Sci DOI: 10.1186/s12929-016-0236-5 sha: doc_id: 1921 cord_uid: 73esrper file: cache/cord-000012-p56v8wi1.json key: cord-000012-p56v8wi1 authors: Bigot, Yves; Samain, Sylvie; Augé-Gouillou, Corinne; Federici, Brian A title: Molecular evidence for the evolution of ichnoviruses from ascoviruses by symbiogenesis date: 2008-09-18 journal: BMC Evol Biol DOI: 10.1186/1471-2148-8-253 sha: doc_id: 12 cord_uid: p56v8wi1 file: cache/cord-000492-ec5qzurk.json key: cord-000492-ec5qzurk authors: Devaney, James; Contreras, Maya; Laffey, John G title: Clinical Review: Gene-based therapies for ALI/ARDS: where are we now? date: 2011-06-20 journal: Crit Care DOI: 10.1186/cc10216 sha: doc_id: 492 cord_uid: ec5qzurk file: cache/cord-003514-yyzbv7ys.json key: cord-003514-yyzbv7ys authors: Arslan, Mehboob; Yang, Xin; Santhakumar, Diwakar; Liu, Xingjian; Hu, Xiaoyuan; 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Berman, David; Chasalow, Scott D; Wang, Lisu; Tsuchihashi, Zenta; Hu, Beihong; Panting, Lisa; Jure-Kunkel, Maria; Ji, Rui-Ru title: Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events date: 2013-03-22 journal: J Transl Med DOI: 10.1186/1479-5876-11-75 sha: doc_id: 311430 cord_uid: o32d3kaw file: cache/cord-315072-b28yikvj.json key: cord-315072-b28yikvj authors: Giotis, Efstathios S.; Robey, Rebecca C.; Skinner, Natalie G.; Tomlinson, Christopher D.; Goodbourn, Stephen; Skinner, Michael A. title: Chicken interferome: avian interferon-stimulated genes identified by microarray and RNA-seq of primary chick embryo fibroblasts treated with a chicken type I interferon (IFN-α) date: 2016-08-05 journal: Vet Res DOI: 10.1186/s13567-016-0363-8 sha: doc_id: 315072 cord_uid: b28yikvj file: cache/cord-319517-denczc6t.json key: cord-319517-denczc6t authors: Salipalli, Sandeep; Singh, Prafull Kumar; 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Li, Juan; Yu, Tianqi; Jin, Yulan; Yan, Yan; Zhou, Jiyong; Gu, Jinyan title: Comprehensive Genomic Characterization Analysis of lncRNAs in Cells With Porcine Delta Coronavirus Infection date: 2020-01-28 journal: Front Microbiol DOI: 10.3389/fmicb.2019.03036 sha: doc_id: 347917 cord_uid: fmb5nyxu file: cache/cord-328287-3qgzulgj.json key: cord-328287-3qgzulgj authors: Moni, Mohammad Ali; Liò, Pietro title: Network-based analysis of comorbidities risk during an infection: SARS and HIV case studies date: 2014-10-24 journal: BMC Bioinformatics DOI: 10.1186/1471-2105-15-333 sha: doc_id: 328287 cord_uid: 3qgzulgj file: cache/cord-345475-ttrcmtu4.json key: cord-345475-ttrcmtu4 authors: de Oliveira, Luisa Abruzzi; Breton, Michèle Claire; Bastolla, Fernanda Macedo; Camargo, Sandro da Silva; Margis, Rogério; Frazzon, Jeverson; Pasquali, Giancarlo title: Reference Genes for the Normalization of Gene Expression in Eucalyptus Species date: 2011-12-24 journal: Plant Cell Physiol DOI: 10.1093/pcp/pcr187 sha: doc_id: 345475 cord_uid: ttrcmtu4 file: cache/cord-314915-b6aqwubh.json key: cord-314915-b6aqwubh authors: Futas, Jan; Oppelt, Jan; Jelinek, April; Elbers, Jean P.; Wijacki, Jan; Knoll, Ales; Burger, Pamela A.; Horin, Petr title: Natural Killer Cell Receptor Genes in Camels: Another Mammalian Model date: 2019-07-02 journal: Front Genet DOI: 10.3389/fgene.2019.00620 sha: doc_id: 314915 cord_uid: b6aqwubh file: cache/cord-328899-kog99kk5.json key: cord-328899-kog99kk5 authors: Ferrari, Stefano; Geddes, Duncan M; Alton, Eric W.F.W title: Barriers to and new approaches for gene therapy and gene delivery in cystic fibrosis date: 2002-12-05 journal: Adv Drug Deliv Rev DOI: 10.1016/s0169-409x(02)00145-x sha: doc_id: 328899 cord_uid: kog99kk5 file: cache/cord-352200-i05h8csb.json key: cord-352200-i05h8csb authors: Xu, Yi; Zhou, Wenwu; Zhou, Yijun; Wu, Jianxiang; Zhou, Xueping title: Transcriptome and Comparative Gene Expression Analysis of Sogatella furcifera (Horváth) in Response to Southern Rice Black-Streaked Dwarf Virus date: 2012-04-27 journal: PLoS One DOI: 10.1371/journal.pone.0036238 sha: doc_id: 352200 cord_uid: i05h8csb file: cache/cord-307769-rjseio5s.json key: cord-307769-rjseio5s authors: Sim, Winnie H; Wagner, Josef; Cameron, Donald J; Catto‐Smith, Anthony G; Bishop, Ruth F; Kirkwood, Carl D title: Expression profile of genes involved in pathogenesis of pediatric Crohn's disease date: 2012-05-24 journal: J Gastroenterol Hepatol DOI: 10.1111/j.1440-1746.2011.06973.x sha: doc_id: 307769 cord_uid: rjseio5s file: cache/cord-332006-if46jycd.json key: cord-332006-if46jycd authors: Whitehead, Kathryn A.; Langer, Robert; Anderson, Daniel G. title: Knocking down barriers: advances in siRNA delivery date: 2009 journal: Nat Rev Drug Discov DOI: 10.1038/nrd2742 sha: doc_id: 332006 cord_uid: if46jycd file: cache/cord-317779-j67vb7f3.json key: cord-317779-j67vb7f3 authors: Irizarry, Kristopher J. L.; Downs, Eileen; Bryden, Randall; Clark, Jory; Griggs, Lisa; Kopulos, Renee; Boettger, Cynthia M.; Carr, Thomas J.; Keeler, Calvin L.; Collisson, Ellen; Drechsler, Yvonne title: RNA sequencing demonstrates large-scale temporal dysregulation of gene expression in stimulated macrophages derived from MHC-defined chicken haplotypes date: 2017-08-28 journal: PLoS One DOI: 10.1371/journal.pone.0179391 sha: doc_id: 317779 cord_uid: j67vb7f3 file: cache/cord-351845-bli3qm8w.json key: cord-351845-bli3qm8w authors: Prasad, Kartikay; Khatoon, Fatima; Rashid, Summya; Ali, Nemat; AlAsmari, Abdullah F.; Ahmed, Mohammad Z.; Alqahtani, Ali S.; Alqahtani, Mohammed S.; Kumar, Vijay title: Targeting hub genes and pathways of innate immune response in COVID-19: A network biology perspective date: 2020-06-26 journal: Int J Biol Macromol DOI: 10.1016/j.ijbiomac.2020.06.228 sha: doc_id: 351845 cord_uid: bli3qm8w file: cache/cord-329617-gzivtsho.json key: cord-329617-gzivtsho authors: Lee, Albert K.; Kulcsar, Kirsten A.; Elliott, Oliver; Khiabanian, Hossein; Nagle, Elyse R.; Jones, Megan E.B.; Amman, Brian R.; Sanchez-Lockhart, Mariano; Towner, Jonathan S.; Palacios, Gustavo; Rabadan, Raul title: De novo transcriptome reconstruction and annotation of the Egyptian rousette bat date: 2015-12-07 journal: BMC Genomics DOI: 10.1186/s12864-015-2124-x sha: doc_id: 329617 cord_uid: gzivtsho file: cache/cord-336573-bpg1dg24.json key: cord-336573-bpg1dg24 authors: Greenaway, Hui Yee; Kurniawan, Monica; Price, David A; Douek, Daniel C; Davenport, Miles P; Venturi, Vanessa title: Extraction and characterization of the rhesus macaque T cell receptor β-chain genes date: 2009-06-09 journal: Immunol Cell Biol DOI: 10.1038/icb.2009.38 sha: doc_id: 336573 cord_uid: bpg1dg24 file: cache/cord-331592-l44rupmi.json key: cord-331592-l44rupmi authors: Wang, Tzu-Hao; Chao, Angel title: Microarray Analysis of Gene Expression of Cancer to Guide the Use of Chemotherapeutics date: 2007-09-30 journal: Taiwanese Journal of Obstetrics and Gynecology DOI: 10.1016/s1028-4559(08)60024-8 sha: doc_id: 331592 cord_uid: l44rupmi file: cache/cord-352190-1987sfyz.json key: cord-352190-1987sfyz authors: Xia, Hongyue; Li, Xibao; Zhao, Wenliang; Jia, Shuran; Zhang, Xiaoqing; Irwin, David M.; Zhang, Shuyi title: Adaptive Evolution of Feline Coronavirus Genes Based on Selection Analysis date: 2020-08-13 journal: Biomed Res Int DOI: 10.1155/2020/9089768 sha: doc_id: 352190 cord_uid: 1987sfyz file: cache/cord-354829-god79qzw.json key: cord-354829-god79qzw authors: Mao, Kaimin; Geng, Wei; Liao, Yuhan; Luo, Ping; Zhong, Hua; Ma, Pei; Xu, Juanjuan; Zhang, Shuai; Tan, Qi; Jin, Yang title: Identification of robust genetic signatures associated with lipopolysaccharide-induced acute lung injury onset and astaxanthin therapeutic effects by integrative analysis of RNA sequencing data and GEO datasets date: 2020-09-23 journal: Aging (Albany NY) DOI: 10.18632/aging.104042 sha: doc_id: 354829 cord_uid: god79qzw file: cache/cord-351548-jvl63652.json key: cord-351548-jvl63652 authors: Juranic Lisnic, Vanda; Babic Cac, Marina; Lisnic, Berislav; Trsan, Tihana; Mefferd, Adam; Das Mukhopadhyay, Chitrangada; Cook, Charles H.; Jonjic, Stipan; Trgovcich, Joanne title: Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface date: 2013-09-26 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1003611 sha: doc_id: 351548 cord_uid: jvl63652 file: cache/cord-346308-9h2fk9qt.json key: cord-346308-9h2fk9qt authors: Kaur, Rajwinder; Yadav, Bhoomika; Tyagi, R.D. title: Microbiology of hospital wastewater date: 2020-05-01 journal: Current Developments in Biotechnology and Bioengineering DOI: 10.1016/b978-0-12-819722-6.00004-3 sha: doc_id: 346308 cord_uid: 9h2fk9qt file: cache/cord-350019-4nlbu54e.json key: cord-350019-4nlbu54e authors: Robinson, Elektra K.; Covarrubias, Sergio; Carpenter, Susan title: The how and why of lncRNA function: An innate immune perspective() date: 2019-09-02 journal: Biochim Biophys Acta Gene Regul Mech DOI: 10.1016/j.bbagrm.2019.194419 sha: doc_id: 350019 cord_uid: 4nlbu54e file: cache/cord-348815-lthz75oc.json key: cord-348815-lthz75oc authors: Kurreck, Jens title: RNA Interference: From Basic Research to Therapeutic Applications date: 2009-01-19 journal: Angew Chem Int Ed Engl DOI: 10.1002/anie.200802092 sha: doc_id: 348815 cord_uid: lthz75oc file: cache/cord-356197-js7l86fh.json key: cord-356197-js7l86fh authors: Zhou, Ping; Zhai, Shanli; Zhou, Xiang; Lin, Ping; Jiang, Tengfei; Hu, Xueying; Jiang, Yunbo; Wu, Bin; Zhang, Qingde; Xu, Xuewen; Li, Jin-ping; Liu, Bang title: Molecular Characterization of Transcriptome-wide Interactions between Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Porcine Alveolar Macrophages in vivo date: 2011-08-07 journal: Int J Biol Sci DOI: nan sha: doc_id: 356197 cord_uid: js7l86fh file: cache/cord-344297-qqohijqi.json key: cord-344297-qqohijqi authors: Smith, Jacqueline; Sadeyen, Jean-Remy; Cavanagh, David; Kaiser, Pete; Burt, David W. title: The early immune response to infection of chickens with Infectious Bronchitis Virus (IBV) in susceptible and resistant birds date: 2015-10-09 journal: BMC Vet Res DOI: 10.1186/s12917-015-0575-6 sha: doc_id: 344297 cord_uid: qqohijqi file: cache/cord-337492-o6sy4zi4.json key: cord-337492-o6sy4zi4 authors: Baric, Ralph S.; Crosson, Sean; Damania, Blossom; Miller, Samuel I.; Rubin, Eric J. title: Next-Generation High-Throughput Functional Annotation of Microbial Genomes date: 2016-10-04 journal: mBio DOI: 10.1128/mbio.01245-16 sha: doc_id: 337492 cord_uid: o6sy4zi4 file: cache/cord-355075-ieb35upi.json key: cord-355075-ieb35upi authors: Papenfuss, Anthony T; Baker, Michelle L; Feng, Zhi-Ping; Tachedjian, Mary; Crameri, Gary; Cowled, Chris; Ng, Justin; Janardhana, Vijaya; Field, Hume E; Wang, Lin-Fa title: The immune gene repertoire of an important viral reservoir, the Australian black flying fox date: 2012-06-20 journal: BMC Genomics DOI: 10.1186/1471-2164-13-261 sha: doc_id: 355075 cord_uid: ieb35upi file: cache/cord-318576-dc5n6ni4.json key: cord-318576-dc5n6ni4 authors: Jitobaom, Kunlakanya; Phakaratsakul, Supinya; Sirihongthong, Thanyaporn; Chotewutmontri, Sasithorn; Suriyaphol, Prapat; Suptawiwat, Ornpreya; Auewarakul, Prasert title: Codon usage similarity between viral and some host genes suggests a codon-specific translational regulation date: 2020-05-08 journal: Heliyon DOI: 10.1016/j.heliyon.2020.e03915 sha: doc_id: 318576 cord_uid: dc5n6ni4 file: cache/cord-335382-fk4um9nw.json key: cord-335382-fk4um9nw authors: Farver, Carol F.; Zander, Dani S. title: Molecular Basis of Pulmonary Disease date: 2012-08-10 journal: Molecular Pathology DOI: 10.1016/b978-0-12-374419-7.00018-4 sha: doc_id: 335382 cord_uid: fk4um9nw file: cache/cord-355927-nzoiv9pj.json key: cord-355927-nzoiv9pj authors: Lemmon, Alan R.; Brown, Jeremy M.; Stanger-Hall, Kathrin; Lemmon, Emily Moriarty title: The Effect of Ambiguous Data on Phylogenetic Estimates Obtained by Maximum Likelihood and Bayesian Inference date: 2009-05-21 journal: Syst Biol DOI: 10.1093/sysbio/syp017 sha: doc_id: 355927 cord_uid: nzoiv9pj file: cache/cord-022940-atbjwpo5.json key: cord-022940-atbjwpo5 authors: nan title: Poster Sessions date: 2016-09-07 journal: FEBS J DOI: 10.1111/febs.13808 sha: doc_id: 22940 cord_uid: atbjwpo5 Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named keyword-gene-cord === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46913 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 41952 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 42649 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43109 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43686 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43994 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 44555 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45009 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45695 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46204 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46667 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 47236 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43561 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 44080 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 44954 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45044 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45540 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45985 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45909 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46136 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46153 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46415 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46929 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 47357 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 47386 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48489 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46077 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45385 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 47077 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43201 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43885 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46275 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 47139 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 47955 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48242 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50284 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46631 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 47391 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48367 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48514 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49117 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50304 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48009 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43583 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 47622 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49999 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50116 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-000159-8y8ho2x5 author: Bekaert, Michaël title: Recode-2: new design, new search tools, and many more genes date: 2009-09-25 pages: extension: .txt txt: ./txt/cord-000159-8y8ho2x5.txt cache: ./cache/cord-000159-8y8ho2x5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000159-8y8ho2x5.txt' === file2bib.sh === id: cord-005216-potmzdfs author: Sun, Dong title: Bioinformatics Analysis of Genes and Pathways of CD11b(+)/Ly6C(intermediate) Macrophages after Renal Ischemia-Reperfusion Injury date: 2018-03-15 pages: extension: .txt txt: ./txt/cord-005216-potmzdfs.txt cache: ./cache/cord-005216-potmzdfs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-005216-potmzdfs.txt' === file2bib.sh === id: cord-020101-5rib7pe8 author: nan title: Cumulative Author Index for 2008 date: 2008-11-17 pages: extension: .txt txt: ./txt/cord-020101-5rib7pe8.txt cache: ./cache/cord-020101-5rib7pe8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-020101-5rib7pe8.txt' === file2bib.sh === id: cord-272378-umvi0veu author: Subramanian, Subbaya title: Special Issue: MicroRNA Regulation in Health and Disease date: 2019-06-15 pages: extension: .txt txt: ./txt/cord-272378-umvi0veu.txt cache: ./cache/cord-272378-umvi0veu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-272378-umvi0veu.txt' === file2bib.sh === id: cord-000402-unr44dvp author: Yoo, Hyun Jung title: Gene Expression Profile during Chondrogenesis in Human Bone Marrow derived Mesenchymal Stem Cells using a cDNA Microarray date: 2011-06-20 pages: extension: .txt txt: ./txt/cord-000402-unr44dvp.txt cache: ./cache/cord-000402-unr44dvp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000402-unr44dvp.txt' === file2bib.sh === id: cord-002366-t94aufs3 author: Aurrecoechea, Cristina title: EuPathDB: the eukaryotic pathogen genomics database resource date: 2017-01-04 pages: extension: .txt txt: ./txt/cord-002366-t94aufs3.txt cache: ./cache/cord-002366-t94aufs3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002366-t94aufs3.txt' === file2bib.sh === id: cord-004893-28mrzvsc author: Pavesi, Angelo title: On the Informational Content of Overlapping Genes in Prokaryotic and Eukaryotic Viruses date: 1997 pages: extension: .txt txt: ./txt/cord-004893-28mrzvsc.txt cache: ./cache/cord-004893-28mrzvsc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-004893-28mrzvsc.txt' === file2bib.sh === id: cord-004222-z4butywi author: Joyce, Collin title: Comparisons of the antibody repertoires of a humanized rodent and humans by high throughput sequencing date: 2020-01-24 pages: extension: .txt txt: ./txt/cord-004222-z4butywi.txt cache: ./cache/cord-004222-z4butywi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-004222-z4butywi.txt' === file2bib.sh === id: cord-103505-9adtbwp2 author: Hale, A. T. title: The genetic architecture of human infectious diseases and pathogen-induced cellular phenotypes date: 2020-07-21 pages: extension: .txt txt: ./txt/cord-103505-9adtbwp2.txt cache: ./cache/cord-103505-9adtbwp2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103505-9adtbwp2.txt' === file2bib.sh === id: cord-003196-fdb6az0v author: Casalino-Matsuda, S. Marina title: Hypercapnia Alters Expression of Immune Response, Nucleosome Assembly and Lipid Metabolism Genes in Differentiated Human Bronchial Epithelial Cells date: 2018-09-10 pages: extension: .txt txt: ./txt/cord-003196-fdb6az0v.txt cache: ./cache/cord-003196-fdb6az0v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003196-fdb6az0v.txt' === file2bib.sh === id: cord-007259-vj9tv3or author: Guo, Feng-Biao title: Accurate prediction of human essential genes using only nucleotide composition and association information date: 2017-06-15 pages: extension: .txt txt: ./txt/cord-007259-vj9tv3or.txt cache: ./cache/cord-007259-vj9tv3or.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-007259-vj9tv3or.txt' === file2bib.sh === id: cord-005432-mqyvpepo author: Ma, Z title: Redirecting adenovirus to pulmonary endothelium by cationic liposomes date: 2002-02-22 pages: extension: .txt txt: ./txt/cord-005432-mqyvpepo.txt cache: ./cache/cord-005432-mqyvpepo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-005432-mqyvpepo.txt' === file2bib.sh === id: cord-024290-8z6us7v4 author: Allen, Edward E. title: Time Series Adjustment Enhancement of Hierarchical Modeling of Arabidopsis Thaliana Gene Interactions date: 2020-02-01 pages: extension: .txt txt: ./txt/cord-024290-8z6us7v4.txt cache: ./cache/cord-024290-8z6us7v4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-024290-8z6us7v4.txt' === file2bib.sh === id: cord-266521-vovas81d author: Yokobayashi, Yohei title: Aptamer-based and aptazyme-based riboswitches in mammalian cells date: 2019-06-22 pages: extension: .txt txt: ./txt/cord-266521-vovas81d.txt cache: ./cache/cord-266521-vovas81d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-266521-vovas81d.txt' === file2bib.sh === id: cord-000580-dcid9emx author: Sällman Almén, Markus title: The Dispanins: A Novel Gene Family of Ancient Origin That Contains 14 Human Members date: 2012-02-20 pages: extension: .txt txt: ./txt/cord-000580-dcid9emx.txt cache: ./cache/cord-000580-dcid9emx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000580-dcid9emx.txt' === file2bib.sh === id: cord-104073-vsa5y7ip author: Warner, Emily F. title: Cross kingdom analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets to ameliorate fungal pathogenicity? date: 2020-09-23 pages: extension: .txt txt: ./txt/cord-104073-vsa5y7ip.txt cache: ./cache/cord-104073-vsa5y7ip.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-104073-vsa5y7ip.txt' === file2bib.sh === id: cord-003514-yyzbv7ys author: Arslan, Mehboob title: Dynamic Expression of Interferon Lambda Regulated Genes in Primary Fibroblasts and Immune Organs of the Chicken date: 2019-02-14 pages: extension: .txt txt: ./txt/cord-003514-yyzbv7ys.txt cache: ./cache/cord-003514-yyzbv7ys.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003514-yyzbv7ys.txt' === file2bib.sh === id: cord-007760-it9wach2 author: Jiao, Long R. title: Suicide Gene Therapy in Liver Tumors date: 2004 pages: extension: .txt txt: ./txt/cord-007760-it9wach2.txt cache: ./cache/cord-007760-it9wach2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-007760-it9wach2.txt' === file2bib.sh === id: cord-103465-6udhvl9n author: Schierding, William title: Low tolerance for transcriptional variation at cohesin genes is accompanied by functional links to disease-relevant pathways date: 2020-04-13 pages: extension: .txt txt: ./txt/cord-103465-6udhvl9n.txt cache: ./cache/cord-103465-6udhvl9n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103465-6udhvl9n.txt' === file2bib.sh === id: cord-003898-y6zpvw84 author: Tan, Kai Sen title: RNA Sequencing of H3N2 Influenza Virus-Infected Human Nasal Epithelial Cells from Multiple Subjects Reveals Molecular Pathways Associated with Tissue Injury and Complications date: 2019-08-27 pages: extension: .txt txt: ./txt/cord-003898-y6zpvw84.txt cache: ./cache/cord-003898-y6zpvw84.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003898-y6zpvw84.txt' === file2bib.sh === id: cord-001858-nmi39n6h author: Petriccione, Milena title: Reference gene selection for normalization of RT-qPCR gene expression data from Actinidia deliciosa leaves infected with Pseudomonas syringae pv. actinidiae date: 2015-11-19 pages: extension: .txt txt: ./txt/cord-001858-nmi39n6h.txt cache: ./cache/cord-001858-nmi39n6h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001858-nmi39n6h.txt' === file2bib.sh === id: cord-000492-ec5qzurk author: Devaney, James title: Clinical Review: Gene-based therapies for ALI/ARDS: where are we now? date: 2011-06-20 pages: extension: .txt txt: ./txt/cord-000492-ec5qzurk.txt cache: ./cache/cord-000492-ec5qzurk.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000492-ec5qzurk.txt' === file2bib.sh === id: cord-005476-q6o5239w author: Griesenbach, U title: Gene therapy for cystic fibrosis: an example for lung gene therapy date: 2004-09-29 pages: extension: .txt txt: ./txt/cord-005476-q6o5239w.txt cache: ./cache/cord-005476-q6o5239w.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-005476-q6o5239w.txt' === file2bib.sh === id: cord-000012-p56v8wi1 author: Bigot, Yves title: Molecular evidence for the evolution of ichnoviruses from ascoviruses by symbiogenesis date: 2008-09-18 pages: extension: .txt txt: ./txt/cord-000012-p56v8wi1.txt cache: ./cache/cord-000012-p56v8wi1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000012-p56v8wi1.txt' === file2bib.sh === id: cord-016200-zfh20im0 author: Saxena, Jyoti title: Edible Vaccines date: 2013-10-22 pages: extension: .txt txt: ./txt/cord-016200-zfh20im0.txt cache: ./cache/cord-016200-zfh20im0.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-016200-zfh20im0.txt' === file2bib.sh === id: cord-003254-yiqdsf9z author: Schlub, Timothy E title: A Simple Method to Detect Candidate Overlapping Genes in Viruses Using Single Genome Sequences date: 2018-08-07 pages: extension: .txt txt: ./txt/cord-003254-yiqdsf9z.txt cache: ./cache/cord-003254-yiqdsf9z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003254-yiqdsf9z.txt' === file2bib.sh === id: cord-001541-5d64esp4 author: Walker, Peter J. title: Evolution of Genome Size and Complexity in the Rhabdoviridae date: 2015-02-13 pages: extension: .txt txt: ./txt/cord-001541-5d64esp4.txt cache: ./cache/cord-001541-5d64esp4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001541-5d64esp4.txt' === file2bib.sh === id: cord-019050-a9datsoo author: Ambrogi, Federico title: Bioinformatics and Nanotechnologies: Nanomedicine date: 2014 pages: extension: .txt txt: ./txt/cord-019050-a9datsoo.txt cache: ./cache/cord-019050-a9datsoo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-019050-a9datsoo.txt' === file2bib.sh === id: cord-252781-06hs9pit author: Lai, Wing-Fu title: Cyclodextrins in non-viral gene delivery date: 2013-10-05 pages: extension: .txt txt: ./txt/cord-252781-06hs9pit.txt cache: ./cache/cord-252781-06hs9pit.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-252781-06hs9pit.txt' === file2bib.sh === id: cord-258035-2tk7maqk author: DeFilippis, Victor title: Functional genomics in virology and antiviral drug discovery date: 2003-10-31 pages: extension: .txt txt: ./txt/cord-258035-2tk7maqk.txt cache: ./cache/cord-258035-2tk7maqk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-258035-2tk7maqk.txt' === file2bib.sh === id: cord-003044-9uqa39j9 author: Cervera, Héctor title: Viral Fitness Correlates with the Magnitude and Direction of the Perturbation Induced in the Host’s Transcriptome: The Tobacco Etch Potyvirus—Tobacco Case Study date: 2018-03-19 pages: extension: .txt txt: ./txt/cord-003044-9uqa39j9.txt cache: ./cache/cord-003044-9uqa39j9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003044-9uqa39j9.txt' === file2bib.sh === id: cord-263470-vmqvropy author: Rukavtsova, E. B. title: Tissue specific expression of hepatitis B virus surface antigen in transgenic plant cells and tissue culture date: 2007 pages: extension: .txt txt: ./txt/cord-263470-vmqvropy.txt cache: ./cache/cord-263470-vmqvropy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-263470-vmqvropy.txt' === file2bib.sh === id: cord-280924-g6062fwk author: Hachim, Mahmood Yaseen title: Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells date: 2020-06-10 pages: extension: .txt txt: ./txt/cord-280924-g6062fwk.txt cache: ./cache/cord-280924-g6062fwk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-280924-g6062fwk.txt' === file2bib.sh === id: cord-301546-yck1t3pp author: Kozaki, Toshinori title: Comparison of two acetylcholinesterase gene cDNAs of the lesser mealworm, Alphitobius diaperinus, in insecticide susceptible and resistant strains date: 2007-12-28 pages: extension: .txt txt: ./txt/cord-301546-yck1t3pp.txt cache: ./cache/cord-301546-yck1t3pp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-301546-yck1t3pp.txt' === file2bib.sh === id: cord-277491-q18b88lm author: Cao, Ying-Li title: Identification and Characterization of Three Novel Small Interference RNAs That Effectively Down-Regulate the Isolated Nucleocapsid Gene Expression of SARS Coronavirus date: 2011-02-11 pages: extension: .txt txt: ./txt/cord-277491-q18b88lm.txt cache: ./cache/cord-277491-q18b88lm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-277491-q18b88lm.txt' === file2bib.sh === id: cord-278136-ol2buwld author: Gonzales, Natalia M. title: 29th International Mammalian Genome Conference meeting report date: 2016-05-02 pages: extension: .txt txt: ./txt/cord-278136-ol2buwld.txt cache: ./cache/cord-278136-ol2buwld.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-278136-ol2buwld.txt' === file2bib.sh === id: cord-284933-flbibrcm author: Kim, Jong-Oh title: Characterization of the Transcriptome and Gene Expression of Brain Tissue in Sevenband Grouper (Hyporthodus septemfasciatus) in Response to NNV Infection date: 2017-01-13 pages: extension: .txt txt: ./txt/cord-284933-flbibrcm.txt cache: ./cache/cord-284933-flbibrcm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-284933-flbibrcm.txt' === file2bib.sh === id: cord-268098-71g1w1mc author: Beckman, M. F. title: Comorbidities and Susceptibility to COVID-19: A Generalized Gene Set Meta-Analysis Approach date: 2020-09-15 pages: extension: .txt txt: ./txt/cord-268098-71g1w1mc.txt cache: ./cache/cord-268098-71g1w1mc.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-268098-71g1w1mc.txt' === file2bib.sh === id: cord-280897-el7bdkcf author: Wang, Hai-Fang title: Relationship between mRNA stability and intron presence date: 2007-03-02 pages: extension: .txt txt: ./txt/cord-280897-el7bdkcf.txt cache: ./cache/cord-280897-el7bdkcf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-280897-el7bdkcf.txt' === file2bib.sh === id: cord-273910-fna7s9te author: Bochud, Pierre-Yves title: Innate immunogenetics: a tool for exploring new frontiers of host defence date: 2007-07-20 pages: extension: .txt txt: ./txt/cord-273910-fna7s9te.txt cache: ./cache/cord-273910-fna7s9te.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-273910-fna7s9te.txt' === file2bib.sh === id: cord-260496-s2ba7uy3 author: Moncany, Maurice L.J. title: Identification of conserved lentiviral sequences as landmarks of genomic flexibility date: 2006-08-08 pages: extension: .txt txt: ./txt/cord-260496-s2ba7uy3.txt cache: ./cache/cord-260496-s2ba7uy3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-260496-s2ba7uy3.txt' === file2bib.sh === id: cord-290282-oxyzndsj author: Ortego, Javier title: Transmissible gastroenteritis coronavirus gene 7 is not essential but influences in vivo virus replication and virulence date: 2003-03-30 pages: extension: .txt txt: ./txt/cord-290282-oxyzndsj.txt cache: ./cache/cord-290282-oxyzndsj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-290282-oxyzndsj.txt' === file2bib.sh === id: cord-275720-kf9m4zho author: Cho, Won Kyong title: Genome-wide expression profiling shows transcriptional reprogramming in Fusarium graminearum by Fusarium graminearum virus 1-DK21 infection date: 2012-05-06 pages: extension: .txt txt: ./txt/cord-275720-kf9m4zho.txt cache: ./cache/cord-275720-kf9m4zho.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-275720-kf9m4zho.txt' === file2bib.sh === id: cord-303939-7knzjnyr author: Hu, Fang title: Identification of a metabolic gene panel to predict the prognosis of myelodysplastic syndrome date: 2020-04-26 pages: extension: .txt txt: ./txt/cord-303939-7knzjnyr.txt cache: ./cache/cord-303939-7knzjnyr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-303939-7knzjnyr.txt' === file2bib.sh === id: cord-273609-whm2ce4u author: Li, Qingdi Quentin title: Evaluation of reference genes for real-time quantitative PCR studies in Candida glabrata following azole treatment date: 2012-06-29 pages: extension: .txt txt: ./txt/cord-273609-whm2ce4u.txt cache: ./cache/cord-273609-whm2ce4u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-273609-whm2ce4u.txt' === file2bib.sh === id: cord-274241-biqbsggu author: Shaw, Timothy I. title: Transcriptome Sequencing and Annotation for the Jamaican Fruit Bat (Artibeus jamaicensis) date: 2012-11-15 pages: extension: .txt txt: ./txt/cord-274241-biqbsggu.txt cache: ./cache/cord-274241-biqbsggu.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-274241-biqbsggu.txt' === file2bib.sh === id: cord-020969-lh2ergpm author: STRAUSS, JAMES H. title: Gene Therapy date: 2012-07-27 pages: extension: .txt txt: ./txt/cord-020969-lh2ergpm.txt cache: ./cache/cord-020969-lh2ergpm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-020969-lh2ergpm.txt' === file2bib.sh === id: cord-016062-h4vjkufn author: Gontier, Nathalie title: Evolutionary epistemology and the origin and evolution of language: Taking symbiogenesis seriously date: 2006 pages: extension: .txt txt: ./txt/cord-016062-h4vjkufn.txt cache: ./cache/cord-016062-h4vjkufn.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-016062-h4vjkufn.txt' === file2bib.sh === id: cord-267733-fuz8r3vj author: Al Ali, Sally title: Use of Reporter Genes in the Generation of Vaccinia Virus-Derived Vectors date: 2016-05-21 pages: extension: .txt txt: ./txt/cord-267733-fuz8r3vj.txt cache: ./cache/cord-267733-fuz8r3vj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-267733-fuz8r3vj.txt' === file2bib.sh === id: cord-285656-7o7ofk1e author: Dawson, Harry D. title: The porcine translational research database: a manually curated, genomics and proteomics-based research resource date: 2017-08-22 pages: extension: .txt txt: ./txt/cord-285656-7o7ofk1e.txt cache: ./cache/cord-285656-7o7ofk1e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-285656-7o7ofk1e.txt' === file2bib.sh === id: cord-306380-msk9p1yy author: Lee, C.-W. title: Evidence of genetic diversity generated by recombination among avian coronavirus IBV date: 2000 pages: extension: .txt txt: ./txt/cord-306380-msk9p1yy.txt cache: ./cache/cord-306380-msk9p1yy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-306380-msk9p1yy.txt' === file2bib.sh === id: cord-260345-ugd8kkor author: Giles, Ian G. title: A compendium of reviews in biochemistry and molecular biology published in the first half of 1992 date: 1992-12-31 pages: extension: .txt txt: ./txt/cord-260345-ugd8kkor.txt cache: ./cache/cord-260345-ugd8kkor.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-260345-ugd8kkor.txt' === file2bib.sh === id: cord-018798-yzxy9ogf author: Jain, Pradeep Kumar title: RNAi for Resistance Against Biotic Stresses in Crop Plants date: 2018-07-10 pages: extension: .txt txt: ./txt/cord-018798-yzxy9ogf.txt cache: ./cache/cord-018798-yzxy9ogf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-018798-yzxy9ogf.txt' === file2bib.sh === id: cord-284015-vvtv492b author: Nikaido, Masato title: Comparative genomic analyses illuminate the distinct evolution of megabats within Chiroptera date: 2020-09-23 pages: extension: .txt txt: ./txt/cord-284015-vvtv492b.txt cache: ./cache/cord-284015-vvtv492b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-284015-vvtv492b.txt' === file2bib.sh === id: cord-290861-5bxvenue author: Ashwell, M. title: Characterization of gene expression in naturally occurring feline degenerative joint disease-associated pain date: 2018-11-19 pages: extension: .txt txt: ./txt/cord-290861-5bxvenue.txt cache: ./cache/cord-290861-5bxvenue.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-290861-5bxvenue.txt' === file2bib.sh === id: cord-289033-vfh3op6a author: Algammal, Abdelazeem M. title: Genes Encoding the Virulence and the Antimicrobial Resistance in Enterotoxigenic and Shiga-toxigenic E. coli Isolated from Diarrheic Calves date: 2020-06-10 pages: extension: .txt txt: ./txt/cord-289033-vfh3op6a.txt cache: ./cache/cord-289033-vfh3op6a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-289033-vfh3op6a.txt' === file2bib.sh === id: cord-294725-wyrg0nq8 author: Bourdon, Julie A. title: Gene expression profiling to identify potentially relevant disease outcomes and support human health risk assessment for carbon black nanoparticle exposure date: 2013-01-07 pages: extension: .txt txt: ./txt/cord-294725-wyrg0nq8.txt cache: ./cache/cord-294725-wyrg0nq8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-294725-wyrg0nq8.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70021 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 69497 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-017752-ofzm3x3a author: nan title: Theories of Carcinogenesis date: 2007 pages: extension: .txt txt: ./txt/cord-017752-ofzm3x3a.txt cache: ./cache/cord-017752-ofzm3x3a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-017752-ofzm3x3a.txt' === file2bib.sh === id: cord-273347-eyxc4rt0 author: Mohammadinejad, Reza title: In vivo gene delivery mediated by non-viral vectors for cancer therapy date: 2020-07-04 pages: extension: .txt txt: ./txt/cord-273347-eyxc4rt0.txt cache: ./cache/cord-273347-eyxc4rt0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-273347-eyxc4rt0.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 71343 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70177 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 71335 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 71168 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-309556-xv3413k1 author: Chow, Ryan D. title: The aging transcriptome and cellular landscape of the human lung in relation to SARS-CoV-2 date: 2020-04-15 pages: extension: .txt txt: ./txt/cord-309556-xv3413k1.txt cache: ./cache/cord-309556-xv3413k1.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-309556-xv3413k1.txt' === file2bib.sh === id: cord-264746-gfn312aa author: Muse, Spencer title: GENOMICS AND BIOINFORMATICS date: 2012-03-29 pages: extension: .txt txt: ./txt/cord-264746-gfn312aa.txt cache: ./cache/cord-264746-gfn312aa.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-264746-gfn312aa.txt' === file2bib.sh === id: cord-312551-w4tps34p author: Razvi, Mohammad H. title: Transcriptional oncogenomic hot spots in Barrett's adenocarcinomas: Serial analysis of gene expression date: 2007-07-17 pages: extension: .txt txt: ./txt/cord-312551-w4tps34p.txt cache: ./cache/cord-312551-w4tps34p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-312551-w4tps34p.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 65620 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-303132-m3j1dekj author: Smith, S. E. title: Chicken Interferon-Inducible Transmembrane Protein 3 Restricts Influenza Viruses and Lyssaviruses In Vitro date: 2013-12-17 pages: extension: .txt txt: ./txt/cord-303132-m3j1dekj.txt cache: ./cache/cord-303132-m3j1dekj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-303132-m3j1dekj.txt' === file2bib.sh === id: cord-292004-9rpoll7y author: Mitchell, Hugh D. title: The Role of EGFR in Influenza Pathogenicity: Multiple Network-Based Approaches to Identify a Key Regulator of Non-lethal Infections date: 2019-09-20 pages: extension: .txt txt: ./txt/cord-292004-9rpoll7y.txt cache: ./cache/cord-292004-9rpoll7y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-292004-9rpoll7y.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70507 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70991 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-291719-1ku6cmwj author: Hajjo, Rima title: A Systems Biology Workflow for Drug and Vaccine Repurposing: Identifying Small-Molecule BCG Mimics to Reduce or Prevent COVID-19 Mortality date: 2020-10-06 pages: extension: .txt txt: ./txt/cord-291719-1ku6cmwj.txt cache: ./cache/cord-291719-1ku6cmwj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-291719-1ku6cmwj.txt' === file2bib.sh === id: cord-282968-kjvvoveq author: Qu, Renjun title: Selection of reference genes for the quantitative real-time PCR normalization of gene expression in Isatis indigotica fortune date: 2019-03-25 pages: extension: .txt txt: ./txt/cord-282968-kjvvoveq.txt cache: ./cache/cord-282968-kjvvoveq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-282968-kjvvoveq.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 71965 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-295019-8tf8ah6g author: Weber, Wilfried title: Emerging biomedical applications of synthetic biology date: 2011-11-29 pages: extension: .txt txt: ./txt/cord-295019-8tf8ah6g.txt cache: ./cache/cord-295019-8tf8ah6g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-295019-8tf8ah6g.txt' === file2bib.sh === id: cord-320005-i30t7cvr author: Pardo, A. title: The Human Genome and Advances in Medicine: Limits and Future Prospects date: 2004-03-31 pages: extension: .txt txt: ./txt/cord-320005-i30t7cvr.txt cache: ./cache/cord-320005-i30t7cvr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-320005-i30t7cvr.txt' === file2bib.sh === id: cord-308034-9b219k0v author: Murray, James L. title: A Role for H/ACA and C/D Small Nucleolar RNAs in Viral Replication date: 2014-01-30 pages: extension: .txt txt: ./txt/cord-308034-9b219k0v.txt cache: ./cache/cord-308034-9b219k0v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-308034-9b219k0v.txt' === file2bib.sh === id: cord-287396-18p171nr author: Schroyen, Martine title: Current transcriptomics in pig immunity research date: 2014-11-15 pages: extension: .txt txt: ./txt/cord-287396-18p171nr.txt cache: ./cache/cord-287396-18p171nr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-287396-18p171nr.txt' === file2bib.sh === id: cord-301218-zsp5sh9o author: Weeraratna, Ashani T. title: Gene Expression Profiling: From Microarrays to Medicine date: 2004 pages: extension: .txt txt: ./txt/cord-301218-zsp5sh9o.txt cache: ./cache/cord-301218-zsp5sh9o.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-301218-zsp5sh9o.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70820 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-315498-gpzee1f2 author: Parkinson, N. title: Systematic review and meta-analysis identifies potential host therapeutic targets in COVID-19. date: 2020-09-01 pages: extension: .txt txt: ./txt/cord-315498-gpzee1f2.txt cache: ./cache/cord-315498-gpzee1f2.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-315498-gpzee1f2.txt' === file2bib.sh === id: cord-015684-q10sx1dm author: Cacabelos, Ramón title: Pharmacogenomic Biomarkers in Neuropsychiatry: The Path to Personalized Medicine in Mental Disorders date: 2009 pages: extension: .txt txt: ./txt/cord-015684-q10sx1dm.txt cache: ./cache/cord-015684-q10sx1dm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-015684-q10sx1dm.txt' === file2bib.sh === id: cord-298131-zolwjl9u author: Xiao, Shuqi title: Understanding PRRSV Infection in Porcine Lung Based on Genome-Wide Transcriptome Response Identified by Deep Sequencing date: 2010-06-29 pages: extension: .txt txt: ./txt/cord-298131-zolwjl9u.txt cache: ./cache/cord-298131-zolwjl9u.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-298131-zolwjl9u.txt' === file2bib.sh === id: cord-018647-bveks6t1 author: Butnariu, Monica title: Plant Nanobionics: Application of Nanobiosensors in Plant Biology date: 2019-10-01 pages: extension: .txt txt: ./txt/cord-018647-bveks6t1.txt cache: ./cache/cord-018647-bveks6t1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-018647-bveks6t1.txt' === file2bib.sh === id: cord-339012-4juhmjaj author: Hou, Wei title: Rapid host response to an infection with Coronavirus. Study of transcriptional responses with Porcine Epidemic Diarrhea Virus date: 2020-07-28 pages: extension: .txt txt: ./txt/cord-339012-4juhmjaj.txt cache: ./cache/cord-339012-4juhmjaj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-339012-4juhmjaj.txt' === file2bib.sh === id: cord-279781-5ldpz9m9 author: Chen, Chi-Yuan title: Baculovirus as a gene delivery vector: Recent understandings of molecular alterations in transduced cells and latest applications date: 2011-04-28 pages: extension: .txt txt: ./txt/cord-279781-5ldpz9m9.txt cache: ./cache/cord-279781-5ldpz9m9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-279781-5ldpz9m9.txt' === file2bib.sh === id: cord-305177-i71z2sf4 author: Neshat, Sarah Y title: Gene delivery for immunoengineering date: 2020-06-15 pages: extension: .txt txt: ./txt/cord-305177-i71z2sf4.txt cache: ./cache/cord-305177-i71z2sf4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-305177-i71z2sf4.txt' === file2bib.sh === id: cord-314642-oobbdgzh author: Campbell, Allan title: The future of bacteriophage biology date: 2003 pages: extension: .txt txt: ./txt/cord-314642-oobbdgzh.txt cache: ./cache/cord-314642-oobbdgzh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-314642-oobbdgzh.txt' === file2bib.sh === id: cord-345516-fgn7rps3 author: Miller, Laura C title: Analysis of the swine tracheobronchial lymph node transcriptomic response to infection with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus date: 2012-10-30 pages: extension: .txt txt: ./txt/cord-345516-fgn7rps3.txt cache: ./cache/cord-345516-fgn7rps3.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-345516-fgn7rps3.txt' === file2bib.sh === id: cord-016313-n4ewq0pt author: Baranyi, Lajos title: Advances in Lentiviral Vector-based Cell Therapy with Mesenchymal Stem Cells date: 2012-09-27 pages: extension: .txt txt: ./txt/cord-016313-n4ewq0pt.txt cache: ./cache/cord-016313-n4ewq0pt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-016313-n4ewq0pt.txt' === file2bib.sh === id: cord-296979-8r851j4t author: Zhong, Ying title: Host genes regulate transcription of sperm-introduced hepatitis B virus genes in embryo date: 2017-10-31 pages: extension: .txt txt: ./txt/cord-296979-8r851j4t.txt cache: ./cache/cord-296979-8r851j4t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-296979-8r851j4t.txt' === file2bib.sh === id: cord-252147-bvtchcbt author: Domingo-Espín, Joan title: Engineered Biological Entities for Drug Delivery and Gene Therapy: Protein Nanoparticles date: 2011-11-15 pages: extension: .txt txt: ./txt/cord-252147-bvtchcbt.txt cache: ./cache/cord-252147-bvtchcbt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-252147-bvtchcbt.txt' === file2bib.sh === id: cord-280691-nzc8ir0n author: Guo, Sun-Wei title: China’s “Gene War of the Century” and Its Aftermath: The Contest Goes On date: 2013-08-30 pages: extension: .txt txt: ./txt/cord-280691-nzc8ir0n.txt cache: ./cache/cord-280691-nzc8ir0n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-280691-nzc8ir0n.txt' === file2bib.sh === id: cord-304913-qb9zeazk author: Thibivilliers, Sandra title: Generation of Phaseolus vulgaris ESTs and investigation of their regulation upon Uromyces appendiculatus infection date: 2009-04-27 pages: extension: .txt txt: ./txt/cord-304913-qb9zeazk.txt cache: ./cache/cord-304913-qb9zeazk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-304913-qb9zeazk.txt' === file2bib.sh === id: cord-016713-pw4f8asc author: Goyal, Amit K. title: Nanotechnological Approaches for Genetic Immunization date: 2013-05-24 pages: extension: .txt txt: ./txt/cord-016713-pw4f8asc.txt cache: ./cache/cord-016713-pw4f8asc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-016713-pw4f8asc.txt' === file2bib.sh === id: cord-347917-fmb5nyxu author: Liu, Junli title: Comprehensive Genomic Characterization Analysis of lncRNAs in Cells With Porcine Delta Coronavirus Infection date: 2020-01-28 pages: extension: .txt txt: ./txt/cord-347917-fmb5nyxu.txt cache: ./cache/cord-347917-fmb5nyxu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-347917-fmb5nyxu.txt' === file2bib.sh === id: cord-311430-o32d3kaw author: Shahabi, Vafa title: Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events date: 2013-03-22 pages: extension: .txt txt: ./txt/cord-311430-o32d3kaw.txt cache: ./cache/cord-311430-o32d3kaw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-311430-o32d3kaw.txt' === file2bib.sh === id: cord-351845-bli3qm8w author: Prasad, Kartikay title: Targeting hub genes and pathways of innate immune response in COVID-19: A network biology perspective date: 2020-06-26 pages: extension: .txt txt: ./txt/cord-351845-bli3qm8w.txt cache: ./cache/cord-351845-bli3qm8w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-351845-bli3qm8w.txt' === file2bib.sh === id: cord-319519-mb9ofh12 author: Ding, J. title: A network-informed analysis of SARS-CoV-2 and hemophagocytic lymphohistiocytosis genes' interactions points to Neutrophil Extracellular Traps as mediators of thrombosis in COVID-19 date: 2020-07-02 pages: extension: .txt txt: ./txt/cord-319519-mb9ofh12.txt cache: ./cache/cord-319519-mb9ofh12.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-319519-mb9ofh12.txt' === file2bib.sh === id: cord-307769-rjseio5s author: Sim, Winnie H title: Expression profile of genes involved in pathogenesis of pediatric Crohn's disease date: 2012-05-24 pages: extension: .txt txt: ./txt/cord-307769-rjseio5s.txt cache: ./cache/cord-307769-rjseio5s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-307769-rjseio5s.txt' === file2bib.sh === id: cord-022226-qxp0gfp3 author: Meager, Anthony title: Interferons Alpha, Beta, and Omega date: 2007-09-02 pages: extension: .txt txt: ./txt/cord-022226-qxp0gfp3.txt cache: ./cache/cord-022226-qxp0gfp3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-022226-qxp0gfp3.txt' === file2bib.sh === id: cord-291349-tq2n4mx3 author: Smith, Kevin R title: Gene transfer in higher animals: theoretical considerations and key concepts date: 2002-10-09 pages: extension: .txt txt: ./txt/cord-291349-tq2n4mx3.txt cache: ./cache/cord-291349-tq2n4mx3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-291349-tq2n4mx3.txt' === file2bib.sh === id: cord-322566-ye27nqj2 author: Huang, Yuxiang title: Stable Internal Reference Genes for Normalizing Real-Time Quantitative PCR in Baphicacanthus cusia under Hormonal Stimuli and UV Irradiation, and in Different Plant Organs date: 2017-05-03 pages: extension: .txt txt: ./txt/cord-322566-ye27nqj2.txt cache: ./cache/cord-322566-ye27nqj2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-322566-ye27nqj2.txt' === file2bib.sh === id: cord-352200-i05h8csb author: Xu, Yi title: Transcriptome and Comparative Gene Expression Analysis of Sogatella furcifera (Horváth) in Response to Southern Rice Black-Streaked Dwarf Virus date: 2012-04-27 pages: extension: .txt txt: ./txt/cord-352200-i05h8csb.txt cache: ./cache/cord-352200-i05h8csb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-352200-i05h8csb.txt' === file2bib.sh === id: cord-314503-u1y1bznk author: Jaluria, Pratik title: A perspective on microarrays: current applications, pitfalls, and potential uses date: 2007-01-25 pages: extension: .txt txt: ./txt/cord-314503-u1y1bznk.txt cache: ./cache/cord-314503-u1y1bznk.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-314503-u1y1bznk.txt' === file2bib.sh === id: cord-326719-p1ma4akz author: Enjuanes, Luis title: Virus-based vectors for gene expression in mammalian cells: Coronavirus date: 2003-12-31 pages: extension: .txt txt: ./txt/cord-326719-p1ma4akz.txt cache: ./cache/cord-326719-p1ma4akz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-326719-p1ma4akz.txt' === file2bib.sh === id: cord-315072-b28yikvj author: Giotis, Efstathios S. title: Chicken interferome: avian interferon-stimulated genes identified by microarray and RNA-seq of primary chick embryo fibroblasts treated with a chicken type I interferon (IFN-α) date: 2016-08-05 pages: extension: .txt txt: ./txt/cord-315072-b28yikvj.txt cache: ./cache/cord-315072-b28yikvj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-315072-b28yikvj.txt' === file2bib.sh === id: cord-336573-bpg1dg24 author: Greenaway, Hui Yee title: Extraction and characterization of the rhesus macaque T cell receptor β-chain genes date: 2009-06-09 pages: extension: .txt txt: ./txt/cord-336573-bpg1dg24.txt cache: ./cache/cord-336573-bpg1dg24.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-336573-bpg1dg24.txt' === file2bib.sh === id: cord-340125-il35gs97 author: Jayapal, Manikandan title: Genome-wide gene expression profiling of human mast cells stimulated by IgE or FcεRI-aggregation reveals a complex network of genes involved in inflammatory responses date: 2006-08-16 pages: extension: .txt txt: ./txt/cord-340125-il35gs97.txt cache: ./cache/cord-340125-il35gs97.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-340125-il35gs97.txt' === file2bib.sh === id: cord-322286-2de6r1h6 author: Vandewege, Michael W title: Positive Selection and Gene Expression Analyses from Salivary Glands Reveal Discrete Adaptations within the Ecologically Diverse Bat Family Phyllostomidae date: 2020-07-22 pages: extension: .txt txt: ./txt/cord-322286-2de6r1h6.txt cache: ./cache/cord-322286-2de6r1h6.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-322286-2de6r1h6.txt' === file2bib.sh === id: cord-016293-pyb00pt5 author: Newell-McGloughlin, Martina title: The flowering of the age of Biotechnology 1990–2000 date: 2006 pages: extension: .txt txt: ./txt/cord-016293-pyb00pt5.txt cache: ./cache/cord-016293-pyb00pt5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-016293-pyb00pt5.txt' === file2bib.sh === id: cord-304607-td0776wj author: Paszkiewicz, Konrad H. title: Omics, Bioinformatics, and Infectious Disease Research date: 2010-12-24 pages: extension: .txt txt: ./txt/cord-304607-td0776wj.txt cache: ./cache/cord-304607-td0776wj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-304607-td0776wj.txt' === file2bib.sh === id: cord-323307-nu9ib62h author: Dong, Dong title: The genomes of two bat species with long constant frequency echolocation calls date: 2016-10-26 pages: extension: .txt txt: ./txt/cord-323307-nu9ib62h.txt cache: ./cache/cord-323307-nu9ib62h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-323307-nu9ib62h.txt' === file2bib.sh === id: cord-332006-if46jycd author: Whitehead, Kathryn A. title: Knocking down barriers: advances in siRNA delivery date: 2009 pages: extension: .txt txt: ./txt/cord-332006-if46jycd.txt cache: ./cache/cord-332006-if46jycd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-332006-if46jycd.txt' === file2bib.sh === id: cord-329617-gzivtsho author: Lee, Albert K. title: De novo transcriptome reconstruction and annotation of the Egyptian rousette bat date: 2015-12-07 pages: extension: .txt txt: ./txt/cord-329617-gzivtsho.txt cache: ./cache/cord-329617-gzivtsho.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-329617-gzivtsho.txt' === file2bib.sh === id: cord-313138-y485ev30 author: Magor, Katharine E. title: Defense genes missing from the flight division date: 2013-04-24 pages: extension: .txt txt: ./txt/cord-313138-y485ev30.txt cache: ./cache/cord-313138-y485ev30.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-313138-y485ev30.txt' === file2bib.sh === id: cord-328899-kog99kk5 author: Ferrari, Stefano title: Barriers to and new approaches for gene therapy and gene delivery in cystic fibrosis date: 2002-12-05 pages: extension: .txt txt: ./txt/cord-328899-kog99kk5.txt cache: ./cache/cord-328899-kog99kk5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-328899-kog99kk5.txt' === file2bib.sh === id: cord-319517-denczc6t author: Salipalli, Sandeep title: Recent advances in live cell imaging of hepatoma cells date: 2014-07-08 pages: extension: .txt txt: ./txt/cord-319517-denczc6t.txt cache: ./cache/cord-319517-denczc6t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-319517-denczc6t.txt' === file2bib.sh === id: cord-328287-3qgzulgj author: Moni, Mohammad Ali title: Network-based analysis of comorbidities risk during an infection: SARS and HIV case studies date: 2014-10-24 pages: extension: .txt txt: ./txt/cord-328287-3qgzulgj.txt cache: ./cache/cord-328287-3qgzulgj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-328287-3qgzulgj.txt' === file2bib.sh === id: cord-295307-zrtixzgu author: Delgado-Chaves, Fernando M. title: Computational Analysis of the Global Effects of Ly6E in the Immune Response to Coronavirus Infection Using Gene Networks date: 2020-07-21 pages: extension: .txt txt: ./txt/cord-295307-zrtixzgu.txt cache: ./cache/cord-295307-zrtixzgu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-295307-zrtixzgu.txt' === file2bib.sh === id: cord-345475-ttrcmtu4 author: de Oliveira, Luisa Abruzzi title: Reference Genes for the Normalization of Gene Expression in Eucalyptus Species date: 2011-12-24 pages: extension: .txt txt: ./txt/cord-345475-ttrcmtu4.txt cache: ./cache/cord-345475-ttrcmtu4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-345475-ttrcmtu4.txt' === file2bib.sh === id: cord-017208-7oew461e author: Aurigemma, Rosemarie title: Regulatory Aspects in the Development of Gene Therapies date: 2005 pages: extension: .txt txt: ./txt/cord-017208-7oew461e.txt cache: ./cache/cord-017208-7oew461e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-017208-7oew461e.txt' === file2bib.sh === id: cord-314915-b6aqwubh author: Futas, Jan title: Natural Killer Cell Receptor Genes in Camels: Another Mammalian Model date: 2019-07-02 pages: extension: .txt txt: ./txt/cord-314915-b6aqwubh.txt cache: ./cache/cord-314915-b6aqwubh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-314915-b6aqwubh.txt' === file2bib.sh === id: cord-302047-vv5gpldi author: Willemsen, Anouk title: On the stability of sequences inserted into viral genomes date: 2019-11-14 pages: extension: .txt txt: ./txt/cord-302047-vv5gpldi.txt cache: ./cache/cord-302047-vv5gpldi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-302047-vv5gpldi.txt' === file2bib.sh === id: cord-317779-j67vb7f3 author: Irizarry, Kristopher J. L. title: RNA sequencing demonstrates large-scale temporal dysregulation of gene expression in stimulated macrophages derived from MHC-defined chicken haplotypes date: 2017-08-28 pages: extension: .txt txt: ./txt/cord-317779-j67vb7f3.txt cache: ./cache/cord-317779-j67vb7f3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-317779-j67vb7f3.txt' === file2bib.sh === id: cord-318576-dc5n6ni4 author: Jitobaom, Kunlakanya title: Codon usage similarity between viral and some host genes suggests a codon-specific translational regulation date: 2020-05-08 pages: extension: .txt txt: ./txt/cord-318576-dc5n6ni4.txt cache: ./cache/cord-318576-dc5n6ni4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-318576-dc5n6ni4.txt' === file2bib.sh === id: cord-355927-nzoiv9pj author: Lemmon, Alan R. title: The Effect of Ambiguous Data on Phylogenetic Estimates Obtained by Maximum Likelihood and Bayesian Inference date: 2009-05-21 pages: extension: .txt txt: ./txt/cord-355927-nzoiv9pj.txt cache: ./cache/cord-355927-nzoiv9pj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-355927-nzoiv9pj.txt' === file2bib.sh === id: cord-306535-j26eqmxt author: Robertson, Matthew J. title: Large-scale discovery of male reproductive tract-specific genes through analysis of RNA-seq datasets date: 2020-08-19 pages: extension: .txt txt: ./txt/cord-306535-j26eqmxt.txt cache: ./cache/cord-306535-j26eqmxt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-306535-j26eqmxt.txt' === file2bib.sh === id: cord-264996-og3sg0qw author: Howell, Gareth J. title: Cell Biology of Membrane Trafficking in Human Disease date: 2006-09-17 pages: extension: .txt txt: ./txt/cord-264996-og3sg0qw.txt cache: ./cache/cord-264996-og3sg0qw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-264996-og3sg0qw.txt' === file2bib.sh === id: cord-014462-11ggaqf1 author: nan title: Abstracts of the Papers Presented in the XIX National Conference of Indian Virological Society, “Recent Trends in Viral Disease Problems and Management”, on 18–20 March, 2010, at S.V. University, Tirupati, Andhra Pradesh date: 2011-04-21 pages: extension: .txt txt: ./txt/cord-014462-11ggaqf1.txt cache: ./cache/cord-014462-11ggaqf1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-014462-11ggaqf1.txt' === file2bib.sh === id: cord-346308-9h2fk9qt author: Kaur, Rajwinder title: Microbiology of hospital wastewater date: 2020-05-01 pages: extension: .txt txt: ./txt/cord-346308-9h2fk9qt.txt cache: ./cache/cord-346308-9h2fk9qt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-346308-9h2fk9qt.txt' === file2bib.sh === id: cord-267475-6f4h3cck author: Kozak, Marilyn title: Pushing the limits of the scanning mechanism for initiation of translation date: 2002-10-16 pages: extension: .txt txt: ./txt/cord-267475-6f4h3cck.txt cache: ./cache/cord-267475-6f4h3cck.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-267475-6f4h3cck.txt' === file2bib.sh === id: cord-264884-ydkigome author: Villarreal, Luis P. title: The Widespread Evolutionary Significance of Viruses date: 2008-07-05 pages: extension: .txt txt: ./txt/cord-264884-ydkigome.txt cache: ./cache/cord-264884-ydkigome.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-264884-ydkigome.txt' === file2bib.sh === id: cord-000248-zueoyesj author: Berretta, Regina title: Cancer Biomarker Discovery: The Entropic Hallmark date: 2010-08-18 pages: extension: .txt txt: ./txt/cord-000248-zueoyesj.txt cache: ./cache/cord-000248-zueoyesj.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000248-zueoyesj.txt' === file2bib.sh === id: cord-016095-jop2rx61 author: Vignais, Pierre V. title: Challenges for Experimentation on Living Beings at the Dawn of the 21(st) Century date: 2010-06-08 pages: extension: .txt txt: ./txt/cord-016095-jop2rx61.txt cache: ./cache/cord-016095-jop2rx61.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-016095-jop2rx61.txt' === file2bib.sh === id: cord-335382-fk4um9nw author: Farver, Carol F. title: Molecular Basis of Pulmonary Disease date: 2012-08-10 pages: extension: .txt txt: ./txt/cord-335382-fk4um9nw.txt cache: ./cache/cord-335382-fk4um9nw.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-335382-fk4um9nw.txt' === file2bib.sh === id: cord-014597-66vd2mdu author: nan title: Abstracts from the 25th European Society for Animal Cell Technology Meeting: Cell Technologies for Innovative Therapies: Lausanne, Switzerland. 14-17 May 2017 date: 2018-03-15 pages: extension: .txt txt: ./txt/cord-014597-66vd2mdu.txt cache: ./cache/cord-014597-66vd2mdu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 7 resourceName b'cord-014597-66vd2mdu.txt' === file2bib.sh === id: cord-023055-ntbvmssh author: nan title: Immunogenicity date: 2004-02-19 pages: extension: .txt txt: ./txt/cord-023055-ntbvmssh.txt cache: ./cache/cord-023055-ntbvmssh.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023055-ntbvmssh.txt' === file2bib.sh === id: cord-009664-kb9fnbgy author: nan title: Oral presentations date: 2014-12-24 pages: extension: .txt txt: ./txt/cord-009664-kb9fnbgy.txt cache: ./cache/cord-009664-kb9fnbgy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 7 resourceName b'cord-009664-kb9fnbgy.txt' === file2bib.sh === id: cord-004879-pgyzluwp author: nan title: Programmed cell death date: 1994 pages: extension: .txt txt: ./txt/cord-004879-pgyzluwp.txt cache: ./cache/cord-004879-pgyzluwp.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-004879-pgyzluwp.txt' === file2bib.sh === id: cord-005147-mvoq9vln author: nan title: Autorenregister date: 2017-02-23 pages: extension: .txt txt: ./txt/cord-005147-mvoq9vln.txt cache: ./cache/cord-005147-mvoq9vln.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 9 resourceName b'cord-005147-mvoq9vln.txt' === file2bib.sh === id: cord-028721-x6f26ahr author: Nistal, Manuel title: Non-neoplastic diseases of the testis date: 2020-06-22 pages: extension: .txt txt: ./txt/cord-028721-x6f26ahr.txt cache: ./cache/cord-028721-x6f26ahr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 9 resourceName b'cord-028721-x6f26ahr.txt' === file2bib.sh === id: cord-006230-xta38e7j author: nan title: Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V. date: 2012-02-22 pages: extension: .txt txt: ./txt/cord-006230-xta38e7j.txt cache: ./cache/cord-006230-xta38e7j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 14 resourceName b'cord-006230-xta38e7j.txt' === file2bib.sh === id: cord-008777-i2reanan author: nan title: ECB12: 12th European Congess on Biotechnology date: 2005-07-19 pages: extension: .txt txt: ./txt/cord-008777-i2reanan.txt cache: ./cache/cord-008777-i2reanan.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 28 resourceName b'cord-008777-i2reanan.txt' === file2bib.sh === id: cord-022940-atbjwpo5 author: nan title: Poster Sessions date: 2016-09-07 pages: extension: .txt txt: ./txt/cord-022940-atbjwpo5.txt cache: ./cache/cord-022940-atbjwpo5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 17 resourceName b'cord-022940-atbjwpo5.txt' Que is empty; done keyword-gene-cord === reduce.pl bib === id = cord-001541-5d64esp4 author = Walker, Peter J. title = Evolution of Genome Size and Complexity in the Rhabdoviridae date = 2015-02-13 pages = extension = .txt mime = text/plain words = 9157 sentences = 398 flesch = 45 summary = We demonstrate that remarkable changes in genome size and complexity have occurred in rhabdoviruses in a clade-specific manner, primarily by extension and insertion of additional transcriptional units in the structural protein gene junctions, followed by occasional losses. All rhabdovirus genomes contained the five canonical structural protein genes (N, P, M, G and L); however, there was remarkable diversity in the number and location of other long ORFs. Across the data set, we identified 179 additional ORFs 180 nt in length of which 142 shared no detectable protein sequence similarity with any other protein in our data set or with those in public databases (S2 Table) . Interestingly, although substantial variation in the length of gene junctions was observed in several genera (including ephemeroviruses and lyssaviruses), most variation in genome size occurred as the result of the presence of new, non-canonical ORFs in the regions between the structural protein genes (Table 1) . cache = ./cache/cord-001541-5d64esp4.txt txt = ./txt/cord-001541-5d64esp4.txt === reduce.pl bib === id = cord-000159-8y8ho2x5 author = Bekaert, Michaël title = Recode-2: new design, new search tools, and many more genes date = 2009-09-25 pages = extension = .txt mime = text/plain words = 2625 sentences = 138 flesch = 42 summary = 'Recoding' is a term used to describe non-standard read-out of the genetic code, and encompasses such phenomena as programmed ribosomal frameshifting, stop codon readthrough, selenocysteine insertion and translational bypassing. It provides access to detailed information on genes known to utilize translational recoding and allows complex search queries, browsing of recoding data and enhanced visualization of annotated sequence elements. The term 'translational recoding' describes the utilization of non-standard decoding during protein synthesis and encompasses such processes as ribosomal frameshifting, codon redefinition, translational bypassing and StopGo (1) (2) (3) (4) (5) (6) (7) . To facilitate further development of computational tools for the prediction of recoded genes in the ever faster growing body of sequence data, as well as to provide bench researchers with upto-date information on recoding, an efficient means of Recode database population and annotation are now required. RECODE: a database of frameshifting, bypassing and codon redefinition utilized for gene expression cache = ./cache/cord-000159-8y8ho2x5.txt txt = ./txt/cord-000159-8y8ho2x5.txt === reduce.pl bib === === reduce.pl bib === id = cord-000580-dcid9emx author = Sällman Almén, Markus title = The Dispanins: A Novel Gene Family of Ancient Origin That Contains 14 Human Members date = 2012-02-20 pages = extension = .txt mime = text/plain words = 4662 sentences = 237 flesch = 48 summary = We show that the IFITM genes are a subfamily in a larger family of transmembrane (TM) proteins that we call Dispanins, which refers to a common 2TM structure. We mined 36 eukaryotic species, covering all major eukaryotic groups, and found that the IFITMs form a subfamily in a larger novel family that has ten human members in addition to the four IFITM genes. By combining the results of the phylogenetic analysis and BLAST classification, we created a schematic overview of the organisms' gene repertoire and a schematic picture of the Dispanin family's evolutionary history, which suggests that the invertebrate Dispanins share more similarity towards the DSPC and D subfamilies than DSPA and B ( Figure 2 ). We provide evidence that the four IFITM genes together with ten additional human genes, known as TUSC5, TMEM233, PRRT2, TMEM90A, DSPC2, TMEM90B, TMEM91, AC023157, AL160276 and AC068580, form a novel gene family that we call the Dispanins, which refers to the 2TM membrane topology that is common to all identified members. cache = ./cache/cord-000580-dcid9emx.txt txt = ./txt/cord-000580-dcid9emx.txt === reduce.pl bib === id = cord-003044-9uqa39j9 author = Cervera, Héctor title = Viral Fitness Correlates with the Magnitude and Direction of the Perturbation Induced in the Host’s Transcriptome: The Tobacco Etch Potyvirus—Tobacco Case Study date = 2018-03-19 pages = extension = .txt mime = text/plain words = 10863 sentences = 533 flesch = 46 summary = As viral fitness is reduced, interactions are less optimal and, consequently, the gene expression profile of the plant will be increasingly different from that resulting from the infection with the WT virus. Figure 2A shows the clustering (unweighted average distance method; UPGMA) of average expression data for those genes that significantly changed expression (62-fold) among plants infected with the seven viral genotypes (1-way ANOVAs with false discovery rate (FDR) correction; overall P < 0.05) relative to the mock-inoculated plants. tabacum into a novel, poorly susceptible one, Arabidopsis thaliana, have shown that adaptation of TEV to the novel host (i.e., concomitant to large increases in fitness) was associated with a profound change in the way the ancestral and evolved viruses interacted with the plant's transcriptome, with genes involved in the response to biotic stresses, including signal transduction and innate immunity pathways, being significantly underexpressed in plants infected with the evolved virus than in plants infected with the ancestral one (Agudelo-Romero et al. cache = ./cache/cord-003044-9uqa39j9.txt txt = ./txt/cord-003044-9uqa39j9.txt === reduce.pl bib === id = cord-002366-t94aufs3 author = Aurrecoechea, Cristina title = EuPathDB: the eukaryotic pathogen genomics database resource date = 2017-01-04 pages = extension = .txt mime = text/plain words = 3783 sentences = 204 flesch = 47 summary = To facilitate the discovery of meaningful biological relationships, the databases couple preconfigured searches with visualization and analysis tools for comprehensive data mining via intuitive graphical interfaces and APIs. All data are analyzed with the same workflows, including creation of gene orthology profiles, so data are easily compared across data sets, data types and organisms. Expanded data content is mostly genomic and functional genomic data while new data types include protein microarray, metabolic pathways, compounds, quantitative proteomics, copy number variation, and polysomal transcriptomics. New features include consistent categorization of searches, data sets and genome browser tracks; redesigned gene pages; effective integration of alternative transcripts; and a EuPathDB Galaxy instance for private analyses of a user's data. The near-seamless integration of strategy results with tools for functional enrichment analyses and transcript interpretation as well as our new Galaxy workspace and the availability of publicly shared strategies augment the data mining experience in EuPathDB. cache = ./cache/cord-002366-t94aufs3.txt txt = ./txt/cord-002366-t94aufs3.txt === reduce.pl bib === id = cord-003254-yiqdsf9z author = Schlub, Timothy E title = A Simple Method to Detect Candidate Overlapping Genes in Viruses Using Single Genome Sequences date = 2018-08-07 pages = extension = .txt mime = text/plain words = 6313 sentences = 292 flesch = 49 summary = Herein, we present a new statistical method for detecting overlapping genes in different reading frames that relies on only a single nucleotide sequence of a gene or genome. For the synonymous mutation test (C), codons that preserve the original amino acid sequence are randomly generated and the length of ORFs on alternative reading frames subsequently measured (note that codon replacement is not restricted to the example mutations shown in the figure, all of which occur in the third nucleotide positions, and that codon replacement with the original codon is also possible). Accordingly, whole genome sequences were downloaded from 2548 reference linear RNA viruses available on GenBank; this produced a total of 6408 coding regions that were used to estimate the sensitivity and false discovery rate of each test. where C is the empirical cumulative distribution function of the theoretical distribution of lengths calculated by permuting codons in the original coding sequence: that is, C(L) is the Simple Method to Detect Candidate Overlapping Genes . cache = ./cache/cord-003254-yiqdsf9z.txt txt = ./txt/cord-003254-yiqdsf9z.txt === reduce.pl bib === id = cord-003196-fdb6az0v author = Casalino-Matsuda, S. Marina title = Hypercapnia Alters Expression of Immune Response, Nucleosome Assembly and Lipid Metabolism Genes in Differentiated Human Bronchial Epithelial Cells date = 2018-09-10 pages = extension = .txt mime = text/plain words = 4652 sentences = 252 flesch = 37 summary = title: Hypercapnia Alters Expression of Immune Response, Nucleosome Assembly and Lipid Metabolism Genes in Differentiated Human Bronchial Epithelial Cells These changes in gene expression indicate the potential for hypercapnia to impact bronchial epithelial cell function in ways that may contribute to poor clinical outcomes in patients with severe acute or advanced chronic lung diseases. Major clusters from hypercapnia-downregulated genes are linked to immune response, nucleosome assembly, cell differentiation, oxidation reduction, and ion and lipid transport (Fig. 2) . In addition, the suppressive effect of elevated CO 2 on immune gene expression in the airway epithelium, along with similar effects on immune cells, suggest a reason why severe COPD and other lung disease associated with hypercapnia all carry a high risk of pulmonary infection. Thus, CO 2 -induced alterations in airway epithelial gene expression may underlie the increase in mortality associated with hypercapnia in advanced COPD, as well as community-acquired pneumonia 9 , adenoviral lung infections 10 and cystic fibrosis 11 . cache = ./cache/cord-003196-fdb6az0v.txt txt = ./txt/cord-003196-fdb6az0v.txt === reduce.pl bib === id = cord-001858-nmi39n6h author = Petriccione, Milena title = Reference gene selection for normalization of RT-qPCR gene expression data from Actinidia deliciosa leaves infected with Pseudomonas syringae pv. actinidiae date = 2015-11-19 pages = extension = .txt mime = text/plain words = 5567 sentences = 286 flesch = 50 summary = title: Reference gene selection for normalization of RT-qPCR gene expression data from Actinidia deliciosa leaves infected with Pseudomonas syringae pv. Primer sequence (5′-3′) BestKeeper and the deltaCt method) were used to evaluate the stability of expression of selected RGs. The analyses were performed for three comparison groups considering both low-and high-dose bacterial inocula in the leaves and their combined dataset. In kiwifruit leaves with a high dose of bacterial inoculum, BestKeeper revealed that only the expression of TUB overcame the stability threshold; CYP and GAPDH were considered to be the most stable genes, with SD values of 0.50 and 0.61, respectively (Table 3 ). The expression of three genes encoding the reactive oxygen species (ROS) scavenging enzymes ascorbate peroxidase (APX), superoxide dismutase (SOD) and catalase (CAT), induced during the systemic infection of kiwifruit leaves with PSA, were chosen to further validate the reliability of the selected RGs for the normalization of RT-qPCR data. cache = ./cache/cord-001858-nmi39n6h.txt txt = ./txt/cord-001858-nmi39n6h.txt === reduce.pl bib === id = cord-000402-unr44dvp author = Yoo, Hyun Jung title = Gene Expression Profile during Chondrogenesis in Human Bone Marrow derived Mesenchymal Stem Cells using a cDNA Microarray date = 2011-06-20 pages = extension = .txt mime = text/plain words = 3178 sentences = 165 flesch = 44 summary = title: Gene Expression Profile during Chondrogenesis in Human Bone Marrow derived Mesenchymal Stem Cells using a cDNA Microarray The expression levels of the 10 genes selected (Hrad 6B, annexin A2, BMP-7, contactin-1, peroxiredoxin-1, heat shock transcription factor-2, synaptotagmin IV, serotonin receptor-7, Axl, and IL-15) were analyzed by RT-PCR, by using total RNAs obtained from 5 samples (Fig. 4B) . The expression levels of 9 genes (Hrad 6B, annexin A2, BMP-7, contactin-1, peroxiredoxin-1, heat shock transcription factor-2, synaptotagmin IV, serotonin receptor-7, Axl) were low in undifferentiated cells and increased in differentiated cells by RT-PCR and microarray, but the expression pattern of IL-15 was different. Microarray data showed that Axl, synaptotagmin IV, Hrad6B, peroxiredoxin-1, BMP-7, heat shock transcription factor-2, annexin A2, contactin-1 and serotonin receptor-7 expressions were maintained in differentiating BM-MSCs until day 14. Gene expression profile of cytokine and growth factor during differentiation of bone marrow-derived mesenchymal stem cell cache = ./cache/cord-000402-unr44dvp.txt txt = ./txt/cord-000402-unr44dvp.txt === reduce.pl bib === === reduce.pl bib === id = cord-000012-p56v8wi1 author = Bigot, Yves title = Molecular evidence for the evolution of ichnoviruses from ascoviruses by symbiogenesis date = 2008-09-18 pages = extension = .txt mime = text/plain words = 6419 sentences = 293 flesch = 44 summary = CONCLUSION: Our results provide molecular evidence supporting the origin of ichnoviruses from ascoviruses by lateral transfer of ascoviral genes into ichneumonid wasp genomes, perhaps the first example of symbiogenesis between large DNA viruses and eukaryotic organisms. With respect to both species number and mechanisms that lead to successful parasitism, endoparasitic wasps are known to inject secretions at oviposition, but only a few lineages use viruses or virus-like particles (VLPs) to evade or to suppress host defences. Extending our investigations to proteins encoded by open reading frames of certain ascoviruses and bracoviruses, hosts and bacteria, in the light of recent analyses about the involvement of the replication machinery of virus groups related to ascoviruses in lateral gene transfer [29] , we discuss the robustness and the limits of the molecular evidence supporting an ascovirus origin for ichnovirus lineages. cache = ./cache/cord-000012-p56v8wi1.txt txt = ./txt/cord-000012-p56v8wi1.txt === reduce.pl bib === id = cord-005216-potmzdfs author = Sun, Dong title = Bioinformatics Analysis of Genes and Pathways of CD11b(+)/Ly6C(intermediate) Macrophages after Renal Ischemia-Reperfusion Injury date = 2018-03-15 pages = extension = .txt mime = text/plain words = 3294 sentences = 180 flesch = 49 summary = Signet analysis showed that Atp5al, Atp5o, Cox4i, Cdc42, Rac2 and Nhp2 were the key genes involved in oxidation-reduction, apoptosis, migration, M1-M2 differentiation, and proliferation of macrophages. The identified DEGs and their enriched pathways investigate factors that may participate in the functional changes of CD 1lb(+)Ly6C(intermediate) macrophages after renal IRI. We used microarray analysis to identify the differentially expressed genes (DEGs) in CD11b + /Ly6C int macrophages of C57BL/6 mice and mice undergoing sham surgery or IRI for 4 h, 24 h or 9 days. To identify functional changes in macrophages, we analysed the role of DEGs in each significant expression profile. To identify the main biological function of CD11b + /Ly6C int macrophages, pathways of genes with similar expression trend were analysed. In this study, we analysed DEGs from CD11b + / Ly6C int macrophages, which were isolated from kidneys of mice undergoing sham surgery (n=2), and IRI at 4 h, 24 h, and 9 days (n=3 per group). cache = ./cache/cord-005216-potmzdfs.txt txt = ./txt/cord-005216-potmzdfs.txt === reduce.pl bib === id = cord-000492-ec5qzurk author = Devaney, James title = Clinical Review: Gene-based therapies for ALI/ARDS: where are we now? date = 2011-06-20 pages = extension = .txt mime = text/plain words = 6012 sentences = 313 flesch = 39 summary = Plasmid transfer (closed Easily produced at low cost No specifi c cell targeting Electroporation-mediated gene transfer of the dsDNA circles) Very ineffi cient Na + ,K + -ATPase rescues endotoxin-induced lung injury [60] Nonviral DNA complexes Complexes protect DNA Less effi cient than viral vectors Cationic lipid-mediated transfer of the Na + ,K + -(lipoplexes or polyplexes) Modifying transgene DNA to eliminate bacterial motifs [75, 76] Development of high-effi ciency tissue-specifi c promoters [77] [78] [79] [80] Development of promoters that regulate gene expression [83] Enhanced therapeutic targeting Nebulization technologies [9] Strategies to target the pulmonary endothelium [10] Improved cellular uptake of vector Surface active agents to enhance vector spread [84] Reduce ubiquitination of viral capsid proteins [85] Better therapeutic targets Enhancement or restoration of lung epithelial and/or endothelial cell function [86] Strengthening lung defense mechanisms against injury [87] Speeding clearance of infl ammation and infection Enhancement of the repair process following ALI/ARDS [88] . cache = ./cache/cord-000492-ec5qzurk.txt txt = ./txt/cord-000492-ec5qzurk.txt === reduce.pl bib === id = cord-003514-yyzbv7ys author = Arslan, Mehboob title = Dynamic Expression of Interferon Lambda Regulated Genes in Primary Fibroblasts and Immune Organs of the Chicken date = 2019-02-14 pages = extension = .txt mime = text/plain words = 6080 sentences = 326 flesch = 44 summary = The transcriptional profiling using RNA-seq and subsequent bioinformatics analysis (gene ontology, differential expressed genes, and KEGGs analysis) of the bursa of Fabricious and the thymus demonstrated an upregulation of crucial immune genes (viperin, IKKB, CCL5, IL1β, and AP1) as well as the antiviral signaling pathways. Although CEF do not possess receptors for IFN-λ, slight temporal expression of DEGs in response to chIFN-λ treatment signifies its antiviral potential in primary cells. Furthermore, studies have also revealed that a high degree of cell type specificity in receptor-ligand interactions make avian IFNs distinct from mammalian IFNs. Recently, it has been established that chicken IFN-λ inhibits low pathogenic influenza virus replication in CEFs; however, as compared to chIFN-γ and chIFN-β, higher doses are required to induce ISGs and maintain the strong antiviral state in the cells [14] . Our data suggest that significant antiviral, cell cycle regulators, and biologically active genes are expressed in response to administered chicken IFN. cache = ./cache/cord-003514-yyzbv7ys.txt txt = ./txt/cord-003514-yyzbv7ys.txt === reduce.pl bib === id = cord-000248-zueoyesj author = Berretta, Regina title = Cancer Biomarker Discovery: The Entropic Hallmark date = 2010-08-18 pages = extension = .txt mime = text/plain words = 33594 sentences = 1678 flesch = 43 summary = These authors cite, for example, ''mitochondrial dysfunction'' [5, 6] (including, but not limited to ''glucose avidity'' [7] and ''a shift in glucosemetabolism from oxidative phosphorylation to glycolysis'' [6, 8] , ''altered glycolysis'' [9] , ''altered bioenergetic function of mitochondria'' [10] ), ''dysregulation of cell cycle and defective genome-integrity checkpoints'' [11] , ''aberrant DNA methylation'' [12] (''promoter hypermethylation of hallmark cancer genes'' [13] and ''CpG island hypermethylation and global genomic hypomethylation'' [14] ), ''shift in cellular metabolism'' [15, 16, 17] , ''regional hypoxia'' [18] , ''microenviroment acidosis'' [19] , ''abnormal microRNA regulation'' [20, 21] , ''aneuploidy'' and ''chromosome aberrations'' [22, 23, 24, 25, 26] , ''disruption of cellular junctions'' [27] , ''avoidance of the immune response'' [28] , ''pre-existing chronic inflammatory conditions'' [29, 30] , ''cancerrelated inflammation'' [29] , ''disabled autophagy'' [28] , ''impaired cellular senescence'' [31] , ''altered NF-kappaB signalling'' [32] , ''altered growth patterns, not altered growth per se'' [33] , ''disregulated DNA methylation and histone modifications'' [34] , ''tissue dedifferentiation'' [35, 36] , and ''somatically heritable molecular alterations'' [37] . cache = ./cache/cord-000248-zueoyesj.txt txt = ./txt/cord-000248-zueoyesj.txt === reduce.pl bib === id = cord-003898-y6zpvw84 author = Tan, Kai Sen title = RNA Sequencing of H3N2 Influenza Virus-Infected Human Nasal Epithelial Cells from Multiple Subjects Reveals Molecular Pathways Associated with Tissue Injury and Complications date = 2019-08-27 pages = extension = .txt mime = text/plain words = 7671 sentences = 386 flesch = 44 summary = title: RNA Sequencing of H3N2 Influenza Virus-Infected Human Nasal Epithelial Cells from Multiple Subjects Reveals Molecular Pathways Associated with Tissue Injury and Complications The aim of this study was to utilize RNA sequencing (RNAseq) technology to not only reveal the hNEC responses (from multiple individuals) against influenza infection, but also to identify those genes with high magnitude changes to serve as potential reference markers of the innate responses of influenza infection. After deriving the transcriptomes by RNAseq, we then further investigated whether the changes in expression of genes resulted in alterations in secretory cytokines and chemokines early in the infection of hNECs. Initially, we detected significant reductions in multiple cytokines at 8 hpi, with the exception of IL-15 which was increased ( Figure S2 ). In conclusion, RNAseq technology allowed us to accurately quantify the magnitude of gene expression changes, as well as the relevant enriched pathways during H3N2 influenza virus infection of hNECs, which can serve as a baseline for future clinical studies. cache = ./cache/cord-003898-y6zpvw84.txt txt = ./txt/cord-003898-y6zpvw84.txt === reduce.pl bib === === reduce.pl bib === id = cord-004893-28mrzvsc author = Pavesi, Angelo title = On the Informational Content of Overlapping Genes in Prokaryotic and Eukaryotic Viruses date = 1997 pages = extension = .txt mime = text/plain words = 3783 sentences = 161 flesch = 48 summary = At the level of codon usage, a low degree of correlation between overlapping and nonoverlapping coding regions characterized the first pattern, whereas a close link was found in tymoviruses, indicating a fine adaptation of the overlapping frame to the original codon choice of the virus. Here, we present an analysis at different levels of complexity (divergence from randomness of mono-and dinucleotide composition, choice of synonymous codons, and frequency of occurrence of amino acid residues) of the informational content of overlapping genes. The graphical representation ( Fig. 2) of the average values of the D 1 and D 2 indices, calculated by grouping the 12 viruses under examination in the five corresponding families (coliphage, hepatitis B virus, HIV-1 lentivirus, luteovirus, and tymovirus), led to the identification of two different informational patterns in the viral coding sequences. cache = ./cache/cord-004893-28mrzvsc.txt txt = ./txt/cord-004893-28mrzvsc.txt === reduce.pl bib === id = cord-005476-q6o5239w author = Griesenbach, U title = Gene therapy for cystic fibrosis: an example for lung gene therapy date = 2004-09-29 pages = extension = .txt mime = text/plain words = 5903 sentences = 290 flesch = 44 summary = Over the last decade, the gene therapy community has recognized that there is not even one vector that is good for all applications, but that the gene transfer agent (GTA) has to be carefully chosen depending on the cell type to be targeted, the number of treatments (one versus repeat administration) required, and the size and nature (secreted versus cellular product) of the gene to be delivered. In an attempt to increase the transfection efficiency of adenoviral vectors in vivo, Gregory et al 17 assessed the effects of sodium caprate (a tight junction opener) application to the luminal surface of AECs in mouse lung, with the rationale that CAR expression is higher on the basolateral surface of epithelial cells. RSV and PIV3 target human ciliated airway epithelial cells: efficient gene transfer vectors for cystic fibrosis lung disease cache = ./cache/cord-005476-q6o5239w.txt txt = ./txt/cord-005476-q6o5239w.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-007259-vj9tv3or author = Guo, Feng-Biao title = Accurate prediction of human essential genes using only nucleotide composition and association information date = 2017-06-15 pages = extension = .txt mime = text/plain words = 5656 sentences = 315 flesch = 52 summary = RESULTS: Our model accurately predicted human gene essentiality with an AUC higher than 0.88 both for 5-fold cross-validation and jackknife tests. reported a machine learningbased method that integrated various intrinsic and predicted features to identify essential genes in yeast S.cerevisiae genomes (Seringhaus et al., 2006) . The data from these three groups provided a rare opportunity to theoretically study the function, sequence composition, evolution and network topology of human essential genes. Based on the k-interval Z curve, we obtained excellent performance in human essential gene identification. For human essential gene identification, we only used the sequence composition and interval association information in the present study and still obtained an AUC of 0.8854. Considering that this result is better than the results obtained in previous studies using integrated features, the gene essentiality of the human genome can be accurately reflected based on only the sequence information. cache = ./cache/cord-007259-vj9tv3or.txt txt = ./txt/cord-007259-vj9tv3or.txt === reduce.pl bib === === reduce.pl bib === id = cord-004222-z4butywi author = Joyce, Collin title = Comparisons of the antibody repertoires of a humanized rodent and humans by high throughput sequencing date = 2020-01-24 pages = extension = .txt mime = text/plain words = 3718 sentences = 187 flesch = 46 summary = We characterized the heavy chain and kappa light chain antibody repertoires of a model animal, the OmniRat, by high throughput antibody sequencing and made use of two novel datasets for comparison to human repertoires. Multiple differences were found in both the heavy and kappa chain repertoires between OmniRats and humans including gene segment usage, CDR3 length distributions, class switch recombination, somatic hypermutation levels and in features of V(D)J recombination. We individually separated total RNA from spleens and lymph nodes of three unimmunized OmniRats and PCR amplified the heavy and kappa chain antibody V gene segments. We started by making intra-animal comparisons, intra-species comparisons and inter-species comparisons of the immunoglobulin gene segment usage frequencies for each antibody repertoire by performing hierarchical clustering ( Fig. 1 ) and linear regression analysis (Figs. cache = ./cache/cord-004222-z4butywi.txt txt = ./txt/cord-004222-z4butywi.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-005432-mqyvpepo author = Ma, Z title = Redirecting adenovirus to pulmonary endothelium by cationic liposomes date = 2002-02-22 pages = extension = .txt mime = text/plain words = 3980 sentences = 235 flesch = 50 summary = A recent study has shown that the use of a bispecific antibody to endothelial cells and Ad vectors efficiently redirects Ad vectors to pulmonary endothelium and improves gene expression in the lung. 10 To test whether preinjection of cationic liposomes can also enhance Ad vector-mediated pulmonary gene transfer, groups of six mice received tail vein injection of various amounts of DOTAP:cholesterol liposomes followed by injection of AdCMVLuc. Gene expression was assayed 3 days following the injection. 12 To Gene Therapy examine whether lipid complexation can similarly enhance pulmonary gene transfer by Ad vectors via the vascular route, AdCMVLuc was mixed with various amounts of DOTAP:cholesterol liposomes and gene expression was assayed 3 days following the injection of the complexed AdCMVLuc. In contrast to sequential injection, premixing of cationic liposomes with AdCM-VLuc resulted in a decreased gene expression in all major organs examined ( Figure 2 ). cache = ./cache/cord-005432-mqyvpepo.txt txt = ./txt/cord-005432-mqyvpepo.txt === reduce.pl bib === id = cord-016095-jop2rx61 author = Vignais, Pierre V. title = Challenges for Experimentation on Living Beings at the Dawn of the 21(st) Century date = 2010-06-08 pages = extension = .txt mime = text/plain words = 42843 sentences = 1503 flesch = 43 summary = Instead of setting out to discover unknown mechanisms by analyzing effects that are dependent on specific causes, with some uncertainty as to the possible success of the enterprise being undertaken, which is the foundation stone of the Bernardian paradigm of the experimental method, many current research projects give themselves achievable and programmable objectives that depend upon the means available to them: sequencing of genomes with a view to comparing them, recognition of sequence similarities in proteins coded for by genes belonging to different species, with the aim of putting together phylogenetic trees, synthesis of interesting proteins in transgenic animals and plants, analysis of the three-dimensional structure of proteins, in order to find sites that are likely to fix medicinal substances, and synthesis of molecular species able to recognize pathogenic targets. cache = ./cache/cord-016095-jop2rx61.txt txt = ./txt/cord-016095-jop2rx61.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-005147-mvoq9vln author = nan title = Autorenregister date = 2017-02-23 pages = extension = .txt mime = text/plain words = 86573 sentences = 4356 flesch = 45 summary = Using whole-exome sequencing and trio-based de novo analysis, we identified a novel heterozygous de novo frameshift variant in the leukemia inhibitory factor receptor (LIFR) gene causing instability of the mRNA in a patient presenting with bilateral CAKUT and requiring kidney transplantation at one year of age. Loss of cdkl5 associated with deficient mammalian target of rapamycin (mTOR) signaling in mice and human cells We and other groups have shown that mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene cause a severe neurodevelopmental disorder with clinical features including intellectual disability, early-onset intractable seizures and autism, that are closely related to those present in Rett syndrome (RTT) patients. Functional characterization of novel GNB1 mutations as a rare cause of global developmental delay Over the past years, prioritization strategies that combined the molecular predictors of sequence variants from exomes and genomes of patients with rare Mendelian disorders with computer-readable phenotype information became a highly effective method for detecting disease-causing mutations. cache = ./cache/cord-005147-mvoq9vln.txt txt = ./txt/cord-005147-mvoq9vln.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-007760-it9wach2 author = Jiao, Long R. title = Suicide Gene Therapy in Liver Tumors date = 2004 pages = extension = .txt mime = text/plain words = 7100 sentences = 352 flesch = 51 summary = have recently published the result of a phase I clinical trial using intratumoral injection of escalating doses of adenovirus-mediated suicide gene followed by intravenous GCV at a fixed dose in patients with colorectal liver metastases (13). The study seeks to determine the safety, biological efficacy, and effect of the Ad-TK-GCV dose in the locoregional gene therapy of primary malignant tumors of the liver. The following must be performed within 2 wk prior to study admission: complete medical history; physical examination; toxicity evaluation; performance status; height and weight and body surface area; laboratory screening (*eligibility criteria) for full blood count with differential, platelet count*, serum electrolytes (sodium, potassium, chloride, bicarbonate), urea, creatinine*, glucose, uric acid, albumin, liver function tests, including total protein, calcium, phosphorus, magnesium, aspartate transaminase (AST*), alanine transaminase (ALT*), total bilirubin*, alkaline phosphatase, lactate dehydrogenase (LDH), PT*, partial thomboplastin time (PTT*); urinalysis; α-fetoprotein; electrocardiogram (12-lead); chest X-ray (PA and lateral views); abdomen and pelvis CT or MRI scan. cache = ./cache/cord-007760-it9wach2.txt txt = ./txt/cord-007760-it9wach2.txt === reduce.pl bib === === reduce.pl bib === id = cord-016293-pyb00pt5 author = Newell-McGloughlin, Martina title = The flowering of the age of Biotechnology 1990–2000 date = 2006 pages = extension = .txt mime = text/plain words = 22402 sentences = 943 flesch = 47 summary = In the course of the project, especially in the early years, the plan stated that "much new technology will be developed that will facilitate biomedical and a broad range of biological research, bring down the cost of many experiments (mapping and sequencing), and finding applications in numerous other fields." The plan built upon the 1988 reports of the Office of Technology Assessment and the National Research Council on mapping and sequencing the human genome. These DNA chips have broad commercial applications and are now used in many areas of basic and clinical research including the detection of drug resistance mutations in infectious organisms, direct DNA sequence comparison of large segments of the human genome, the monitoring of multiple human genes for disease associated mutations, the quantitative and parallel measurement of mRNA expression for thousands of human genes, and the physical and genetic mapping of genomes. cache = ./cache/cord-016293-pyb00pt5.txt txt = ./txt/cord-016293-pyb00pt5.txt === reduce.pl bib === id = cord-014462-11ggaqf1 author = nan title = Abstracts of the Papers Presented in the XIX National Conference of Indian Virological Society, “Recent Trends in Viral Disease Problems and Management”, on 18–20 March, 2010, at S.V. University, Tirupati, Andhra Pradesh date = 2011-04-21 pages = extension = .txt mime = text/plain words = 35453 sentences = 1711 flesch = 49 summary = Molecular diagnosis based on reverse transcription (RT)-PCR s.a. one step or nested PCR, nucleic acid sequence based amplification (NASBA), or real time RT-PCR, has gradually replaced the virus isolation method as the new standard for the detection of dengue virus in acute phase serum samples. Non-genetic methods of management of these diseases include quarantine measures, eradication of infected plants and weed hosts, crop rotation, use of certified virus-free seed or planting stock and use of pesticides to control insect vector populations implicated in transmission of viruses. The results of this study indicate that NS1 antigen based ELISA test can be an useful tool to detect the dengue virus infection in patients during the early acute phase of disease since appearance of IgM antibodies usually occur after fifth day of the infection. The studies showed high level of expression in case of constructed vector as compared to infected virus for the specific protein. cache = ./cache/cord-014462-11ggaqf1.txt txt = ./txt/cord-014462-11ggaqf1.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-015684-q10sx1dm author = Cacabelos, Ramón title = Pharmacogenomic Biomarkers in Neuropsychiatry: The Path to Personalized Medicine in Mental Disorders date = 2009 pages = extension = .txt mime = text/plain words = 16968 sentences = 1033 flesch = 43 summary = With the advent of recent knowledge on the human genome 69,70 and the identifi cation and characterization of many genes associated with CNS disorders, 8, 19 as well as novel data regarding CYP family genes and other genes whose enzymatic products are responsible for drug metabolism in the liver (e.g., NATs, ABCBs/ MDRs, TPMT), it has been convincingly postulated that the incorporation of pharmacogenetic and pharmacogenomic procedures ( Fig. 40 .6) in drug development might bring about substantial benefi ts in terms of therapeutics optimization in CNS disorders and in many other complex disorders, assuming that genetic factors are determinant for both neuronal dysregulation (and/or neuronal death) 8,16-22 and drug metabolism. The natural course of technical events to achieve effi cient goals in pharmacogenetics and pharmacogenomics include the following steps: (a) genetic testing of mutant genes and/or polymorphic variants of risk; (b) genomic screening, and understanding of transcriptomic, proteomic, and metabolomic networks; (c) functional genomics studies and genotype-phenotype correlation analysis; and (d) pharmacogenetics and pharmacogenomics developments, addressing drug safety and effi cacy, respectively. cache = ./cache/cord-015684-q10sx1dm.txt txt = ./txt/cord-015684-q10sx1dm.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-017752-ofzm3x3a author = nan title = Theories of Carcinogenesis date = 2007 pages = extension = .txt mime = text/plain words = 12289 sentences = 692 flesch = 47 summary = Others attributed the simplified enzyme patterns of cancerous cells to a regression of the tumor tissues to early embryonal stages of development. Viral DNA is frequently integrated into the cancer cells, but additional agents or factors may be involved at various stages of the progression to invasive carcinoma. The encounter with a family, in which many members developed breast or liver cancer, led Pierre Paul Broca to hypothesize, in 1866, that an inherited abnormality within the affected tissue caused the tumor development [Broca 1866 Theodor Boveri (1862 Boveri ( -1915 then proposed that defects in chromosomes lead to malignancy [Boveri 1914 ]. Any mutation of cancer associated genes can be handed on to following generations and predispose the affected cells to malignant transformation in the case of additional DNA damage. Further developments in tumor immunology have led to models of selection and evolution of cancer cells. cache = ./cache/cord-017752-ofzm3x3a.txt txt = ./txt/cord-017752-ofzm3x3a.txt === reduce.pl bib === === reduce.pl bib === id = cord-016200-zfh20im0 author = Saxena, Jyoti title = Edible Vaccines date = 2013-10-22 pages = extension = .txt mime = text/plain words = 7627 sentences = 417 flesch = 51 summary = In 1998 a new era was opened in vaccine delivery when researchers supported by the National Institute of allergy and infectious diseases (NIAID) have shown for the first time that an edible vaccine can safely generate significant immune responses in people. Transgenic tobacco is successfully engineered for the production of edible vaccines against hepatitis B antigen using 's' gene of hepatitis B virus (HBV). Egyptian scientists have genetically engineered the maize plants to produce a protein known as HbsAg which elicits an immune response against the hepatitis B virus and could be used as a vaccine. It has been studied that genes are successfully expressed in experimental model plants and when given orally to animals, the extract of transgenic plant containing the antigen induced serum antibodies, thus can be used to produce the edible vaccine. cache = ./cache/cord-016200-zfh20im0.txt txt = ./txt/cord-016200-zfh20im0.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-004879-pgyzluwp author = nan title = Programmed cell death date = 1994 pages = extension = .txt mime = text/plain words = 81677 sentences = 4465 flesch = 51 summary = Furthermore kinetic experiments after complementation of HIV=RT p66 with KIV-RT pSl indicated that HIV-RT pSl can restore rate and extent of strand displacement activity by HIV-RT p66 compared to the HIV-RT heterodimer D66/D51, suggesting a function of the 51 kDa polypeptide, The mouse mammary tumor virus proviral DNA contains an open reading frame in the 3' long terminal repeat which can code for a 36 kDa polypeptide with a putative transmembrane sequence and five N-linked glycosylation sites. To this end we used constructs encoding the c-fos (and c-jun) genes fused to the hormone-binding domain of the human estrogen receptor, designated c-FosER (and c-JunER), We could show that short-term activation (30 mins.) of c-FosER by estradiole (E2) led to the disruption of epithelial cell polarity within 24 hours, as characterized by the expression of apical and basolateral marker proteins. cache = ./cache/cord-004879-pgyzluwp.txt txt = ./txt/cord-004879-pgyzluwp.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-016062-h4vjkufn author = Gontier, Nathalie title = Evolutionary epistemology and the origin and evolution of language: Taking symbiogenesis seriously date = 2006 pages = extension = .txt mime = text/plain words = 12419 sentences = 576 flesch = 49 summary = Given this minor role that natural selection plays within evolution, it is too short-sighted to only develop general normative frameworks based upon Neo-Darwinian theory to study all of life's phenomena. Again, we need to be more cautious with our definition: vertical evolution at the animal level implies that two members of the same species, of the opposite sexes, mate, and that during this mating process, one sex cell from each parent merges with the other to form a fertilized cell, from whereupon an embryo develops. Since it mostly only involves the passing on or recombining of existing genes, I prefer to call this a form of horizontal evolution contrary to regarding this as part of the process of individual variation that occurs because of vertical genetic recombinations without there actually being vertical evolution (because no species evolves or goes extinct). cache = ./cache/cord-016062-h4vjkufn.txt txt = ./txt/cord-016062-h4vjkufn.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-016313-n4ewq0pt author = Baranyi, Lajos title = Advances in Lentiviral Vector-based Cell Therapy with Mesenchymal Stem Cells date = 2012-09-27 pages = extension = .txt mime = text/plain words = 20575 sentences = 824 flesch = 39 summary = The field of possible application of mesenchymal stem cells in medicine and research expanded tremendously with the advent of improved Lentiviral-vectors capable of inserting stable copies of genes of interest and expressing proteins or biologically active RNA species ad libitum, performing delicate gene editing or active gene silencing or serving as advanced drug delivery systems utilized in ex vivo cell therapy. Implantation of Lentiviral vector-transduced human bone marrow mesenchymal cells using collagen scaffolds into immunode fi cient mice resulted in ef fi cient engraftment of gene-engineered cells and provided sites for transgene-expression in vivo. Moreover, it did not alter the differentiation potential of either HSCs or MSCs. In addition, the therapeutic potential of CD133+ and MSC progenitor cells transduced ex vivo with Lentiviral vector encoding the mature form of vascular endothelial growth factor D (VEGF-D ) or the enhanced green fl uorescent protein (eGFP) marker gene achieved permanent gene expression. cache = ./cache/cord-016313-n4ewq0pt.txt txt = ./txt/cord-016313-n4ewq0pt.txt === reduce.pl bib === === reduce.pl bib === id = cord-018647-bveks6t1 author = Butnariu, Monica title = Plant Nanobionics: Application of Nanobiosensors in Plant Biology date = 2019-10-01 pages = extension = .txt mime = text/plain words = 16812 sentences = 779 flesch = 40 summary = Chemical or biological NBS functions on the principle of signal emission (voltage or electrical, photonic) in response to a chemical reaction involve a chemical or biological receptor, R (macrocyclic ligand, antibody enzyme), that binds to a specific target molecule of a sample to be studied, the analyte, A. Analysis of signals in plant nanobionics aims at processing signals recorded by measurements in order to extract the maximum of useful information for diagnostics and These devices are mostly used in genetic engineering in agriculture, where it is necessary to know the mechanisms of reaction and the affinity of enzymes and microorganisms for different substrates of interest and signaling molecules. The reaction is monitored by an integrated detector (transducer) that measures the stationary or transition states or the final reaction product via the immobilized biocidal product in NBSs. Types of commonly used biocatalysts are enzymes (simple or enzymatic complexes)-most commonly used as recognition systems, cells, microorganisms (bacteria, fungi, eukaryotic cells, or yeasts), cellular organs, or component (cell walls, mitochondria) sections of plant or animal tissues. cache = ./cache/cord-018647-bveks6t1.txt txt = ./txt/cord-018647-bveks6t1.txt === reduce.pl bib === id = cord-024290-8z6us7v4 author = Allen, Edward E. title = Time Series Adjustment Enhancement of Hierarchical Modeling of Arabidopsis Thaliana Gene Interactions date = 2020-02-01 pages = extension = .txt mime = text/plain words = 3236 sentences = 209 flesch = 53 summary = Network models of gene interactions, using time course gene transcript abundance data, are computationally created using a genetic algorithm designed to incorporate hierarchical Bayesian methods with time series adjustments. Second, the addition of time series adjustment to improve the independence of the model's residuals gives these techniques stronger statistical foundations. In complicated modeling situations (e.g., like ours where we need to obtain closed form likelihoods of DAGs within a hierarchical structure in order to produce posterior probabilities of edges), it is common to derive results as if there were non-correlated residuals, as we have done in previous work. The use of the time series adjusted next state Norris-Patton likelihood, along with a tailor-made genetic algorithm and Bayesian model averaging, allows for the rigorous estimation of posterior probabilities for all gene pair interactions. Using the transcript abundance data for 26 Arabidopsis thaliana genes stimulated by ACC, gene interaction models for a next state with and without time series adjustment were computationally created, shown in Fig. 3 . cache = ./cache/cord-024290-8z6us7v4.txt txt = ./txt/cord-024290-8z6us7v4.txt === reduce.pl bib === id = cord-103505-9adtbwp2 author = Hale, A. T. title = The genetic architecture of human infectious diseases and pathogen-induced cellular phenotypes date = 2020-07-21 pages = extension = .txt mime = text/plain words = 1408 sentences = 105 flesch = 41 summary = Host genetic variation is likely to contribute to ID risk and downstream clinical outcomes, but there is a need for a genetics-anchored framework to decipher molecular mechanisms of disease risk, infer causal effect on potential complications, and identify instruments for drug target discovery. The rich resource of genetic information linked to serologic tests and pathogen cultures from bronchoalveolar lavage, sputum, sinus/nasopharyngeal, tracheal, and blood samples (up to 7,699 positive pathogen cultures across 92 unique genera) that we leverage provides a platform to interrogate the genetic basis of compartment-specific infection and colonization. To accelerate insights into cellular mechanisms, we develop a TWAS repository of gene-level associations in a broad collection of human tissues with 79 pathogen-exposure induced cellular phenotypes as a discovery and replication platform. We hypothesized that tissue expression profiling of ID-associated genes 216 can provide additional insights into disease etiologies and mechanisms. These data identify specific molecular mechanisms across ID traits with critical 239 regulatory roles (e.g., protein modifications) in host response among the ID-associated genes. cache = ./cache/cord-103505-9adtbwp2.txt txt = ./txt/cord-103505-9adtbwp2.txt === reduce.pl bib === id = cord-019050-a9datsoo author = Ambrogi, Federico title = Bioinformatics and Nanotechnologies: Nanomedicine date = 2014 pages = extension = .txt mime = text/plain words = 8851 sentences = 367 flesch = 31 summary = In this chapter we focus on the bioinformatics strategies for translating genome-wide expression analyses into clinically useful cancer markers with a specific focus on breast cancer with a perspective on new diagnostic device tools coming from the field of nanobiotechnology and the challenges related to high-throughput data integration, analysis, and assessment from multiple sources. In this chapter we focus on the bioinformatics strategies for translating genome-wide expression analyses into clinically useful cancer markers with a specific focus on breast cancer with a perspective on new diagnostic device tools coming from the field of nanobiotechnology and the challenges related to high-throughput data integration, analysis, and assessment from multiple sources. In particular, DNA microarray-based technology, with the simultaneous evaluation of thousands of genes, has provided researchers with an opportunity to perform comprehensive molecular and genetic profiling of breast cancer able to classify it into some clinically relevant subtypes and in the attempt to predict the prognosis or the response to treatment [32.5-8]. cache = ./cache/cord-019050-a9datsoo.txt txt = ./txt/cord-019050-a9datsoo.txt === reduce.pl bib === id = cord-252781-06hs9pit author = Lai, Wing-Fu title = Cyclodextrins in non-viral gene delivery date = 2013-10-05 pages = extension = .txt mime = text/plain words = 6592 sentences = 357 flesch = 44 summary = CDs have practical potential in gene delivery, but due to their failure to form stable complexes with plasmid DNA (pDNA) [40] , native CDs have limited transfection efficiency. Luciferase activity assays in K562 leukemia cells found that the transfection efficiency of the nanoparticles surface-modified with transferrin-PEG-AD conjugates was 4-fold higher than that of the unmodified counterparts [57] . In HEK293 cells, the polyrotaxanes fabricated showed higher transfection efficiency than PEI 25 kDa [58] , and deserve further evaluation as gene carriers for both in vitro and in vivo applications. The polymer showed more than 1-fold higher transfection efficiency, but lower cytotoxicity, than the PAMAM control (G4, with an ethylenediamine core) in human neuroblastoma SH-SY5Y cells. Efficient gene transfection in the neurotypic cells by star-shaped polymer consisting of b-cyclodextrin core and poly(amidoamine) dendron arms Enhancing effects of galactosylated dendrimer/a-cyclodextrin conjugates on gene transfer efficiency cache = ./cache/cord-252781-06hs9pit.txt txt = ./txt/cord-252781-06hs9pit.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-009664-kb9fnbgy author = nan title = Oral presentations date = 2014-12-24 pages = extension = .txt mime = text/plain words = 71112 sentences = 3948 flesch = 47 summary = Because of the conflicting reports and lack of published data from paediatric patients, we sought to assess possible MIC change over time and to compare results generated by using different methodologies including Etest, agar dilution, and broth microdilution (MicroScan) methods. Recently, in vitro and in vivo studies have shown that NO plays a key role in the eradication of the leishmania parasite Objective: To determine whether a NO donor patch (developed by electrospinning technique) is as effective as meglumine antimoniate in the treatment of CL while causing less adverse events Methods: A double-blind, randomised, placebo-controlled clinical trial was conducted with 178 patients diagnosed with CL in Santander, Colombia, South-America. To follow the development and spread of the resistance among these strains is difficult, as antibiotic susceptibility testing of clinically relevant anaerobes in different routine laboratories in Europe is less and less frequently carried out due to the fact, that clinicians treat many presumed anaerobic infections empirically. cache = ./cache/cord-009664-kb9fnbgy.txt txt = ./txt/cord-009664-kb9fnbgy.txt === reduce.pl bib === id = cord-020969-lh2ergpm author = STRAUSS, JAMES H. title = Gene Therapy date = 2012-07-27 pages = extension = .txt mime = text/plain words = 11793 sentences = 597 flesch = 52 summary = Together with methods for cloning and manipulating viral genomes, this information has made possible the use of viruses as vectors to express foreign genes. The use of minus-strand RNA viruses as vectors was delayed because the virion RNA itself is not infectious, but recent developments has made it possible to rescue virus from cloned DNA by using coexpression of the appropriate viral proteins in a transfected cell. It is also possible to transfect cells with the E1 or E3 expression cassette together with DNA clones encoding the rest of the adenovirus genome, in which case homologous recombination results in the production of virus. Because the poliovirus replicon lacks a full complement of the structural genes (it is a suicide vector), packaging to produce particles requires infection of a cell that expresses the polioviral structural proteins by some mechanism. cache = ./cache/cord-020969-lh2ergpm.txt txt = ./txt/cord-020969-lh2ergpm.txt === reduce.pl bib === === reduce.pl bib === id = cord-103465-6udhvl9n author = Schierding, William title = Low tolerance for transcriptional variation at cohesin genes is accompanied by functional links to disease-relevant pathways date = 2020-04-13 pages = extension = .txt mime = text/plain words = 6450 sentences = 323 flesch = 41 summary = Results 140 genetic variants with regulatory potential are associated with cohesin loci Mitotic cohesin genes (SMC1A, SMC3, STAG1, STAG2, and RAD21), meiotic cohesin genes (SMC1B, STAG3, REC8, and RAD21L1), cohesin support genes (WAPL, NIPBL, PDS5A, PDS5B, and MAU2) and CTCF were investigated to determine if they contain non-coding genetic variants (SNPs) that make contact in 3D with genes and therefore could directly affect gene expression (GWAS-attributed and eQTL-attributed; Table 1, Table S1 ). Intriguingly, Haploreg motif prediction identified 16 of the 209 variants (7 different loci: MAU2, PDS5B, REC8, SMC1B, STAG3, RAD21L1, STAG1) as residing within protein binding domains associated with cohesin-related DNA interactions (i.e. RAD21, SMC3, and CTCF). Pathway enrichment implicates coordinated regulation of cohesin with essential cell cycle genes CoDeS3D identified 140 variants as being physically connected to, and associated with the expression levels of 310 genes (243 genes from eQTL-attributed variants, 141 from GWAS-attributed variants, and 74 overlap) across 6,795 significant tissue-specific regulatory connections (FDR p<0.05). cache = ./cache/cord-103465-6udhvl9n.txt txt = ./txt/cord-103465-6udhvl9n.txt === reduce.pl bib === id = cord-018798-yzxy9ogf author = Jain, Pradeep Kumar title = RNAi for Resistance Against Biotic Stresses in Crop Plants date = 2018-07-10 pages = extension = .txt mime = text/plain words = 12555 sentences = 711 flesch = 47 summary = This chapter also reviews the rich history of RNAi research, gene regulation by small RNAs across different organisms, and application potential of RNAi for generating transgenic plants resistant to major pests(.) But, there are some limitations too which restrict wider applications of this technology to its full potential. Different delivery methods of dsRNA that have been used for successful RNAi in insects and nematodes include microinjection, feeding on either artificial diet (Table 4 .2), and/or host-mediated delivery through transgenic plants (Fig. 4.1) . RNAi mechanism partly occurs in the host itself and partly in nematodes feeding on the transgenic host plant expressing dsRNA for the target gene. despite the absence of Sid-1 and Sid-2 genes exhibit systemic RNAi when subjected to silencing technology indicating a presence of similar receptor-mediated endocytic process for dsRNA uptake as reported in insects ). cache = ./cache/cord-018798-yzxy9ogf.txt txt = ./txt/cord-018798-yzxy9ogf.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-104073-vsa5y7ip author = Warner, Emily F. title = Cross kingdom analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets to ameliorate fungal pathogenicity? date = 2020-09-23 pages = extension = .txt mime = text/plain words = 3218 sentences = 207 flesch = 54 summary = PQS in the clinically important pathogens Aspergillus fumigatus, Cryptococcus neoformans, and Candida albicans were located within genes (particularly coding regions), mRNA, repeat regions, mobile elements, tRNA, ncRNA, rRNA, and the centromere. Finally, PQS were found in over 100 genes associated with virulence, drug resistance, or key biological processes in these pathogenic fungi and were found in genes which were highly upregulated during germination, hypoxia, oxidative stress, iron limitation, and in biofilms. Using a computational approach, we identified putative quadruplex-forming 30 sequences (PQS) in 1362 genomes across the fungal kingdom and explored their potential 31 involvement in virulence, drug resistance, and pathogenicity. Using a computational approach, we identified putative quadruplex-forming 30 sequences (PQS) in 1362 genomes across the fungal kingdom and explored their potential 31 involvement in virulence, drug resistance, and pathogenicity. PQS in the 35 clinically important pathogens Aspergillus fumigatus, Cryptococcus neoformans, and Candida 36 albicans were located within genes (particularly coding regions), mRNA, repeat regions, 37 cache = ./cache/cord-104073-vsa5y7ip.txt txt = ./txt/cord-104073-vsa5y7ip.txt === reduce.pl bib === === reduce.pl bib === id = cord-020101-5rib7pe8 author = nan title = Cumulative Author Index for 2008 date = 2008-11-17 pages = extension = .txt mime = text/plain words = 2140 sentences = 126 flesch = 29 summary = Cauliflower mosaic virus gene VI product N-terminus contains regions involved in resistance-breakage, self-association and interactions with movement protein Intrahost evolution of envelope glycoprotein and OrfA sequences after experimental infection of cats with a molecular clone and a biological isolate of feline immunodeficiency virus DC-SIGN enhances infection of cells with glycosylated West Nile virus in vitro and virus replication in human dendritic cells induces production of Increase in proto-oncogene mRNA transcript levels in bovine lymphoid cells infected with a cytopathic type 2 bovine viral diarrhea virus Complete genome sequence analysis of dengue virus type 2 isolated in Modulation of hepatitis B virus replication by expression of polymerasesurface fusion protein through splicing: Implications for viral persistence Induction of apoptosis in Vero cells by Newcastle disease virus requires viral replication, de-novo protein synthesis and caspase activation Mechanisms of inhibition of HIV replication by non-nucleoside reverse transcriptase inhibitors cache = ./cache/cord-020101-5rib7pe8.txt txt = ./txt/cord-020101-5rib7pe8.txt === reduce.pl bib === === reduce.pl bib === id = cord-022226-qxp0gfp3 author = Meager, Anthony title = Interferons Alpha, Beta, and Omega date = 2007-09-02 pages = extension = .txt mime = text/plain words = 16375 sentences = 813 flesch = 46 summary = PRDI and PRDIII act as binding sites for a nuclear transcription factor, designated "interferon regulatory factor-l" (IRF-1) , whose expression is transiently increased by virus infection and which appears to mediate the activation of transcription of the IFNB gene (Fujita et al., 1988; Harada et al., 1989; Xanthoudakis et al., 1989) . For example, the IFN-inducible Mx proteins block the replication of influenza virus, probably by inhibiting the nuclear phase of viral transcription (mouse cells) or later cytoplasmic phases (human cells), without affecting the replication of many other viruses (Staeheli, 1990; Mel6n et al., 1992; Ronni et al., 1993) . A number of other negative regulatory factors, including IRF2 (Harada et al., 1989) and the ISGF2 (IRF1)/ISGF3yrelated "human interferon consensus sequence binding protein" (ICSBP) (Weisz et al., 1992; Bovolenta et al., 1994) , which also bind to ISRE, are also probably involved in the regulation of transcription of IFN-inducible genes. cache = ./cache/cord-022226-qxp0gfp3.txt txt = ./txt/cord-022226-qxp0gfp3.txt === reduce.pl bib === === reduce.pl bib === id = cord-016713-pw4f8asc author = Goyal, Amit K. title = Nanotechnological Approaches for Genetic Immunization date = 2013-05-24 pages = extension = .txt mime = text/plain words = 16034 sentences = 814 flesch = 34 summary = The use of nonviral particulate carriers for DNA-based vaccination could provide better and safe delivery of encapsulated genetic material, circumvent the need for muscle involvement and facilitate instead the uptake of the Fig. 4 Schematic representation of immunological response greeted by novel DNA-loaded nanocarrier DNA by APCs. However, transfection of APCs with encapsulated DNA into particulate carrier systems will be dependent upon choice of carrier surface charge, size, and lipid/polymer composition, or presence of other biological [e.g., interleukin 2 and interferon-γ (IFN-γ)]. Modification of lipid/DNA complexes by the polymer poly(D,L-lactic acid) was found to be consistently and significantly more effective than either unmodified liposomal DNA or naked DNA in eliciting transgene-specific immune responses to plasmid-encoded antigen when administered by the s.c. route (Bramwell et al. cache = ./cache/cord-016713-pw4f8asc.txt txt = ./txt/cord-016713-pw4f8asc.txt === reduce.pl bib === id = cord-023055-ntbvmssh author = nan title = Immunogenicity date = 2004-02-19 pages = extension = .txt mime = text/plain words = 64563 sentences = 3952 flesch = 59 summary = Antigen is internalized into acidic vesicles, proteolyzed, and peptides containing T ceU antigenic determinants are transported to the APC surface where they are recognized by the antigen-specific T cell in conjunction with Ia. Most Ia-"pressing cells are competent APC, however, only B cells have antigen-specilic receptors on their surface aUowing bound antigen to be processed and presented at 1/lW the antigen concentration required by nonspecific APC Little is known about B cell antigen processing function during differentiation, or if Ig-mediated APC function is altered at different maturational stages, thus allowing regulation of B cell-helper T cell interactions. These results indicate that the poor response of murine CTL to human class I antigens is not determined by selection in the thymus, but by species-specific constraints on the interaction of MHC antigens with T-cell recognition structures. cache = ./cache/cord-023055-ntbvmssh.txt txt = ./txt/cord-023055-ntbvmssh.txt === reduce.pl bib === id = cord-266521-vovas81d author = Yokobayashi, Yohei title = Aptamer-based and aptazyme-based riboswitches in mammalian cells date = 2019-06-22 pages = extension = .txt mime = text/plain words = 3228 sentences = 155 flesch = 43 summary = In this report, recent advances in synthetic riboswitches that function in mammalian cells are reviewed focusing on the regulatory mechanisms they exploit such as mRNA degradation, microRNA processing, and programmed ribosomal frameshifting. In this report, recent advances in synthetic riboswitches that function in mammalian cells are reviewed focusing on the regulatory mechanisms they exploit such as mRNA degradation, microRNA processing, and programmed ribosomal frameshifting. While the ribozyme was not specifically regulated by a small molecule via an aptamer, this work paved the way for the subsequent riboswitches that employ allosterically regulated ribozymes (aptazymes) embedded in the 5 0 and/or 3 0 UTR to chemically regulate gene expression in mammalian cells (Figure 1a ) [13] [14] [15] [16] . A new mode of engineered RNA-based gene regulation in mammalian cells was demonstrated by controlling the accessibility of a miRNA target site by aptamer-ligand interaction cache = ./cache/cord-266521-vovas81d.txt txt = ./txt/cord-266521-vovas81d.txt === reduce.pl bib === === reduce.pl bib === id = cord-014597-66vd2mdu author = nan title = Abstracts from the 25th European Society for Animal Cell Technology Meeting: Cell Technologies for Innovative Therapies: Lausanne, Switzerland. 14-17 May 2017 date = 2018-03-15 pages = extension = .txt mime = text/plain words = 50613 sentences = 2624 flesch = 46 summary = Irrespective of the cell culture-based system and production scale, PEIpro® and PEIpro®-HQ have led to efficient viral vector yields superior to 10 7 IG/mL and 10 9 VG/mL, respectively for lentiviruses and AAVs Background Continuous perfusion process is making a comeback as a competing upstream manufacturing technology for the production of Biopharmaceuticals compared to the standard fed batch processes. To evaluate the impact of feed-spiking compared with cultivation in basal medium only, the cell line was grown in bioreactors under controlled conditions to determine cellspecific metabolic rates, nutrient consumption, and byproduct accumulation over the process time. Through the interchangeability of signal peptides between products and even species, a large variety can be used to enhance protein expression in already existing production systems Materials and methods At first the influence of four different natural SPs (SP (7), (8), (9) and (10)) was compared on the secreted amount of an IgG4 model antibody (product A) in fed batches using a CHO DG44 host cell line. cache = ./cache/cord-014597-66vd2mdu.txt txt = ./txt/cord-014597-66vd2mdu.txt === reduce.pl bib === id = cord-272378-umvi0veu author = Subramanian, Subbaya title = Special Issue: MicroRNA Regulation in Health and Disease date = 2019-06-15 pages = extension = .txt mime = text/plain words = 2126 sentences = 120 flesch = 47 summary = MicroRNAs are single-stranded non-coding RNAs that are typically 18-25 nucleotides (nts) in length and are best known for their role in the post-transcriptional regulation of gene expression. However, it is possible that the frequency of MREs in the entire transcriptome of a given cell contributes to the dynamic gene regulatory process by acting as a sponge for mature miRNAs, thus regulating their functional availability. Thus, gene expression regulation is a complex process involving the dynamic interactions between miRNA-mRNA-lncRNA-circRNA. This Special Issue of Genes, entitled "MicroRNA Regulation in Health and Disease" consists of a series of articles spanning the clinical realm from colorectal cancer to pulmonary fibrosis. Somatostatin (SST) analogues were used to control the proliferation and symptoms of neuroendocrine tumors (NETs) in an article by Døssing et al., entitled "Somatostatin Analogue Treatment Primarily Induce miRNA Expression Changes and Up-Regulates Growth Inhibitory miR-7 and miR-148a in Neuroendocrine Cells" [15] . cache = ./cache/cord-272378-umvi0veu.txt txt = ./txt/cord-272378-umvi0veu.txt === reduce.pl bib === id = cord-252147-bvtchcbt author = Domingo-Espín, Joan title = Engineered Biological Entities for Drug Delivery and Gene Therapy: Protein Nanoparticles date = 2011-11-15 pages = extension = .txt mime = text/plain words = 17193 sentences = 888 flesch = 39 summary = Modular protein engineering, virus-like particles (VLPs), and other self-assembling entities are envisioned as modulatable novel protein nanoparticles able to include many desirable properties in the correct delivery of drugs and nucleic acids. 120 Modular fusion proteins that combine distinct functions required for cell type-specific uptake and intracellular delivery of DNA or drugs present an attractive approach for the development of self-assembling vectors for targeted gene or drug delivery. 215, 216 Although VLP-based vaccines have been primarily developed for their use against the corresponding virus, in the last decades genetic engineering or chemical modifications have been applied in order to generate chimeric VLPs. Thus, on the one hand, commonly short heterologous peptide epitopes or full proteins that are unable to form VLPs or that are unsafe for vaccination have been presented on surface-exposed loops or fused to N-or C-exposed termini of structural viral capsid proteins on VLPs. 154, 161, 210 Different HPV, 217-219 HBV, 220,221 parvovirus, 222, 223 and chimeric polyoma VLPs have been engineered 170, 175 and tested for different applications including vaccination against viral or bacterial diseases, against virus-induced tumors, and more recently, for immunotherapy of nonviral cancer. cache = ./cache/cord-252147-bvtchcbt.txt txt = ./txt/cord-252147-bvtchcbt.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-258035-2tk7maqk author = DeFilippis, Victor title = Functional genomics in virology and antiviral drug discovery date = 2003-10-31 pages = extension = .txt mime = text/plain words = 4769 sentences = 255 flesch = 39 summary = Given that virus replication involves use and manipulation of multiple host proteins and molecular processes, cellular pathways related to transcription and translation, signal transduction, metabolism, host defense and cell cycle control are Review commonly altered in response to, or as a result of, infection with diverse virus types. A special case of virus modulation of host cell gene expression in which functional genomics will reveal novel targets and treatments is viral oncogenesis. The most recent method for analyzing gene inhibition studies has been RNAi or siRNA, where small 21 -23-nucleotide (nt) RNA duplexes interfere with the transcription program by directing degradation of homologous mRNA [34] [35] [36] [37] . Both new-generation antisense oligomers and siRNA can be used to knockdown expression of genes that were found by DNA microarrays to be upregulated in virally infected cells or organisms. RNA interference directed against viral and cellular targets inhibits human immunodeficiency virus type 1 replication cache = ./cache/cord-258035-2tk7maqk.txt txt = ./txt/cord-258035-2tk7maqk.txt === reduce.pl bib === id = cord-267475-6f4h3cck author = Kozak, Marilyn title = Pushing the limits of the scanning mechanism for initiation of translation date = 2002-10-16 pages = extension = .txt mime = text/plain words = 24538 sentences = 1234 flesch = 50 summary = This depends on careful structural arrangements, however, which are rarely present in cellular mRNAs. Understanding the rules for initiation of translation enables understanding of human diseases in which the expression of a critical gene is reduced by mutations that add upstream AUG codons or change the context around the AUG(START) codon. (Whether the second AUG codon resides in a strong or weak context is not relevant; the ribosome reads the mRNA linearly and thus the decision to stop or to bypass the first AUG is not influenced by whether there is a better initiation site downstream.) The large number of genes that employ leaky scanning precludes discussion of the biological significance of the proteins thereby produced, but it merits noting that, for many of the viruses in Table 3 , replication requires production of both listed proteins. cache = ./cache/cord-267475-6f4h3cck.txt txt = ./txt/cord-267475-6f4h3cck.txt === reduce.pl bib === id = cord-264746-gfn312aa author = Muse, Spencer title = GENOMICS AND BIOINFORMATICS date = 2012-03-29 pages = extension = .txt mime = text/plain words = 10976 sentences = 583 flesch = 58 summary = The success of this project (it came in almost 3 years ahead of time and 10% under budget, while at the same time providing more data than originally planned) depended on innovations in a variety of areas: breakthroughs in basic molecular biology to allow manipulation of DNA and other compounds; improved engineering and manufacturing technology to produce equipment for reading the sequences of DNA; advances in robotics and laboratory automation; development of statistical methods to interpret data from sequencing projects; and the creation of specialized computing hardware and software systems to circumvent massive computational barriers that faced genome scientists. Although the list of important biotechnologies changes on an almost daily basis, there are three prominent data types in today's environment: (1) genome sequences provide the starting point that allows scientists to begin understanding the genetic underpinnings of an organism; (2) measurements of gene expression levels facilitate studies of gene regulation, which, among other things, help us to understand how an organism's genome interacts with its environment; and (3) genetic polymorphisms are variations from individual to individual within species, and understanding how these variations correlate with phenotypes such as disease susceptibility is a crucial element of modern biomedical research. cache = ./cache/cord-264746-gfn312aa.txt txt = ./txt/cord-264746-gfn312aa.txt === reduce.pl bib === id = cord-017208-7oew461e author = Aurigemma, Rosemarie title = Regulatory Aspects in the Development of Gene Therapies date = 2005 pages = extension = .txt mime = text/plain words = 18290 sentences = 816 flesch = 37 summary = Table 1 Beyond a Good Idea: What the Successful Investigator Has Already Done With a Project Leading to Commercial Development Defined candidate biologic (or molecule) Made comparisons with similar products Characteristics of product are consistent with pharmaceutical requirements Production scale is adequate Product characterization is adequate Laboratory reference standard exists In vitro potency assay has been developed Stability studies develop confidence product is a "drug" Reproducible model systems have confirmed in vivo activity with clinical product Early animal work includes some toxicology Scale-up requirements practical for initial clinical trials In general, reflects experience and scientific maturity of investigator In addition to the US agencies that develop the regulations that govern drug development and licensing, the International Conference on Harmonization (ICH) was formed in April 1990 involving the United States, the European Union, and Japan to address the issue of globalizing such regulations. cache = ./cache/cord-017208-7oew461e.txt txt = ./txt/cord-017208-7oew461e.txt === reduce.pl bib === id = cord-263470-vmqvropy author = Rukavtsova, E. B. title = Tissue specific expression of hepatitis B virus surface antigen in transgenic plant cells and tissue culture date = 2007 pages = extension = .txt mime = text/plain words = 2902 sentences = 170 flesch = 56 summary = The level of HBs-antigen in plants carrying the HBsAg gene controlled by (Aocs)(3)AmasPmas, the hybrid agrobacterium-derived promoter, was the highest in roots and made up to 0.01% of total amount of soluble protein. Earlier we have obtained the tobacco plants expressing the synthetic gene of the hepatitis B surface antigen ( HBsAg ) controlled by single and dual 35S RNA cauliflower mosaic virus promoters (CaMV 35S and CaMV 35SS, respectively) [10, 11] . The objective of this study was to obtain transgenic tobacco plants synthesizing the hepatitis B surface antigen controlled by ( Aocs ) 3 AmasPmas promoters and regulated by the elements of agrobacterial octopine synthase and mannopine synthase genes and also to analyze the expression profile of the HBsAg gene in different cells of the whole plant as well as that in callus and hairy root tissue cultures. cache = ./cache/cord-263470-vmqvropy.txt txt = ./txt/cord-263470-vmqvropy.txt === reduce.pl bib === id = cord-273609-whm2ce4u author = Li, Qingdi Quentin title = Evaluation of reference genes for real-time quantitative PCR studies in Candida glabrata following azole treatment date = 2012-06-29 pages = extension = .txt mime = text/plain words = 8166 sentences = 373 flesch = 47 summary = title: Evaluation of reference genes for real-time quantitative PCR studies in Candida glabrata following azole treatment BACKGROUND: The selection of stable and suitable reference genes for real-time quantitative PCR (RT-qPCR) is a crucial prerequisite for reliable gene expression analysis under different experimental conditions. The most commonly used reference genes, including β-actin, cyclophilin, GAPDH, tubulin, and 18S and 28S ribosomal RNAs, have shown variable expression levels in different cells and tissues under different conditions, and therefore they are unsuitable for normalization purposes owing to large measurement error [6, . As seen in Table 7 , normalization of the RT-qPCR data against the reference genes suggested as optimal by the four software packages (hkgFinder, geNorm, BestKeeper, and NormFinder) or the 2 -ΔΔCT method, gave comparable relative expression levels of the target genes under fluconazole treatment in C. cache = ./cache/cord-273609-whm2ce4u.txt txt = ./txt/cord-273609-whm2ce4u.txt === reduce.pl bib === id = cord-260496-s2ba7uy3 author = Moncany, Maurice L.J. title = Identification of conserved lentiviral sequences as landmarks of genomic flexibility date = 2006-08-08 pages = extension = .txt mime = text/plain words = 5991 sentences = 296 flesch = 51 summary = Comparison of entire genomes, including 237 human, simian and non-primate mammal lentiviruses and 103 negative control viruses, led to identify 28 Conserved Lentiviral Sequences (CLSs). Immunodeficiency lentiviral genomes correspond to 171 human viruses (155 HIV-1s and 16 HIV-2s), 33 simian viruses (3 CPZ, 9 AGM, 8 Macaque, 2 Mandrill, 10 Sooty Mangabey, 1 Sykes' monkey viruses) and 33 non-primate mammal viruses (2 bovine, 2 caprine, 11 equine, 9 feline, 3 ovine and 6 ovine/caprine viruses). From the particular organization of the HIV-1 and HIV-2 ( Fig. 1) , AGM and macaque (Fig. 2) , CPZ, feline, equine and D-particle-forming viruses (Fig. 3) and that of sooty mangabey, mandrill and other non-primate lentiviruses (supplementary data), it appears that a given CLS occupied on the viral genome a specific position that was roughly conserved in the different viral families. cache = ./cache/cord-260496-s2ba7uy3.txt txt = ./txt/cord-260496-s2ba7uy3.txt === reduce.pl bib === id = cord-279781-5ldpz9m9 author = Chen, Chi-Yuan title = Baculovirus as a gene delivery vector: Recent understandings of molecular alterations in transduced cells and latest applications date = 2011-04-28 pages = extension = .txt mime = text/plain words = 13111 sentences = 665 flesch = 38 summary = Concurrent with the aforementioned findings, we also discovered that baculovirus transduction of human BMSCs disturbed the expression of 816 genes, most of which were related to 5 signaling pathways: cell adhesion molecules, TLR, Jak-STAT, apoptosis as well as antigen processing and presentation (Chen et al., 2009b) . immunization of chickens with another VSVG-pseudotyped baculovirus expressing HA of H5N1 avian influenza virus (AIV) also evoked significantly higher levels of H5-specific antibody and cellular immunity than those receiving DNA vaccines, and conferred protection against lethal challenge with the homologous virus strain (Wu et al., 2009b) . Transient and stable gene expression in mammalian cells transduced with a recombinant baculovirus vector Baculovirus as a highly efficient gene delivery vector for the expression of hepatitis delta virus antigens in mammalian cells cache = ./cache/cord-279781-5ldpz9m9.txt txt = ./txt/cord-279781-5ldpz9m9.txt === reduce.pl bib === id = cord-260345-ugd8kkor author = Giles, Ian G. title = A compendium of reviews in biochemistry and molecular biology published in the first half of 1992 date = 1992-12-31 pages = extension = .txt mime = text/plain words = 5327 sentences = 701 flesch = 45 summary = 203, sodium dodecyl-sulfate.; ted blood-cells; phosphoenolpyruvate carboxylase activity; nucleotide-linked dehydrogenases; alkaline-phosphatase isoenzymes; pathogenesis-related proteins; cr-L-fucosidase; polyactylamide-gel; produce phosphate; general-method. low-density~l&protein; high-performance liquid; chrcmatogmphy mass spectmmetry; chicken vitellogam gene; thin-layer chmmatography; apolipoprotein-VLDL-II; fatty-acid composition; laying turkey hens; egg-yolk; plasma-lipoproteins. human-skin fibroblests; IGF binding-protein; messenger ribonucleic-acid; cooh-teminal truncation; monoclonal-antibody; endothelial-cells; factor receptoc amniotic-fluid; DNA-synthesis; rat-heart. factor-binding-protein; erythroid colony formation; cultured human-tibroblasts; factor messenger-RNA, N-terminal sequence; fetal bovine serum; IGF-I; somatomedin C, clinical-applicstians; stimulating factors. shon-hved protein; dependent pmteolytic system; ubiquitin-conjugating enzyme; repair gene ra&, Escherichia coli; transfer RNA; Sacclurroqces cercvisiue; endoplasmic-reticulum; cell-cycle; amino-acid. polymense chain-reaction; fragment length polymorphisms; dependent diabetes-mellitus; sickle-cell anemia; factor-M gene; enzymatic AMPlificatiat; genomic DNA; mutations; sequence; diagnosis; predisposition; genetics. T-cell receptor; messenger-RNA degradation; gamma-delta; stress proteins; antigen-receptor, lymphocytes-T; ~ycobactcrium fuberc&arir. Wiskott-Aldrich syndrome; heat-shock proteins; receptor-delta; ataxia telangiectasia; transgenic mice; lymphocytes T; bearing cells; recognition; expression; incmase. human granulocyte-macmphage; protein kinase-c; recombinant human interleukin-3; cell growth-factor, murine bone-marrow; express functional receptors; acute lymphocytic-leukemia; GTPase-activating pm&n; factor-independent growth. cache = ./cache/cord-260345-ugd8kkor.txt txt = ./txt/cord-260345-ugd8kkor.txt === reduce.pl bib === id = cord-284933-flbibrcm author = Kim, Jong-Oh title = Characterization of the Transcriptome and Gene Expression of Brain Tissue in Sevenband Grouper (Hyporthodus septemfasciatus) in Response to NNV Infection date = 2017-01-13 pages = extension = .txt mime = text/plain words = 4259 sentences = 266 flesch = 54 summary = title: Characterization of the Transcriptome and Gene Expression of Brain Tissue in Sevenband Grouper (Hyporthodus septemfasciatus) in Response to NNV Infection Ubiquitin-like protein 4a (UBL4a), C-C motif chemokine 2 (CCL2), lysozyme g (LYG_EPICO) and two novel genes (ID: SGU016297, SGU008676) were highly expressed in the NNV-infected group compared to that in the mock group. In this study, we performed a transcriptome analysis of the brain tissue of sevenband grouper infected with NNV compared to mock brain tissue using a RNA-Seq. The total number of unigenes and the average length of the unigenes were 104,348 and 845 bp, respectively. In this study, we performed a transcriptome analysis of the brain tissue of sevenband grouper infected with NNV compared to mock brain tissue using a RNA-Seq. The total number of unigenes and the average length of the unigenes were 104,348 and 845 bp, respectively. In this study, we identified innate immune response relevant genes of sevenband grouper involved in NNV infection. cache = ./cache/cord-284933-flbibrcm.txt txt = ./txt/cord-284933-flbibrcm.txt === reduce.pl bib === id = cord-264884-ydkigome author = Villarreal, Luis P. title = The Widespread Evolutionary Significance of Viruses date = 2008-07-05 pages = extension = .txt mime = text/plain words = 23138 sentences = 1203 flesch = 47 summary = For example, common structural motifs from phage to eukaryotic DNA viruses (T4 and herpesvirus) suggest very ancient links in virus evolution that span all domains of life (see below). On an evolutionary time-scale, the majority of viral lineages tend to exist as species-specifi c persistent (aka temperate, latent, and chronic) infections in which individual hosts will be colonized by mostly silent (asymptomatic) viruses for the duration of their life . It has distinct genetic, fi tness, and evolutionary characteristics that require intimate, host (tissue)-specifi c viral strategies and precise gene functions to attain stable maintenance in the presence of immunity and to allow biologically controlled reactivation. Thus, the phycodnaviruses appear to represent a basal but diverse viral lineage that has both acute and persistent lifestyle and have some clear relationships to most large eukaryotic DNA viruses and many phage. cache = ./cache/cord-264884-ydkigome.txt txt = ./txt/cord-264884-ydkigome.txt === reduce.pl bib === id = cord-267733-fuz8r3vj author = Al Ali, Sally title = Use of Reporter Genes in the Generation of Vaccinia Virus-Derived Vectors date = 2016-05-21 pages = extension = .txt mime = text/plain words = 7966 sentences = 392 flesch = 41 summary = This broad host range allows infection of cell lines with recombinant viruses for large-scale expression of heterologous proteins, which reduces its cost This broad host range allows infection of cell lines with recombinant viruses for large-scale expression of heterologous proteins, which reduces its cost in comparison to other production systems [21, 24] . This reporter gene system has been widely used in transgenic plants, and it has also been successfully used in mammalian cells for VACV recombinant virus selection [54] . Reporter-gene assays have helped the pox virologists in basic research, for example for the study of the location, structure and function of many VACV proteins during the infection cycle and their interaction with proteins of the host cell [44, 70] . The main limitation of using VACV as a vector is the short-term gene expression, since it is a lytic virus killing the infected cells. Insertion sites for recombinant vaccinia virus construction: Effects on expression of a foreign protein cache = ./cache/cord-267733-fuz8r3vj.txt txt = ./txt/cord-267733-fuz8r3vj.txt === reduce.pl bib === id = cord-028721-x6f26ahr author = Nistal, Manuel title = Non-neoplastic diseases of the testis date = 2020-06-22 pages = extension = .txt mime = text/plain words = 78172 sentences = 5138 flesch = 41 summary = Congenital decrease of germ cells occurs in numerous conditions, including trisomies 13, 18, and 21, some forms of primary hypogonadism such as Klinefelter's syndrome, anencephaly, many cryptorchid testes, and in patients with posterior urethral valves and severe obstruction of the urinary ducts. 728, 729 Leydig cell hypoplasia This variant of male pseudohermaphroditism is defi ned by insuffi cient testosterone secretion 422 and the following characteristics: predominance of female external genitalia; absence of male secondary sex characteristics at puberty; absence of uterus and fallopian tubes and the presence of epididymis and vas deferens; 46XY karyotype; lack of response to human chorionic gonadotropin stimulation; absence of an enzymatic defect in testosterone synthesis; and small undescended testes that are gray and mucous on section. cache = ./cache/cord-028721-x6f26ahr.txt txt = ./txt/cord-028721-x6f26ahr.txt === reduce.pl bib === id = cord-008777-i2reanan author = nan title = ECB12: 12th European Congess on Biotechnology date = 2005-07-19 pages = extension = .txt mime = text/plain words = 151383 sentences = 7577 flesch = 43 summary = Mollerup Department of Chemical Engineering, Building 229, DTU, 2800 Lyngby, Denmark A variety of factors that govern the properties of proteins are utilized in the development of chromatographic processes for the recovery of biological products including the binding and release of protons, the non-covalent association with non-polar groups (often hydrophobic interactions), the association of small ions (ion exchange) and the highly specific antigen-antibody interaction (affinity interactions). Such fermenters will be needed in order to meet the increasing pressure on costs for low price commodity type products such as single cell protein or food and technical grade enzymes, and to meet the demands of the new wave of white biotech, in which bio-produced chemicals must be made at prices competitive with those of the traditional chemical industry. The presentation will focus on use of the sensitive sandwich hybridization technology for the quantitative analysis of process relevant marker genes in different kind of microbial cell cultures with a focus on the production of recombinant proteins. cache = ./cache/cord-008777-i2reanan.txt txt = ./txt/cord-008777-i2reanan.txt === reduce.pl bib === id = cord-278136-ol2buwld author = Gonzales, Natalia M. title = 29th International Mammalian Genome Conference meeting report date = 2016-05-02 pages = extension = .txt mime = text/plain words = 4685 sentences = 180 flesch = 34 summary = The session showcased tools such as recombinant inbred lines (RILs), outbred populations, classic crosses, and ENU mutagenesis to yield new understanding and identify candidate genes for disease susceptibility, while knockout and patient-derived xenograft mice enabled further mechanistic insight. Other features of this session included a GWAS of aerobic capacity in rats segregated on running ability by Yu Wang German Center for Neurodegenerative Diseases Tuebingen) conducted a massive forward genetic screen using human exome data, followed by systematic RNAi screens in worms, flies, and human cell lines to identify genes and pathways involved in Parkinson's disease. This plenary session encompassed the use of mouse embryonic stem cells (mESCs), gene expression analysis, and recent advances in genome engineering to address fundamental questions about development and degenerative disease. A common approach featured at the IMGC each year is the use of the mouse as a model for understanding how biological processes influence and respond to changes in the mammalian genomic landscape. cache = ./cache/cord-278136-ol2buwld.txt txt = ./txt/cord-278136-ol2buwld.txt === reduce.pl bib === id = cord-268098-71g1w1mc author = Beckman, M. F. title = Comorbidities and Susceptibility to COVID-19: A Generalized Gene Set Meta-Analysis Approach date = 2020-09-15 pages = extension = .txt mime = text/plain words = 4203 sentences = 316 flesch = 49 summary = Visualization of protein-protein interaction networks was completed using STRINGv11.0 [31] program by testing different confidence levels to identify ontologies of biological significance for the significant pathways associated with comorbidities. Possible comorbidity significant associated gene sets/pathways were checked for quality control by generating Quantile-Quantile (Q-Q) plots using observed quantiles and residual Z-scores of genes within the gene set, based on the MAGMAv1.07b publicly available Rv3.6.2 script (posthoc_qc_107a.r) [32, 33] . . https://doi.org /10.1101 was used to test the top 250 human mRNA gene expressions for each comorbidity based on available human data using NCBI GEO[39] , by only including comorbidities that had significant pathways identified by MAGMAv1.07b and VEP STRING analyses. For each comorbidity, human mRNA gene expression data corresponding to average log-fold change (aLFC) were formatted for clustering of genes identified by MAGMAv1.07b and VEP and subsequently matched to STRING protein-protein interactions. cache = ./cache/cord-268098-71g1w1mc.txt txt = ./txt/cord-268098-71g1w1mc.txt === reduce.pl bib === id = cord-264996-og3sg0qw author = Howell, Gareth J. title = Cell Biology of Membrane Trafficking in Human Disease date = 2006-09-17 pages = extension = .txt mime = text/plain words = 20320 sentences = 1072 flesch = 42 summary = Many of these transport intermediates or vesicles, whether derived from the ER, other internal organelles, or the plasma membrane, are ''coated'' with unique protein complexes, tethering factors, and regulatory factors that ensure correct targeting to an acceptor compartment. Breast cancer Caveolin-1 Deletion or dominant negative mutation of caveolin-1 promotes tumor progression Breast cancer (Bouras et al., 2004; Williams and Lisanti, 2005) (Hayasaka et al., 1993; Matsuyama et al., 2002) Chediak-Higashi syndrome (CHS) CHS1/Lyst Lyst involved in regulation of protein secretion from lysosomes -enlarged lysosomes Partial albinism, recurrent bacterial infections, impaired chemotaxis and abnormal natural killer cell function (Shiflett et al., 2002; Ward et al., 2003) 214500 Choroideremia (CHM) Rab Escort Protein 1 (REP1) RAB27a remains cytosolic due to defective geranylgeranyl modification in CHM lymphoblasts X-linked form of retinal degeneration 303100 Various mechanisms control the traYcking of proteins from the TGN by the formation and delivery of membrane-derived transport vesicles to the plasma membrane, endosomes, or lysosomal structures (Ponnambalam and Baldwin, 2003) . cache = ./cache/cord-264996-og3sg0qw.txt txt = ./txt/cord-264996-og3sg0qw.txt === reduce.pl bib === id = cord-273910-fna7s9te author = Bochud, Pierre-Yves title = Innate immunogenetics: a tool for exploring new frontiers of host defence date = 2007-07-20 pages = extension = .txt mime = text/plain words = 7063 sentences = 391 flesch = 39 summary = Recent immunogenetic studies have associated polymorphisms of the genes encoding TLRs, NLRs, and key signal-transducing molecules, such as interleukin-1 receptor-associated kinase 4 (IRAK4), with increased susceptibility to, or outcome of, infectious diseases. With the availability of high-throughput genotyping techniques, it is becoming increasingly evident that analyses of genetic polymorphisms of innate immune genes will further improve our knowledge of the host antimicrobial defence response and help in identifying individuals who are at increased risk of life-threatening infections. Since the innate immune system senses only a limited number of highly conserved microbial-associated molecular patterns 23 via a limited number of receptors and signalling molecules, as anticipated, several polymorphisms have been found to confer an increased susceptibility to specifi c pathogens (table 2, table 3 , and fi gure 4). [36] [37] [38] Taken together, these data clearly show that mutations in the genes encoding TLRs and downstream signal-transducing molecules infl uence innate immune responses and increase susceptibility to many infectious diseases. cache = ./cache/cord-273910-fna7s9te.txt txt = ./txt/cord-273910-fna7s9te.txt === reduce.pl bib === id = cord-274241-biqbsggu author = Shaw, Timothy I. title = Transcriptome Sequencing and Annotation for the Jamaican Fruit Bat (Artibeus jamaicensis) date = 2012-11-15 pages = extension = .txt mime = text/plain words = 6003 sentences = 339 flesch = 52 summary = Annotated genes are involved in a broad range of activities ranging from cellular metabolism to genome regulation through ncRNAs. Reciprocal BLAST best hits yielded 8,785 sequences that are orthologous to mouse, rat, cattle, horse and human. Species tree analysis of sequences from 2,378 loci was used to achieve 95% bootstrap support for the placement of bat as sister to the clade containing horse, dog, and cattle. Through substitution rate estimation between bat and human, 32 genes were identified with evidence for positive selection. To address some of these deficiencies, we have performed transcriptome sequencing and analysis of spleen, lung, kidney and poly-IC-stimulated primary kidney cells to identify genes of interest for assessing the host response to TCRV infection. There were 20,145 contigs that mapped to Pteropus alecto, Australian flying fruit bat, and 18,359 that overlapped between genomic and transcriptome sequences for all three datasets ( Figure 5 ). cache = ./cache/cord-274241-biqbsggu.txt txt = ./txt/cord-274241-biqbsggu.txt === reduce.pl bib === id = cord-275720-kf9m4zho author = Cho, Won Kyong title = Genome-wide expression profiling shows transcriptional reprogramming in Fusarium graminearum by Fusarium graminearum virus 1-DK21 infection date = 2012-05-06 pages = extension = .txt mime = text/plain words = 7132 sentences = 390 flesch = 47 summary = At the early point of growth of an infected strain as compared to an uninfected strain, genes associated with protein synthesis, including ribosome assembly, nucleolus, and ribosomal RNA processing, were significantly up-regulated. This is the first report of a genome-wide fungal gene expression analysis during mycovirus infection using a 3′ tiling microarray, and our findings show global differences in host cellular pathways in F. For example, according to the qRT-PCR and microarray results, the transcript levels for three genes, including FGSG_01379, FGSG_03143, and FGSG_03911, were highly reduced at both 36 h and 120 h, whereas FGSG_03788, FGSG_00023, FGSG_07804, FGSG_07801, and FGSG_13222 were strongly induced regardless of the time point ( Figure 3A -C). graminearum harboring FgV1-DK21 in detail, samples were harvested at two different time points, thus providing lists of differentially expressed genes early and late in the host containing FgV1-DK21 as compared to an uninfected strain. cache = ./cache/cord-275720-kf9m4zho.txt txt = ./txt/cord-275720-kf9m4zho.txt === reduce.pl bib === id = cord-280924-g6062fwk author = Hachim, Mahmood Yaseen title = Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells date = 2020-06-10 pages = extension = .txt mime = text/plain words = 2851 sentences = 147 flesch = 42 summary = title: Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells We identified IFITM3 as an early upregulated gene, and valproic acid was found to enhance its mRNA expression as well as induce its antiviral action. To effectively address the ongoing COVID-19 pandemic, there is a recognized need for a framework for rapid identification of novel targets for diagnostic and therapeutic interventions as well as determine clinically approved drugs with high potential for repurposed use against SARS-CoV-2. In this study, we have applied this approach, and our findings have identified IFITM3 as an early upregulated gene and indicate that valproic acid enhances IFITM3 mRNA expression and antiviral action. Our toxicogenomic analysis showed that valproic acid increased the mRNA expression of IFITM3, supporting a new report that the SARS-CoV-2-human protein-protein interaction map showed that valproic acid might be a potential repurposing drug for COVID-19 (34) . cache = ./cache/cord-280924-g6062fwk.txt txt = ./txt/cord-280924-g6062fwk.txt === reduce.pl bib === id = cord-277491-q18b88lm author = Cao, Ying-Li title = Identification and Characterization of Three Novel Small Interference RNAs That Effectively Down-Regulate the Isolated Nucleocapsid Gene Expression of SARS Coronavirus date = 2011-02-11 pages = extension = .txt mime = text/plain words = 3988 sentences = 210 flesch = 53 summary = title: Identification and Characterization of Three Novel Small Interference RNAs That Effectively Down-Regulate the Isolated Nucleocapsid Gene Expression of SARS Coronavirus Nucleocapsid (N) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is a major pathological determinant in the host that may cause host cell apoptosis, upregulate the proinflammatory cytokine production, and block innate immune responses. In the current study, we compared the N gene sequences derived from 16 different isolates of SARS-CoV and selected three novel siRNA targeting sites in the N gene, including one targeting the 3' terminus of the gene. Overall, the above results provide strong evidence to show that all three novel siRNAs (si-N213, si-N863 and si-N1240) are specific and effective inhibitors to block the isolated SARS-CoV N gene expression. Small interfering RNA inhibits SARS-CoV nucleocapsid gene expression in cultured cells and mouse muscles Small interfering RNA effectively inhibits the expression of SARS coronavirus membrane gene at two novel targeting sites cache = ./cache/cord-277491-q18b88lm.txt txt = ./txt/cord-277491-q18b88lm.txt === reduce.pl bib === id = cord-285656-7o7ofk1e author = Dawson, Harry D. title = The porcine translational research database: a manually curated, genomics and proteomics-based research resource date = 2017-08-22 pages = extension = .txt mime = text/plain words = 5697 sentences = 295 flesch = 48 summary = The data in the Porcine Translational Research Database ((http://www.ars.usda.gov/Services/docs.htm?docid=6065) is supported by >5800 references, and contains 65 data fields for each entry, including >9700 full length (5′ and 3′) unambiguous pig sequences, >2400 real time PCR assays and reactivity information on >1700 antibodies. This database provides the first comprehensive description of three major Super-families or functionally related groups of proteins (Cluster of Differentiation (CD) Marker genes, Solute Carrier Superfamily, ATP binding Cassette Superfamily), and a comparative description of porcine microRNAs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-4009-7) contains supplementary material, which is available to authorized users. Five of these genes are present in other porcine genomes, but missing from Ensembl build 10.2, 21 are truncated, and 18 of these genes are duplicated gene artifacts, Eleven full-length mRNA sequences, assembled from macrophage RNA-Seq reads, have been deposited in Genbank and an additional 24 in silico constructs are provided. cache = ./cache/cord-285656-7o7ofk1e.txt txt = ./txt/cord-285656-7o7ofk1e.txt === reduce.pl bib === id = cord-284015-vvtv492b author = Nikaido, Masato title = Comparative genomic analyses illuminate the distinct evolution of megabats within Chiroptera date = 2020-09-23 pages = extension = .txt mime = text/plain words = 8594 sentences = 502 flesch = 51 summary = We identified that megabat genomes are distinct in that they have extremely low activity of SINE retrotranspositions, expansion of two chemosensory gene families, including the trace amine receptor (TAAR) and olfactory receptor (OR), and elevation of the dN/dS ratio in genes for immunity and protein catabolism. The protein-coding genes in the genomes of Egyptian fruit bat and Leschenault's rousette were identified based on the alignment with annotated gene sequences of 14 mammals (cat, dog, horse, cow, hedgehog, human, macaque, mouse, rat, Black flying fox, Little brown bat, Brandt's bat, David's myotis, and Large flying fox; Supplementary Table S2 ) that are available in the database. 71 Suggesting that FPR-mediated chemodetection is not directly linked with the difference in their habitats, mega-and microbats both possess two to eight FPRs. However, a previous study, by comparing the orthologous sequences among a broad range of mammals, found the signatures for the operation of positive selection in FPRs. 72 Therefore, to examine the possible contribution of FPRs to the adaptive evolution of megabats, more detailed investigation is necessary by focussing on the dN/dS values among orthologous FPR sequences of many bat species, which are lacking at present. cache = ./cache/cord-284015-vvtv492b.txt txt = ./txt/cord-284015-vvtv492b.txt === reduce.pl bib === id = cord-273347-eyxc4rt0 author = Mohammadinejad, Reza title = In vivo gene delivery mediated by non-viral vectors for cancer therapy date = 2020-07-04 pages = extension = .txt mime = text/plain words = 7777 sentences = 485 flesch = 39 summary = We will also highlight the in vivo gene delivery mediated by non-viral vectors to treat cancer in different tissue and organs including brain, breast, lung, liver, stomach, and prostate. Since various routes of administration have been used to transfer non-viral delivery systems for gene therapy, it seems that the route is highly dependent on the characteristics of the carrier and nucleic acids as well the prepared complex and the final formulation. Synthesis and Application of a Novel Gene Delivery Vector for Non-Small-Cell Lung Cancer Therapy Chloroquine in combination with aptamer-modified nanocomplexes for tumor vessel normalization and efficient erlotinib/Survivin shRNA co-delivery to overcome drug resistance in EGFR-mutated non-small cell lung cancer Enhanced delivery of siRNA to triple negative breast cancer cells in vitro and in vivo through functionalizing lipid-coated calcium phosphate nanoparticles with dual target ligands Highly efficient cationic hydroxyethylated cholesterol-based nanoparticle-mediated gene transfer in vivo and in vitro in prostate carcinoma PC-3 cells cache = ./cache/cord-273347-eyxc4rt0.txt txt = ./txt/cord-273347-eyxc4rt0.txt === reduce.pl bib === id = cord-291349-tq2n4mx3 author = Smith, Kevin R title = Gene transfer in higher animals: theoretical considerations and key concepts date = 2002-10-09 pages = extension = .txt mime = text/plain words = 12232 sentences = 661 flesch = 45 summary = The prospects for germline transgenesis via nuclear transfer (NT) are very significant: transgenes can be introduced to donor cells in vitro, permitting the production of genetically modified animals by NT . However, although retroviral-mediated gene therapy has been used successfully for (nonhuman) germline modifications, the most used */and to date the most useful */method for germline transgenesis is microinjection, reviewed in the following section. Because there are no special problems with microinjecting large transgene constructs, it is possible to incorporate structural gene-plus-promoter (plus other potentially useful sequences such as enhancers) combinations into the host genome. Therefore, the use of germline gene targeting as a means to avoiding transgene expression problems awaits progress in ES cell technology and NT technology. Following liposome-mediated gene transfer, amongst transgene molecules reaching the nucleus, only a minority integrate into the host cell chromosomes. cache = ./cache/cord-291349-tq2n4mx3.txt txt = ./txt/cord-291349-tq2n4mx3.txt === reduce.pl bib === id = cord-280691-nzc8ir0n author = Guo, Sun-Wei title = China’s “Gene War of the Century” and Its Aftermath: The Contest Goes On date = 2013-08-30 pages = extension = .txt mime = text/plain words = 12487 sentences = 563 flesch = 52 summary = Around 1997, and amid the talks of Hong Kong's upcoming return to China and later the Asian financial crisis, a recurring topic in the Chinese media was the so-called ''gene war of the century'': the lopsided condemnation of foreign scientists coming purportedly to pilfer China's vast genetic resources for a profit. Despite his repeated proclamation as a staunch and unwavering patriot loyal to his beloved motherland and dedicated to the advancement of China's science and technology, he nonetheless later became embroiled in an avalanche of controversies surrounding the ''gene war.'' He effectively became a lightning rod for all the controversy on genetic resources, intellectual rights, informed consent, and the protection of human research subjects. (2) Chinese scientists should immediately grasp the opportunity to find disease genes and patent them; (3) We should educate the people, and raise the awareness and importance of protection of our genetic resources; (4) We welcome all international collaborations based on fairness and mutual benefits; (5) Through various avenues, the Chinese scientists should be vocal about certain views deemed to be harmful to China's genetic research (Xiao et al. cache = ./cache/cord-280691-nzc8ir0n.txt txt = ./txt/cord-280691-nzc8ir0n.txt === reduce.pl bib === id = cord-298131-zolwjl9u author = Xiao, Shuqi title = Understanding PRRSV Infection in Porcine Lung Based on Genome-Wide Transcriptome Response Identified by Deep Sequencing date = 2010-06-29 pages = extension = .txt mime = text/plain words = 9349 sentences = 429 flesch = 39 summary = Upregulation expression of virus-induced pro-inflammatory cytokines, chemokines, adhesion molecules and inflammatory enzymes and inflammatory cells, antibodies, complement activation were likely to result in the development of inflammatory responses during N-PRRSV infection processes. To investigate the regulation of the host response to the N-PRRSV virus, we considered the global gene expression profiles in lungs using Solexa/Illumina's DGE system, a tag-based transcriptome sequencing method. From the data presented in the paper, a model for the relationship between pulmonary gene expression profiles and infection pathology can be surmised in Figure 7 , N-PRRSV virus replicates and spreads by subverting host innate immune response and hijacking host lipid metabolism as well as inducing an antiapoptotic and anti-inflammatory state, as indicated by suppression expression of SPI IFN, IFN-a, down-regulation expression of proapoptotic genes for BAK, APR-1, SARP3, high levels expression of genes involved in lipid metabolism, such as APOE, LDLB, PIK3C3, anti-apoptotic genes for MCL1, BCL2A1, CHFR, ADM, NFKB, IL10, and anti-inflammatory molecule PGE2 as well as CD163. cache = ./cache/cord-298131-zolwjl9u.txt txt = ./txt/cord-298131-zolwjl9u.txt === reduce.pl bib === id = cord-290282-oxyzndsj author = Ortego, Javier title = Transmissible gastroenteritis coronavirus gene 7 is not essential but influences in vivo virus replication and virulence date = 2003-03-30 pages = extension = .txt mime = text/plain words = 4287 sentences = 215 flesch = 53 summary = Transmissible gastroenteritis coronavirus (TGEV) contains eight overlapping genes that are expressed from a 3′-coterminal nested set of leader-containing mRNAs. To facilitate the genetic manipulation of the viral genome, genes were separated by duplication of transcription regulating sequences (TRSs) and introduction of unique restriction endonuclease sites at the 5′ end of each gene using an infectious cDNA clone. All the rTGEV viruses conserved the modifications engineered in the cDNAs (data not shown), indicating that the ORF separation and the insertion of unique endonuclease restriction sites between genes were stably maintained in the rTGEV genomes. Interestingly, analysis of viral growth in the gut of infected piglets showed a 100-to 5000-fold reduction of recombinant viruses containing one or more restriction sites in relation to the rTGEV-wt virus ( Fig. 5D and E) . cache = ./cache/cord-290282-oxyzndsj.txt txt = ./txt/cord-290282-oxyzndsj.txt === reduce.pl bib === id = cord-280897-el7bdkcf author = Wang, Hai-Fang title = Relationship between mRNA stability and intron presence date = 2007-03-02 pages = extension = .txt mime = text/plain words = 3037 sentences = 169 flesch = 55 summary = By analyzing the genome-wide data of mRNA stability published by someone previously, we found that human intron-containing genes have more stable mRNAs than intronless genes, and the Arabidopsis thaliana genes with the most unstable mRNAs have fewer introns than other genes in the genome. [10] found that insertion of a 138-bp intron into SARS-CoV spike protein gene can enhance the protein expression in mammalian cells, but the mRNAs exhibited similar decay rates as the intronless control mRNA. As a stable mRNA can be measured by lower decay rate or longer half-life, our analyses of different sources of data consistently showed that the mRNAs of intron-containing genes are more stable than those of intronless genes in human cells. We found that the mRNAs of intronless genes are less stable (i.e. have higher decay rates or shorter half-lives) than the intron-containing genes with similar mRNA lengths and functions (Fig. 1) . cache = ./cache/cord-280897-el7bdkcf.txt txt = ./txt/cord-280897-el7bdkcf.txt === reduce.pl bib === id = cord-295019-8tf8ah6g author = Weber, Wilfried title = Emerging biomedical applications of synthetic biology date = 2011-11-29 pages = extension = .txt mime = text/plain words = 9511 sentences = 475 flesch = 36 summary = Synthetic mammalian transcription circuits consisting of a chimeric small-molecule-responsive transcription factor and a cognate synthetic promoter were originally designed for future gene-based therapies, and the aim was to adjust therapeutic transgene expression in mammalian cells in response to a pharmacologically active substance 34, 47, 49, 91 . When mammalian cells that are transgenic for the screening circuit are exposed to a compound library, they detect and modulate reporter gene expression in the presence of a non-toxic, cellpermeable and bioavailable molecule that has a classspecific core structure and corresponding drug activity (for example, antibiotic activity) (FIG. The availability of compact RNA sensor-actuators that are easy to design and to alter and that control transgene expression in response to intracellular levels of key proteins may also improve the ability to link metabolic disease states with gene-based therapeutic interventions. cache = ./cache/cord-295019-8tf8ah6g.txt txt = ./txt/cord-295019-8tf8ah6g.txt === reduce.pl bib === id = cord-301546-yck1t3pp author = Kozaki, Toshinori title = Comparison of two acetylcholinesterase gene cDNAs of the lesser mealworm, Alphitobius diaperinus, in insecticide susceptible and resistant strains date = 2007-12-28 pages = extension = .txt mime = text/plain words = 2505 sentences = 152 flesch = 52 summary = title: Comparison of two acetylcholinesterase gene cDNAs of the lesser mealworm, Alphitobius diaperinus, in insecticide susceptible and resistant strains Two cDNAs encoding different acetylcholinesterase (AChE) genes (AdAce1 and AdAce2) were sequenced and analyzed from the lesser mealworm, Alphitobius diaperinus. Partial cDNA sequences of the Alphitobius Ace genes were compared between two tetrachlorvinphos resistant (Kennebec and Waycross) and one susceptible strain of beetles. The alignment of this gene with the Drosophila Ace paralogous AChEs showed that, as expected for an insecticide-susceptible strain, beetles from the Denmark-S strain had an organophosphate and carbamate sensitive type. The Drosophila Ace orthologous gene, AdAce1, was sequenced from two susceptible Denmark-S, four Waycross (tetrachlorvinphos-resistant), and two Kennebec (tetrachlorvinphos-resistant) adults. diaperinus is not due to mutations in the Ace genes (i.e., is not an altered acetylcholinesterase).Alignments of the deduced amino acid sequences from the Drosophila Ace orthologous and paralogous genes in Coleoptera are shown in Figures 4 and 5, respectively. cache = ./cache/cord-301546-yck1t3pp.txt txt = ./txt/cord-301546-yck1t3pp.txt === reduce.pl bib === id = cord-290861-5bxvenue author = Ashwell, M. title = Characterization of gene expression in naturally occurring feline degenerative joint disease-associated pain date = 2018-11-19 pages = extension = .txt mime = text/plain words = 4901 sentences = 225 flesch = 51 summary = Expression of an investigator-selected set of pain signaling genes (including ASIC3, ATF3, COX2, CX3CL1, NAV1.7, NAV1.8, NAV1.9, NGF, NK1R, TNFα, TRKA) in lumbar spinal cord dorsal horn and lumbar dorsal root ganglia tissues from clinically healthy cats and cats with DJD were studied using quantitative RT-PCR (qPCR). After the most stable reference genes were identified, a selection of genes previously associated with nociception in rodent models, and of interest to the authors, were examined using qPCR in the same samples to allow us to start characterizing the neurobiological signature of pain associated with DJD in cats. After a set of stable reference genes were identified for each tissue type, 13 genes associated with pain in rodents were selected (based on current knowledge of genes involved in pain states (Foulkes and Wood, 2008) and their expression levels compared in the DRG from DJD-affected and healthy samples. cache = ./cache/cord-290861-5bxvenue.txt txt = ./txt/cord-290861-5bxvenue.txt === reduce.pl bib === id = cord-282968-kjvvoveq author = Qu, Renjun title = Selection of reference genes for the quantitative real-time PCR normalization of gene expression in Isatis indigotica fortune date = 2019-03-25 pages = extension = .txt mime = text/plain words = 6267 sentences = 315 flesch = 47 summary = indigotica, and evaluated their expression stabilities in different tissues (root, stem, leaf, and petiole) and leaves exposed to three abiotic treatments (low-nitrogen, ABA, and MeJA) using geNorm, NormFinder, BestKeeper, and comprehensive RefFind algorithms. TIP41 as the optimal reference gene for low-nitrogen stress and MeJA treatment, while ACT had the highest ranking for ABA treatment and CYP was the most suitable for different tissues. Excel-based tools, such as geNorm [34] , NormFinder [35] and BestKeeper [36] , have been developed to select the most suitable reference genes from a set of biological samples under investigation to be used in an expression stability analysis. indigotica (SRR1051997) to determine appropriate reference genes for qRT-PCR normalization in different plant tissues, and under low-nitrogen stress and exposure to hormonal stimuli (ABA and MeJA). The results were normalized using the selected stable reference genes (singly or in combination) and the unstable genes in sample sets across treatment with a N, b different tissues, c ABA, and d MeJA. cache = ./cache/cord-282968-kjvvoveq.txt txt = ./txt/cord-282968-kjvvoveq.txt === reduce.pl bib === id = cord-294725-wyrg0nq8 author = Bourdon, Julie A. title = Gene expression profiling to identify potentially relevant disease outcomes and support human health risk assessment for carbon black nanoparticle exposure date = 2013-01-07 pages = extension = .txt mime = text/plain words = 6413 sentences = 288 flesch = 39 summary = Comparison to inflammatory lung disease models (i.e., allergic airway inflammation, bacterial infection and tissue injury and fibrosis) and human disease profiles revealed that induced gene expression changes in Printex 90 exposed mice were similar to those typical for pulmonary injury and fibrosis. In the present study we investigate the utility of gene expression profiles derived from mice exposed to Printex 90 carbon black nanoparticles (CBNPs) by intratracheal installation to identify potential hazards, modes of action, and doses above which adverse effects may be expected for specific toxicological outcomes. In addition to the examination of BMDs and BMDLs, we compare CBNP-modified gene expression profiles to various models of lung disease in mice and humans reported in the literature, in order to explore the utility of our data in predicting the potential risk of adverse health outcomes and the human relevance of expression changes. cache = ./cache/cord-294725-wyrg0nq8.txt txt = ./txt/cord-294725-wyrg0nq8.txt === reduce.pl bib === id = cord-289033-vfh3op6a author = Algammal, Abdelazeem M. title = Genes Encoding the Virulence and the Antimicrobial Resistance in Enterotoxigenic and Shiga-toxigenic E. coli Isolated from Diarrheic Calves date = 2020-06-10 pages = extension = .txt mime = text/plain words = 4893 sentences = 208 flesch = 47 summary = coli (ETEC) incriminated in calf diarrhea, with special reference to Shigatoxins genes (stx1 and stx2) and enterotoxins genes (lt and sta) that govern their pathogenesis, as well as the virulence genes; eaeA (intimin) and f41(fimbrial adhesion), and the screening of their antibiogram and antimicrobial resistance genes; aadB, sul1, and bla-TEM, a total of 274 fecal samples were collected (April 2018–Feb 2019) from diarrheic calves at different farms in El-Sharqia Governorate, Egypt. This study was aimed at determining the prevalence of STEC and ETEC incriminated in calf diarrhea, with special reference to the Shiga-toxins genes (stx1 and stx2) and enterotoxins genes (lt and sta) that govern their pathogenesis, as well as the virulence genes; eaeA and f 41, and the screening of their antimicrobial resistance profiles and antimicrobial resistance genes; aadB, sul1, and bla-TEM. cache = ./cache/cord-289033-vfh3op6a.txt txt = ./txt/cord-289033-vfh3op6a.txt === reduce.pl bib === id = cord-292004-9rpoll7y author = Mitchell, Hugh D. title = The Role of EGFR in Influenza Pathogenicity: Multiple Network-Based Approaches to Identify a Key Regulator of Non-lethal Infections date = 2019-09-20 pages = extension = .txt mime = text/plain words = 8357 sentences = 373 flesch = 43 summary = The role of epidermal growth factor receptor (EGFR) in influenza pathogenesis, one of the bottleneck regulators with corroborating signals across transcript and protein expression data, was tested and validated in additional mouse infection experiments. The role of epidermal growth factor receptor (EGFR) in influenza pathogenesis, one of the bottleneck regulators with corroborating signals across transcript and protein expression data, was tested and validated in additional mouse infection experiments. The same relationships between network topology, viral pathogenicity, and gene expression that were observed for influenza virus were also noted when we used a similar dataset of SARS-CoV infections, thus further validating our analysis and demonstrating that these relationships appear to apply to respiratory viruses in general. cache = ./cache/cord-292004-9rpoll7y.txt txt = ./txt/cord-292004-9rpoll7y.txt === reduce.pl bib === id = cord-287396-18p171nr author = Schroyen, Martine title = Current transcriptomics in pig immunity research date = 2014-11-15 pages = extension = .txt mime = text/plain words = 9824 sentences = 467 flesch = 44 summary = Other meta-analysis studies, examining the immune response to Salmonella typhimurium, combine microarray information with data such as serum cytokine measurements or microbiota differences. typhimurium will be discussed in the section ''Overall value of transcriptomics in important infectious swine diseases.'' In addition, whole genome microarrays were used to study pig response to Haemophilus parasuis infection by Zhao et al. In 2010, Xiao and collaborators performed a 3' tag digital gene expression (DGE) analysis of the porcine lung transcriptome on pigs infected with the PRRS virus (Xiao et al. Most pig immune studies conducted to identify host response to common porcine pathogens or to immune response stimulators such as LPS or PMA/ionomycin described in this review provide gene expression data from a single tissue or isolated cell type, and this at a limited number of times post-infection/stimulation. Recently, such a meta-analysis was performed by combining results of several microarray-based pig immune studies to find PRRS-specific responses (Badaoui et al. cache = ./cache/cord-287396-18p171nr.txt txt = ./txt/cord-287396-18p171nr.txt === reduce.pl bib === id = cord-303939-7knzjnyr author = Hu, Fang title = Identification of a metabolic gene panel to predict the prognosis of myelodysplastic syndrome date = 2020-04-26 pages = extension = .txt mime = text/plain words = 2281 sentences = 171 flesch = 42 summary = title: Identification of a metabolic gene panel to predict the prognosis of myelodysplastic syndrome A prognostic model was constructed by the least absolute shrinkage and selection operator (LASSO) regression analysis for MDS patients based on the identified metabolic gene panel in training cohort, followed by external validation in an independent cohort. Therefore, we established a prognostic panel of metabolic gene by downloading data from Gene Expression Omnibus (GEO) datasets in the training cohort, which was further validated in an independent external cohort. In total, 201 patients with complete clinical data including age, gender, WHO category, karyotype, IPSS, transfusion dependent, haemoglobin, bone marrow blasts cells, platelet count and absolute neutrophil count were included in the training and validation cohort. In summary, we constructed a novel prognostic prediction model based on metabolic genes from GEO database for MDS, and further validated in the validation cohort. Identification of a metabolic gene panel to predict the prognosis of myelodysplastic syndrome cache = ./cache/cord-303939-7knzjnyr.txt txt = ./txt/cord-303939-7knzjnyr.txt === reduce.pl bib === id = cord-306380-msk9p1yy author = Lee, C.-W. title = Evidence of genetic diversity generated by recombination among avian coronavirus IBV date = 2000 pages = extension = .txt mime = text/plain words = 2796 sentences = 146 flesch = 58 summary = Phylogenetic analysis of selected regions of the genome of the DE072 serotype field isolates further support those results and indicate that isolates within the same serotype may have different amounts of nucleotide sequence similarity with each other in individual genes other than the S gene. Further, we conducted sequence analysis of six isolates of the DE072 serotype in order to determine if recombination is frequently occurring in this region in field isolates of IBV. We conducted phylogenetic analysis by dividing 3.8 kb of the 3 end of the genome among five IBV strains at the IG sequences. However, these 6 isolates had a much different level of nucleotide sequence similarity with each other in gene 3 and gene 4, and clustered randomly with other serotypes of IBV (Fig. 3) . Sequence analysis of gene 3, gene 4 and gene 5 of avian infectious bronchitis virus strain CU-T2 Sequence evidence for RNA recombination in field isolates of avian coronavirus infectious bronchitis virus cache = ./cache/cord-306380-msk9p1yy.txt txt = ./txt/cord-306380-msk9p1yy.txt === reduce.pl bib === id = cord-291719-1ku6cmwj author = Hajjo, Rima title = A Systems Biology Workflow for Drug and Vaccine Repurposing: Identifying Small-Molecule BCG Mimics to Reduce or Prevent COVID-19 Mortality date = 2020-10-06 pages = extension = .txt mime = text/plain words = 6493 sentences = 315 flesch = 41 summary = METHODS: We developed and employed a systems biology workflow capable of identifying small-molecule antiviral drugs and vaccines that can boast immunity and affect a wide variety of viral disease pathways to protect from the fatal consequences of emerging viruses. RESULTS: Our analysis demonstrates that BCG vaccine affects the production and maturation of naïve T cells resulting in enhanced, long-lasting trained innate immune responses that can provide protection against novel viruses. Herein, we describe a unique drug and vaccine repurposing workflow, and list high confidence proteins and pharmacological classes of compounds, that work as BCG mimics at the system level by inducing beneficial long lasting trained immune response. Earlier studies suggested that the documented beneficial off-target effects of BCG in protecting from non-TB infections, including perhaps COVID-19, involve a potentiation of innate immune responses through epigenetic mechanisms (56) (57) (58) . cache = ./cache/cord-291719-1ku6cmwj.txt txt = ./txt/cord-291719-1ku6cmwj.txt === reduce.pl bib === id = cord-301218-zsp5sh9o author = Weeraratna, Ashani T. title = Gene Expression Profiling: From Microarrays to Medicine date = 2004 pages = extension = .txt mime = text/plain words = 6384 sentences = 284 flesch = 35 summary = One of the challenges in array data analysis is to distinguish specific physiologic changes in gene expression from the noise and variability inherent within the microarray technique. If an analysis technique can be developed and validated that can identify the genes that undergo a significant change in expression and remove those that do not, it could alter microarray design and construction in favor of smaller focused arrays that query only biologically relevant genes. Presently, most large-scale projects examining genome-wide SNP expression are based on differential hybridization affinity using either spotted or in situ synthesized oligonucleotide arrays (45, 46) or utilize mass spectroscopy for genotype analysis (7, 47) . In addition, potential usefulness of microarray-derived gene expression data has been shown in several recent studies of lymphoma, leukemia (25, 50) , and multiple myeloma (51) where modeling techniques that incorporate outcome and drug response during treatment were used to define tumor types or patient groups and to suggest rational targets for drug therapy or development. cache = ./cache/cord-301218-zsp5sh9o.txt txt = ./txt/cord-301218-zsp5sh9o.txt === reduce.pl bib === id = cord-309556-xv3413k1 author = Chow, Ryan D. title = The aging transcriptome and cellular landscape of the human lung in relation to SARS-CoV-2 date = 2020-04-15 pages = extension = .txt mime = text/plain words = 5761 sentences = 373 flesch = 53 summary = In aggregate, these analyses showed that the age-associated genes with functional roles in SARS-CoV are expressed in specific cell types of the human lung. Of note, the overlap between lung ageassociated genes and SARS-CoV-2 regulated genes was statistically significant across all 3 cell lines (Figure 6d-f) , suggesting a degree of similarity between the transcriptional changes associated with aging and with SARS-CoV-2 infection. Among the age-associated genes that were induced by SARS-CoV-2 infection, the majority of these genes increase in expression with age (Cluster 1) (Figure 6g-i) . To identify a consensus set of age-associated genes that are regulated by SARS-CoV-2 infection, we integrated the analyses from all 3 cell lines. By integrating these data with single cell transcriptomes of human lung tissue, we further pinpointed the specific cell types that normally express the age-associated genes. cache = ./cache/cord-309556-xv3413k1.txt txt = ./txt/cord-309556-xv3413k1.txt === reduce.pl bib === id = cord-312551-w4tps34p author = Razvi, Mohammad H. title = Transcriptional oncogenomic hot spots in Barrett's adenocarcinomas: Serial analysis of gene expression date = 2007-07-17 pages = extension = .txt mime = text/plain words = 5047 sentences = 291 flesch = 46 summary = Analyses of the human transcriptome map of normal tissues have shown clustering of highly expressed genes in chromosomal domains (Caron et al., 2001) . In this study, we explored the BA transcriptome using SAGE and mapped gene-expression changes to chromosomal positions, thereby generating a map of transcriptional oncogenomic hot spots of this deadly cancer. We confirmed over-expression of ANPEP, ECGF1, PP1201, and EIF5A1 and downregulation of GKN1 in primary GEJ and lower esophageal adenocarcinoma samples (Table 5 , Fig. 2) . GKN1 shows downregulation ( 0.4-fold expression) whereas ANPEP, PP1201, EIF5A1, and ECGF1 demonstrate overexpression (!2.5 fold expression) in primary tumors as compared to normal tissue samples. Discovery of new markers of cancer through serial analysis of gene expression: Prostate stem cell antigen is overexpressed in pancreatic adenocarcinoma cache = ./cache/cord-312551-w4tps34p.txt txt = ./txt/cord-312551-w4tps34p.txt === reduce.pl bib === id = cord-303132-m3j1dekj author = Smith, S. E. title = Chicken Interferon-Inducible Transmembrane Protein 3 Restricts Influenza Viruses and Lyssaviruses In Vitro date = 2013-12-17 pages = extension = .txt mime = text/plain words = 5177 sentences = 253 flesch = 47 summary = The chicken IFITM3 protein restricts cell infection by influenza A viruses and lyssaviruses to a similar level as its human orthologue. Despite being highly divergent at the amino acid level, IFITM3 proteins of birds and mammals can restrict replication of viruses that are able to infect different host species, suggesting IFITM proteins may provide a crucial barrier for zoonotic infections. Expression of the interferon-inducible transmembrane (IFITM) genes (new members of the ISG family) restricts the replication of several highly pathogenic human viruses, including severe acute respiratory syndrome (SARS) coronavirus, filoviruses (Marburg virus and Ebola virus), influenza A viruses (IAVs), and flaviviruses (dengue virus) (1, 2) . We then compared the level of antiviral restriction of chicken IFITM2 and -3 to that of their orthologous human proteins in A549 cells. Furthermore, we show that DF-1 chicken cells constitutively express chIFITM3, and this is able to restrict influenza virus infection in vitro. cache = ./cache/cord-303132-m3j1dekj.txt txt = ./txt/cord-303132-m3j1dekj.txt === reduce.pl bib === id = cord-304913-qb9zeazk author = Thibivilliers, Sandra title = Generation of Phaseolus vulgaris ESTs and investigation of their regulation upon Uromyces appendiculatus infection date = 2009-04-27 pages = extension = .txt mime = text/plain words = 6680 sentences = 344 flesch = 52 summary = RESULTS: A subtractive bean cDNA library composed of 10,581 unisequences was constructed and enriched in sequences regulated by either bean rust race 41, a virulent strain, or race 49, an avirulent strain on cultivar Early Gallatin carrying the resistance gene Ur-4. Plant gene expression was similar for both race 41 and 49 during the first 48 hours of the infection process but varied significantly at the later time points (72–96 hours after inoculation) mainly due to the presence of the Avr4 gene in the race 49 leading to a hypersensitive response in the bean plants. The stability of the expression level of the 3 remaining genes, TC127, cons6 and cons7 was evaluated by qRT-PCR on cDNAs from bean uninfected or infected with bean rust race 41 or 49 at 6, 12, 24, 48, 72, and 96 hours after inoculation (HAI). cache = ./cache/cord-304913-qb9zeazk.txt txt = ./txt/cord-304913-qb9zeazk.txt === reduce.pl bib === id = cord-306535-j26eqmxt author = Robertson, Matthew J. title = Large-scale discovery of male reproductive tract-specific genes through analysis of RNA-seq datasets date = 2020-08-19 pages = extension = .txt mime = text/plain words = 16758 sentences = 846 flesch = 49 summary = The majority of candidate genes identified in our screen that were testis-specific were already identified by the Human Protein Atlas [9] and/or our reanalysis of (See figure on previous page.) Fig. 1 Summary of the human and mouse RNA-seq samples used in the identification of novel male reproductive tract-specific drug targets. Additional file 14: Fig. S6 shows the complete list of male reproductive tract-specific human genes for which a previously generated mouse model shows male infertility phenotype, as identified in each of the respective cell and/or tissue datasets. Through the integration of hundreds of published and newly acquired human and mouse reproductive and non-reproductive tissue and cell RNA-seq datasets, we have generated a list of novel genes expressed predominantly or exclusively in the male reproductive tract that are worthy of consideration for functional validation in an animal model and potential targeting for a male contraceptive. cache = ./cache/cord-306535-j26eqmxt.txt txt = ./txt/cord-306535-j26eqmxt.txt === reduce.pl bib === id = cord-320005-i30t7cvr author = Pardo, A. title = The Human Genome and Advances in Medicine: Limits and Future Prospects date = 2004-03-31 pages = extension = .txt mime = text/plain words = 4919 sentences = 211 flesch = 49 summary = The HGP's initial objectives were fulfilled 2 years ahead of schedule, and, in addition to compiling a highly accurate sequence of the human genome which has been made freely available and accessible to everyone, the Consortium has developed a set of new technologies and has constructed genetic maps of the genomes of various organisms. Around the same time, the public consortium known as the Human Genome Project was formed, and this organization announced a 15-year plan (from 1990 to 2005) with the following objectives: a) to determine the complete nucleotide sequence of human DNA and identify all the genes in human DNA (estimated to number between 50 000 and 100 000); b) to build physical and genetic maps; c) to analyze the genomes of selected organisms used in research as model systems (eg, the mouse); d) to develop new technologies; and e) to analyze and debate the ethical and legal implications for individuals and for society as a whole. cache = ./cache/cord-320005-i30t7cvr.txt txt = ./txt/cord-320005-i30t7cvr.txt === reduce.pl bib === id = cord-313138-y485ev30 author = Magor, Katharine E. title = Defense genes missing from the flight division date = 2013-04-24 pages = extension = .txt mime = text/plain words = 10638 sentences = 610 flesch = 51 summary = Whether cause or effect, the lack of TLR8 in avian monocytes/ macrophages likely does contribute to the susceptibility of birds to RNA viruses (West Nile virus, Newcastle disease virus, influenza virus and others) and intracellular bacterial infections, including mycobacteria. The gene encoding RIG-I, DDX58, is not annotated in the chicken genome sequence, and is missing in some fish species, but MDA5 homologues are present in all vertebrate families (Zou et 2009). Riplet/RNF135 is a cytoplasmic E3-ligase identified by yeast two-hybrid as one of the proteins binding RIG-I, and is essential for RIG-I activation in human cell lines upon infection with an RNA virus (Oshiumi et al., 2009; Oshiumi et al., 2010) . The upregulation of IFIT5 following viral infection of chicken cells expressing duck RIG-I ( Barber et al., 2013) or infection of ducks (Vanderven et al., 2012) suggests IFIT5 is an important antiviral effector in avian species. cache = ./cache/cord-313138-y485ev30.txt txt = ./txt/cord-313138-y485ev30.txt === reduce.pl bib === id = cord-296979-8r851j4t author = Zhong, Ying title = Host genes regulate transcription of sperm-introduced hepatitis B virus genes in embryo date = 2017-10-31 pages = extension = .txt mime = text/plain words = 6753 sentences = 322 flesch = 49 summary = Eighteen healthy donors were randomly divided into six groups, and their sperm samples were used to fertilize zona-free hamster oocytes in vitro and assess the effects of the silencing of five target genes (CSH2, EIF4G2, PCBD2, PSG4 and TTN) and a control gene (ESRRG) on transcription of HBV s and x genes by real-time quantitative (q)RT-PCR. Eighteen healthy donors were randomly divided into six groups, and their sperm sample were used to fertilize zona-free hamster oocytes in vitro and assess the effects of the silencing of five target genes (CSH2, EIF4G2, PCBD2, PSG4 and TTN) and a control gene (ESRRG) on transcription of HBV S and X genes in two-cell embryos using real time qRT-PCR and 2 − CT method. cache = ./cache/cord-296979-8r851j4t.txt txt = ./txt/cord-296979-8r851j4t.txt === reduce.pl bib === id = cord-308034-9b219k0v author = Murray, James L. title = A Role for H/ACA and C/D Small Nucleolar RNAs in Viral Replication date = 2014-01-30 pages = extension = .txt mime = text/plain words = 3654 sentences = 218 flesch = 12 summary = We have employed gene-trap insertional mutagenesis to identify candidate genes whose disruption confer phenotypic resistance to lytic infection, in independent studies using 12 distinct viruses and several different cell lines. Expression of nine SNORA/Ds encoded within RCC1 (which also encodes the shorter non-coding SNHG3 gene), or SNHG1 were silenced with siRNAs for 2 days prior to infection with either cowpox virus (CPV), Dengue Fever virus (DFV), influenza A (FLU), human rhinovirus 16 (HRV16), herpes simplex virus 2 (HSV2), or respiratory syncytial virus (RSV). While a previous study showed that RCC1 supports HSV1 replication [21] , we did not observe that silencing RCC1 or the non-coding Small Nucleolar RNA Host Gene 3 (SNHG3) inhibits HSV2 (data not shown), whereas inhibiting expression of the RCC1encoded SNORA73A did. The discovery of these classes of non-coding genes prominently represented in the mutant clones selected in our virus surviving cell lines suggests an importance of SNORAs and SNORDs in facilitating viral replication. cache = ./cache/cord-308034-9b219k0v.txt txt = ./txt/cord-308034-9b219k0v.txt === reduce.pl bib === id = cord-302047-vv5gpldi author = Willemsen, Anouk title = On the stability of sequences inserted into viral genomes date = 2019-11-14 pages = extension = .txt mime = text/plain words = 12557 sentences = 598 flesch = 43 summary = Viruses are widely used as vectors for heterologous gene expression in cultured cells or natural hosts, and therefore a large number of viruses with exogenous sequences inserted into their genomes have been engineered. Viruses genera covered in relevant studies Conclusions of this review All viruses • Inserted sequences are often unstable and rapidly lost upon passaging of an engineered virus • The position at which a sequence is integrated in the genome can be important for stability • Sequence stability is not an intrinsic property of genomes because demographic parameters, such as population size and bottleneck size, can have important effects on sequence stability • The multiplicity of cellular infection affects sequence stability, and can in some cases directly affect whether there is selection for deletion variants • Deletions are not the only class of mutations that can reduce the cost of inserted sequences, although they are the most common I: dsDNA cache = ./cache/cord-302047-vv5gpldi.txt txt = ./txt/cord-302047-vv5gpldi.txt === reduce.pl bib === id = cord-295307-zrtixzgu author = Delgado-Chaves, Fernando M. title = Computational Analysis of the Global Effects of Ly6E in the Immune Response to Coronavirus Infection Using Gene Networks date = 2020-07-21 pages = extension = .txt mime = text/plain words = 10169 sentences = 541 flesch = 51 summary = Through the integration of differential expression analyses and reconstructed networks exploration, significant differences in the immune response to virus were observed in Ly6E [Formula: see text] compared to wild type animals. Among the different types of GNs, gene co-expression networks (GCNs) are widely used in the literature due to their computational simplicity and good performance in order to study biological processes or diseases [8] [9] [10] . In the present work mice samples were compared organ-wise depending on whether these corresponded to control, 3 d p.i. and 5 d p.i. The identification of DEG was performed using the Limma [63] R package, which provides non-parametric robust estimation of the gene expression variance. In this work four gene networks were reconstructed to model the genetic response MHV infection in two tissues, liver and spleen, and in two different genetic backgrounds, wild type and Ly6E ∆HSC . cache = ./cache/cord-295307-zrtixzgu.txt txt = ./txt/cord-295307-zrtixzgu.txt === reduce.pl bib === id = cord-315498-gpzee1f2 author = Parkinson, N. title = Systematic review and meta-analysis identifies potential host therapeutic targets in COVID-19. date = 2020-09-01 pages = extension = .txt mime = text/plain words = 4964 sentences = 296 flesch = 46 summary = 2, 6, 7, 8, 9, 10 In this analysis we systematically identify and combine existing data from human betacoronavirus research to generate a comprehensive ranked list of host genes as a resource to inform further work on COVID-19. To identify existing literature which could provide informative datasets for host gene prioritisation, we conducted a systematic review of published studies and preprint manuscripts pertaining to host gene involvement in human betacoronavirus infection and associated disease. Results from identified studies, in the form of lists of implicated host factor genes, were combined using meta-analysis by information content (MAIC), 3 an approach we previously developed to identify host genes necessary for Influenza A virus (IAV) replication. Table 2 Candidate-gene human genetic studies < 5 hosts in virus group or control group in patient studies Meta-analyses, in silico anayses, re-analysis of data published elsewhere Potentially relevant pre-print manuscripts were identified by screening all papers categorised as COVID-19-related in the bioRxiv and medRxiv servers. cache = ./cache/cord-315498-gpzee1f2.txt txt = ./txt/cord-315498-gpzee1f2.txt === reduce.pl bib === id = cord-314642-oobbdgzh author = Campbell, Allan title = The future of bacteriophage biology date = 2003 pages = extension = .txt mime = text/plain words = 5945 sentences = 308 flesch = 53 summary = Several molecules of λ-integrase form an assemblage (the INTASOME) that binds to a specific segment of phage DNA, recruits the bacterial insertion sites into the complex, then makes concerted single-strand cuts in the two DNAs. The strand cutting proceeds through the covalent joining of a 3′ phosphate to a tyrosine of the integrase protein. Further efforts in this direction are desirable, not just for their intrinsic interest but also as models for viruses that infect eukaryotic hosts; for example, it is well documented that members of the coronavirus group, which has attracted attention recently through the emergence of a deadly new human pathogen that causes severe acute respiratory syndrome (SARS), undergo frequent recombination in nature 10, 11 . cache = ./cache/cord-314642-oobbdgzh.txt txt = ./txt/cord-314642-oobbdgzh.txt === reduce.pl bib === === reduce.pl bib === id = cord-314503-u1y1bznk author = Jaluria, Pratik title = A perspective on microarrays: current applications, pitfalls, and potential uses date = 2007-01-25 pages = extension = .txt mime = text/plain words = 7764 sentences = 349 flesch = 38 summary = Therefore, this text aims to outline key features in microarray technology, paying particular attention to current applications as outlined in recent publications, experimental design, statistical methods, and potential uses. Several organizations such as the Microarray Gene Expression Data (MGED) Society and the European Bioinformatics Institute (EBI) have established guidelines to aid researchers in the design and implementation of microarray experiments [8, 9, 16] . As mentioned earlier, verification is critical in order to assign distinct expression patterns to specific genes with certainty (i.e. statistical significance) because of the inherent variability present in microarray data. To verify the results generated from microarray experiments, a combinatorial approach is usually needed; checking the statistical significance associated with the expression levels of specific genes, reviewing the literature, and conducting additional experiments such as RT-PCR or Northern blotting. A large number of microarray-related studies in the past have aimed to either characterize diseased cells in comparison to healthy cells or highlight the genes involved in a particular biological pathway [4, 8] . cache = ./cache/cord-314503-u1y1bznk.txt txt = ./txt/cord-314503-u1y1bznk.txt === reduce.pl bib === id = cord-304607-td0776wj author = Paszkiewicz, Konrad H. title = Omics, Bioinformatics, and Infectious Disease Research date = 2010-12-24 pages = extension = .txt mime = text/plain words = 7022 sentences = 367 flesch = 46 summary = This chapter discusses the current state of play of bioinformatics related to genomics and transcriptomics, briefs metagenomics that finds use in infectious disease research as well as the random sequencing of genomes from a variety of organisms. Bioinformatics plays a key role at several steps in genomics, comparative genomics, and functional genomics: sequence alignment, assembly, identification of single nucleotide polymorphisms (SNP), gene prediction, quantitative analysis of transcription data, etc. The term "metagenomics" was originally used to describe the sequencing of genomes of uncultured microorganisms in order to explore their abilities to produce natural products (Handelsman et al., 1998 , Rondon et al., 2000 and subsequently resulted in novel insights into the ecology and evolution of microorganisms on a scale not imagined possible before (see Cardenas and Tiedje, 2008; Hugenholtz and Tyson, 2008 for an overview). However, metagenomics now finds use in infectious disease research as well as the random sequencing of genomes from a variety of organisms from, for example, patient material that could lead to the identification of the cause of disease. cache = ./cache/cord-304607-td0776wj.txt txt = ./txt/cord-304607-td0776wj.txt === reduce.pl bib === id = cord-305177-i71z2sf4 author = Neshat, Sarah Y title = Gene delivery for immunoengineering date = 2020-06-15 pages = extension = .txt mime = text/plain words = 5261 sentences = 234 flesch = 32 summary = Major strategies that have been explored for cancer immunotherapy [7] center on increasing the immunogenicity of the tumor microenvironment, enhancing the ability of antigen-presenting cells (APCs) to be activated, improving the activation of T cells and other lymphocytes in the context of the tumor while lessening the effect of suppressive immune cells, and vaccinating the patient with a tumor-specific antigen in order to generate a tumor-targeted immune response ( Figure 1 ). Additionally, anti-viral vaccines have been engineered with self-amplifying mRNA (SAM) encapsulated in lipid nanoparticles and show an induced type 1 IFN Gene delivery for immunoengineering Neshat, Tzeng and Green 7 response locally when compared to TLR7 agonists [45 ] . Using lipid nanoparticles, the authors describe an antigen-agnostic combination immunotherapy via direct intratumoral injection of mRNA encoding immunostimulatory genes, leading to anti-tumor effect even at sites distant from the local treatment site. cache = ./cache/cord-305177-i71z2sf4.txt txt = ./txt/cord-305177-i71z2sf4.txt === reduce.pl bib === id = cord-326719-p1ma4akz author = Enjuanes, Luis title = Virus-based vectors for gene expression in mammalian cells: Coronavirus date = 2003-12-31 pages = extension = .txt mime = text/plain words = 5923 sentences = 282 flesch = 52 summary = Coronaviruses have several advantages as vectors over other viral expression systems: (1) coronaviruses are single-stranded RNA viruses that replicate within the cytoplasm without a DNA intermediary, making integration of the virus genome into the host cell chromosome unlikely, (2) these viruses have the largest RNA virus genome and, in principle, have room for the insertion of large foreign genes, (3) a pleiotropic secretory immune response is best induced by the stimulation of gut-associated lymphoid tissues, (4) the tropism of coronaviruses may be modified by manipulation of the spike (S) protein allowing engineering of the tropism of the vector, (5) non-pathogenic coronavirus strains infecting most species of interest (human, porcine, bovine, canine, feline, and avian) are available to develop expression systems, and (6) infectious coronavirus cDNA clones are available to design expression systems. cache = ./cache/cord-326719-p1ma4akz.txt txt = ./txt/cord-326719-p1ma4akz.txt === reduce.pl bib === id = cord-319519-mb9ofh12 author = Ding, J. title = A network-informed analysis of SARS-CoV-2 and hemophagocytic lymphohistiocytosis genes' interactions points to Neutrophil Extracellular Traps as mediators of thrombosis in COVID-19 date = 2020-07-02 pages = extension = .txt mime = text/plain words = 7247 sentences = 474 flesch = 52 summary = The algorithm establishes the shortest path between 118 the candidate genes and the known host interacting proteins with SARS-CoV-2 and calculates an 119 overall connectivity score for the network (a smaller value represents a greater connectivity) ( Fig 120 1 and Supplementary Table S1 ). The network-informed analysis presented in this paper, 262 revealed that 1) the top GO biological function associated with HLH genes is neutrophil 263 degranulation, consistent with a recent report highlighting the undervalued role of neutrophils in 264 HLH 36 ; 2) HLH genes are significantly enriched with the SARS-CoV-2 human interactome; 3) the 265 top-ranked HLH gene, AP3B1, has roles in cargo loading of type II pneumocytes, where it may 266 interact with SARS-CoV-2 to disturb surfactant physiological functions to promote 267 inflammation/pro-coagulation activities; 4) diseases/syndromes-associated with increased release 268 of Neutrophil Extracellular Traps (NETs) may predict vulnerable populations, including those 269 affecting children. cache = ./cache/cord-319519-mb9ofh12.txt txt = ./txt/cord-319519-mb9ofh12.txt === reduce.pl bib === id = cord-340125-il35gs97 author = Jayapal, Manikandan title = Genome-wide gene expression profiling of human mast cells stimulated by IgE or FcεRI-aggregation reveals a complex network of genes involved in inflammatory responses date = 2006-08-16 pages = extension = .txt mime = text/plain words = 7377 sentences = 380 flesch = 48 summary = title: Genome-wide gene expression profiling of human mast cells stimulated by IgE or FcεRI-aggregation reveals a complex network of genes involved in inflammatory responses A substantial number of genes were regulated by IgE sensitization alone; and following FcεRI aggregation, a wide range of genes were triggered, including genes for cytokines, chemokines, transcription factors, anti-apoptosis, and several genes involved in innate and acquired immunity. Other than these, several genes coding for other receptors involved in immune-responses; immunoregulatory genes; adhesion and/or cytoskeleton remodeling; regulators of apoptosis; signal transduction; transcription factors; were also upregulated by monomeric IgE (Table. Here we studied, whether monomeric-IgE alone, may activate FcεRI intracellular signaling pathways, leading to physiological responses of mast cells, by analyzing the overall tyrosine phosphorylation; fluctuations in cytosolic Ca 2+ concentration; and degranulation by measuring β-hexosaminidase release (Fig. 6A,B &6C) . cache = ./cache/cord-340125-il35gs97.txt txt = ./txt/cord-340125-il35gs97.txt === reduce.pl bib === id = cord-345516-fgn7rps3 author = Miller, Laura C title = Analysis of the swine tracheobronchial lymph node transcriptomic response to infection with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus date = 2012-10-30 pages = extension = .txt mime = text/plain words = 4730 sentences = 204 flesch = 43 summary = title: Analysis of the swine tracheobronchial lymph node transcriptomic response to infection with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus Emergence in 2006 of a novel highly pathogenic PRRSV (HP-PRRSV) isolate in China necessitated a comparative investigation into the host transcriptome response in tracheobronchial lymph nodes (TBLN) 13 days post-infection with HP-PRRSV rJXwn06, PRRSV strain VR-2332 or sham inocula. Gene IDs and log2 fold-change expression values for significant hits, that had FPKM values in both the control and the infected differential expression testing for transcripts (Cuffdiff output files), were then analyzed using the Ingenuity Pathway Analysis software. cache = ./cache/cord-345516-fgn7rps3.txt txt = ./txt/cord-345516-fgn7rps3.txt === reduce.pl bib === id = cord-339012-4juhmjaj author = Hou, Wei title = Rapid host response to an infection with Coronavirus. Study of transcriptional responses with Porcine Epidemic Diarrhea Virus date = 2020-07-28 pages = extension = .txt mime = text/plain words = 6756 sentences = 344 flesch = 48 summary = Instead, PEDV down-regulated the expression of a set of zinc finger proteins with putative antiviral activity and enhanced the expression of the transmembrane serine protease gene TMPRSS13 (alias MSPL) to support its own infection by virus-cell membrane fusion (Shi et al, 2017, Viruses, 9(5):114). Furthermore, by comprehensive datamining in biological and chemical databases and consulting related literature we identified sets of PEDV-response genes with potential to influence i) the metabolism of biogenic amines (e.g. histamine), ii) the formation of cilia and "synaptic clefts" between cells, iii) epithelial mucus production, iv) platelets activation, and v) physiological processes in the body regulated by androgenic hormones (like blood pressure, salt/water balance and energy homeostasis). The detected sets of differential expressed genes (DEGs) for PEDV and MRV were analyzed by gene set enrichment analysis (GSEA) using functional bioinformatic programs to retrieve biological processes (pathways and Gene Ontology terms [GO-term]) and associations with chemical compounds, including drugs. cache = ./cache/cord-339012-4juhmjaj.txt txt = ./txt/cord-339012-4juhmjaj.txt === reduce.pl bib === id = cord-322566-ye27nqj2 author = Huang, Yuxiang title = Stable Internal Reference Genes for Normalizing Real-Time Quantitative PCR in Baphicacanthus cusia under Hormonal Stimuli and UV Irradiation, and in Different Plant Organs date = 2017-05-03 pages = extension = .txt mime = text/plain words = 5805 sentences = 305 flesch = 49 summary = title: Stable Internal Reference Genes for Normalizing Real-Time Quantitative PCR in Baphicacanthus cusia under Hormonal Stimuli and UV Irradiation, and in Different Plant Organs cusia in this study, and the expression stability was assessed across 60 samples representing different tissues and organs under various conditions, including ultraviolet (UV) irradiation, hormonal stimuli (jasmonic acid methyl ester and abscisic acid), and in different plant organs. However, it is necessary to select suitable reference genes as internal controls under different experimental conditions for accurate RT-qPCR evaluation because of the variability in initial material, RNA integrity, RT-PCR efficiency, and RT-qPCR efficiency (Derveaux et al., 2010) . cusia was evaluated by RNA-Seq (unpublished data) in this study to identify potential reference genes suitable for transcript normalization in experiments under UV irradiation and hormonal stimuli (MeJA and ABA), and also in different plant organs. cache = ./cache/cord-322566-ye27nqj2.txt txt = ./txt/cord-322566-ye27nqj2.txt === reduce.pl bib === id = cord-323307-nu9ib62h author = Dong, Dong title = The genomes of two bat species with long constant frequency echolocation calls date = 2016-10-26 pages = extension = .txt mime = text/plain words = 7642 sentences = 381 flesch = 49 summary = For homology-based gene prediction, the protein sequences of human, mouse, dog, cow, little brown bat and large flying fox were downloaded from Ensembl Release 72 and mapped onto the repeat-masked genome using GenBlastA (She, et al. Moreover, we identified 577, 453 and 182 positively selected genes in the great leaf-nosed bat, the Chinese rufous horseshoe bat and the large flying fox, (Supplementary Tables S10, 11, 12), respectively. Clade model C implemented in PAML was employed (Weadick and Chang 2012) , and the result also persisted that more positively selected genes were detected in the branches leading to echolocating bats (Supplementary Table S20 ). The genome re-sequencing analysis has been performed based generally on the following considerations: 1) to characterize the genetic diversity and patterns of evolution; 2) to understand the genetic bases of adaptation to high altitude in the great leaf-nosed bats. cache = ./cache/cord-323307-nu9ib62h.txt txt = ./txt/cord-323307-nu9ib62h.txt === reduce.pl bib === id = cord-311430-o32d3kaw author = Shahabi, Vafa title = Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events date = 2013-03-22 pages = extension = .txt mime = text/plain words = 6477 sentences = 299 flesch = 49 summary = METHODS: To identify candidate predictive biomarkers associated with GI irAEs, gene expression profiling was performed on whole blood samples from 162 advanced melanoma patients at baseline, 3 and 11 weeks after the start of ipilimumab treatment in two phase II clinical trials (CA184004 and CA184007). In particular, on-treatment expression increases of CD177 and CEACAM1, two neutrophil-activation markers, were closely associated with GI irAEs, suggesting a possible role of neutrophils in ipilimumab-associated GI irAEs. In addition, the expression of several immunoglobulin genes increased over time, with greater increases in patients with grade 2+ GI irAEs. CONCLUSIONS: Gene expression profiling of peripheral blood, sampled before or early in the course of treatment with ipilimumab, resulted in the identification of a set of potential biomarkers that were associated with occurrence of GI irAEs. However, because of the low sensitivity of these biomarkers, they cannot be used alone to predict which patients will develop GI irAEs. Further investigation of these biomarkers in a larger patient cohort is warranted. To understand the underlying causes of ipilimumabassociated GI irAEs and identify potential predictive biomarkers, gene expression profiling was performed on whole blood samples collected from metastatic melanoma patients before and during ipilimumab treatment in two phase II clinical trials, CA184004 and CA184007 [6, 8] . cache = ./cache/cord-311430-o32d3kaw.txt txt = ./txt/cord-311430-o32d3kaw.txt === reduce.pl bib === id = cord-315072-b28yikvj author = Giotis, Efstathios S. title = Chicken interferome: avian interferon-stimulated genes identified by microarray and RNA-seq of primary chick embryo fibroblasts treated with a chicken type I interferon (IFN-α) date = 2016-08-05 pages = extension = .txt mime = text/plain words = 5878 sentences = 285 flesch = 48 summary = title: Chicken interferome: avian interferon-stimulated genes identified by microarray and RNA-seq of primary chick embryo fibroblasts treated with a chicken type I interferon (IFN-α) To generate a chicken ISG database we have compared data from three transcriptomic technology platforms: (i) the classical 3′-biased GeneChip Chicken Genome Array (32K; Affymetrix, High Wycombe, UK), (ii) the Chicken Gene 1.0 Sense Target (ST) whole transcriptome Array (Affymetrix) and (iii) Illumina (Little Chesterford, UK) RNA-seq. One of the most highly-expressed contigs was one which, when analysed by BLAST, proved to represent a homologue of STAT2, which is missing from the current ENSEMBL annotated reference chicken genome In (B) PYURF shows 24-fold suppression by IFN but the sequence surrounding PYURF shows 87-fold induction from the right-hand end of the unannotated, antisense LOC422513 and considerably higher upregulation from the left-hand end (due to its lower uninduced levels), consistent with these representing homologues of IFN-inducible human genes HERC6 and HERC5. Technologies identifying significant IRGs are listed as "1" RNA-seq (using Kal's Z test); "2" Affymetrix 32K GeneChip Chicken Genome Array and "3" Chicken Gene 1.0 ST Array' . cache = ./cache/cord-315072-b28yikvj.txt txt = ./txt/cord-315072-b28yikvj.txt === reduce.pl bib === id = cord-319517-denczc6t author = Salipalli, Sandeep title = Recent advances in live cell imaging of hepatoma cells date = 2014-07-08 pages = extension = .txt mime = text/plain words = 9184 sentences = 433 flesch = 46 summary = This review aims to provide an overview of the recent developments in the field of marker proteins (bioluminescence and fluorescent) and methodologies (fluorescent resonance energy transfer, fluorescent recovery after photobleaching and proximity ligation assay) employed as to achieve an improved imaging of biological processes in hepatoma cells. The success of live cell imaging relies on various factors including the specific imaging system, climate controlling devices for cultured cells under investigation, construction of recombinant plasmid DNA, transfer and expression of candidate genes and/or fluorescent proteins in mammalian cells. T4SS (Bartonella sp.) 60-70% 50% >70% >60% 50-60% [76] [77] [78] lipofection (1 μg) methods were used for transfection of plasmid encoding fluorescent protein (pEGFP and pEYFP) tagged to human and mouse ADRP genes in Huh-7 cells as to study the pathways of lipid droplet metabolism. cache = ./cache/cord-319517-denczc6t.txt txt = ./txt/cord-319517-denczc6t.txt === reduce.pl bib === id = cord-006230-xta38e7j author = nan title = Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V. date = 2012-02-22 pages = extension = .txt mime = text/plain words = 135419 sentences = 7042 flesch = 43 summary = Here, we will present our analysis of Ca 2+ signaling following stimulation of the FcεRI receptor and application of secretagogues that are supposed to affect Ca 2+ -dependent mast cell activation such as adenosine, endothelin-1, substance P and compound 48/80 in BMMCs and PMCs derived from mouse lines with inactivation of TRPC1, TRPC3, TRPC4, TRPC5 or TRPC6 since specific antagonists are still lacking for these TRP channels. These data indicate that increased PP2A activity is associated with modified gene expression in TG hearts possibly affecting stress response and regulation of cell signalling. As demonstrated by qPCR and Western blot experiments, mesangial cells showed a marked time-and dose-dependent upregulation of CSE mRNA and protein levels after treatment with platelet-derived growth factor (PDGF-BB). The transcription factor cAMP response element (CRE)-binding protein (CREB) plays a critical role in regulating gene expression in response to activation of the cAMPdependent signaling pathway, which is implicated in the pathophysiology of heart failure. cache = ./cache/cord-006230-xta38e7j.txt txt = ./txt/cord-006230-xta38e7j.txt === reduce.pl bib === id = cord-322286-2de6r1h6 author = Vandewege, Michael W title = Positive Selection and Gene Expression Analyses from Salivary Glands Reveal Discrete Adaptations within the Ecologically Diverse Bat Family Phyllostomidae date = 2020-07-22 pages = extension = .txt mime = text/plain words = 6211 sentences = 344 flesch = 46 summary = title: Positive Selection and Gene Expression Analyses from Salivary Glands Reveal Discrete Adaptations within the Ecologically Diverse Bat Family Phyllostomidae We sequenced expressed transcripts from phyllostomid salivary glands and found strong signals of selection among immune-related genes. We sequenced the SMG transcriptomes of nine phyllostomid bats representing different subfamilies and different diets, and through analysis of orthologs characterized how selection on coding sequence and expression differences have shaped SMGs. Nine species from seven out of the 11 recognized subfamilies were chosen to maximize representation of the phylogenetic and dietary diversity of Phyllostomidae ( fig. After correcting for FDR, we found 53 genes where models of evolution allowing positive selection were significantly better fit to the data than neutrality in both M2a and M8 tests (supplementary table S2, Supplementary Material online). Moreover, given that some Golgi body-related genes appeared under selection in all branch-site tests, this organelle played some role in the adaptive radiation of phyllostomids. cache = ./cache/cord-322286-2de6r1h6.txt txt = ./txt/cord-322286-2de6r1h6.txt === reduce.pl bib === id = cord-347917-fmb5nyxu author = Liu, Junli title = Comprehensive Genomic Characterization Analysis of lncRNAs in Cells With Porcine Delta Coronavirus Infection date = 2020-01-28 pages = extension = .txt mime = text/plain words = 4651 sentences = 251 flesch = 49 summary = In this study, genome-wide profiling of lncRNAs in swine testicular (ST) cells infected with PDCoV was performed using RNA-seq. An integrative analysis of lncRNA alterations suggested their putative role in regulating the expression of several key genes in metabolic and TNF signaling pathways during infection. There have been reports of using genome-wide association analysis between lncRNAs and the co-expressed and/or co-regulated protein-coding genes to characterize the function of the lncRNA (Huarte et al., 2010) . GO and KEGG pathway enrichment analysis of target genes revealed that lncRNAs may act in cis or trans to participate in the regulation of expression of multiple important genes in different processes including protein binding, DNA transcription, metabolism, and immune response. The functional association between regulatory lncRNA and protein-coding gene transcripts can be determined by performing expression correlation analysis coupled with ascertaining their putative role in related physiological processes. cache = ./cache/cord-347917-fmb5nyxu.txt txt = ./txt/cord-347917-fmb5nyxu.txt === reduce.pl bib === id = cord-328287-3qgzulgj author = Moni, Mohammad Ali title = Network-based analysis of comorbidities risk during an infection: SARS and HIV case studies date = 2014-10-24 pages = extension = .txt mime = text/plain words = 10643 sentences = 547 flesch = 43 summary = Then based on the gene expression, PPI and signalling pathways data, we investigate the comorbidity association of these 2 infective pathologies with other 7 diseases (heart failure, kidney disorder, breast cancer, neurodegenerative disorders, bone diseases, Type 1 and Type 2 diabetes). The differential gene expression profiling strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response and statistically dysregulates a large number of genes, pathways and PPIs subnetworks in different pathologies such as chronic heart failure (21 genes), breast cancer (16 genes) and bone diseases (11 genes). To observe the association of SARS and HIV infections with other 7 important diseases (chronic heart failure, kidney disorders, breast cancer, parkinson, osteoporosis, type 1 and type 2 diabetes), we have collected mRNA microarray raw data associated with each disease from the Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/) accession numbers are GSE9006, GSE9128, GSE15072, GSE7158, GSE8977 and GSE7621 [59] . cache = ./cache/cord-328287-3qgzulgj.txt txt = ./txt/cord-328287-3qgzulgj.txt === reduce.pl bib === id = cord-345475-ttrcmtu4 author = de Oliveira, Luisa Abruzzi title = Reference Genes for the Normalization of Gene Expression in Eucalyptus Species date = 2011-12-24 pages = extension = .txt mime = text/plain words = 9744 sentences = 595 flesch = 54 summary = Given the increasing interest in the functional genomics of Eucalyptus and the need for validated reference genes for a broader set of species and experimental conditions, we sought to identify the most stably expressed genes in a set of 21,432 genes assayed by microarray developed to compare stem vascular (xylem) and leaf tissues of E. According to the NormFinder analysis of gene expression in leaves, xylem tissues and among species, the stability values of the 15 genes studied were <0.138, with error bars no greater than 0.044 ( Fig. 3C ; Table 3 ). When we analyzed the gene expression in all tissues/organs and species, the stability value was in the range between 0.017 and 0.106, proving again that all genes elected are good references for RT-qPCR studies in Eucalyptus. By RT-qPCR, the expression stability of eight of the 50 best candidate genes selected by SAM and SDMA was addressed in different organs (leaves and flowers) and vascular tissues (xylem) derived from six species of Eucalyptus. cache = ./cache/cord-345475-ttrcmtu4.txt txt = ./txt/cord-345475-ttrcmtu4.txt === reduce.pl bib === id = cord-314915-b6aqwubh author = Futas, Jan title = Natural Killer Cell Receptor Genes in Camels: Another Mammalian Model date = 2019-07-02 pages = extension = .txt mime = text/plain words = 10040 sentences = 520 flesch = 54 summary = Here, we analyzed genes encoding selected natural killer cell receptors with a special focus on genes encoding receptors for major histocompatibility complex (MHC) class I ligands in the two domestic camel species, Camelus dromedarius and Camelus bactrianus. In the context of our work on the camelid immunogenome, the objective of this study was to characterize the genomic content of NKC and LRC with special focus on genes encoding natural killer cell receptors for MHC class I ligands in the two domestic camel species, C. dromedarius NCBI reference genome by tblastn algorithm of NCBI's BLAST ®1 for orthologous protein sequences to killer-cell lectin-like receptors recently identified in cattle as KLR genes (Schwartz et al., 2017) . The general organization of the two genomic regions, the natural killer complex (NKC) and the leukocyte receptor complex (LRC), containing genes and gene families encoding the NK cell receptors annotated based on the dromedary genome assembly CamDro2, was established and is represented in Figure 1 . cache = ./cache/cord-314915-b6aqwubh.txt txt = ./txt/cord-314915-b6aqwubh.txt === reduce.pl bib === id = cord-328899-kog99kk5 author = Ferrari, Stefano title = Barriers to and new approaches for gene therapy and gene delivery in cystic fibrosis date = 2002-12-05 pages = extension = .txt mime = text/plain words = 10491 sentences = 536 flesch = 45 summary = Strategies to overcome these barriers will be addressed in this review and include the use of: (i) clinically relevant adjuncts to overcome the extraand intracellular barriers; (ii) less-conventional delivery routes, such as intravenous or in utero administration; (iii) more efficient non-viral vectors and 'stealth' viruses which can be re-administered; and (iv) new approaches to prolong transgene expression by means of alternative promoters or integrating vectors. Interesting-Using an ex vivo sheep trachea model, we demonly, despite non-viral vectors being arguably less strated that cationic lipid-mediated gene transfer, but efficient than viruses in animal models and labora-not adenoviral vectors or recombinant Sendai virus tory studies, clinical trials have shown that this might [22] , was inhibited by normal mucus, with removal Extracellular barriers include the presence of infected mucus and sputum, mucociliary clearance and tight junctions between the cells, which limit the access of viral vectors to receptors localised on the basolateral membrane. cache = ./cache/cord-328899-kog99kk5.txt txt = ./txt/cord-328899-kog99kk5.txt === reduce.pl bib === id = cord-352200-i05h8csb author = Xu, Yi title = Transcriptome and Comparative Gene Expression Analysis of Sogatella furcifera (Horváth) in Response to Southern Rice Black-Streaked Dwarf Virus date = 2012-04-27 pages = extension = .txt mime = text/plain words = 5286 sentences = 278 flesch = 47 summary = title: Transcriptome and Comparative Gene Expression Analysis of Sogatella furcifera (Horváth) in Response to Southern Rice Black-Streaked Dwarf Virus METHODOLOGY/PRINCIPAL FINDINGS: By de novo transcriptome assembling and massive parallel pyrosequencing, we constructed two transcriptomes of WBPH and profiled the alternation of gene expression in response to SRBSDV infection in transcriptional level. As a whole, 81388 distinct unigenes have been identified and the results indicated that SRBSDV infection can potentially perturb primary metabolism and the ubiquitin-proteasome pathway of WBPH and activate immune regulatory systems, such as RNA interfering, autophagy and antimicrobial peptide production. However, some unigenes were obtained only from viruliferous or non-viruliferous samples (data not shown) and we believe these differences may be caused by distinctions that arise from long-term ecological adaptation to virus infection. In addition, GO analysis also showed a similar distribution of gene functions for non-viruliferous and viruliferous WBPH (Figure 4 ), indicating that the number of genes expressed in each GO category was not significantly affected by SRBSDV infection. cache = ./cache/cord-352200-i05h8csb.txt txt = ./txt/cord-352200-i05h8csb.txt === reduce.pl bib === id = cord-307769-rjseio5s author = Sim, Winnie H title = Expression profile of genes involved in pathogenesis of pediatric Crohn's disease date = 2012-05-24 pages = extension = .txt mime = text/plain words = 4673 sentences = 270 flesch = 41 summary = Methods: We used suppressive subtractive hybridization (SSH) and differential screening analysis to profile the mRNA expression patterns of children with CD and age‐ and sex‐matched controls without inflammatory bowel disease (IBD). The real-time RT-PCR results validated that genes represented by > 10 clones enriched by subtractive hybridization were expressed in higher abundance in CD as compared with non-IBD ileal biopsies. To contextualize our SSH findings, we compared our results with the data tables from seven microarray studies published previously, that had reported differential expression of genes between inflamed biopsies of CD and non-inflamed biopsies of non-IBD controls. The antigen presentation, inflammatory response and cancer gene network (Network 1) comprise one-third Figure 1 The relative expression levels of REG1A, MMP2 and ANPEP in ileal biopsies from 13 Crohn's disease (CD) and nine non-inflammatory bowel disease (IBD) patients. Primers used for real-time reverse transcription polymerase chain reaction quantification of ANPEP, REG1A, MMP2 and RPL32 Table S2 Differentially expressed genes specific to Crohn's Disease (CD) ileum. cache = ./cache/cord-307769-rjseio5s.txt txt = ./txt/cord-307769-rjseio5s.txt === reduce.pl bib === id = cord-332006-if46jycd author = Whitehead, Kathryn A. title = Knocking down barriers: advances in siRNA delivery date = 2009 pages = extension = .txt mime = text/plain words = 6655 sentences = 391 flesch = 42 summary = Three years later, Tuschl and co-workers published their celebrated proof-of-principle experiment demonstrating that synthetic small interfering RNA (siRNA) could achieve sequence-specific gene knockdown in a mammalian cell line 2 . Toxicity of certain cationic lipid particles has been reported both in vitro and in vivo [76] [77] [78] , and certain synthetic agents have been found to induce a gene signature of their own that might increase the off-target effects of siRNA 79, 80 . Tumour growth in a mouse model of metastatic Ewing's sarcoma was shown to be inhibited by the systemic delivery of nanoparticles formed by cyclodextrin, the targeting ligand transferrin, and siRNA specific for the EWS-FLI1 fusion gene commonly associated with the condition. Toxicogenomics of non-viral drug delivery systems for RNAi: potential impact on siRNA-mediated gene silencing activity and specificity cache = ./cache/cord-332006-if46jycd.txt txt = ./txt/cord-332006-if46jycd.txt === reduce.pl bib === id = cord-317779-j67vb7f3 author = Irizarry, Kristopher J. L. title = RNA sequencing demonstrates large-scale temporal dysregulation of gene expression in stimulated macrophages derived from MHC-defined chicken haplotypes date = 2017-08-28 pages = extension = .txt mime = text/plain words = 9733 sentences = 443 flesch = 42 summary = Our experimental design leveraged an initial 6 day window for monocytes to differentiate into macrophages, which was followed by IFNγ stimulation between 1 and 24 h to further characterize subsequent RNA gene expression and the molecular basis for dramatically different nitric oxide production and immune function between the B2 and the B19 haplotype chicken macrophages The t-3 day time point, representing 3 days of differentiation in cell culture, exhibited the greatest expression of genes with a total of 11,429 expressed in both B19 and B2 birds while just 4068 genes lacked evidence of expression in both haplotypes. Overall, the gene enrichment analysis of the RNA sequence data provides a cellular-level picture of the specific biological processes that occur over time following activation of monocyte-derived macrophages. cache = ./cache/cord-317779-j67vb7f3.txt txt = ./txt/cord-317779-j67vb7f3.txt === reduce.pl bib === id = cord-351845-bli3qm8w author = Prasad, Kartikay title = Targeting hub genes and pathways of innate immune response in COVID-19: A network biology perspective date = 2020-06-26 pages = extension = .txt mime = text/plain words = 4626 sentences = 293 flesch = 46 summary = Towards this goal, in this study, we have generated a human-SARS-CoV-2 interactome based on recently published RNA-Seq analysis of human adenocarcinomic alveolar basal epithelial (A549) cells infected with SARS-CoV-2, and identified disease-related functional genes that will provide the insights into the patho-J o u r n a l P r e -p r o o f 4 mechanisms of COVID-19. Overall, the analysis demonstrated that the upregulated genes are mainly linked to the host response to SARS-CoV-2 infection, type I interferon signaling and the cytokine-mediated signaling pathway. The PPI network analysis indicates that the pathways are enriched in host response to virus infection, type I interferons signaling, and cytokine activation. [74] reported high SARS-CoV-2 loads very early during infection, suggesting that the virus may have developed arsenals that is able to delay the IFN response by inhibiting innate immune signaling. cache = ./cache/cord-351845-bli3qm8w.txt txt = ./txt/cord-351845-bli3qm8w.txt === reduce.pl bib === id = cord-329617-gzivtsho author = Lee, Albert K. title = De novo transcriptome reconstruction and annotation of the Egyptian rousette bat date = 2015-12-07 pages = extension = .txt mime = text/plain words = 5058 sentences = 292 flesch = 52 summary = BACKGROUND: The Egyptian Rousette bat (Rousettus aegyptiacus), a common fruit bat species found throughout Africa and the Middle East, was recently identified as a natural reservoir host of Marburg virus. We performed de novo transcriptome assembly using deep RNA sequencing data from 11 distinct tissues from one male and one female bat. Rousettus aegyptiacus, commonly known as the Egyptian rousette bat, has been identified as a natural reservoir host for MARV through ecological, epidemiological, and experimental studies [10, 12, 13, 18, 19, 24] . aegyptiacus from a de novo assembly of RNA sequencing data from 11 tissues isolated from a male and a female bat. Without a common ground for comparison, it was difficult to perform downstream comparative analyses such as differential gene expression analysis; therefore, we combined contigs from all tissues into one unified, nonredundant reference transcriptome (Fig. 1d) . We further assessed biological validity of our transcriptome assembly through gene Ontology (GO) analysis of tissue-specific expression profiles. cache = ./cache/cord-329617-gzivtsho.txt txt = ./txt/cord-329617-gzivtsho.txt === reduce.pl bib === === reduce.pl bib === id = cord-336573-bpg1dg24 author = Greenaway, Hui Yee title = Extraction and characterization of the rhesus macaque T cell receptor β-chain genes date = 2009-06-09 pages = extension = .txt mime = text/plain words = 3721 sentences = 167 flesch = 55 summary = To demonstrate the use of the TRB genes extracted from the rhesus macaque genome by expressed TCRβ sequences, we used an existing database of 7218 TCRβ sequences involved in CD8 + T cell responses specific for the immunodominant Mamu-A*01-restricted SIV-SL8/TL8 and SIV-CM9 epitopes in 20 rhesus macaques30, 45. Here, we report a reference set of TRB genes extracted from the rhesus macaque genome, most of which were expressed by TCRβ sequences in our extensive database of TCRβ repertoires involved in CD8 + T cell responses to the immunodominant Mamu-A*01-restricted SL8/TL8 and CM9 epitopes derived from SIV. The best human match to each macaque region was identified and then used as a guide to determine the exact length and terminal ends of the rhesus macaque TRB gene sequences, as well as intron and exon positions. cache = ./cache/cord-336573-bpg1dg24.txt txt = ./txt/cord-336573-bpg1dg24.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-346308-9h2fk9qt author = Kaur, Rajwinder title = Microbiology of hospital wastewater date = 2020-05-01 pages = extension = .txt mime = text/plain words = 14673 sentences = 648 flesch = 34 summary = The study of hospital wastewater (HWW) microbiology is important to understand the pollution load, growth of particular pathogenic microbes, shift and drift in microbial community, development and spread of antibiotic resistance in microbes, and subsequent change in treatment efficiencies. Within past years, pieces of evidence have shown mobilization of these resistance genes from the environment into pathogenic bacteria causing health risks to humans and animals and also, demonstrating a link between environmental and clinical resistance [123] . The HWW has been reported to have two overexpressed β-lactam-resistance genes (bla GES and bla OXA ) as compared with the water collected from other aquatic bodies, which could be correlated with antibiotic usage over the time in hospitals and discharge of the residues of antibiotics in the wastewater [176] . Urban wastewater treatment plants as hotspots for antibiotic resistant bacteria and genes spread into the environment: a review cache = ./cache/cord-346308-9h2fk9qt.txt txt = ./txt/cord-346308-9h2fk9qt.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-318576-dc5n6ni4 author = Jitobaom, Kunlakanya title = Codon usage similarity between viral and some host genes suggests a codon-specific translational regulation date = 2020-05-08 pages = extension = .txt mime = text/plain words = 6821 sentences = 345 flesch = 53 summary = From the previous section, we demonstrated that human genes in the GO terms of the cell cycle and the regulation of the cell cycle process adopt codon usage patterns similar to those of þssRNA (subgroups 6, 7), -ssRNA (subgroup 4), retrovirus (HIV-1), and ambisense (subgroup 4) viruses. The lists of upregulated proteins upon viral infection were submitted to GO-TermFinder (Supplementary File 3) , and the enriched GO terms were compared to the enriched GO terms of human genes with codon usage patterns similar to RNA viruses from every subgroup. Several enriched GO terms of upregulated protein profiles during viral infections were found to be identical to the GO terms of human genes with codon usage patterns similar to RNA viruses ( Figure 4 ). Several GO terms of human genes with codon usage patterns similar to RNA viruses have been found by previous studies to be identical to the GO terms of upregulated protein profiles in viral infections. cache = ./cache/cord-318576-dc5n6ni4.txt txt = ./txt/cord-318576-dc5n6ni4.txt === reduce.pl bib === id = cord-335382-fk4um9nw author = Farver, Carol F. title = Molecular Basis of Pulmonary Disease date = 2012-08-10 pages = extension = .txt mime = text/plain words = 32320 sentences = 1613 flesch = 40 summary = When lung cancer is suspected, evaluation of the patient includes a thorough clinical, radiologic, and laboratory assessment, with collection of tissue or cytology samples to establish a pathologic diagnosis of malignancy and to classify the tumor type. Development of lung cancer occurs with multiple, complex, stepwise genetic and epigenetic changes involving allelic losses, chromosomal instability and imbalance, mutations in tumor suppressor genes (TSGs) and dominant oncogenes, epigenetic gene silencing through promoter hypermethylation, and aberrant expression of genes participating in control of cell proliferation and apoptosis [7] . In recent years, atypical adenomatous hyperplasia (AAH) has been recognized as a precursor lesion for peripheral pulmonary ACs. This lesion is defined as "a localized proliferation of mild to moderately atypical cells lining involved alveoli and, sometimes, respiratory bronchioles, resulting in focal lesions in peripheral Part IV Molecular Pathology of Human Disease alveolated lung, usually less than 5 mm in diameter and generally in the absence of underlying interstitial inflammation and fibrosis" (Figure 18 .8) [36] . cache = ./cache/cord-335382-fk4um9nw.txt txt = ./txt/cord-335382-fk4um9nw.txt === reduce.pl bib === id = cord-355927-nzoiv9pj author = Lemmon, Alan R. title = The Effect of Ambiguous Data on Phylogenetic Estimates Obtained by Maximum Likelihood and Bayesian Inference date = 2009-05-21 pages = extension = .txt mime = text/plain words = 9468 sentences = 455 flesch = 50 summary = Furthermore, within a Bayesian framework, priors on branch lengths and rate heterogeneity parameters can exacerbate the effects of ambiguous data, resulting in strongly misleading bipartition posterior probabilities. The results of this study have major implications for all analyses that rely on accurate estimates of topology or branch lengths, including divergence time estimation, ancestral state reconstruction, tree-dependent comparative methods, rate variation analysis, phylogenetic hypothesis testing, and phylogeographic analysis. We show that at least 5 factors determine the direction and magnitude of bias resulting from ambiguous characters: the number and taxonomic distribution of ambiguous characters, the strength of topological support from unambiguous characters, the degree of among-site rate variation, and the method and assumptions of the analysis (including the priors assumed in a Bayesian analysis). These rates were chosen, based on preliminary simulations, to produce data sets containing a range of phylogenetic information, resulting in posterior probabilities (given 500 unambiguous sites) for the true topology of 1/3, 2/3, 1, 1, 2/3, and 1/3, respectively. cache = ./cache/cord-355927-nzoiv9pj.txt txt = ./txt/cord-355927-nzoiv9pj.txt === reduce.pl bib === id = cord-022940-atbjwpo5 author = nan title = Poster Sessions date = 2016-09-07 pages = extension = .txt mime = text/plain words = 241182 sentences = 12746 flesch = 47 summary = We have studied the effect of inhibition of IRE1 (inositol requiring enzyme 1), which is a central mediator of endoplasmic reticulum stress and controls cell proliferation and tumor growth, on hypoxic regulation of the expression of different proliferation related genes in U87 glioma cells. Transient inhibition of Akt and mTOR protein kinase activation in tumor cells followed by reactivation of signaling pathway did not result in a time-dependent difference on EGFR, HER2 and HER3 expression levels. In our study we aimed to determine cytotoxic effect of RES in K562 human CML cell line and to evaluate the expressions of miRNAs that are associated with genetics of leukemia after treatment with RES; to investigate target genes of miRNAs which show significant expression alterations and molecular mechanisms of RES treatment. cache = ./cache/cord-022940-atbjwpo5.txt txt = ./txt/cord-022940-atbjwpo5.txt ===== Reducing email addresses cord-003254-yiqdsf9z cord-018526-rz7id5mt cord-252781-06hs9pit cord-252536-gfx4cq03 cord-014597-66vd2mdu cord-273609-whm2ce4u cord-008777-i2reanan cord-302047-vv5gpldi Creating transaction Updating adr table ===== Reducing keywords cord-001541-5d64esp4 cord-001060-9g8rwsm1 cord-000159-8y8ho2x5 cord-000580-dcid9emx cord-003044-9uqa39j9 cord-002366-t94aufs3 cord-003254-yiqdsf9z cord-003196-fdb6az0v cord-001858-nmi39n6h cord-000402-unr44dvp cord-001921-73esrper cord-000492-ec5qzurk cord-000012-p56v8wi1 cord-005216-potmzdfs cord-003514-yyzbv7ys cord-000248-zueoyesj cord-003898-y6zpvw84 cord-005476-q6o5239w cord-003387-82573enr cord-012035-rhpfpku9 cord-004893-28mrzvsc cord-002142-tdgu9sr9 cord-004222-z4butywi cord-007259-vj9tv3or cord-007390-3txwm6wr cord-010278-loey5xq9 cord-015935-r2wd1yfa cord-016095-jop2rx61 cord-012542-rsqon0w0 cord-005089-jwcmmfdw cord-005432-mqyvpepo cord-005147-mvoq9vln cord-013171-wgn529rc cord-014368-4nasrbs6 cord-007708-hr4smx24 cord-007760-it9wach2 cord-003900-5p4ektzv cord-023928-9a1w174h cord-016588-f8uvhstb cord-016293-pyb00pt5 cord-010038-0m2f0eh4 cord-014462-11ggaqf1 cord-015684-q10sx1dm cord-016364-80l5mua2 cord-011630-lfm34fsw cord-016200-zfh20im0 cord-017752-ofzm3x3a cord-004879-pgyzluwp cord-033692-txfuuu7d cord-048322-5eqdrd52 cord-102219-d3gkfo7s cord-018924-wo42j0ps cord-018145-kssjdn8y cord-018526-rz7id5mt cord-016062-h4vjkufn cord-016187-58rqc0cg cord-017156-ximzvqbm cord-017932-vmtjc8ct cord-021063-4y8m33ea cord-023647-dlqs8ay9 cord-016313-n4ewq0pt cord-020969-lh2ergpm cord-022177-j0qcjbxg cord-019050-a9datsoo cord-018647-bveks6t1 cord-252781-06hs9pit cord-015850-ef6svn8f cord-024290-8z6us7v4 cord-103505-9adtbwp2 cord-023605-zibwrv76 cord-022178-4oh02tlr cord-017853-mgsuwft0 cord-009664-kb9fnbgy cord-103465-6udhvl9n cord-103150-e9q8e62v cord-102729-b1q7gbd6 cord-252536-gfx4cq03 cord-018798-yzxy9ogf cord-102935-cx3elpb8 cord-104073-vsa5y7ip cord-020101-5rib7pe8 cord-257843-nj2707mv cord-256837-100ir651 cord-022226-qxp0gfp3 cord-260793-bb4h255w cord-023055-ntbvmssh cord-016713-pw4f8asc cord-266617-z8uecyl6 cord-266521-vovas81d cord-014597-66vd2mdu cord-272378-umvi0veu cord-252147-bvtchcbt cord-253973-zr28uujh cord-269352-0o3mryu1 cord-253450-k7p510p4 cord-258035-2tk7maqk cord-252859-zir02q69 cord-267475-6f4h3cck cord-264746-gfn312aa cord-017208-7oew461e cord-273609-whm2ce4u cord-260496-s2ba7uy3 cord-263470-vmqvropy cord-284933-flbibrcm cord-279781-5ldpz9m9 cord-260345-ugd8kkor cord-264884-ydkigome cord-267733-fuz8r3vj cord-028721-x6f26ahr cord-008777-i2reanan cord-278136-ol2buwld cord-268098-71g1w1mc cord-264996-og3sg0qw cord-275720-kf9m4zho cord-274241-biqbsggu cord-280924-g6062fwk cord-277491-q18b88lm cord-285656-7o7ofk1e cord-273910-fna7s9te cord-273347-eyxc4rt0 cord-291349-tq2n4mx3 cord-284015-vvtv492b cord-280691-nzc8ir0n cord-298131-zolwjl9u cord-290282-oxyzndsj cord-280897-el7bdkcf cord-295019-8tf8ah6g cord-301546-yck1t3pp cord-290861-5bxvenue cord-282968-kjvvoveq cord-294725-wyrg0nq8 cord-289033-vfh3op6a cord-292004-9rpoll7y cord-287396-18p171nr cord-303939-7knzjnyr cord-291719-1ku6cmwj cord-306380-msk9p1yy cord-301218-zsp5sh9o cord-309556-xv3413k1 cord-303132-m3j1dekj cord-306535-j26eqmxt cord-312551-w4tps34p cord-304913-qb9zeazk cord-320005-i30t7cvr cord-313138-y485ev30 cord-296979-8r851j4t cord-308034-9b219k0v cord-302047-vv5gpldi cord-295307-zrtixzgu cord-315498-gpzee1f2 cord-314642-oobbdgzh cord-314503-u1y1bznk cord-307202-iz1bo218 cord-304607-td0776wj cord-305177-i71z2sf4 cord-326719-p1ma4akz cord-340125-il35gs97 cord-319519-mb9ofh12 cord-345516-fgn7rps3 cord-339012-4juhmjaj cord-322566-ye27nqj2 cord-323307-nu9ib62h cord-311430-o32d3kaw cord-006230-xta38e7j cord-315072-b28yikvj cord-322286-2de6r1h6 cord-319517-denczc6t cord-347917-fmb5nyxu cord-328287-3qgzulgj cord-345475-ttrcmtu4 cord-314915-b6aqwubh cord-328899-kog99kk5 cord-352200-i05h8csb cord-332006-if46jycd cord-307769-rjseio5s cord-317779-j67vb7f3 cord-351845-bli3qm8w cord-329617-gzivtsho cord-331592-l44rupmi cord-336573-bpg1dg24 cord-352190-1987sfyz cord-354829-god79qzw cord-351548-jvl63652 cord-346308-9h2fk9qt cord-348815-lthz75oc cord-350019-4nlbu54e cord-344297-qqohijqi cord-356197-js7l86fh cord-337492-o6sy4zi4 cord-355075-ieb35upi cord-318576-dc5n6ni4 cord-355927-nzoiv9pj cord-335382-fk4um9nw cord-022940-atbjwpo5 Creating transaction Updating wrd table ===== Reducing urls cord-001541-5d64esp4 cord-000159-8y8ho2x5 cord-001060-9g8rwsm1 cord-000580-dcid9emx cord-002366-t94aufs3 cord-003254-yiqdsf9z cord-003196-fdb6az0v cord-000012-p56v8wi1 cord-005216-potmzdfs cord-003898-y6zpvw84 cord-003514-yyzbv7ys cord-000248-zueoyesj cord-003387-82573enr cord-004222-z4butywi cord-012035-rhpfpku9 cord-007259-vj9tv3or cord-012542-rsqon0w0 cord-005089-jwcmmfdw cord-005147-mvoq9vln cord-003900-5p4ektzv cord-007708-hr4smx24 cord-023928-9a1w174h cord-016588-f8uvhstb cord-010038-0m2f0eh4 cord-016364-80l5mua2 cord-102219-d3gkfo7s cord-018145-kssjdn8y cord-017932-vmtjc8ct cord-020969-lh2ergpm cord-016313-n4ewq0pt cord-015850-ef6svn8f cord-009664-kb9fnbgy cord-103465-6udhvl9n cord-103150-e9q8e62v cord-102729-b1q7gbd6 cord-252536-gfx4cq03 cord-102935-cx3elpb8 cord-256837-100ir651 cord-260793-bb4h255w cord-266617-z8uecyl6 cord-252147-bvtchcbt cord-252859-zir02q69 cord-253450-k7p510p4 cord-273609-whm2ce4u cord-258035-2tk7maqk cord-264746-gfn312aa cord-008777-i2reanan cord-278136-ol2buwld cord-268098-71g1w1mc cord-274241-biqbsggu cord-275720-kf9m4zho cord-280924-g6062fwk cord-285656-7o7ofk1e cord-284015-vvtv492b cord-280691-nzc8ir0n cord-298131-zolwjl9u cord-280897-el7bdkcf cord-301546-yck1t3pp cord-282968-kjvvoveq cord-290861-5bxvenue cord-294725-wyrg0nq8 cord-292004-9rpoll7y cord-303939-7knzjnyr cord-301218-zsp5sh9o cord-309556-xv3413k1 cord-312551-w4tps34p cord-306535-j26eqmxt cord-304913-qb9zeazk cord-296979-8r851j4t cord-302047-vv5gpldi cord-315498-gpzee1f2 cord-304607-td0776wj cord-319519-mb9ofh12 cord-339012-4juhmjaj cord-322566-ye27nqj2 cord-323307-nu9ib62h cord-311430-o32d3kaw cord-006230-xta38e7j cord-322286-2de6r1h6 cord-347917-fmb5nyxu cord-345475-ttrcmtu4 cord-328287-3qgzulgj cord-314915-b6aqwubh cord-352200-i05h8csb cord-317779-j67vb7f3 cord-331592-l44rupmi cord-354829-god79qzw cord-336573-bpg1dg24 cord-350019-4nlbu54e cord-351548-jvl63652 cord-348815-lthz75oc cord-344297-qqohijqi cord-356197-js7l86fh cord-318576-dc5n6ni4 cord-355075-ieb35upi cord-355927-nzoiv9pj cord-022940-atbjwpo5 Creating transaction Updating url table ===== Reducing named entities cord-001541-5d64esp4 cord-001060-9g8rwsm1 cord-000159-8y8ho2x5 cord-000580-dcid9emx cord-002366-t94aufs3 cord-003254-yiqdsf9z cord-003044-9uqa39j9 cord-003196-fdb6az0v cord-001858-nmi39n6h cord-001921-73esrper cord-000402-unr44dvp cord-000012-p56v8wi1 cord-005216-potmzdfs cord-000492-ec5qzurk cord-003514-yyzbv7ys cord-003898-y6zpvw84 cord-005476-q6o5239w cord-012035-rhpfpku9 cord-003387-82573enr cord-000248-zueoyesj cord-004893-28mrzvsc cord-002142-tdgu9sr9 cord-004222-z4butywi cord-007259-vj9tv3or cord-007390-3txwm6wr cord-010278-loey5xq9 cord-015935-r2wd1yfa cord-012542-rsqon0w0 cord-005432-mqyvpepo cord-016095-jop2rx61 cord-005089-jwcmmfdw cord-014368-4nasrbs6 cord-013171-wgn529rc cord-003900-5p4ektzv cord-007708-hr4smx24 cord-007760-it9wach2 cord-016293-pyb00pt5 cord-023928-9a1w174h cord-016588-f8uvhstb cord-014462-11ggaqf1 cord-010038-0m2f0eh4 cord-015684-q10sx1dm cord-016200-zfh20im0 cord-011630-lfm34fsw cord-016364-80l5mua2 cord-017752-ofzm3x3a cord-033692-txfuuu7d cord-102219-d3gkfo7s cord-048322-5eqdrd52 cord-005147-mvoq9vln cord-018924-wo42j0ps cord-018145-kssjdn8y cord-018526-rz7id5mt cord-016062-h4vjkufn cord-016187-58rqc0cg cord-017932-vmtjc8ct cord-021063-4y8m33ea cord-017156-ximzvqbm cord-020969-lh2ergpm cord-023647-dlqs8ay9 cord-016313-n4ewq0pt cord-022177-j0qcjbxg cord-004879-pgyzluwp cord-018647-bveks6t1 cord-019050-a9datsoo cord-015850-ef6svn8f cord-252781-06hs9pit cord-024290-8z6us7v4 cord-103505-9adtbwp2 cord-022178-4oh02tlr cord-023605-zibwrv76 cord-017853-mgsuwft0 cord-103465-6udhvl9n cord-102729-b1q7gbd6 cord-103150-e9q8e62v cord-252536-gfx4cq03 cord-102935-cx3elpb8 cord-018798-yzxy9ogf cord-104073-vsa5y7ip cord-020101-5rib7pe8 cord-260793-bb4h255w cord-009664-kb9fnbgy cord-257843-nj2707mv cord-256837-100ir651 cord-022226-qxp0gfp3 cord-016713-pw4f8asc cord-266617-z8uecyl6 cord-266521-vovas81d cord-272378-umvi0veu cord-253973-zr28uujh cord-252147-bvtchcbt cord-269352-0o3mryu1 cord-252859-zir02q69 cord-253450-k7p510p4 cord-258035-2tk7maqk cord-264746-gfn312aa cord-273609-whm2ce4u cord-267475-6f4h3cck cord-017208-7oew461e cord-014597-66vd2mdu cord-263470-vmqvropy cord-023055-ntbvmssh cord-260496-s2ba7uy3 cord-284933-flbibrcm cord-260345-ugd8kkor cord-279781-5ldpz9m9 cord-264884-ydkigome cord-267733-fuz8r3vj cord-278136-ol2buwld cord-273910-fna7s9te cord-268098-71g1w1mc cord-274241-biqbsggu cord-275720-kf9m4zho cord-264996-og3sg0qw cord-280924-g6062fwk cord-285656-7o7ofk1e cord-284015-vvtv492b cord-273347-eyxc4rt0 cord-277491-q18b88lm cord-028721-x6f26ahr cord-298131-zolwjl9u cord-290282-oxyzndsj cord-280691-nzc8ir0n cord-291349-tq2n4mx3 cord-280897-el7bdkcf cord-295019-8tf8ah6g cord-301546-yck1t3pp cord-290861-5bxvenue cord-294725-wyrg0nq8 cord-282968-kjvvoveq cord-289033-vfh3op6a cord-292004-9rpoll7y cord-287396-18p171nr cord-303939-7knzjnyr cord-291719-1ku6cmwj cord-306380-msk9p1yy cord-301218-zsp5sh9o cord-309556-xv3413k1 cord-312551-w4tps34p cord-303132-m3j1dekj cord-008777-i2reanan cord-306535-j26eqmxt cord-304913-qb9zeazk cord-320005-i30t7cvr cord-313138-y485ev30 cord-296979-8r851j4t cord-308034-9b219k0v cord-302047-vv5gpldi cord-295307-zrtixzgu cord-315498-gpzee1f2 cord-314642-oobbdgzh cord-314503-u1y1bznk cord-307202-iz1bo218 cord-304607-td0776wj cord-305177-i71z2sf4 cord-326719-p1ma4akz cord-340125-il35gs97 cord-319519-mb9ofh12 cord-345516-fgn7rps3 cord-339012-4juhmjaj cord-322566-ye27nqj2 cord-323307-nu9ib62h cord-311430-o32d3kaw cord-315072-b28yikvj cord-319517-denczc6t cord-322286-2de6r1h6 cord-347917-fmb5nyxu cord-328287-3qgzulgj cord-345475-ttrcmtu4 cord-314915-b6aqwubh cord-328899-kog99kk5 cord-352200-i05h8csb cord-307769-rjseio5s cord-317779-j67vb7f3 cord-332006-if46jycd cord-351845-bli3qm8w cord-329617-gzivtsho cord-331592-l44rupmi cord-336573-bpg1dg24 cord-352190-1987sfyz cord-354829-god79qzw cord-351548-jvl63652 cord-346308-9h2fk9qt cord-356197-js7l86fh cord-348815-lthz75oc cord-337492-o6sy4zi4 cord-344297-qqohijqi cord-350019-4nlbu54e cord-355075-ieb35upi cord-355927-nzoiv9pj cord-318576-dc5n6ni4 cord-335382-fk4um9nw cord-006230-xta38e7j cord-022940-atbjwpo5 Creating transaction Updating ent table ===== Reducing parts of speech cord-000159-8y8ho2x5 cord-000580-dcid9emx cord-002366-t94aufs3 cord-003196-fdb6az0v cord-000402-unr44dvp cord-001060-9g8rwsm1 cord-001541-5d64esp4 cord-001858-nmi39n6h cord-003254-yiqdsf9z cord-005216-potmzdfs cord-003044-9uqa39j9 cord-000492-ec5qzurk cord-004893-28mrzvsc cord-000012-p56v8wi1 cord-003514-yyzbv7ys cord-005476-q6o5239w cord-001921-73esrper cord-003898-y6zpvw84 cord-003387-82573enr cord-004222-z4butywi cord-010278-loey5xq9 cord-007259-vj9tv3or cord-012035-rhpfpku9 cord-002142-tdgu9sr9 cord-007390-3txwm6wr cord-012542-rsqon0w0 cord-005432-mqyvpepo cord-005089-jwcmmfdw cord-015935-r2wd1yfa cord-014368-4nasrbs6 cord-003900-5p4ektzv cord-007708-hr4smx24 cord-013171-wgn529rc cord-010038-0m2f0eh4 cord-007760-it9wach2 cord-016588-f8uvhstb cord-023928-9a1w174h cord-011630-lfm34fsw cord-102219-d3gkfo7s cord-016364-80l5mua2 cord-016200-zfh20im0 cord-048322-5eqdrd52 cord-018924-wo42j0ps cord-033692-txfuuu7d cord-017752-ofzm3x3a cord-018526-rz7id5mt cord-016062-h4vjkufn cord-018145-kssjdn8y cord-000248-zueoyesj cord-015684-q10sx1dm cord-017932-vmtjc8ct cord-016187-58rqc0cg cord-017156-ximzvqbm cord-021063-4y8m33ea cord-023647-dlqs8ay9 cord-016293-pyb00pt5 cord-019050-a9datsoo cord-020969-lh2ergpm cord-022177-j0qcjbxg cord-015850-ef6svn8f cord-252781-06hs9pit cord-024290-8z6us7v4 cord-103505-9adtbwp2 cord-023605-zibwrv76 cord-017853-mgsuwft0 cord-022178-4oh02tlr cord-103465-6udhvl9n cord-103150-e9q8e62v cord-018647-bveks6t1 cord-014462-11ggaqf1 cord-252536-gfx4cq03 cord-016313-n4ewq0pt cord-102935-cx3elpb8 cord-102729-b1q7gbd6 cord-104073-vsa5y7ip cord-016095-jop2rx61 cord-018798-yzxy9ogf cord-020101-5rib7pe8 cord-257843-nj2707mv cord-256837-100ir651 cord-260793-bb4h255w cord-266617-z8uecyl6 cord-266521-vovas81d cord-272378-umvi0veu cord-253973-zr28uujh cord-252859-zir02q69 cord-269352-0o3mryu1 cord-016713-pw4f8asc cord-253450-k7p510p4 cord-258035-2tk7maqk cord-264746-gfn312aa cord-263470-vmqvropy cord-273609-whm2ce4u cord-260496-s2ba7uy3 cord-022226-qxp0gfp3 cord-252147-bvtchcbt cord-284933-flbibrcm cord-260345-ugd8kkor cord-267733-fuz8r3vj cord-278136-ol2buwld cord-268098-71g1w1mc cord-017208-7oew461e cord-279781-5ldpz9m9 cord-273910-fna7s9te cord-274241-biqbsggu cord-275720-kf9m4zho cord-280924-g6062fwk cord-277491-q18b88lm cord-264884-ydkigome cord-284015-vvtv492b cord-267475-6f4h3cck cord-273347-eyxc4rt0 cord-285656-7o7ofk1e cord-298131-zolwjl9u cord-291349-tq2n4mx3 cord-290282-oxyzndsj cord-280897-el7bdkcf cord-264996-og3sg0qw cord-280691-nzc8ir0n cord-295019-8tf8ah6g cord-301546-yck1t3pp cord-290861-5bxvenue cord-282968-kjvvoveq cord-294725-wyrg0nq8 cord-289033-vfh3op6a cord-292004-9rpoll7y cord-287396-18p171nr cord-303939-7knzjnyr cord-291719-1ku6cmwj cord-301218-zsp5sh9o cord-306380-msk9p1yy cord-312551-w4tps34p cord-309556-xv3413k1 cord-303132-m3j1dekj cord-304913-qb9zeazk cord-320005-i30t7cvr cord-296979-8r851j4t cord-308034-9b219k0v cord-315498-gpzee1f2 cord-314642-oobbdgzh cord-313138-y485ev30 cord-314503-u1y1bznk cord-304607-td0776wj cord-302047-vv5gpldi cord-295307-zrtixzgu cord-306535-j26eqmxt cord-340125-il35gs97 cord-305177-i71z2sf4 cord-326719-p1ma4akz cord-319519-mb9ofh12 cord-339012-4juhmjaj cord-345516-fgn7rps3 cord-322566-ye27nqj2 cord-311430-o32d3kaw cord-323307-nu9ib62h cord-005147-mvoq9vln cord-315072-b28yikvj cord-322286-2de6r1h6 cord-307202-iz1bo218 cord-014597-66vd2mdu cord-319517-denczc6t cord-345475-ttrcmtu4 cord-023055-ntbvmssh cord-347917-fmb5nyxu cord-328287-3qgzulgj cord-328899-kog99kk5 cord-352200-i05h8csb cord-314915-b6aqwubh cord-307769-rjseio5s cord-332006-if46jycd cord-329617-gzivtsho cord-351845-bli3qm8w cord-331592-l44rupmi cord-336573-bpg1dg24 cord-352190-1987sfyz cord-354829-god79qzw cord-337492-o6sy4zi4 cord-317779-j67vb7f3 cord-356197-js7l86fh cord-004879-pgyzluwp cord-344297-qqohijqi cord-318576-dc5n6ni4 cord-355075-ieb35upi cord-348815-lthz75oc cord-351548-jvl63652 cord-346308-9h2fk9qt cord-350019-4nlbu54e cord-355927-nzoiv9pj cord-009664-kb9fnbgy cord-335382-fk4um9nw cord-028721-x6f26ahr cord-006230-xta38e7j cord-008777-i2reanan cord-022940-atbjwpo5 Creating transaction Updating pos table Building ./etc/reader.txt cord-022940-atbjwpo5 cord-028721-x6f26ahr cord-006230-xta38e7j cord-022940-atbjwpo5 cord-000248-zueoyesj cord-291349-tq2n4mx3 number of items: 194 sum of words: 2,063,956 average size in words: 15,176 average readability score: 45 nouns: gene; cells; genes; cell; expression; protein; virus; analysis; data; dna; study; proteins; patients; disease; results; cancer; studies; genome; infection; levels; response; activity; sequence; receptor; type; treatment; production; development; system; time; number; role; viruses; mice; control; effects; sequences; samples; species; host; acid; growth; group; therapy; function; effect; tissue; model; level; factor verbs: used; shown; identified; include; find; expressed; associated; increasing; based; induced; contains; compared; involved; suggests; cause; produced; developed; determine; provide; mediating; leading; reveal; followed; binding; observed; performed; resulting; known; indicates; relates; regulate; obtained; reduce; detected; reported; demonstrating; investigated; required; encoded; targeted; makes; studied; affect; allows; occurs; generates; gives; analyzed; describe; derive adjectives: human; different; specific; high; viral; genetic; new; clinical; molecular; important; immune; several; non; many; significant; first; low; large; similar; functional; single; small; higher; present; novel; cellular; biological; major; common; normal; various; recombinant; possible; anti; positive; dependent; potential; multiple; genomic; therapeutic; early; like; available; additional; bacterial; inflammatory; respiratory; primary; mammalian; recent adverbs: also; however; well; significantly; therefore; respectively; highly; previously; even; recently; often; furthermore; now; together; still; currently; differentially; moreover; usually; especially; directly; first; interestingly; less; far; relatively; finally; approximately; mainly; already; specifically; widely; rather; potentially; particularly; yet; much; commonly; probably; genetically; least; hence; strongly; generally; frequently; successfully; rapidly; subsequently; similarly; additionally pronouns: we; it; their; its; our; they; i; them; us; his; he; itself; one; you; her; themselves; your; she; my; him; dnae; mrnas; me; ifitm3; himself; ourselves; mir-3906; s; ifih1; imagej; wtgfp; mutationtaster3; mine; itims; ifit5; yourself; thy; thee; t98hr; snoz40; ours; n40np; mrs; mg; itsn2; imm+; ifnyr-/-mice; ifn-[3; herself; em proper nouns: RNA; PCR; T; C; Fig; DNA; University; SARS; Gene; E.; IFN; B; S.; Table; C.; mRNA; siRNA; A; II; mg; RT; M; M.; S; Institute; fi; PRRSV; N; HIV; A.; MHC; TNF; Germany; Department; Turkey; L.; Human; B.; CD4; CoV-2; ALI; P.; der; HIV-1; CHO; China; Research; USA; G; J. keywords: gene; dna; rna; cell; expression; protein; human; virus; pcr; sars; study; disease; sequence; genome; university; ifn; cancer; result; response; mouse; delivery; analysis; tnf; table; receptor; plant; patient; infection; increase; bat; vaccine; tumor; therapy; target; prrsv; pei; institute; hiv-1; high; evolution; covid-19; ali; activity; acid; vector; type; supplementary; resistance; research; production one topic; one dimension: gene file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334499/ titles(s): Evolution of Genome Size and Complexity in the Rhabdoviridae three topics; one dimension: gene; gene; cells file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166418/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339753/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164006/ titles(s): Immunogenicity | Non-neoplastic diseases of the testis | Poster Sessions five topics; three dimensions: genes gene expression; cell cells protein; cells gene cell; cells cell study; genes gene human file(s): https://doi.org/10.1101/2020.03.25.009084, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339753/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166418/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153743/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088617/ titles(s): Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia | Non-neoplastic diseases of the testis | Immunogenicity | Genome | Autorenregister Type: cord title: keyword-gene-cord date: 2021-05-24 time: 23:51 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: keywords:gene ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-012542-rsqon0w0 author: Abbas, Mostafa title: Machine learning based refined differential gene expression analysis of pediatric sepsis date: 2020-08-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Differential expression (DE) analysis of transcriptomic data enables genome-wide analysis of gene expression changes associated with biological conditions of interest. Such analysis often provides a wide list of genes that are differentially expressed between two or more groups. In general, identified differentially expressed genes (DEGs) can be subject to further downstream analysis for obtaining more biological insights such as determining enriched functional pathways or gene ontologies. Furthermore, DEGs are treated as candidate biomarkers and a small set of DEGs might be identified as biomarkers using either biological knowledge or data-driven approaches. METHODS: In this work, we present a novel approach for identifying biomarkers from a list of DEGs by re-ranking them according to the Minimum Redundancy Maximum Relevance (MRMR) criteria using repeated cross-validation feature selection procedure. RESULTS: Using gene expression profiles for 199 children with sepsis and septic shock, we identify 108 DEGs and propose a 10-gene signature for reliably predicting pediatric sepsis mortality with an estimated Area Under ROC Curve (AUC) score of 0.89. CONCLUSIONS: Machine learning based refinement of DE analysis is a promising tool for prioritizing DEGs and discovering biomarkers from gene expression profiles. Moreover, our reported 10-gene signature for pediatric sepsis mortality may facilitate the development of reliable diagnosis and prognosis biomarkers for sepsis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453705/ doi: 10.1186/s12920-020-00771-4 id: cord-048322-5eqdrd52 author: Aigner, Achim title: Delivery Systems for the Direct Application of siRNAs to Induce RNA Interference (RNAi) In Vivo date: 2006-05-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: RNA interference (RNAi) is a powerful method for specific gene silencing which may also lead to promising novel therapeutic strategies. It is mediated through small interfering RNAs (siRNAs) which sequence-specifically trigger the cleavage and subsequent degradation of their target mRNA. One critical factor is the ability to deliver intact siRNAs into target cells/organs in vivo. This review highlights the mechanism of RNAi and the guidelines for the design of optimal siRNAs. It gives an overview of studies based on the systemic or local application of naked siRNAs or the use of various nonviral siRNA delivery systems. One promising avenue is the the complexation of siRNAs with the polyethylenimine (PEI), which efficiently stabilizes siRNAs and, upon systemic administration, leads to the delivery of the intact siRNAs into different organs. The antitumorigenic effects of PEI/siRNA-mediated in vivo gene-targeting of tumor-relevant proteins like in mouse tumor xenograft models are described. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1559929/ doi: 10.1155/jbb/2006/71659 id: cord-267733-fuz8r3vj author: Al Ali, Sally title: Use of Reporter Genes in the Generation of Vaccinia Virus-Derived Vectors date: 2016-05-21 words: 7966.0 sentences: 392.0 pages: flesch: 41.0 cache: ./cache/cord-267733-fuz8r3vj.txt txt: ./txt/cord-267733-fuz8r3vj.txt summary: This broad host range allows infection of cell lines with recombinant viruses for large-scale expression of heterologous proteins, which reduces its cost This broad host range allows infection of cell lines with recombinant viruses for large-scale expression of heterologous proteins, which reduces its cost in comparison to other production systems [21, 24] . This reporter gene system has been widely used in transgenic plants, and it has also been successfully used in mammalian cells for VACV recombinant virus selection [54] . Reporter-gene assays have helped the pox virologists in basic research, for example for the study of the location, structure and function of many VACV proteins during the infection cycle and their interaction with proteins of the host cell [44, 70] . The main limitation of using VACV as a vector is the short-term gene expression, since it is a lytic virus killing the infected cells. Insertion sites for recombinant vaccinia virus construction: Effects on expression of a foreign protein abstract: Vaccinia virus (VACV) is one of the most extensively-studied viruses of the Poxviridae family. It is easy to genetically modify, so it has become a key tool for many applications. In this context, reporter genes facilitate the study of the role of foreign genes introduced into the genome of VACV. In this review, we describe the type of reporter genes that have been used to generate reporter-expressing VACV and the applications of the recombinant viruses obtained. Reporter-expressing VACV are currently employed in basic and immunology research, in the development of vaccines and cancer treatment. url: https://doi.org/10.3390/v8050134 doi: 10.3390/v8050134 id: cord-289033-vfh3op6a author: Algammal, Abdelazeem M. title: Genes Encoding the Virulence and the Antimicrobial Resistance in Enterotoxigenic and Shiga-toxigenic E. coli Isolated from Diarrheic Calves date: 2020-06-10 words: 4893.0 sentences: 208.0 pages: flesch: 47.0 cache: ./cache/cord-289033-vfh3op6a.txt txt: ./txt/cord-289033-vfh3op6a.txt summary: coli (ETEC) incriminated in calf diarrhea, with special reference to Shigatoxins genes (stx1 and stx2) and enterotoxins genes (lt and sta) that govern their pathogenesis, as well as the virulence genes; eaeA (intimin) and f41(fimbrial adhesion), and the screening of their antibiogram and antimicrobial resistance genes; aadB, sul1, and bla-TEM, a total of 274 fecal samples were collected (April 2018–Feb 2019) from diarrheic calves at different farms in El-Sharqia Governorate, Egypt. This study was aimed at determining the prevalence of STEC and ETEC incriminated in calf diarrhea, with special reference to the Shiga-toxins genes (stx1 and stx2) and enterotoxins genes (lt and sta) that govern their pathogenesis, as well as the virulence genes; eaeA and f 41, and the screening of their antimicrobial resistance profiles and antimicrobial resistance genes; aadB, sul1, and bla-TEM. abstract: Calf diarrhea is one of the considerable infectious diseases in calves, which results in tremendous economic losses globally. To determine the prevalence of Shiga-toxigenic E. coli (STEC) and Enterotoxigenic E. coli (ETEC) incriminated in calf diarrhea, with special reference to Shiga- toxins genes (stx1 and stx2) and enterotoxins genes (lt and sta) that govern their pathogenesis, as well as the virulence genes; eaeA (intimin) and f41(fimbrial adhesion), and the screening of their antibiogram and antimicrobial resistance genes; aadB, sul1, and bla-TEM, a total of 274 fecal samples were collected (April 2018–Feb 2019) from diarrheic calves at different farms in El-Sharqia Governorate, Egypt. The bacteriological examination revealed that the prevalence of E. coli in diarrheic calves was 28.8%. The serotyping of the isolated E. coli revealed 7 serogroups; O(26), O(128), O(111), O(125), O(45), O(119) and O(91). Furthermore, the Congo red binding test was carried out, where 89.8% of the examined strains (n = 71) were positive. The antibiogram of the isolated strains was investigated; the majority of E. coli serotypes exhibit multidrug resistance (MDR) to four antimicrobial agents; neomycin, gentamycin, streptomycin, and amikacin. Polymerase chain reaction (PCR) was used to detect the prevalence of the virulence genes; stx1, stx2 lt, sta, f41 and eaeA, as well as the antimicrobial resistance genes; aadB, sul1, and bla-TEM. The prevalence of STEC was 20.2% (n = 16), while the prevalence of ETEC was 30.4% (n = 24). Briefly, the Shiga toxins genes; stx1 and stx2, are the most prevalent virulence genes associated with STEC, which are responsible for the pathogenesis of the disease and helped by the intimin gene (eaeA). In addition, the lt gene is the most prevalent enterotoxin gene accompanied by the ETEC strains, either alone or in combination with sta and/or f41 genes. The majority of pathogenic E. coli incriminated in calf diarrhea possesses the aadB resistance gene, followed by the sul1 gene. Enrofloxacin, florfenicol, amoxicillin-clavulanic acid, and ampicillin-sulbactam, are the most effective antimicrobial agents against the isolated STEC and ETEC strains. url: https://www.ncbi.nlm.nih.gov/pubmed/32532070/ doi: 10.3390/toxins12060383 id: cord-024290-8z6us7v4 author: Allen, Edward E. title: Time Series Adjustment Enhancement of Hierarchical Modeling of Arabidopsis Thaliana Gene Interactions date: 2020-02-01 words: 3236.0 sentences: 209.0 pages: flesch: 53.0 cache: ./cache/cord-024290-8z6us7v4.txt txt: ./txt/cord-024290-8z6us7v4.txt summary: Network models of gene interactions, using time course gene transcript abundance data, are computationally created using a genetic algorithm designed to incorporate hierarchical Bayesian methods with time series adjustments. Second, the addition of time series adjustment to improve the independence of the model''s residuals gives these techniques stronger statistical foundations. In complicated modeling situations (e.g., like ours where we need to obtain closed form likelihoods of DAGs within a hierarchical structure in order to produce posterior probabilities of edges), it is common to derive results as if there were non-correlated residuals, as we have done in previous work. The use of the time series adjusted next state Norris-Patton likelihood, along with a tailor-made genetic algorithm and Bayesian model averaging, allows for the rigorous estimation of posterior probabilities for all gene pair interactions. Using the transcript abundance data for 26 Arabidopsis thaliana genes stimulated by ACC, gene interaction models for a next state with and without time series adjustment were computationally created, shown in Fig. 3 . abstract: Network models of gene interactions, using time course gene transcript abundance data, are computationally created using a genetic algorithm designed to incorporate hierarchical Bayesian methods with time series adjustments. The posterior probabilities of interaction between pairs of genes are based on likelihoods of directed acyclic graphs. This algorithm is applied to transcript abundance data collected from Arabidopsis thaliana genes. This study extends the underlying statistical and mathematical theory of the Norris-Patton likelihood by including time series adjustments. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197098/ doi: 10.1007/978-3-030-42266-0_11 id: cord-019050-a9datsoo author: Ambrogi, Federico title: Bioinformatics and Nanotechnologies: Nanomedicine date: 2014 words: 8851.0 sentences: 367.0 pages: flesch: 31.0 cache: ./cache/cord-019050-a9datsoo.txt txt: ./txt/cord-019050-a9datsoo.txt summary: In this chapter we focus on the bioinformatics strategies for translating genome-wide expression analyses into clinically useful cancer markers with a specific focus on breast cancer with a perspective on new diagnostic device tools coming from the field of nanobiotechnology and the challenges related to high-throughput data integration, analysis, and assessment from multiple sources. In this chapter we focus on the bioinformatics strategies for translating genome-wide expression analyses into clinically useful cancer markers with a specific focus on breast cancer with a perspective on new diagnostic device tools coming from the field of nanobiotechnology and the challenges related to high-throughput data integration, analysis, and assessment from multiple sources. In particular, DNA microarray-based technology, with the simultaneous evaluation of thousands of genes, has provided researchers with an opportunity to perform comprehensive molecular and genetic profiling of breast cancer able to classify it into some clinically relevant subtypes and in the attempt to predict the prognosis or the response to treatment [32.5-8]. abstract: In this chapter we focus on the bioinformatics strategies for translating genome-wide expression analyses into clinically useful cancer markers with a specific focus on breast cancer with a perspective on new diagnostic device tools coming from the field of nanobiotechnology and the challenges related to high-throughput data integration, analysis, and assessment from multiple sources. Great progress in the development of molecular biology techniques has been seen since the discovery of the structure of deoxyribonucleic acid (DNA) and the implementation of a polymerase chain reaction (PCR) method. This started a new era of research on the structure of nucleic acids molecules, the development of new analytical tools, and DNA-based analyses that allowed the sequencing of the human genome, the completion of which has led to intensified efforts toward comprehensive analysis of mammalian cell struc ture and metabolism in order to better understand the mechanisms that regulate normal cell behavior and identify the gene alterations responsible for a broad spectrum of human diseases, such as cancer, diabetes, cardiovascular diseases, neurodegenerative disorders, and others. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124100/ doi: 10.1007/978-3-642-30574-0_32 id: cord-001060-9g8rwsm1 author: Arruebo, Manuel title: Assessment of the Evolution of Cancer Treatment Therapies date: 2011-08-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.). In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine). We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759197/ doi: 10.3390/cancers3033279 id: cord-003514-yyzbv7ys author: Arslan, Mehboob title: Dynamic Expression of Interferon Lambda Regulated Genes in Primary Fibroblasts and Immune Organs of the Chicken date: 2019-02-14 words: 6080.0 sentences: 326.0 pages: flesch: 44.0 cache: ./cache/cord-003514-yyzbv7ys.txt txt: ./txt/cord-003514-yyzbv7ys.txt summary: The transcriptional profiling using RNA-seq and subsequent bioinformatics analysis (gene ontology, differential expressed genes, and KEGGs analysis) of the bursa of Fabricious and the thymus demonstrated an upregulation of crucial immune genes (viperin, IKKB, CCL5, IL1β, and AP1) as well as the antiviral signaling pathways. Although CEF do not possess receptors for IFN-λ, slight temporal expression of DEGs in response to chIFN-λ treatment signifies its antiviral potential in primary cells. Furthermore, studies have also revealed that a high degree of cell type specificity in receptor-ligand interactions make avian IFNs distinct from mammalian IFNs. Recently, it has been established that chicken IFN-λ inhibits low pathogenic influenza virus replication in CEFs; however, as compared to chIFN-γ and chIFN-β, higher doses are required to induce ISGs and maintain the strong antiviral state in the cells [14] . Our data suggest that significant antiviral, cell cycle regulators, and biologically active genes are expressed in response to administered chicken IFN. abstract: Interferons (IFNs) are pleiotropic cytokines that establish a first line of defense against viral infections in vertebrates. Several types of IFN have been identified; however, limited information is available in poultry, especially using live animal experimental models. IFN-lambda (IFN-λ) has recently been shown to exert a significant antiviral impact against viral pathogens in mammals. In order to investigate the in vivo potential of chicken IFN-λ (chIFN-λ) as a regulator of innate immunity, and potential antiviral therapeutics, we profiled the transcriptome of chIFN-λ-stimulated chicken immune organs (in vivo) and compared it with primary chicken embryo fibroblasts (in vitro). Employing the baculovirus expression vector system (BEVS), recombinant chIFN-λ3 (rchIFN-λ3) was produced and its biological activities were demonstrated. The rchIFNλ3 induced a great array of IFN-regulated genes in primary chicken fibroblast cells. The transcriptional profiling using RNA-seq and subsequent bioinformatics analysis (gene ontology, differential expressed genes, and KEGGs analysis) of the bursa of Fabricious and the thymus demonstrated an upregulation of crucial immune genes (viperin, IKKB, CCL5, IL1β, and AP1) as well as the antiviral signaling pathways. Interestingly, this experimental approach revealed contrasting evidence of the antiviral potential of chIFN-λ in both in vivo and in vitro models. Taken together, our data signifies the potential of chIFN-λ as a potent antiviral cytokine and highlights its future possible use as an antiviral therapeutic in poultry. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409627/ doi: 10.3390/genes10020145 id: cord-290861-5bxvenue author: Ashwell, M. title: Characterization of gene expression in naturally occurring feline degenerative joint disease-associated pain date: 2018-11-19 words: 4901.0 sentences: 225.0 pages: flesch: 51.0 cache: ./cache/cord-290861-5bxvenue.txt txt: ./txt/cord-290861-5bxvenue.txt summary: Expression of an investigator-selected set of pain signaling genes (including ASIC3, ATF3, COX2, CX3CL1, NAV1.7, NAV1.8, NAV1.9, NGF, NK1R, TNFα, TRKA) in lumbar spinal cord dorsal horn and lumbar dorsal root ganglia tissues from clinically healthy cats and cats with DJD were studied using quantitative RT-PCR (qPCR). After the most stable reference genes were identified, a selection of genes previously associated with nociception in rodent models, and of interest to the authors, were examined using qPCR in the same samples to allow us to start characterizing the neurobiological signature of pain associated with DJD in cats. After a set of stable reference genes were identified for each tissue type, 13 genes associated with pain in rodents were selected (based on current knowledge of genes involved in pain states (Foulkes and Wood, 2008) and their expression levels compared in the DRG from DJD-affected and healthy samples. abstract: Degenerative joint disease (DJD) associated-pain is a clinically relevant and common condition affecting domesticated cats and other species including humans. Identification of the neurobiological signature of pain is well developed in rodent pain models, however such information is lacking from animals or humans with naturally occurring painful conditions. In this study, identification of housekeeping genes (HKG) for neuronal tissue and expression levels of genes considered associated with chronic pain in rodent models were explored in cats with naturally occurring osteoarthritic pain. Fourteen adult cats were evaluated — seven without clinical signs of osteoarthritic pain, and seven with hind limb radiographic DJD and pain. Expression of an investigator-selected set of pain signaling genes (including ASIC3, ATF3, COX2, CX3CL1, NAV1.7, NAV1.8, NAV1.9, NGF, NK1R, TNFα, TRKA) in lumbar spinal cord dorsal horn and lumbar dorsal root ganglia tissues from clinically healthy cats and cats with DJD were studied using quantitative RT-PCR (qPCR). HKG identified as the most stable across all tissue samples were many of the ribosomal protein genes, such as RPL30 and RPS19. qPCR results showed ATF3 and CX3CL1 up-regulated in DJD-affected dorsal root ganglia compared to clinically healthy controls. In spinal cord, CX3CL1 was up-regulated and NGF was down-regulated when DJD-affected samples were compared to healthy samples. Further work is needed to understand the neurobiology of pain in naturally occurring disease and what rodent models are predictive of these changes in more heterogeneous populations such as domestic cats. url: https://api.elsevier.com/content/article/pii/S1090023318307524 doi: 10.1016/j.tvjl.2018.11.008 id: cord-017208-7oew461e author: Aurigemma, Rosemarie title: Regulatory Aspects in the Development of Gene Therapies date: 2005 words: 18290.0 sentences: 816.0 pages: flesch: 37.0 cache: ./cache/cord-017208-7oew461e.txt txt: ./txt/cord-017208-7oew461e.txt summary: Table 1 Beyond a Good Idea: What the Successful Investigator Has Already Done With a Project Leading to Commercial Development Defined candidate biologic (or molecule) Made comparisons with similar products Characteristics of product are consistent with pharmaceutical requirements Production scale is adequate Product characterization is adequate Laboratory reference standard exists In vitro potency assay has been developed Stability studies develop confidence product is a "drug" Reproducible model systems have confirmed in vivo activity with clinical product Early animal work includes some toxicology Scale-up requirements practical for initial clinical trials In general, reflects experience and scientific maturity of investigator In addition to the US agencies that develop the regulations that govern drug development and licensing, the International Conference on Harmonization (ICH) was formed in April 1990 involving the United States, the European Union, and Japan to address the issue of globalizing such regulations. abstract: Preclinical therapeutics development research is directed toward fulfilling two overlapping sets of goals. A set of scientific goals includes defining the best molecule or biologic construct for the task at hand, and proving the case for its development. The second set of goals addresses regulatory requirements necessary to introduce the agent into human subjects. In the case of “small molecule” drugs, in most cases the identity of the molecule and appropriate safety studies are straightforward. In contrast, the development of biologic agents, including gene therapies discussed here, presents distinct challenges. The nature of the “drug” may be an organism subject to mutation or selection of variants through recombination. Its properties may vary depending on the scale and method of its preparation, purification, and storage. How to test adequately for its safety prior to first introduction in humans may not be straightforward owing to intrinsic differences in response to the agent expected in humans as compared to animals. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121712/ doi: 10.1007/978-1-59259-785-7_29 id: cord-002366-t94aufs3 author: Aurrecoechea, Cristina title: EuPathDB: the eukaryotic pathogen genomics database resource date: 2017-01-04 words: 3783.0 sentences: 204.0 pages: flesch: 47.0 cache: ./cache/cord-002366-t94aufs3.txt txt: ./txt/cord-002366-t94aufs3.txt summary: To facilitate the discovery of meaningful biological relationships, the databases couple preconfigured searches with visualization and analysis tools for comprehensive data mining via intuitive graphical interfaces and APIs. All data are analyzed with the same workflows, including creation of gene orthology profiles, so data are easily compared across data sets, data types and organisms. Expanded data content is mostly genomic and functional genomic data while new data types include protein microarray, metabolic pathways, compounds, quantitative proteomics, copy number variation, and polysomal transcriptomics. New features include consistent categorization of searches, data sets and genome browser tracks; redesigned gene pages; effective integration of alternative transcripts; and a EuPathDB Galaxy instance for private analyses of a user''s data. The near-seamless integration of strategy results with tools for functional enrichment analyses and transcript interpretation as well as our new Galaxy workspace and the availability of publicly shared strategies augment the data mining experience in EuPathDB. abstract: The Eukaryotic Pathogen Genomics Database Resource (EuPathDB, http://eupathdb.org) is a collection of databases covering 170+ eukaryotic pathogens (protists & fungi), along with relevant free-living and non-pathogenic species, and select pathogen hosts. To facilitate the discovery of meaningful biological relationships, the databases couple preconfigured searches with visualization and analysis tools for comprehensive data mining via intuitive graphical interfaces and APIs. All data are analyzed with the same workflows, including creation of gene orthology profiles, so data are easily compared across data sets, data types and organisms. EuPathDB is updated with numerous new analysis tools, features, data sets and data types. New tools include GO, metabolic pathway and word enrichment analyses plus an online workspace for analysis of personal, non-public, large-scale data. Expanded data content is mostly genomic and functional genomic data while new data types include protein microarray, metabolic pathways, compounds, quantitative proteomics, copy number variation, and polysomal transcriptomics. New features include consistent categorization of searches, data sets and genome browser tracks; redesigned gene pages; effective integration of alternative transcripts; and a EuPathDB Galaxy instance for private analyses of a user's data. Forthcoming upgrades include user workspaces for private integration of data with existing EuPathDB data and improved integration and presentation of host–pathogen interactions. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210576/ doi: 10.1093/nar/gkw1105 id: cord-003900-5p4ektzv author: Bai, Hao title: Allele-Specific Expression of CD4(+) T Cells in Response to Marek’s Disease Virus Infection date: 2019-09-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Marek’s disease (MD) is a T cell lymphoma disease induced by Marek’s disease virus (MDV), a highly oncogenic α herpesvirus primarily affecting chickens. MD is a chronic infectious disease that threatens the poultry industry. However, the mechanisms of genetic resistance for MD are complex and not completely understood. In this study, to identify high-confidence candidate genes of MD genetic resistance, high throughput sequencing (RNA-seq) was used to obtain transcriptomic data of CD4(+) T cells isolated from MDV-infected and non-infected groups of two reciprocal crosses of individuals mating by two highly inbred chicken lines (6(3) MD-resistant and 7(2) MD-susceptible). After RNA-seq analysis with two biological replicates in each group, we identified 61 and 123 single nucleotide polymorphisms (SNPs) (false discovery rate (FDR) < 0.05) annotated in 39 and 132 genes in intercrosses 6(3) × 7(2) and 7(2) × 6(3), respectively, which exhibited allele-specific expression (ASE) in response to MDV infection. Similarly, we identified 62 and 79 SNPs annotated in 66 and 96 genes in infected and non-infected groups, respectively. We identified 534 and 1543 differentially expressed genes (DEGs) (FDR < 0.05) related to MDV infection in intercrosses 6(3) × 7(2) and 7(2) × 6(3), respectively. We also identified 328 and 20 DEGs in infected and non-infected groups, respectively. The qRT-PCR using seven DEGs further verified our results of RNA-seq analysis. The qRT-PCR of 11 important ASE genes was performed for gene functional validation in CD4(+) T cells and tumors. Combining the analyses, six genes (MCL1, SLC43A2, PDE3B, ADAM33, BLB1, and DMB2), especially MCL1, were highlighted as the candidate genes with the potential to be involved in MDV infection. Gene-set enrichment analysis revealed that many ASE genes are linked to T cell activation, T cell receptor (TCR), B cell receptor (BCR), ERK/MAPK, and PI3K/AKT-mTOR signaling pathways, which play potentially important roles in MDV infection. Our approach underlines the importance of comprehensive functional studies for gaining valuable biological insight into the genetic factors behind MD and other complex traits, and our findings provide additional insights into the mechanisms of MD and disease resistance breeding in poultry. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770979/ doi: 10.3390/genes10090718 id: cord-016313-n4ewq0pt author: Baranyi, Lajos title: Advances in Lentiviral Vector-based Cell Therapy with Mesenchymal Stem Cells date: 2012-09-27 words: 20575.0 sentences: 824.0 pages: flesch: 39.0 cache: ./cache/cord-016313-n4ewq0pt.txt txt: ./txt/cord-016313-n4ewq0pt.txt summary: The field of possible application of mesenchymal stem cells in medicine and research expanded tremendously with the advent of improved Lentiviral-vectors capable of inserting stable copies of genes of interest and expressing proteins or biologically active RNA species ad libitum, performing delicate gene editing or active gene silencing or serving as advanced drug delivery systems utilized in ex vivo cell therapy. Implantation of Lentiviral vector-transduced human bone marrow mesenchymal cells using collagen scaffolds into immunode fi cient mice resulted in ef fi cient engraftment of gene-engineered cells and provided sites for transgene-expression in vivo. Moreover, it did not alter the differentiation potential of either HSCs or MSCs. In addition, the therapeutic potential of CD133+ and MSC progenitor cells transduced ex vivo with Lentiviral vector encoding the mature form of vascular endothelial growth factor D (VEGF-D ) or the enhanced green fl uorescent protein (eGFP) marker gene achieved permanent gene expression. abstract: The field of possible application of mesenchymal stem cells in medicine and research expanded tremendously with the advent of improved Lentiviral-vectors capable of inserting stable copies of genes of interest and expressing proteins or biologically active RNA species ad libitum, performing delicate gene editing or active gene silencing or serving as advanced drug delivery systems utilized in ex vivo cell therapy. The combination of these two fields has created a number of new areas of research in the landscape of modern medicine which are now extensively studied and discussed here. These areas include tissue engineering, tissue repair, wound healing and tissue implants, anticancer therapies, angiogenesis, myocardial infarction and repair as well as understanding and treating acute lung damage and injury. In addition, genetically modified, tagged MSCs are being intensively deployed in research and therapeutic attempts of the various ailments of the central nervous system including Parkinson’s disease, Alzheimer’s disease, various phases of acute ischemia and trauma. The emergence of new and important data for type II diabetes research is being followed with treatment suggestions and studies of senescence to find novel applications for genetically engineered MSCs. We find in ­general that genetically modified MSCs are at the cusp of breaking through from basic research into the next phase of clinical trials. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120558/ doi: 10.1007/978-1-62703-200-1_14 id: cord-337492-o6sy4zi4 author: Baric, Ralph S. title: Next-Generation High-Throughput Functional Annotation of Microbial Genomes date: 2016-10-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Host infection by microbial pathogens cues global changes in microbial and host cell biology that facilitate microbial replication and disease. The complete maps of thousands of bacterial and viral genomes have recently been defined; however, the rate at which physiological or biochemical functions have been assigned to genes has greatly lagged. The National Institute of Allergy and Infectious Diseases (NIAID) addressed this gap by creating functional genomics centers dedicated to developing high-throughput approaches to assign gene function. These centers require broad-based and collaborative research programs to generate and integrate diverse data to achieve a comprehensive understanding of microbial pathogenesis. High-throughput functional genomics can lead to new therapeutics and better understanding of the next generation of emerging pathogens by rapidly defining new general mechanisms by which organisms cause disease and replicate in host tissues and by facilitating the rate at which functional data reach the scientific community. url: https://doi.org/10.1128/mbio.01245-16 doi: 10.1128/mbio.01245-16 id: cord-268098-71g1w1mc author: Beckman, M. F. title: Comorbidities and Susceptibility to COVID-19: A Generalized Gene Set Meta-Analysis Approach date: 2020-09-15 words: 4203.0 sentences: 316.0 pages: flesch: 49.0 cache: ./cache/cord-268098-71g1w1mc.txt txt: ./txt/cord-268098-71g1w1mc.txt summary: Visualization of protein-protein interaction networks was completed using STRINGv11.0 [31] program by testing different confidence levels to identify ontologies of biological significance for the significant pathways associated with comorbidities. Possible comorbidity significant associated gene sets/pathways were checked for quality control by generating Quantile-Quantile (Q-Q) plots using observed quantiles and residual Z-scores of genes within the gene set, based on the MAGMAv1.07b publicly available Rv3.6.2 script (posthoc_qc_107a.r) [32, 33] . . https://doi.org /10.1101 was used to test the top 250 human mRNA gene expressions for each comorbidity based on available human data using NCBI GEO[39] , by only including comorbidities that had significant pathways identified by MAGMAv1.07b and VEP STRING analyses. For each comorbidity, human mRNA gene expression data corresponding to average log-fold change (aLFC) were formatted for clustering of genes identified by MAGMAv1.07b and VEP and subsequently matched to STRING protein-protein interactions. abstract: Background The COVID-19 pandemic has led to over 820,000 deaths for almost 24 million confirmed cases worldwide, as of August 27th, 2020, per WHO report. Risk factors include pre-existing conditions such as cancer, cardiovascular disease, diabetes, obesity, and cancer. There are currently no effective treatments. Our objective was to complete a meta-analysis to identify comorbidity-associated single nucleotide polymorphisms (SNPs), potentially conferring increased susceptibility to SARS-CoV-2 infection using a computational approach. Results SNP datasets were downloaded from publicly available GWAS catalog for 141 of 258 candidate COVID-19 comorbidities. Gene-level SNP analysis was performed to identify significant pathways by using MAGMA program. SNP annotation program was used to analyze MAGMA-identified genes. COVID-19 comorbidities from six disease categories were found to have significant associated pathways, which were validated by Q-Q plots (p<0.05). The top 250 human mRNA gene expressions for SNP-affected pathways, extracted from publicly accessible gene expression profiles, were evaluated for significant pathways. Protein-protein interactions of identified differentially expressed genes, visualized with STRING program, were significant (p<0.05). Gene interaction networks were found to be relevant to SARS and influenza pathogenesis. Conclusion Pathways potentially affected by or affecting SARS-CoV-2 infection were identified in underlying medical conditions likely to confer susceptibility and/or severity to COVID-19. Our findings have implications in COVID-19 treatment development. Keywords: SARS-CoV-2, COVID-19, comorbidity, susceptibility, severity url: https://doi.org/10.1101/2020.09.14.20192609 doi: 10.1101/2020.09.14.20192609 id: cord-000159-8y8ho2x5 author: Bekaert, Michaël title: Recode-2: new design, new search tools, and many more genes date: 2009-09-25 words: 2625.0 sentences: 138.0 pages: flesch: 42.0 cache: ./cache/cord-000159-8y8ho2x5.txt txt: ./txt/cord-000159-8y8ho2x5.txt summary: ''Recoding'' is a term used to describe non-standard read-out of the genetic code, and encompasses such phenomena as programmed ribosomal frameshifting, stop codon readthrough, selenocysteine insertion and translational bypassing. It provides access to detailed information on genes known to utilize translational recoding and allows complex search queries, browsing of recoding data and enhanced visualization of annotated sequence elements. The term ''translational recoding'' describes the utilization of non-standard decoding during protein synthesis and encompasses such processes as ribosomal frameshifting, codon redefinition, translational bypassing and StopGo (1) (2) (3) (4) (5) (6) (7) . To facilitate further development of computational tools for the prediction of recoded genes in the ever faster growing body of sequence data, as well as to provide bench researchers with upto-date information on recoding, an efficient means of Recode database population and annotation are now required. RECODE: a database of frameshifting, bypassing and codon redefinition utilized for gene expression abstract: ‘Recoding’ is a term used to describe non-standard read-out of the genetic code, and encompasses such phenomena as programmed ribosomal frameshifting, stop codon readthrough, selenocysteine insertion and translational bypassing. Although only a small proportion of genes utilize recoding in protein synthesis, accurate annotation of ‘recoded’ genes lags far behind annotation of ‘standard’ genes. In order to address this issue, provide a service to researchers in the field, and offer training data for developers of gene-annotation software, we have gathered together known cases of recoding within the Recode database. Recode-2 is an improved and updated version of the database. It provides access to detailed information on genes known to utilize translational recoding and allows complex search queries, browsing of recoding data and enhanced visualization of annotated sequence elements. At present, the Recode-2 database stores information on approximately 1500 genes that are known to utilize recoding in their expression—a factor of approximately three increase over the previous version of the database. Recode-2 is available at http://recode.ucc.ie url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808893/ doi: 10.1093/nar/gkp788 id: cord-000248-zueoyesj author: Berretta, Regina title: Cancer Biomarker Discovery: The Entropic Hallmark date: 2010-08-18 words: 33594.0 sentences: 1678.0 pages: flesch: 43.0 cache: ./cache/cord-000248-zueoyesj.txt txt: ./txt/cord-000248-zueoyesj.txt summary: These authors cite, for example, ''''mitochondrial dysfunction'''' [5, 6] (including, but not limited to ''''glucose avidity'''' [7] and ''''a shift in glucosemetabolism from oxidative phosphorylation to glycolysis'''' [6, 8] , ''''altered glycolysis'''' [9] , ''''altered bioenergetic function of mitochondria'''' [10] ), ''''dysregulation of cell cycle and defective genome-integrity checkpoints'''' [11] , ''''aberrant DNA methylation'''' [12] (''''promoter hypermethylation of hallmark cancer genes'''' [13] and ''''CpG island hypermethylation and global genomic hypomethylation'''' [14] ), ''''shift in cellular metabolism'''' [15, 16, 17] , ''''regional hypoxia'''' [18] , ''''microenviroment acidosis'''' [19] , ''''abnormal microRNA regulation'''' [20, 21] , ''''aneuploidy'''' and ''''chromosome aberrations'''' [22, 23, 24, 25, 26] , ''''disruption of cellular junctions'''' [27] , ''''avoidance of the immune response'''' [28] , ''''pre-existing chronic inflammatory conditions'''' [29, 30] , ''''cancerrelated inflammation'''' [29] , ''''disabled autophagy'''' [28] , ''''impaired cellular senescence'''' [31] , ''''altered NF-kappaB signalling'''' [32] , ''''altered growth patterns, not altered growth per se'''' [33] , ''''disregulated DNA methylation and histone modifications'''' [34] , ''''tissue dedifferentiation'''' [35, 36] , and ''''somatically heritable molecular alterations'''' [37] . abstract: BACKGROUND: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. METHODOLOGY/PRINCIPAL FINDINGS: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. CONCLUSIONS/SIGNIFICANCE: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-througput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923618/ doi: 10.1371/journal.pone.0012262 id: cord-252536-gfx4cq03 author: Bieniossek, Christoph title: MultiBac: expanding the research toolbox for multiprotein complexes date: 2011-12-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Protein complexes composed of many subunits carry out most essential processes in cells and, therefore, have become the focus of intense research. However, deciphering the structure and function of these multiprotein assemblies imposes the challenging task of producing them in sufficient quality and quantity. To overcome this bottleneck, powerful recombinant expression technologies are being developed. In this review, we describe the use of one of these technologies, MultiBac, a baculovirus expression vector system that is particularly tailored for the production of eukaryotic multiprotein complexes. Among other applications, MultiBac has been used to produce many important proteins and their complexes for their structural characterization, revealing fundamental cellular mechanisms. url: https://www.ncbi.nlm.nih.gov/pubmed/22154230/ doi: 10.1016/j.tibs.2011.10.005 id: cord-000012-p56v8wi1 author: Bigot, Yves title: Molecular evidence for the evolution of ichnoviruses from ascoviruses by symbiogenesis date: 2008-09-18 words: 6419.0 sentences: 293.0 pages: flesch: 44.0 cache: ./cache/cord-000012-p56v8wi1.txt txt: ./txt/cord-000012-p56v8wi1.txt summary: CONCLUSION: Our results provide molecular evidence supporting the origin of ichnoviruses from ascoviruses by lateral transfer of ascoviral genes into ichneumonid wasp genomes, perhaps the first example of symbiogenesis between large DNA viruses and eukaryotic organisms. With respect to both species number and mechanisms that lead to successful parasitism, endoparasitic wasps are known to inject secretions at oviposition, but only a few lineages use viruses or virus-like particles (VLPs) to evade or to suppress host defences. Extending our investigations to proteins encoded by open reading frames of certain ascoviruses and bracoviruses, hosts and bacteria, in the light of recent analyses about the involvement of the replication machinery of virus groups related to ascoviruses in lateral gene transfer [29] , we discuss the robustness and the limits of the molecular evidence supporting an ascovirus origin for ichnovirus lineages. abstract: BACKGROUND: Female endoparasitic ichneumonid wasps inject virus-like particles into their caterpillar hosts to suppress immunity. These particles are classified as ichnovirus virions and resemble ascovirus virions, which are also transmitted by parasitic wasps and attack caterpillars. Ascoviruses replicate DNA and produce virions. Polydnavirus DNA consists of wasp DNA replicated by the wasp from its genome, which also directs particle synthesis. Structural similarities between ascovirus and ichnovirus particles and the biology of their transmission suggest that ichnoviruses evolved from ascoviruses, although molecular evidence for this hypothesis is lacking. RESULTS: Here we show that a family of unique pox-D5 NTPase proteins in the Glypta fumiferanae ichnovirus are related to three Diadromus pulchellus ascovirus proteins encoded by ORFs 90, 91 and 93. A new alignment technique also shows that two proteins from a related ichnovirus are orthologs of other ascovirus virion proteins. CONCLUSION: Our results provide molecular evidence supporting the origin of ichnoviruses from ascoviruses by lateral transfer of ascoviral genes into ichneumonid wasp genomes, perhaps the first example of symbiogenesis between large DNA viruses and eukaryotic organisms. We also discuss the limits of this evidence through complementary studies, which revealed that passive lateral transfer of viral genes among polydnaviral, bacterial, and wasp genomes may have occurred repeatedly through an intimate coupling of both recombination and replication of viral genomes during evolution. The impact of passive lateral transfers on evolutionary relationships between polydnaviruses and viruses with large double-stranded genomes is considered in the context of the theory of symbiogenesis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567993/ doi: 10.1186/1471-2148-8-253 id: cord-273910-fna7s9te author: Bochud, Pierre-Yves title: Innate immunogenetics: a tool for exploring new frontiers of host defence date: 2007-07-20 words: 7063.0 sentences: 391.0 pages: flesch: 39.0 cache: ./cache/cord-273910-fna7s9te.txt txt: ./txt/cord-273910-fna7s9te.txt summary: Recent immunogenetic studies have associated polymorphisms of the genes encoding TLRs, NLRs, and key signal-transducing molecules, such as interleukin-1 receptor-associated kinase 4 (IRAK4), with increased susceptibility to, or outcome of, infectious diseases. With the availability of high-throughput genotyping techniques, it is becoming increasingly evident that analyses of genetic polymorphisms of innate immune genes will further improve our knowledge of the host antimicrobial defence response and help in identifying individuals who are at increased risk of life-threatening infections. Since the innate immune system senses only a limited number of highly conserved microbial-associated molecular patterns 23 via a limited number of receptors and signalling molecules, as anticipated, several polymorphisms have been found to confer an increased susceptibility to specifi c pathogens (table 2, table 3 , and fi gure 4). [36] [37] [38] Taken together, these data clearly show that mutations in the genes encoding TLRs and downstream signal-transducing molecules infl uence innate immune responses and increase susceptibility to many infectious diseases. abstract: The discovery of innate immune genes, such as those encoding Toll-like receptors (TLRs), nucleotide-binding oligomerisation domain-like receptors (NLRs), and related signal-transducing molecules, has led to a substantial improvement of our understanding of innate immunity. Recent immunogenetic studies have associated polymorphisms of the genes encoding TLRs, NLRs, and key signal-transducing molecules, such as interleukin-1 receptor-associated kinase 4 (IRAK4), with increased susceptibility to, or outcome of, infectious diseases. With the availability of high-throughput genotyping techniques, it is becoming increasingly evident that analyses of genetic polymorphisms of innate immune genes will further improve our knowledge of the host antimicrobial defence response and help in identifying individuals who are at increased risk of life-threatening infections. This is likely to open new perspectives for the development of diagnostic, predictive, and preventive management strategies to combat infectious diseases. url: https://api.elsevier.com/content/article/pii/S1473309907701858 doi: 10.1016/s1473-3099(07)70185-8 id: cord-294725-wyrg0nq8 author: Bourdon, Julie A. title: Gene expression profiling to identify potentially relevant disease outcomes and support human health risk assessment for carbon black nanoparticle exposure date: 2013-01-07 words: 6413.0 sentences: 288.0 pages: flesch: 39.0 cache: ./cache/cord-294725-wyrg0nq8.txt txt: ./txt/cord-294725-wyrg0nq8.txt summary: Comparison to inflammatory lung disease models (i.e., allergic airway inflammation, bacterial infection and tissue injury and fibrosis) and human disease profiles revealed that induced gene expression changes in Printex 90 exposed mice were similar to those typical for pulmonary injury and fibrosis. In the present study we investigate the utility of gene expression profiles derived from mice exposed to Printex 90 carbon black nanoparticles (CBNPs) by intratracheal installation to identify potential hazards, modes of action, and doses above which adverse effects may be expected for specific toxicological outcomes. In addition to the examination of BMDs and BMDLs, we compare CBNP-modified gene expression profiles to various models of lung disease in mice and humans reported in the literature, in order to explore the utility of our data in predicting the potential risk of adverse health outcomes and the human relevance of expression changes. abstract: New approaches are urgently needed to evaluate potential hazards posed by exposure to nanomaterials. Gene expression profiling provides information on potential modes of action and human relevance, and tools have recently become available for pathway-based quantitative risk assessment. The objective of this study was to use toxicogenomics in the context of human health risk assessment. We explore the utility of toxicogenomics in risk assessment, using published gene expression data from C57BL/6 mice exposed to 18, 54 and 162 μg Printex 90 carbon black nanoparticles (CBNP). Analysis of CBNP-perturbed pathways, networks and transcription factors revealed concomitant changes in predicted phenotypes (e.g., pulmonary inflammation and genotoxicity), that correlated with dose and time. Benchmark doses (BMDs) for apical endpoints were comparable to minimum BMDs for relevant pathway-specific expression changes. Comparison to inflammatory lung disease models (i.e., allergic airway inflammation, bacterial infection and tissue injury and fibrosis) and human disease profiles revealed that induced gene expression changes in Printex 90 exposed mice were similar to those typical for pulmonary injury and fibrosis. Very similar fibrotic pathways were perturbed in CBNP-exposed mice and human fibrosis disease models. Our synthesis demonstrates how toxicogenomic profiles may be used in human health risk assessment of nanoparticles and constitutes an important step forward in the ultimate recognition of toxicogenomic endpoints in human health risk. As our knowledge of molecular pathways, dose–response characteristics and relevance to human disease continues to grow, we anticipate that toxicogenomics will become increasingly useful in assessing chemical toxicities and in human health risk assessment. url: https://doi.org/10.1016/j.tox.2012.10.014 doi: 10.1016/j.tox.2012.10.014 id: cord-260793-bb4h255w author: Brann, David H. title: Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia date: 2020-05-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 – affects olfaction directly by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing revealed that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing and immunostaining demonstrated ACE2 expression in support cells, stem cells, and perivascular cells; in contrast, neurons in both the olfactory epithelium and bulb did not express ACE2 message or protein. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients. url: https://doi.org/10.1101/2020.03.25.009084 doi: 10.1101/2020.03.25.009084 id: cord-018526-rz7id5mt author: Braun, Serge title: Non-viral Vector for Muscle-Mediated Gene Therapy date: 2018-12-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Non-viral gene delivery to skeletal muscle was one of the first applications of gene therapy that went into the clinic, mainly because skeletal muscle is an easily accessible tissue for local gene transfer and non-viral vectors have a relatively safe and low immunogenic track record. However, plasmid DNA, naked or complexed to the various chemistries, turn out to be moderately efficient in humans when injected locally and very inefficient (and very toxic in some cases) when injected systemically. A number of clinical applications have been initiated however, based on transgenes that were adapted to good local impact and/or to a wide physiological outcome (i.e., strong humoral and cellular immune responses following the introduction of DNA vaccines). Neuromuscular diseases seem more challenging for non-viral vectors. Nevertheless, the local production of therapeutic proteins that may act distantly from the injected site and/or the hydrodynamic perfusion of safe plasmids remains a viable basis for the non-viral gene therapy of muscle disorders, cachexia, as well as peripheral neuropathies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123420/ doi: 10.1007/978-3-030-03095-7_9 id: cord-018647-bveks6t1 author: Butnariu, Monica title: Plant Nanobionics: Application of Nanobiosensors in Plant Biology date: 2019-10-01 words: 16812.0 sentences: 779.0 pages: flesch: 40.0 cache: ./cache/cord-018647-bveks6t1.txt txt: ./txt/cord-018647-bveks6t1.txt summary: Chemical or biological NBS functions on the principle of signal emission (voltage or electrical, photonic) in response to a chemical reaction involve a chemical or biological receptor, R (macrocyclic ligand, antibody enzyme), that binds to a specific target molecule of a sample to be studied, the analyte, A. Analysis of signals in plant nanobionics aims at processing signals recorded by measurements in order to extract the maximum of useful information for diagnostics and These devices are mostly used in genetic engineering in agriculture, where it is necessary to know the mechanisms of reaction and the affinity of enzymes and microorganisms for different substrates of interest and signaling molecules. The reaction is monitored by an integrated detector (transducer) that measures the stationary or transition states or the final reaction product via the immobilized biocidal product in NBSs. Types of commonly used biocatalysts are enzymes (simple or enzymatic complexes)-most commonly used as recognition systems, cells, microorganisms (bacteria, fungi, eukaryotic cells, or yeasts), cellular organs, or component (cell walls, mitochondria) sections of plant or animal tissues. abstract: Nanobiosensors (NBSs) are a class of chemical sensors which are sensitive to a physical or chemical stimulus (heat, acidity, metabolism transformations) that conveys information about vital processes. NBSs detect physiological signals and convert them into standardized signals, often electrical, to be quantified from analog to digital. NBSs are classified according to the transducer element (electrochemical, piezoelectric, optical, and thermal) in accordance with biorecognition principle (enzyme recognition, affinity immunoassay, whole sensors, DNA). NBSs have varied forms, depending on the degree of interpretation of natural processes in plants. Plant nanobionics uses mathematical models based on qualitative and less quantitative records. NBSs can give information about endogenous concentrations or endogenous fluxes of signaling molecules (phytohormones). The properties of NBSs are temporal and spatial resolution, the ability of being used without significantly interfering with the system. NBSs with the best properties are the optically genetically coded NBSs, but each NBS needs specific development efforts. NBS technologies using antibodies as a recognition domain are generic and tend to be more invasive, and there are examples of their use in plant nanobionics. Through opportunities that develop along with technologies, we hope that more and more NBSs will become available for plant nanobionics. The main advantages of NBSs are short analysis time, low-cost tests and portability, real-time measurements, and remote control. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123577/ doi: 10.1007/978-3-030-16379-2_12 id: cord-015684-q10sx1dm author: Cacabelos, Ramón title: Pharmacogenomic Biomarkers in Neuropsychiatry: The Path to Personalized Medicine in Mental Disorders date: 2009 words: 16968.0 sentences: 1033.0 pages: flesch: 43.0 cache: ./cache/cord-015684-q10sx1dm.txt txt: ./txt/cord-015684-q10sx1dm.txt summary: With the advent of recent knowledge on the human genome 69,70 and the identifi cation and characterization of many genes associated with CNS disorders, 8, 19 as well as novel data regarding CYP family genes and other genes whose enzymatic products are responsible for drug metabolism in the liver (e.g., NATs, ABCBs/ MDRs, TPMT), it has been convincingly postulated that the incorporation of pharmacogenetic and pharmacogenomic procedures ( Fig. 40 .6) in drug development might bring about substantial benefi ts in terms of therapeutics optimization in CNS disorders and in many other complex disorders, assuming that genetic factors are determinant for both neuronal dysregulation (and/or neuronal death) 8,16-22 and drug metabolism. The natural course of technical events to achieve effi cient goals in pharmacogenetics and pharmacogenomics include the following steps: (a) genetic testing of mutant genes and/or polymorphic variants of risk; (b) genomic screening, and understanding of transcriptomic, proteomic, and metabolomic networks; (c) functional genomics studies and genotype-phenotype correlation analysis; and (d) pharmacogenetics and pharmacogenomics developments, addressing drug safety and effi cacy, respectively. abstract: Neuropsychiatric disorders and dementia represent a major cause of disability and high cost in developed societies. Most disorders of the central nervous system (CNS) share some common features, such as a genomic background in which hundreds of genes might be involved, genome-environment interactions, complex pathogenic pathways, poor therapeutic outcomes, and chronic disability. Recent advances in genomic medicine can contribute to accelerate our understanding on the pathogenesis of CNS disorders, improve diagnostic accuracy with the introduction of novel biomarkers, and personalize therapeutics with the incorporation of pharmacogenetic and pharmacogenomic procedures to drug development and clinical practice. The pharmacological treatment of CNS disorders, in general, accounts for 10–20% of direct costs, and less than 30–40% of the patients are moderate responders to conventional drugs, some of which may cause important adverse drugs reactions (ADRs). Pharmacogenetic and pharmacogenomic factors may account for 60–90% of drug variability in drug disposition and pharmacodynamics. Approximately 60–80% of CNS drugs are metabolized via enzymes of the CYP gene superfamily; 18% of neuroleptics are major substrates of CYP1A2 enzymes, 40% of CYP2D6, and 23% of CYP3A4; 24% of antidepressants are major substrates of CYP1A2 enzymes, 5% of CYP2B6, 38% of CYP2C19, 85% of CYP2D6, and 38% of CYP3A4; 7% of benzodiazepines are major substrates of CYP2C19 enzymes, 20% of CYP2D6, and 95% of CYP3A4. About 10–20% of Caucasians are carriers of defective CYP2D6 polymorphic variants that alter the metabolism of many psychotropic agents. Other 100 genes participate in the efficacy and safety of psychotropic drugs. The incorporation of pharmacogenetic/ pharmacogenomic protocols to CNS research and clinical practice can foster therapeutics optimization by helping to develop cost-effective pharmaceuticals and improving drug efficacy and safety. To achieve this goal several measures have to be taken, including: (a) educate physicians and the public on the use of genetic/ genomic screening in the daily clinical practice; (b) standardize genetic testing for major categories of drugs; (c) validate pharmacogenetic and pharmacogenomic procedures according to drug category and pathology; (d) regulate ethical, social, and economic issues; and (e) incorporate pharmacogenetic and pharmacogenomic procedures to both drugs in development and drugs in the market to optimize therapeutics. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115027/ doi: 10.1007/978-90-481-2298-1_1 id: cord-314642-oobbdgzh author: Campbell, Allan title: The future of bacteriophage biology date: 2003 words: 5945.0 sentences: 308.0 pages: flesch: 53.0 cache: ./cache/cord-314642-oobbdgzh.txt txt: ./txt/cord-314642-oobbdgzh.txt summary: Several molecules of λ-integrase form an assemblage (the INTASOME) that binds to a specific segment of phage DNA, recruits the bacterial insertion sites into the complex, then makes concerted single-strand cuts in the two DNAs. The strand cutting proceeds through the covalent joining of a 3′ phosphate to a tyrosine of the integrase protein. Further efforts in this direction are desirable, not just for their intrinsic interest but also as models for viruses that infect eukaryotic hosts; for example, it is well documented that members of the coronavirus group, which has attracted attention recently through the emergence of a deadly new human pathogen that causes severe acute respiratory syndrome (SARS), undergo frequent recombination in nature 10, 11 . abstract: After an illustrious history as one of the primary tools that established the foundations of molecular biology, bacteriophage research is now undergoing a renaissance in which the primary focus is on the phages themselves rather than the molecular mechanisms that they explain. Studies of the evolution of phages and their role in natural ecosystems are flourishing. Practical questions, such as how to use phages to combat human diseases that are caused by bacteria, how to eradicate phage pests in the food industry and what role they have in the causation of human diseases, are receiving increased attention. Phages are also useful in the deeper exploration of basic molecular and biophysical questions. url: https://www.ncbi.nlm.nih.gov/pubmed/12776216/ doi: 10.1038/nrg1089 id: cord-277491-q18b88lm author: Cao, Ying-Li title: Identification and Characterization of Three Novel Small Interference RNAs That Effectively Down-Regulate the Isolated Nucleocapsid Gene Expression of SARS Coronavirus date: 2011-02-11 words: 3988.0 sentences: 210.0 pages: flesch: 53.0 cache: ./cache/cord-277491-q18b88lm.txt txt: ./txt/cord-277491-q18b88lm.txt summary: title: Identification and Characterization of Three Novel Small Interference RNAs That Effectively Down-Regulate the Isolated Nucleocapsid Gene Expression of SARS Coronavirus Nucleocapsid (N) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is a major pathological determinant in the host that may cause host cell apoptosis, upregulate the proinflammatory cytokine production, and block innate immune responses. In the current study, we compared the N gene sequences derived from 16 different isolates of SARS-CoV and selected three novel siRNA targeting sites in the N gene, including one targeting the 3'' terminus of the gene. Overall, the above results provide strong evidence to show that all three novel siRNAs (si-N213, si-N863 and si-N1240) are specific and effective inhibitors to block the isolated SARS-CoV N gene expression. Small interfering RNA inhibits SARS-CoV nucleocapsid gene expression in cultured cells and mouse muscles Small interfering RNA effectively inhibits the expression of SARS coronavirus membrane gene at two novel targeting sites abstract: Nucleocapsid (N) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is a major pathological determinant in the host that may cause host cell apoptosis, upregulate the proinflammatory cytokine production, and block innate immune responses. Therefore, N gene has long been thought an ideal target for the design of small interference RNA (siRNA). siRNA is a class of small non-coding RNAs with a size of 21-25nt that functions post-transcriptionally to block targeted gene expression. In this study, we analyzed the N gene coding sequences derived from 16 different isolates, and found that nucleotide deletions and substitutions are mainly located at the first 440nt sequence. Combining previous reports and the above sequence information, we create three novel siRNAs that specifically target the conserved and unexploited regions in the N gene. We show that these siRNAs could effectively and specifically block the isolated N gene expression in mammal cells. Furthermore, we provide evidence to show that N gene can effectively up-regulate M gene mediated interferon β (IFNβ) production, while blocking N gene expression by specific siRNA significantly reduces IFNβ gene expression. Our data indicate that the inhibitory effect of siRNA on the isolated N gene expression might be influenced by the sequence context around the targeted sites. url: https://doi.org/10.3390/molecules16021544 doi: 10.3390/molecules16021544 id: cord-003196-fdb6az0v author: Casalino-Matsuda, S. Marina title: Hypercapnia Alters Expression of Immune Response, Nucleosome Assembly and Lipid Metabolism Genes in Differentiated Human Bronchial Epithelial Cells date: 2018-09-10 words: 4652.0 sentences: 252.0 pages: flesch: 37.0 cache: ./cache/cord-003196-fdb6az0v.txt txt: ./txt/cord-003196-fdb6az0v.txt summary: title: Hypercapnia Alters Expression of Immune Response, Nucleosome Assembly and Lipid Metabolism Genes in Differentiated Human Bronchial Epithelial Cells These changes in gene expression indicate the potential for hypercapnia to impact bronchial epithelial cell function in ways that may contribute to poor clinical outcomes in patients with severe acute or advanced chronic lung diseases. Major clusters from hypercapnia-downregulated genes are linked to immune response, nucleosome assembly, cell differentiation, oxidation reduction, and ion and lipid transport (Fig. 2) . In addition, the suppressive effect of elevated CO 2 on immune gene expression in the airway epithelium, along with similar effects on immune cells, suggest a reason why severe COPD and other lung disease associated with hypercapnia all carry a high risk of pulmonary infection. Thus, CO 2 -induced alterations in airway epithelial gene expression may underlie the increase in mortality associated with hypercapnia in advanced COPD, as well as community-acquired pneumonia 9 , adenoviral lung infections 10 and cystic fibrosis 11 . abstract: Hypercapnia, the elevation of CO(2) in blood and tissues, commonly occurs in severe acute and chronic respiratory diseases, and is associated with increased risk of mortality. Recent studies have shown that hypercapnia adversely affects innate immunity, host defense, lung edema clearance and cell proliferation. Airway epithelial dysfunction is a feature of advanced lung disease, but the effect of hypercapnia on airway epithelium is unknown. Thus, in the current study we examined the effect of normoxic hypercapnia (20% CO(2) for 24 h) vs normocapnia (5% CO(2)), on global gene expression in differentiated normal human airway epithelial cells. Gene expression was assessed on Affymetrix microarrays, and subjected to gene ontology analysis for biological process and cluster-network representation. We found that hypercapnia downregulated the expression of 183 genes and upregulated 126. Among these, major gene clusters linked to immune responses and nucleosome assembly were largely downregulated, while lipid metabolism genes were largely upregulated. The overwhelming majority of these genes were not previously known to be regulated by CO(2). These changes in gene expression indicate the potential for hypercapnia to impact bronchial epithelial cell function in ways that may contribute to poor clinical outcomes in patients with severe acute or advanced chronic lung diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131151/ doi: 10.1038/s41598-018-32008-x id: cord-010038-0m2f0eh4 author: Caspi, Jonathan title: Distribution of split DnaE inteins in cyanobacteria date: 2003-11-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Inteins are genetic elements found inside the coding regions of different host proteins and are translated in frame with them. The intein‐encoded protein region is removed by an autocatalytic protein‐splicing reaction that ligates the host protein flanks with a peptide bond. This reaction can also occur in trans with the intein and host protein split in two. After translation of the two genes, the two intein parts ligate their flanking protein parts to each other, producing the mature protein. Naturally split inteins are only known in the DNA polymerase III alpha subunit (polC or dnaE gene) of a few cyanobacteria. Analysing the phylogenetic distribution and probable genetic propagation mode of these split inteins, we conclude that they are genetically fixed in several large cyanobacterial lineages. To test our hypothesis, we sequenced parts of the dnaE genes from five diverse cyanobacteria and found all species to have the same type of split intein. Our results suggest the occurrence of a genetic rearrangement in the ancestor of a large division of cyanobacteria. This event fixed the dnaE gene in a unique two‐genes one‐protein configuration in the progenitor of many cyanobacteria. Our hypothesis, findings and the cloning procedure that we established allow the identification and acquisition of many naturally split inteins. Having a large and diverse repertoire of these unique inteins will enable studies of their distinct activity and enhance their use in biotechnology. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168405/ doi: 10.1046/j.1365-2958.2003.03825.x id: cord-003044-9uqa39j9 author: Cervera, Héctor title: Viral Fitness Correlates with the Magnitude and Direction of the Perturbation Induced in the Host’s Transcriptome: The Tobacco Etch Potyvirus—Tobacco Case Study date: 2018-03-19 words: 10863.0 sentences: 533.0 pages: flesch: 46.0 cache: ./cache/cord-003044-9uqa39j9.txt txt: ./txt/cord-003044-9uqa39j9.txt summary: As viral fitness is reduced, interactions are less optimal and, consequently, the gene expression profile of the plant will be increasingly different from that resulting from the infection with the WT virus. Figure 2A shows the clustering (unweighted average distance method; UPGMA) of average expression data for those genes that significantly changed expression (62-fold) among plants infected with the seven viral genotypes (1-way ANOVAs with false discovery rate (FDR) correction; overall P < 0.05) relative to the mock-inoculated plants. tabacum into a novel, poorly susceptible one, Arabidopsis thaliana, have shown that adaptation of TEV to the novel host (i.e., concomitant to large increases in fitness) was associated with a profound change in the way the ancestral and evolved viruses interacted with the plant''s transcriptome, with genes involved in the response to biotic stresses, including signal transduction and innate immunity pathways, being significantly underexpressed in plants infected with the evolved virus than in plants infected with the ancestral one (Agudelo-Romero et al. abstract: Determining the fitness of viral genotypes has become a standard practice in virology as it is essential to evaluate their evolutionary potential. Darwinian fitness, defined as the advantage of a given genotype with respect to a reference one, is a complex property that captures, in a single figure, differences in performance at every stage of viral infection. To what extent does viral fitness result from specific molecular interactions with host factors and regulatory networks during infection? Can we identify host genes in functional classes whose expression depends on viral fitness? Here, we compared the transcriptomes of tobacco plants infected with seven genotypes of tobacco etch potyvirus that differ in fitness. We found that the larger the fitness differences among genotypes, the more dissimilar the transcriptomic profiles are. Consistently, two different mutations, one in the viral RNA polymerase and another in the viral suppressor of RNA silencing, resulted in significantly similar gene expression profiles. Moreover, we identified host genes whose expression showed a significant correlation, positive or negative, with the virus' fitness. Differentially expressed genes which were positively correlated with viral fitness activate hormone- and RNA silencing-mediated pathways of plant defense. In contrast, those that were negatively correlated with fitness affect metabolism, reducing growth, and development. Overall, these results reveal the high information content of viral fitness and suggest its potential use to predict differences in genomic profiles of infected hosts. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995217/ doi: 10.1093/molbev/msy038 id: cord-279781-5ldpz9m9 author: Chen, Chi-Yuan title: Baculovirus as a gene delivery vector: Recent understandings of molecular alterations in transduced cells and latest applications date: 2011-04-28 words: 13111.0 sentences: 665.0 pages: flesch: 38.0 cache: ./cache/cord-279781-5ldpz9m9.txt txt: ./txt/cord-279781-5ldpz9m9.txt summary: Concurrent with the aforementioned findings, we also discovered that baculovirus transduction of human BMSCs disturbed the expression of 816 genes, most of which were related to 5 signaling pathways: cell adhesion molecules, TLR, Jak-STAT, apoptosis as well as antigen processing and presentation (Chen et al., 2009b) . immunization of chickens with another VSVG-pseudotyped baculovirus expressing HA of H5N1 avian influenza virus (AIV) also evoked significantly higher levels of H5-specific antibody and cellular immunity than those receiving DNA vaccines, and conferred protection against lethal challenge with the homologous virus strain (Wu et al., 2009b) . Transient and stable gene expression in mammalian cells transduced with a recombinant baculovirus vector Baculovirus as a highly efficient gene delivery vector for the expression of hepatitis delta virus antigens in mammalian cells abstract: Baculovirus infects insects in nature and is non-pathogenic to humans, but can transduce a broad range of mammalian and avian cells. Thanks to the biosafety, large cloning capacity, low cytotoxicity and non-replication nature in the transduced cells as well as the ease of manipulation and production, baculovirus has gained explosive popularity as a gene delivery vector for a wide variety of applications. This article extensively reviews the recent understandings of the molecular mechanisms pertinent to baculovirus entry and cellular responses, and covers the latest advances in the vector improvements and applications, with special emphasis on antiviral therapy, cancer therapy, regenerative medicine and vaccine. url: https://doi.org/10.1016/j.biotechadv.2011.04.004 doi: 10.1016/j.biotechadv.2011.04.004 id: cord-275720-kf9m4zho author: Cho, Won Kyong title: Genome-wide expression profiling shows transcriptional reprogramming in Fusarium graminearum by Fusarium graminearum virus 1-DK21 infection date: 2012-05-06 words: 7132.0 sentences: 390.0 pages: flesch: 47.0 cache: ./cache/cord-275720-kf9m4zho.txt txt: ./txt/cord-275720-kf9m4zho.txt summary: At the early point of growth of an infected strain as compared to an uninfected strain, genes associated with protein synthesis, including ribosome assembly, nucleolus, and ribosomal RNA processing, were significantly up-regulated. This is the first report of a genome-wide fungal gene expression analysis during mycovirus infection using a 3′ tiling microarray, and our findings show global differences in host cellular pathways in F. For example, according to the qRT-PCR and microarray results, the transcript levels for three genes, including FGSG_01379, FGSG_03143, and FGSG_03911, were highly reduced at both 36 h and 120 h, whereas FGSG_03788, FGSG_00023, FGSG_07804, FGSG_07801, and FGSG_13222 were strongly induced regardless of the time point ( Figure 3A -C). graminearum harboring FgV1-DK21 in detail, samples were harvested at two different time points, thus providing lists of differentially expressed genes early and late in the host containing FgV1-DK21 as compared to an uninfected strain. abstract: BACKGROUND: Fusarium graminearum virus 1 strain-DK21 (FgV1-DK21) is a mycovirus that confers hypovirulence to F. graminearum, which is the primary phytopathogenic fungus that causes Fusarium head blight (FHB) disease in many cereals. Understanding the interaction between mycoviruses and plant pathogenic fungi is necessary for preventing damage caused by F. graminearum. Therefore, we investigated important cellular regulatory processes in a host containing FgV1-DK21 as compared to an uninfected parent using a transcriptional approach. RESULTS: Using a 3′-tiling microarray covering all known F. graminearum genes, we carried out genome-wide expression analyses of F. graminearum at two different time points. At the early point of growth of an infected strain as compared to an uninfected strain, genes associated with protein synthesis, including ribosome assembly, nucleolus, and ribosomal RNA processing, were significantly up-regulated. In addition, genes required for transcription and signal transduction, including fungal-specific transcription factors and cAMP signaling, respectively, were actively up-regulated. In contrast, genes involved in various metabolic pathways, particularly in producing carboxylic acids, aromatic amino acids, nitrogen compounds, and polyamines, showed dramatic down-regulation at the early time point. Moreover, genes associated with transport systems localizing to transmembranes were down-regulated at both time points. CONCLUSION: This is the first report of global change in the prominent cellular pathways in the Fusarium host containing FgV1-DK21. The significant increase in transcripts for transcription and translation machinery in fungal host cells seems to be related to virus replication. In addition, significant down-regulation of genes required for metabolism and transporting systems in a fungal host containing the virus appears to be related to the host defense mechanism and fungal virulence. Taken together, our data aid in the understanding of how FgV1-DK21 regulates the transcriptional reprogramming of F. graminearum. url: https://www.ncbi.nlm.nih.gov/pubmed/22559730/ doi: 10.1186/1471-2164-13-173 id: cord-309556-xv3413k1 author: Chow, Ryan D. title: The aging transcriptome and cellular landscape of the human lung in relation to SARS-CoV-2 date: 2020-04-15 words: 5761.0 sentences: 373.0 pages: flesch: 53.0 cache: ./cache/cord-309556-xv3413k1.txt txt: ./txt/cord-309556-xv3413k1.txt summary: In aggregate, these analyses showed that the age-associated genes with functional roles in SARS-CoV are expressed in specific cell types of the human lung. Of note, the overlap between lung ageassociated genes and SARS-CoV-2 regulated genes was statistically significant across all 3 cell lines (Figure 6d-f) , suggesting a degree of similarity between the transcriptional changes associated with aging and with SARS-CoV-2 infection. Among the age-associated genes that were induced by SARS-CoV-2 infection, the majority of these genes increase in expression with age (Cluster 1) (Figure 6g-i) . To identify a consensus set of age-associated genes that are regulated by SARS-CoV-2 infection, we integrated the analyses from all 3 cell lines. By integrating these data with single cell transcriptomes of human lung tissue, we further pinpointed the specific cell types that normally express the age-associated genes. abstract: Since the emergence of SARS-CoV-2 in December 2019, Coronavirus Disease-2019 (COVID-19) has rapidly spread across the globe. Epidemiologic studies have demonstrated that age is one of the strongest risk factors influencing the morbidity and mortality of COVID-19. Here, we interrogate the transcriptional features and cellular landscapes of the aging human lung through integrative analysis of bulk and single-cell transcriptomics. By intersecting these age-associated changes with experimental data on host interactions between SARS-CoV-2 or its relative SARS-CoV, we identify several age-associated factors that may contribute to the heightened severity of COVID-19 in older populations. We observed that age-associated gene expression and cell populations are significantly linked to the heightened severity of COVID-19 in older populations. The aging lung is characterized by increased vascular smooth muscle contraction, reduced mitochondrial activity, and decreased lipid metabolism. Lung epithelial cells, macrophages, and Th1 cells decrease in abundance with age, whereas fibroblasts, pericytes and CD4+ Tcm cells increase in abundance with age. Several age-associated genes have functional effects on SARS-CoV replication, and directly interact with the SARS-CoV-2 proteome. Interestingly, age-associated genes are heavily enriched among those induced or suppressed by SARS-CoV-2 infection. These analyses illuminate potential avenues for further studies on the relationship between the aging lung and COVID-19 pathogenesis, which may inform strategies to more effectively treat this disease. url: https://doi.org/10.1101/2020.04.07.030684 doi: 10.1101/2020.04.07.030684 id: cord-252859-zir02q69 author: Chung, T. Philip title: Molecular Diagnostics in Sepsis: From Bedside to Bench date: 2006-09-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Based on recent in vitro data, we tested the hypothesis that microarray expression profiles can be used to diagnose sepsis, distinguishing in vivo between sterile and infectious causes of systemic inflammation. STUDY DESIGN: Exploratory studies were conducted using spleens from septic patients and from mice with abdominal sepsis. Seven patients with sepsis after injury were identified retrospectively and compared with six injured patients. C57BL/6 male mice were subjected to cecal ligation and puncture, or to IP lipopolysaccharide. Control mice had sham laparotomy or injection of IP saline, respectively. A sepsis classification model was created and tested on blood samples from septic mice. RESULTS: Accuracy of sepsis prediction was obtained using cross-validation of gene expression data from 12 human spleen samples and from 16 mouse spleen samples. For blood studies, classifiers were constructed using data from a training data set of 26 microarrays. The error rate of the classifiers was estimated on seven de-identified microarrays, and then on a subsequent cross-validation for all 33 blood microarrays. Estimates of classification accuracy of sepsis in human spleen were 67.1%; in mouse spleen, 96%; and in mouse blood, 94.4% (all estimates were based on nested cross-validation). Lists of genes with substantial changes in expression between study and control groups were used to identify nine mouse common inflammatory response genes, six of which were mapped into a single pathway using contemporary pathway analysis tools. CONCLUSIONS: Sepsis induces changes in mouse leukocyte gene expression that can be used to diagnose sepsis apart from systemic inflammation. url: https://www.ncbi.nlm.nih.gov/pubmed/17084318/ doi: 10.1016/j.jamcollsurg.2006.06.028 id: cord-285656-7o7ofk1e author: Dawson, Harry D. title: The porcine translational research database: a manually curated, genomics and proteomics-based research resource date: 2017-08-22 words: 5697.0 sentences: 295.0 pages: flesch: 48.0 cache: ./cache/cord-285656-7o7ofk1e.txt txt: ./txt/cord-285656-7o7ofk1e.txt summary: The data in the Porcine Translational Research Database ((http://www.ars.usda.gov/Services/docs.htm?docid=6065) is supported by >5800 references, and contains 65 data fields for each entry, including >9700 full length (5′ and 3′) unambiguous pig sequences, >2400 real time PCR assays and reactivity information on >1700 antibodies. This database provides the first comprehensive description of three major Super-families or functionally related groups of proteins (Cluster of Differentiation (CD) Marker genes, Solute Carrier Superfamily, ATP binding Cassette Superfamily), and a comparative description of porcine microRNAs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-4009-7) contains supplementary material, which is available to authorized users. Five of these genes are present in other porcine genomes, but missing from Ensembl build 10.2, 21 are truncated, and 18 of these genes are duplicated gene artifacts, Eleven full-length mRNA sequences, assembled from macrophage RNA-Seq reads, have been deposited in Genbank and an additional 24 in silico constructs are provided. abstract: BACKGROUND: The use of swine in biomedical research has increased dramatically in the last decade. Diverse genomic- and proteomic databases have been developed to facilitate research using human and rodent models. Current porcine gene databases, however, lack the robust annotation to study pig models that are relevant to human studies and for comparative evaluation with rodent models. Furthermore, they contain a significant number of errors due to their primary reliance on machine-based annotation. To address these deficiencies, a comprehensive literature-based survey was conducted to identify certain selected genes that have demonstrated function in humans, mice or pigs. RESULTS: The process identified 13,054 candidate human, bovine, mouse or rat genes/proteins used to select potential porcine homologs by searching multiple online sources of porcine gene information. The data in the Porcine Translational Research Database ((http://www.ars.usda.gov/Services/docs.htm?docid=6065) is supported by >5800 references, and contains 65 data fields for each entry, including >9700 full length (5′ and 3′) unambiguous pig sequences, >2400 real time PCR assays and reactivity information on >1700 antibodies. It also contains gene and/or protein expression data for >2200 genes and identifies and corrects 8187 errors (gene duplications artifacts, mis-assemblies, mis-annotations, and incorrect species assignments) for 5337 porcine genes. CONCLUSIONS: This database is the largest manually curated database for any single veterinary species and is unique among porcine gene databases in regard to linking gene expression to gene function, identifying related gene pathways, and connecting data with other porcine gene databases. This database provides the first comprehensive description of three major Super-families or functionally related groups of proteins (Cluster of Differentiation (CD) Marker genes, Solute Carrier Superfamily, ATP binding Cassette Superfamily), and a comparative description of porcine microRNAs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-4009-7) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1186/s12864-017-4009-7 doi: 10.1186/s12864-017-4009-7 id: cord-258035-2tk7maqk author: DeFilippis, Victor title: Functional genomics in virology and antiviral drug discovery date: 2003-10-31 words: 4769.0 sentences: 255.0 pages: flesch: 39.0 cache: ./cache/cord-258035-2tk7maqk.txt txt: ./txt/cord-258035-2tk7maqk.txt summary: Given that virus replication involves use and manipulation of multiple host proteins and molecular processes, cellular pathways related to transcription and translation, signal transduction, metabolism, host defense and cell cycle control are Review commonly altered in response to, or as a result of, infection with diverse virus types. A special case of virus modulation of host cell gene expression in which functional genomics will reveal novel targets and treatments is viral oncogenesis. The most recent method for analyzing gene inhibition studies has been RNAi or siRNA, where small 21 -23-nucleotide (nt) RNA duplexes interfere with the transcription program by directing degradation of homologous mRNA [34] [35] [36] [37] . Both new-generation antisense oligomers and siRNA can be used to knockdown expression of genes that were found by DNA microarrays to be upregulated in virally infected cells or organisms. RNA interference directed against viral and cellular targets inhibits human immunodeficiency virus type 1 replication abstract: Abstract Virology research and antiviral drug discovery are poised to benefit from the post-genomic revolution for three main reasons. First, viruses need the host to replicate and are therefore vulnerable to inhibition of cellular pathways. Knowledge of complete genomic sequences of both virus and host now permits the study of this interplay on a global scale. Combining transcriptomics and proteomics with large-scale gene knockdown experiments will enable the identification of novel antiviral targets. Second, massive parallel assay systems, such as DNA microarrays, which define the post-genomic era, will facilitate viral diagnostics. Third, the combination of genetics with genomics will enable the analysis of viral mutants and strains on an unprecedented scale. The dramatic effects of viral infection on host cell transcriptional patterns have been well-documented and will be briefly highlighted. In addition, we discuss recent trends that apply functional genomics methods to the discovery of new targets and therapies for viral disease. url: https://www.ncbi.nlm.nih.gov/pubmed/14512232/ doi: 10.1016/s0167-7799(03)00207-5 id: cord-295307-zrtixzgu author: Delgado-Chaves, Fernando M. title: Computational Analysis of the Global Effects of Ly6E in the Immune Response to Coronavirus Infection Using Gene Networks date: 2020-07-21 words: 10169.0 sentences: 541.0 pages: flesch: 51.0 cache: ./cache/cord-295307-zrtixzgu.txt txt: ./txt/cord-295307-zrtixzgu.txt summary: Through the integration of differential expression analyses and reconstructed networks exploration, significant differences in the immune response to virus were observed in Ly6E [Formula: see text] compared to wild type animals. Among the different types of GNs, gene co-expression networks (GCNs) are widely used in the literature due to their computational simplicity and good performance in order to study biological processes or diseases [8] [9] [10] . In the present work mice samples were compared organ-wise depending on whether these corresponded to control, 3 d p.i. and 5 d p.i. The identification of DEG was performed using the Limma [63] R package, which provides non-parametric robust estimation of the gene expression variance. In this work four gene networks were reconstructed to model the genetic response MHV infection in two tissues, liver and spleen, and in two different genetic backgrounds, wild type and Ly6E ∆HSC . abstract: Gene networks have arisen as a promising tool in the comprehensive modeling and analysis of complex diseases. Particularly in viral infections, the understanding of the host-pathogen mechanisms, and the immune response to these, is considered a major goal for the rational design of appropriate therapies. For this reason, the use of gene networks may well encourage therapy-associated research in the context of the coronavirus pandemic, orchestrating experimental scrutiny and reducing costs. In this work, gene co-expression networks were reconstructed from RNA-Seq expression data with the aim of analyzing the time-resolved effects of gene Ly6E in the immune response against the coronavirus responsible for murine hepatitis (MHV). Through the integration of differential expression analyses and reconstructed networks exploration, significant differences in the immune response to virus were observed in Ly6E [Formula: see text] compared to wild type animals. Results show that Ly6E ablation at hematopoietic stem cells (HSCs) leads to a progressive impaired immune response in both liver and spleen. Specifically, depletion of the normal leukocyte mediated immunity and chemokine signaling is observed in the liver of Ly6E [Formula: see text] mice. On the other hand, the immune response in the spleen, which seemed to be mediated by an intense chromatin activity in the normal situation, is replaced by ECM remodeling in Ly6E [Formula: see text] mice. These findings, which require further experimental characterization, could be extrapolated to other coronaviruses and motivate the efforts towards novel antiviral approaches. url: https://www.ncbi.nlm.nih.gov/pubmed/32708319/ doi: 10.3390/genes11070831 id: cord-000492-ec5qzurk author: Devaney, James title: Clinical Review: Gene-based therapies for ALI/ARDS: where are we now? date: 2011-06-20 words: 6012.0 sentences: 313.0 pages: flesch: 39.0 cache: ./cache/cord-000492-ec5qzurk.txt txt: ./txt/cord-000492-ec5qzurk.txt summary: Plasmid transfer (closed Easily produced at low cost No specifi c cell targeting Electroporation-mediated gene transfer of the dsDNA circles) Very ineffi cient Na + ,K + -ATPase rescues endotoxin-induced lung injury [60] Nonviral DNA complexes Complexes protect DNA Less effi cient than viral vectors Cationic lipid-mediated transfer of the Na + ,K + -(lipoplexes or polyplexes) Modifying transgene DNA to eliminate bacterial motifs [75, 76] Development of high-effi ciency tissue-specifi c promoters [77] [78] [79] [80] Development of promoters that regulate gene expression [83] Enhanced therapeutic targeting Nebulization technologies [9] Strategies to target the pulmonary endothelium [10] Improved cellular uptake of vector Surface active agents to enhance vector spread [84] Reduce ubiquitination of viral capsid proteins [85] Better therapeutic targets Enhancement or restoration of lung epithelial and/or endothelial cell function [86] Strengthening lung defense mechanisms against injury [87] Speeding clearance of infl ammation and infection Enhancement of the repair process following ALI/ARDS [88] . abstract: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) confer substantial morbidity and mortality, and have no specific therapy. The accessibility of the distal lung epithelium via the airway route, and the relatively transient nature of ALI/ARDS, suggest that the disease may be amenable to gene-based therapies. Ongoing advances in our understanding of the pathophysiology of ALI/ARDS have revealed multiple therapeutic targets for gene-based approaches. Strategies to enhance or restore lung epithelial and/or endothelial cell function, to strengthen lung defense mechanisms against injury, to speed clearance of infection and to enhance the repair process following ALI/ARDS have all demonstrated promise in preclinical models. Despite three decades of gene therapy research, however, the clinical potential for gene-based approaches to lung diseases including ALI/ARDS remains to be realized. Multiple barriers to effective pulmonary gene therapy exist, including the pulmonary architecture, pulmonary defense mechanisms against inhaled particles, the immunogenicity of viral vectors and the poor transfection efficiency of nonviral delivery methods. Deficits remain in our knowledge regarding the optimal molecular targets for gene-based approaches. Encouragingly, recent progress in overcoming these barriers offers hope for the successful translation of gene-based approaches for ALI/ARDS to the clinical setting. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218971/ doi: 10.1186/cc10216 id: cord-269352-0o3mryu1 author: Dhama, K. title: DNA vaccines and their applications in veterinary practice: current perspectives date: 2008-04-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Inoculation of plasmid DNA, encoding an immunogenic protein gene of an infectious agent, stands out as a novel approach for developing new generation vaccines for prevention of infectious diseases of animals. The potential of DNA vaccines to act in presence of maternal antibodies, its stability and cost effectiveness and the non-requirement of cold chain have heightened the prospects. Even though great strides have been made in nucleic acid vaccination, still there are many areas that need further research for its wholesome practical implementation. Major areas of concern are vaccine delivery, designing of suitable vectors and cytotoxic T cell responses. Also, the induction of immune responses by DNA vaccines is inconclusive due to the lack of knowledge regarding the concentration of the protein expressed in vivo. Alternative delivery systems having higher transfection efficiency and the use of cytokines, as immunomodulators, needs to be further explored. Recently, efforts are being made to modulate and prolong the active life of dendritic cells, in order to make antigen presentation a more efficacious one. For combating diseases like acquired immunodeficiency syndrome (AIDS), influenza, malaria and tuberculosis in humans; and foot and mouth disease, Aujesky’s disease, swine fever, rabies, canine distemper and brucellosis in animals, DNA vaccine clinical trials are underway. This review highlights the salient features of DNA vaccines, and measures to enhance their efficacy so as to devise an effective and novel vaccination strategy against animal diseases. url: https://doi.org/10.1007/s11259-008-9040-3 doi: 10.1007/s11259-008-9040-3 id: cord-319519-mb9ofh12 author: Ding, J. title: A network-informed analysis of SARS-CoV-2 and hemophagocytic lymphohistiocytosis genes'' interactions points to Neutrophil Extracellular Traps as mediators of thrombosis in COVID-19 date: 2020-07-02 words: 7247.0 sentences: 474.0 pages: flesch: 52.0 cache: ./cache/cord-319519-mb9ofh12.txt txt: ./txt/cord-319519-mb9ofh12.txt summary: The algorithm establishes the shortest path between 118 the candidate genes and the known host interacting proteins with SARS-CoV-2 and calculates an 119 overall connectivity score for the network (a smaller value represents a greater connectivity) ( Fig 120 1 and Supplementary Table S1 ). The network-informed analysis presented in this paper, 262 revealed that 1) the top GO biological function associated with HLH genes is neutrophil 263 degranulation, consistent with a recent report highlighting the undervalued role of neutrophils in 264 HLH 36 ; 2) HLH genes are significantly enriched with the SARS-CoV-2 human interactome; 3) the 265 top-ranked HLH gene, AP3B1, has roles in cargo loading of type II pneumocytes, where it may 266 interact with SARS-CoV-2 to disturb surfactant physiological functions to promote 267 inflammation/pro-coagulation activities; 4) diseases/syndromes-associated with increased release 268 of Neutrophil Extracellular Traps (NETs) may predict vulnerable populations, including those 269 affecting children. abstract: Abnormal coagulation and an increased risk of thrombosis are features of severe COVID-19, with parallels proposed with hemophagocytic lymphohistiocytosis (HLH), a life-threating condition associated with hyperinflammation. The presence of HLH was described in severely ill patients during the H1N1 influenza epidemic, presenting with pulmonary vascular thrombosis. We tested the hypothesis that genes causing primary HLH regulate pathways linking pulmonary thromboembolism to the presence of SARS-CoV-2 using novel network-informed computational algorithms. This approach led to the identification of Neutrophils Extracellular Traps (NETs) as plausible mediators of vascular thrombosis in severe COVID-19 in children and adults. Taken together, the network-informed analysis led us to propose the following model: the release of NETs in response to inflammatory signals acting in concert with SARS-CoV-2 damage the endothelium and direct platelet-activation promoting abnormal coagulation leading to serious complications of COVID-19. The underlying hypothesis is that genetic and/or environmental conditions that favor the release of NETs may predispose individuals to thrombotic complications of COVID-19 due to an increase risk of abnormal coagulation. This would be a common pathogenic mechanism in conditions including autoimmune/infectious diseases, hematologic and metabolic disorders. url: http://medrxiv.org/cgi/content/short/2020.07.01.20144121v1?rss=1 doi: 10.1101/2020.07.01.20144121 id: cord-252147-bvtchcbt author: Domingo-Espín, Joan title: Engineered Biological Entities for Drug Delivery and Gene Therapy: Protein Nanoparticles date: 2011-11-15 words: 17193.0 sentences: 888.0 pages: flesch: 39.0 cache: ./cache/cord-252147-bvtchcbt.txt txt: ./txt/cord-252147-bvtchcbt.txt summary: Modular protein engineering, virus-like particles (VLPs), and other self-assembling entities are envisioned as modulatable novel protein nanoparticles able to include many desirable properties in the correct delivery of drugs and nucleic acids. 120 Modular fusion proteins that combine distinct functions required for cell type-specific uptake and intracellular delivery of DNA or drugs present an attractive approach for the development of self-assembling vectors for targeted gene or drug delivery. 215, 216 Although VLP-based vaccines have been primarily developed for their use against the corresponding virus, in the last decades genetic engineering or chemical modifications have been applied in order to generate chimeric VLPs. Thus, on the one hand, commonly short heterologous peptide epitopes or full proteins that are unable to form VLPs or that are unsafe for vaccination have been presented on surface-exposed loops or fused to N-or C-exposed termini of structural viral capsid proteins on VLPs. 154, 161, 210 Different HPV, 217-219 HBV, 220,221 parvovirus, 222, 223 and chimeric polyoma VLPs have been engineered 170, 175 and tested for different applications including vaccination against viral or bacterial diseases, against virus-induced tumors, and more recently, for immunotherapy of nonviral cancer. abstract: The development of genetic engineering techniques has speeded up the growth of the biotechnological industry, resulting in a significant increase in the number of recombinant protein products on the market. The deep knowledge of protein function, structure, biological interactions, and the possibility to design new polypeptides with desired biological activities have been the main factors involved in the increase of intensive research and preclinical and clinical approaches. Consequently, new biological entities with added value for innovative medicines such as increased stability, improved targeting, and reduced toxicity, among others have been obtained. Proteins are complex nanoparticles with sizes ranging from a few nanometers to a few hundred nanometers when complex supramolecular interactions occur, as for example, in viral capsids. However, even though protein production is a delicate process that imposes the use of sophisticated analytical methods and negative secondary effects have been detected in some cases as immune and inflammatory reactions, the great potential of biodegradable and tunable protein nanoparticles indicates that protein-based biotechnological products are expected to increase in the years to come. url: https://doi.org/10.1016/b978-0-12-416020-0.00006-1 doi: 10.1016/b978-0-12-416020-0.00006-1 id: cord-323307-nu9ib62h author: Dong, Dong title: The genomes of two bat species with long constant frequency echolocation calls date: 2016-10-26 words: 7642.0 sentences: 381.0 pages: flesch: 49.0 cache: ./cache/cord-323307-nu9ib62h.txt txt: ./txt/cord-323307-nu9ib62h.txt summary: For homology-based gene prediction, the protein sequences of human, mouse, dog, cow, little brown bat and large flying fox were downloaded from Ensembl Release 72 and mapped onto the repeat-masked genome using GenBlastA (She, et al. Moreover, we identified 577, 453 and 182 positively selected genes in the great leaf-nosed bat, the Chinese rufous horseshoe bat and the large flying fox, (Supplementary Tables S10, 11, 12), respectively. Clade model C implemented in PAML was employed (Weadick and Chang 2012) , and the result also persisted that more positively selected genes were detected in the branches leading to echolocating bats (Supplementary Table S20 ). The genome re-sequencing analysis has been performed based generally on the following considerations: 1) to characterize the genetic diversity and patterns of evolution; 2) to understand the genetic bases of adaptation to high altitude in the great leaf-nosed bats. abstract: Bats can perceive the world by using a wide range of sensory systems, and some of the systems have become highly specialized, such as auditory sensory perception. Among bat species, the Old World leaf-nosed bats and horseshoe bats (rhinolophoid bats) possess the most sophisticated echolocation systems. Here, we reported the whole-genome sequencing and de novo assembles of two rhinolophoid bats – the great leaf-nosed bat (Hipposideros armiger) and the Chinese rufous horseshoe bat (Rhinolophus sinicus). Comparative genomic analyses revealed the adaptation of auditory sensory perception in the rhinolophoid bat lineages, probably resulting from the extreme selectivity used in the auditory processing by these bats. Pseudogenization of some vision-related genes in rhinolophoid bats was observed, suggesting that these genes have undergone relaxed natural selection. An extensive contraction of olfactory receptor gene repertoires was observed in the lineage leading to the common ancestor of bats. Further extensive gene contractions can be observed in the branch leading to the rhinolophoid bats. Such concordance suggested that molecular changes at one sensory gene might have direct consequences for genes controlling for other sensory modalities. To characterize the population genetic structure and patterns of evolution, we re-sequenced the genome of 20 great leaf-nosed bats from four different geographical locations of China. The result showed similar sequence diversity values and little differentiation among populations. Moreover, evidence of genetic adaptations to high altitudes in the great leaf-nosed bats was observed. Taken together, our work provided a useful resource for future research on the evolution of bats. url: https://doi.org/10.1093/molbev/msw231 doi: 10.1093/molbev/msw231 id: cord-326719-p1ma4akz author: Enjuanes, Luis title: Virus-based vectors for gene expression in mammalian cells: Coronavirus date: 2003-12-31 words: 5923.0 sentences: 282.0 pages: flesch: 52.0 cache: ./cache/cord-326719-p1ma4akz.txt txt: ./txt/cord-326719-p1ma4akz.txt summary: Coronaviruses have several advantages as vectors over other viral expression systems: (1) coronaviruses are single-stranded RNA viruses that replicate within the cytoplasm without a DNA intermediary, making integration of the virus genome into the host cell chromosome unlikely, (2) these viruses have the largest RNA virus genome and, in principle, have room for the insertion of large foreign genes, (3) a pleiotropic secretory immune response is best induced by the stimulation of gut-associated lymphoid tissues, (4) the tropism of coronaviruses may be modified by manipulation of the spike (S) protein allowing engineering of the tropism of the vector, (5) non-pathogenic coronavirus strains infecting most species of interest (human, porcine, bovine, canine, feline, and avian) are available to develop expression systems, and (6) infectious coronavirus cDNA clones are available to design expression systems. abstract: Publisher Summary The coronavirus and the torovirus genera form the Coronaviridae family, which is closely related to the Arteriviridae family. Both families are included in the Nidovirales order. Recently, a new group of invertebrate viruses, the Roniviridae, with a genetic structure and replication strategy similar to those of coronaviruses, has been described. This new virus family has been included within the Nidovirales. Coronaviruses have several advantages as vectors over other viral expression systems: (1) coronaviruses are single-stranded RNA viruses that replicate within the cytoplasm without a DNA intermediary, making integration of the virus genome into the host cell chromosome unlikely, (2) these viruses have the largest RNA virus genome and, in principle, have room for the insertion of large foreign genes, (3) a pleiotropic secretory immune response is best induced by the stimulation of gut-associated lymphoid tissues, (4) the tropism of coronaviruses may be modified by manipulation of the spike (S) protein allowing engineering of the tropism of the vector, (5) non-pathogenic coronavirus strains infecting most species of interest (human, porcine, bovine, canine, feline, and avian) are available to develop expression systems, and (6) infectious coronavirus cDNA clones are available to design expression systems. Within the coronavirus two types of expression vectors have been developed: one requires two components (helper–dependent expression system) and the other a single genome that is modified either by targeted recombination or by engineering a cDNA encoding an infectious RNA. This chapter focuses on the advantages and limitations of these coronavirus expression systems, the attempts to increase their expression levels by studying the transcription-regulating sequences (TRSs), and the proven possibility of modifying their tissue and species-specificity. url: https://www.sciencedirect.com/science/article/pii/S016773060338010X doi: 10.1016/s0167-7306(03)38010-x id: cord-335382-fk4um9nw author: Farver, Carol F. title: Molecular Basis of Pulmonary Disease date: 2012-08-10 words: 32320.0 sentences: 1613.0 pages: flesch: 40.0 cache: ./cache/cord-335382-fk4um9nw.txt txt: ./txt/cord-335382-fk4um9nw.txt summary: When lung cancer is suspected, evaluation of the patient includes a thorough clinical, radiologic, and laboratory assessment, with collection of tissue or cytology samples to establish a pathologic diagnosis of malignancy and to classify the tumor type. Development of lung cancer occurs with multiple, complex, stepwise genetic and epigenetic changes involving allelic losses, chromosomal instability and imbalance, mutations in tumor suppressor genes (TSGs) and dominant oncogenes, epigenetic gene silencing through promoter hypermethylation, and aberrant expression of genes participating in control of cell proliferation and apoptosis [7] . In recent years, atypical adenomatous hyperplasia (AAH) has been recognized as a precursor lesion for peripheral pulmonary ACs. This lesion is defined as "a localized proliferation of mild to moderately atypical cells lining involved alveoli and, sometimes, respiratory bronchioles, resulting in focal lesions in peripheral Part IV Molecular Pathology of Human Disease alveolated lung, usually less than 5 mm in diameter and generally in the absence of underlying interstitial inflammation and fibrosis" (Figure 18 .8) [36] . abstract: Pulmonary pathology includes a large spectrum of both neoplastic and non-neoplastic diseases that affect the lung. Many of these are a result of the unusual relationship of the lung with the outside world. Every breath that a human takes brings the outside world into the body in the form of infectious agents, organic and inorganic particles, and noxious agents of all types. Although the lung has many defense mechanisms to protect itself from these insults, these are not infallible; therefore, lung pathology arises. Damage to the lung is particularly important given the role of the lung in the survival of the organism. Any impairment of lung function has widespread effects throughout the body, since all organs depend on the lungs for the oxygen they need. Pulmonary pathology catalogs the changes in the lung tissues and the mechanisms through which these occur. This chapter presents a review of lung pathology and the current state of knowledge about the pathogenesis of each disease. It suggests that a clear understanding of both morphology and mechanism is required for the development of new therapies and preventive measures. url: https://api.elsevier.com/content/article/pii/B9780123744197000184 doi: 10.1016/b978-0-12-374419-7.00018-4 id: cord-328899-kog99kk5 author: Ferrari, Stefano title: Barriers to and new approaches for gene therapy and gene delivery in cystic fibrosis date: 2002-12-05 words: 10491.0 sentences: 536.0 pages: flesch: 45.0 cache: ./cache/cord-328899-kog99kk5.txt txt: ./txt/cord-328899-kog99kk5.txt summary: Strategies to overcome these barriers will be addressed in this review and include the use of: (i) clinically relevant adjuncts to overcome the extraand intracellular barriers; (ii) less-conventional delivery routes, such as intravenous or in utero administration; (iii) more efficient non-viral vectors and ''stealth'' viruses which can be re-administered; and (iv) new approaches to prolong transgene expression by means of alternative promoters or integrating vectors. Interesting-Using an ex vivo sheep trachea model, we demonly, despite non-viral vectors being arguably less strated that cationic lipid-mediated gene transfer, but efficient than viruses in animal models and labora-not adenoviral vectors or recombinant Sendai virus tory studies, clinical trials have shown that this might [22] , was inhibited by normal mucus, with removal Extracellular barriers include the presence of infected mucus and sputum, mucociliary clearance and tight junctions between the cells, which limit the access of viral vectors to receptors localised on the basolateral membrane. abstract: Clinical trials of gene therapy for cystic fibrosis suggest that current levels of gene transfer efficiency are probably too low to result in clinical benefit, largely as a result of the barriers faced by gene transfer vectors within the airways. The respiratory epithelium has evolved a complex series of extracellular barriers (mucus, lack of receptors, immune surveillance, etc.) aimed at preventing penetration of lumenally delivered materials, including gene therapy vectors. In addition, once in the cell, further hurdles have to be overcome, including DNA degradation, nuclear import and the ability to maintain long-term transgene expression. Strategies to overcome these barriers will be addressed in this review and include the use of: (i) clinically relevant adjuncts to overcome the extra- and intracellular barriers; (ii) less-conventional delivery routes, such as intravenous or in utero administration; (iii) more efficient non-viral vectors and ‘stealth’ viruses which can be re-administered; and (iv) new approaches to prolong transgene expression by means of alternative promoters or integrating vectors. These advances have the potential to improve the efficiency of gene delivery to the airway epithelium, thus making gene therapy a more realistic option for cystic fibrosis. url: https://www.ncbi.nlm.nih.gov/pubmed/12458150/ doi: 10.1016/s0169-409x(02)00145-x id: cord-017156-ximzvqbm author: Forsdyke, Donald R. title: Chargaff’s GC rule date: 2010-05-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Evolutionary selective pressures sometimes act to preserve nucleic acid features at the expense of encoded proteins. That this might occur in the case of nucleic acid secondary structure was noted in Chapter 5. That this might also apply to the species-dependent component of the base composition, (G+C)%, was shown by Sueoka in 1961 [2]. The amino acid composition of the proteins of bacteria is influenced, not only by the demands of the environment on the proteins, but also by the (G+C)% of the genome encoding those proteins. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121649/ doi: 10.1007/978-0-387-33419-6_8 id: cord-314915-b6aqwubh author: Futas, Jan title: Natural Killer Cell Receptor Genes in Camels: Another Mammalian Model date: 2019-07-02 words: 10040.0 sentences: 520.0 pages: flesch: 54.0 cache: ./cache/cord-314915-b6aqwubh.txt txt: ./txt/cord-314915-b6aqwubh.txt summary: Here, we analyzed genes encoding selected natural killer cell receptors with a special focus on genes encoding receptors for major histocompatibility complex (MHC) class I ligands in the two domestic camel species, Camelus dromedarius and Camelus bactrianus. In the context of our work on the camelid immunogenome, the objective of this study was to characterize the genomic content of NKC and LRC with special focus on genes encoding natural killer cell receptors for MHC class I ligands in the two domestic camel species, C. dromedarius NCBI reference genome by tblastn algorithm of NCBI''s BLAST ®1 for orthologous protein sequences to killer-cell lectin-like receptors recently identified in cattle as KLR genes (Schwartz et al., 2017) . The general organization of the two genomic regions, the natural killer complex (NKC) and the leukocyte receptor complex (LRC), containing genes and gene families encoding the NK cell receptors annotated based on the dromedary genome assembly CamDro2, was established and is represented in Figure 1 . abstract: Due to production of special homodimeric heavy chain antibodies, somatic hypermutation of their T-cell receptor genes and unusually low diversity of their major histocompatibility complex genes, camels represent an important model for immunogenetic studies. Here, we analyzed genes encoding selected natural killer cell receptors with a special focus on genes encoding receptors for major histocompatibility complex (MHC) class I ligands in the two domestic camel species, Camelus dromedarius and Camelus bactrianus. Based on the dromedary genome assembly CamDro2, we characterized the genetic contents, organization, and variability of two complex genomic regions, the leukocyte receptor complex and the natural killer complex, along with the natural cytotoxicity receptor genes NCR1, NCR2, and NCR3. The genomic organization of the natural killer complex region of camels differs from cattle, the phylogenetically most closely related species. With its minimal set of KLR genes, it resembles this complex in the domestic pig. Similarly, the leukocyte receptor complex of camels is strikingly different from its cattle counterpart. With KIR pseudogenes and few LILR genes, it seems to be simpler than in the pig. The syntenies and protein sequences of the NCR1, NCR2, and NCR3 genes in the dromedary suggest that they could be human orthologues. However, only NCR1 and NCR2 have a structure of functional genes, while NCR3 appears to be a pseudogene. High sequence similarities between the two camel species as well as with the alpaca Vicugna pacos were observed. The polymorphism in all genes analyzed seems to be generally low, similar to the rest of the camel genomes. This first report on natural killer cell receptor genes in camelids adds new data to our understanding of specificities of the camel immune system and its functions, extends our genetic knowledge of the innate immune variation in dromedaries and Bactrian camels, and contributes to studies of natural killer cell receptors evolution in mammals. url: https://doi.org/10.3389/fgene.2019.00620 doi: 10.3389/fgene.2019.00620 id: cord-017932-vmtjc8ct author: Georgiev, Vassil St. title: Genomic and Postgenomic Research date: 2009 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The word genomics was first coined by T. Roderick from the Jackson Laboratories in 1986 as the name for the new field of science focused on the analysis and comparison of complete genome sequences of organisms and related high-throughput technologies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122628/ doi: 10.1007/978-1-60327-297-1_25 id: cord-260345-ugd8kkor author: Giles, Ian G. title: A compendium of reviews in biochemistry and molecular biology published in the first half of 1992 date: 1992-12-31 words: 5327.0 sentences: 701.0 pages: flesch: 45.0 cache: ./cache/cord-260345-ugd8kkor.txt txt: ./txt/cord-260345-ugd8kkor.txt summary: 203, sodium dodecyl-sulfate.; ted blood-cells; phosphoenolpyruvate carboxylase activity; nucleotide-linked dehydrogenases; alkaline-phosphatase isoenzymes; pathogenesis-related proteins; cr-L-fucosidase; polyactylamide-gel; produce phosphate; general-method. low-density~l&protein; high-performance liquid; chrcmatogmphy mass spectmmetry; chicken vitellogam gene; thin-layer chmmatography; apolipoprotein-VLDL-II; fatty-acid composition; laying turkey hens; egg-yolk; plasma-lipoproteins. human-skin fibroblests; IGF binding-protein; messenger ribonucleic-acid; cooh-teminal truncation; monoclonal-antibody; endothelial-cells; factor receptoc amniotic-fluid; DNA-synthesis; rat-heart. factor-binding-protein; erythroid colony formation; cultured human-tibroblasts; factor messenger-RNA, N-terminal sequence; fetal bovine serum; IGF-I; somatomedin C, clinical-applicstians; stimulating factors. shon-hved protein; dependent pmteolytic system; ubiquitin-conjugating enzyme; repair gene ra&, Escherichia coli; transfer RNA; Sacclurroqces cercvisiue; endoplasmic-reticulum; cell-cycle; amino-acid. polymense chain-reaction; fragment length polymorphisms; dependent diabetes-mellitus; sickle-cell anemia; factor-M gene; enzymatic AMPlificatiat; genomic DNA; mutations; sequence; diagnosis; predisposition; genetics. T-cell receptor; messenger-RNA degradation; gamma-delta; stress proteins; antigen-receptor, lymphocytes-T; ~ycobactcrium fuberc&arir. Wiskott-Aldrich syndrome; heat-shock proteins; receptor-delta; ataxia telangiectasia; transgenic mice; lymphocytes T; bearing cells; recognition; expression; incmase. human granulocyte-macmphage; protein kinase-c; recombinant human interleukin-3; cell growth-factor, murine bone-marrow; express functional receptors; acute lymphocytic-leukemia; GTPase-activating pm&n; factor-independent growth. abstract: Abstract 1. 1. A compendium of reviews and mini-reviews in Biochemistry and Molecular Biology published in the first half of 1992 is presented. In all 499 titles are listed from 95 different publications. 2. 2. This compendium presents the references by Journal Name. Keywords have been included with each reference to increase the value of the collection. Keyword and author cross-reference indexes are not included but are available in the electronic database from which this version was constructed. Should anyone wish to have this information in electronic form it can be distributed on MS-DOS formatted flopppy disks in either Reference Manager or Medline format. The author should be contacted for details of the number of preformatted floppy disks required. url: https://www.sciencedirect.com/science/article/pii/0020711X92902837 doi: 10.1016/0020-711x(92)90283-7 id: cord-315072-b28yikvj author: Giotis, Efstathios S. title: Chicken interferome: avian interferon-stimulated genes identified by microarray and RNA-seq of primary chick embryo fibroblasts treated with a chicken type I interferon (IFN-α) date: 2016-08-05 words: 5878.0 sentences: 285.0 pages: flesch: 48.0 cache: ./cache/cord-315072-b28yikvj.txt txt: ./txt/cord-315072-b28yikvj.txt summary: title: Chicken interferome: avian interferon-stimulated genes identified by microarray and RNA-seq of primary chick embryo fibroblasts treated with a chicken type I interferon (IFN-α) To generate a chicken ISG database we have compared data from three transcriptomic technology platforms: (i) the classical 3′-biased GeneChip Chicken Genome Array (32K; Affymetrix, High Wycombe, UK), (ii) the Chicken Gene 1.0 Sense Target (ST) whole transcriptome Array (Affymetrix) and (iii) Illumina (Little Chesterford, UK) RNA-seq. One of the most highly-expressed contigs was one which, when analysed by BLAST, proved to represent a homologue of STAT2, which is missing from the current ENSEMBL annotated reference chicken genome In (B) PYURF shows 24-fold suppression by IFN but the sequence surrounding PYURF shows 87-fold induction from the right-hand end of the unannotated, antisense LOC422513 and considerably higher upregulation from the left-hand end (due to its lower uninduced levels), consistent with these representing homologues of IFN-inducible human genes HERC6 and HERC5. Technologies identifying significant IRGs are listed as "1" RNA-seq (using Kal''s Z test); "2" Affymetrix 32K GeneChip Chicken Genome Array and "3" Chicken Gene 1.0 ST Array'' . abstract: Viruses that infect birds pose major threats—to the global supply of chicken, the major, universally-acceptable meat, and as zoonotic agents (e.g. avian influenza viruses H5N1 and H7N9). Controlling these viruses in birds as well as understanding their emergence into, and transmission amongst, humans will require considerable ingenuity and understanding of how different species defend themselves. The type I interferon-coordinated response constitutes the major antiviral innate defence. Although interferon was discovered in chicken cells, details of the response, particularly the identity of hundreds of stimulated genes, are far better described in mammals. Viruses induce interferon-stimulated genes but they also regulate the expression of many hundreds of cellular metabolic and structural genes to facilitate their replication. This study focusses on the potentially anti-viral genes by identifying those induced just by interferon in primary chick embryo fibroblasts. Three transcriptomic technologies were exploited: RNA-seq, a classical 3′-biased chicken microarray and a high density, “sense target”, whole transcriptome chicken microarray, with each recognising 120–150 regulated genes (curated for duplication and incorrect assignment of some microarray probesets). Overall, the results are considered robust because 128 of the compiled, curated list of 193 regulated genes were detected by two, or more, of the technologies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0363-8) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pubmed/27494935/ doi: 10.1186/s13567-016-0363-8 id: cord-016062-h4vjkufn author: Gontier, Nathalie title: Evolutionary epistemology and the origin and evolution of language: Taking symbiogenesis seriously date: 2006 words: 12419.0 sentences: 576.0 pages: flesch: 49.0 cache: ./cache/cord-016062-h4vjkufn.txt txt: ./txt/cord-016062-h4vjkufn.txt summary: Given this minor role that natural selection plays within evolution, it is too short-sighted to only develop general normative frameworks based upon Neo-Darwinian theory to study all of life''s phenomena. Again, we need to be more cautious with our definition: vertical evolution at the animal level implies that two members of the same species, of the opposite sexes, mate, and that during this mating process, one sex cell from each parent merges with the other to form a fertilized cell, from whereupon an embryo develops. Since it mostly only involves the passing on or recombining of existing genes, I prefer to call this a form of horizontal evolution contrary to regarding this as part of the process of individual variation that occurs because of vertical genetic recombinations without there actually being vertical evolution (because no species evolves or goes extinct). abstract: Symbiogenesis is a form of horizontal evolution that occurred 2 billion years ago, with the evolution of eukaryotic cells. It will be argued that, just as we can develop universal selection theories based upon a general account of natural selection, we can also develop a universal symbiogenetic principle that can serve as a general framework to study the origin and evolution of language. (1) Horizontal evolution will be compared with and distinguished from vertical evolution. (2) Different examples of intra- and interspecific horizontal evolution will be given to show that horizontal evolution is quantitatively and qualitatively the most commonly occurring form of evolution throughout the history of life. (3) Finally, three examples are given of how a universal symbiogenesis principle can be implemented in the study of language origins and evolution, more specifically within: (a) the study of language variation, (b) language genes and (c) conceptual blending. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120221/ doi: 10.1007/1-4020-3395-8_10 id: cord-278136-ol2buwld author: Gonzales, Natalia M. title: 29th International Mammalian Genome Conference meeting report date: 2016-05-02 words: 4685.0 sentences: 180.0 pages: flesch: 34.0 cache: ./cache/cord-278136-ol2buwld.txt txt: ./txt/cord-278136-ol2buwld.txt summary: The session showcased tools such as recombinant inbred lines (RILs), outbred populations, classic crosses, and ENU mutagenesis to yield new understanding and identify candidate genes for disease susceptibility, while knockout and patient-derived xenograft mice enabled further mechanistic insight. Other features of this session included a GWAS of aerobic capacity in rats segregated on running ability by Yu Wang German Center for Neurodegenerative Diseases Tuebingen) conducted a massive forward genetic screen using human exome data, followed by systematic RNAi screens in worms, flies, and human cell lines to identify genes and pathways involved in Parkinson''s disease. This plenary session encompassed the use of mouse embryonic stem cells (mESCs), gene expression analysis, and recent advances in genome engineering to address fundamental questions about development and degenerative disease. A common approach featured at the IMGC each year is the use of the mouse as a model for understanding how biological processes influence and respond to changes in the mammalian genomic landscape. abstract: nan url: https://doi.org/10.1007/s00335-016-9640-0 doi: 10.1007/s00335-016-9640-0 id: cord-016713-pw4f8asc author: Goyal, Amit K. title: Nanotechnological Approaches for Genetic Immunization date: 2013-05-24 words: 16034.0 sentences: 814.0 pages: flesch: 34.0 cache: ./cache/cord-016713-pw4f8asc.txt txt: ./txt/cord-016713-pw4f8asc.txt summary: The use of nonviral particulate carriers for DNA-based vaccination could provide better and safe delivery of encapsulated genetic material, circumvent the need for muscle involvement and facilitate instead the uptake of the Fig. 4 Schematic representation of immunological response greeted by novel DNA-loaded nanocarrier DNA by APCs. However, transfection of APCs with encapsulated DNA into particulate carrier systems will be dependent upon choice of carrier surface charge, size, and lipid/polymer composition, or presence of other biological [e.g., interleukin 2 and interferon-γ (IFN-γ)]. Modification of lipid/DNA complexes by the polymer poly(D,L-lactic acid) was found to be consistently and significantly more effective than either unmodified liposomal DNA or naked DNA in eliciting transgene-specific immune responses to plasmid-encoded antigen when administered by the s.c. route (Bramwell et al. abstract: Genetic immunization is one of the important findings that provide multifaceted immunological response against infectious diseases. With the advent of r-DNA technology, it is possible to construct vector with immunologically active genes against specific pathogens. Nevertheless, site-specific delivery of constructed genetic material is an important contributory factor for eliciting specific cellular and humoral immune response. Nanotechnology has demonstrated immense potential for the site-specific delivery of biomolecules. Several polymeric and lipidic nanocarriers have been utilized for the delivery of genetic materials. These systems seem to have better compatibility, low toxicity, economical and capable to delivering biomolecules to intracellular site for the better expression of desired antigens. Further, surface engineering of nanocarriers and targeting approaches have an ability to offer better presentation of antigenic material to immunological cells. This chapter gives an overview of existing and emerging nanotechnological approaches for the delivery of genetic materials. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121080/ doi: 10.1007/978-3-642-36853-0_4 id: cord-336573-bpg1dg24 author: Greenaway, Hui Yee title: Extraction and characterization of the rhesus macaque T cell receptor β-chain genes date: 2009-06-09 words: 3721.0 sentences: 167.0 pages: flesch: 55.0 cache: ./cache/cord-336573-bpg1dg24.txt txt: ./txt/cord-336573-bpg1dg24.txt summary: To demonstrate the use of the TRB genes extracted from the rhesus macaque genome by expressed TCRβ sequences, we used an existing database of 7218 TCRβ sequences involved in CD8 + T cell responses specific for the immunodominant Mamu-A*01-restricted SIV-SL8/TL8 and SIV-CM9 epitopes in 20 rhesus macaques30, 45. Here, we report a reference set of TRB genes extracted from the rhesus macaque genome, most of which were expressed by TCRβ sequences in our extensive database of TCRβ repertoires involved in CD8 + T cell responses to the immunodominant Mamu-A*01-restricted SL8/TL8 and CM9 epitopes derived from SIV. The best human match to each macaque region was identified and then used as a guide to determine the exact length and terminal ends of the rhesus macaque TRB gene sequences, as well as intron and exon positions. abstract: Rhesus macaque models have been instrumental for the development and testing of vaccines prior to human studies and have provided fundamental insights into the determinants of immune efficacy in a variety of infectious diseases. However, the characterization of antigen-specific T cell receptor (TCR) repertoires during adaptive immune responses in these models has previously relied on human TCR gene assignments. Here, we extracted and characterized TCR β-chain (TRB) genes from the recently sequenced rhesus macaque genome that are homologous to the human TRB genes. Comparison of the rhesus macaque TRB genes with the human TRB genes revealed an average best-match similarity of 92.9%. Furthermore, we confirmed the usage of most rhesus macaque TRB genes by expressed TCRβ sequences within epitope-specific TCR repertoires. This primary description of the rhesus macaque TRB genes will provide a standardized nomenclature and enable better characterization of TCR usage in studies that utilize this species. url: https://www.ncbi.nlm.nih.gov/pubmed/19506572/ doi: 10.1038/icb.2009.38 id: cord-005476-q6o5239w author: Griesenbach, U title: Gene therapy for cystic fibrosis: an example for lung gene therapy date: 2004-09-29 words: 5903.0 sentences: 290.0 pages: flesch: 44.0 cache: ./cache/cord-005476-q6o5239w.txt txt: ./txt/cord-005476-q6o5239w.txt summary: Over the last decade, the gene therapy community has recognized that there is not even one vector that is good for all applications, but that the gene transfer agent (GTA) has to be carefully chosen depending on the cell type to be targeted, the number of treatments (one versus repeat administration) required, and the size and nature (secreted versus cellular product) of the gene to be delivered. In an attempt to increase the transfection efficiency of adenoviral vectors in vivo, Gregory et al 17 assessed the effects of sodium caprate (a tight junction opener) application to the luminal surface of AECs in mouse lung, with the rationale that CAR expression is higher on the basolateral surface of epithelial cells. RSV and PIV3 target human ciliated airway epithelial cells: efficient gene transfer vectors for cystic fibrosis lung disease abstract: Gene therapy is currently being evaluated for a wide range of acute and chronic lung diseases. The requirement of gene transfer into the individual cell types of the complex lung structure will very much depend on the target disease. Over the last decade, the gene therapy community has recognized that there is not even one vector that is good for all applications, but that the gene transfer agent has to be carefully chosen. Gene therapy is particularly attractive for diseases that currently do not have satisfactory treatment options and probably easier for monogenic disorders than for complex diseases. Cystic fibrosis (CF) fulfills these criteria and is therefore a good candidate for gene therapy-based treatment. This review will focus on CF as an example for lung gene therapy and discuss the progress made in this field over the last couple of years. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092152/ doi: 10.1038/sj.gt.3302368 id: cord-007259-vj9tv3or author: Guo, Feng-Biao title: Accurate prediction of human essential genes using only nucleotide composition and association information date: 2017-06-15 words: 5656.0 sentences: 315.0 pages: flesch: 52.0 cache: ./cache/cord-007259-vj9tv3or.txt txt: ./txt/cord-007259-vj9tv3or.txt summary: RESULTS: Our model accurately predicted human gene essentiality with an AUC higher than 0.88 both for 5-fold cross-validation and jackknife tests. reported a machine learningbased method that integrated various intrinsic and predicted features to identify essential genes in yeast S.cerevisiae genomes (Seringhaus et al., 2006) . The data from these three groups provided a rare opportunity to theoretically study the function, sequence composition, evolution and network topology of human essential genes. Based on the k-interval Z curve, we obtained excellent performance in human essential gene identification. For human essential gene identification, we only used the sequence composition and interval association information in the present study and still obtained an AUC of 0.8854. Considering that this result is better than the results obtained in previous studies using integrated features, the gene essentiality of the human genome can be accurately reflected based on only the sequence information. abstract: MOTIVATION: Previously constructed classifiers in predicting eukaryotic essential genes integrated a variety of features including experimental ones. If we can obtain satisfactory prediction using only nucleotide (sequence) information, it would be more promising. Three groups recently identified essential genes in human cancer cell lines using wet experiments and it provided wonderful opportunity to accomplish our idea. Here we improved the Z curve method into the λ-interval form to denote nucleotide composition and association information and used it to construct the SVM classifying model. RESULTS: Our model accurately predicted human gene essentiality with an AUC higher than 0.88 both for 5-fold cross-validation and jackknife tests. These results demonstrated that the essentiality of human genes could be reliably reflected by only sequence information. We re-predicted the negative dataset by our Pheg server and 118 genes were additionally predicted as essential. Among them, 20 were found to be homologues in mouse essential genes, indicating that some of the 118 genes were indeed essential, however previous experiments overlooked them. As the first available server, Pheg could predict essentiality for anonymous gene sequences of human. It is also hoped the λ-interval Z curve method could be effectively extended to classification issues of other DNA elements. AVAILABILITY AND IMPLEMENTATION: http://cefg.uestc.edu.cn/Pheg SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110051/ doi: 10.1093/bioinformatics/btx055 id: cord-280691-nzc8ir0n author: Guo, Sun-Wei title: China’s “Gene War of the Century” and Its Aftermath: The Contest Goes On date: 2013-08-30 words: 12487.0 sentences: 563.0 pages: flesch: 52.0 cache: ./cache/cord-280691-nzc8ir0n.txt txt: ./txt/cord-280691-nzc8ir0n.txt summary: Around 1997, and amid the talks of Hong Kong''s upcoming return to China and later the Asian financial crisis, a recurring topic in the Chinese media was the so-called ''''gene war of the century'''': the lopsided condemnation of foreign scientists coming purportedly to pilfer China''s vast genetic resources for a profit. Despite his repeated proclamation as a staunch and unwavering patriot loyal to his beloved motherland and dedicated to the advancement of China''s science and technology, he nonetheless later became embroiled in an avalanche of controversies surrounding the ''''gene war.'''' He effectively became a lightning rod for all the controversy on genetic resources, intellectual rights, informed consent, and the protection of human research subjects. (2) Chinese scientists should immediately grasp the opportunity to find disease genes and patent them; (3) We should educate the people, and raise the awareness and importance of protection of our genetic resources; (4) We welcome all international collaborations based on fairness and mutual benefits; (5) Through various avenues, the Chinese scientists should be vocal about certain views deemed to be harmful to China''s genetic research (Xiao et al. abstract: Following the successful cloning of genes for mostly rare genetic diseases in the early 1990s, there was a nearly universal enthusiasm that similar approaches could be employed to hunt down genes predisposing people to complex diseases. Around 1996, several well-funded international gene-hunting teams, enticed by the low cost of collecting biological samples and China’s enormous population, and ushered in by some well-connected Chinese intermediaries, came to China to hunt down disease susceptibility genes. This alarmed and, in some cases, enraged many poorly funded Chinese scientists, who perceived them as formidable competitors. Some depicted foreign gene-hunters as greedy pilferers of the vast Chinese genetic gold mine, comparing it to the plundering of national treasures from China by invaders in the past, and called upon the government and their fellow countrymen to rise up and protect China’s genetic gold mine. Media uproar ensued, proclaiming the imminent “gene war of the century.” This article chronicles the key events surrounding this “war” and its aftermath, exposes some inherent complexities in identifying susceptibility genes for complex diseases, highlights some issues obscured or completely overlooked in the passionate and patriotic rhetoric, and debunks some misconceptions embedded in this conflict. In addition, it argues that during the entire course of this “war,” the public’s interest went conspicuously unmentioned. Finally, it articulates several lessons that can be learned from this conflict, and outlines challenges facing human genetics researchers. url: https://www.ncbi.nlm.nih.gov/pubmed/32214463/ doi: 10.1007/s11024-013-9237-7 id: cord-280924-g6062fwk author: Hachim, Mahmood Yaseen title: Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells date: 2020-06-10 words: 2851.0 sentences: 147.0 pages: flesch: 42.0 cache: ./cache/cord-280924-g6062fwk.txt txt: ./txt/cord-280924-g6062fwk.txt summary: title: Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells We identified IFITM3 as an early upregulated gene, and valproic acid was found to enhance its mRNA expression as well as induce its antiviral action. To effectively address the ongoing COVID-19 pandemic, there is a recognized need for a framework for rapid identification of novel targets for diagnostic and therapeutic interventions as well as determine clinically approved drugs with high potential for repurposed use against SARS-CoV-2. In this study, we have applied this approach, and our findings have identified IFITM3 as an early upregulated gene and indicate that valproic acid enhances IFITM3 mRNA expression and antiviral action. Our toxicogenomic analysis showed that valproic acid increased the mRNA expression of IFITM3, supporting a new report that the SARS-CoV-2-human protein-protein interaction map showed that valproic acid might be a potential repurposing drug for COVID-19 (34) . abstract: Current guidelines for COVID-19 management recommend the utilization of various repurposed drugs. Despite ongoing research toward the development of a vaccine against SARS-CoV-2, such a vaccine will not be available in time to contribute to the containment of the ongoing pandemic. Therefore, there is an urgent need to develop a framework for the rapid identification of novel targets for diagnostic and therapeutic interventions. We analyzed publicly available transcriptomic datasets of SARS-CoV infected humans and mammals to identify consistent differentially expressed genes then validated in SARS-CoV-2 infected epithelial cells transcriptomic datasets. Comprehensive toxicogenomic analysis of the identified genes to identify possible interactions with clinically proven drugs was carried out. We identified IFITM3 as an early upregulated gene, and valproic acid was found to enhance its mRNA expression as well as induce its antiviral action. These findings indicate that analysis of publicly available transcriptomic and toxicogenomic data represents a rapid approach for the identification of novel targets and molecules that can modify the action of such targets during the early phases of emerging infections like COVID-19. url: https://doi.org/10.3389/fimmu.2020.01372 doi: 10.3389/fimmu.2020.01372 id: cord-291719-1ku6cmwj author: Hajjo, Rima title: A Systems Biology Workflow for Drug and Vaccine Repurposing: Identifying Small-Molecule BCG Mimics to Reduce or Prevent COVID-19 Mortality date: 2020-10-06 words: 6493.0 sentences: 315.0 pages: flesch: 41.0 cache: ./cache/cord-291719-1ku6cmwj.txt txt: ./txt/cord-291719-1ku6cmwj.txt summary: METHODS: We developed and employed a systems biology workflow capable of identifying small-molecule antiviral drugs and vaccines that can boast immunity and affect a wide variety of viral disease pathways to protect from the fatal consequences of emerging viruses. RESULTS: Our analysis demonstrates that BCG vaccine affects the production and maturation of naïve T cells resulting in enhanced, long-lasting trained innate immune responses that can provide protection against novel viruses. Herein, we describe a unique drug and vaccine repurposing workflow, and list high confidence proteins and pharmacological classes of compounds, that work as BCG mimics at the system level by inducing beneficial long lasting trained immune response. Earlier studies suggested that the documented beneficial off-target effects of BCG in protecting from non-TB infections, including perhaps COVID-19, involve a potentiation of innate immune responses through epigenetic mechanisms (56) (57) (58) . abstract: PURPOSE: Coronavirus disease 2019 (COVID-19) is expected to continue to cause worldwide fatalities until the World population develops ‘herd immunity’, or until a vaccine is developed and used as a prevention. Meanwhile, there is an urgent need to identify alternative means of antiviral defense. Bacillus Calmette–Guérin (BCG) vaccine that has been recognized for its off-target beneficial effects on the immune system can be exploited to boast immunity and protect from emerging novel viruses. METHODS: We developed and employed a systems biology workflow capable of identifying small-molecule antiviral drugs and vaccines that can boast immunity and affect a wide variety of viral disease pathways to protect from the fatal consequences of emerging viruses. RESULTS: Our analysis demonstrates that BCG vaccine affects the production and maturation of naïve T cells resulting in enhanced, long-lasting trained innate immune responses that can provide protection against novel viruses. We have identified small-molecule BCG mimics, including antiviral drugs such as raltegravir and lopinavir as high confidence hits. Strikingly, our top hits emetine and lopinavir were independently validated by recent experimental findings that these compounds inhibit the growth of SARS-CoV-2 in vitro. CONCLUSIONS: Our results provide systems biology support for using BCG and small-molecule BCG mimics as putative vaccine and drug candidates against emergent viruses including SARS-CoV-2. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11095-020-02930-9) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pubmed/33025261/ doi: 10.1007/s11095-020-02930-9 id: cord-103505-9adtbwp2 author: Hale, A. T. title: The genetic architecture of human infectious diseases and pathogen-induced cellular phenotypes date: 2020-07-21 words: 1408.0 sentences: 105.0 pages: flesch: 41.0 cache: ./cache/cord-103505-9adtbwp2.txt txt: ./txt/cord-103505-9adtbwp2.txt summary: Host genetic variation is likely to contribute to ID risk and downstream clinical outcomes, but there is a need for a genetics-anchored framework to decipher molecular mechanisms of disease risk, infer causal effect on potential complications, and identify instruments for drug target discovery. The rich resource of genetic information linked to serologic tests and pathogen cultures from bronchoalveolar lavage, sputum, sinus/nasopharyngeal, tracheal, and blood samples (up to 7,699 positive pathogen cultures across 92 unique genera) that we leverage provides a platform to interrogate the genetic basis of compartment-specific infection and colonization. To accelerate insights into cellular mechanisms, we develop a TWAS repository of gene-level associations in a broad collection of human tissues with 79 pathogen-exposure induced cellular phenotypes as a discovery and replication platform. We hypothesized that tissue expression profiling of ID-associated genes 216 can provide additional insights into disease etiologies and mechanisms. These data identify specific molecular mechanisms across ID traits with critical 239 regulatory roles (e.g., protein modifications) in host response among the ID-associated genes. abstract: Infectious diseases (ID) represent a significant proportion of morbidity and mortality across the world. Host genetic variation is likely to contribute to ID risk and downstream clinical outcomes, but there is a need for a genetics-anchored framework to decipher molecular mechanisms of disease risk, infer causal effect on potential complications, and identify instruments for drug target discovery. Here we perform transcriptome-wide association studies (TWAS) of 35 clinical ID traits in a cohort of 23,294 individuals, identifying 70 gene-level associations with 26 ID traits. Replication in two large-scale biobanks provides additional support for the identified associations. A phenome-scale scan of the 70 gene-level associations across hematologic, respiratory, cardiovascular, and neurologic traits proposes a molecular basis for known complications of the ID traits. Using Mendelian Randomization, we then provide causal support for the effect of the ID traits on adverse outcomes. The rich resource of genetic information linked to serologic tests and pathogen cultures from bronchoalveolar lavage, sputum, sinus/nasopharyngeal, tracheal, and blood samples (up to 7,699 positive pathogen cultures across 92 unique genera) that we leverage provides a platform to interrogate the genetic basis of compartment-specific infection and colonization. To accelerate insights into cellular mechanisms, we develop a TWAS repository of gene-level associations in a broad collection of human tissues with 79 pathogen-exposure induced cellular phenotypes as a discovery and replication platform. Cellular phenotypes of infection by 8 pathogens included pathogen invasion, intercellular spread, cytokine production, and pyroptosis. These rich datasets will facilitate mechanistic insights into the role of host genetic variation on ID risk and pathophysiology, with important implications for our molecular understanding of potentially severe phenotypic outcomes. url: http://medrxiv.org/cgi/content/short/2020.07.19.20157404v1?rss=1 doi: 10.1101/2020.07.19.20157404 id: cord-102935-cx3elpb8 author: Hassani-Pak, Keywan title: KnetMiner: a comprehensive approach for supporting evidence-based gene discovery and complex trait analysis across species date: 2020-04-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Generating new ideas and scientific hypotheses is often the result of extensive literature and database reviews, overlaid with scientists’ own novel data and a creative process of making connections that were not made before. We have developed a comprehensive approach to guide this technically challenging data integration task and to make knowledge discovery and hypotheses generation easier for plant and crop researchers. KnetMiner can digest large volumes of scientific literature and biological research to find and visualise links between the genetic and biological properties of complex traits and diseases. Here we report the main design principles behind KnetMiner and provide use cases for mining public datasets to identify unknown links between traits such grain colour and pre-harvest sprouting in Triticum aestivum, as well as, an evidence-based approach to identify candidate genes under an Arabidopsis thaliana petal size QTL. We have developed KnetMiner knowledge graphs and applications for a range of species including plants, crops and pathogens. KnetMiner is the first open-source gene discovery platform that can leverage genome-scale knowledge graphs, generate evidence-based biological networks and be deployed for any species with a sequenced genome. KnetMiner is available at http://knetminer.org. url: https://doi.org/10.1101/2020.04.02.017004 doi: 10.1101/2020.04.02.017004 id: cord-339012-4juhmjaj author: Hou, Wei title: Rapid host response to an infection with Coronavirus. Study of transcriptional responses with Porcine Epidemic Diarrhea Virus date: 2020-07-28 words: 6756.0 sentences: 344.0 pages: flesch: 48.0 cache: ./cache/cord-339012-4juhmjaj.txt txt: ./txt/cord-339012-4juhmjaj.txt summary: Instead, PEDV down-regulated the expression of a set of zinc finger proteins with putative antiviral activity and enhanced the expression of the transmembrane serine protease gene TMPRSS13 (alias MSPL) to support its own infection by virus-cell membrane fusion (Shi et al, 2017, Viruses, 9(5):114). Furthermore, by comprehensive datamining in biological and chemical databases and consulting related literature we identified sets of PEDV-response genes with potential to influence i) the metabolism of biogenic amines (e.g. histamine), ii) the formation of cilia and "synaptic clefts" between cells, iii) epithelial mucus production, iv) platelets activation, and v) physiological processes in the body regulated by androgenic hormones (like blood pressure, salt/water balance and energy homeostasis). The detected sets of differential expressed genes (DEGs) for PEDV and MRV were analyzed by gene set enrichment analysis (GSEA) using functional bioinformatic programs to retrieve biological processes (pathways and Gene Ontology terms [GO-term]) and associations with chemical compounds, including drugs. abstract: The transcriptional response in Vero cells (ATCC® CCL-81) infected with the coronavirus Porcine Epidemic Diarrhea Virus (PEDV) was measured by RNAseq analysis 4 and 6 hours after infection. Differential expressed genes (DEGs) in PEDV infected cells were compared to DEGs responding in Vero cells infected with Mammalian Orthoreovirus (MRV). Functional analysis of MRV and PEDV DEGs showed that MRV increased the expression level of several cytokines and chemokines (e.g. IL6, CXCL10, IL1A, CXCL8 [alias IL8]) and antiviral genes (e.g. IFI44, IFIT1, MX1, OASL), whereas for PEDV no enhanced expression was observed for these “hallmark” antiviral and immune effector genes. Pathway and Gene Ontology “enrichment analysis” revealed that PEDV infection did not stimulate expression of genes able to activate an acquired immune response, whereas MRV did so within 6h. Instead, PEDV down-regulated the expression of a set of zinc finger proteins with putative antiviral activity and enhanced the expression of the transmembrane serine protease gene TMPRSS13 (alias MSPL) to support its own infection by virus-cell membrane fusion (Shi et al, 2017, Viruses, 9(5):114). PEDV also down-regulated expression of Ectodysplasin A, a cytokine of the TNF-family able to activate the canonical NFKB-pathway responsible for transcription of inflammatory genes like IL1B, TNF, CXCL8 and PTGS2. The only 2 cytokine genes found up-regulated by PEDV were Cardiotrophin-1, an IL6-type cytokine with pleiotropic functions on different tissues and types of cells, and Endothelin 2, a neuroactive peptide with vasoconstrictive properties. Furthermore, by comprehensive datamining in biological and chemical databases and consulting related literature we identified sets of PEDV-response genes with potential to influence i) the metabolism of biogenic amines (e.g. histamine), ii) the formation of cilia and “synaptic clefts” between cells, iii) epithelial mucus production, iv) platelets activation, and v) physiological processes in the body regulated by androgenic hormones (like blood pressure, salt/water balance and energy homeostasis). The information in this study describing a “very early” response of epithelial cells to an infection with a coronavirus may provide pharmacologists, immunological and medical specialists additional insights in the underlying mechanisms of coronavirus associated severe clinical symptoms including those induced by SARS-CoV-2. This may help them to fine-tune therapeutic treatments and apply specific approved drugs to treat COVID-19 patients. url: https://doi.org/10.1101/2020.07.28.224576 doi: 10.1101/2020.07.28.224576 id: cord-264996-og3sg0qw author: Howell, Gareth J. title: Cell Biology of Membrane Trafficking in Human Disease date: 2006-09-17 words: 20320.0 sentences: 1072.0 pages: flesch: 42.0 cache: ./cache/cord-264996-og3sg0qw.txt txt: ./txt/cord-264996-og3sg0qw.txt summary: Many of these transport intermediates or vesicles, whether derived from the ER, other internal organelles, or the plasma membrane, are ''''coated'''' with unique protein complexes, tethering factors, and regulatory factors that ensure correct targeting to an acceptor compartment. Breast cancer Caveolin-1 Deletion or dominant negative mutation of caveolin-1 promotes tumor progression Breast cancer (Bouras et al., 2004; Williams and Lisanti, 2005) (Hayasaka et al., 1993; Matsuyama et al., 2002) Chediak-Higashi syndrome (CHS) CHS1/Lyst Lyst involved in regulation of protein secretion from lysosomes -enlarged lysosomes Partial albinism, recurrent bacterial infections, impaired chemotaxis and abnormal natural killer cell function (Shiflett et al., 2002; Ward et al., 2003) 214500 Choroideremia (CHM) Rab Escort Protein 1 (REP1) RAB27a remains cytosolic due to defective geranylgeranyl modification in CHM lymphoblasts X-linked form of retinal degeneration 303100 Various mechanisms control the traYcking of proteins from the TGN by the formation and delivery of membrane-derived transport vesicles to the plasma membrane, endosomes, or lysosomal structures (Ponnambalam and Baldwin, 2003) . abstract: Understanding the molecular and cellular mechanisms underlying membrane traffic pathways is crucial to the treatment and cure of human disease. Various human diseases caused by changes in cellular homeostasis arise through a single gene mutation(s) resulting in compromised membrane trafficking. Many pathogenic agents such as viruses, bacteria, or parasites have evolved mechanisms to subvert the host cell response to infection, or have hijacked cellular mechanisms to proliferate and ensure pathogen survival. Understanding the consequence of genetic mutations or pathogenic infection on membrane traffic has also enabled greater understanding of the interactions between organisms and the surrounding environment. This review focuses on human genetic defects and molecular mechanisms that underlie eukaryote exocytosis and endocytosis and current and future prospects for alleviation of a variety of human diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/16984815/ doi: 10.1016/s0074-7696(06)52005-4 id: cord-303939-7knzjnyr author: Hu, Fang title: Identification of a metabolic gene panel to predict the prognosis of myelodysplastic syndrome date: 2020-04-26 words: 2281.0 sentences: 171.0 pages: flesch: 42.0 cache: ./cache/cord-303939-7knzjnyr.txt txt: ./txt/cord-303939-7knzjnyr.txt summary: title: Identification of a metabolic gene panel to predict the prognosis of myelodysplastic syndrome A prognostic model was constructed by the least absolute shrinkage and selection operator (LASSO) regression analysis for MDS patients based on the identified metabolic gene panel in training cohort, followed by external validation in an independent cohort. Therefore, we established a prognostic panel of metabolic gene by downloading data from Gene Expression Omnibus (GEO) datasets in the training cohort, which was further validated in an independent external cohort. In total, 201 patients with complete clinical data including age, gender, WHO category, karyotype, IPSS, transfusion dependent, haemoglobin, bone marrow blasts cells, platelet count and absolute neutrophil count were included in the training and validation cohort. In summary, we constructed a novel prognostic prediction model based on metabolic genes from GEO database for MDS, and further validated in the validation cohort. Identification of a metabolic gene panel to predict the prognosis of myelodysplastic syndrome abstract: Myelodysplastic syndrome (MDS) is clonal disease featured by ineffective haematopoiesis and potential progression into acute myeloid leukaemia (AML). At present, the risk stratification and prognosis of MDS need to be further optimized. A prognostic model was constructed by the least absolute shrinkage and selection operator (LASSO) regression analysis for MDS patients based on the identified metabolic gene panel in training cohort, followed by external validation in an independent cohort. The patients with lower risk had better prognosis than patients with higher risk. The constructed model was verified as an independent prognostic factor for MDS patients with hazard ratios of 3.721 (1.814‐7.630) and 2.047 (1.013‐4.138) in the training cohort and validation cohort, respectively. The AUC of 3‐year overall survival was 0.846 and 0.743 in the training cohort and validation cohort, respectively. The high‐risk score was significantly related to other clinical prognostic characteristics, including higher bone marrow blast cells and lower absolute neutrophil count. Moreover, gene set enrichment analyses (GSEA) showed several significantly enriched pathways, with potential indication of the pathogenesis. In this study, we identified a novel stable metabolic panel, which might not only reveal the dysregulated metabolic microenvironment, but can be used to predict the prognosis of MDS. url: https://doi.org/10.1111/jcmm.15283 doi: 10.1111/jcmm.15283 id: cord-007390-3txwm6wr author: Hu, Yu‐Chen title: Baculovirus Vectors for Gene Therapy date: 2006-09-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Since the discovery that baculoviruses can efficiently transduce mammalian cells, baculoviruses have been extensively studied as potential vectors for both in vitro and in vivo gene therapy. This chapter reviews the history of this research area, cells permissive to baculovirus transduction, factors influencing transduction and transgene expression, efforts to improve transduction, mechanisms of virus entry and intracellular trafficking, applications for in vivo and ex vivo gene therapy, as well as advantages, limitations, and safety issues concerning use of baculoviruses as gene therapy vectors. Recent progress and efforts directed toward overcoming existing bottlenecks are emphasized. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112335/ doi: 10.1016/s0065-3527(06)68008-1 id: cord-322566-ye27nqj2 author: Huang, Yuxiang title: Stable Internal Reference Genes for Normalizing Real-Time Quantitative PCR in Baphicacanthus cusia under Hormonal Stimuli and UV Irradiation, and in Different Plant Organs date: 2017-05-03 words: 5805.0 sentences: 305.0 pages: flesch: 49.0 cache: ./cache/cord-322566-ye27nqj2.txt txt: ./txt/cord-322566-ye27nqj2.txt summary: title: Stable Internal Reference Genes for Normalizing Real-Time Quantitative PCR in Baphicacanthus cusia under Hormonal Stimuli and UV Irradiation, and in Different Plant Organs cusia in this study, and the expression stability was assessed across 60 samples representing different tissues and organs under various conditions, including ultraviolet (UV) irradiation, hormonal stimuli (jasmonic acid methyl ester and abscisic acid), and in different plant organs. However, it is necessary to select suitable reference genes as internal controls under different experimental conditions for accurate RT-qPCR evaluation because of the variability in initial material, RNA integrity, RT-PCR efficiency, and RT-qPCR efficiency (Derveaux et al., 2010) . cusia was evaluated by RNA-Seq (unpublished data) in this study to identify potential reference genes suitable for transcript normalization in experiments under UV irradiation and hormonal stimuli (MeJA and ABA), and also in different plant organs. abstract: Baphicacanthus cusia (Nees) Bremek, the plant source for many kinds of drugs in traditional Chinese medicine, is widely distributed in South China, especially in Fujian. Recent studies about B. cusia mainly focus on its chemical composition and pharmacological effects, but further analysis of the plant's gene functions and expression is required to better understand the synthesis of its effective compounds. Real-time quantitative polymerase chain reaction (RT-qPCR) is a powerful method for gene expression analysis. It is necessary to select a suitable reference gene for expression normalization to ensure the accuracy of RT-qPCR results. Ten candidate reference genes were selected from the transcriptome datasets of B. cusia in this study, and the expression stability was assessed across 60 samples representing different tissues and organs under various conditions, including ultraviolet (UV) irradiation, hormonal stimuli (jasmonic acid methyl ester and abscisic acid), and in different plant organs. By employing different algorithms, such as geNorm, NormFinder, and BestKeeper, which are complementary approaches based on different statistical procedures, 18S rRNA was found to be the most stable gene under UV irradiation and hormonal stimuli, whereas ubiquitin-conjugating enzyme E2 was the best suitable gene for different plant organs. This novel study aimed to screen for suitable reference genes and corresponding primer pairs specifically designed for gene expression studies in B. cusia, in particular for RT-qPCR analyses. url: https://doi.org/10.3389/fpls.2017.00668 doi: 10.3389/fpls.2017.00668 id: cord-021063-4y8m33ea author: Hug, Peter title: Chapter 18 The advantages of liposome-based gene therapy: A comparison of viral versus liposome-based gene delivery date: 2007-09-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Viruses have evolved in such a way they are able to efficiently introduce and express exogenous genes in eukaryotic cells. Most viruses need to maintain high-level expression of their proteins for only a short time and need not be concerned with the viability of the host cell after infection. Attempts to modify a virus into a gene therapy vector can be hampered by this conflict. Virus-based methods of gene therapy are likely to be most useful in applications that require a burst of high-level expression in many of the patient's cells, such as in cancer therapy. Liposomal methods of gene therapy are flexible in that all the components of the system are controlled by designers. As these systems have become more sophisticated, they have begun to take on several characteristics of the viruses that they are intended to replace. The use of basic substances to condense DNA has increased the efficiency of encapsulation. The addition of nucleophilic proteins raises the efficiency of transfection. By adding antibodies or other targeting molecules to the surface of liposomes, preferential binding of vesicles to a desired cell type has been increased. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148944/ doi: 10.1016/s1569-2582(97)80043-8 id: cord-010278-loey5xq9 author: Huh, Changgoo title: Structural organization, expression and chromosomal mapping of the mouse cystatin-C-encoding gene (Cst3) date: 1995-01-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Cystatin C (CstC) is a potent cysteine-proteinase inhibitor. The structure of the mouse CstC-encoding gene (Cst3) was examined by sequencing a 6.1-kb genomic DNA containing the entire gene, as well as 0.9 kb of 5′ flanking and 1.7 kb of its 3′ flanking region. The sequence revealed that the overall organization of the gene is very similar to those of the genes encoding human CstC and other type-2 Cst, with two introns at positions identical to those in the human gene. The promoter area does not contain typical TATA or CAAT ☐es. Two copies of a Spl-binding motif, GGGCGG, are present in the 5′ flanking region within 300 bp upstream from the initiation codon. A hexa-nucleotide, TGTTCT, which is a core sequence of the androgen-responsive element (ARE), is found in the promoter region. This region also contains a 21-nucleotide sequence, 5′-AGACTAGCAGCTGACTGAAGC, which contains two potential binding sites for the transcription factor, AP-1. The mouse Cst3 mRNA was detected in all of thirteen tissues examined by Northern blot analysis. Cst3 was mapped in the mouse to a position on distal chromosome 2. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173308/ doi: 10.1016/0378-1119(94)00728-b id: cord-317779-j67vb7f3 author: Irizarry, Kristopher J. L. title: RNA sequencing demonstrates large-scale temporal dysregulation of gene expression in stimulated macrophages derived from MHC-defined chicken haplotypes date: 2017-08-28 words: 9733.0 sentences: 443.0 pages: flesch: 42.0 cache: ./cache/cord-317779-j67vb7f3.txt txt: ./txt/cord-317779-j67vb7f3.txt summary: Our experimental design leveraged an initial 6 day window for monocytes to differentiate into macrophages, which was followed by IFNγ stimulation between 1 and 24 h to further characterize subsequent RNA gene expression and the molecular basis for dramatically different nitric oxide production and immune function between the B2 and the B19 haplotype chicken macrophages The t-3 day time point, representing 3 days of differentiation in cell culture, exhibited the greatest expression of genes with a total of 11,429 expressed in both B19 and B2 birds while just 4068 genes lacked evidence of expression in both haplotypes. Overall, the gene enrichment analysis of the RNA sequence data provides a cellular-level picture of the specific biological processes that occur over time following activation of monocyte-derived macrophages. abstract: Discovering genetic biomarkers associated with disease resistance and enhanced immunity is critical to developing advanced strategies for controlling viral and bacterial infections in different species. Macrophages, important cells of innate immunity, are directly involved in cellular interactions with pathogens, the release of cytokines activating other immune cells and antigen presentation to cells of the adaptive immune response. IFNγ is a potent activator of macrophages and increased production has been associated with disease resistance in several species. This study characterizes the molecular basis for dramatically different nitric oxide production and immune function between the B2 and the B19 haplotype chicken macrophages.A large-scale RNA sequencing approach was employed to sequence the RNA of purified macrophages from each haplotype group (B2 vs. B19) during differentiation and after stimulation. Our results demonstrate that a large number of genes exhibit divergent expression between B2 and B19 haplotype cells both prior and after stimulation. These differences in gene expression appear to be regulated by complex epigenetic mechanisms that need further investigation. url: https://www.ncbi.nlm.nih.gov/pubmed/28846708/ doi: 10.1371/journal.pone.0179391 id: cord-018798-yzxy9ogf author: Jain, Pradeep Kumar title: RNAi for Resistance Against Biotic Stresses in Crop Plants date: 2018-07-10 words: 12555.0 sentences: 711.0 pages: flesch: 47.0 cache: ./cache/cord-018798-yzxy9ogf.txt txt: ./txt/cord-018798-yzxy9ogf.txt summary: This chapter also reviews the rich history of RNAi research, gene regulation by small RNAs across different organisms, and application potential of RNAi for generating transgenic plants resistant to major pests(.) But, there are some limitations too which restrict wider applications of this technology to its full potential. Different delivery methods of dsRNA that have been used for successful RNAi in insects and nematodes include microinjection, feeding on either artificial diet (Table 4 .2), and/or host-mediated delivery through transgenic plants (Fig. 4.1) . RNAi mechanism partly occurs in the host itself and partly in nematodes feeding on the transgenic host plant expressing dsRNA for the target gene. despite the absence of Sid-1 and Sid-2 genes exhibit systemic RNAi when subjected to silencing technology indicating a presence of similar receptor-mediated endocytic process for dsRNA uptake as reported in insects ). abstract: RNA interference (RNAi)-based gene silencing has become one of the most successful strategies in not only identifying gene function but also in improving agronomical traits of crops by silencing genes of different pathogens/pests and also plant genes for improvement of desired trait. The conserved nature of RNAi pathway across different organisms increases its applicability in various basic and applied fields. Here we attempt to summarize the knowledge generated on the fundamental mechanisms of RNAi over the years, with emphasis on insects and plant-parasitic nematodes (PPNs). This chapter also reviews the rich history of RNAi research, gene regulation by small RNAs across different organisms, and application potential of RNAi for generating transgenic plants resistant to major pests(.) But, there are some limitations too which restrict wider applications of this technology to its full potential. Further refinement of this technology in terms of resolving these shortcomings constitutes one of the thrust areas in present RNAi research. Nevertheless, its application especially in breeding agricultural crops resistant against biotic stresses will certainly offer the possible solutions for some of the breeding objectives which are otherwise unattainable. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123769/ doi: 10.1007/978-3-319-90650-8_4 id: cord-314503-u1y1bznk author: Jaluria, Pratik title: A perspective on microarrays: current applications, pitfalls, and potential uses date: 2007-01-25 words: 7764.0 sentences: 349.0 pages: flesch: 38.0 cache: ./cache/cord-314503-u1y1bznk.txt txt: ./txt/cord-314503-u1y1bznk.txt summary: Therefore, this text aims to outline key features in microarray technology, paying particular attention to current applications as outlined in recent publications, experimental design, statistical methods, and potential uses. Several organizations such as the Microarray Gene Expression Data (MGED) Society and the European Bioinformatics Institute (EBI) have established guidelines to aid researchers in the design and implementation of microarray experiments [8, 9, 16] . As mentioned earlier, verification is critical in order to assign distinct expression patterns to specific genes with certainty (i.e. statistical significance) because of the inherent variability present in microarray data. To verify the results generated from microarray experiments, a combinatorial approach is usually needed; checking the statistical significance associated with the expression levels of specific genes, reviewing the literature, and conducting additional experiments such as RT-PCR or Northern blotting. A large number of microarray-related studies in the past have aimed to either characterize diseased cells in comparison to healthy cells or highlight the genes involved in a particular biological pathway [4, 8] . abstract: With advances in robotics, computational capabilities, and the fabrication of high quality glass slides coinciding with increased genomic information being available on public databases, microarray technology is increasingly being used in laboratories around the world. In fact, fields as varied as: toxicology, evolutionary biology, drug development and production, disease characterization, diagnostics development, cellular physiology and stress responses, and forensics have benefiting from its use. However, for many researchers not familiar with microarrays, current articles and reviews often address neither the fundamental principles behind the technology nor the proper designing of experiments. Although, microarray technology is relatively simple, conceptually, its practice does require careful planning and detailed understanding of the limitations inherently present. Without these considerations, it can be exceedingly difficult to ascertain valuable information from microarray data. Therefore, this text aims to outline key features in microarray technology, paying particular attention to current applications as outlined in recent publications, experimental design, statistical methods, and potential uses. Furthermore, this review is not meant to be comprehensive, but rather substantive; highlighting important concepts and detailing steps necessary to conduct and interpret microarray experiments. Collectively, the information included in this text will highlight the versatility of microarray technology and provide a glimpse of what the future may hold. url: https://www.ncbi.nlm.nih.gov/pubmed/17254338/ doi: 10.1186/1475-2859-6-4 id: cord-340125-il35gs97 author: Jayapal, Manikandan title: Genome-wide gene expression profiling of human mast cells stimulated by IgE or FcεRI-aggregation reveals a complex network of genes involved in inflammatory responses date: 2006-08-16 words: 7377.0 sentences: 380.0 pages: flesch: 48.0 cache: ./cache/cord-340125-il35gs97.txt txt: ./txt/cord-340125-il35gs97.txt summary: title: Genome-wide gene expression profiling of human mast cells stimulated by IgE or FcεRI-aggregation reveals a complex network of genes involved in inflammatory responses A substantial number of genes were regulated by IgE sensitization alone; and following FcεRI aggregation, a wide range of genes were triggered, including genes for cytokines, chemokines, transcription factors, anti-apoptosis, and several genes involved in innate and acquired immunity. Other than these, several genes coding for other receptors involved in immune-responses; immunoregulatory genes; adhesion and/or cytoskeleton remodeling; regulators of apoptosis; signal transduction; transcription factors; were also upregulated by monomeric IgE (Table. Here we studied, whether monomeric-IgE alone, may activate FcεRI intracellular signaling pathways, leading to physiological responses of mast cells, by analyzing the overall tyrosine phosphorylation; fluctuations in cytosolic Ca 2+ concentration; and degranulation by measuring β-hexosaminidase release (Fig. 6A,B &6C) . abstract: BACKGROUND: Mast cells are well established effectors of IgE-triggered allergic reactions and immune responses to parasitic infections. Recent studies indicate that mast cells may play roles in adaptive and innate immunity, suggesting an innovative view of the regulation of immune responses. Here, we profiled the transcriptome of human mast cells sensitized with IgE alone, or stimulated by FcεRI aggregation. RESULTS: Our data show that among 8,793 genes examined, 559 genes are differentially regulated in stimulated mast cells when compared with resting/unstimulated mast cells. The major functional categories of upregulated genes include cytokines, chemokines, and other genes involved in innate and adaptive immune-responses. We observed the increased expression of over 63 gene-transcripts following IgE-sensitization alone. Our data was validated using Real-Time-PCR; ELISA and western blot. We confirmed that IgE alone does not trigger mast cell-immediate responses, such as calcium signals, degranulation or protein-phosphorylation. CONCLUSION: This report represents a substantial advance in our understanding of the genome wide effects triggered by "passive sensitization" or active stimulation of human mast cells, supporting mast cells' potential involvement in a wide range of inflammatory responses. url: https://www.ncbi.nlm.nih.gov/pubmed/16911805/ doi: 10.1186/1471-2164-7-210 id: cord-007760-it9wach2 author: Jiao, Long R. title: Suicide Gene Therapy in Liver Tumors date: 2004 words: 7100.0 sentences: 352.0 pages: flesch: 51.0 cache: ./cache/cord-007760-it9wach2.txt txt: ./txt/cord-007760-it9wach2.txt summary: have recently published the result of a phase I clinical trial using intratumoral injection of escalating doses of adenovirus-mediated suicide gene followed by intravenous GCV at a fixed dose in patients with colorectal liver metastases (13). The study seeks to determine the safety, biological efficacy, and effect of the Ad-TK-GCV dose in the locoregional gene therapy of primary malignant tumors of the liver. The following must be performed within 2 wk prior to study admission: complete medical history; physical examination; toxicity evaluation; performance status; height and weight and body surface area; laboratory screening (*eligibility criteria) for full blood count with differential, platelet count*, serum electrolytes (sodium, potassium, chloride, bicarbonate), urea, creatinine*, glucose, uric acid, albumin, liver function tests, including total protein, calcium, phosphorus, magnesium, aspartate transaminase (AST*), alanine transaminase (ALT*), total bilirubin*, alkaline phosphatase, lactate dehydrogenase (LDH), PT*, partial thomboplastin time (PTT*); urinalysis; α-fetoprotein; electrocardiogram (12-lead); chest X-ray (PA and lateral views); abdomen and pelvis CT or MRI scan. abstract: Charaterization of a variety of genomic defects in malignant cells (1) has led to attempts to treat cancer by gene therapy. Gene therapy is a therapeutic approach in which therapeutic nucleic acids are transferred into the affected organs. Although the ideal concept would be the replacement of the abnormal gene by a copy of the functional gene, currently there have not been reliable and safe techniques to allow the site-specific integration of DNA into the human genome (2). Thus, almost all gene therapies are developed by simply transferring the therapeutic gene into somatic cells without replacing the abnormal gene. The goal is to identify and correct genetic abnormalities interfering with the cell cycle and to correct them in all cells. Technically, there are two methods amenable for gene transfer: reintroduction of in vitro transferred gene into the body and direct transfer of gene into the target cells in vivo. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122362/ doi: 10.1385/1-59259-429-8:433 id: cord-318576-dc5n6ni4 author: Jitobaom, Kunlakanya title: Codon usage similarity between viral and some host genes suggests a codon-specific translational regulation date: 2020-05-08 words: 6821.0 sentences: 345.0 pages: flesch: 53.0 cache: ./cache/cord-318576-dc5n6ni4.txt txt: ./txt/cord-318576-dc5n6ni4.txt summary: From the previous section, we demonstrated that human genes in the GO terms of the cell cycle and the regulation of the cell cycle process adopt codon usage patterns similar to those of þssRNA (subgroups 6, 7), -ssRNA (subgroup 4), retrovirus (HIV-1), and ambisense (subgroup 4) viruses. The lists of upregulated proteins upon viral infection were submitted to GO-TermFinder (Supplementary File 3) , and the enriched GO terms were compared to the enriched GO terms of human genes with codon usage patterns similar to RNA viruses from every subgroup. Several enriched GO terms of upregulated protein profiles during viral infections were found to be identical to the GO terms of human genes with codon usage patterns similar to RNA viruses ( Figure 4 ). Several GO terms of human genes with codon usage patterns similar to RNA viruses have been found by previous studies to be identical to the GO terms of upregulated protein profiles in viral infections. abstract: The codon usage pattern is a specific characteristic of each species; however, the codon usage of all of the genes in a genome is not uniform. Intriguingly, most viruses have codon usage patterns that are vastly different from the optimal codon usage of their hosts. How viral genes with different codon usage patterns are efficiently expressed during a viral infection is unclear. An analysis of the similarity between viral codon usage and the codon usage of the individual genes of a host genome has never been performed. In this study, we demonstrated that the codon usage of human RNA viruses is similar to that of some human genes, especially those involved in the cell cycle. This finding was substantiated by its concordance with previous reports of an upregulation at the protein level of some of these biological processes. It therefore suggests that some suboptimal viral codon usage patterns may actually be compatible with cellular translational machineries in infected conditions. url: https://www.ncbi.nlm.nih.gov/pubmed/32395662/ doi: 10.1016/j.heliyon.2020.e03915 id: cord-004222-z4butywi author: Joyce, Collin title: Comparisons of the antibody repertoires of a humanized rodent and humans by high throughput sequencing date: 2020-01-24 words: 3718.0 sentences: 187.0 pages: flesch: 46.0 cache: ./cache/cord-004222-z4butywi.txt txt: ./txt/cord-004222-z4butywi.txt summary: We characterized the heavy chain and kappa light chain antibody repertoires of a model animal, the OmniRat, by high throughput antibody sequencing and made use of two novel datasets for comparison to human repertoires. Multiple differences were found in both the heavy and kappa chain repertoires between OmniRats and humans including gene segment usage, CDR3 length distributions, class switch recombination, somatic hypermutation levels and in features of V(D)J recombination. We individually separated total RNA from spleens and lymph nodes of three unimmunized OmniRats and PCR amplified the heavy and kappa chain antibody V gene segments. We started by making intra-animal comparisons, intra-species comparisons and inter-species comparisons of the immunoglobulin gene segment usage frequencies for each antibody repertoire by performing hierarchical clustering ( Fig. 1 ) and linear regression analysis (Figs. abstract: The humanization of animal model immune systems by genetic engineering has shown great promise for antibody discovery, tolerance studies and for the evaluation of vaccines. Assessment of the baseline antibody repertoires of unimmunized model animals will be useful as a benchmark for future immunization experiments. We characterized the heavy chain and kappa light chain antibody repertoires of a model animal, the OmniRat, by high throughput antibody sequencing and made use of two novel datasets for comparison to human repertoires. Intra-animal and inter-animal repertoire comparisons reveal a high level of conservation in antibody diversity between the lymph node and spleen and between members of the species. Multiple differences were found in both the heavy and kappa chain repertoires between OmniRats and humans including gene segment usage, CDR3 length distributions, class switch recombination, somatic hypermutation levels and in features of V(D)J recombination. The Inference and Generation of Repertoires (IGoR) software tool was used to model recombination in VH regions which allowed for the quantification of some of these differences. Diversity estimates of the OmniRat heavy chain repertoires almost reached that of humans, around two orders of magnitude less. Despite variation between the species repertoires, a high frequency of OmniRat clonotypes were also found in the human repertoire. These data give insights into the development and selection of humanized animal antibodies and provide actionable information for use in vaccine studies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981180/ doi: 10.1038/s41598-020-57764-7 id: cord-351548-jvl63652 author: Juranic Lisnic, Vanda title: Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface date: 2013-09-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases. url: https://doi.org/10.1371/journal.ppat.1003611 doi: 10.1371/journal.ppat.1003611 id: cord-346308-9h2fk9qt author: Kaur, Rajwinder title: Microbiology of hospital wastewater date: 2020-05-01 words: 14673.0 sentences: 648.0 pages: flesch: 34.0 cache: ./cache/cord-346308-9h2fk9qt.txt txt: ./txt/cord-346308-9h2fk9qt.txt summary: The study of hospital wastewater (HWW) microbiology is important to understand the pollution load, growth of particular pathogenic microbes, shift and drift in microbial community, development and spread of antibiotic resistance in microbes, and subsequent change in treatment efficiencies. Within past years, pieces of evidence have shown mobilization of these resistance genes from the environment into pathogenic bacteria causing health risks to humans and animals and also, demonstrating a link between environmental and clinical resistance [123] . The HWW has been reported to have two overexpressed β-lactam-resistance genes (bla GES and bla OXA ) as compared with the water collected from other aquatic bodies, which could be correlated with antibiotic usage over the time in hospitals and discharge of the residues of antibiotics in the wastewater [176] . Urban wastewater treatment plants as hotspots for antibiotic resistant bacteria and genes spread into the environment: a review abstract: The study of hospital wastewater (HWW) microbiology is important to understand the pollution load, growth of particular pathogenic microbes, shift and drift in microbial community, development and spread of antibiotic resistance in microbes, and subsequent change in treatment efficiencies. This chapter investigates the potential microbes such as bacteria, viruses, fungi, and parasites present in HWW along with the diseases associated and methods of treatment used. Due to the indiscriminate release of antibiotics from hospitals, HWW serves as a hotspot for emergence of antibiotic-resistance genes (ARGs) and antibiotic-resistance bacteria. This chapter discusses the ARGs occurrence in HWW, their prevalence in the environment, the molecular tools used for identification, and different mechanisms of horizontal gene transfer. Thus better understanding of the microbiology of HWW could further help in development of advanced treatment technologies for effective removal of microbes and their bioproducts (toxins and infectious nucleic acid) from HWW and contaminated water. url: https://www.sciencedirect.com/science/article/pii/B9780128197226000043 doi: 10.1016/b978-0-12-819722-6.00004-3 id: cord-284933-flbibrcm author: Kim, Jong-Oh title: Characterization of the Transcriptome and Gene Expression of Brain Tissue in Sevenband Grouper (Hyporthodus septemfasciatus) in Response to NNV Infection date: 2017-01-13 words: 4259.0 sentences: 266.0 pages: flesch: 54.0 cache: ./cache/cord-284933-flbibrcm.txt txt: ./txt/cord-284933-flbibrcm.txt summary: title: Characterization of the Transcriptome and Gene Expression of Brain Tissue in Sevenband Grouper (Hyporthodus septemfasciatus) in Response to NNV Infection Ubiquitin-like protein 4a (UBL4a), C-C motif chemokine 2 (CCL2), lysozyme g (LYG_EPICO) and two novel genes (ID: SGU016297, SGU008676) were highly expressed in the NNV-infected group compared to that in the mock group. In this study, we performed a transcriptome analysis of the brain tissue of sevenband grouper infected with NNV compared to mock brain tissue using a RNA-Seq. The total number of unigenes and the average length of the unigenes were 104,348 and 845 bp, respectively. In this study, we performed a transcriptome analysis of the brain tissue of sevenband grouper infected with NNV compared to mock brain tissue using a RNA-Seq. The total number of unigenes and the average length of the unigenes were 104,348 and 845 bp, respectively. In this study, we identified innate immune response relevant genes of sevenband grouper involved in NNV infection. abstract: Grouper is one of the favorite sea food resources in Southeast Asia. However, the outbreaks of the viral nervous necrosis (VNN) disease due to nervous necrosis virus (NNV) infection have caused mass mortality of grouper larvae. Many aqua-farms have suffered substantial financial loss due to the occurrence of VNN. To better understand the infection mechanism of NNV, we performed the transcriptome analysis of sevenband grouper brain tissue, the main target of NNV infection. After artificial NNV challenge, transcriptome of brain tissues of sevenband grouper was subjected to next generation sequencing (NGS) using an Illumina Hi-seq 2500 system. Both mRNAs from pooled samples of mock and NNV-infected sevenband grouper brains were sequenced. Clean reads of mock and NNV-infected samples were de novo assembled and obtained 104,348 unigenes. In addition, 628 differentially expressed genes (DEGs) in response to NNV infection were identified. This result could provide critical information not only for the identification of genes involved in NNV infection, but for the understanding of the response of sevenband groupers to NNV infection. url: https://doi.org/10.3390/genes8010031 doi: 10.3390/genes8010031 id: cord-267475-6f4h3cck author: Kozak, Marilyn title: Pushing the limits of the scanning mechanism for initiation of translation date: 2002-10-16 words: 24538.0 sentences: 1234.0 pages: flesch: 50.0 cache: ./cache/cord-267475-6f4h3cck.txt txt: ./txt/cord-267475-6f4h3cck.txt summary: This depends on careful structural arrangements, however, which are rarely present in cellular mRNAs. Understanding the rules for initiation of translation enables understanding of human diseases in which the expression of a critical gene is reduced by mutations that add upstream AUG codons or change the context around the AUG(START) codon. (Whether the second AUG codon resides in a strong or weak context is not relevant; the ribosome reads the mRNA linearly and thus the decision to stop or to bypass the first AUG is not influenced by whether there is a better initiation site downstream.) The large number of genes that employ leaky scanning precludes discussion of the biological significance of the proteins thereby produced, but it merits noting that, for many of the viruses in Table 3 , replication requires production of both listed proteins. abstract: Selection of the translational initiation site in most eukaryotic mRNAs appears to occur via a scanning mechanism which predicts that proximity to the 5′ end plays a dominant role in identifying the start codon. This ‘position effect’ is seen in cases where a mutation creates an AUG codon upstream from the normal start site and translation shifts to the upstream site. The position effect is evident also in cases where a silent internal AUG codon is activated upon being relocated closer to the 5′ end. Two mechanisms for escaping the first-AUG rule – reinitiation and context-dependent leaky scanning – enable downstream AUG codons to be accessed in some mRNAs. Although these mechanisms are not new, many new examples of their use have emerged. Via these escape pathways, the scanning mechanism operates even in extreme cases, such as a plant virus mRNA in which translation initiates from three start sites over a distance of 900 nt. This depends on careful structural arrangements, however, which are rarely present in cellular mRNAs. Understanding the rules for initiation of translation enables understanding of human diseases in which the expression of a critical gene is reduced by mutations that add upstream AUG codons or change the context around the AUG(START) codon. The opposite problem occurs in the case of hereditary thrombocythemia: translational efficiency is increased by mutations that remove or restructure a small upstream open reading frame in thrombopoietin mRNA, and the resulting overproduction of the cytokine causes the disease. This and other examples support the idea that 5′ leader sequences are sometimes structured deliberately in a way that constrains scanning in order to prevent harmful overproduction of potent regulatory proteins. The accumulated evidence reveals how the scanning mechanism dictates the pattern of transcription – forcing production of monocistronic mRNAs – and the pattern of translation of eukaryotic cellular and viral genes. url: https://api.elsevier.com/content/article/pii/S0378111902010569 doi: 10.1016/s0378-1119(02)01056-9 id: cord-301546-yck1t3pp author: Kozaki, Toshinori title: Comparison of two acetylcholinesterase gene cDNAs of the lesser mealworm, Alphitobius diaperinus, in insecticide susceptible and resistant strains date: 2007-12-28 words: 2505.0 sentences: 152.0 pages: flesch: 52.0 cache: ./cache/cord-301546-yck1t3pp.txt txt: ./txt/cord-301546-yck1t3pp.txt summary: title: Comparison of two acetylcholinesterase gene cDNAs of the lesser mealworm, Alphitobius diaperinus, in insecticide susceptible and resistant strains Two cDNAs encoding different acetylcholinesterase (AChE) genes (AdAce1 and AdAce2) were sequenced and analyzed from the lesser mealworm, Alphitobius diaperinus. Partial cDNA sequences of the Alphitobius Ace genes were compared between two tetrachlorvinphos resistant (Kennebec and Waycross) and one susceptible strain of beetles. The alignment of this gene with the Drosophila Ace paralogous AChEs showed that, as expected for an insecticide-susceptible strain, beetles from the Denmark-S strain had an organophosphate and carbamate sensitive type. The Drosophila Ace orthologous gene, AdAce1, was sequenced from two susceptible Denmark-S, four Waycross (tetrachlorvinphos-resistant), and two Kennebec (tetrachlorvinphos-resistant) adults. diaperinus is not due to mutations in the Ace genes (i.e., is not an altered acetylcholinesterase).Alignments of the deduced amino acid sequences from the Drosophila Ace orthologous and paralogous genes in Coleoptera are shown in Figures 4 and 5, respectively. abstract: Two cDNAs encoding different acetylcholinesterase (AChE) genes (AdAce1 and AdAce2) were sequenced and analyzed from the lesser mealworm, Alphitobius diaperinus. Both AdAce1 and AdAce2 were highly similar (95 and 93% amino acid identity, respectively) with the Ace genes of Tribolium castaneum. Both AdAce1 and AdAce2 have the conserved residues characteristic of AChE (catalytic triad, intra‐disulfide bonds, and so on). Partial cDNA sequences of the Alphitobius Ace genes were compared between two tetrachlorvinphos resistant (Kennebec and Waycross) and one susceptible strain of beetles. Several single nucleotide polymorphisms (SNPs) were detected, but only one non‐synonymous mutation was found (A271S in AdAce2). No SNPs were exclusively found in the resistant strains, the A271S mutation does not correspond to any mutations previously reported to alter sensitivity of AChE to organophosphates or carbamates, and the A271S was found only as a heterozygote in one individual from one of the resistant A. diaperinus strains. This suggests that tetrachlorvinphos resistance in the Kennebec and Waycross strains of A. diaperinus is not due to mutations in either AChE gene. The sequences of AdAce1 and AdAce2 provide new information about the evolution of these important genes in insects. Arch Insect Biochem Physiol. © 2007 Wiley‐Liss, Inc. url: https://doi.org/10.1002/arch.20229 doi: 10.1002/arch.20229 id: cord-348815-lthz75oc author: Kurreck, Jens title: RNA Interference: From Basic Research to Therapeutic Applications date: 2009-01-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: An efficient mechanism for the sequence‐specific inhibition of gene expression is RNA interference. In this process, double‐stranded RNA molecules induce cleavage of a selected target RNA (see picture). This technique has in recent years developed into a standard method of molecular biology. Successful applications in animal models have already led to the initiation of RNAi‐based clinical trials as a new therapeutic option.[Image: see text] Only ten years ago Andrew Fire and Craig Mello were able to show that double‐stranded RNA molecules could inhibit the expression of homologous genes in eukaryotes. This process, termed RNA interference, has developed into a standard method of molecular biology. This Review provides an overview of the molecular processes involved, with a particular focus on the posttranscriptional inhibition of gene expression in mammalian cells, the possible applications in research, and the results of the first clinical studies. url: https://www.ncbi.nlm.nih.gov/pubmed/19153977/ doi: 10.1002/anie.200802092 id: cord-252781-06hs9pit author: Lai, Wing-Fu title: Cyclodextrins in non-viral gene delivery date: 2013-10-05 words: 6592.0 sentences: 357.0 pages: flesch: 44.0 cache: ./cache/cord-252781-06hs9pit.txt txt: ./txt/cord-252781-06hs9pit.txt summary: CDs have practical potential in gene delivery, but due to their failure to form stable complexes with plasmid DNA (pDNA) [40] , native CDs have limited transfection efficiency. Luciferase activity assays in K562 leukemia cells found that the transfection efficiency of the nanoparticles surface-modified with transferrin-PEG-AD conjugates was 4-fold higher than that of the unmodified counterparts [57] . In HEK293 cells, the polyrotaxanes fabricated showed higher transfection efficiency than PEI 25 kDa [58] , and deserve further evaluation as gene carriers for both in vitro and in vivo applications. The polymer showed more than 1-fold higher transfection efficiency, but lower cytotoxicity, than the PAMAM control (G4, with an ethylenediamine core) in human neuroblastoma SH-SY5Y cells. Efficient gene transfection in the neurotypic cells by star-shaped polymer consisting of b-cyclodextrin core and poly(amidoamine) dendron arms Enhancing effects of galactosylated dendrimer/a-cyclodextrin conjugates on gene transfer efficiency abstract: Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides. They consist of (α-1,4)-linked glucose units, and possess a basket-shaped topology with an “inner–outer” amphiphilic character. Over the years, substantial efforts have been undertaken to investigate the possible use of CDs in drug delivery and controlled drug release, yet the potential of CDs in gene delivery has received comparatively less discussion in the literature. In this article, we will first discuss the properties of CDs for gene delivery, followed by a synopsis of the use of CDs in development and modification of non-viral gene carriers. Finally, areas that are noteworthy in CD-based gene delivery will be highlighted for future research. Due to the application prospects of CDs, it is anticipated that CDs will continue to emerge as an important tool for vector development, and will play significant roles in facilitating non-viral gene delivery in the forthcoming decades. url: https://api.elsevier.com/content/article/pii/S0142961213011617 doi: 10.1016/j.biomaterials.2013.09.061 id: cord-329617-gzivtsho author: Lee, Albert K. title: De novo transcriptome reconstruction and annotation of the Egyptian rousette bat date: 2015-12-07 words: 5058.0 sentences: 292.0 pages: flesch: 52.0 cache: ./cache/cord-329617-gzivtsho.txt txt: ./txt/cord-329617-gzivtsho.txt summary: BACKGROUND: The Egyptian Rousette bat (Rousettus aegyptiacus), a common fruit bat species found throughout Africa and the Middle East, was recently identified as a natural reservoir host of Marburg virus. We performed de novo transcriptome assembly using deep RNA sequencing data from 11 distinct tissues from one male and one female bat. Rousettus aegyptiacus, commonly known as the Egyptian rousette bat, has been identified as a natural reservoir host for MARV through ecological, epidemiological, and experimental studies [10, 12, 13, 18, 19, 24] . aegyptiacus from a de novo assembly of RNA sequencing data from 11 tissues isolated from a male and a female bat. Without a common ground for comparison, it was difficult to perform downstream comparative analyses such as differential gene expression analysis; therefore, we combined contigs from all tissues into one unified, nonredundant reference transcriptome (Fig. 1d) . We further assessed biological validity of our transcriptome assembly through gene Ontology (GO) analysis of tissue-specific expression profiles. abstract: BACKGROUND: The Egyptian Rousette bat (Rousettus aegyptiacus), a common fruit bat species found throughout Africa and the Middle East, was recently identified as a natural reservoir host of Marburg virus. With Ebola virus, Marburg virus is a member of the family Filoviridae that causes severe hemorrhagic fever disease in humans and nonhuman primates, but results in little to no pathological consequences in bats. Understanding host-pathogen interactions within reservoir host species and how it differs from hosts that experience severe disease is an important aspect of evaluating viral pathogenesis and developing novel therapeutics and methods of prevention. RESULTS: Progress in studying bat reservoir host responses to virus infection is hampered by the lack of host-specific reagents required for immunological studies. In order to establish a basis for the design of reagents, we sequenced, assembled, and annotated the R. aegyptiacus transcriptome. We performed de novo transcriptome assembly using deep RNA sequencing data from 11 distinct tissues from one male and one female bat. We observed high similarity between this transcriptome and those available from other bat species. Gene expression analysis demonstrated clustering of expression profiles by tissue, where we also identified enrichment of tissue-specific gene ontology terms. In addition, we identified and experimentally validated the expression of novel coding transcripts that may be specific to this species. CONCLUSION: We comprehensively characterized the R. aegyptiacus transcriptome de novo. This transcriptome will be an important resource for understanding bat immunology, physiology, disease pathogenesis, and virus transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2124-x) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pubmed/26643810/ doi: 10.1186/s12864-015-2124-x id: cord-306380-msk9p1yy author: Lee, C.-W. title: Evidence of genetic diversity generated by recombination among avian coronavirus IBV date: 2000 words: 2796.0 sentences: 146.0 pages: flesch: 58.0 cache: ./cache/cord-306380-msk9p1yy.txt txt: ./txt/cord-306380-msk9p1yy.txt summary: Phylogenetic analysis of selected regions of the genome of the DE072 serotype field isolates further support those results and indicate that isolates within the same serotype may have different amounts of nucleotide sequence similarity with each other in individual genes other than the S gene. Further, we conducted sequence analysis of six isolates of the DE072 serotype in order to determine if recombination is frequently occurring in this region in field isolates of IBV. We conducted phylogenetic analysis by dividing 3.8 kb of the 3 end of the genome among five IBV strains at the IG sequences. However, these 6 isolates had a much different level of nucleotide sequence similarity with each other in gene 3 and gene 4, and clustered randomly with other serotypes of IBV (Fig. 3) . Sequence analysis of gene 3, gene 4 and gene 5 of avian infectious bronchitis virus strain CU-T2 Sequence evidence for RNA recombination in field isolates of avian coronavirus infectious bronchitis virus abstract: Previously, we demonstrated that the DE072 strain of IBV is a recombinant which has an IBV strain D1466-like sequence in the S gene. Herein, we analyzed the remaining 3.8 kb 3′ end of the genome, which includes Gene 3, Gene 4, Gene 5, Gene 6, and the 3′ non-coding region of the DE072 and D1466 strains. Those two viruses had high nucleotide similarity in Gene 4. However, the other individual genes had a much different level of sequence similarity with the same gene of the other IBV strains. The genome of five IBV strains, of which the complete sequence of the 3′ end of the genome has been determined, were divided at an intergenic (IG) consensus sequence (CTGAACAA or CTTAACAA) and compared phylogenetically. Phylogenetic trees of different topology indicated that the consensus IG sequences and the highly conserved sequence around this regions may serve as recombination ‘hot spots’. Phylogenetic analysis of selected regions of the genome of the DE072 serotype field isolates further support those results and indicate that isolates within the same serotype may have different amounts of nucleotide sequence similarity with each other in individual genes other than the S gene. Presumably this occurs because the consensus IG sequence serves as the template switching site for the viral encoded polymerase. url: https://www.ncbi.nlm.nih.gov/pubmed/11087096/ doi: 10.1007/s007050070044 id: cord-355927-nzoiv9pj author: Lemmon, Alan R. title: The Effect of Ambiguous Data on Phylogenetic Estimates Obtained by Maximum Likelihood and Bayesian Inference date: 2009-05-21 words: 9468.0 sentences: 455.0 pages: flesch: 50.0 cache: ./cache/cord-355927-nzoiv9pj.txt txt: ./txt/cord-355927-nzoiv9pj.txt summary: Furthermore, within a Bayesian framework, priors on branch lengths and rate heterogeneity parameters can exacerbate the effects of ambiguous data, resulting in strongly misleading bipartition posterior probabilities. The results of this study have major implications for all analyses that rely on accurate estimates of topology or branch lengths, including divergence time estimation, ancestral state reconstruction, tree-dependent comparative methods, rate variation analysis, phylogenetic hypothesis testing, and phylogeographic analysis. We show that at least 5 factors determine the direction and magnitude of bias resulting from ambiguous characters: the number and taxonomic distribution of ambiguous characters, the strength of topological support from unambiguous characters, the degree of among-site rate variation, and the method and assumptions of the analysis (including the priors assumed in a Bayesian analysis). These rates were chosen, based on preliminary simulations, to produce data sets containing a range of phylogenetic information, resulting in posterior probabilities (given 500 unambiguous sites) for the true topology of 1/3, 2/3, 1, 1, 2/3, and 1/3, respectively. abstract: Although an increasing number of phylogenetic data sets are incomplete, the effect of ambiguous data on phylogenetic accuracy is not well understood. We use 4-taxon simulations to study the effects of ambiguous data (i.e., missing characters or gaps) in maximum likelihood (ML) and Bayesian frameworks. By introducing ambiguous data in a way that removes confounding factors, we provide the first clear understanding of 1 mechanism by which ambiguous data can mislead phylogenetic analyses. We find that in both ML and Bayesian frameworks, among-site rate variation can interact with ambiguous data to produce misleading estimates of topology and branch lengths. Furthermore, within a Bayesian framework, priors on branch lengths and rate heterogeneity parameters can exacerbate the effects of ambiguous data, resulting in strongly misleading bipartition posterior probabilities. The magnitude and direction of the ambiguous data bias are a function of the number and taxonomic distribution of ambiguous characters, the strength of topological support, and whether or not the model is correctly specified. The results of this study have major implications for all analyses that rely on accurate estimates of topology or branch lengths, including divergence time estimation, ancestral state reconstruction, tree-dependent comparative methods, rate variation analysis, phylogenetic hypothesis testing, and phylogeographic analysis. url: https://doi.org/10.1093/sysbio/syp017 doi: 10.1093/sysbio/syp017 id: cord-273609-whm2ce4u author: Li, Qingdi Quentin title: Evaluation of reference genes for real-time quantitative PCR studies in Candida glabrata following azole treatment date: 2012-06-29 words: 8166.0 sentences: 373.0 pages: flesch: 47.0 cache: ./cache/cord-273609-whm2ce4u.txt txt: ./txt/cord-273609-whm2ce4u.txt summary: title: Evaluation of reference genes for real-time quantitative PCR studies in Candida glabrata following azole treatment BACKGROUND: The selection of stable and suitable reference genes for real-time quantitative PCR (RT-qPCR) is a crucial prerequisite for reliable gene expression analysis under different experimental conditions. The most commonly used reference genes, including β-actin, cyclophilin, GAPDH, tubulin, and 18S and 28S ribosomal RNAs, have shown variable expression levels in different cells and tissues under different conditions, and therefore they are unsuitable for normalization purposes owing to large measurement error [6, . As seen in Table 7 , normalization of the RT-qPCR data against the reference genes suggested as optimal by the four software packages (hkgFinder, geNorm, BestKeeper, and NormFinder) or the 2 -ΔΔCT method, gave comparable relative expression levels of the target genes under fluconazole treatment in C. abstract: BACKGROUND: The selection of stable and suitable reference genes for real-time quantitative PCR (RT-qPCR) is a crucial prerequisite for reliable gene expression analysis under different experimental conditions. The present study aimed to identify reference genes as internal controls for gene expression studies by RT-qPCR in azole-stimulated Candida glabrata. RESULTS: The expression stability of 16 reference genes under fluconazole stress was evaluated using fold change and standard deviation computations with the hkgFinder tool. Our data revealed that the mRNA expression levels of three ribosomal RNAs (RDN5.8, RDN18, and RDN25) remained stable in response to fluconazole, while PGK1, UBC7, and UBC13 mRNAs showed only approximately 2.9-, 3.0-, and 2.5-fold induction by azole, respectively. By contrast, mRNA levels of the other 10 reference genes (ACT1, EF1α, GAPDH, PPIA, RPL2A, RPL10, RPL13A, SDHA, TUB1, and UBC4) were dramatically increased in C. glabrata following antifungal treatment, exhibiting changes ranging from 4.5- to 32.7-fold. We also assessed the expression stability of these reference genes using the 2(-ΔΔCT) method and three other software packages. The stability rankings of the reference genes by geNorm and the 2(-ΔΔCT) method were identical to those by hkgFinder, whereas the stability rankings by BestKeeper and NormFinder were notably different. We then validated the suitability of six candidate reference genes (ACT1, PGK1, RDN5.8, RDN18, UBC7, and UBC13) as internal controls for ten target genes in this system using the comparative C(T) method. Our validation experiments passed for all six reference genes analyzed except RDN18, where the amplification efficiency of RDN18 was different from that of the ten target genes. Finally, we demonstrated that the relative quantification of target gene expression varied according to the endogenous control used, highlighting the importance of the choice of internal controls in such experiments. CONCLUSIONS: We recommend the use of RDN5.8, UBC13, and PGK1 alone or the combination of RDN5.8 plus UBC13 or PGK1 as reference genes for RT-qPCR analysis of gene expression in C. glabrata following azole treatment. In contrast, we show that ACT1 and other commonly used reference genes (GAPDH, PPIA, RPL13A, TUB1, etc.) were not validated as good internal controls in the current model. url: https://www.ncbi.nlm.nih.gov/pubmed/22747760/ doi: 10.1186/1471-2199-13-22 id: cord-011630-lfm34fsw author: Li, Yan title: Epigenetic inheritance of circadian period in clonal cells date: 2020-05-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Circadian oscillations are generated via transcriptional-translational negative feedback loops. However, individual cells from fibroblast cell lines have heterogeneous rhythms, oscillating independently and with different period lengths. Here we showed that heterogeneity in circadian period is heritable and used a multi-omics approach to investigate underlying mechanisms. By examining large-scale phenotype-associated gene expression profiles in hundreds of mouse clonal cell lines, we identified and validated multiple novel candidate genes involved in circadian period determination in the absence of significant genomic variants. We also discovered differentially co-expressed gene networks that were functionally associated with period length. We further demonstrated that global differential DNA methylation bidirectionally regulated these same gene networks. Interestingly, we found that depletion of DNMT1 and DNMT3A had opposite effects on circadian period, suggesting non-redundant roles in circadian gene regulation. Together, our findings identify novel gene candidates involved in periodicity, and reveal DNA methylation as an important regulator of circadian periodicity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289596/ doi: 10.7554/elife.54186 id: cord-033692-txfuuu7d author: Lim, Byeonghwi title: Integrated time-serial transcriptome networks reveal common innate and tissue-specific adaptive immune responses to PRRSV infection date: 2020-10-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) infection is the most important viral disease causing severe economic losses in the swine industry. However, mechanisms underlying gene expression control in immunity-responsible tissues at different time points during PRRSV infection are poorly understood. We constructed an integrated gene co-expression network and identified tissue- and time-dependent biological mechanisms of PRRSV infection through bioinformatics analysis using three tissues (lungs, bronchial lymph nodes [BLNs], and tonsils) via RNA-Seq. Three groups with specific expression patterns (i.e., the 3-dpi, lung, and BLN groups) were discovered. The 3 dpi-specific group showed antiviral and innate-immune signalling similar to the case for influenza A infection. Moreover, we observed adaptive immune responses in the lung-specific group based on various cytokines, while the BLN-specific group showed down-regulated AMPK signalling related to viral replication. Our study may provide comprehensive insights into PRRSV infection, as well as useful information for vaccine development. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552595/ doi: 10.1186/s13567-020-00850-5 id: cord-001921-73esrper author: Lin, Cheng-Yung title: Zebrafish and Medaka: new model organisms for modern biomedical research date: 2016-01-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Although they are primitive vertebrates, zebrafish (Danio rerio) and medaka (Oryzias latipes) have surpassed other animals as the most used model organisms based on their many advantages. Studies on gene expression patterns, regulatory cis-elements identification, and gene functions can be facilitated by using zebrafish embryos via a number of techniques, including transgenesis, in vivo transient assay, overexpression by injection of mRNAs, knockdown by injection of morpholino oligonucleotides, knockout and gene editing by CRISPR/Cas9 system and mutagenesis. In addition, transgenic lines of model fish harboring a tissue-specific reporter have become a powerful tool for the study of biological sciences, since it is possible to visualize the dynamic expression of a specific gene in the transparent embryos. In particular, some transgenic fish lines and mutants display defective phenotypes similar to those of human diseases. Therefore, a wide variety of fish model not only sheds light on the molecular mechanisms underlying disease pathogenesis in vivo but also provides a living platform for high-throughput screening of drug candidates. Interestingly, transgenic model fish lines can also be applied as biosensors to detect environmental pollutants, and even as pet fish to display beautiful fluorescent colors. Therefore, transgenic model fish possess a broad spectrum of applications in modern biomedical research, as exampled in the following review. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730764/ doi: 10.1186/s12929-016-0236-5 id: cord-347917-fmb5nyxu author: Liu, Junli title: Comprehensive Genomic Characterization Analysis of lncRNAs in Cells With Porcine Delta Coronavirus Infection date: 2020-01-28 words: 4651.0 sentences: 251.0 pages: flesch: 49.0 cache: ./cache/cord-347917-fmb5nyxu.txt txt: ./txt/cord-347917-fmb5nyxu.txt summary: In this study, genome-wide profiling of lncRNAs in swine testicular (ST) cells infected with PDCoV was performed using RNA-seq. An integrative analysis of lncRNA alterations suggested their putative role in regulating the expression of several key genes in metabolic and TNF signaling pathways during infection. There have been reports of using genome-wide association analysis between lncRNAs and the co-expressed and/or co-regulated protein-coding genes to characterize the function of the lncRNA (Huarte et al., 2010) . GO and KEGG pathway enrichment analysis of target genes revealed that lncRNAs may act in cis or trans to participate in the regulation of expression of multiple important genes in different processes including protein binding, DNA transcription, metabolism, and immune response. The functional association between regulatory lncRNA and protein-coding gene transcripts can be determined by performing expression correlation analysis coupled with ascertaining their putative role in related physiological processes. abstract: Porcine delta coronavirus (PDCoV) is a novel emerging enterocytetropic virus causing diarrhea, vomiting, dehydration, and mortality in suckling piglets. Long non-coding RNAs (lncRNAs) are known to be important regulators during virus infection. Here, we describe a comprehensive transcriptome profile of lncRNA in PDCoV-infected swine testicular (ST) cells. In total, 1,308 annotated and 1,190 novel lncRNA candidate sequences were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these lncRNAs might be involved in numerous biological processes. Clustering analysis of differentially expressed lncRNAs showed that 454 annotated and 376 novel lncRNAs were regulated after PDCoV infection. Furthermore, we constructed a lncRNA-protein-coding gene co-expression interaction network. The KEGG analysis of the co-expressed genes showed that these differentially expressed lncRNAs were enriched in pathways related to metabolism and TNF signaling. Our study provided comprehensive information about lncRNAs that would be a useful resource for studying the pathogenesis of and designing antiviral therapy for PDCoV infection. url: https://doi.org/10.3389/fmicb.2019.03036 doi: 10.3389/fmicb.2019.03036 id: cord-005432-mqyvpepo author: Ma, Z title: Redirecting adenovirus to pulmonary endothelium by cationic liposomes date: 2002-02-22 words: 3980.0 sentences: 235.0 pages: flesch: 50.0 cache: ./cache/cord-005432-mqyvpepo.txt txt: ./txt/cord-005432-mqyvpepo.txt summary: A recent study has shown that the use of a bispecific antibody to endothelial cells and Ad vectors efficiently redirects Ad vectors to pulmonary endothelium and improves gene expression in the lung. 10 To test whether preinjection of cationic liposomes can also enhance Ad vector-mediated pulmonary gene transfer, groups of six mice received tail vein injection of various amounts of DOTAP:cholesterol liposomes followed by injection of AdCMVLuc. Gene expression was assayed 3 days following the injection. 12 To Gene Therapy examine whether lipid complexation can similarly enhance pulmonary gene transfer by Ad vectors via the vascular route, AdCMVLuc was mixed with various amounts of DOTAP:cholesterol liposomes and gene expression was assayed 3 days following the injection of the complexed AdCMVLuc. In contrast to sequential injection, premixing of cationic liposomes with AdCM-VLuc resulted in a decreased gene expression in all major organs examined ( Figure 2 ). abstract: Somatic gene transfer to the pulmonary endothelium may be a useful strategy for modifying the phenotype of endothelium and/or vascular smooth muscle in disorders such as primary pulmonary hypertension, ARDS or pulmonary metastatic disease. Adenoviral (Ad) vectors, although highly efficient in liver gene transfer, have proven to be limited for pulmonary gene transfer with respect to efficiency, in part because of difficulty in assuring significant residence time in the lung and/or paucity of receptors for adenovirus on the endothelium. A recent study has shown that the use of a bispecific antibody to endothelial cells and Ad vectors efficiently redirects Ad vectors to pulmonary endothelium and improves gene expression in the lung. In this study, we report that pulmonary gene transfer by Ad vectors can also be improved significantly via the use of cationic liposomes. Preinjection of cationic liposomes followed by adenovirus led to a significant increase in the level of gene expression in the lung. The improvement in pulmonary gene transfer was associated with a decrease in the level of gene expression in the liver. Gene expression in the lung lasted for up to 2 weeks. This protocol, together with genetic modification of adenovirus, may prove to be useful for pulmonary gene transfer for the treatment of pulmonary diseases. This method may also be extended to pulmonary gene transfer using other types of viral vectors via vascular route. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091708/ doi: 10.1038/sj.gt.3301636 id: cord-253973-zr28uujh author: Maccoux, Lindsey J title: Identification of new reference genes for the normalisation of canine osteoarthritic joint tissue transcripts from microarray data date: 2007-07-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Real-time reverse transcriptase quantitative polymerase chain reaction (real-time RT-qPCR) is the most accurate measure of gene expression in biological systems. The comparison of different samples requires the transformation of data through a process called normalisation. Reference or housekeeping genes are candidate genes which are selected on the basis of constitutive expression across samples, and allow the quantification of changes in gene expression. At present, no reference gene has been identified for any organism which is universally optimal for use across different tissue types or disease situations. We used microarray data to identify new reference genes generated from total RNA isolated from normal and osteoarthritic canine articular tissues (bone, ligament, cartilage, synovium and fat). RT-qPCR assays were designed and applied to each different articular tissue. Reference gene expression stability and ranking was compared using three different mathematical algorithms. RESULTS: Twelve new potential reference genes were identified from microarray data. One gene (mitochondrial ribosomal protein S7 [MRPS7]) was stably expressed in all five of the articular tissues evaluated. One gene HIRA interacting protein 5 isoform 2 [HIRP5]) was stably expressed in four of the tissues evaluated. A commonly used reference gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was not stably expressed in any of the tissues evaluated. Most consistent agreement between rank ordering of reference genes was observed between Bestkeeper© and geNorm, although each method tended to agree on the identity of the most stably expressed genes and the least stably expressed genes for each tissue. New reference genes identified using microarray data normalised in a conventional manner were more stable than those identified by microarray data normalised by using a real-time RT-qPCR methodology. CONCLUSION: Microarray data normalised by a conventional manner can be filtered using a simple stepwise procedure to identify new reference genes, some of which will demonstrate good measures of stability. Mitochondrial ribosomal protein S7 is a new reference gene worthy of investigation in other canine tissues and diseases. Different methods of reference gene stability assessment will generally agree on the most and least stably expressed genes, when co-regulation is not present. url: https://www.ncbi.nlm.nih.gov/pubmed/17651481/ doi: 10.1186/1471-2199-8-62 id: cord-017853-mgsuwft0 author: Machado, Roberto F. title: Genomics of Acute Lung Injury and Vascular Barrier Dysfunction date: 2010-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Acute lung injury (ALI) is a devastating ­syndrome of diffuse alveolar damage that develops via a variety of local and systemic insults such as sepsis, trauma, ­pneumonia, and aspiration. It is interestingly to note that only a subset of individuals exposed to potential ALI-inciting insults develop the disorder and the severity of the disease varies from complete resolution to death. In addition, ALI susceptibility and severity are also affected by ethnicity as evidenced by the higher mortality rates observed in African-American ALI patients compared with other ethnic groups in the USA. Moreover, marked differences in strain-specific ALI responses to inflammatory and injurious agents are observed in preclinical animal models. Together, these observations strongly indicate genetic components to be involved in the pathogenesis of ALI. The identification of genes contributing to ALI would potentially provide a better understanding of ALI pathobiology, yield novel biomarkers, identify individuals or populations at risk, and prove useful for the development of novel and individualized therapies. Genome-wide searches in animal models have identified a number of quantitative trait loci that associate with ALI susceptibility. In this chapter, we utilize a systems biology approach combining cellular signaling pathway analysis with population- based association studies to review established and suspected candidate genes that contribute to dysfunction of endothelial cell barrier integrity and ALI susceptibility. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122529/ doi: 10.1007/978-0-387-87429-6_63 id: cord-313138-y485ev30 author: Magor, Katharine E. title: Defense genes missing from the flight division date: 2013-04-24 words: 10638.0 sentences: 610.0 pages: flesch: 51.0 cache: ./cache/cord-313138-y485ev30.txt txt: ./txt/cord-313138-y485ev30.txt summary: Whether cause or effect, the lack of TLR8 in avian monocytes/ macrophages likely does contribute to the susceptibility of birds to RNA viruses (West Nile virus, Newcastle disease virus, influenza virus and others) and intracellular bacterial infections, including mycobacteria. The gene encoding RIG-I, DDX58, is not annotated in the chicken genome sequence, and is missing in some fish species, but MDA5 homologues are present in all vertebrate families (Zou et 2009). Riplet/RNF135 is a cytoplasmic E3-ligase identified by yeast two-hybrid as one of the proteins binding RIG-I, and is essential for RIG-I activation in human cell lines upon infection with an RNA virus (Oshiumi et al., 2009; Oshiumi et al., 2010) . The upregulation of IFIT5 following viral infection of chicken cells expressing duck RIG-I ( Barber et al., 2013) or infection of ducks (Vanderven et al., 2012) suggests IFIT5 is an important antiviral effector in avian species. abstract: Birds have a smaller repertoire of immune genes than mammals. In our efforts to study antiviral responses to influenza in avian hosts, we have noted key genes that appear to be missing. As a result, we speculate that birds have impaired detection of viruses and intracellular pathogens. Birds are missing TLR8, a detector for single-stranded RNA. Chickens also lack RIG-I, the intracellular detector for single-stranded viral RNA. Riplet, an activator for RIG-I, is also missing in chickens. IRF3, the nuclear activator of interferon-beta in the RIG-I pathway is missing in birds. Downstream of interferon (IFN) signaling, some of the antiviral effectors are missing, including ISG15, and ISG54 and ISG56 (IFITs). Birds have only three antibody isotypes and IgD is missing. Ducks, but not chickens, make an unusual truncated IgY antibody that is missing the Fc fragment. Chickens have an expanded family of LILR leukocyte receptor genes, called CHIR genes, with hundreds of members, including several that encode IgY Fc receptors. Intriguingly, LILR homologues appear to be missing in ducks, including these IgY Fc receptors. The truncated IgY in ducks, and the duplicated IgY receptor genes in chickens may both have resulted from selective pressure by a pathogen on IgY FcR interactions. Birds have a minimal MHC, and the TAP transport and presentation of peptides on MHC class I is constrained, limiting function. Perhaps removing some constraint, ducks appear to lack tapasin, a chaperone involved in loading peptides on MHC class I. Finally, the absence of lymphotoxin-alpha and beta may account for the observed lack of lymph nodes in birds. As illustrated by these examples, the picture that emerges is some impairment of immune response to viruses in birds, either a cause or consequence of the host-pathogen arms race and long evolutionary relationship of birds and RNA viruses. url: https://api.elsevier.com/content/article/pii/S0145305X13001146 doi: 10.1016/j.dci.2013.04.010 id: cord-354829-god79qzw author: Mao, Kaimin title: Identification of robust genetic signatures associated with lipopolysaccharide-induced acute lung injury onset and astaxanthin therapeutic effects by integrative analysis of RNA sequencing data and GEO datasets date: 2020-09-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening clinical conditions predominantly arising from uncontrolled inflammatory reactions. It has been found that the administration of astaxanthin (AST) can exert protective effects against lipopolysaccharide (LPS)-induced ALI; however, the robust genetic signatures underlying LPS induction and AST treatment remain obscure. Here we performed a statistical meta-analysis of five publicly available gene expression datasets from LPS-induced ALI mouse models, conducted RNA-sequencing (RNA-seq) to screen differentially expressed genes (DEGs) in response to LPS administration and AST treatment, and integrative analysis to determine robust genetic signatures associated with LPS-induced ALI onset and AST administration. Both the meta-analyses and our experimental data identified a total of 198 DEGs in response to LPS administration, and 11 core DEGs (Timp1, Ly6i, Cxcl13, Irf7, Cxcl5, Ccl7, Isg15, Saa3, Saa1, Tgtp1, and Gbp11) were identified to be associated with AST therapeutic effects. Further, the 11 core DEGs were verified by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC), and functional enrichment analysis revealed that these genes are primarily associated with neutrophils and chemokines. Collectively, these findings unearthed the robust genetic signatures underlying LPS administration and the molecular targets of AST for ameliorating ALI/ARDS which provide directions for further research. url: https://www.ncbi.nlm.nih.gov/pubmed/32969837/ doi: 10.18632/aging.104042 id: cord-257843-nj2707mv author: Mariani, Thomas J title: Association of Dynamic Changes in the CD4 T-Cell Transcriptome With Disease Severity During Primary Respiratory Syncytial Virus Infection in Young Infants date: 2017-08-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Nearly all children are infected with respiratory syncytial virus (RSV) within the first 2 years of life, with a minority developing severe disease (1%–3% hospitalized). We hypothesized that an assessment of the adaptive immune system, using CD4(+) T-lymphocyte transcriptomics, would identify gene expression correlates of disease severity. METHODS: Infants infected with RSV representing extremes of clinical severity were studied. Mild illness (n = 23) was defined as a respiratory rate (RR) < 55 and room air oxygen saturation (SaO(2)) ≥ 97%, and severe illness (n = 23) was defined as RR ≥ 65 and SaO2 ≤ 92%. RNA from fresh, sort-purified CD4(+) T cells was assessed by RNA sequencing. RESULTS: Gestational age, age at illness onset, exposure to environmental tobacco smoke, bacterial colonization, and breastfeeding were associated (adjusted P < .05) with disease severity. RNA sequencing analysis reliably measured approximately 60% of the genome. Severity of RSV illness had the greatest effect size upon CD4 T-cell gene expression. Pathway analysis identified correlates of severity, including JAK/STAT, prolactin, and interleukin 9 signaling. We also identified genes and pathways associated with timing of symptoms and RSV group (A/B). CONCLUSIONS: These data suggest fundamental changes in adaptive immune cell phenotypes may be associated with RSV clinical severity. url: https://doi.org/10.1093/infdis/jix400 doi: 10.1093/infdis/jix400 id: cord-022177-j0qcjbxg author: Markl, Jürgen title: Genome date: 2018-10-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Canis lupus familiaris, der Haushund, wurde vor rund 15.000 Jahren von den Menschen domestiziert. Obwohl es viele verschiedene Varianten von Wölfen gibt, ähneln sich diese ziemlich stark, doch das trifft auf den „besten Freund des Menschen“ nicht zu. Die Fédération Cynologique Internationale (FCI), weltweit größter Dachverband der Hundezüchter, erkennt über 300 Hunderassen an. Genetiker gehen von rund 100 echten Hunderassen aus, der Rest seien Varietäten. Hunderassen sehen nicht nur recht unterschiedlich aus, sondern sie unterscheiden sich auch stark in ihrer Körpergröße. So wiegt beispielsweise ein durchschnittlicher Chihuahua nur 1,5 kg, während ein Schottischer Jagdhund 70 kg auf die Waage bringt. Kein anderes Säugetier zeigt eine so starke phänotypische Variabilität. Außerdem gibt es Hunderte von genetisch bedingten Krankheiten bei Hunden, und für viele davon findet sich auch ein Gegenstück bei Menschen. Das Hundegenomprojekt begann in den späten 1990er-Jahren, um herauszufinden, welche Gene für die genetische Variabilität verantwortlich sind und welche Zusammenhänge zwischen Genen und Krankheiten bestehen. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153743/ doi: 10.1007/978-3-662-58172-8_17 id: cord-022178-4oh02tlr author: Markl, Jürgen title: Evolution von Genen und Genomen date: 2018-10-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Der Erste Weltkrieg endete im November 1918. Die Zahl der Todesfälle in den vier Kriegsjahren wurde jedoch schon bald übertroffen von den Opfern einer massiven Grippeepidemie, an der weltweit über 50 Mio. Menschen starben – und damit mehr als doppelt so viele wie in den Schlachten des Ersten Weltkriegs. Die Pandemie von 1918/1919 war insofern bemerkenswert, als die Sterberate unter jungen Erwachsenen, die einer Grippe gewöhnlich mit viel geringerer Wahrscheinlichkeit zum Opfer fallen als Kinder und Greise, um das 20-Fache höher lag als bei den vorherigen und später folgenden Grippeepidemien. Warum erwies sich dieses Grippevirus speziell unter den normalerweise widerstandsfähigsten Menschen als so tödlich? Der Virusstamm von 1918 löste im menschlichen Immunsystem eine besonders starke Reaktion aus. Infolge dieser Überreaktion waren Menschen mit einem leistungsfähigen Immunsystem tendenziell stärker betroffen. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153744/ doi: 10.1007/978-3-662-58172-8_23 id: cord-022226-qxp0gfp3 author: Meager, Anthony title: Interferons Alpha, Beta, and Omega date: 2007-09-02 words: 16375.0 sentences: 813.0 pages: flesch: 46.0 cache: ./cache/cord-022226-qxp0gfp3.txt txt: ./txt/cord-022226-qxp0gfp3.txt summary: PRDI and PRDIII act as binding sites for a nuclear transcription factor, designated "interferon regulatory factor-l" (IRF-1) , whose expression is transiently increased by virus infection and which appears to mediate the activation of transcription of the IFNB gene (Fujita et al., 1988; Harada et al., 1989; Xanthoudakis et al., 1989) . For example, the IFN-inducible Mx proteins block the replication of influenza virus, probably by inhibiting the nuclear phase of viral transcription (mouse cells) or later cytoplasmic phases (human cells), without affecting the replication of many other viruses (Staeheli, 1990; Mel6n et al., 1992; Ronni et al., 1993) . A number of other negative regulatory factors, including IRF2 (Harada et al., 1989) and the ISGF2 (IRF1)/ISGF3yrelated "human interferon consensus sequence binding protein" (ICSBP) (Weisz et al., 1992; Bovolenta et al., 1994) , which also bind to ISRE, are also probably involved in the regulation of transcription of IFN-inducible genes. abstract: Interferon alpha (IFN-α) is a mixture of closely related proteins, termed “subtypes,” expressed from distinct chromosomal genes. Interferon β (IFN-β) is a single protein species and is molecularly related to IFN-α subtypes, although it is antigenically distinct from them. IFN omega (IFN-ω) is antigenically distinct from IFN-α and IFN-β but is molecularly related to both. The genes of three IFN subtypes are tandemly arranged on the short arm of chromosome 9. They are transiently expressed following induction by various exogenous stimuli, including viruses. They are synthesized from their respective mRNAs for relatively short periods following gene activation and are secreted to act, via specific cell surface receptors, on other cells. IFN-α subtypes are secreted proteins and as such are transcribed from mRNAs as precursor proteins, pre-IFN-α, containing N-terminal signal polypeptides of 23 hydrophobic amino acids (aa) mainly. Pre-IFN-β contains 187 aa, of which 21 comprise the N-terminal signal polypeptide and 166 comprise the mature IFN-β protein. IFN-ω contains 195 aa—the N-terminal 23 comprising the signal sequence and the remaining 172, the mature IFN-ω protein. At the C-terminus, the aa sequence of IFN-ω is six residues longer than that of IFN-α or IFN-β proteins. IFN-α, as a mixture of subtypes, and IFN-ω may be produced together following viral infection of null lymphocytes or monocytes/macrophages. The biological activities of IFNs are mostly dependent upon protein synthesis with selective subsets of proteins mediating individual activities. IFNs can also stimulate indirect antiviral and antitumor mechanisms, depending upon cellular differentiation and the induction of cytotoxic activity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155463/ doi: 10.1016/b978-012498340-3/50026-9 id: cord-016364-80l5mua2 author: Menotti-Raymond, Marilyn title: The Domestic Cat, Felis catus, as a Model of Hereditary and Infectious Disease date: 2008 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The domestic cat, currently the most frequent of companion animals, has enjoyed a medical surveillance, as a nonprimate species, second only to the dog. With over 200 hereditary disease pathologies reported in the cat, the clinical and physiological study of these feline hereditary diseases provides a strong comparative medicine opportunity for prevention, diagnostics, and treatment studies in a laboratory setting. Causal mutations have been characterized in 19 felid genes, with the largest representation from lysosomal storage enzyme disorders. Corrective therapeutic strategies for several disorders have been proposed and examined in the cat, including enzyme replacement, heterologous bone marrow transplantation, and substrate reduction therapy. Genomics tools developed in the cat, including the recent completion of the 2-fold whole genome sequence of the cat and genome browser, radiation hybrid map of 1793 integrated coding and microsatellite loci, a 5-cM genetic linkage map, arrayed BAC libraries, and flow sorted chromosomes, are providing resources that are being utilized in mapping and characterization of genes of interest. A recent report of the mapping and characterization of a novel causative gene for feline spinal muscular atrophy marked the first identification of a disease gene purely from positional reasoning. With the development of genomic resources in the cat and the application of complementary comparative tools developed in other species, the domestic cat is emerging as a promising resource of phenotypically defined genetic variation of biomedical significance. Additionally, the cat has provided several useful models for infectious disease. These include feline leukemia and feline sarcoma virus, feline coronavirus, and Type C retroviruses that interact with cellular oncogenes to induce leukemia, lymphoma, and sarcoma. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120622/ doi: 10.1007/978-1-59745-285-4_25 id: cord-102729-b1q7gbd6 author: Mickael, Alexandra title: Asip (Agouti-signaling protein) aggression gene regulate auditory processing genes in mice date: 2020-06-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Covid-19 strategy of lockdown has affected the lives of millions. The strict actions to enclose the epidemic have exposed many households to inner tensions. Domestic violence has been reported to increase during the lockdown. However, the reasons for this phenomenon have not been thoroughly investigated. Melanocortin GPCRs family contribution to aggression is well documented. ASIP (nonagouti) gene plays a vital role in regulating the melanocortin GPCRs family function, and it is responsible for regulating aggression in mice. We conducted a selection analysis of ASIP. We found that it negatively purified from Shark to humans. In order to better asses the effect of this gene in mammals, we performed RNA-seq analysis of a knockout of an ASIP crisper-cas mouse model. We found that ASIP KO in mice upregulates several genes controlling auditory function, including Phox2b, Mpk13, Fat2, Neurod2, Slc18a3, Gon4l Gbx2, Slc6a3(Dat1) Aldh1a7 Tyrp1 and Lbx1. Interestingly, we found that Slc6a5, and Lamp5 as well as IL33, which are associated with startle disease, are also upregulated in response to knocking out ASIP. These findings are indicative of a direct autoimmune effect between aggression-associated genes and startle disease. Furthermore, in order to validate the link between aggression and auditory inputs processing. We conducted psychological tests of persons who experienced lockdown. We found that aggression has risen by 16 % during the lockdown. Furthermore, 3% of the subjects interviewed reported a change in their hearing abilities. Our data shed light on the importance of the auditory input in aggression and open perceptions to interpret how hearing and aggression interact at the molecular neural circuit level. url: https://doi.org/10.1101/2020.06.10.141325 doi: 10.1101/2020.06.10.141325 id: cord-345516-fgn7rps3 author: Miller, Laura C title: Analysis of the swine tracheobronchial lymph node transcriptomic response to infection with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus date: 2012-10-30 words: 4730.0 sentences: 204.0 pages: flesch: 43.0 cache: ./cache/cord-345516-fgn7rps3.txt txt: ./txt/cord-345516-fgn7rps3.txt summary: title: Analysis of the swine tracheobronchial lymph node transcriptomic response to infection with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus Emergence in 2006 of a novel highly pathogenic PRRSV (HP-PRRSV) isolate in China necessitated a comparative investigation into the host transcriptome response in tracheobronchial lymph nodes (TBLN) 13 days post-infection with HP-PRRSV rJXwn06, PRRSV strain VR-2332 or sham inocula. Gene IDs and log2 fold-change expression values for significant hits, that had FPKM values in both the control and the infected differential expression testing for transcripts (Cuffdiff output files), were then analyzed using the Ingenuity Pathway Analysis software. abstract: BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen of swine worldwide. Emergence in 2006 of a novel highly pathogenic PRRSV (HP-PRRSV) isolate in China necessitated a comparative investigation into the host transcriptome response in tracheobronchial lymph nodes (TBLN) 13 days post-infection with HP-PRRSV rJXwn06, PRRSV strain VR-2332 or sham inocula. RNA from each was prepared for next-generation sequencing. Amplified library constructs were directly sequenced and a list of sequence transcripts and counts was generated using an RNAseq analysis pipeline to determine differential gene expression. Transcripts were annotated and relative abundance was calculated based upon the number of times a given transcript was represented in the library. RESULTS: Major changes in transcript abundance occurred in response to infection with either PRRSV strain, each with over 630 differentially expressed transcripts. The largest increase in transcript level for either virus versus sham-inoculated controls were three serum amyloid A2 acute-phase isoforms. However, the degree of up or down-regulation of transcripts following infection with HP-PRRSV rJXwn06 was greater than transcript changes observed with US PRRSV VR-2332. Also, of 632 significantly altered transcripts within the HP-PRRSV rJXwn06 library 55 were up-regulated and 69 were down-regulated more than 3-fold, whilst in the US PRRSV VR-2332 library only 4 transcripts were up-regulated and 116 were down-regulated more than 3-fold. CONCLUSIONS: The magnitude of differentially expressed gene profiles detected in HP-PRRSV rJXwn06 infected pigs as compared to VR-2332 infected pigs was consistent with the increased pathogenicity of the HP-PRRSV in vivo. url: https://doi.org/10.1186/1746-6148-8-208 doi: 10.1186/1746-6148-8-208 id: cord-103150-e9q8e62v author: Mishra, Shreya title: Improving gene-network inference with graph-wavelets and making insights about ageing associated regulatory changes in lungs date: 2020-11-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Using gene-regulatory-networks based approach for single-cell expression profiles can reveal un-precedented details about the effects of external and internal factors. However, noise and batch effect in sparse single-cell expression profiles can hamper correct estimation of dependencies among genes and regulatory changes. Here we devise a conceptually different method using graph-wavelet filters for improving gene-network (GWNet) based analysis of the transcriptome. Our approach improved the performance of several gene-network inference methods. Most Importantly, GWNet improved consistency in the prediction of generegulatory-network using single-cell transcriptome even in presence of batch effect. Consistency of predicted gene-network enabled reliable estimates of changes in the influence of genes not highlighted by differential-expression analysis. Applying GWNet on the single-cell transcriptome profile of lung cells, revealed biologically-relevant changes in the influence of pathways and master-regulators due to ageing. Surprisingly, the regulatory influence of ageing on pneumocytes type II cells showed noticeable similarity with patterns due to effect of novel coronavirus infection in Human Lung. url: https://doi.org/10.1101/2020.07.24.219196 doi: 10.1101/2020.07.24.219196 id: cord-292004-9rpoll7y author: Mitchell, Hugh D. title: The Role of EGFR in Influenza Pathogenicity: Multiple Network-Based Approaches to Identify a Key Regulator of Non-lethal Infections date: 2019-09-20 words: 8357.0 sentences: 373.0 pages: flesch: 43.0 cache: ./cache/cord-292004-9rpoll7y.txt txt: ./txt/cord-292004-9rpoll7y.txt summary: The role of epidermal growth factor receptor (EGFR) in influenza pathogenesis, one of the bottleneck regulators with corroborating signals across transcript and protein expression data, was tested and validated in additional mouse infection experiments. The role of epidermal growth factor receptor (EGFR) in influenza pathogenesis, one of the bottleneck regulators with corroborating signals across transcript and protein expression data, was tested and validated in additional mouse infection experiments. The same relationships between network topology, viral pathogenicity, and gene expression that were observed for influenza virus were also noted when we used a similar dataset of SARS-CoV infections, thus further validating our analysis and demonstrating that these relationships appear to apply to respiratory viruses in general. abstract: Despite high sequence similarity between pandemic and seasonal influenza viruses, there is extreme variation in host pathogenicity from one viral strain to the next. Identifying the underlying mechanisms of variability in pathogenicity is a critical task for understanding influenza virus infection and effective management of highly pathogenic influenza virus disease. We applied a network-based modeling approach to identify critical functions related to influenza virus pathogenicity using large transcriptomic and proteomic datasets from mice infected with six influenza virus strains or mutants. Our analysis revealed two pathogenicity-related gene expression clusters; these results were corroborated by matching proteomics data. We also identified parallel downstream processes that were altered during influenza pathogenesis. We found that network bottlenecks (nodes that bridge different network regions) were highly enriched in pathogenicity-related genes, while network hubs (highly connected network nodes) were significantly depleted in these genes. We confirmed that this trend persisted in a distinct virus: Severe Acute Respiratory Syndrome Coronavirus (SARS). The role of epidermal growth factor receptor (EGFR) in influenza pathogenesis, one of the bottleneck regulators with corroborating signals across transcript and protein expression data, was tested and validated in additional mouse infection experiments. We demonstrate that EGFR is important during influenza infection, but the role it plays changes for lethal versus non-lethal infections. Our results show that by using association networks, bottleneck genes that lack hub characteristics can be used to predict a gene’s involvement in influenza virus pathogenicity. We also demonstrate the utility of employing multiple network approaches for analyzing host response data from viral infections. url: https://www.ncbi.nlm.nih.gov/pubmed/31616667/ doi: 10.3389/fcell.2019.00200 id: cord-273347-eyxc4rt0 author: Mohammadinejad, Reza title: In vivo gene delivery mediated by non-viral vectors for cancer therapy date: 2020-07-04 words: 7777.0 sentences: 485.0 pages: flesch: 39.0 cache: ./cache/cord-273347-eyxc4rt0.txt txt: ./txt/cord-273347-eyxc4rt0.txt summary: We will also highlight the in vivo gene delivery mediated by non-viral vectors to treat cancer in different tissue and organs including brain, breast, lung, liver, stomach, and prostate. Since various routes of administration have been used to transfer non-viral delivery systems for gene therapy, it seems that the route is highly dependent on the characteristics of the carrier and nucleic acids as well the prepared complex and the final formulation. Synthesis and Application of a Novel Gene Delivery Vector for Non-Small-Cell Lung Cancer Therapy Chloroquine in combination with aptamer-modified nanocomplexes for tumor vessel normalization and efficient erlotinib/Survivin shRNA co-delivery to overcome drug resistance in EGFR-mutated non-small cell lung cancer Enhanced delivery of siRNA to triple negative breast cancer cells in vitro and in vivo through functionalizing lipid-coated calcium phosphate nanoparticles with dual target ligands Highly efficient cationic hydroxyethylated cholesterol-based nanoparticle-mediated gene transfer in vivo and in vitro in prostate carcinoma PC-3 cells abstract: Gene therapy by expression constructs or down-regulation of certain genes has shown great potential for the treatment of various diseases. The wide clinical application of nucleic acid materials dependents on the development of biocompatible gene carriers. There are enormous various compounds widely investigated to be used as non-viral gene carriers including lipids, polymers, carbon materials, and inorganic structures. In this review, we will discuss the recent discoveries on non-viral gene delivery systems. We will also highlight the in vivo gene delivery mediated by non-viral vectors to treat cancer in different tissue and organs including brain, breast, lung, liver, stomach, and prostate. Finally, we will delineate the state-of-the-art and promising perspective of in vivo gene editing using non-viral nano-vectors. url: https://www.ncbi.nlm.nih.gov/pubmed/32634464/ doi: 10.1016/j.jconrel.2020.06.038 id: cord-260496-s2ba7uy3 author: Moncany, Maurice L.J. title: Identification of conserved lentiviral sequences as landmarks of genomic flexibility date: 2006-08-08 words: 5991.0 sentences: 296.0 pages: flesch: 51.0 cache: ./cache/cord-260496-s2ba7uy3.txt txt: ./txt/cord-260496-s2ba7uy3.txt summary: Comparison of entire genomes, including 237 human, simian and non-primate mammal lentiviruses and 103 negative control viruses, led to identify 28 Conserved Lentiviral Sequences (CLSs). Immunodeficiency lentiviral genomes correspond to 171 human viruses (155 HIV-1s and 16 HIV-2s), 33 simian viruses (3 CPZ, 9 AGM, 8 Macaque, 2 Mandrill, 10 Sooty Mangabey, 1 Sykes'' monkey viruses) and 33 non-primate mammal viruses (2 bovine, 2 caprine, 11 equine, 9 feline, 3 ovine and 6 ovine/caprine viruses). From the particular organization of the HIV-1 and HIV-2 ( Fig. 1) , AGM and macaque (Fig. 2) , CPZ, feline, equine and D-particle-forming viruses (Fig. 3) and that of sooty mangabey, mandrill and other non-primate lentiviruses (supplementary data), it appears that a given CLS occupied on the viral genome a specific position that was roughly conserved in the different viral families. abstract: Considering that recombinations produce quasispecies in lentivirus spreading, we identified and localized highly conserved sequences that may play an important role in viral ontology. Comparison of entire genomes, including 237 human, simian and non-primate mammal lentiviruses and 103 negative control viruses, led to identify 28 Conserved Lentiviral Sequences (CLSs). They were located mainly in the structural genes forming hot spots particularly in the gag and pol genes and to a lesser extent in LTRs and regulatory genes. The CLS pattern was the same throughout the different HIV-1 subtypes, except for some HIV-1-O strains. Only CLS 3 and 4 were detected in both negative control HTLV-1 oncornaviruses and D-particle-forming simian viruses, which are not immunodeficiency inducers and display a genetic stability. CLSs divided the virus genomes into domains allowing us to distinguish sequence families leading to the notion of ‘species self’ besides that of ‘lentiviral self’. Most of acutely localized CLSs in HIV-1s (82%) corresponded to wide recombination segments being currently reported. To cite this article: M.L.J. Moncany et al., C. R. Biologies 329 (2006). url: https://www.sciencedirect.com/science/article/pii/S1631069106001661 doi: 10.1016/j.crvi.2006.07.001 id: cord-328287-3qgzulgj author: Moni, Mohammad Ali title: Network-based analysis of comorbidities risk during an infection: SARS and HIV case studies date: 2014-10-24 words: 10643.0 sentences: 547.0 pages: flesch: 43.0 cache: ./cache/cord-328287-3qgzulgj.txt txt: ./txt/cord-328287-3qgzulgj.txt summary: Then based on the gene expression, PPI and signalling pathways data, we investigate the comorbidity association of these 2 infective pathologies with other 7 diseases (heart failure, kidney disorder, breast cancer, neurodegenerative disorders, bone diseases, Type 1 and Type 2 diabetes). The differential gene expression profiling strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response and statistically dysregulates a large number of genes, pathways and PPIs subnetworks in different pathologies such as chronic heart failure (21 genes), breast cancer (16 genes) and bone diseases (11 genes). To observe the association of SARS and HIV infections with other 7 important diseases (chronic heart failure, kidney disorders, breast cancer, parkinson, osteoporosis, type 1 and type 2 diabetes), we have collected mRNA microarray raw data associated with each disease from the Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/) accession numbers are GSE9006, GSE9128, GSE15072, GSE7158, GSE8977 and GSE7621 [59] . abstract: BACKGROUND: Infections are often associated to comorbidity that increases the risk of medical conditions which can lead to further morbidity and mortality. SARS is a threat which is similar to MERS virus, but the comorbidity is the key aspect to underline their different impacts. One UK doctor says "I’d rather have HIV than diabetes" as life expectancy among diabetes patients is lower than that of HIV. However, HIV has a comorbidity impact on the diabetes. RESULTS: We present a quantitative framework to compare and explore comorbidity between diseases. By using neighbourhood based benchmark and topological methods, we have built comorbidity relationships network based on the OMIM and our identified significant genes. Then based on the gene expression, PPI and signalling pathways data, we investigate the comorbidity association of these 2 infective pathologies with other 7 diseases (heart failure, kidney disorder, breast cancer, neurodegenerative disorders, bone diseases, Type 1 and Type 2 diabetes). Phenotypic association is measured by calculating both the Relative Risk as the quantified measures of comorbidity tendency of two disease pairs and the ϕ-correlation to measure the robustness of the comorbidity associations. The differential gene expression profiling strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response and statistically dysregulates a large number of genes, pathways and PPIs subnetworks in different pathologies such as chronic heart failure (21 genes), breast cancer (16 genes) and bone diseases (11 genes). HIV-1 induces comorbidities relationship with many other diseases, particularly strong correlation with the neurological, cancer, metabolic and immunological diseases. Similar comorbidities risk is observed from the clinical information. Moreover, SARS and HIV infections dysregulate 4 genes (ANXA3, GNS, HIST1H1C, RASA3) and 3 genes (HBA1, TFRC, GHITM) respectively that affect the ageing process. It is notable that HIV and SARS similarly dysregulated 11 genes and 3 pathways. Only 4 significantly dysregulated genes are common between SARS-CoV and MERS-CoV, including NFKBIA that is a key regulator of immune responsiveness implicated in susceptibility to infectious and inflammatory diseases. CONCLUSIONS: Our method presents a ripe opportunity to use data-driven approaches for advancing our current knowledge on disease mechanism and predicting disease comorbidities in a quantitative way. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2105-15-333) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1186/1471-2105-15-333 doi: 10.1186/1471-2105-15-333 id: cord-308034-9b219k0v author: Murray, James L. title: A Role for H/ACA and C/D Small Nucleolar RNAs in Viral Replication date: 2014-01-30 words: 3654.0 sentences: 218.0 pages: flesch: 12.0 cache: ./cache/cord-308034-9b219k0v.txt txt: ./txt/cord-308034-9b219k0v.txt summary: We have employed gene-trap insertional mutagenesis to identify candidate genes whose disruption confer phenotypic resistance to lytic infection, in independent studies using 12 distinct viruses and several different cell lines. Expression of nine SNORA/Ds encoded within RCC1 (which also encodes the shorter non-coding SNHG3 gene), or SNHG1 were silenced with siRNAs for 2 days prior to infection with either cowpox virus (CPV), Dengue Fever virus (DFV), influenza A (FLU), human rhinovirus 16 (HRV16), herpes simplex virus 2 (HSV2), or respiratory syncytial virus (RSV). While a previous study showed that RCC1 supports HSV1 replication [21] , we did not observe that silencing RCC1 or the non-coding Small Nucleolar RNA Host Gene 3 (SNHG3) inhibits HSV2 (data not shown), whereas inhibiting expression of the RCC1encoded SNORA73A did. The discovery of these classes of non-coding genes prominently represented in the mutant clones selected in our virus surviving cell lines suggests an importance of SNORAs and SNORDs in facilitating viral replication. abstract: We have employed gene-trap insertional mutagenesis to identify candidate genes whose disruption confer phenotypic resistance to lytic infection, in independent studies using 12 distinct viruses and several different cell lines. Analysis of >2,000 virus-resistant clones revealed >1,000 candidate host genes, approximately 20 % of which were disrupted in clones surviving separate infections with 2–6 viruses. Interestingly, there were 83 instances in which the insertional mutagenesis vector disrupted transcripts encoding H/ACA-class and C/D-class small nucleolar RNAs (SNORAs and SNORDs, respectively). Of these, 79 SNORAs and SNORDs reside within introns of 29 genes (predominantly protein-coding), while 4 appear to be independent transcription units. siRNA studies targeting candidate SNORA/Ds provided independent confirmation of their roles in infection when tested against cowpox virus, Dengue Fever virus, influenza A virus, human rhinovirus 16, herpes simplex virus 2, or respiratory syncytial virus. Significantly, eight of the nine SNORA/Ds targeted with siRNAs enhanced cellular resistance to multiple viruses suggesting widespread involvement of SNORA/Ds in virus–host interactions and/or virus-induced cell death. url: https://www.ncbi.nlm.nih.gov/pubmed/24477674/ doi: 10.1007/s12033-013-9730-0 id: cord-264746-gfn312aa author: Muse, Spencer title: GENOMICS AND BIOINFORMATICS date: 2012-03-29 words: 10976.0 sentences: 583.0 pages: flesch: 58.0 cache: ./cache/cord-264746-gfn312aa.txt txt: ./txt/cord-264746-gfn312aa.txt summary: The success of this project (it came in almost 3 years ahead of time and 10% under budget, while at the same time providing more data than originally planned) depended on innovations in a variety of areas: breakthroughs in basic molecular biology to allow manipulation of DNA and other compounds; improved engineering and manufacturing technology to produce equipment for reading the sequences of DNA; advances in robotics and laboratory automation; development of statistical methods to interpret data from sequencing projects; and the creation of specialized computing hardware and software systems to circumvent massive computational barriers that faced genome scientists. Although the list of important biotechnologies changes on an almost daily basis, there are three prominent data types in today''s environment: (1) genome sequences provide the starting point that allows scientists to begin understanding the genetic underpinnings of an organism; (2) measurements of gene expression levels facilitate studies of gene regulation, which, among other things, help us to understand how an organism''s genome interacts with its environment; and (3) genetic polymorphisms are variations from individual to individual within species, and understanding how these variations correlate with phenotypes such as disease susceptibility is a crucial element of modern biomedical research. abstract: This chapter discusses the basic principles of molecular biology regarding genome science and describes the major types of data involved in genome projects, including technologies for collecting them. Genome science is heavily driven by new technological advances that allow for rapid and inexpensive collection of various types of data. The emergence of genomic science has not simply provided a rich set of tools and data for studying molecular biology. It has been the catalyst for an astounding burst of interdisciplinary research, and it has challenged long-established hierarchies found in most institutions of higher learning. The next generation of biologists needs to be as comfortable at a computer workstation as they are at the lab bench. Recognizing this fact, many universities have already reorganized their departments and their curricula to accommodate the demands of genomic science.The chapter discusses practical applications and uses of genomic data. For example, in the foreseeable future, are gene therapies that can repair genetic defects. url: https://api.elsevier.com/content/article/pii/B978012238662650015X doi: 10.1016/b978-0-12-238662-6.50015-x id: cord-003387-82573enr author: Nam, Gyu-Hwi title: Gene expression profiles alteration after infection of virus, bacteria, and parasite in the Olive flounder (Paralichthys olivaceus) date: 2018-12-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Olive flounder (Paralichthys olivaceus) is one of economically valuable fish species in the East Asia. In comparison with its economic importance, available genomic information of the olive flounder is very limited. The mass mortality caused by variety of pathogens (virus, bacteria and parasites) is main problem in aquaculture industry, including in olive flounder culture. In this study, we carried out transcriptome analysis using the olive flounder gill tissues after infection of three types of pathogens (Virus; Viral hemorrhagic septicemia virus, Bacteria; Streptococcus parauberis, and Parasite; Miamiensis avidus), respectively. As a result, we identified total 12,415 differentially expressed genes (DEG) from viral infection, 1,754 from bacterial infection, and 795 from parasite infection, respectively. To investigate the effects of pathogenic infection on immune response, we analyzed Gene ontology (GO) enrichment analysis with DEGs and sorted immune-related GO terms per three pathogen groups. Especially, we verified various GO terms, and genes in these terms showed down-regulated expression pattern. In addition, we identified 67 common genes (10 up-regulated and 57 down-regulated) present in three pathogen infection groups. Our goals are to provide plenty of genomic knowledge about olive flounder transcripts for further research and report genes, which were changed in their expression after specific pathogen infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305387/ doi: 10.1038/s41598-018-36342-y id: cord-305177-i71z2sf4 author: Neshat, Sarah Y title: Gene delivery for immunoengineering date: 2020-06-15 words: 5261.0 sentences: 234.0 pages: flesch: 32.0 cache: ./cache/cord-305177-i71z2sf4.txt txt: ./txt/cord-305177-i71z2sf4.txt summary: Major strategies that have been explored for cancer immunotherapy [7] center on increasing the immunogenicity of the tumor microenvironment, enhancing the ability of antigen-presenting cells (APCs) to be activated, improving the activation of T cells and other lymphocytes in the context of the tumor while lessening the effect of suppressive immune cells, and vaccinating the patient with a tumor-specific antigen in order to generate a tumor-targeted immune response ( Figure 1 ). Additionally, anti-viral vaccines have been engineered with self-amplifying mRNA (SAM) encapsulated in lipid nanoparticles and show an induced type 1 IFN Gene delivery for immunoengineering Neshat, Tzeng and Green 7 response locally when compared to TLR7 agonists [45 ] . Using lipid nanoparticles, the authors describe an antigen-agnostic combination immunotherapy via direct intratumoral injection of mRNA encoding immunostimulatory genes, leading to anti-tumor effect even at sites distant from the local treatment site. abstract: A growing number of gene delivery strategies are being employed for immunoengineering in applications ranging from infectious disease prevention to cancer therapy. Viral vectors tend to have high gene transfer capability but may be hampered by complications related to their intrinsic immunogenicity. Non-viral methods of gene delivery, including polymeric, lipid-based, and inorganic nanoparticles as well as physical delivery techniques, have also been widely investigated. By using either ex vivo engineering of immune cells that are subsequently adoptively transferred or in vivo transfection of cells for in situ genetic programming, researchers have developed different approaches to precisely modulate immune responses. In addition to expressing a gene of interest through intracellular delivery of plasmid DNA and mRNA, researchers are also delivering oligonucleotides to knock down gene expression and immunostimulatory nucleic acids to tune immune activity. Many of these biotechnologies are now in clinical trials and have high potential to impact medicine. url: https://doi.org/10.1016/j.copbio.2020.05.008 doi: 10.1016/j.copbio.2020.05.008 id: cord-018924-wo42j0ps author: Nettelbeck, Dirk M. title: Bispecific Antibodies and Gene Therapy date: 2011-07-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Gene therapy is the transfer of therapeutic genes, via gene transfer vectors, into patients for therapeutic purposes. Different gene therapy strategies are being pursued, including long-term gene correction of monogenetic diseases, eradication of tumor cells in cancer patients, or genetic vaccination for infectious diseases. Bispecific antibodies and gene therapy are connected in two ways. First, bispecific antibodies are tools of interest for the development of targeted gene transfer vectors. Different gene therapy strategies require different vectors, frequently replication-ablated viruses. Similar to the role of antibody engineering in antibody therapy, the engineering of gene transfer vectors has become key to the implementation of genetic therapies. Cytoablative cancer gene therapy and efficient genetic vaccination, for example, depend on vectors that are targeted to cancer cells and antigen-presenting cells, respectively, in order to avoid side effects and vector sequestration. To this end, bispecific antibodies have been engineered as adapters that link the vector to a specific molecule on the targeted cell and at the same time block the interaction with the native virus receptor. Different formats of bispecific antibodies and related molecules have been developed and succeeded in re-directing vectors to target cells in vitro and in vivo. These adapters also improved gene therapies in animal models. Second, gene transfer is a promising tool for delivery of bispecific antibodies to patients. Therefore, vectors can be injected directly into patients for antibody gene transfer, or cells isolated from patients can be genetically modified in vitro and then re-injected for in vivo antibody production. Genetic antibody delivery, compared with standard antibody injection, can be advantageous with respect to achieving persistent antibody titers or effective antibody biodistribution in patients. Initial studies have shown antibody production and therapeutic activity in animal models, setting the stage for more widespread investigations. Moreover, gene therapy can enable novel therapeutic applications for bispecific antibodies by facilitating the delivery of membrane associated or intracellular antibody formats. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123931/ doi: 10.1007/978-3-642-20910-9_18 id: cord-016293-pyb00pt5 author: Newell-McGloughlin, Martina title: The flowering of the age of Biotechnology 1990–2000 date: 2006 words: 22402.0 sentences: 943.0 pages: flesch: 47.0 cache: ./cache/cord-016293-pyb00pt5.txt txt: ./txt/cord-016293-pyb00pt5.txt summary: In the course of the project, especially in the early years, the plan stated that "much new technology will be developed that will facilitate biomedical and a broad range of biological research, bring down the cost of many experiments (mapping and sequencing), and finding applications in numerous other fields." The plan built upon the 1988 reports of the Office of Technology Assessment and the National Research Council on mapping and sequencing the human genome. These DNA chips have broad commercial applications and are now used in many areas of basic and clinical research including the detection of drug resistance mutations in infectious organisms, direct DNA sequence comparison of large segments of the human genome, the monitoring of multiple human genes for disease associated mutations, the quantitative and parallel measurement of mRNA expression for thousands of human genes, and the physical and genetic mapping of genomes. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120537/ doi: 10.1007/1-4020-5149-2_4 id: cord-018145-kssjdn8y author: Niemann, Heiner title: Transgenic Farm Animals: Current Status and Perspectives for Agriculture and Biomedicine date: 2009 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The first transgenic livestock were produced in 1985 by microinjection of foreign DNA into zygotic pronuclei. This was the method of choice for more than 20 years, but more efficient protocols are now available, based on somatic cell nuclear transfer (SCNT) which permits targeted genetic modifications. Although the efficiency of transgenic animal production by microinjection technology is low, many animals with agriculturally important transgenic traits were produced. Typical applications included improved carcass composition, lactational performance, and wool production as well as enhanced disease resistance and reduced environmental impact. Transgenic animal production for biomedical applications has found broad acceptance. In 2006 the European Medicines Agency (EMEA) approved the commercialization of the first recombinant protein drug produced by transgenic animals. Recombinant antithrombin III, produced in the mammary gland of transgenic goats, was launched as ATryn® for prophylactic treatment of patients with congenital antithrombin deficiency. Pigs expressing human immunomodulatory genes have contributed to significant progress in xenotransplantation research with survival periods of non-human primates receiving transgenic porcine hearts or kidneys approaching six months. Lentiviral vectors and small interfering ribonucleic acid (siRNA) technology are also emerging as important tools for transgenesis. As the genome sequencing projects for various farm animal species progress, it has become increasingly practical to target the removal or modification of individual genes. We anticipate that this approach to animal breeding will be instrumental in meeting global challenges in agricultural production in the future and will open new horizons in biomedicine. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122947/ doi: 10.1007/978-3-540-85843-0_1 id: cord-284015-vvtv492b author: Nikaido, Masato title: Comparative genomic analyses illuminate the distinct evolution of megabats within Chiroptera date: 2020-09-23 words: 8594.0 sentences: 502.0 pages: flesch: 51.0 cache: ./cache/cord-284015-vvtv492b.txt txt: ./txt/cord-284015-vvtv492b.txt summary: We identified that megabat genomes are distinct in that they have extremely low activity of SINE retrotranspositions, expansion of two chemosensory gene families, including the trace amine receptor (TAAR) and olfactory receptor (OR), and elevation of the dN/dS ratio in genes for immunity and protein catabolism. The protein-coding genes in the genomes of Egyptian fruit bat and Leschenault''s rousette were identified based on the alignment with annotated gene sequences of 14 mammals (cat, dog, horse, cow, hedgehog, human, macaque, mouse, rat, Black flying fox, Little brown bat, Brandt''s bat, David''s myotis, and Large flying fox; Supplementary Table S2 ) that are available in the database. 71 Suggesting that FPR-mediated chemodetection is not directly linked with the difference in their habitats, mega-and microbats both possess two to eight FPRs. However, a previous study, by comparing the orthologous sequences among a broad range of mammals, found the signatures for the operation of positive selection in FPRs. 72 Therefore, to examine the possible contribution of FPRs to the adaptive evolution of megabats, more detailed investigation is necessary by focussing on the dN/dS values among orthologous FPR sequences of many bat species, which are lacking at present. abstract: The revision of the sub-order Microchiroptera is one of the most intriguing outcomes in recent mammalian molecular phylogeny. The unexpected sister–taxon relationship between rhinolophoid microbats and megabats, with the exclusion of other microbats, suggests that megabats arose in a relatively short period of time from a microbat-like ancestor. In order to understand the genetic mechanism underlying adaptive evolution in megabats, we determined the whole-genome sequences of two rousette megabats, Leschenault’s rousette (Rousettus leschenaultia) and the Egyptian fruit bat (R. aegyptiacus). The sequences were compared with those of 22 other mammals, including nine bats, available in the database. We identified that megabat genomes are distinct in that they have extremely low activity of SINE retrotranspositions, expansion of two chemosensory gene families, including the trace amine receptor (TAAR) and olfactory receptor (OR), and elevation of the dN/dS ratio in genes for immunity and protein catabolism. The adaptive signatures discovered in the genomes of megabats may provide crucial insight into their distinct evolution, including key processes such as virus resistance, loss of echolocation, and frugivorous feeding. url: https://www.ncbi.nlm.nih.gov/pubmed/32966557/ doi: 10.1093/dnares/dsaa021 id: cord-028721-x6f26ahr author: Nistal, Manuel title: Non-neoplastic diseases of the testis date: 2020-06-22 words: 78172.0 sentences: 5138.0 pages: flesch: 41.0 cache: ./cache/cord-028721-x6f26ahr.txt txt: ./txt/cord-028721-x6f26ahr.txt summary: Congenital decrease of germ cells occurs in numerous conditions, including trisomies 13, 18, and 21, some forms of primary hypogonadism such as Klinefelter''s syndrome, anencephaly, many cryptorchid testes, and in patients with posterior urethral valves and severe obstruction of the urinary ducts. 728, 729 Leydig cell hypoplasia This variant of male pseudohermaphroditism is defi ned by insuffi cient testosterone secretion 422 and the following characteristics: predominance of female external genitalia; absence of male secondary sex characteristics at puberty; absence of uterus and fallopian tubes and the presence of epididymis and vas deferens; 46XY karyotype; lack of response to human chorionic gonadotropin stimulation; absence of an enzymatic defect in testosterone synthesis; and small undescended testes that are gray and mucous on section. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339753/ doi: 10.1016/b978-0-323-01970-5.50014-2 id: cord-016187-58rqc0cg author: Opal, S. M. title: The Challenge of Emerging Infections and Progressive Antibiotic Resistance date: 2006 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120399/ doi: 10.1007/3-540-29730-8_6 id: cord-290282-oxyzndsj author: Ortego, Javier title: Transmissible gastroenteritis coronavirus gene 7 is not essential but influences in vivo virus replication and virulence date: 2003-03-30 words: 4287.0 sentences: 215.0 pages: flesch: 53.0 cache: ./cache/cord-290282-oxyzndsj.txt txt: ./txt/cord-290282-oxyzndsj.txt summary: Transmissible gastroenteritis coronavirus (TGEV) contains eight overlapping genes that are expressed from a 3′-coterminal nested set of leader-containing mRNAs. To facilitate the genetic manipulation of the viral genome, genes were separated by duplication of transcription regulating sequences (TRSs) and introduction of unique restriction endonuclease sites at the 5′ end of each gene using an infectious cDNA clone. All the rTGEV viruses conserved the modifications engineered in the cDNAs (data not shown), indicating that the ORF separation and the insertion of unique endonuclease restriction sites between genes were stably maintained in the rTGEV genomes. Interestingly, analysis of viral growth in the gut of infected piglets showed a 100-to 5000-fold reduction of recombinant viruses containing one or more restriction sites in relation to the rTGEV-wt virus ( Fig. 5D and E) . abstract: Transmissible gastroenteritis coronavirus (TGEV) contains eight overlapping genes that are expressed from a 3′-coterminal nested set of leader-containing mRNAs. To facilitate the genetic manipulation of the viral genome, genes were separated by duplication of transcription regulating sequences (TRSs) and introduction of unique restriction endonuclease sites at the 5′ end of each gene using an infectious cDNA clone. The recombinant TGEV (rTGEV) replicated in cell culture with similar efficiency to the wild-type virus and stably maintained the modifications introduced into the genome. In contrast, the rTGEV replication level in the lungs and gut of infected piglets and virulence were significantly reduced. rTGEV in which gene 7 expression was abrogated (rTGEV-Δ7) were recovered from cDNA constructs, indicating that TGEV gene 7 was a nonessential gene for virus replication. Interestingly, in vivo infections with rTGEV-Δ7 showed an additional reduction in virus replication in the lung and gut, and in virulence, indicating that TGEV gene 7 influences virus pathogenesis. url: https://www.ncbi.nlm.nih.gov/pubmed/12706086/ doi: 10.1016/s0042-6822(02)00096-x id: cord-355075-ieb35upi author: Papenfuss, Anthony T title: The immune gene repertoire of an important viral reservoir, the Australian black flying fox date: 2012-06-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Bats are the natural reservoir host for a range of emerging and re-emerging viruses, including SARS-like coronaviruses, Ebola viruses, henipaviruses and Rabies viruses. However, the mechanisms responsible for the control of viral replication in bats are not understood and there is little information available on any aspect of antiviral immunity in bats. Massively parallel sequencing of the bat transcriptome provides the opportunity for rapid gene discovery. Although the genomes of one megabat and one microbat have now been sequenced to low coverage, no transcriptomic datasets have been reported from any bat species. In this study, we describe the immune transcriptome of the Australian flying fox, Pteropus alecto, providing an important resource for identification of genes involved in a range of activities including antiviral immunity. RESULTS: Towards understanding the adaptations that have allowed bats to coexist with viruses, we have de novo assembled transcriptome sequence from immune tissues and stimulated cells from P. alecto. We identified about 18,600 genes involved in a broad range of activities with the most highly expressed genes involved in cell growth and maintenance, enzyme activity, cellular components and metabolism and energy pathways. 3.5% of the bat transcribed genes corresponded to immune genes and a total of about 500 immune genes were identified, providing an overview of both innate and adaptive immunity. A small proportion of transcripts found no match with annotated sequences in any of the public databases and may represent bat-specific transcripts. CONCLUSIONS: This study represents the first reported bat transcriptome dataset and provides a survey of expressed bat genes that complement existing bat genomic data. In addition, these data provide insight into genes relevant to the antiviral responses of bats, and form a basis for examining the roles of these molecules in immune response to viral infection. url: https://doi.org/10.1186/1471-2164-13-261 doi: 10.1186/1471-2164-13-261 id: cord-320005-i30t7cvr author: Pardo, A. title: The Human Genome and Advances in Medicine: Limits and Future Prospects date: 2004-03-31 words: 4919.0 sentences: 211.0 pages: flesch: 49.0 cache: ./cache/cord-320005-i30t7cvr.txt txt: ./txt/cord-320005-i30t7cvr.txt summary: The HGP''s initial objectives were fulfilled 2 years ahead of schedule, and, in addition to compiling a highly accurate sequence of the human genome which has been made freely available and accessible to everyone, the Consortium has developed a set of new technologies and has constructed genetic maps of the genomes of various organisms. Around the same time, the public consortium known as the Human Genome Project was formed, and this organization announced a 15-year plan (from 1990 to 2005) with the following objectives: a) to determine the complete nucleotide sequence of human DNA and identify all the genes in human DNA (estimated to number between 50 000 and 100 000); b) to build physical and genetic maps; c) to analyze the genomes of selected organisms used in research as model systems (eg, the mouse); d) to develop new technologies; and e) to analyze and debate the ethical and legal implications for individuals and for society as a whole. abstract: nan url: https://www.sciencedirect.com/science/article/pii/S1579212906700787 doi: 10.1016/s1579-2129(06)70078-7 id: cord-315498-gpzee1f2 author: Parkinson, N. title: Systematic review and meta-analysis identifies potential host therapeutic targets in COVID-19. date: 2020-09-01 words: 4964.0 sentences: 296.0 pages: flesch: 46.0 cache: ./cache/cord-315498-gpzee1f2.txt txt: ./txt/cord-315498-gpzee1f2.txt summary: 2, 6, 7, 8, 9, 10 In this analysis we systematically identify and combine existing data from human betacoronavirus research to generate a comprehensive ranked list of host genes as a resource to inform further work on COVID-19. To identify existing literature which could provide informative datasets for host gene prioritisation, we conducted a systematic review of published studies and preprint manuscripts pertaining to host gene involvement in human betacoronavirus infection and associated disease. Results from identified studies, in the form of lists of implicated host factor genes, were combined using meta-analysis by information content (MAIC), 3 an approach we previously developed to identify host genes necessary for Influenza A virus (IAV) replication. Table 2 Candidate-gene human genetic studies < 5 hosts in virus group or control group in patient studies Meta-analyses, in silico anayses, re-analysis of data published elsewhere Potentially relevant pre-print manuscripts were identified by screening all papers categorised as COVID-19-related in the bioRxiv and medRxiv servers. abstract: An increasing body of literature describes the role of host factors in COVID-19 pathogenesis. There is a need to combine diverse, multi-omic data in order to evaluate and substantiate the most robust evidence and inform development of future therapies. We conducted a systematic review of experiments identifying host factors involved in human betacoronavirus infection (SARS-CoV-2, SARS-CoV, MERS-CoV, seasonal coronaviruses). Gene lists from these diverse sources were integrated using Meta-Analysis by Information Content (MAIC). This previously described algorithm uses data-driven gene list weightings to produce a comprehensive ranked list of implicated host genes. 5,418 genes implicated in human betacoronavirus infection were identified from 32 datasets. The top ranked gene was *PPIA*, encoding cyclophilin A. Pharmacological inhibition with cyclosporine in vitro exerts antiviral activity against several coronaviruses including SARS-CoV. Other highly-ranked genes included proposed prognostic factors (*CXCL10*, *CD4*, *CD3E*) and investigational therapeutic targets (*IL1A*) for COVID-19, but also previously overlooked genes with potential as therapeutic targets. Gene rankings also inform the interpretation of COVID-19 GWAS results, implicating *FYCO1* over other nearby genes in a disease-associated locus on chromosome 3. Pathways enriched in gene rankings included T-cell receptor signalling, protein processing, and viral infections. We identified limited overlap of our gene list with host genes implicated in ARDS (innate immune and inflammation genes) and Influenza A virus infection (RNA-binding and ribosome-associated genes). We will continue to update this dynamic ranked list of host genes as the field develops, as a resource to inform and prioritise future studies. Updated results are available at https://baillielab.net/maic/covid19. url: https://doi.org/10.1101/2020.08.27.20182238 doi: 10.1101/2020.08.27.20182238 id: cord-304607-td0776wj author: Paszkiewicz, Konrad H. title: Omics, Bioinformatics, and Infectious Disease Research date: 2010-12-24 words: 7022.0 sentences: 367.0 pages: flesch: 46.0 cache: ./cache/cord-304607-td0776wj.txt txt: ./txt/cord-304607-td0776wj.txt summary: This chapter discusses the current state of play of bioinformatics related to genomics and transcriptomics, briefs metagenomics that finds use in infectious disease research as well as the random sequencing of genomes from a variety of organisms. Bioinformatics plays a key role at several steps in genomics, comparative genomics, and functional genomics: sequence alignment, assembly, identification of single nucleotide polymorphisms (SNP), gene prediction, quantitative analysis of transcription data, etc. The term "metagenomics" was originally used to describe the sequencing of genomes of uncultured microorganisms in order to explore their abilities to produce natural products (Handelsman et al., 1998 , Rondon et al., 2000 and subsequently resulted in novel insights into the ecology and evolution of microorganisms on a scale not imagined possible before (see Cardenas and Tiedje, 2008; Hugenholtz and Tyson, 2008 for an overview). However, metagenomics now finds use in infectious disease research as well as the random sequencing of genomes from a variety of organisms from, for example, patient material that could lead to the identification of the cause of disease. abstract: Bioinformatics is basically the study of informatic processes in biotic systems. Actually what constitutes bioinformatics is not entirely clear and arguably varies depending on who tries to define it. This chapter discusses the considerable progress in infectious diseases research that has been made in recent years using various “omics” case studies. Bioinformatics is tasked with making sense of it, mining it, storing it, disseminating it, and ensuring valid biological conclusions can be drawn from it. This chapter discusses the current state of play of bioinformatics related to genomics and transcriptomics, briefs metagenomics that finds use in infectious disease research as well as the random sequencing of genomes from a variety of organisms. This chapter explains the various possibilities of pan-genome, transcriptional reshaping and also enormous progress of proteomics study. Bioinformatic algorithms and tools are crucial tools in analyzing the data. The chapter also attempts to provide some details on the various problems and solution in bioinformatics that current-day scientists face while concentrating on second-generation sequencing strategies. url: https://api.elsevier.com/content/article/pii/B9780123848901000182 doi: 10.1016/b978-0-12-384890-1.00018-2 id: cord-004893-28mrzvsc author: Pavesi, Angelo title: On the Informational Content of Overlapping Genes in Prokaryotic and Eukaryotic Viruses date: 1997 words: 3783.0 sentences: 161.0 pages: flesch: 48.0 cache: ./cache/cord-004893-28mrzvsc.txt txt: ./txt/cord-004893-28mrzvsc.txt summary: At the level of codon usage, a low degree of correlation between overlapping and nonoverlapping coding regions characterized the first pattern, whereas a close link was found in tymoviruses, indicating a fine adaptation of the overlapping frame to the original codon choice of the virus. Here, we present an analysis at different levels of complexity (divergence from randomness of mono-and dinucleotide composition, choice of synonymous codons, and frequency of occurrence of amino acid residues) of the informational content of overlapping genes. The graphical representation ( Fig. 2) of the average values of the D 1 and D 2 indices, calculated by grouping the 12 viruses under examination in the five corresponding families (coliphage, hepatitis B virus, HIV-1 lentivirus, luteovirus, and tymovirus), led to the identification of two different informational patterns in the viral coding sequences. abstract: In genetic language a peculiar arrangement of biological information is provided by overlapping genes in which the same region of DNA can code for functionally unrelated messages. In this work, the informational content of overlapping genes belonging to prokaryotic and eukaryotic viruses was analyzed. Using information theory indices, we identified in the regions of overlap a first pattern, exhibiting a more uniform base composition and more severe constraints in base ordering with respect to the nonoverlapping regions. This pattern was found to be peculiar to coliphage, avian hepatitis B virus, human lentivirus, and plant luteovirus families. A second pattern, characterized by the occurrence of similar compositional constraints in both types of coding regions, was found to be limited to plant tymoviruses. At the level of codon usage, a low degree of correlation between overlapping and nonoverlapping coding regions characterized the first pattern, whereas a close link was found in tymoviruses, indicating a fine adaptation of the overlapping frame to the original codon choice of the virus. As a result of codon usage correlation analysis, deductions concerning the origin and evolution of several overlapping frames were also proposed. Comparison of amino acid composition revealed an increased frequency of amino acid residues with a high level of degeneracy (arginine, leucine, and serine) in the proteins encoded by overlapping genes; this peculiar feature of overlapping genes can be viewed as a way with which they may expand their coding ability and gain new, specialized functions. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087557/ doi: 10.1007/pl00006185 id: cord-266617-z8uecyl6 author: Pavesi, Angelo title: Asymmetric evolution in viral overlapping genes is a source of selective protein adaptation date: 2019-04-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Overlapping genes represent an intriguing puzzle, as they encode two proteins whose ability to evolve is constrained by each other. Overlapping genes can undergo “symmetric evolution” (similar selection pressures on the two proteins) or “asymmetric evolution” (significantly different selection pressures on the two proteins). By sequence analysis of 75 pairs of homologous viral overlapping genes, I evaluated their accordance with one or the other model. Analysis of nucleotide and amino acid sequences revealed that half of overlaps undergo asymmetric evolution, as the protein from one frame shows a number of substitutions significantly higher than that of the protein from the other frame. Interestingly, the most variable protein (often known to interact with the host proteins) appeared to be encoded by the de novo frame in all cases examined. These findings suggest that overlapping genes, besides to increase the coding ability of viruses, are also a source of selective protein adaptation. url: https://www.sciencedirect.com/science/article/pii/S0042682219300881 doi: 10.1016/j.virol.2019.03.017 id: cord-102219-d3gkfo7s author: Perzel Mandell, Kira A. title: Characterizing the dynamic and functional DNA methylation landscape in the developing human cortex date: 2019-10-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: DNA methylation (DNAm) is a key epigenetic regulator of gene expression across development. The developing prenatal brain is a highly dynamic tissue, but our understanding of key drivers of epigenetic variability across development is limited. We therefore assessed genomic methylation at over 39 million sites in the prenatal cortex using whole genome bisulfite sequencing and found loci and regions in which methylation levels are dynamic across development. We saw that DNAm at these loci was associated with nearby gene expression and enriched for enhancer chromatin states in prenatal brain tissue. Additionally, these loci were enriched for genes associated with psychiatric disorders and genes involved with neurogenesis. We also found autosomal differences in DNAm between the sexes during prenatal development, though these have less clear functional consequences. We lastly confirmed that the dynamic methylation at this critical period is specifically CpG methylation, with very low levels of CpH methylation. Our findings provide detailed insight into prenatal brain development as well as clues to the pathogenesis of psychiatric traits seen later in life. url: https://doi.org/10.1101/823781 doi: 10.1101/823781 id: cord-001858-nmi39n6h author: Petriccione, Milena title: Reference gene selection for normalization of RT-qPCR gene expression data from Actinidia deliciosa leaves infected with Pseudomonas syringae pv. actinidiae date: 2015-11-19 words: 5567.0 sentences: 286.0 pages: flesch: 50.0 cache: ./cache/cord-001858-nmi39n6h.txt txt: ./txt/cord-001858-nmi39n6h.txt summary: title: Reference gene selection for normalization of RT-qPCR gene expression data from Actinidia deliciosa leaves infected with Pseudomonas syringae pv. Primer sequence (5′-3′) BestKeeper and the deltaCt method) were used to evaluate the stability of expression of selected RGs. The analyses were performed for three comparison groups considering both low-and high-dose bacterial inocula in the leaves and their combined dataset. In kiwifruit leaves with a high dose of bacterial inoculum, BestKeeper revealed that only the expression of TUB overcame the stability threshold; CYP and GAPDH were considered to be the most stable genes, with SD values of 0.50 and 0.61, respectively (Table 3 ). The expression of three genes encoding the reactive oxygen species (ROS) scavenging enzymes ascorbate peroxidase (APX), superoxide dismutase (SOD) and catalase (CAT), induced during the systemic infection of kiwifruit leaves with PSA, were chosen to further validate the reliability of the selected RGs for the normalization of RT-qPCR data. abstract: Normalization of data, by choosing the appropriate reference genes (RGs), is fundamental for obtaining reliable results in reverse transcription-quantitative PCR (RT-qPCR). In this study, we assessed Actinidia deliciosa leaves inoculated with two doses of Pseudomonas syringae pv. actinidiae during a period of 13 days for the expression profile of nine candidate RGs. Their expression stability was calculated using four algorithms: geNorm, NormFinder, BestKeeper and the deltaCt method. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and protein phosphatase 2A (PP2A) were the most stable genes, while β-tubulin and 7s-globulin were the less stable. Expression analysis of three target genes, chosen for RGs validation, encoding the reactive oxygen species scavenging enzymes ascorbate peroxidase (APX), superoxide dismutase (SOD) and catalase (CAT) indicated that a combination of stable RGs, such as GAPDH and PP2A, can lead to an accurate quantification of the expression levels of such target genes. The APX level varied during the experiment time course and according to the inoculum doses, whereas both SOD and CAT resulted down-regulated during the first four days, and up-regulated afterwards, irrespective of inoculum dose. These results can be useful for better elucidating the molecular interaction in the A. deliciosa/P. s. pv. actinidiae pathosystem and for RGs selection in bacteria-plant pathosystems. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4652207/ doi: 10.1038/srep16961 id: cord-351845-bli3qm8w author: Prasad, Kartikay title: Targeting hub genes and pathways of innate immune response in COVID-19: A network biology perspective date: 2020-06-26 words: 4626.0 sentences: 293.0 pages: flesch: 46.0 cache: ./cache/cord-351845-bli3qm8w.txt txt: ./txt/cord-351845-bli3qm8w.txt summary: Towards this goal, in this study, we have generated a human-SARS-CoV-2 interactome based on recently published RNA-Seq analysis of human adenocarcinomic alveolar basal epithelial (A549) cells infected with SARS-CoV-2, and identified disease-related functional genes that will provide the insights into the patho-J o u r n a l P r e -p r o o f 4 mechanisms of COVID-19. Overall, the analysis demonstrated that the upregulated genes are mainly linked to the host response to SARS-CoV-2 infection, type I interferon signaling and the cytokine-mediated signaling pathway. The PPI network analysis indicates that the pathways are enriched in host response to virus infection, type I interferons signaling, and cytokine activation. [74] reported high SARS-CoV-2 loads very early during infection, suggesting that the virus may have developed arsenals that is able to delay the IFN response by inhibiting innate immune signaling. abstract: The current pandemic of 2019 novel coronavirus disease (COVID-19) caused by a novel virus strain, 2019-nCoV/SARS-CoV-2 have posed a serious threat to global public health and economy. It is largely unknown how the human immune system responds to this infection. A better understanding of the immune response to SARS-CoV-2 will be important to develop therapeutics against COVID-19. Here, we have used transcriptomic profile of human alveolar adenocarcinoma cells (A549) infected with SARS-CoV-2 and employed a network biology approach to generate human-virus interactome. Network topological analysis discovers 15 SARS-CoV-2 targets, which belongs to a subset of interferon (IFN) stimulated genes (ISGs). These ISGs (IFIT1, IFITM1, IRF7, ISG15, MX1, and OAS2) can be considered as potential candidates for drug targets in the treatments of COVID-19. We have identified significant interaction between ISGs and TLR3 agonists, like poly I: C, and imiquimod, and suggests that TLR3 agonists can be considered as a potential drug for drug repurposing in COVID-19. Our network centric analysis suggests that moderating the innate immune response is a valuable approach to target COVID-19. url: https://www.sciencedirect.com/science/article/pii/S0141813020336837?v=s5 doi: 10.1016/j.ijbiomac.2020.06.228 id: cord-282968-kjvvoveq author: Qu, Renjun title: Selection of reference genes for the quantitative real-time PCR normalization of gene expression in Isatis indigotica fortune date: 2019-03-25 words: 6267.0 sentences: 315.0 pages: flesch: 47.0 cache: ./cache/cord-282968-kjvvoveq.txt txt: ./txt/cord-282968-kjvvoveq.txt summary: indigotica, and evaluated their expression stabilities in different tissues (root, stem, leaf, and petiole) and leaves exposed to three abiotic treatments (low-nitrogen, ABA, and MeJA) using geNorm, NormFinder, BestKeeper, and comprehensive RefFind algorithms. TIP41 as the optimal reference gene for low-nitrogen stress and MeJA treatment, while ACT had the highest ranking for ABA treatment and CYP was the most suitable for different tissues. Excel-based tools, such as geNorm [34] , NormFinder [35] and BestKeeper [36] , have been developed to select the most suitable reference genes from a set of biological samples under investigation to be used in an expression stability analysis. indigotica (SRR1051997) to determine appropriate reference genes for qRT-PCR normalization in different plant tissues, and under low-nitrogen stress and exposure to hormonal stimuli (ABA and MeJA). The results were normalized using the selected stable reference genes (singly or in combination) and the unstable genes in sample sets across treatment with a N, b different tissues, c ABA, and d MeJA. abstract: BACKGROUND: Isatis indigotica, a traditional Chinese medicine, produces a variety of active ingredients. However, little is known about the key genes and corresponding expression profiling involved in the biosynthesis pathways of these ingredients. Quantitative real-time polymerase chain reaction (qRT-PCR) is a powerful, commonly-used method for gene expression analysis, but the accuracy of the quantitative data produced depends on the appropriate selection of reference genes. RESULTS: In this study, the systematic analysis of the reference genes was performed for quantitative real-Time PCR normalization in I. indigotica. We selected nine candidate reference genes, including six traditional housekeeping genes (ACT, α-TUB, β-TUB, UBC, CYP, and EF1-α), and three newly stable internal control genes (MUB, TIP41, and RPL) from a transcriptome dataset of I. indigotica, and evaluated their expression stabilities in different tissues (root, stem, leaf, and petiole) and leaves exposed to three abiotic treatments (low-nitrogen, ABA, and MeJA) using geNorm, NormFinder, BestKeeper, and comprehensive RefFind algorithms. The results demonstrated that MUB and EF1-α were the two most stable reference genes for all samples. TIP41 as the optimal reference gene for low-nitrogen stress and MeJA treatment, while ACT had the highest ranking for ABA treatment and CYP was the most suitable for different tissues. CONCLUSIONS: The results revealed that the selection and validation of appropriate reference genes for normalizing data is mandatory to acquire accurate quantification results. The necessity of specific internal control for specific conditions was also emphasized. Furthermore, this work will provide valuable information to enhance further research in gene function and molecular biology on I. indigotica and other related species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12867-019-0126-y) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1186/s12867-019-0126-y doi: 10.1186/s12867-019-0126-y id: cord-312551-w4tps34p author: Razvi, Mohammad H. title: Transcriptional oncogenomic hot spots in Barrett''s adenocarcinomas: Serial analysis of gene expression date: 2007-07-17 words: 5047.0 sentences: 291.0 pages: flesch: 46.0 cache: ./cache/cord-312551-w4tps34p.txt txt: ./txt/cord-312551-w4tps34p.txt summary: Analyses of the human transcriptome map of normal tissues have shown clustering of highly expressed genes in chromosomal domains (Caron et al., 2001) . In this study, we explored the BA transcriptome using SAGE and mapped gene-expression changes to chromosomal positions, thereby generating a map of transcriptional oncogenomic hot spots of this deadly cancer. We confirmed over-expression of ANPEP, ECGF1, PP1201, and EIF5A1 and downregulation of GKN1 in primary GEJ and lower esophageal adenocarcinoma samples (Table 5 , Fig. 2) . GKN1 shows downregulation ( 0.4-fold expression) whereas ANPEP, PP1201, EIF5A1, and ECGF1 demonstrate overexpression (!2.5 fold expression) in primary tumors as compared to normal tissue samples. Discovery of new markers of cancer through serial analysis of gene expression: Prostate stem cell antigen is overexpressed in pancreatic adenocarcinoma abstract: Serial analysis of gene expression (SAGE) provides quantitative and comprehensive expression profiling in a given cell population. In our efforts to define gene expression alterations in Barrett's‐related adenocarcinomas (BA), we produced eight SAGE libraries and obtained a total of 457,894 expressed tags with 32,035 (6.9%) accounting for singleton tags. The tumor samples produced an average of 71,804 tags per library, whereas normal samples produced an average of 42,669 tags per library. Our libraries contained 67,200 unique tags representing 16,040 known gene symbols. Five hundred and sixty‐eight unique tags were differentially expressed between BAs and normal tissue samples (at least twofold; P ≤ 0.05), 395 of these matched to known genes. Interestingly, the distribution of altered genes was not uniform across the human genome. Overexpressed genes tended to cluster in well‐defined hot spots located in certain chromosomes. For example, chromosome 19 had 26 overexpressed genes, of which 18 mapped to 19q13. Using the gene ontology approach for functional classification of genes, we identified several groups that are relevant to carcinogenesis. We validated the SAGE results of five representative genes (ANPEP, ECGF1, PP1201, EIF5A1, and GKN1) using quantitative real‐time reverse‐transcription PCR on 31 BA samples and 26 normal samples. In addition, we performed an immunohistochemistry analysis for ANPEP, which demonstrated overexpression of ANPEP in 6/7 (86%) Barrett's dysplasias and 35/65 (54%) BAs. ANPEP is a secreted protein that may have diagnostic and/or prognostic significance for Barrett's progression. The use of genomic approaches in this study provided useful information about the molecular pathobiology of BAs. © 2007 Wiley‐Liss, Inc. url: https://www.ncbi.nlm.nih.gov/pubmed/17636545/ doi: 10.1002/gcc.20479 id: cord-002142-tdgu9sr9 author: Reniere, Michelle L. title: An In Vivo Selection Identifies Listeria monocytogenes Genes Required to Sense the Intracellular Environment and Activate Virulence Factor Expression date: 2016-07-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Listeria monocytogenes is an environmental saprophyte and facultative intracellular bacterial pathogen with a well-defined life-cycle that involves escape from a phagosome, rapid cytosolic growth, and ActA-dependent cell-to-cell spread, all of which are dependent on the master transcriptional regulator PrfA. The environmental cues that lead to temporal and spatial control of L. monocytogenes virulence gene expression are poorly understood. In this study, we took advantage of the robust up-regulation of ActA that occurs intracellularly and expressed Cre recombinase from the actA promoter and 5’ untranslated region in a strain in which loxP sites flanked essential genes, so that activation of actA led to bacterial death. Upon screening for transposon mutants that survived intracellularly, six genes were identified as necessary for ActA expression. Strikingly, most of the genes, including gshF, spxA1, yjbH, and ohrA, are predicted to play important roles in bacterial redox regulation. The mutants identified in the genetic selection fell into three broad categories: (1) those that failed to reach the cytosolic compartment; (2) mutants that entered the cytosol, but failed to activate the master virulence regulator PrfA; and (3) mutants that entered the cytosol and activated transcription of actA, but failed to synthesize it. The identification of mutants defective in vacuolar escape suggests that up-regulation of ActA occurs in the host cytosol and not the vacuole. Moreover, these results provide evidence for two non-redundant cytosolic cues; the first results in allosteric activation of PrfA via increased glutathione levels and transcriptional activation of actA while the second results in translational activation of actA and requires yjbH. Although the precise host cues have not yet been identified, we suggest that intracellular redox stress occurs as a consequence of both host and pathogen remodeling their metabolism upon infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945081/ doi: 10.1371/journal.ppat.1005741 id: cord-306535-j26eqmxt author: Robertson, Matthew J. title: Large-scale discovery of male reproductive tract-specific genes through analysis of RNA-seq datasets date: 2020-08-19 words: 16758.0 sentences: 846.0 pages: flesch: 49.0 cache: ./cache/cord-306535-j26eqmxt.txt txt: ./txt/cord-306535-j26eqmxt.txt summary: The majority of candidate genes identified in our screen that were testis-specific were already identified by the Human Protein Atlas [9] and/or our reanalysis of (See figure on previous page.) Fig. 1 Summary of the human and mouse RNA-seq samples used in the identification of novel male reproductive tract-specific drug targets. Additional file 14: Fig. S6 shows the complete list of male reproductive tract-specific human genes for which a previously generated mouse model shows male infertility phenotype, as identified in each of the respective cell and/or tissue datasets. Through the integration of hundreds of published and newly acquired human and mouse reproductive and non-reproductive tissue and cell RNA-seq datasets, we have generated a list of novel genes expressed predominantly or exclusively in the male reproductive tract that are worthy of consideration for functional validation in an animal model and potential targeting for a male contraceptive. abstract: BACKGROUND: The development of a safe, effective, reversible, non-hormonal contraceptive method for men has been an ongoing effort for the past few decades. However, despite significant progress on elucidating the function of key proteins involved in reproduction, understanding male reproductive physiology is limited by incomplete information on the genes expressed in reproductive tissues, and no contraceptive targets have so far reached clinical trials. To advance product development, further identification of novel reproductive tract-specific genes leading to potentially druggable protein targets is imperative. RESULTS: In this study, we expand on previous single tissue, single species studies by integrating analysis of publicly available human and mouse RNA-seq datasets whose initial published purpose was not focused on identifying male reproductive tract-specific targets. We also incorporate analysis of additional newly acquired human and mouse testis and epididymis samples to increase the number of targets identified. We detected a combined total of 1178 genes for which no previous evidence of male reproductive tract-specific expression was annotated, many of which are potentially druggable targets. Through RT-PCR, we confirmed the reproductive tract-specific expression of 51 novel orthologous human and mouse genes without a reported mouse model. Of these, we ablated four epididymis-specific genes (Spint3, Spint4, Spint5, and Ces5a) and two testis-specific genes (Pp2d1 and Saxo1) in individual or double knockout mice generated through the CRISPR/Cas9 system. Our results validate a functional requirement for Spint4/5 and Ces5a in male mouse fertility, while demonstrating that Spint3, Pp2d1, and Saxo1 are each individually dispensable for male mouse fertility. CONCLUSIONS: Our work provides a plethora of novel testis- and epididymis-specific genes and elucidates the functional requirement of several of these genes, which is essential towards understanding the etiology of male infertility and the development of male contraceptives. url: https://www.ncbi.nlm.nih.gov/pubmed/32814578/ doi: 10.1186/s12915-020-00826-z id: cord-350019-4nlbu54e author: Robinson, Elektra K. title: The how and why of lncRNA function: An innate immune perspective() date: 2019-09-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Next-generation sequencing has provided a more complete picture of the composition of the human transcriptome indicating that much of the “blueprint” is a vastness of poorly understood non-protein-coding transcripts. This includes a newly identified class of genes called long noncoding RNAs (lncRNAs). The lack of sequence conservation for lncRNAs across species meant that their biological importance was initially met with some skepticism. LncRNAs mediate their functions through interactions with proteins, RNA, DNA, or a combination of these. Their functions can often be dictated by their localization, sequence, and/or secondary structure. Here we provide a review of the approaches typically adopted to study the complexity of these genes with an emphasis on recent discoveries within the innate immune field. Finally, we discuss the challenges, as well as the emergence of new technologies that will continue to move this field forward and provide greater insight into the biological importance of this class of genes. This article is part of a Special Issue entitled: ncRNA in control of gene expression edited by Kotb Abdelmohsen. url: https://www.ncbi.nlm.nih.gov/pubmed/31487549/ doi: 10.1016/j.bbagrm.2019.194419 id: cord-263470-vmqvropy author: Rukavtsova, E. B. title: Tissue specific expression of hepatitis B virus surface antigen in transgenic plant cells and tissue culture date: 2007 words: 2902.0 sentences: 170.0 pages: flesch: 56.0 cache: ./cache/cord-263470-vmqvropy.txt txt: ./txt/cord-263470-vmqvropy.txt summary: The level of HBs-antigen in plants carrying the HBsAg gene controlled by (Aocs)(3)AmasPmas, the hybrid agrobacterium-derived promoter, was the highest in roots and made up to 0.01% of total amount of soluble protein. Earlier we have obtained the tobacco plants expressing the synthetic gene of the hepatitis B surface antigen ( HBsAg ) controlled by single and dual 35S RNA cauliflower mosaic virus promoters (CaMV 35S and CaMV 35SS, respectively) [10, 11] . The objective of this study was to obtain transgenic tobacco plants synthesizing the hepatitis B surface antigen controlled by ( Aocs ) 3 AmasPmas promoters and regulated by the elements of agrobacterial octopine synthase and mannopine synthase genes and also to analyze the expression profile of the HBsAg gene in different cells of the whole plant as well as that in callus and hairy root tissue cultures. abstract: The tobacco plants (Nicotiana tabacum L.) carrying the HBsAg gene controlled by (Aocs)(3)AmasPmas, the hybrid promoter that includes regulatory elements of the agrobacterial octopine and mannopine synthase genes, as well as plants controlled by the same promoter and adh1, maize alcohol dehydrogenase gene intron were obtained. The presence of the adh1 gene intron did not significantly change the level of expression of the HBsAg gene in plants. The analysis of expression of hepatitis B virus surface antigen (HBs-antigen) in transformed plants expressing the HBsAg under the control of different promoters was made. The level of HBs-antigen in plants carrying the HBsAg gene controlled by (Aocs)(3)AmasPmas, the hybrid agrobacterium-derived promoter, was the highest in roots and made up to 0.01% of total amount of soluble protein. The level of HBs-antigen in plants carrying the HBsAg gene controlled by the dual 35S RNA cauliflower mosaic virus promoter was the same in all organs of the plant and made up to 0.06% of the total amount of soluble protein. Hairy root and callus cultures of plants carrying the HBsAg gene and expressing the HBs-antigen were obtained. url: https://doi.org/10.1134/s1021443707060088 doi: 10.1134/s1021443707060088 id: cord-020969-lh2ergpm author: STRAUSS, JAMES H. title: Gene Therapy date: 2012-07-27 words: 11793.0 sentences: 597.0 pages: flesch: 52.0 cache: ./cache/cord-020969-lh2ergpm.txt txt: ./txt/cord-020969-lh2ergpm.txt summary: Together with methods for cloning and manipulating viral genomes, this information has made possible the use of viruses as vectors to express foreign genes. The use of minus-strand RNA viruses as vectors was delayed because the virion RNA itself is not infectious, but recent developments has made it possible to rescue virus from cloned DNA by using coexpression of the appropriate viral proteins in a transfected cell. It is also possible to transfect cells with the E1 or E3 expression cassette together with DNA clones encoding the rest of the adenovirus genome, in which case homologous recombination results in the production of virus. Because the poliovirus replicon lacks a full complement of the structural genes (it is a suicide vector), packaging to produce particles requires infection of a cell that expresses the polioviral structural proteins by some mechanism. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148746/ doi: 10.1016/b978-0-12-373741-0.50014-3 id: cord-015850-ef6svn8f author: Saitou, Naruya title: Eukaryote Genomes date: 2013-08-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: General overviews of eukaryote genomes are first discussed, including organelle genomes, introns, and junk DNAs. We then discuss the evolutionary features of eukaryote genomes, such as genome duplication, C-value paradox, and the relationship between genome size and mutation rates. Genomes of multicellular organisms, plants, fungi, and animals are then briefly discussed. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119937/ doi: 10.1007/978-1-4471-5304-7_8 id: cord-319517-denczc6t author: Salipalli, Sandeep title: Recent advances in live cell imaging of hepatoma cells date: 2014-07-08 words: 9184.0 sentences: 433.0 pages: flesch: 46.0 cache: ./cache/cord-319517-denczc6t.txt txt: ./txt/cord-319517-denczc6t.txt summary: This review aims to provide an overview of the recent developments in the field of marker proteins (bioluminescence and fluorescent) and methodologies (fluorescent resonance energy transfer, fluorescent recovery after photobleaching and proximity ligation assay) employed as to achieve an improved imaging of biological processes in hepatoma cells. The success of live cell imaging relies on various factors including the specific imaging system, climate controlling devices for cultured cells under investigation, construction of recombinant plasmid DNA, transfer and expression of candidate genes and/or fluorescent proteins in mammalian cells. T4SS (Bartonella sp.) 60-70% 50% >70% >60% 50-60% [76] [77] [78] lipofection (1 μg) methods were used for transfection of plasmid encoding fluorescent protein (pEGFP and pEYFP) tagged to human and mouse ADRP genes in Huh-7 cells as to study the pathways of lipid droplet metabolism. abstract: Live cell imaging enables the study of dynamic processes of living cells in real time by use of suitable reporter proteins and the staining of specific cellular structures and/or organelles. With the availability of advanced optical devices and improved cell culture protocols it has become a rapidly growing research methodology. The success of this technique relies mainly on the selection of suitable reporter proteins, construction of recombinant plasmids possessing cell type specific promoters as well as reliable methods of gene transfer. This review aims to provide an overview of the recent developments in the field of marker proteins (bioluminescence and fluorescent) and methodologies (fluorescent resonance energy transfer, fluorescent recovery after photobleaching and proximity ligation assay) employed as to achieve an improved imaging of biological processes in hepatoma cells. Moreover, different expression systems of marker proteins and the modes of gene transfer are discussed with emphasis on the study of lipid droplet formation in hepatocytes as an example. url: https://doi.org/10.1186/1471-2121-15-26 doi: 10.1186/1471-2121-15-26 id: cord-016200-zfh20im0 author: Saxena, Jyoti title: Edible Vaccines date: 2013-10-22 words: 7627.0 sentences: 417.0 pages: flesch: 51.0 cache: ./cache/cord-016200-zfh20im0.txt txt: ./txt/cord-016200-zfh20im0.txt summary: In 1998 a new era was opened in vaccine delivery when researchers supported by the National Institute of allergy and infectious diseases (NIAID) have shown for the first time that an edible vaccine can safely generate significant immune responses in people. Transgenic tobacco is successfully engineered for the production of edible vaccines against hepatitis B antigen using ''s'' gene of hepatitis B virus (HBV). Egyptian scientists have genetically engineered the maize plants to produce a protein known as HbsAg which elicits an immune response against the hepatitis B virus and could be used as a vaccine. It has been studied that genes are successfully expressed in experimental model plants and when given orally to animals, the extract of transgenic plant containing the antigen induced serum antibodies, thus can be used to produce the edible vaccine. abstract: In recent years edible vaccine emerged as a new concept developed by biotechnologists. Edible vaccines are subunit vaccines where the selected genes are introduced into the plants and the transgenic plant is then induced to manufacture the encoded protein. Foods under such application include potato, banana, lettuce, corn, soybean, rice, and legumes. They are easy to administer, easy to store and readily acceptable delivery system for different age group patients yet cost effective. Edible vaccines present exciting possibilities for significantly reducing various diseases such as measles, hepatitis B, cholera, diarrhea, etc., mainly in developing countries. However, various technical and regulatory challenges need to overcome in the path of this emerging vaccine technology to make edible vaccine more efficient and applicable. This chapter attempts to discuss key aspects of edible vaccines like host plants, production, mechanism of action, advantages and limitations, applications, and different regulatory issues concerned to edible vaccines. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120417/ doi: 10.1007/978-81-322-1554-7_12 id: cord-103465-6udhvl9n author: Schierding, William title: Low tolerance for transcriptional variation at cohesin genes is accompanied by functional links to disease-relevant pathways date: 2020-04-13 words: 6450.0 sentences: 323.0 pages: flesch: 41.0 cache: ./cache/cord-103465-6udhvl9n.txt txt: ./txt/cord-103465-6udhvl9n.txt summary: Results 140 genetic variants with regulatory potential are associated with cohesin loci Mitotic cohesin genes (SMC1A, SMC3, STAG1, STAG2, and RAD21), meiotic cohesin genes (SMC1B, STAG3, REC8, and RAD21L1), cohesin support genes (WAPL, NIPBL, PDS5A, PDS5B, and MAU2) and CTCF were investigated to determine if they contain non-coding genetic variants (SNPs) that make contact in 3D with genes and therefore could directly affect gene expression (GWAS-attributed and eQTL-attributed; Table 1, Table S1 ). Intriguingly, Haploreg motif prediction identified 16 of the 209 variants (7 different loci: MAU2, PDS5B, REC8, SMC1B, STAG3, RAD21L1, STAG1) as residing within protein binding domains associated with cohesin-related DNA interactions (i.e. RAD21, SMC3, and CTCF). Pathway enrichment implicates coordinated regulation of cohesin with essential cell cycle genes CoDeS3D identified 140 variants as being physically connected to, and associated with the expression levels of 310 genes (243 genes from eQTL-attributed variants, 141 from GWAS-attributed variants, and 74 overlap) across 6,795 significant tissue-specific regulatory connections (FDR p<0.05). abstract: Variants in DNA regulatory elements can alter the regulation of distant genes through spatial-regulatory connections. In humans, these spatial-regulatory connections are largely set during early development, when the cohesin complex plays an essential role in genome organisation and cell division. A full complement of the cohesin complex and its regulators is important for normal development, since heterozygous mutations in genes encoding these components are often sufficient to produce a disease phenotype. The implication that genes encoding the cohesin complex and cohesin regulators must be tightly controlled and resistant to variability in expression has not yet been formally tested. Here, we identify spatial-regulatory connections with potential to regulate expression of cohesin loci, including linking their expression to that of other genes. Connections that centre on the cohesin ring subunits (Mitotic: SMC1A, SMC3, STAG1, STAG2, RAD21/RAD21-AS; Meiotic: SMC1B, STAG3, REC8, RAD21L1), cohesin-ring support genes (NIPBL, MAU2, WAPL, PDS5A and PDS5B), and CTCF provide evidence of coordinated regulation that has little tolerance for perturbation. We identified transcriptional changes across a set of genes co-regulated with the cohesin loci that include biological pathways such as extracellular matrix production and proteasome-mediated protein degradation. Remarkably, many of the genes that are co-regulated with cohesin loci are themselves intolerant to loss-of-function. The results highlight the importance of robust regulation of cohesin genes, indicating novel pathways that may be important in the human cohesinopathy disorders. url: https://doi.org/10.1101/2020.04.11.037358 doi: 10.1101/2020.04.11.037358 id: cord-003254-yiqdsf9z author: Schlub, Timothy E title: A Simple Method to Detect Candidate Overlapping Genes in Viruses Using Single Genome Sequences date: 2018-08-07 words: 6313.0 sentences: 292.0 pages: flesch: 49.0 cache: ./cache/cord-003254-yiqdsf9z.txt txt: ./txt/cord-003254-yiqdsf9z.txt summary: Herein, we present a new statistical method for detecting overlapping genes in different reading frames that relies on only a single nucleotide sequence of a gene or genome. For the synonymous mutation test (C), codons that preserve the original amino acid sequence are randomly generated and the length of ORFs on alternative reading frames subsequently measured (note that codon replacement is not restricted to the example mutations shown in the figure, all of which occur in the third nucleotide positions, and that codon replacement with the original codon is also possible). Accordingly, whole genome sequences were downloaded from 2548 reference linear RNA viruses available on GenBank; this produced a total of 6408 coding regions that were used to estimate the sensitivity and false discovery rate of each test. where C is the empirical cumulative distribution function of the theoretical distribution of lengths calculated by permuting codons in the original coding sequence: that is, C(L) is the Simple Method to Detect Candidate Overlapping Genes . abstract: Overlapping genes in viruses maximize the coding capacity of their genomes and allow the generation of new genes without major increases in genome size. Despite their importance, the evolution and function of overlapping genes are often not well understood, in part due to difficulties in their detection. In addition, most bioinformatic approaches for the detection of overlapping genes require the comparison of multiple genome sequences that may not be available in metagenomic surveys of virus biodiversity. We introduce a simple new method for identifying candidate functional overlapping genes using single virus genome sequences. Our method uses randomization tests to estimate the expected length of open reading frames and then identifies overlapping open reading frames that significantly exceed this length and are thus predicted to be functional. We applied this method to 2548 reference RNA virus genomes and find that it has both high sensitivity and low false discovery for genes that overlap by at least 50 nucleotides. Notably, this analysis provided evidence for 29 previously undiscovered functional overlapping genes, some of which are coded in the antisense direction suggesting there are limitations in our current understanding of RNA virus replication. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188560/ doi: 10.1093/molbev/msy155 id: cord-287396-18p171nr author: Schroyen, Martine title: Current transcriptomics in pig immunity research date: 2014-11-15 words: 9824.0 sentences: 467.0 pages: flesch: 44.0 cache: ./cache/cord-287396-18p171nr.txt txt: ./txt/cord-287396-18p171nr.txt summary: Other meta-analysis studies, examining the immune response to Salmonella typhimurium, combine microarray information with data such as serum cytokine measurements or microbiota differences. typhimurium will be discussed in the section ''''Overall value of transcriptomics in important infectious swine diseases.'''' In addition, whole genome microarrays were used to study pig response to Haemophilus parasuis infection by Zhao et al. In 2010, Xiao and collaborators performed a 3'' tag digital gene expression (DGE) analysis of the porcine lung transcriptome on pigs infected with the PRRS virus (Xiao et al. Most pig immune studies conducted to identify host response to common porcine pathogens or to immune response stimulators such as LPS or PMA/ionomycin described in this review provide gene expression data from a single tissue or isolated cell type, and this at a limited number of times post-infection/stimulation. Recently, such a meta-analysis was performed by combining results of several microarray-based pig immune studies to find PRRS-specific responses (Badaoui et al. abstract: Swine performance in the face of disease challenge is becoming progressively more important. To improve the pig’s robustness and resilience against pathogens through selection, a better understanding of the genetic and epigenetic factors in the immune response is required. This review highlights results from the most recent transcriptome research, and the meta-analyses performed, in the context of pig immunity. A technological overview is given including wholegenome microarrays, immune-specific arrays, small-scale high-throughput expression methods, high-density tiling arrays, and next generation sequencing (NGS). Although whole genome microarray techniques will remain complementary to NGS for some time in domestic species, research will transition to sequencing-based methods due to cost-effectiveness and the extra information that such methods provide. Furthermore, upcoming high-throughput epigenomic studies, which will add greatly to our knowledge concerning the impact of epigenetic modifications on pig immune response, are listed in this review. With emphasis on the insights obtained from transcriptomic analyses for porcine immunity, we also discuss the experimental design in pig immunity research and the value of the newly published porcine genome assembly in using the pig as a model for human immune response. We conclude by discussing the importance of establishing community standards to maximize the possibility of integrative computational analyses, such as was clearly beneficial for the human ENCODE project. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00335-014-9549-4) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1007/s00335-014-9549-4 doi: 10.1007/s00335-014-9549-4 id: cord-311430-o32d3kaw author: Shahabi, Vafa title: Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events date: 2013-03-22 words: 6477.0 sentences: 299.0 pages: flesch: 49.0 cache: ./cache/cord-311430-o32d3kaw.txt txt: ./txt/cord-311430-o32d3kaw.txt summary: METHODS: To identify candidate predictive biomarkers associated with GI irAEs, gene expression profiling was performed on whole blood samples from 162 advanced melanoma patients at baseline, 3 and 11 weeks after the start of ipilimumab treatment in two phase II clinical trials (CA184004 and CA184007). In particular, on-treatment expression increases of CD177 and CEACAM1, two neutrophil-activation markers, were closely associated with GI irAEs, suggesting a possible role of neutrophils in ipilimumab-associated GI irAEs. In addition, the expression of several immunoglobulin genes increased over time, with greater increases in patients with grade 2+ GI irAEs. CONCLUSIONS: Gene expression profiling of peripheral blood, sampled before or early in the course of treatment with ipilimumab, resulted in the identification of a set of potential biomarkers that were associated with occurrence of GI irAEs. However, because of the low sensitivity of these biomarkers, they cannot be used alone to predict which patients will develop GI irAEs. Further investigation of these biomarkers in a larger patient cohort is warranted. To understand the underlying causes of ipilimumabassociated GI irAEs and identify potential predictive biomarkers, gene expression profiling was performed on whole blood samples collected from metastatic melanoma patients before and during ipilimumab treatment in two phase II clinical trials, CA184004 and CA184007 [6, 8] . abstract: BACKGROUND: Treatment with ipilimumab, a fully human anti-CTLA-4 antibody approved for the treatment of advanced melanoma, is associated with some immune-related adverse events (irAEs) such as colitis (gastrointestinal irAE, or GI irAE) and skin rash, which are managed by treatment guidelines. Nevertheless, predictive biomarkers that can help identify patients more likely to develop these irAEs could enhance the management of these toxicities. METHODS: To identify candidate predictive biomarkers associated with GI irAEs, gene expression profiling was performed on whole blood samples from 162 advanced melanoma patients at baseline, 3 and 11 weeks after the start of ipilimumab treatment in two phase II clinical trials (CA184004 and CA184007). Overall, 49 patients developed Grade 2 or higher (grade 2+) GI irAEs during the course of treatment. A repeated measures analysis of variance (ANOVA) was used to evaluate the differences in mean expression levels between the GI irAE and No-GI irAE groups of patients at the three time points. RESULTS: In baseline samples, 27 probe sets showed differential mean expression (≥ 1.5 fold, P ≤ 0.05) between the GI irAE and No-GI irAE groups. Most of these probe sets belonged to three functional categories: immune system, cell cycle, and intracellular trafficking. Changes in gene expression over time were also characterized. In the GI irAE group, 58 and 247 probe sets had a ≥ 1.5 fold change in expression from baseline to 3 and 11 weeks after first ipilimumab dose, respectively. In particular, on-treatment expression increases of CD177 and CEACAM1, two neutrophil-activation markers, were closely associated with GI irAEs, suggesting a possible role of neutrophils in ipilimumab-associated GI irAEs. In addition, the expression of several immunoglobulin genes increased over time, with greater increases in patients with grade 2+ GI irAEs. CONCLUSIONS: Gene expression profiling of peripheral blood, sampled before or early in the course of treatment with ipilimumab, resulted in the identification of a set of potential biomarkers that were associated with occurrence of GI irAEs. However, because of the low sensitivity of these biomarkers, they cannot be used alone to predict which patients will develop GI irAEs. Further investigation of these biomarkers in a larger patient cohort is warranted. url: https://doi.org/10.1186/1479-5876-11-75 doi: 10.1186/1479-5876-11-75 id: cord-307202-iz1bo218 author: Shaw, Dominick title: Asthma date: 2014-05-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Asthma is a common respiratory disease with a complex etiology involving a combination of genetic and environmental components. Current asthma management involves a step-up and step-down approach based on asthma control with a large degree of heterogeneity in responses to the main drug classes currently in use: β(2)-adrenergic receptor agonists, corticosteroids, and leukotriene modifiers. Importantly, asthma is heterogeneous with respect to clinical presentation and the inflammatory mechanisms that underlie it. This heterogeneity likely contributes to variable results in clinical trials, particularly when targeting specific inflammatory mediators. These factors have motivated a drive toward stratified medicine in asthma based on clinical/cellular outcomes or genetics (i.e., pharmacogenetics). Significant progress has been made in identifying genetic polymorphisms that influence the efficacy and potential for adverse effects of all main classes of asthma drugs. Importantly an emerging role for genetics in phase II development of newer therapies has been demonstrated (e.g., anti-IL4). Similarly, the stratification of patients based on clinical characteristics (e.g., blood and sputum eosinophil levels) has been critical in evaluating newer therapies (e.g., anti-IL5). As a proof of concept, anti-IgE is the latest therapy to be introduced into clinical practice, although only for severe, allergic patients (i.e., in a stratified manner). As new asthma genes are identified using genome-wide association, among other technologies, new targets (e.g., IL33/IL33 receptor (IL1RL1)) will emerge and pharmacogenetics in these development programs will be essential. In this chapter we review the current understanding of asthma pathobiology and its clinical presentation, as well as the use of stratified medicine, which holds great promise for maximizing clinical outcomes and minimizing adverse effects in existing and new therapies. url: https://www.sciencedirect.com/science/article/pii/B9780123868824000281 doi: 10.1016/b978-0-12-386882-4.00028-1 id: cord-274241-biqbsggu author: Shaw, Timothy I. title: Transcriptome Sequencing and Annotation for the Jamaican Fruit Bat (Artibeus jamaicensis) date: 2012-11-15 words: 6003.0 sentences: 339.0 pages: flesch: 52.0 cache: ./cache/cord-274241-biqbsggu.txt txt: ./txt/cord-274241-biqbsggu.txt summary: Annotated genes are involved in a broad range of activities ranging from cellular metabolism to genome regulation through ncRNAs. Reciprocal BLAST best hits yielded 8,785 sequences that are orthologous to mouse, rat, cattle, horse and human. Species tree analysis of sequences from 2,378 loci was used to achieve 95% bootstrap support for the placement of bat as sister to the clade containing horse, dog, and cattle. Through substitution rate estimation between bat and human, 32 genes were identified with evidence for positive selection. To address some of these deficiencies, we have performed transcriptome sequencing and analysis of spleen, lung, kidney and poly-IC-stimulated primary kidney cells to identify genes of interest for assessing the host response to TCRV infection. There were 20,145 contigs that mapped to Pteropus alecto, Australian flying fruit bat, and 18,359 that overlapped between genomic and transcriptome sequences for all three datasets ( Figure 5 ). abstract: The Jamaican fruit bat (Artibeus jamaicensis) is one of the most common bats in the tropical Americas. It is thought to be a potential reservoir host of Tacaribe virus, an arenavirus closely related to the South American hemorrhagic fever viruses. We performed transcriptome sequencing and annotation from lung, kidney and spleen tissues using 454 and Illumina platforms to develop this species as an animal model. More than 100,000 contigs were assembled, with 25,000 genes that were functionally annotated. Of the remaining unannotated contigs, 80% were found within bat genomes or transcriptomes. Annotated genes are involved in a broad range of activities ranging from cellular metabolism to genome regulation through ncRNAs. Reciprocal BLAST best hits yielded 8,785 sequences that are orthologous to mouse, rat, cattle, horse and human. Species tree analysis of sequences from 2,378 loci was used to achieve 95% bootstrap support for the placement of bat as sister to the clade containing horse, dog, and cattle. Through substitution rate estimation between bat and human, 32 genes were identified with evidence for positive selection. We also identified 466 immune-related genes, which may be useful for studying Tacaribe virus infection of this species. The Jamaican fruit bat transcriptome dataset is a resource that should provide additional candidate markers for studying bat evolution and ecology, and tools for analysis of the host response and pathology of disease. url: https://www.ncbi.nlm.nih.gov/pubmed/23166587/ doi: 10.1371/journal.pone.0048472 id: cord-307769-rjseio5s author: Sim, Winnie H title: Expression profile of genes involved in pathogenesis of pediatric Crohn''s disease date: 2012-05-24 words: 4673.0 sentences: 270.0 pages: flesch: 41.0 cache: ./cache/cord-307769-rjseio5s.txt txt: ./txt/cord-307769-rjseio5s.txt summary: Methods: We used suppressive subtractive hybridization (SSH) and differential screening analysis to profile the mRNA expression patterns of children with CD and age‐ and sex‐matched controls without inflammatory bowel disease (IBD). The real-time RT-PCR results validated that genes represented by > 10 clones enriched by subtractive hybridization were expressed in higher abundance in CD as compared with non-IBD ileal biopsies. To contextualize our SSH findings, we compared our results with the data tables from seven microarray studies published previously, that had reported differential expression of genes between inflamed biopsies of CD and non-inflamed biopsies of non-IBD controls. The antigen presentation, inflammatory response and cancer gene network (Network 1) comprise one-third Figure 1 The relative expression levels of REG1A, MMP2 and ANPEP in ileal biopsies from 13 Crohn''s disease (CD) and nine non-inflammatory bowel disease (IBD) patients. Primers used for real-time reverse transcription polymerase chain reaction quantification of ANPEP, REG1A, MMP2 and RPL32 Table S2 Differentially expressed genes specific to Crohn''s Disease (CD) ileum. abstract: Background and Aim: Expression profiling of genes specific to pediatric Crohn's Disease (CD) patients was performed to elucidate the molecular mechanisms underlying disease cause and pathogenesis at disease onset. Methods: We used suppressive subtractive hybridization (SSH) and differential screening analysis to profile the mRNA expression patterns of children with CD and age‐ and sex‐matched controls without inflammatory bowel disease (IBD). Results: Sequence analysis of 1000 clones enriched by SSH identified 75 functionally annotated human genes, represented by 430 clones. The 75 genes have potential involvement in gene networks, such as antigen presentation, inflammation, infection mechanism, connective tissue development, cell cycle and cancer. Twenty‐eight genes were previously described in association with CD, while 47 were new genes not previously reported in the context of IBD. Additionally, 29 of the 75 genes have been previously implicated in bacterial and viral infections. Quantitative real‐time reverse transcription polymerase chain reaction performed on ileal‐derived RNA from 13 CD and nine non‐IBD patients confirmed the upregulation of extracellular matrix gene MMP2 (P = 0.001), and cell proliferation gene REG1A (P = 0.063) in our pediatric CD cohort. Conclusion: The retrieval of 28 genes previously reported in association with adult CD emphasizes the importance of these genes in the pediatric setting. The observed upregulation of REG1A and MMP2, and their known impact on cell proliferation and extracellular matrix remodeling, agrees with the clinical behavior of the disease. Moreover, the expressions of bacterial‐ and virus‐related genes in our CD‐patient tissues support the concept that microbial agents are important in the etiopathogenesis of CD. url: https://www.ncbi.nlm.nih.gov/pubmed/22098497/ doi: 10.1111/j.1440-1746.2011.06973.x id: cord-016588-f8uvhstb author: Sintchenko, Vitali title: Informatics for Infectious Disease Research and Control date: 2009-10-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The goal of infectious disease informatics is to optimize the clinical and public health management of infectious diseases through improvements in the development and use of antimicrobials, the design of more effective vaccines, the identification of biomarkers for life-threatening infections, a better understanding of host-pathogen interactions, and biosurveillance and clinical decision support. Infectious disease informatics can lead to more targeted and effective approaches for the prevention, diagnosis and treatment of infections through a comprehensive review of the genetic repertoire and metabolic profiles of a pathogen. The developments in informatics have been critical in boosting the translational science and in supporting both reductionist and integrative research paradigms. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120928/ doi: 10.1007/978-1-4419-1327-2_1 id: cord-344297-qqohijqi author: Smith, Jacqueline title: The early immune response to infection of chickens with Infectious Bronchitis Virus (IBV) in susceptible and resistant birds date: 2015-10-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Infectious Bronchitis is a highly contagious respiratory disease which causes tracheal lesions and also affects the reproductive tract and is responsible for large economic losses to the poultry industry every year. This is due to both mortality (either directly provoked by IBV itself or due to subsequent bacterial infection) and lost egg production. The virus is difficult to control by vaccination, so new methods to curb the impact of the disease need to be sought. Here, we seek to identify genes conferring resistance to this coronavirus, which could help in selective breeding programs to rear chickens which do not succumb to the effects of this disease. METHODS: Whole genome gene expression microarrays were used to analyse the gene expression differences, which occur upon infection of birds with Infectious Bronchitis Virus (IBV). Tracheal tissue was examined from control and infected birds at 2, 3 and 4 days post-infection in birds known to be either susceptible or resistant to the virus. The host innate immune response was evaluated over these 3 days and differences between the susceptible and resistant lines examined. RESULTS: Genes and biological pathways involved in the early host response to IBV infection were determined andgene expression differences between susceptible and resistant birds were identified. Potential candidate genes for resistance to IBV are highlighted. CONCLUSIONS: The early host response to IBV is analysed and potential candidate genes for disease resistance are identified. These putative resistance genes can be used as targets for future genetic and functional studies to prove a causative link with resistance to IBV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0575-6) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1186/s12917-015-0575-6 doi: 10.1186/s12917-015-0575-6 id: cord-291349-tq2n4mx3 author: Smith, Kevin R title: Gene transfer in higher animals: theoretical considerations and key concepts date: 2002-10-09 words: 12232.0 sentences: 661.0 pages: flesch: 45.0 cache: ./cache/cord-291349-tq2n4mx3.txt txt: ./txt/cord-291349-tq2n4mx3.txt summary: The prospects for germline transgenesis via nuclear transfer (NT) are very significant: transgenes can be introduced to donor cells in vitro, permitting the production of genetically modified animals by NT . However, although retroviral-mediated gene therapy has been used successfully for (nonhuman) germline modifications, the most used */and to date the most useful */method for germline transgenesis is microinjection, reviewed in the following section. Because there are no special problems with microinjecting large transgene constructs, it is possible to incorporate structural gene-plus-promoter (plus other potentially useful sequences such as enhancers) combinations into the host genome. Therefore, the use of germline gene targeting as a means to avoiding transgene expression problems awaits progress in ES cell technology and NT technology. Following liposome-mediated gene transfer, amongst transgene molecules reaching the nucleus, only a minority integrate into the host cell chromosomes. abstract: Gene transfer technology provides the ability to genetically manipulate the cells of higher animals. Gene transfer permits both germline and somatic alterations. Such genetic manipulation is the basis for animal transgenesis goals and gene therapy attempts. Improvements in gene transfer are required in terms of transgene design to permit gene targeting, and in terms of transfection approaches to allow improved transgene uptake efficiencies. url: https://www.ncbi.nlm.nih.gov/pubmed/12204554/ doi: 10.1016/s0168-1656(02)00105-0 id: cord-303132-m3j1dekj author: Smith, S. E. title: Chicken Interferon-Inducible Transmembrane Protein 3 Restricts Influenza Viruses and Lyssaviruses In Vitro date: 2013-12-17 words: 5177.0 sentences: 253.0 pages: flesch: 47.0 cache: ./cache/cord-303132-m3j1dekj.txt txt: ./txt/cord-303132-m3j1dekj.txt summary: The chicken IFITM3 protein restricts cell infection by influenza A viruses and lyssaviruses to a similar level as its human orthologue. Despite being highly divergent at the amino acid level, IFITM3 proteins of birds and mammals can restrict replication of viruses that are able to infect different host species, suggesting IFITM proteins may provide a crucial barrier for zoonotic infections. Expression of the interferon-inducible transmembrane (IFITM) genes (new members of the ISG family) restricts the replication of several highly pathogenic human viruses, including severe acute respiratory syndrome (SARS) coronavirus, filoviruses (Marburg virus and Ebola virus), influenza A viruses (IAVs), and flaviviruses (dengue virus) (1, 2) . We then compared the level of antiviral restriction of chicken IFITM2 and -3 to that of their orthologous human proteins in A549 cells. Furthermore, we show that DF-1 chicken cells constitutively express chIFITM3, and this is able to restrict influenza virus infection in vitro. abstract: Interferon-inducible transmembrane protein 3 (IFITM3) is an effector protein of the innate immune system. It confers potent, cell-intrinsic resistance to infection by diverse enveloped viruses both in vitro and in vivo, including influenza viruses, West Nile virus, and dengue virus. IFITM3 prevents cytosolic entry of these viruses by blocking complete virus envelope fusion with cell endosome membranes. Although the IFITM locus, which includes IFITM1, -2, -3, and -5, is present in mammalian species, this locus has not been unambiguously identified or functionally characterized in avian species. Here, we show that the IFITM locus exists in chickens and is syntenic with the IFITM locus in mammals. The chicken IFITM3 protein restricts cell infection by influenza A viruses and lyssaviruses to a similar level as its human orthologue. Furthermore, we show that chicken IFITM3 is functional in chicken cells and that knockdown of constitutive expression in chicken fibroblasts results in enhanced infection by influenza A virus. Chicken IFITM2 and -3 are constitutively expressed in all tissues examined, whereas IFITM1 is only expressed in the bursa of Fabricius, gastrointestinal tract, cecal tonsil, and trachea. Despite being highly divergent at the amino acid level, IFITM3 proteins of birds and mammals can restrict replication of viruses that are able to infect different host species, suggesting IFITM proteins may provide a crucial barrier for zoonotic infections. url: https://doi.org/10.1128/jvi.01443-13 doi: 10.1128/jvi.01443-13 id: cord-256837-100ir651 author: Smith, Steven B. title: Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis date: 2012-03-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Pandemic and seasonal respiratory viruses are a major global health concern. Given the genetic diversity of respiratory viruses and the emergence of drug resistant strains, the targeted disruption of human host-virus interactions is a potential therapeutic strategy for treating multi-viral infections. The availability of large-scale genomic datasets focused on host-pathogen interactions can be used to discover novel drug targets as well as potential opportunities for drug repositioning. METHODS/RESULTS: In this study, we performed a large-scale analysis of microarray datasets involving host response to infections by influenza A virus, respiratory syncytial virus, rhinovirus, SARS-coronavirus, metapneumonia virus, coxsackievirus and cytomegalovirus. Common genes and pathways were found through a rigorous, iterative analysis pipeline where relevant host mRNA expression datasets were identified, analyzed for quality and gene differential expression, then mapped to pathways for enrichment analysis. Possible repurposed drugs targets were found through database and literature searches. A total of 67 common biological pathways were identified among the seven different respiratory viruses analyzed, representing fifteen laboratories, nine different cell types, and seven different array platforms. A large overlap in the general immune response was observed among the top twenty of these 67 pathways, adding validation to our analysis strategy. Of the top five pathways, we found 53 differentially expressed genes affected by at least five of the seven viruses. We suggest five new therapeutic indications for existing small molecules or biological agents targeting proteins encoded by the genes F3, IL1B, TNF, CASP1 and MMP9. Pathway enrichment analysis also identified a potential novel host response, the Parkin-Ubiquitin Proteasomal System (Parkin-UPS) pathway, which is known to be involved in the progression of neurodegenerative Parkinson's disease. CONCLUSIONS: Our study suggests that multiple and diverse respiratory viruses invoke several common host response pathways. Further analysis of these pathways suggests potential opportunities for therapeutic intervention. url: https://doi.org/10.1371/journal.pone.0033174 doi: 10.1371/journal.pone.0033174 id: cord-015935-r2wd1yfa author: Sokol, Deborah K. title: The Genetics of Autism date: 2011-02-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: This chapter is written to make the fast-paced, expanding field of the genetics of autism accessible to those practitioners who help children with autism. New genetic knowledge and technology have quickly developed over the past 30 years, particularly within the past decade, and have made many optimistic about our ability to explain autism. Among these advances include the sequencing of the human genome (Lander et al., 2001) and the identification of common genetic variants via the HapMap project (International HapMap Consortium, 2005), and the development of cost-efficient genotyping and analysis technologies (Losh, Sullivan, Trembath, & Piven, 2008). Improvement in technology has led to improved visualization of chromosomal abnormality down to the molecular level. The four most common syndromes associated with autism include fragile X syndrome, tuberous sclerosis, 15q duplications, and untreated phenylketonuria (PKU; Costa e Silva, 2008). FXS and 15q duplications are discussed within the context of cytogenetics. TSC is illustrated within the description of linkage analysis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120060/ doi: 10.1007/978-1-4419-8065-6_6 id: cord-272378-umvi0veu author: Subramanian, Subbaya title: Special Issue: MicroRNA Regulation in Health and Disease date: 2019-06-15 words: 2126.0 sentences: 120.0 pages: flesch: 47.0 cache: ./cache/cord-272378-umvi0veu.txt txt: ./txt/cord-272378-umvi0veu.txt summary: MicroRNAs are single-stranded non-coding RNAs that are typically 18-25 nucleotides (nts) in length and are best known for their role in the post-transcriptional regulation of gene expression. However, it is possible that the frequency of MREs in the entire transcriptome of a given cell contributes to the dynamic gene regulatory process by acting as a sponge for mature miRNAs, thus regulating their functional availability. Thus, gene expression regulation is a complex process involving the dynamic interactions between miRNA-mRNA-lncRNA-circRNA. This Special Issue of Genes, entitled "MicroRNA Regulation in Health and Disease" consists of a series of articles spanning the clinical realm from colorectal cancer to pulmonary fibrosis. Somatostatin (SST) analogues were used to control the proliferation and symptoms of neuroendocrine tumors (NETs) in an article by Døssing et al., entitled "Somatostatin Analogue Treatment Primarily Induce miRNA Expression Changes and Up-Regulates Growth Inhibitory miR-7 and miR-148a in Neuroendocrine Cells" [15] . abstract: Our understanding of non-coding RNA has significantly changed based on recent advances in genomics and molecular biology, and their role is recognized to include far more than a link between the sequence of DNA and synthesized proteins [...]. url: https://doi.org/10.3390/genes10060457 doi: 10.3390/genes10060457 id: cord-005216-potmzdfs author: Sun, Dong title: Bioinformatics Analysis of Genes and Pathways of CD11b(+)/Ly6C(intermediate) Macrophages after Renal Ischemia-Reperfusion Injury date: 2018-03-15 words: 3294.0 sentences: 180.0 pages: flesch: 49.0 cache: ./cache/cord-005216-potmzdfs.txt txt: ./txt/cord-005216-potmzdfs.txt summary: Signet analysis showed that Atp5al, Atp5o, Cox4i, Cdc42, Rac2 and Nhp2 were the key genes involved in oxidation-reduction, apoptosis, migration, M1-M2 differentiation, and proliferation of macrophages. The identified DEGs and their enriched pathways investigate factors that may participate in the functional changes of CD 1lb(+)Ly6C(intermediate) macrophages after renal IRI. We used microarray analysis to identify the differentially expressed genes (DEGs) in CD11b + /Ly6C int macrophages of C57BL/6 mice and mice undergoing sham surgery or IRI for 4 h, 24 h or 9 days. To identify functional changes in macrophages, we analysed the role of DEGs in each significant expression profile. To identify the main biological function of CD11b + /Ly6C int macrophages, pathways of genes with similar expression trend were analysed. In this study, we analysed DEGs from CD11b + / Ly6C int macrophages, which were isolated from kidneys of mice undergoing sham surgery (n=2), and IRI at 4 h, 24 h, and 9 days (n=3 per group). abstract: Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), which could induce the poor prognosis. The purpose of this study was to characterize the molecular mechanism of the functional changes of CDllb+/Ly6C(intermediate) macrophages after renal IRI. The gene expression profiles of CDllb+/Ly6Cintermcdiate macrophages of the sham surgery mice, and the mice 4 h, 24 h and 9 days after renal IRI were downloaded from the Gene Expression Omnibus database. Analysis of mRNA expression profiles was conducted to identify differentially expressed genes (DEGs), biological processes and pathways by the series test of cluster. Protein-protein interaction network was constructed and analysed to discover the key genes. A total of 6738 DEGs were identified and assigned to 20 model profiles. DEGs in profile 13 were one of the predominant expression profiles, which are involved in immune cell chemotaxis and proliferation. Signet analysis showed that Atp5al, Atp5o, Cox4i, Cdc42, Rac2 and Nhp2 were the key genes involved in oxidation-reduction, apoptosis, migration, M1-M2 differentiation, and proliferation of macrophages. RPS18 may be an appreciate reference gene as it was stable in macrophages. The identified DEGs and their enriched pathways investigate factors that may participate in the functional changes of CD 1lb(+)Ly6C(intermediate) macrophages after renal IRI. Moreover, the vital gene Nhp2 may involve the polarization of macrophages, which may be a new target to affect the process of AKI url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089064/ doi: 10.1007/s11596-018-1848-7 id: cord-000580-dcid9emx author: Sällman Almén, Markus title: The Dispanins: A Novel Gene Family of Ancient Origin That Contains 14 Human Members date: 2012-02-20 words: 4662.0 sentences: 237.0 pages: flesch: 48.0 cache: ./cache/cord-000580-dcid9emx.txt txt: ./txt/cord-000580-dcid9emx.txt summary: We show that the IFITM genes are a subfamily in a larger family of transmembrane (TM) proteins that we call Dispanins, which refers to a common 2TM structure. We mined 36 eukaryotic species, covering all major eukaryotic groups, and found that the IFITMs form a subfamily in a larger novel family that has ten human members in addition to the four IFITM genes. By combining the results of the phylogenetic analysis and BLAST classification, we created a schematic overview of the organisms'' gene repertoire and a schematic picture of the Dispanin family''s evolutionary history, which suggests that the invertebrate Dispanins share more similarity towards the DSPC and D subfamilies than DSPA and B ( Figure 2 ). We provide evidence that the four IFITM genes together with ten additional human genes, known as TUSC5, TMEM233, PRRT2, TMEM90A, DSPC2, TMEM90B, TMEM91, AC023157, AL160276 and AC068580, form a novel gene family that we call the Dispanins, which refers to the 2TM membrane topology that is common to all identified members. abstract: The Interferon induced transmembrane proteins (IFITM) are a family of transmembrane proteins that is known to inhibit cell invasion of viruses such as HIV-1 and influenza. We show that the IFITM genes are a subfamily in a larger family of transmembrane (TM) proteins that we call Dispanins, which refers to a common 2TM structure. We mined the Dispanins in 36 eukaryotic species, covering all major eukaryotic groups, and investigated their evolutionary history using Bayesian and maximum likelihood approaches to infer a phylogenetic tree. We identified ten human genes that together with the known IFITM genes form the Dispanin family. We show that the Dispanins first emerged in eukaryotes in a common ancestor of choanoflagellates and metazoa, and that the family later expanded in vertebrates where it forms four subfamilies (A–D). Interestingly, we also find that the family is found in several different phyla of bacteria and propose that it was horizontally transferred to eukaryotes from bacteria in the common ancestor of choanoflagellates and metazoa. The bacterial and eukaryotic sequences have a considerably conserved protein structure. In conclusion, we introduce a novel family, the Dispanins, together with a nomenclature based on the evolutionary origin. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282796/ doi: 10.1371/journal.pone.0031961 id: cord-003898-y6zpvw84 author: Tan, Kai Sen title: RNA Sequencing of H3N2 Influenza Virus-Infected Human Nasal Epithelial Cells from Multiple Subjects Reveals Molecular Pathways Associated with Tissue Injury and Complications date: 2019-08-27 words: 7671.0 sentences: 386.0 pages: flesch: 44.0 cache: ./cache/cord-003898-y6zpvw84.txt txt: ./txt/cord-003898-y6zpvw84.txt summary: title: RNA Sequencing of H3N2 Influenza Virus-Infected Human Nasal Epithelial Cells from Multiple Subjects Reveals Molecular Pathways Associated with Tissue Injury and Complications The aim of this study was to utilize RNA sequencing (RNAseq) technology to not only reveal the hNEC responses (from multiple individuals) against influenza infection, but also to identify those genes with high magnitude changes to serve as potential reference markers of the innate responses of influenza infection. After deriving the transcriptomes by RNAseq, we then further investigated whether the changes in expression of genes resulted in alterations in secretory cytokines and chemokines early in the infection of hNECs. Initially, we detected significant reductions in multiple cytokines at 8 hpi, with the exception of IL-15 which was increased ( Figure S2 ). In conclusion, RNAseq technology allowed us to accurately quantify the magnitude of gene expression changes, as well as the relevant enriched pathways during H3N2 influenza virus infection of hNECs, which can serve as a baseline for future clinical studies. abstract: The human nasal epithelium is the primary site of exposure to influenza virus, the initiator of host responses to influenza and the resultant pathologies. Influenza virus may cause serious respiratory infection resulting in major complications, as well as severe impairment of the airways. Here, we elucidated the global transcriptomic changes during H3N2 infection of human nasal epithelial cells from multiple individuals. Using RNA sequencing, we characterized the differentially-expressed genes and pathways associated with changes occurring at the nasal epithelium following infection. We used in vitro differentiated human nasal epithelial cell culture model derived from seven different donors who had no concurrent history of viral infections. Statistical analysis highlighted strong transcriptomic signatures significantly associated with 24 and 48 h after infection, but not at the earlier 8-h time point. In particular, we found that the influenza infection induced in the nasal epithelium early and altered responses in interferon gamma signaling, B-cell signaling, apoptosis, necrosis, smooth muscle proliferation, and metabolic alterations. These molecular events initiated at the infected nasal epithelium may potentially adversely impact the airway, and thus the genes we identified could serve as potential diagnostic biomarkers or therapeutic targets for influenza infection and associated disease management. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770044/ doi: 10.3390/cells8090986 id: cord-304913-qb9zeazk author: Thibivilliers, Sandra title: Generation of Phaseolus vulgaris ESTs and investigation of their regulation upon Uromyces appendiculatus infection date: 2009-04-27 words: 6680.0 sentences: 344.0 pages: flesch: 52.0 cache: ./cache/cord-304913-qb9zeazk.txt txt: ./txt/cord-304913-qb9zeazk.txt summary: RESULTS: A subtractive bean cDNA library composed of 10,581 unisequences was constructed and enriched in sequences regulated by either bean rust race 41, a virulent strain, or race 49, an avirulent strain on cultivar Early Gallatin carrying the resistance gene Ur-4. Plant gene expression was similar for both race 41 and 49 during the first 48 hours of the infection process but varied significantly at the later time points (72–96 hours after inoculation) mainly due to the presence of the Avr4 gene in the race 49 leading to a hypersensitive response in the bean plants. The stability of the expression level of the 3 remaining genes, TC127, cons6 and cons7 was evaluated by qRT-PCR on cDNAs from bean uninfected or infected with bean rust race 41 or 49 at 6, 12, 24, 48, 72, and 96 hours after inoculation (HAI). abstract: BACKGROUND: Phaseolus vulgaris (common bean) is the second most important legume crop in the world after soybean. Consequently, yield losses due to fungal infection, like Uromyces appendiculatus (bean rust), have strong consequences. Several resistant genes were identified that confer resistance to bean rust infection. However, the downstream genes and mechanisms involved in bean resistance to infection are poorly characterized. RESULTS: A subtractive bean cDNA library composed of 10,581 unisequences was constructed and enriched in sequences regulated by either bean rust race 41, a virulent strain, or race 49, an avirulent strain on cultivar Early Gallatin carrying the resistance gene Ur-4. The construction of this library allowed the identification of 6,202 new bean ESTs, significantly adding to the available sequences for this plant. Regulation of selected bean genes in response to bean rust infection was confirmed by qRT-PCR. Plant gene expression was similar for both race 41 and 49 during the first 48 hours of the infection process but varied significantly at the later time points (72–96 hours after inoculation) mainly due to the presence of the Avr4 gene in the race 49 leading to a hypersensitive response in the bean plants. A biphasic pattern of gene expression was observed for several genes regulated in response to fungal infection. CONCLUSION: The enrichment of the public database with over 6,000 bean ESTs significantly adds to the genomic resources available for this important crop plant. The analysis of these genes in response to bean rust infection provides a foundation for further studies of the mechanism of fungal disease resistance. The expression pattern of 90 bean genes upon rust infection shares several features with other legumes infected by biotrophic fungi. This finding suggests that the P. vulgaris-U. appendiculatus pathosystem could serve as a model to explore legume-rust interaction. url: https://www.ncbi.nlm.nih.gov/pubmed/19397807/ doi: 10.1186/1471-2229-9-46 id: cord-023928-9a1w174h author: Thomas, Neal J. title: Genetic Predisposition to Critical Illness in the Pediatric Intensive Care Unit date: 2011-12-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Much progress has been made in the past decade in the understanding of the genetic contribution to the development of human disease in general, and critical care illness specifically. With the mapping of the human genome and on-going mapping of genetic polymorphisms and haplotypes in humans, the field of critical care is now in prime position to study the impact of genetics on common illnesses that affect children who require critical care, to examine how differences of the host defense response lead to variable outcomes in outwardly appearing similar disease states, and to study how genetic differences in response to therapy will help practitioners tailor therapeutic interventions to an individual child’s genetic composition. While we are still years away from true individualized medicine, we are now closer than ever to understanding why two might children respond to the same environmental insult in vastly different ways. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178837/ doi: 10.1007/978-0-85729-923-9_11 id: cord-322286-2de6r1h6 author: Vandewege, Michael W title: Positive Selection and Gene Expression Analyses from Salivary Glands Reveal Discrete Adaptations within the Ecologically Diverse Bat Family Phyllostomidae date: 2020-07-22 words: 6211.0 sentences: 344.0 pages: flesch: 46.0 cache: ./cache/cord-322286-2de6r1h6.txt txt: ./txt/cord-322286-2de6r1h6.txt summary: title: Positive Selection and Gene Expression Analyses from Salivary Glands Reveal Discrete Adaptations within the Ecologically Diverse Bat Family Phyllostomidae We sequenced expressed transcripts from phyllostomid salivary glands and found strong signals of selection among immune-related genes. We sequenced the SMG transcriptomes of nine phyllostomid bats representing different subfamilies and different diets, and through analysis of orthologs characterized how selection on coding sequence and expression differences have shaped SMGs. Nine species from seven out of the 11 recognized subfamilies were chosen to maximize representation of the phylogenetic and dietary diversity of Phyllostomidae ( fig. After correcting for FDR, we found 53 genes where models of evolution allowing positive selection were significantly better fit to the data than neutrality in both M2a and M8 tests (supplementary table S2, Supplementary Material online). Moreover, given that some Golgi body-related genes appeared under selection in all branch-site tests, this organelle played some role in the adaptive radiation of phyllostomids. abstract: The leaf-nosed bats (Phyllostomidae) are outliers among chiropterans with respect to the unusually high diversity of dietary strategies within the family. Salivary glands, owing to their functions and high ultrastructural variability among lineages, are proposed to have played an important role during the phyllostomid radiation. To identify genes underlying salivary gland functional diversification, we sequenced submandibular gland transcriptomes from phyllostomid species representative of divergent dietary strategies. From the assembled transcriptomes, we performed an array of selection tests and gene expression analyses to identify signatures of adaptation. Overall, we identified an enrichment of immunity-related gene ontology terms among 53 genes evolving under positive selection. Lineage-specific selection tests revealed several endomembrane system genes under selection in the vampire bat. Many genes that respond to insulin were under selection and differentially expressed genes pointed to modifications of amino acid synthesis pathways in plant-visitors. Results indicate salivary glands have diversified in various ways across a functional diverse clade of mammals in response to niche specializations. url: https://doi.org/10.1093/gbe/evaa151 doi: 10.1093/gbe/evaa151 id: cord-016095-jop2rx61 author: Vignais, Pierre V. title: Challenges for Experimentation on Living Beings at the Dawn of the 21(st) Century date: 2010-06-08 words: 42843.0 sentences: 1503.0 pages: flesch: 43.0 cache: ./cache/cord-016095-jop2rx61.txt txt: ./txt/cord-016095-jop2rx61.txt summary: Instead of setting out to discover unknown mechanisms by analyzing effects that are dependent on specific causes, with some uncertainty as to the possible success of the enterprise being undertaken, which is the foundation stone of the Bernardian paradigm of the experimental method, many current research projects give themselves achievable and programmable objectives that depend upon the means available to them: sequencing of genomes with a view to comparing them, recognition of sequence similarities in proteins coded for by genes belonging to different species, with the aim of putting together phylogenetic trees, synthesis of interesting proteins in transgenic animals and plants, analysis of the three-dimensional structure of proteins, in order to find sites that are likely to fix medicinal substances, and synthesis of molecular species able to recognize pathogenic targets. abstract: “We can talk endlessly about moral progress, about social progress, about poetic progress, about progress made in happiness; nevertheless, there is a type of progress that defies any discussion, and that is scientific progress, as soon as we judge it within the hierarchy of knowledge, from a specifically intellectual point of view.” url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120277/ doi: 10.1007/978-90-481-3767-1_5 id: cord-264884-ydkigome author: Villarreal, Luis P. title: The Widespread Evolutionary Significance of Viruses date: 2008-07-05 words: 23138.0 sentences: 1203.0 pages: flesch: 47.0 cache: ./cache/cord-264884-ydkigome.txt txt: ./txt/cord-264884-ydkigome.txt summary: For example, common structural motifs from phage to eukaryotic DNA viruses (T4 and herpesvirus) suggest very ancient links in virus evolution that span all domains of life (see below). On an evolutionary time-scale, the majority of viral lineages tend to exist as species-specifi c persistent (aka temperate, latent, and chronic) infections in which individual hosts will be colonized by mostly silent (asymptomatic) viruses for the duration of their life . It has distinct genetic, fi tness, and evolutionary characteristics that require intimate, host (tissue)-specifi c viral strategies and precise gene functions to attain stable maintenance in the presence of immunity and to allow biologically controlled reactivation. Thus, the phycodnaviruses appear to represent a basal but diverse viral lineage that has both acute and persistent lifestyle and have some clear relationships to most large eukaryotic DNA viruses and many phage. abstract: In the last 30 years, the study of virus evolution has undergone a transformation. Originally concerned with disease and its emergence, virus evolution had not been well integrated into the general study of evolution. This chapter reviews the developments that have brought us to this new appreciation for the general significance of virus evolution to all life. We now know that viruses numerically dominate all habitats of life, especially the oceans. Theoretical developments in the 1970s regarding quasispecies, error rates, and error thresholds have yielded many practical insights into virus–host dynamics. The human diseases of HIV-1 and hepatitis C virus cannot be understood without this evolutionary framework. Yet recent developments with poliovirus demonstrate that viral fitness can be the result of a consortia, not one fittest type, a basic Darwinian concept in evolutionary biology. Darwinian principles do apply to viruses, such as with Fisher population genetics, but other features, such as reticulated and quasispecies-based evolution distinguish virus evolution from classical studies. The available phylogenetic tools have greatly aided our analysis of virus evolution, but these methods struggle to characterize the role of virus populations. Missing from many of these considerations has been the major role played by persisting viruses in stable virus evolution and disease emergence. In many cases, extreme stability is seen with persisting RNA viruses. Indeed, examples are known in which it is the persistently infected host that has better survival. We have also recently come to appreciate the vast diversity of phage (DNA viruses) of prokaryotes as a system that evolves by genetic exchanges across vast populations (Chapter 10). This has been proposed to be the “big bang” of biological evolution. In the large DNA viruses of aquatic microbes we see surprisingly large, complex and diverse viruses. With both prokaryotic and eukaryotic DNA viruses, recombination is the main engine of virus evolution, and virus host co-evolution is common, although not uniform. Viral emergence appears to be an unending phenomenon and we can currently witness a selective sweep by retroviruses that infect and become endogenized in koala bears. url: https://api.elsevier.com/content/article/pii/B9780123741530000217 doi: 10.1016/b978-0-12-374153-0.00021-7 id: cord-001541-5d64esp4 author: Walker, Peter J. title: Evolution of Genome Size and Complexity in the Rhabdoviridae date: 2015-02-13 words: 9157.0 sentences: 398.0 pages: flesch: 45.0 cache: ./cache/cord-001541-5d64esp4.txt txt: ./txt/cord-001541-5d64esp4.txt summary: We demonstrate that remarkable changes in genome size and complexity have occurred in rhabdoviruses in a clade-specific manner, primarily by extension and insertion of additional transcriptional units in the structural protein gene junctions, followed by occasional losses. All rhabdovirus genomes contained the five canonical structural protein genes (N, P, M, G and L); however, there was remarkable diversity in the number and location of other long ORFs. Across the data set, we identified 179 additional ORFs 180 nt in length of which 142 shared no detectable protein sequence similarity with any other protein in our data set or with those in public databases (S2 Table) . Interestingly, although substantial variation in the length of gene junctions was observed in several genera (including ephemeroviruses and lyssaviruses), most variation in genome size occurred as the result of the presence of new, non-canonical ORFs in the regions between the structural protein genes (Table 1) . abstract: RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334499/ doi: 10.1371/journal.ppat.1004664 id: cord-280897-el7bdkcf author: Wang, Hai-Fang title: Relationship between mRNA stability and intron presence date: 2007-03-02 words: 3037.0 sentences: 169.0 pages: flesch: 55.0 cache: ./cache/cord-280897-el7bdkcf.txt txt: ./txt/cord-280897-el7bdkcf.txt summary: By analyzing the genome-wide data of mRNA stability published by someone previously, we found that human intron-containing genes have more stable mRNAs than intronless genes, and the Arabidopsis thaliana genes with the most unstable mRNAs have fewer introns than other genes in the genome. [10] found that insertion of a 138-bp intron into SARS-CoV spike protein gene can enhance the protein expression in mammalian cells, but the mRNAs exhibited similar decay rates as the intronless control mRNA. As a stable mRNA can be measured by lower decay rate or longer half-life, our analyses of different sources of data consistently showed that the mRNAs of intron-containing genes are more stable than those of intronless genes in human cells. We found that the mRNAs of intronless genes are less stable (i.e. have higher decay rates or shorter half-lives) than the intron-containing genes with similar mRNA lengths and functions (Fig. 1) . abstract: Abstract Introns were found to enhance almost every steps of gene expression except increasing mRNA stability. By analyzing the genome-wide data of mRNA stability published by someone previously, we found that human intron-containing genes have more stable mRNAs than intronless genes, and the Arabidopsis thaliana genes with the most unstable mRNAs have fewer introns than other genes in the genome. After controlling for mRNA length, we found mRNA stability is still positively correlated with intron number in human intron-containing genes. But in yeast Saccharomyces cerevisiae, two different datasets on mRNA half-life gave conflicting results. The components of messenger ribonucleoprotein particles recruited during intron splicing may be retained in cytoplasmic mRNPs and act as signals of mRNA stability or simply insulators to avoid mRNA degradation. url: https://api.elsevier.com/content/article/pii/S0006291X06028592 doi: 10.1016/j.bbrc.2006.12.184 id: cord-331592-l44rupmi author: Wang, Tzu-Hao title: Microarray Analysis of Gene Expression of Cancer to Guide the Use of Chemotherapeutics date: 2007-09-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Summary The beauty of microarray analysis of gene expression (MAGE) is that it can be used to discover some genes that were previously thought to be unrelated to a physiologic or pathologic event. During the period from 1999 to 2007, applications of MAGE in cancer investigation have shifted from molecular profiling, identifying previously undiscovered cancer types, predicting outcomes of cancer patients, revealing metastasis signatures of solid tumors, to guiding the use of therapeutics. The roles of cancer genomic signatures have evolved through three phases. In the first phase, genomic signatures were described in stored cancer specimens and dubbed as molecular portraits of cancer. When gene expression profiles were carefully correlated with sufficient clinical information of cancer patients, new subgroups of cancers with distinct outcomes were revealed. In studies of the second phase, validation of cancer signatures was emphasized and commonly performed with independent groups of cancer specimens or independent data set. In the third phase, cancer genomic signatures have been further expanded beyond depicting the molecular portrait of cancer to predicting patient outcomes and guiding the use of cancer therapeutics. Cancer genomic signatures have become an essential part of a new generation of cancer clinical trials. It is advocated that, in future clinical trials of cancer therapy, the cancer specimens of each participant should be tested for currently available predictor genomic signatures, so that the most effective treatment with the least adverse effects for each patient can be identified. Then, participants can be triaged to an appropriate study group. url: https://www.ncbi.nlm.nih.gov/pubmed/17962100/ doi: 10.1016/s1028-4559(08)60024-8 id: cord-104073-vsa5y7ip author: Warner, Emily F. title: Cross kingdom analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets to ameliorate fungal pathogenicity? date: 2020-09-23 words: 3218.0 sentences: 207.0 pages: flesch: 54.0 cache: ./cache/cord-104073-vsa5y7ip.txt txt: ./txt/cord-104073-vsa5y7ip.txt summary: PQS in the clinically important pathogens Aspergillus fumigatus, Cryptococcus neoformans, and Candida albicans were located within genes (particularly coding regions), mRNA, repeat regions, mobile elements, tRNA, ncRNA, rRNA, and the centromere. Finally, PQS were found in over 100 genes associated with virulence, drug resistance, or key biological processes in these pathogenic fungi and were found in genes which were highly upregulated during germination, hypoxia, oxidative stress, iron limitation, and in biofilms. Using a computational approach, we identified putative quadruplex-forming 30 sequences (PQS) in 1362 genomes across the fungal kingdom and explored their potential 31 involvement in virulence, drug resistance, and pathogenicity. Using a computational approach, we identified putative quadruplex-forming 30 sequences (PQS) in 1362 genomes across the fungal kingdom and explored their potential 31 involvement in virulence, drug resistance, and pathogenicity. PQS in the 35 clinically important pathogens Aspergillus fumigatus, Cryptococcus neoformans, and Candida 36 albicans were located within genes (particularly coding regions), mRNA, repeat regions, 37 abstract: Fungi contribute to upwards of 1.5 million human deaths annually, are involved in the spoilage of up to a third of food crops, and have a devastating effect on plant and animal biodiversity. Moreover, this already significant issue is exacerbated by a rise in antifungal resistance and a critical requirement for novel drug targets. Quadruplexes are four-stranded secondary structures in nucleic acids which can regulate processes such as transcription, translation, replication, and recombination. They are also found in genes linked to virulence in microbes, and quadruplex-binding ligands have been demonstrated to eliminate drug resistant pathogens. Using a computational approach, we identified putative quadruplex-forming sequences (PQS) in 1362 genomes across the fungal kingdom and explored their potential involvement in virulence, drug resistance, and pathogenicity. Here we present the largest analysis of PQS in fungi and identified significant heterogeneity of these sequences throughout phyla, genera, and species. Moreover, PQS were genetically conserved. Notably, loss of PQS in cryptococci and aspergilli was associated with pathogenicity. PQS in the clinically important pathogens Aspergillus fumigatus, Cryptococcus neoformans, and Candida albicans were located within genes (particularly coding regions), mRNA, repeat regions, mobile elements, tRNA, ncRNA, rRNA, and the centromere. Genes containing PQS in these organisms were found to be primarily associated with metabolism, nucleic acid binding, transporter activity, and protein modification. Finally, PQS were found in over 100 genes associated with virulence, drug resistance, or key biological processes in these pathogenic fungi and were found in genes which were highly upregulated during germination, hypoxia, oxidative stress, iron limitation, and in biofilms. Taken together, quadruplexes in fungi could present interesting novel targets to ameliorate fungal virulence and overcome drug resistance. url: https://doi.org/10.1101/2020.09.23.310581 doi: 10.1101/2020.09.23.310581 id: cord-295019-8tf8ah6g author: Weber, Wilfried title: Emerging biomedical applications of synthetic biology date: 2011-11-29 words: 9511.0 sentences: 475.0 pages: flesch: 36.0 cache: ./cache/cord-295019-8tf8ah6g.txt txt: ./txt/cord-295019-8tf8ah6g.txt summary: Synthetic mammalian transcription circuits consisting of a chimeric small-molecule-responsive transcription factor and a cognate synthetic promoter were originally designed for future gene-based therapies, and the aim was to adjust therapeutic transgene expression in mammalian cells in response to a pharmacologically active substance 34, 47, 49, 91 . When mammalian cells that are transgenic for the screening circuit are exposed to a compound library, they detect and modulate reporter gene expression in the presence of a non-toxic, cellpermeable and bioavailable molecule that has a classspecific core structure and corresponding drug activity (for example, antibiotic activity) (FIG. The availability of compact RNA sensor-actuators that are easy to design and to alter and that control transgene expression in response to intracellular levels of key proteins may also improve the ability to link metabolic disease states with gene-based therapeutic interventions. abstract: Synthetic biology aims to create functional devices, systems and organisms with novel and useful functions on the basis of catalogued and standardized biological building blocks. Although they were initially constructed to elucidate the dynamics of simple processes, designed devices now contribute to the understanding of disease mechanisms, provide novel diagnostic tools, enable economic production of therapeutics and allow the design of novel strategies for the treatment of cancer, immune diseases and metabolic disorders, such as diabetes and gout, as well as a range of infectious diseases. In this Review, we cover the impact and potential of synthetic biology for biomedical applications. url: https://www.ncbi.nlm.nih.gov/pubmed/22124480/ doi: 10.1038/nrg3094 id: cord-301218-zsp5sh9o author: Weeraratna, Ashani T. title: Gene Expression Profiling: From Microarrays to Medicine date: 2004 words: 6384.0 sentences: 284.0 pages: flesch: 35.0 cache: ./cache/cord-301218-zsp5sh9o.txt txt: ./txt/cord-301218-zsp5sh9o.txt summary: One of the challenges in array data analysis is to distinguish specific physiologic changes in gene expression from the noise and variability inherent within the microarray technique. If an analysis technique can be developed and validated that can identify the genes that undergo a significant change in expression and remove those that do not, it could alter microarray design and construction in favor of smaller focused arrays that query only biologically relevant genes. Presently, most large-scale projects examining genome-wide SNP expression are based on differential hybridization affinity using either spotted or in situ synthesized oligonucleotide arrays (45, 46) or utilize mass spectroscopy for genotype analysis (7, 47) . In addition, potential usefulness of microarray-derived gene expression data has been shown in several recent studies of lymphoma, leukemia (25, 50) , and multiple myeloma (51) where modeling techniques that incorporate outcome and drug response during treatment were used to define tumor types or patient groups and to suggest rational targets for drug therapy or development. abstract: With the mapping of the human genome comes the ability to identify genes of interest in specific diseases and the pathways involved therein. Laboratory technology has evolved in parallel, providing us with the ability to assay thousands of these genes at once, a technique known as microarray analysis. The main #x003Fion that this type of technology raises is how we can apply this powerful technology to clinical medicine. Recently, advances in data analysis, as well as standardization of the technology, have allowed us to examine this #x003Fion, and indeed a few clinical trials currently being performed include microarrays as part of their protocol. In this review we outline the microarray technique and describe these types of studies in further detail. url: https://www.ncbi.nlm.nih.gov/pubmed/15114052/ doi: 10.1023/b:joci.0000025443.44833.1d id: cord-332006-if46jycd author: Whitehead, Kathryn A. title: Knocking down barriers: advances in siRNA delivery date: 2009 words: 6655.0 sentences: 391.0 pages: flesch: 42.0 cache: ./cache/cord-332006-if46jycd.txt txt: ./txt/cord-332006-if46jycd.txt summary: Three years later, Tuschl and co-workers published their celebrated proof-of-principle experiment demonstrating that synthetic small interfering RNA (siRNA) could achieve sequence-specific gene knockdown in a mammalian cell line 2 . Toxicity of certain cationic lipid particles has been reported both in vitro and in vivo [76] [77] [78] , and certain synthetic agents have been found to induce a gene signature of their own that might increase the off-target effects of siRNA 79, 80 . Tumour growth in a mouse model of metastatic Ewing''s sarcoma was shown to be inhibited by the systemic delivery of nanoparticles formed by cyclodextrin, the targeting ligand transferrin, and siRNA specific for the EWS-FLI1 fusion gene commonly associated with the condition. Toxicogenomics of non-viral drug delivery systems for RNAi: potential impact on siRNA-mediated gene silencing activity and specificity abstract: In the 10 years that have passed since the Nobel prize-winning discovery of RNA interference (RNAi), billions of dollars have been invested in the therapeutic application of gene silencing in humans. Today, there are promising data from ongoing clinical trials for the treatment of age-related macular degeneration and respiratory syncytial virus. Despite these early successes, however, the widespread use of RNAi therapeutics for disease prevention and treatment requires the development of clinically suitable, safe and effective drug delivery vehicles. Here, we provide an update on the progress of RNAi therapeutics and highlight novel synthetic materials for the encapsulation and intracellular delivery of nucleic acids. url: https://www.ncbi.nlm.nih.gov/pubmed/19180106/ doi: 10.1038/nrd2742 id: cord-302047-vv5gpldi author: Willemsen, Anouk title: On the stability of sequences inserted into viral genomes date: 2019-11-14 words: 12557.0 sentences: 598.0 pages: flesch: 43.0 cache: ./cache/cord-302047-vv5gpldi.txt txt: ./txt/cord-302047-vv5gpldi.txt summary: Viruses are widely used as vectors for heterologous gene expression in cultured cells or natural hosts, and therefore a large number of viruses with exogenous sequences inserted into their genomes have been engineered. Viruses genera covered in relevant studies Conclusions of this review All viruses • Inserted sequences are often unstable and rapidly lost upon passaging of an engineered virus • The position at which a sequence is integrated in the genome can be important for stability • Sequence stability is not an intrinsic property of genomes because demographic parameters, such as population size and bottleneck size, can have important effects on sequence stability • The multiplicity of cellular infection affects sequence stability, and can in some cases directly affect whether there is selection for deletion variants • Deletions are not the only class of mutations that can reduce the cost of inserted sequences, although they are the most common I: dsDNA abstract: Viruses are widely used as vectors for heterologous gene expression in cultured cells or natural hosts, and therefore a large number of viruses with exogenous sequences inserted into their genomes have been engineered. Many of these engineered viruses are viable and express heterologous proteins at high levels, but the inserted sequences often prove to be unstable over time and are rapidly lost, limiting heterologous protein expression. Although virologists are aware that inserted sequences can be unstable, processes leading to insert instability are rarely considered from an evolutionary perspective. Here, we review experimental work on the stability of inserted sequences over a broad range of viruses, and we present some theoretical considerations concerning insert stability. Different virus genome organizations strongly impact insert stability, and factors such as the position of insertion can have a strong effect. In addition, we argue that insert stability not only depends on the characteristics of a particular genome, but that it will also depend on the host environment and the demography of a virus population. The interplay between all factors affecting stability is complex, which makes it challenging to develop a general model to predict the stability of genomic insertions. We highlight key questions and future directions, finding that insert stability is a surprisingly complex problem and that there is need for mechanism-based, predictive models. Combining theoretical models with experimental tests for stability under varying conditions can lead to improved engineering of viral modified genomes, which is a valuable tool for understanding genome evolution as well as for biotechnological applications, such as gene therapy. url: https://www.ncbi.nlm.nih.gov/pubmed/31741748/ doi: 10.1093/ve/vez045 id: cord-352190-1987sfyz author: Xia, Hongyue title: Adaptive Evolution of Feline Coronavirus Genes Based on Selection Analysis date: 2020-08-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: PURPOSE: We investigated sequences of the feline coronaviruses (FCoV), which include feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV), from China and other countries to gain insight into the adaptive evolution of this virus. METHODS: Ascites samples from 31 cats with suspected FIP and feces samples from 8 healthy cats were screened for the presence of FCoV. Partial viral genome sequences, including parts of the nsp12-nsp14, S, N, and 7b genes, were obtained and aligned with additional sequences obtained from the GenBank database. Bayesian phylogenetic analysis was conducted, and the possibility of recombination within these sequences was assessed. Analysis of the levels of selection pressure experienced by these sequences was assessed using methods on both the PAML and Datamonkey platforms. RESULTS: Of the 31 cats investigated, two suspected FIP cats and one healthy cat tested positive for FCoV. Phylogenetic analysis showed that all of the sequences from mainland China cluster together with a few sequences from the Netherlands as a distinct clade when analyzed with FCoV sequences from other countries. Fewer than 3 recombination breakpoints were detected in the nsp12-nsp14, S, N, and 7b genes, suggesting that analyses for positive selection could be conducted. A total of 4, 12, 4, and 4 positively selected sites were detected in the nsp12-nsp14, S, N, and 7b genes, respectively, with the previously described site 245 of the S gene, which distinguishes FIPV from FECV, being a positive selection site. Conversely, 106, 168, 25, and 17 negative selection sites in the nsp12-14, S, N, and 7b genes, respectively, were identified. CONCLUSION: Our study provides evidence that the FCoV genes encoding replicative, entry, and virulence proteins potentially experienced adaptive evolution. A greater number of sites in each gene experienced negative rather than positive selection, which suggests that most of the protein sequence must be conservatively maintained for virus survival. A few of the sites showing evidence of positive selection might be associated with the more severe pathology of FIPV or help these viruses survive other harmful conditions. url: https://www.ncbi.nlm.nih.gov/pubmed/32923488/ doi: 10.1155/2020/9089768 id: cord-298131-zolwjl9u author: Xiao, Shuqi title: Understanding PRRSV Infection in Porcine Lung Based on Genome-Wide Transcriptome Response Identified by Deep Sequencing date: 2010-06-29 words: 9349.0 sentences: 429.0 pages: flesch: 39.0 cache: ./cache/cord-298131-zolwjl9u.txt txt: ./txt/cord-298131-zolwjl9u.txt summary: Upregulation expression of virus-induced pro-inflammatory cytokines, chemokines, adhesion molecules and inflammatory enzymes and inflammatory cells, antibodies, complement activation were likely to result in the development of inflammatory responses during N-PRRSV infection processes. To investigate the regulation of the host response to the N-PRRSV virus, we considered the global gene expression profiles in lungs using Solexa/Illumina''s DGE system, a tag-based transcriptome sequencing method. From the data presented in the paper, a model for the relationship between pulmonary gene expression profiles and infection pathology can be surmised in Figure 7 , N-PRRSV virus replicates and spreads by subverting host innate immune response and hijacking host lipid metabolism as well as inducing an antiapoptotic and anti-inflammatory state, as indicated by suppression expression of SPI IFN, IFN-a, down-regulation expression of proapoptotic genes for BAK, APR-1, SARP3, high levels expression of genes involved in lipid metabolism, such as APOE, LDLB, PIK3C3, anti-apoptotic genes for MCL1, BCL2A1, CHFR, ADM, NFKB, IL10, and anti-inflammatory molecule PGE2 as well as CD163. abstract: Porcine reproductive and respiratory syndrome (PRRS) has been one of the most economically important diseases affecting swine industry worldwide and causes great economic losses each year. PRRS virus (PRRSV) replicates mainly in porcine alveolar macrophages (PAMs) and dendritic cells (DCs) and develops persistent infections, antibody-dependent enhancement (ADE), interstitial pneumonia and immunosuppression. But the molecular mechanisms of PRRSV infection still are poorly understood. Here we report on the first genome-wide host transcriptional responses to classical North American type PRRSV (N-PRRSV) strain CH 1a infection using Solexa/Illumina's digital gene expression (DGE) system, a tag-based high-throughput transcriptome sequencing method, and analyse systematically the relationship between pulmonary gene expression profiles after N-PRRSV infection and infection pathology. Our results suggest that N-PRRSV appeared to utilize multiple strategies for its replication and spread in infected pigs, including subverting host innate immune response, inducing an anti-apoptotic and anti-inflammatory state as well as developing ADE. Upregulation expression of virus-induced pro-inflammatory cytokines, chemokines, adhesion molecules and inflammatory enzymes and inflammatory cells, antibodies, complement activation were likely to result in the development of inflammatory responses during N-PRRSV infection processes. N-PRRSV-induced immunosuppression might be mediated by apoptosis of infected cells, which caused depletion of immune cells and induced an anti-inflammatory cytokine response in which they were unable to eradicate the primary infection. Our systems analysis will benefit for better understanding the molecular pathogenesis of N-PRRSV infection, developing novel antiviral therapies and identifying genetic components for swine resistance/susceptibility to PRRS. url: https://www.ncbi.nlm.nih.gov/pubmed/20614006/ doi: 10.1371/journal.pone.0011377 id: cord-352200-i05h8csb author: Xu, Yi title: Transcriptome and Comparative Gene Expression Analysis of Sogatella furcifera (Horváth) in Response to Southern Rice Black-Streaked Dwarf Virus date: 2012-04-27 words: 5286.0 sentences: 278.0 pages: flesch: 47.0 cache: ./cache/cord-352200-i05h8csb.txt txt: ./txt/cord-352200-i05h8csb.txt summary: title: Transcriptome and Comparative Gene Expression Analysis of Sogatella furcifera (Horváth) in Response to Southern Rice Black-Streaked Dwarf Virus METHODOLOGY/PRINCIPAL FINDINGS: By de novo transcriptome assembling and massive parallel pyrosequencing, we constructed two transcriptomes of WBPH and profiled the alternation of gene expression in response to SRBSDV infection in transcriptional level. As a whole, 81388 distinct unigenes have been identified and the results indicated that SRBSDV infection can potentially perturb primary metabolism and the ubiquitin-proteasome pathway of WBPH and activate immune regulatory systems, such as RNA interfering, autophagy and antimicrobial peptide production. However, some unigenes were obtained only from viruliferous or non-viruliferous samples (data not shown) and we believe these differences may be caused by distinctions that arise from long-term ecological adaptation to virus infection. In addition, GO analysis also showed a similar distribution of gene functions for non-viruliferous and viruliferous WBPH (Figure 4 ), indicating that the number of genes expressed in each GO category was not significantly affected by SRBSDV infection. abstract: BACKGROUND: The white backed planthopper (WBPH), Sogatella furcifera (Horváth), causes great damage to many crops by direct feeding or transmitting plant viruses. Southern rice black-streaked dwarf virus (SRBSDV), transmitted by WBPH, has become a great threat to rice production in East Asia. METHODOLOGY/PRINCIPAL FINDINGS: By de novo transcriptome assembling and massive parallel pyrosequencing, we constructed two transcriptomes of WBPH and profiled the alternation of gene expression in response to SRBSDV infection in transcriptional level. Over 25 million reads of high-quality DNA sequences and 81388 different unigenes were generated using Illumina technology from both viruliferous and non-viruliferous WBPH. WBPH has a very similar gene ontological distribution to other two closely related rice planthoppers, Nilaparvata lugens and Laodelphax striatellus. 7291 microsatellite loci were also predicted which could be useful for further evolutionary analysis. Furthermore, comparative analysis of the two transcriptomes generated from viruliferous and non-viruliferous WBPH provided a list of candidate transcripts that potentially were elicited as a response to viral infection. Pathway analyses of a subset of these transcripts indicated that SRBSDV infection may perturb primary metabolism and the ubiquitin-proteasome pathways. In addition, 5.5% (181 out of 3315) of the genes in cell cytoskeleton organization pathway showed obvious changes. Our data also demonstrated that SRBSDV infection activated the immunity regulatory systems of WBPH, such as RNA interference, autophagy and antimicrobial peptide production. CONCLUSIONS/SIGNIFICANCE: We employed massively parallel pyrosequencing to collect ESTs from viruliferous and non-viruliferous samples of WBPH. 81388 different unigenes have been obtained. We for the first time described the direct effects of a Reoviridae family plant virus on global gene expression profiles of its insect vector using high-throughput sequencing. Our study will provide a road map for future investigations of the fascinating interactions between Reoviridae viruses and their insect vectors, and provide new strategies for crop protection. url: https://www.ncbi.nlm.nih.gov/pubmed/22558400/ doi: 10.1371/journal.pone.0036238 id: cord-266521-vovas81d author: Yokobayashi, Yohei title: Aptamer-based and aptazyme-based riboswitches in mammalian cells date: 2019-06-22 words: 3228.0 sentences: 155.0 pages: flesch: 43.0 cache: ./cache/cord-266521-vovas81d.txt txt: ./txt/cord-266521-vovas81d.txt summary: In this report, recent advances in synthetic riboswitches that function in mammalian cells are reviewed focusing on the regulatory mechanisms they exploit such as mRNA degradation, microRNA processing, and programmed ribosomal frameshifting. In this report, recent advances in synthetic riboswitches that function in mammalian cells are reviewed focusing on the regulatory mechanisms they exploit such as mRNA degradation, microRNA processing, and programmed ribosomal frameshifting. While the ribozyme was not specifically regulated by a small molecule via an aptamer, this work paved the way for the subsequent riboswitches that employ allosterically regulated ribozymes (aptazymes) embedded in the 5 0 and/or 3 0 UTR to chemically regulate gene expression in mammalian cells (Figure 1a ) [13] [14] [15] [16] . A new mode of engineered RNA-based gene regulation in mammalian cells was demonstrated by controlling the accessibility of a miRNA target site by aptamer-ligand interaction abstract: Molecular recognition by RNA aptamers has been exploited to control gene expression in response to small molecules in mammalian cells. These mammalian synthetic riboswitches offer attractive features such as small genetic size and lower risk of immunological complications compared to protein-based transcriptional gene switches. The diversity of gene regulatory mechanisms that involve RNA has also inspired the development of mammalian riboswitches that harness various regulatory mechanisms. In this report, recent advances in synthetic riboswitches that function in mammalian cells are reviewed focusing on the regulatory mechanisms they exploit such as mRNA degradation, microRNA processing, and programmed ribosomal frameshifting. url: https://api.elsevier.com/content/article/pii/S1367593118302023 doi: 10.1016/j.cbpa.2019.05.018 id: cord-000402-unr44dvp author: Yoo, Hyun Jung title: Gene Expression Profile during Chondrogenesis in Human Bone Marrow derived Mesenchymal Stem Cells using a cDNA Microarray date: 2011-06-20 words: 3178.0 sentences: 165.0 pages: flesch: 44.0 cache: ./cache/cord-000402-unr44dvp.txt txt: ./txt/cord-000402-unr44dvp.txt summary: title: Gene Expression Profile during Chondrogenesis in Human Bone Marrow derived Mesenchymal Stem Cells using a cDNA Microarray The expression levels of the 10 genes selected (Hrad 6B, annexin A2, BMP-7, contactin-1, peroxiredoxin-1, heat shock transcription factor-2, synaptotagmin IV, serotonin receptor-7, Axl, and IL-15) were analyzed by RT-PCR, by using total RNAs obtained from 5 samples (Fig. 4B) . The expression levels of 9 genes (Hrad 6B, annexin A2, BMP-7, contactin-1, peroxiredoxin-1, heat shock transcription factor-2, synaptotagmin IV, serotonin receptor-7, Axl) were low in undifferentiated cells and increased in differentiated cells by RT-PCR and microarray, but the expression pattern of IL-15 was different. Microarray data showed that Axl, synaptotagmin IV, Hrad6B, peroxiredoxin-1, BMP-7, heat shock transcription factor-2, annexin A2, contactin-1 and serotonin receptor-7 expressions were maintained in differentiating BM-MSCs until day 14. Gene expression profile of cytokine and growth factor during differentiation of bone marrow-derived mesenchymal stem cell abstract: Mesenchymal stem cells (MSCs) have the capacity to proliferate and differentiate into multiple connective tissue lineages, which include cartilage, bone, and fat. Cartilage differentiation and chondrocyte maturation are required for normal skeletal development, but the intracellular pathways regulating this process remain largely unclear. This study was designed to identify novel genes that might help clarify the molecular mechanisms of chondrogenesis. Chondrogenesis was induced by culturing human bone marrow (BM) derived MSCs in micromass pellets in the presence of defined medium for 3, 7, 14 or 21 days. Several genes regulated during chondrogenesis were then identified by reverse transcriptase-polymerase chain reaction (RT-PCR). Using an ABI microarray system, we determined the differential gene expression profiles of differentiated chondrocytes and BM-MSCs. Normalization of this data resulted in the identification of 1,486 differentially expressed genes. To verify gene expression profiles determined by microarray analysis, the expression levels of 10 genes with high fold changes were confirmed by RT-PCR. Gene expression patterns of 9 genes (Hrad6B, annexinA2, BMP-7, contactin-1, peroxiredoxin-1, heat shock transcription factor-2, synaptotagmin IV, serotonin receptor-7, Axl) in RT-PCR were similar to the microarray gene expression patterns. These findings provide novel information concerning genes involved in the chondrogenesis of human BM-MSCs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124712/ doi: 10.3346/jkms.2011.26.7.851 id: cord-005089-jwcmmfdw author: Zhao, Yin-He title: Extended expression of B-class MADS-box genes in the paleoherb Asarum caudigerum date: 2009-11-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Asarum caudigerum (Aristolochiaceae) is a paleoherb species that is important for research in origin and evolution of angiosperm flowers due to its basal position in the angiosperm phylogeny. In this study, a subtracted floral cDNA library from floral buds of A. caudigerum was constructed and cDNA arrays by suppression subtractive hybridization were generated. cDNAs of floral buds at different stages before flower opening and of leaves at the seedling stage were used. The macroarray analyses of expression profiles of isolated floral genes showed that 157 genes out of the 612 unique ESTs tested revealed higher transcript abundance in the floral buds and uppermost leaves. Among them, 78 genes were determined to be differentially expressed in the perianth, 62 in the stamens, and 100 genes in the carpels. Quantitative real-time PCR of selected genes validated the macroarray results. Remarkably, APETALA3 (AP3) B-class genes isolated from A. caudigerum were upregulated in the perianth, stamens and carpels, implying that the expression domain of B-class genes in this basal angiosperm was broader than those in their eudicot counterparts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00425-009-1048-6) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088318/ doi: 10.1007/s00425-009-1048-6 id: cord-012035-rhpfpku9 author: Zhong, Hui-hai title: TRAIL-based gene delivery and therapeutic strategies date: 2019-08-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), also known as APO2L, belongs to the tumor necrosis factor family. By binding to the death receptor 4 (DR4) or DR5, TRAIL induces apoptosis of tumor cells without causing side toxicity in normal tissues. In recent years TRAIL-based therapy has attracted great attention for its promise of serving as a cancer drug candidate. However, the treatment efficacy of TRAIL protein was under expectation in the clinical trials because of the short half-life and the resistance of cancer cells. TRAIL gene transfection can produce a “bystander effect” of tumor cell killing and provide a potential solution to TRAIL-based cancer therapy. In this review we focus on TRAIL gene therapy and various design strategies of TRAIL DNA delivery including non-viral vectors and cell-based TRAIL therapy. In order to sensitize the tumor cells to TRAIL-induced apoptosis, combination therapy of TRAIL DNA with other drugs by the codelivery methods for yielding a synergistic antitumor efficacy is summarized. The opportunities and challenges of TRAIL-based gene delivery and therapy are discussed. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889127/ doi: 10.1038/s41401-019-0287-8 id: cord-013171-wgn529rc author: Zhong, Yi title: STAU1 selectively regulates the expression of inflammatory and immune response genes and alternative splicing of the nerve growth factor receptor signaling pathway date: 2020-09-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Double-stranded RNA-binding protein Staufen homolog 1 (STAU1) is a highly conserved multifunctional double-stranded RNA-binding protein, and is a key factor in neuronal differentiation. RNA sequencing was used to analyze the overall transcriptional levels of the upregulated cells by STAU1 and control cells, and select alternative splicing (AS). It was determined that the high expression of STAU1 led to changes in the expression levels of a variety of inflammatory and immune response genes, including IFIT2, IFIT3, OASL, and CCL2. Furthermore, STAU1 was revealed to exert a significant regulatory effect on the AS of genes related to the ‘nerve growth factor receptor signaling pathway’. This is of significant importance for neuronal survival, differentiation, growth, post-damage repair, and regeneration. In conclusion, overexpression of STAU1 was associated with immune response and regulated AS of pathways related to neuronal growth and repair. In the present study, the whole transcriptome of STAU1 expression was first analyzed, which laid a foundation for further understanding the key functions of STAU1. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551455/ doi: 10.3892/or.2020.7769 id: cord-296979-8r851j4t author: Zhong, Ying title: Host genes regulate transcription of sperm-introduced hepatitis B virus genes in embryo date: 2017-10-31 words: 6753.0 sentences: 322.0 pages: flesch: 49.0 cache: ./cache/cord-296979-8r851j4t.txt txt: ./txt/cord-296979-8r851j4t.txt summary: Eighteen healthy donors were randomly divided into six groups, and their sperm samples were used to fertilize zona-free hamster oocytes in vitro and assess the effects of the silencing of five target genes (CSH2, EIF4G2, PCBD2, PSG4 and TTN) and a control gene (ESRRG) on transcription of HBV s and x genes by real-time quantitative (q)RT-PCR. Eighteen healthy donors were randomly divided into six groups, and their sperm sample were used to fertilize zona-free hamster oocytes in vitro and assess the effects of the silencing of five target genes (CSH2, EIF4G2, PCBD2, PSG4 and TTN) and a control gene (ESRRG) on transcription of HBV S and X genes in two-cell embryos using real time qRT-PCR and 2 − CT method. abstract: Abstract Hepatitis B virus (HBV) can invade the male germline, and sperm-introduced HBV genes could be transcribed in embryo. This study was to explore whether viral gene transcription is regulated by host genes. Embryos were produced by in vitro fertilization of hamster oocytes with human sperm containing the HBV genome. Total RNA extracted from test and control embryos were subjected to SMART-PCR, SSH, microarray hybridization, sequencing and BLAST analysis. Twenty-nine sequences showing significant identity to five human gene families were identified, with CSH2, EIF4G2, PCBD2, PSG4 and TTN selected to represent target genes. Using qRT-PCR, when CSH2 and PCBD2 (or EIF4G2, PSG4 and TTN) were silenced by RNAi, transcriptional levels of HBV s and x genes decreased (or increased). This is the first report that host genes participate in regulation of sperm-introduced HBV gene transcription in embryo, which is critical to prevent negative impact of HBV infection on early embryonic development. url: https://doi.org/10.1016/j.reprotox.2017.08.009 doi: 10.1016/j.reprotox.2017.08.009 id: cord-356197-js7l86fh author: Zhou, Ping title: Molecular Characterization of Transcriptome-wide Interactions between Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Porcine Alveolar Macrophages in vivo date: 2011-08-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) infects mainly the porcine alveolar macrophages (PAMs) and causes porcine reproductive and respiratory syndrome (PRRS). Previous studies have analyzed the global gene expression profiles of lung tissue in vivo and PAMs in vitro following infection with PRRSV, however, transcriptome-wide understanding of the interaction between highly pathogenic PRRSV (HP-PRRSV) and PAMs in vivo has not yet been established. In this study, we employed Affymetrix microarrays to investigate the gene expression patterns of PAMs isolated from Tongcheng piglets (a Chinese indigenous breed) after infection with HP-PRRSV. During the infection, Tongcheng piglets exhibited typical clinical signs, e.g. fever, asthma, coughing, anorexia, lethargy and convulsion, but displayed mild regional lung damage at 5 and 7 dpi. Microarray analysis revealed that HP-PRRSV infection has affected PAMs in expression of the important genes involved in cytoskeleton and exocytosis organization, protein degradation and folding, intracellular calcium and zinc homeostasis. Several potential antiviral strategies might be employed in PAMs, including upregulating IFN-induced genes and increasing intracellular zinc ion concentration. And inhibition of the complement system likely attenuated the lung damage during HP-PRRSV infection. Transcriptomic analysis of PAMs in vivo could lead to a better understanding of the HP-PRRSV-host interaction, and to the identification of novel antiviral therapies and genetic components of swine tolerance/susceptibility to HP-PRRS. url: https://www.ncbi.nlm.nih.gov/pubmed/21850204/ doi: nan id: cord-345475-ttrcmtu4 author: de Oliveira, Luisa Abruzzi title: Reference Genes for the Normalization of Gene Expression in Eucalyptus Species date: 2011-12-24 words: 9744.0 sentences: 595.0 pages: flesch: 54.0 cache: ./cache/cord-345475-ttrcmtu4.txt txt: ./txt/cord-345475-ttrcmtu4.txt summary: Given the increasing interest in the functional genomics of Eucalyptus and the need for validated reference genes for a broader set of species and experimental conditions, we sought to identify the most stably expressed genes in a set of 21,432 genes assayed by microarray developed to compare stem vascular (xylem) and leaf tissues of E. According to the NormFinder analysis of gene expression in leaves, xylem tissues and among species, the stability values of the 15 genes studied were <0.138, with error bars no greater than 0.044 ( Fig. 3C ; Table 3 ). When we analyzed the gene expression in all tissues/organs and species, the stability value was in the range between 0.017 and 0.106, proving again that all genes elected are good references for RT-qPCR studies in Eucalyptus. By RT-qPCR, the expression stability of eight of the 50 best candidate genes selected by SAM and SDMA was addressed in different organs (leaves and flowers) and vascular tissues (xylem) derived from six species of Eucalyptus. abstract: Gene expression analysis is increasingly important in biological research, with reverse transcription–quantitative PCR (RT–qPCR) becoming the method of choice for high-throughput and accurate expression profiling of selected genes. Considering the increased sensitivity, reproducibility and large dynamic range of this method, the requirements for proper internal reference gene(s) for relative expression normalization have become much more stringent. Given the increasing interest in the functional genomics of Eucalyptus, we sought to identify and experimentally verify suitable reference genes for the normalization of gene expression associated with the flower, leaf and xylem of six species of the genus. We selected 50 genes that exhibited the least variation in microarrays of E. grandis leaves and xylem, and E. globulus xylem. We further performed the experimental analysis using RT–qPCR for six Eucalyptus species and three different organs/tissues. Employing algorithms geNorm and NormFinder, we assessed the gene expression stability of eight candidate new reference genes. Classic housekeeping genes were also included in the analysis. The stability profiles of candidate genes were in very good agreement. PCR results proved that the expression of novel Eucons04, Eucons08 and Eucons21 genes was the most stable in all Eucalyptus organs/tissues and species studied. We showed that the combination of these genes as references when measuring the expression of a test gene results in more reliable patterns of expression than traditional housekeeping genes. Hence, novel Eucons04, Eucons08 and Eucons21 genes are the best suitable references for the normalization of expression studies in the Eucalyptus genus. url: https://doi.org/10.1093/pcp/pcr187 doi: 10.1093/pcp/pcr187 id: cord-253450-k7p510p4 author: keha, Abi title: Prevalence of a novel bovine coronavirus strain with a recombinant hemagglutinin/esterase gene in dairy calves in China date: 2019-05-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Bovine coronavirus (BCoV) is the causative agent of diarrhoea in newborn calves, winter dysentery in adult cattle and respiratory tract illnesses in cattle across the world. In this study, a total of 190 faecal samples from dairy calves with diarrhoea were collected from 14 farms in six Chinese provinces, and BCoV was detected in 18.95% (36/190) of the samples by reverse transcriptase polymerase chain reaction. Full‐length spike, hemagglutinin/esterase (HE), nucleocapsid and transmembrane genes were simultaneously cloned from 13 clinical samples (eight farms in four provinces), and most of the BCoV strains showed a unique evolutionary pattern based on the phylogenetic analysis of these genes. Interesting, 10 of the 13 strains were identified as HE recombinant strains, and these strains had experienced the same recombination event and carried the same recombination sites located between the esterase and lectin domain. They also shared an identical aa variant (F181V) in the R2‐loop. Moreover, 9/10 strains displayed another identical aa variant (P, S158A) in the adjacent R1‐loop of the HE gene, which differs from the other available BCoV HE sequences in the GenBank database. Our results showed that BCoV is widely circulating in dairy cattle in China, contributing to the diagnosis and control of dairy calves diarrhoea. Furthermore, a BCoV strain that carries a recombinant HE gene has spread in dairy calves in China. To the best of our knowledge, this is the first description of an HE recombination event occurring in BCoV; this is also the first description of the molecular prevalence of BCoV in China. Our findings will enhance current understanding about the genetic evolution of BCoV. url: https://doi.org/10.1111/tbed.13228 doi: 10.1111/tbed.13228 id: cord-004879-pgyzluwp author: nan title: Programmed cell death date: 1994 words: 81677.0 sentences: 4465.0 pages: flesch: 51.0 cache: ./cache/cord-004879-pgyzluwp.txt txt: ./txt/cord-004879-pgyzluwp.txt summary: Furthermore kinetic experiments after complementation of HIV=RT p66 with KIV-RT pSl indicated that HIV-RT pSl can restore rate and extent of strand displacement activity by HIV-RT p66 compared to the HIV-RT heterodimer D66/D51, suggesting a function of the 51 kDa polypeptide, The mouse mammary tumor virus proviral DNA contains an open reading frame in the 3'' long terminal repeat which can code for a 36 kDa polypeptide with a putative transmembrane sequence and five N-linked glycosylation sites. To this end we used constructs encoding the c-fos (and c-jun) genes fused to the hormone-binding domain of the human estrogen receptor, designated c-FosER (and c-JunER), We could show that short-term activation (30 mins.) of c-FosER by estradiole (E2) led to the disruption of epithelial cell polarity within 24 hours, as characterized by the expression of apical and basolateral marker proteins. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087532/ doi: 10.1007/bf02033112 id: cord-005147-mvoq9vln author: nan title: Autorenregister date: 2017-02-23 words: 86573.0 sentences: 4356.0 pages: flesch: 45.0 cache: ./cache/cord-005147-mvoq9vln.txt txt: ./txt/cord-005147-mvoq9vln.txt summary: Using whole-exome sequencing and trio-based de novo analysis, we identified a novel heterozygous de novo frameshift variant in the leukemia inhibitory factor receptor (LIFR) gene causing instability of the mRNA in a patient presenting with bilateral CAKUT and requiring kidney transplantation at one year of age. Loss of cdkl5 associated with deficient mammalian target of rapamycin (mTOR) signaling in mice and human cells We and other groups have shown that mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene cause a severe neurodevelopmental disorder with clinical features including intellectual disability, early-onset intractable seizures and autism, that are closely related to those present in Rett syndrome (RTT) patients. Functional characterization of novel GNB1 mutations as a rare cause of global developmental delay Over the past years, prioritization strategies that combined the molecular predictors of sequence variants from exomes and genomes of patients with rare Mendelian disorders with computer-readable phenotype information became a highly effective method for detecting disease-causing mutations. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088617/ doi: 10.1007/s11825-017-0126-6 id: cord-006230-xta38e7j author: nan title: Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V. date: 2012-02-22 words: 135419.0 sentences: 7042.0 pages: flesch: 43.0 cache: ./cache/cord-006230-xta38e7j.txt txt: ./txt/cord-006230-xta38e7j.txt summary: Here, we will present our analysis of Ca 2+ signaling following stimulation of the FcεRI receptor and application of secretagogues that are supposed to affect Ca 2+ -dependent mast cell activation such as adenosine, endothelin-1, substance P and compound 48/80 in BMMCs and PMCs derived from mouse lines with inactivation of TRPC1, TRPC3, TRPC4, TRPC5 or TRPC6 since specific antagonists are still lacking for these TRP channels. These data indicate that increased PP2A activity is associated with modified gene expression in TG hearts possibly affecting stress response and regulation of cell signalling. As demonstrated by qPCR and Western blot experiments, mesangial cells showed a marked time-and dose-dependent upregulation of CSE mRNA and protein levels after treatment with platelet-derived growth factor (PDGF-BB). The transcription factor cAMP response element (CRE)-binding protein (CREB) plays a critical role in regulating gene expression in response to activation of the cAMPdependent signaling pathway, which is implicated in the pathophysiology of heart failure. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100643/ doi: 10.1007/s00210-012-0736-0 id: cord-008777-i2reanan author: nan title: ECB12: 12th European Congess on Biotechnology date: 2005-07-19 words: 151383.0 sentences: 7577.0 pages: flesch: 43.0 cache: ./cache/cord-008777-i2reanan.txt txt: ./txt/cord-008777-i2reanan.txt summary: Mollerup Department of Chemical Engineering, Building 229, DTU, 2800 Lyngby, Denmark A variety of factors that govern the properties of proteins are utilized in the development of chromatographic processes for the recovery of biological products including the binding and release of protons, the non-covalent association with non-polar groups (often hydrophobic interactions), the association of small ions (ion exchange) and the highly specific antigen-antibody interaction (affinity interactions). Such fermenters will be needed in order to meet the increasing pressure on costs for low price commodity type products such as single cell protein or food and technical grade enzymes, and to meet the demands of the new wave of white biotech, in which bio-produced chemicals must be made at prices competitive with those of the traditional chemical industry. The presentation will focus on use of the sensitive sandwich hybridization technology for the quantitative analysis of process relevant marker genes in different kind of microbial cell cultures with a focus on the production of recombinant proteins. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134330/ doi: 10.1016/j.jbiotec.2005.06.005 id: cord-009664-kb9fnbgy author: nan title: Oral presentations date: 2014-12-24 words: 71112.0 sentences: 3948.0 pages: flesch: 47.0 cache: ./cache/cord-009664-kb9fnbgy.txt txt: ./txt/cord-009664-kb9fnbgy.txt summary: Because of the conflicting reports and lack of published data from paediatric patients, we sought to assess possible MIC change over time and to compare results generated by using different methodologies including Etest, agar dilution, and broth microdilution (MicroScan) methods. Recently, in vitro and in vivo studies have shown that NO plays a key role in the eradication of the leishmania parasite Objective: To determine whether a NO donor patch (developed by electrospinning technique) is as effective as meglumine antimoniate in the treatment of CL while causing less adverse events Methods: A double-blind, randomised, placebo-controlled clinical trial was conducted with 178 patients diagnosed with CL in Santander, Colombia, South-America. To follow the development and spread of the resistance among these strains is difficult, as antibiotic susceptibility testing of clinically relevant anaerobes in different routine laboratories in Europe is less and less frequently carried out due to the fact, that clinicians treat many presumed anaerobic infections empirically. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162236/ doi: 10.1111/j.1469-0691.2009.02857.x id: cord-014368-4nasrbs6 author: nan title: Gene Chip for Viral Discovery date: 2003-11-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC261871/ doi: 10.1371/journal.pbio.0000003 id: cord-014462-11ggaqf1 author: nan title: Abstracts of the Papers Presented in the XIX National Conference of Indian Virological Society, “Recent Trends in Viral Disease Problems and Management”, on 18–20 March, 2010, at S.V. University, Tirupati, Andhra Pradesh date: 2011-04-21 words: 35453.0 sentences: 1711.0 pages: flesch: 49.0 cache: ./cache/cord-014462-11ggaqf1.txt txt: ./txt/cord-014462-11ggaqf1.txt summary: Molecular diagnosis based on reverse transcription (RT)-PCR s.a. one step or nested PCR, nucleic acid sequence based amplification (NASBA), or real time RT-PCR, has gradually replaced the virus isolation method as the new standard for the detection of dengue virus in acute phase serum samples. Non-genetic methods of management of these diseases include quarantine measures, eradication of infected plants and weed hosts, crop rotation, use of certified virus-free seed or planting stock and use of pesticides to control insect vector populations implicated in transmission of viruses. The results of this study indicate that NS1 antigen based ELISA test can be an useful tool to detect the dengue virus infection in patients during the early acute phase of disease since appearance of IgM antibodies usually occur after fifth day of the infection. The studies showed high level of expression in case of constructed vector as compared to infected virus for the specific protein. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639731/ doi: 10.1007/s13337-011-0027-2 id: cord-014597-66vd2mdu author: nan title: Abstracts from the 25th European Society for Animal Cell Technology Meeting: Cell Technologies for Innovative Therapies: Lausanne, Switzerland. 14-17 May 2017 date: 2018-03-15 words: 50613.0 sentences: 2624.0 pages: flesch: 46.0 cache: ./cache/cord-014597-66vd2mdu.txt txt: ./txt/cord-014597-66vd2mdu.txt summary: Irrespective of the cell culture-based system and production scale, PEIpro® and PEIpro®-HQ have led to efficient viral vector yields superior to 10 7 IG/mL and 10 9 VG/mL, respectively for lentiviruses and AAVs Background Continuous perfusion process is making a comeback as a competing upstream manufacturing technology for the production of Biopharmaceuticals compared to the standard fed batch processes. To evaluate the impact of feed-spiking compared with cultivation in basal medium only, the cell line was grown in bioreactors under controlled conditions to determine cellspecific metabolic rates, nutrient consumption, and byproduct accumulation over the process time. Through the interchangeability of signal peptides between products and even species, a large variety can be used to enhance protein expression in already existing production systems Materials and methods At first the influence of four different natural SPs (SP (7), (8), (9) and (10)) was compared on the secreted amount of an IgG4 model antibody (product A) in fed batches using a CHO DG44 host cell line. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5861492/ doi: 10.1186/s12919-018-0097-x id: cord-017752-ofzm3x3a author: nan title: Theories of Carcinogenesis date: 2007 words: 12289.0 sentences: 692.0 pages: flesch: 47.0 cache: ./cache/cord-017752-ofzm3x3a.txt txt: ./txt/cord-017752-ofzm3x3a.txt summary: Others attributed the simplified enzyme patterns of cancerous cells to a regression of the tumor tissues to early embryonal stages of development. Viral DNA is frequently integrated into the cancer cells, but additional agents or factors may be involved at various stages of the progression to invasive carcinoma. The encounter with a family, in which many members developed breast or liver cancer, led Pierre Paul Broca to hypothesize, in 1866, that an inherited abnormality within the affected tissue caused the tumor development [Broca 1866 Theodor Boveri (1862 Boveri ( -1915 then proposed that defects in chromosomes lead to malignancy [Boveri 1914 ]. Any mutation of cancer associated genes can be handed on to following generations and predispose the affected cells to malignant transformation in the case of additional DNA damage. Further developments in tumor immunology have led to models of selection and evolution of cancer cells. abstract: The oldest description of human cancer, referring to eight cases of tumors of the breast, was found in the Egyptian Edwin Smith Papyrus, written around 3000–1500 BC. The oldest specimens of human cancers were detected in the remains of a female skull dating back to the Bronze Age (1900–1600 BC), and in fossilized bones of ancient Egypt. The mummified skeletal remains of Peruvian Incas, dating about 2,400 years ago, contained lesions suggestive of malignant melanoma. The term “cancer” goes back to Hippocrates (460–370 BC), who named a group of diseases καρκινοσ and καρκινομα, the ancient Greek word for crab. It is a metaphor for the hard center and spiny projections of the tumors he studied. Cancer is the Latin word for crab and its use has been traced back to Galen (AD 129–199). A snapshot of theories of carcinogenesis, devised in the course of the last two centuries, reflects the progress of insight from the cellular level via biochemistry to an understanding of damaging influences and oncogenes, and to a more wholistic approach in the regulatory theory. It shows the relative success of reductionism as well as the current need to put the insights of various research endeavors into broader paradigmatic contexts. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122402/ doi: 10.1007/978-1-4020-6016-8_1 id: cord-020101-5rib7pe8 author: nan title: Cumulative Author Index for 2008 date: 2008-11-17 words: 2140.0 sentences: 126.0 pages: flesch: 29.0 cache: ./cache/cord-020101-5rib7pe8.txt txt: ./txt/cord-020101-5rib7pe8.txt summary: Cauliflower mosaic virus gene VI product N-terminus contains regions involved in resistance-breakage, self-association and interactions with movement protein Intrahost evolution of envelope glycoprotein and OrfA sequences after experimental infection of cats with a molecular clone and a biological isolate of feline immunodeficiency virus DC-SIGN enhances infection of cells with glycosylated West Nile virus in vitro and virus replication in human dendritic cells induces production of Increase in proto-oncogene mRNA transcript levels in bovine lymphoid cells infected with a cytopathic type 2 bovine viral diarrhea virus Complete genome sequence analysis of dengue virus type 2 isolated in Modulation of hepatitis B virus replication by expression of polymerasesurface fusion protein through splicing: Implications for viral persistence Induction of apoptosis in Vero cells by Newcastle disease virus requires viral replication, de-novo protein synthesis and caspase activation Mechanisms of inhibition of HIV replication by non-nucleoside reverse transcriptase inhibitors abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134142/ doi: 10.1016/s0168-1702(08)00367-5 id: cord-022940-atbjwpo5 author: nan title: Poster Sessions date: 2016-09-07 words: 241182.0 sentences: 12746.0 pages: flesch: 47.0 cache: ./cache/cord-022940-atbjwpo5.txt txt: ./txt/cord-022940-atbjwpo5.txt summary: We have studied the effect of inhibition of IRE1 (inositol requiring enzyme 1), which is a central mediator of endoplasmic reticulum stress and controls cell proliferation and tumor growth, on hypoxic regulation of the expression of different proliferation related genes in U87 glioma cells. Transient inhibition of Akt and mTOR protein kinase activation in tumor cells followed by reactivation of signaling pathway did not result in a time-dependent difference on EGFR, HER2 and HER3 expression levels. In our study we aimed to determine cytotoxic effect of RES in K562 human CML cell line and to evaluate the expressions of miRNAs that are associated with genetics of leukemia after treatment with RES; to investigate target genes of miRNAs which show significant expression alterations and molecular mechanisms of RES treatment. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164006/ doi: 10.1111/febs.13808 id: cord-023055-ntbvmssh author: nan title: Immunogenicity date: 2004-02-19 words: 64563.0 sentences: 3952.0 pages: flesch: 59.0 cache: ./cache/cord-023055-ntbvmssh.txt txt: ./txt/cord-023055-ntbvmssh.txt summary: Antigen is internalized into acidic vesicles, proteolyzed, and peptides containing T ceU antigenic determinants are transported to the APC surface where they are recognized by the antigen-specific T cell in conjunction with Ia. Most Ia-"pressing cells are competent APC, however, only B cells have antigen-specilic receptors on their surface aUowing bound antigen to be processed and presented at 1/lW the antigen concentration required by nonspecific APC Little is known about B cell antigen processing function during differentiation, or if Ig-mediated APC function is altered at different maturational stages, thus allowing regulation of B cell-helper T cell interactions. These results indicate that the poor response of murine CTL to human class I antigens is not determined by selection in the thymus, but by species-specific constraints on the interaction of MHC antigens with T-cell recognition structures. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166418/ doi: 10.1002/jcb.240410506 id: cord-023605-zibwrv76 author: nan title: Genetics and biotechnology of Bacilli: A.T. Ganesan and J.A. Hoch (Eds.): (Proceedings of the Second International Conference on the Genetics and Biotechnology of Bacilli, Stanford University, Stanford, CA, July 6–8, 1983) Academic Press Inc., Orlando, FL, 1984, xviii + 421 pp. ($41.50) ISBN 0-12-274 60-9 date: 2003-01-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172707/ doi: 10.1016/0378-1119(87)90076-x id: cord-023647-dlqs8ay9 author: nan title: Sequences and topology date: 2003-03-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173161/ doi: 10.1016/0959-440x(91)90051-t id: cord-007708-hr4smx24 author: van Kampen, Antoine H. C. title: Taking Bioinformatics to Systems Medicine date: 2015-08-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Systems medicine promotes a range of approaches and strategies to study human health and disease at a systems level with the aim of improving the overall well-being of (healthy) individuals, and preventing, diagnosing, or curing disease. In this chapter we discuss how bioinformatics critically contributes to systems medicine. First, we explain the role of bioinformatics in the management and analysis of data. In particular we show the importance of publicly available biological and clinical repositories to support systems medicine studies. Second, we discuss how the integration and analysis of multiple types of omics data through integrative bioinformatics may facilitate the determination of more predictive and robust disease signatures, lead to a better understanding of (patho)physiological molecular mechanisms, and facilitate personalized medicine. Third, we focus on network analysis and discuss how gene networks can be constructed from omics data and how these networks can be decomposed into smaller modules. We discuss how the resulting modules can be used to generate experimentally testable hypotheses, provide insight into disease mechanisms, and lead to predictive models. Throughout, we provide several examples demonstrating how bioinformatics contributes to systems medicine and discuss future challenges in bioinformatics that need to be addressed to enable the advancement of systems medicine. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120931/ doi: 10.1007/978-1-4939-3283-2_2 ==== make-pages.sh questions [ERIC WAS HERE] ==== make-pages.sh search /data-disk/reader-compute/reader-cord/bin/make-pages.sh: line 77: /data-disk/reader-compute/reader-cord/tmp/search.htm: No such file or directory Traceback (most recent call last): File "/data-disk/reader-compute/reader-cord/bin/tsv2htm-search.py", line 51, in with open( TEMPLATE, 'r' ) as handle : htm = handle.read() FileNotFoundError: [Errno 2] No such file or directory: '/data-disk/reader-compute/reader-cord/tmp/search.htm' ==== make-pages.sh topic modeling corpus Zipping study carrel