cord-000012-p56v8wi1 2008 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. cord-000159-8y8ho2x5 2009 ''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 cord-000248-zueoyesj 2010 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] . cord-000402-unr44dvp 2011 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 cord-000492-ec5qzurk 2011 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] . cord-000580-dcid9emx 2012 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. cord-001060-9g8rwsm1 2011 cord-001541-5d64esp4 2015 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) . cord-001858-nmi39n6h 2015 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. cord-001921-73esrper 2016 cord-002142-tdgu9sr9 2016 cord-002366-t94aufs3 2017 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. cord-003044-9uqa39j9 2018 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. cord-003196-fdb6az0v 2018 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 . cord-003254-yiqdsf9z 2018 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 . cord-003387-82573enr 2018 cord-003514-yyzbv7ys 2019 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. cord-003898-y6zpvw84 2019 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. cord-003900-5p4ektzv 2019 cord-004222-z4butywi 2020 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. cord-004879-pgyzluwp 1994 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. cord-004893-28mrzvsc 1997 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. cord-005089-jwcmmfdw 2009 cord-005147-mvoq9vln 2017 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. cord-005216-potmzdfs 2018 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). cord-005432-mqyvpepo 2002 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 ). cord-005476-q6o5239w 2004 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 cord-006230-xta38e7j 2012 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. cord-007259-vj9tv3or 2017 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. cord-007390-3txwm6wr 2006 cord-007708-hr4smx24 2015 cord-007760-it9wach2 2004 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. cord-008777-i2reanan 2005 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. cord-009664-kb9fnbgy 2014 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. cord-010038-0m2f0eh4 2003 cord-010278-loey5xq9 1995 cord-011630-lfm34fsw 2020 cord-012035-rhpfpku9 2019 cord-012542-rsqon0w0 2020 cord-013171-wgn529rc 2020 cord-014368-4nasrbs6 2003 cord-014462-11ggaqf1 2011 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. cord-014597-66vd2mdu 2018 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. cord-015684-q10sx1dm 2009 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. cord-015850-ef6svn8f 2013 cord-015935-r2wd1yfa 2011 cord-016062-h4vjkufn 2006 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). cord-016095-jop2rx61 2010 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. cord-016187-58rqc0cg 2006 cord-016200-zfh20im0 2013 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. cord-016293-pyb00pt5 2006 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. cord-016313-n4ewq0pt 2012 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. cord-016364-80l5mua2 2008 cord-016588-f8uvhstb 2009 cord-016713-pw4f8asc 2013 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. cord-017156-ximzvqbm 2010 cord-017208-7oew461e 2005 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. cord-017752-ofzm3x3a 2007 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. cord-017853-mgsuwft0 2010 cord-017932-vmtjc8ct 2009 cord-018145-kssjdn8y 2009 cord-018526-rz7id5mt 2018 cord-018647-bveks6t1 2019 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. cord-018798-yzxy9ogf 2018 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 ). cord-018924-wo42j0ps 2011 cord-019050-a9datsoo 2014 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]. cord-020101-5rib7pe8 2008 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 cord-020969-lh2ergpm 2012 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. cord-021063-4y8m33ea 2007 cord-022177-j0qcjbxg 2018 cord-022178-4oh02tlr 2018 cord-022226-qxp0gfp3 2007 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. cord-022940-atbjwpo5 2016 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. cord-023055-ntbvmssh 2004 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. cord-023605-zibwrv76 2003 cord-023647-dlqs8ay9 2003 cord-023928-9a1w174h 2011 cord-024290-8z6us7v4 2020 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 . cord-028721-x6f26ahr 2020 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. cord-033692-txfuuu7d 2020 cord-048322-5eqdrd52 2006 cord-102219-d3gkfo7s 2019 cord-102729-b1q7gbd6 2020 cord-102935-cx3elpb8 2020 cord-103150-e9q8e62v 2020 cord-103465-6udhvl9n 2020 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). cord-103505-9adtbwp2 2020 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. cord-104073-vsa5y7ip 2020 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 cord-252147-bvtchcbt 2011 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. cord-252536-gfx4cq03 2011 cord-252781-06hs9pit 2013 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 cord-252859-zir02q69 2006 cord-253450-k7p510p4 2019 cord-253973-zr28uujh 2007 cord-256837-100ir651 2012 cord-257843-nj2707mv 2017 cord-258035-2tk7maqk 2003 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 cord-260345-ugd8kkor 1992 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. cord-260496-s2ba7uy3 2006 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. cord-260793-bb4h255w 2020 cord-263470-vmqvropy 2007 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. cord-264746-gfn312aa 2012 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. cord-264884-ydkigome 2008 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. cord-264996-og3sg0qw 2006 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) . cord-266521-vovas81d 2019 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 cord-266617-z8uecyl6 2019 cord-267475-6f4h3cck 2002 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. cord-267733-fuz8r3vj 2016 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 cord-268098-71g1w1mc 2020 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. cord-269352-0o3mryu1 2008 cord-272378-umvi0veu 2019 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] . cord-273347-eyxc4rt0 2020 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 cord-273609-whm2ce4u 2012 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. cord-273910-fna7s9te 2007 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. cord-274241-biqbsggu 2012 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 ). cord-275720-kf9m4zho 2012 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. cord-277491-q18b88lm 2011 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 cord-278136-ol2buwld 2016 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. cord-279781-5ldpz9m9 2011 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 cord-280691-nzc8ir0n 2013 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. cord-280897-el7bdkcf 2007 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) . cord-280924-g6062fwk 2020 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) . cord-282968-kjvvoveq 2019 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. cord-284015-vvtv492b 2020 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. cord-284933-flbibrcm 2017 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. cord-285656-7o7ofk1e 2017 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. cord-287396-18p171nr 2014 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. cord-289033-vfh3op6a 2020 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. cord-290282-oxyzndsj 2003 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) . cord-290861-5bxvenue 2018 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. cord-291349-tq2n4mx3 2002 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. cord-291719-1ku6cmwj 2020 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) . cord-292004-9rpoll7y 2019 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. cord-294725-wyrg0nq8 2013 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. cord-295019-8tf8ah6g 2011 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. cord-295307-zrtixzgu 2020 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 . cord-296979-8r851j4t 2017 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. cord-298131-zolwjl9u 2010 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. cord-301218-zsp5sh9o 2004 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. cord-301546-yck1t3pp 2007 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. cord-302047-vv5gpldi 2019 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 cord-303132-m3j1dekj 2013 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. cord-303939-7knzjnyr 2020 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 cord-304607-td0776wj 2010 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. cord-304913-qb9zeazk 2009 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). cord-305177-i71z2sf4 2020 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. cord-306380-msk9p1yy 2000 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 cord-306535-j26eqmxt 2020 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. cord-307202-iz1bo218 2014 cord-307769-rjseio5s 2012 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. cord-308034-9b219k0v 2014 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. cord-309556-xv3413k1 2020 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. cord-311430-o32d3kaw 2013 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] . cord-312551-w4tps34p 2007 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 cord-313138-y485ev30 2013 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. cord-314503-u1y1bznk 2007 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] . cord-314642-oobbdgzh 2003 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 . cord-314915-b6aqwubh 2019 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 . cord-315072-b28yikvj 2016 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'' . cord-315498-gpzee1f2 2020 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. cord-317779-j67vb7f3 2017 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. cord-318576-dc5n6ni4 2020 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. cord-319517-denczc6t 2014 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. cord-319519-mb9ofh12 2020 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. cord-320005-i30t7cvr 2004 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. cord-322286-2de6r1h6 2020 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. cord-322566-ye27nqj2 2017 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. cord-323307-nu9ib62h 2016 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. cord-326719-p1ma4akz 2003 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. cord-328287-3qgzulgj 2014 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] . cord-328899-kog99kk5 2002 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. cord-329617-gzivtsho 2015 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. cord-331592-l44rupmi 2007 cord-332006-if46jycd 2009 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 cord-335382-fk4um9nw 2012 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] . cord-336573-bpg1dg24 2009 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. cord-337492-o6sy4zi4 2016 cord-339012-4juhmjaj 2020 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. cord-340125-il35gs97 2006 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) . cord-344297-qqohijqi 2015 cord-345475-ttrcmtu4 2011 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. cord-345516-fgn7rps3 2012 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. cord-346308-9h2fk9qt 2020 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 cord-347917-fmb5nyxu 2020 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. cord-348815-lthz75oc 2009 cord-350019-4nlbu54e 2019 cord-351548-jvl63652 2013 cord-351845-bli3qm8w 2020 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. cord-352190-1987sfyz 2020 cord-352200-i05h8csb 2012 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. cord-354829-god79qzw 2020 cord-355075-ieb35upi 2012 cord-355927-nzoiv9pj 2009 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. cord-356197-js7l86fh 2011