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https://www.readbyqxmd.com/read/28735351/multiple-correlation-analyses-revealed-complex-relationship-between-dna-methylation-and-mrna-expression-in-human-peripheral-blood-mononuclear-cells
#1
Fang-Fei Xie, Fei-Yan Deng, Long-Fei Wu, Xing-Bo Mo, Hong Zhu, Jian Wu, Yu-Fan Guo, Ke-Qin Zeng, Ming-Jun Wang, Xiao-Wei Zhu, Wei Xia, Lan Wang, Pei He, Peng-Fei Bing, Xin Lu, Yong-Hong Zhang, Shu-Feng Lei
DNA methylation is an important regulator on the mRNA expression. However, a genome-wide correlation pattern between DNA methylation and mRNA expression in human peripheral blood mononuclear cells (PBMCs) is largely unknown. The comprehensive relationship between mRNA and DNA methylation was explored by using four types of correlation analyses and a genome-wide methylation-mRNA expression quantitative trait locus (eQTL) analysis in PBMCs in 46 unrelated female subjects. An enrichment analysis was performed to detect biological function for the detected genes...
July 22, 2017: Functional & Integrative Genomics
https://www.readbyqxmd.com/read/28735109/design-and-rationale-for-a-real-world-observational-cohort-of-patients-with-nonalcoholic-fatty-liver-disease-the-target-nash-study
#2
A Sidney Barritt, Norman Gitlin, Samuel Klein, Anna S Lok, Rohit Loomba, Laura Malahias, Margaret Powell, Miriam B Vos, L Michael Weiss, Kenneth Cusi, Brent A Neuschwander-Tetri, Arun Sanyal
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can lead to cirrhosis, hepatocellular carcinoma, and end-stage liver disease. NAFLD comprises the spectrum from simple steatosis (nonalcoholic fatty liver, NAFL), to steatosis with inflammation (nonalcoholic steatohepatitis, NASH). Current primary therapy recommended for NAFLD is weight loss induced by lifestyle modification. The difficulty in achieving this has led to robust pharmacological therapy development. While new drugs may show efficacy in selected phase II/III clinical trial populations, their real-world effectiveness is unknown...
July 19, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28735000/application-of-pharmacometrics-and-quantitative-systems-pharmacology-to-cancer-therapy-the-example-of-luminal-a-breast-cancer
#3
REVIEW
Brett Fleisher, Kayla Andrews, Ashley A Brown, Sihem Ait-Oudhia
Breast cancer (BC) is the most common cancer in women, and the second most frequent cause of cancer-related deaths in women worldwide. It is a heterogeneous disease composed of multiple subtypes with distinct morphologies and clinical implications. Quantitative systems pharmacology (QSP) is an emerging discipline bridging systems biology with pharmacokinetics (PK) and pharmacodynamics (PD) leveraging the systematic understanding of drugs' efficacy and toxicity. Despite numerous challenges in applying computational methodologies for QSP and mechanism-based PK/PD models to biological, physiological, and pharmacological data, bridging these disciplines has the potential to enhance our understanding of complex disease systems such as BC...
July 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28734548/ubiquitin-like-modifications-in-the-dna-damage-response
#4
REVIEW
Zhifeng Wang, Wei-Guo Zhu, Xingzhi Xu
Genomic DNA is damaged at an extremely high frequency by both endogenous and environmental factors. An improper response to DNA damage can lead to genome instability, accelerate the aging process and ultimately cause various human diseases, including cancers and neurodegenerative disorders. The mechanisms that underlie the cellular DNA damage response (DDR) are complex and are regulated at many levels, including at the level of post-translational modification (PTM). Since the discovery of ubiquitin in 1975 and ubiquitylation as a form of PTM in the early 1980s, a number of ubiquitin-like modifiers (UBLs) have been identified, including small ubiquitin-like modifiers (SUMOs), neural precursor cell expressed, developmentally down-regulated 8 (NEDD8), interferon-stimulated gene 15 (ISG15), human leukocyte antigen (HLA)-F adjacent transcript 10 (FAT10), ubiquitin-fold modifier 1 (UFRM1), URM1 ubiquitin-related modifier-1 (URM1), autophagy-related protein 12 (ATG12), autophagy-related protein 8 (ATG8), fan ubiquitin-like protein 1 (FUB1) and histone mono-ubiquitylation 1 (HUB1)...
July 11, 2017: Mutation Research
https://www.readbyqxmd.com/read/28734047/preselection-of-recombinant-gene-integration-sites-enabling-high-transcription-rates-in-cho-cells-using-alternate-start-codons-and-recombinase-mediated-cassette-exchange
#5
Martina Baumann, Elisabeth Gludovacz, Natalie Sealover, Scott Bahr, Henry George, Nan Lin, Kevin Kayser, Nicole Borth
Site-specific Recombinase Mediated Cassette Exchange (RMCE) enables the transfer of the gene of interest (GOI) into pre-selected genomic locations with defined expression properties. For the generation of recombinant production cell lines this has the advantage that screening for high transcription rates at the genome integration site would be required only once, with the possibility to reuse the selected site for new products. Here we describe a strategy that aims at the selection of transcriptionally active genome integration sites in Chinese Hamster Ovary (CHO) cells by using alternate start codons in the surface reporter protein CD4, in combination with FACS sorting for high expressers...
July 22, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28733552/new-insights-in-the-clinical-and-translational-relevance-of-mir483-5p-in-adrenocortical-cancer
#6
Francesca Salvianti, Letizia Canu, Giada Poli, Roberta Armignacco, Cristian Scatena, Giulia Cantini, Alessandra Di Franco, Stefania Gelmini, Tonino Ercolino, Mario Pazzagli, Gabriella Nesi, Massimo Mannelli, Pamela Pinzani, Michaela Luconi
Adrenocortical cancer (ACC) is a rare aggressive malignancy. Recent ACC integrated genomics analysis contributed to redefine the risk groups on molecular basis, including tumor microRNAs (miRs), detectable also in the bloodstream. We developed a quantitative real-time (RT) assay for the measurement of miR483 and miR483-5p absolute levels in plasma samples. miR483/miR483-5p levels were evaluated in plasma samples of 27 patients with ACC before surgery and at follow-up.Statistically significant differences in miR483-5p and miR483 levels were found between stage 1/2 and stage 3/4 ACCs in pre-surgery and post-surgery samples...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733429/proteogenomic-analysis-and-discovery-of-immune-antigens-in-mycobacterium-vaccae
#7
Jianhua Zheng, Lihong Chen, Liguo Liu, Haifeng Li, Bo Liu, Dandan Zheng, Tao Liu, Jie Dong, Lilian Sun, Yafang Zhu, Jian Yang, Xiaobing Zhang, Qi Jin
Tuberculosis (TB) is one of the leading causes of death worldwide, especially in developing countries. Neonatal BCG vaccination occurs in various regions, but the level of protection varies in different populations. Recently, Mycobacterium vaccae is found to be an immunomodulating therapeutic agent that could confer a significant level of protection against TB. It is the only vaccine in a phase III trial from WHO to assess its efficacy and safety in preventing TB disease in people with latent TB infection. However, the mechanism of immunotherapy of M...
July 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28732180/the-role-of-noncoding-genetic-variation-in-isolated-orofacial-clefts
#8
F Thieme, K U Ludwig
In the past decade, medical genetic research has generated multiple discoveries, many of which were obtained via genome-wide association studies (GWASs). A major GWAS finding is that the majority of risk variants for complex traits map to noncoding regions. This has resulted in a paradigm shift in terms of the interpretation of human genomic sequence variation, with more attention now being paid to what was previously termed "junk DNA." Translation of genetic findings into biologically meaningful results requires 1) large-scale and cell-specific efforts to annotate non-protein-coding regions and 2) the integration of comprehensive genomic data sets...
July 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28732175/genome-wide-identification-functional-prediction-and-evolutionary-analysis-of-r2r3-myb-superfamily-in-brassica-napus
#9
Ali Hajiebrahimi, Hajar Owji, Shiva Hemmati
R2R3-MYBs are important transcription factors (TFs) in planta, involved in development and various stress conditions. Phylogenetic analysis showed the presence of 249 R2R3-MYB TFs in Brassica napus called BnaR2R3-MYBs, clustered into 38 clades. BnaR2R3-MYBs were distributed on 19 chromosomes of B. napus. Sixteen gene clusters were identified. BnaR2R3-MYBs were characterized by motif prediction, gene structure analysis and gene ontology. Evolutionary analysis revealed that BnaR2R3-MYBs are mainly formed as a result of whole genome duplication...
July 21, 2017: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28732062/a-drosophila-model-for-toxicogenomics-genetic-variation-in-susceptibility-to-heavy-metal-exposure
#10
Shanshan Zhou, Sarah E Luoma, Genevieve E St Armour, Esha Thakkar, Trudy F C Mackay, Robert R H Anholt
The genetic factors that give rise to variation in susceptibility to environmental toxins remain largely unexplored. Studies on genetic variation in susceptibility to environmental toxins are challenging in human populations, due to the variety of clinical symptoms and difficulty in determining which symptoms causally result from toxic exposure; uncontrolled environments, often with exposure to multiple toxicants; and difficulty in relating phenotypic effect size to toxic dose, especially when symptoms become manifest with a substantial time lag...
July 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28730546/mammalian-mitochondrial-rnas-are-degraded-in-the-mitochondrial-intermembrane-space-by-rnaset2
#11
Peipei Liu, Jinliang Huang, Qian Zheng, Leiming Xie, Xinping Lu, Jie Jin, Geng Wang
Mammalian mitochondrial genome encodes a small set of tRNAs, rRNAs, and mRNAs. The RNA synthesis process has been well characterized. How the RNAs are degraded, however, is poorly understood. It was long assumed that the degradation happens in the matrix where transcription and translation machineries reside. Here we show that contrary to the assumption, mammalian mitochondrial RNA degradation occurs in the mitochondrial intermembrane space (IMS) and the IMS-localized RNASET2 is the enzyme that degrades the RNAs...
July 20, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28730487/a-methodology-for-comprehensive-analysis-of-toll-like-receptor-signaling-in-macrophages
#12
Marijke Koppenol-Raab, Aleksandra Nita-Lazar
A combination of high-throughput, multiplexed, quantitative methods with computational modeling and statistical approaches is required to obtain system-level understanding of biological function. Mass spectrometry (MS)-based proteomics has emerged as a preferred tool for the analysis of changes in protein abundance and their post-translational modification (PTM) levels at a global scale, comparable with genomic experiments and generating data suitable for use in mathematical modeling of signaling pathways. Here we describe a set of parallel bottom-up proteomic approaches to detect and quantify the global protein changes in total intracellular proteins, their phosphorylation, and the proteins released by active and passive secretion or shedding mechanisms (referred to as the secretome as reviewed in Makridakis and Vlahou, J Proteome 73:2291-2305, 2010) in response to the stimulation of Toll-like receptors (TLRs) with specific ligands in cultured macrophages...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730473/expression-of-recombinant-phosphoproteins-for-signal-transduction-studies
#13
Karl W Barber, Jesse Rinehart
Complex signaling cascades are difficult to study in vitro without phosphorylated proteins. Here, we describe a technique for the routine production of recombinant phosphoproteins by directly incorporating phosphoserine as a nonstandard amino acid. This protocol utilizes an optimized phosphoserine orthogonal translation system and an engineered strain of E. coli containing no genomic amber codons. This approach has been used to generate a variety of phosphorylated proteins to understand the role of protein phosphorylation in cell signaling...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28729824/mouse-models-of-c9orf72-hexanucleotide-repeat-expansion-in-amyotrophic-lateral-sclerosis-frontotemporal-dementia
#14
REVIEW
Ranjan Batra, Chris W Lee
The presence of hexanucleotide repeat expansion (HRE) in the first intron of the human C9orf72 gene is the most common genetic cause underlying both familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Studies aimed at elucidating the pathogenic mechanisms associated of C9orf72 FTD and ALS (C9FTD/ALS) have focused on the hypothesis of RNA and protein toxic gain-of-function models, including formation of nuclear RNA foci containing GGGGCC (G4C2) HRE, inclusions containing dipeptide repeat proteins through a non-canonical repeat associated non-ATG (RAN) translation mechanism, and on loss-of-function of the C9orf72 protein...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28729413/breast-cancer-suppression-by-progesterone-receptors-is-mediated-by-their-modulation-of-estrogen-receptors-and-rna-polymerase-iii
#15
Jessica Finlay-Schultz, Austin E Gillen, Heather M Brechbuhl, Joshua J Ivie, Shawna B Matthews, Britta M Jacobsen, David L Bentley, Peter Kabos, Carol A Sartorius
Greater than 50% of estrogen receptor (ER)-positive breast cancers co-express the progesterone receptor (PR), which can directly and globally modify ER action to attenuate tumor growth. However, whether this attenuation is mediated only through PR-ER interaction remains unknown. To address this question, we assessed tumor growth in ER/PR-positive PDX models of breast cancer where both natural and synthetic progestins were found to antagonize the mitogenic effects of estrogens. Probing the genome-wide mechanisms by which this occurs, we documented that chronic progestin treatment blunted ER-mediated gene expression up to 2-fold at the level of mRNA transcripts...
July 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28729406/tumor-evolution-as-a-therapeutic-target
#16
REVIEW
Nabil Amirouchene-Angelozzi, Charles Swanton, Alberto Bardelli
Recent technological advances in the field of molecular diagnostics (including blood-based tumor genotyping) allow the measurement of clonal evolution in patients with cancer, thus adding a new dimension to precision medicine: time. The translation of this new knowledge into clinical benefit implies rethinking therapeutic strategies. In essence, it means considering as a target not only individual oncogenes but also the evolving nature of human tumors. Here, we analyze the limitations of targeted therapies and propose approaches for treatment within an evolutionary framework...
July 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28728879/identification-of-universal-diagnostic-peptide-candidates-for-neglected-tropical-diseases-caused-by-cestodes-through-the-integration-of-multi-genome-wide-analyses-and-immunoinformatic-predictions
#17
Sebastián Miles, Marco Navatta, Sylvia Dematteis, Gustavo Mourglia-Ettlin
Neglected tropical diseases caused by helminth infections currently affect millions of people worldwide. Among them, there are three tapeworm species of outstanding importance: Echinococcus granulosus, E. multilocularis, and Taenia solium, which are responsible for cystic echinococcosis, alveolar echinococcosis, and cysticercosis, respectively. Despite several attempts, there is still a need for an effective and low-cost serological diagnostic test that can be used in endemic countries. In the present work, we described an innovative bioinformatic workflow for a rational prediction of putative peptide candidates for one-step serological diagnosis of any of these infections...
July 17, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28724903/co-expression-network-analysis-of-toxin-antitoxin-loci-in-mycobacterium-tuberculosis-reveals-key-modulators-of-cellular-stress
#18
Amita Gupta, Balaji Venkataraman, Madavan Vasudevan, Kiran Gopinath Bankar
Research on toxin-antitoxin loci (TA loci) is gaining impetus due to their ubiquitous presence in bacterial genomes and their observed roles in stress survival, persistence and drug tolerance. The present study investigates the expression profile of all the seventy-nine TA loci found in Mycobacterium tuberculosis. The bacterium was subjected to multiple stress conditions to identify key players of cellular stress response and elucidate a TA-coexpression network. This study provides direct experimental evidence for transcriptional activation of each of the seventy-nine TA loci following mycobacterial exposure to growth-limiting environments clearly establishing TA loci as stress-responsive modules in M...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28719910/correlating-the-genetic-and-physical-map-of-barley-chromosome-3h-revealed-limitations-of-the-fish-based-mapping-of-nearby-single-copy-probes-caused-by-the-dynamic-structure-of-metaphase-chromosomes
#19
Fernanda O Bustamante, Lala Aliyeva-Schnorr, Jörg Fuchs, Sebastian Beier, Andreas Houben
Genetic maps are based on the recombination frequency of molecular markers which often show different positions in comparison to the corresponding physical maps. To decipher the position and order of DNA sequences genetically mapped to terminal and interstitial regions of barley (Hordeum vulgare) chromosome 3H, fluorescence in situ hybridization (FISH) on mitotic metaphase chromosomes was performed with 16 genomic single-copy probes derived from fingerprinted BAC contigs. Long genetic distances at subterminal regions translated into short physical distances, confirming that recombination events occur more often at distal regions of chromosome 3H...
July 19, 2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28717660/a-novel-molecular-diagnostics-platform-for-somatic-and-germline-precision-oncology
#20
Rubén Cabanillas, Marta Diñeiro, David Castillo, Patricia C Pruneda, Cristina Penas, Guadalupe A Cifuentes, Álvaro de Vicente, Noelia S Durán, Rebeca Álvarez, Gonzalo R Ordóñez, Juan Cadiñanos
BACKGROUND: Next-generation sequencing (NGS) opens new options in clinical oncology, from therapy selection to genetic counseling. However, realization of this potential not only requires succeeding in the bioinformatics and interpretation of the results, but also in their integration into the clinical practice. We have developed a novel NGS diagnostic platform aimed at detecting (1) somatic genomic alterations associated with the response to approved targeted cancer therapies and (2) germline mutations predisposing to hereditary malignancies...
July 2017: Molecular Genetics & Genomic Medicine
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