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https://www.readbyqxmd.com/read/29159825/modulation-of-the-intestinal-bile-acid-fxr-fgf15-axis-improves-alcoholic-liver-disease-in-mice
#1
Phillipp Hartmann, Katrin Hochrath, Angela Horvath, Peng Chen, Caroline T Seebauer, Cristina Llorente, Lirui Wang, Yazen Alnouti, Derrick E Fouts, Peter Stärkel, Rohit Loomba, Sally Coulter, Christopher Liddle, Ruth T Yu, Lei Ling, Stephen J Rossi, Alex M DePaoli, Michael Downes, Ronald M Evans, David A Brenner, Bernd Schnabl
Alcoholic liver disease is associated with changes in the intestinal microbiota. Functional consequences of alcohol-associated dysbiosis are largely unknown. The aim of this study was to identify a mechanism of how changes in the intestinal microbiota contribute to alcoholic liver disease. Metagenomic sequencing of intestinal contents demonstrated that chronic ethanol feeding in mice is associated with an overrepresentation of bacterial genomic DNA encoding choloylglycine hydrolase, which deconjugates bile acids in the intestine...
November 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29158530/mrnas-containing-nmd-competent-premature-termination-codons-are-stabilized-and-translated-under-upf1-depletion
#2
Won Kyu Kim, SeongJu Yun, Yujin Kwon, Kwon Tae You, Nara Shin, Jiyoon Kim, Hoguen Kim
mRNAs containing premature termination codons (PTCs) are rapidly degraded through nonsense-mediated mRNA decay (NMD). However, some PTC-containing mRNAs evade NMD, and might generate mutant proteins responsible for various diseases, including cancers. Using PTC-containing human genomic β-globin constructs, we show that a fraction (~30%) of PTC-containing mRNAs expressed from NMD-competent PTC-containing constructs were as stable as their PTC-free counterparts in a steady state. These PTC-containing mRNAs were monosome-enriched and rarely contributed to expression of mutant proteins...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29158291/rad51c-xrcc3-facilitates-mitochondrial-dna-replication-and-maintains-integrity-of-the-mitochondrial-genome
#3
Anup Mishra, Sneha Saxena, Anjali Kaushal, Ganesh Nagaraju
Mechanisms underlying mitochondrial genome maintenance have recently gained wide attention as mutations in mitochondrial DNA (mtDNA) lead to inherited muscular and neurological diseases which are linked to aging. It has been previously reported that human RAD51, RAD51C and XRCC3 localize to mitochondria upon oxidative stress and are required for the maintenance of mtDNA stability. Since RAD51 and RAD51 paralogs are spontaneously imported into mitochondria, their precise role in mtDNA maintenance during unperturbed conditions remains elusive...
November 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29157973/when-the-good-go-bad-mutant-npm1-in-acute-myeloid-leukemia
#4
REVIEW
Preethi Kunchala, Sudhakiranmayi Kuravi, Roy Jensen, Joseph McGuirk, Ramesh Balusu
Nucleophosmin 1 (NPM1) is a nucleolar phosphoprotein that performs diverse biological functions including molecular chaperoning, ribosome biogenesis, DNA repair, and genome stability. Acute myeloid leukemia (AML) is a heterogeneous disease, more than half of the AML cases exhibit normal karyotype (NK). Approximately 50-60 percent of patients with NK-AML carry NPM1 mutations which are characterized by cytoplasmic dislocation of the NPM1 protein. In AML, mutant NPM1 (NPM1c+) acts in a dominant negative fashion and also blocks the differentiation of myeloid cells through gain-of-function for the AML phenotype...
November 4, 2017: Blood Reviews
https://www.readbyqxmd.com/read/29157079/zeb1-inhibition-sensitizes-cells-to-the-atr-inhibitor-ve-821-by-abrogating-epithelial-mesenchymal-transition-and-enhancing-dna-damage
#5
Na Song, Wei Jing, Ce Li, Ming Bai, Yu Cheng, Heming Li, Kezuo Hou, Yanrong Li, Kai Wang, Zhi Li, Yunpeng Liu, Xiujuan Qu, Xiaofang Che
The ataxia-telangiectasia-mutated (ATM) and rad3-related (ATR) checkpoint pathway plays an essential role in modulating cellular responses to replication stress and DNA damage to maintain genomic stability. In various tumors, cancer cells have increased dependence on ATR signaling for survival, making ATR a promising target for cancer therapy. ATR inhibitors sensitize multiple tumor cell types to radiation and DNA-damaging agents, but application of an ATR inhibitor alone shows limited efficacy. In the present study, we investigated the role of epithelial-to-mesenchymal transition (EMT) and the EMT transcription factor ZEB1 in regulating cell sensitivity to the ATR inhibitor VE-821...
November 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29157061/the-dna-pol-%C3%AF%C2%B5-stimulatory-activity-of-mrc1-is-modulated-by-phosphorylation
#6
Zhong-Xin Zhang, Jingjing Zhang, Qinhong Cao, Judith L Campbell, Huiqiang Lou
DNA replication checkpoint (Mec1-Mrc1-Rad53 in budding yeast) is an evolutionarily conserved surveillance system to ensure proper DNA replication and genome stability in all eukaryotes. Compared to its well-known function as a mediator of replication checkpoint, the exact role of Mrc1 as a component of normal replication forks remains relatively unclear. In this study, we provide in vitro biochemical evidence to support that yeast Mrc1 is able to enhance the activity of DNA polymerase ϵ (Pol ϵ), the major leading strand replicase...
November 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29156836/the-role-of-rak-in-the-regulation-of-stability-and-function-of-brca1
#7
Jung-Lye Kim, Geun-Hyoung Ha, Loredana Campo, Mitchell F Denning, Tarun B Patel, Clodia Osipo, Shiaw-Yih Lin, Eun-Kyoung Breuer
BRCA1 is an important player in the DNA damage response signaling, and its deficiency results in genomic instability. A complete loss or significantly reduced BRCA1 protein expression is often found in sporadic breast cancer cases despite the absence of genetic or epigenetic aberrations, suggesting the existence of other regulatory mechanisms controlling BRCA1 protein expression. Herein, we demonstrate that Fyn-related kinase (Frk)/Rak plays an important role in maintaining genomic stability, possibly in part through positively regulating BRCA1 protein stability and function via tyrosine phosphorylation on BRCA1 Tyr1552...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156798/arhi-is-a-novel-epigenetic-silenced-tumor-suppressor-in-sporadic-pheochromocytoma
#8
Dong Wang, Li Song, Liang Wang, Lianmei Zhao, Bai Xiang, Ying Li, Baoen Shan, Jing Liu
Pheochromocytoma (PCC) is related to germline mutations in 12 susceptibility genes. Although comparative genomic hybridization array has revealed some putative tumor suppressor genes on the short arm of chromosome 1 that are likely to be involved in PCC tumorigenesis, the molecules involved, except for those encoded by known susceptibility genes, have not been found in the generation of sporadic tumors. In the present work, we first identified that the unmethylated allele of Aplasia Ras homolog member I (ARHI) was deleted in most PCC tumors which retained a hypermethylated copy, while its mRNA level was significantly correlated with the unmethylated copy...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155820/mass-spectrometry-based-quantification-of-the-cellular-response-to-ultraviolet-radiation-in-hela-cells
#9
Hong Xu, Xuanyi Chen, Nanjiao Ying, Meixia Wang, Xiaoli Xu, Rongyi Shi, Yuejin Hua
Ultraviolet (UV) irradiation is a common form of DNA damage that can cause pyrimidine dimers between DNA, which can cause gene mutations, even double-strand breaks and threaten genome stability. If DNA repair systems default their roles at this stage, the organism can be damaged and result in disease, especially cancer. To better understand the cellular response to this form of damage, we applied highly sensitive mass spectrometry to perform comparative proteomics of phosphorylation in HeLa cells. A total of 4367 phosphorylation sites in 2100 proteins were identified, many of which had not been reported previously...
2017: PloS One
https://www.readbyqxmd.com/read/29154869/evaluating-different-dna-binding-domains-to-modulate-l1-orf2p-driven-site-specific-retrotransposition-events-in-human-cells
#10
Catherine M Ade, Rebecca S Derbes, Bradley J Wagstaff, Sara B Linker, Travis B White, Dawn Deharo, Victoria P Belancio, Zoltán Ivics, Astrid M Roy-Engel
DNA binding domains (DBDs) have been used with great success to impart targeting capabilities to a variety of proteins creating highly useful genomic tools. We evaluated the ability of five types of DBDs and strategies (AAV Rep proteins, Cre, TAL effectors, zinc finger proteins, and Cas9/gRNA system) to target the L1 ORF2 protein to drive retrotransposition of Alu inserts to specific sequences in the human genome. First, we find that the L1 ORF2 protein tolerates the addition of protein domains both at the amino- and carboxy-terminus...
November 14, 2017: Gene
https://www.readbyqxmd.com/read/29154021/diagnosis-of-fanconi-anaemia-by-ionising-radiation-or-mitomycin-c-induced-micronuclei
#11
Flavia Zita Francies, Rosalind Wainwright, Janet Poole, Kim De Leeneer, Ilse Coene, Greet Wieme, Hélène A Poirel, Bénédicte Brichard, Stephanie Vermeulen, Anne Vral, Jacobus Slabbert, Kathleen Claes, Ans Baeyens
Fanconi Anaemia (FA) is an autosomal recessive disorder characterised by defects in DNA repair, associated with chromosomal instability and cellular hypersensitivity to DNA cross-linking agents such as mitomycin C (MMC). The FA repair pathway involves complex DNA repair mechanisms crucial for genomic stability. Deficiencies in DNA repair genes give rise to chromosomal radiosensitivity. FA patients have shown increased clinical radiosensitivity by exhibiting adverse normal tissue side-effects. The study aimed to investigate chromosomal radiosensitivity of homozygous and heterozygous carriers of FA mutations using three micronucleus (MN) assays...
November 8, 2017: DNA Repair
https://www.readbyqxmd.com/read/29153394/vcp-p97-mediated-unfolding-as-a-principle-in-protein-homeostasis-and-signaling
#12
REVIEW
Johannes van den Boom, Hemmo Meyer
The AAA+-type ATPase p97 governs an ever-expanding number of cellular processes reaching from degradation of damaged proteins and organelles to key signaling events and chromatin regulation with thousands of client proteins. With its relevance for cellular homeostasis and genome stability, it is linked to muscular and neuronal degeneration and, conversely, constitutes an attractive anti-cancer drug target. Its molecular function is ATP-driven protein unfolding, which is directed by ubiquitin and assisted by a host of cofactor proteins...
November 15, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29152580/chromosomal-targeting-by-the-type-iii-a-crispr-cas-system-can-reshape-genomes-in-staphylococcus-aureus
#13
Jing Guan, Wanying Wang, Baolin Sun
CRISPR-Cas (clustered regularly interspaced short palindromic repeat [CRISPR]-CRISPR-associated protein [Cas]) systems can provide protection against invading genetic elements by using CRISPR RNAs (crRNAs) as a guide to locate and degrade the target DNA. CRISPR-Cas systems have been classified into two classes and five types according to the content of cas genes. Previous studies have indicated that CRISPR-Cas systems can avoid viral infection and block plasmid transfer. Here we show that chromosomal targeting by the Staphylococcus aureus type III-A CRISPR-Cas system can drive large-scale genome deletion and alteration within integrated staphylococcal cassette chromosome mec (SCCmec)...
November 2017: MSphere
https://www.readbyqxmd.com/read/29151862/profiling-the-immunome-of-little-brown-myotis-provides-a-yardstick-for-measuring-the-genetic-response-to-white-nose-syndrome
#14
Michael E Donaldson, Christina M Davy, Craig K R Willis, Scott McBurney, Allysia Park, Christopher J Kyle
White-nose syndrome (WNS) has devastated populations of hibernating bats in eastern North America, leading to emergency conservation listings for several species including the previously ubiquitous little brown myotis (Myotis lucifugus). However, some bat populations near the epicenter of the WNS panzootic appear to be stabilizing after initial precipitous declines, which could reflect a selective immunogenetic sweep. To investigate the hypothesis that WNS exerts significant selection on the immunome of affected bat populations, we developed a novel, high-throughput sequence capture assay targeting 138 adaptive, intrinsic, and innate immunity genes of putative adaptive significance, as well as their respective regulatory regions (~370 kbp of genomic sequence/individual)...
December 2017: Evolutionary Applications
https://www.readbyqxmd.com/read/29151576/mapping-the-sugar-dependency-for-rational-generation-of-a-dna-rna-hybrid-guided-cas9-endonuclease
#15
Fernando Orden Rueda, Michal Bista, Matthew D Newton, Anne U Goeppert, M Emanuela Cuomo, Euan Gordon, Felix Kröner, Jon A Read, Jonathan D Wrigley, David Rueda, Benjamin J M Taylor
The CRISPR-Cas9 RNA-guided endonuclease system allows precise and efficient modification of complex genomes and is continuously developed to enhance specificity, alter targeting and add new functional moieties. However, one area yet to be explored is the base chemistry of the associated RNA molecules. Here we show the design and optimisation of hybrid DNA-RNA CRISPR and tracr molecules based on structure-guided approaches. Through careful mapping of the ribose requirements of Cas9, we develop hybrid versions possessing minimal RNA residues, which are sufficient to direct specific nuclease activity in vitro and in vivo with reduced off-target activity...
November 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/29150651/comprehensive-functional-enrichment-analysis-of-male-infertility
#16
Seyed Morteza Razavi, Marjan Sabbaghian, Mahdi Jalili, Adeleh Divsalar, Olaf Wolkenhauer, Ali Salehzadeh-Yazdi
Spermatogenesis is a multifactorial process that forms differentiated sperm cells in a complex microenvironment. This process involves the genome, epigenome, transcriptome, and proteome to ensure the stability of the spermatogonia and supporting cells. The identification of signaling pathways linked to infertility has been hampered by the inherent complexity and multifactorial aspects of spermatogenesis. Systems biology is a promising approach to unveil underlying signaling pathways and genes and identify putative biomarkers...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150511/sulfolobus-acidocaldarius-uptakes-pentoses-via-a-cut2-type-abc-transporter-and-metabolizes-them-through-the-aldolase-independent-weimberg-pathway
#17
Michaela Wagner, Lu Shen, Andreas Albersmeier, Nienke van der Kolk, Sujin Kim, Jaeho Cha, Christopher Bräsen, Jörn Kalinowski, Bettina Siebers, Sonja-Verena Albers
Sulfolobus spp. possess a great metabolic versatility and grow heterotrophically on various carbon sources such as different sugars and peptides. Known sugar transporters in Archaea predominantly belong to ABC transport systems. Although several ABC transporters for sugar uptake have been characterized in the crenarchaeon Sulfolobus solfataricus, only one homologue of these transporters, the maltose/maltooligomer transporter, could be identified in the closely related Sulfolobus acidocaldarius Comparison of the transcriptome of S...
November 17, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29150509/the-tape-measure-protein-is-involved-in-the-heat-stability-of-lactococcus-lactis-phages
#18
Hany Geagea, Simon J Labrie, Muriel Subirade, Sylvain Moineau
Virulent lactococcal phages are still a major risk for milk fermentation processes as they may lead to slowdowns and low quality fermented dairy products, particularly cheeses. Some of the phage control strategies used by the industry rely on heat treatments. Recently, a few Lactococcus lactis phages were found to be highly thermo-resistant. To identify the genetic determinant(s) responsible for the thermal resistance of lactococcal phages, we used the virulent phage CB14 (sk1virus/936 group) to select for phage mutants with increased heat stability...
November 17, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29150248/cryopreservation-at-75%C3%A2-c-of-agaricus-subrufescens-on-wheat-grains-with-sucrose
#19
Lienine Luiz Zaghi Júnior, Ana Daniela Lopes, Fábio Aparecido Cordeiro, Itaruã Machri Colla, Míria Benetati Delgado Bertéli, Juliana Silveira do Valle, Giani Andrea Linde, Nelson Barros Colauto
Agaricus subrufescens is a basidiomycete which is studied because of its medicinal and gastronomic importance; however, less attention has been paid to its preservation. This study aimed to evaluate the effect of sucrose addition to substrate and cryotube on the viability of Agaricus subrufescens cryopreserved at -20°C and at -75°C for one and two years. Zero, 10% or 20% sucrose was added to potato dextrose agar or wheat grain. The mycelia were cryopreserved in the absence of cryoprotectant or with sucrose solutions at 15%, 30% or 45%...
October 13, 2017: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
https://www.readbyqxmd.com/read/29149880/analytical-performance-of-envisia-a-genomic-classifier-for-usual-interstitial-pneumonia
#20
Yoonha Choi, Jiayi Lu, Zhanzhi Hu, Daniel G Pankratz, Huimin Jiang, Manqiu Cao, Cristina Marchisano, Jennifer Huiras, Grazyna Fedorowicz, Mei G Wong, Jessica R Anderson, Edward Y Tom, Joshua Babiarz, Urooj Imtiaz, Neil M Barth, P Sean Walsh, Giulia C Kennedy, Jing Huang
BACKGROUND: Clinical guidelines specify that diagnosis of interstitial pulmonary fibrosis (IPF) requires identification of usual interstitial pneumonia (UIP) pattern. While UIP can be identified by high resolution CT of the chest, the results are often inconclusive, making surgical lung biopsy necessary to reach a definitive diagnosis (Raghu et al., Am J Respir Crit Care Med 183(6):788-824, 2011). The Envisia genomic classifier differentiates UIP from non-UIP pathology in transbronchial biopsies (TBB), potentially allowing patients to avoid an invasive procedure (Brown et al...
November 17, 2017: BMC Pulmonary Medicine
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