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https://www.readbyqxmd.com/read/28750325/cryo-em-maps-reveal-five-fold-channel-structures-and-their-modification-by-gatekeeper-mutations-in-the-parvovirus-minute-virus-of-mice-mvm-capsid
#1
Suriyasri Subramanian, Lindsey J Organtini, Alec Grossman, Phillip P Domeier, Javier O Cifuente, Alexander M Makhov, James F Conway, Anthony D'Abramo, Susan F Cotmore, Peter Tattersall, Susan Hafenstein
In minute virus of mice (MVM) capsids, icosahedral five-fold channels serve as portals mediating genome packaging, genome release, and the phased extrusion of viral peptides. Previous studies suggest that residues L172 and V40 are essential for channel function. The structures of MVMi wildtype, and mutant L172T and V40A virus-like particles (VLPs) were solved from cryo-EM data. Two constriction points, termed the mid-gate and inner-gate, were observed in the channels of wildtype particles, involving residues L172 and V40 respectively...
July 24, 2017: Virology
https://www.readbyqxmd.com/read/28749988/switching-of-dominant-retrotransposon-silencing-strategies-from-posttranscriptional-to-transcriptional-mechanisms-during-male-germ-cell-development-in-mice
#2
Kota Inoue, Kenji Ichiyanagi, Kei Fukuda, Michael Glinka, Hiroyuki Sasaki
Mammalian genomes harbor millions of retrotransposon copies, some of which are transpositionally active. In mouse prospermatogonia, PIWI-interacting small RNAs (piRNAs) combat retrotransposon activity to maintain the genomic integrity. The piRNA system destroys retrotransposon-derived RNAs and guides de novo DNA methylation at some retrotransposon promoters. However, it remains unclear whether DNA methylation contributes to retrotransposon silencing in prospermatogonia. We have performed comprehensive studies of DNA methylation and polyA(+) RNAs (transcriptome) in developing male germ cells from Pld6/Mitopld and Dnmt3l knockout mice, which are defective in piRNA biogenesis and de novo DNA methylation, respectively...
July 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28749326/pneumococcal-neuraminidase-activates-tgf-%C3%AE-signalling
#3
Nina Gratz, Lip Nam Loh, Beth Mann, Geli Gao, Robert Carter, Jason Rosch, Elaine I Tuomanen
Neuraminidase A (NanA) is an important virulence factor that is anchored to the pneumococcal cell wall and cleaves sialic acid on host substrates. We noted that a secreted allele of NanA was over-represented in invasive pneumococcal isolates and promoted the development of meningitis when swapped into the genome of non-meningitis isolates replacing cell wall-anchored NanA. Both forms of recombinant NanA directly activated transforming growth factor (TGF)-β, increased SMAD signalling and promoted loss of endothelial tight junction ZO-1...
July 28, 2017: Microbiology
https://www.readbyqxmd.com/read/28747595/nac-ameliorates-dental-composite-induced-dna-double-strand-breaks-and-chromatin-condensation
#4
Panorea Styllou, Marianthi Styllou, Reinhard Hickel, Christof Högg, Franz Xaver Reichl, Harry Scherthan
Released (co)monomers from dental composite components can induce DNA damage of which DNA double-strand breaks (DSBs) threaten genome integrity. Here, we tested whether the administration of the antioxidant N-acetylcysteine (NAC) is able to reduce the dental composite-induced DSBs in primary human gingiva fibroblasts. The dental composites Bis-GMA (bisphenol-A-glycerolate dimethacrylate), GMA (glycidyl methacrylate), HEMA (2-hydroxyethyl methacrylate) and TEGDMA (triethyleneglycol dimethacrylate) were found to induce co-localizing microscopic nuclear foci numbers of the DSB markers γ-H2AX and 53BP1 per cell in the order: GMA>Bis-GMA>TEGDMA>HEMA...
July 26, 2017: Dental Materials Journal
https://www.readbyqxmd.com/read/28747499/effects-of-the-inner-nuclear-membrane-proteins-sun1-unc-84a-and-sun2-unc-84b-on-the-early-steps-of-hiv-1-infection
#5
Torsten Schaller, Lorenzo Bulli, Darja Pollpeter, Gilberto Betancor, Juliane Kutzner, Luis Apolonia, Nikolas Herold, Robin Burk, Michael H Malim
Human immunodeficiency virus type 1 (HIV-1) infection of dividing and non-dividing cells involves regulatory interactions with the nuclear pore complex (NPC), followed by translocation to the nucleus and preferential integration into genomic areas in proximity to the inner nuclear membrane (INM). To identify host proteins that may contribute to these processes, we performed an overexpression screen of known membrane-associated NE proteins. We found that the integral transmembrane proteins SUN1/UNC84A and SUN2/UNC84B are potent or modest inhibitors of HIV-1 infection, respectively, and that suppression corresponds to defects in the accumulation of viral cDNA in the nucleus...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28747380/identification-of-differentially-expressed-splice-variants-by-the-proteogenomic-pipeline-splicify
#6
Malgorzata A Komor, Thang Pham, Annemieke C Hiemstra, Sander R Piersma, Anne S Bolijn, Tim Schelfhorst, Pien M Delis-van Diemen, Marianne Tijssen, Robert P Sebra, Meredith Ashby, Gerrit A Meijer, Connie R Jimenez, Remond J A Fijneman
Proteogenomics, i.e. comprehensive integration of genomics and proteomics data, is a powerful approach identifying novel protein biomarkers. This is especially the case for proteins that differ structurally between disease and control conditions. As tumor development is associated with aberrant splicing, we focus on this rich source of cancer specific biomarkers. To this end, we developed a proteogenomic pipeline, Splicify, which is able to detect differentially expressed protein isoforms. Splicify is based on integrating RNA massive parallel sequencing data and tandem mass spectrometry proteomics data to identify protein isoforms resulting from differential splicing between two conditions...
July 26, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28747339/clinical-significance-of-four-molecular-subtypes-of-gastric-cancer-identified-by-the-cancer-genome-atlas-project
#7
Bo Hwa Sohn, Jun-Eul Hwang, Hee-Jin Jang, Hyun-Sung Lee, Sang Cheul Oh, Jae-Jun Shim, Keun-Wook Lee, Eui Hyun Kim, Sun Young Yim, Sang Ho Lee, Jae-Ho Cheong, Woojin Jeong, Jae Yong Cho, Joohee Kim, Jungsoo Chae, Jeeyun Lee, Won Ki Kang, Sung Kim, Sung Hoon Noh, Jaffer A Ajani, Ju-Seog Lee
Purpose: The Cancer Genome Atlas (TCGA) project recently uncovered four molecular subtypes of gastric cancer: Epstein-Barr virus (EBV), microsatellite instability (MSI), genomically stable (GS), and chromosomal instability (CIN). However, their clinical significances are currently unknown. We aimed to investigate the relationship between subtypes and prognosis of patients with gastric cancer.Experimental Design: Gene expression data from a TCGA cohort (n = 262) were used to develop a subtype prediction model, and the association of each subtype with survival and benefit from adjuvant chemotherapy was tested in 2 other cohorts (n = 267 and 432)...
July 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28746875/kmt5a-controls-hepatic-metabolic-pathways-by-facilitating-rna-pol-ii-release-from-promoter-proximal-regions
#8
Kostas C Nikolaou, Panagiotis Moulos, Vangelis Harokopos, George Chalepakis, Iannis Talianidis
H4K20 monomethylation maintains genome integrity by regulating proper mitotic condensation, DNA damage response, and replication licensing. Here, we show that, in non-dividing hepatic cells, H4K20Me1 is specifically enriched in active gene bodies and dynamically regulated by the antagonistic action of Kmt5a methylase and Kdm7b demethylase. In liver-specific Kmt5a-deficient mice, reduced levels of H4K20Me1 correlated with reduced RNA Pol II release from promoter-proximal regions. Genes regulating glucose and fatty acid metabolism were most sensitive to impairment of RNA Pol II release...
July 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28746311/prolonged-mek1-2-suppression-impairs-the-developmental-potential-of-embryonic-stem-cells
#9
Jiho Choi, Aaron J Huebner, Kendell Clement, Ryan M Walsh, Andrej Savol, Kaixuan Lin, Hongcang Gu, Bruno Di Stefano, Justin Brumbaugh, Sang-Yong Kim, Jafar Sharif, Christopher M Rose, Arman Mohammad, Junko Odajima, Jean Charron, Toshi Shioda, Andreas Gnirke, Steven Gygi, Haruhiko Koseki, Ruslan I Sadreyev, Andrew Xiao, Alexander Meissner, Konrad Hochedlinger
Concomitant activation of the Wnt pathway and suppression of Mapk signalling by two small molecule inhibitors (2i) in the presence of leukaemia inhibitory factor (LIF) (hereafter termed 2i/L) induces a naive state in mouse embryonic stem (ES) cells that resembles the inner cell mass (ICM) of the pre-implantation embryo. Since the ICM exists only transiently in vivo, it remains unclear how sustained propagation of naive ES cells in vitro affects their stability and functionality. Here we show that prolonged culture of male mouse ES cells in 2i/L results in irreversible epigenetic and genomic changes that impair their developmental potential...
July 26, 2017: Nature
https://www.readbyqxmd.com/read/28746207/integrating-nested-pcr-with-high-throughput-sequencing-to-characterize-mutations-of-hbv-genome-in-low-viral-load-samples
#10
Xianjun Wang, Lihui Xu, Yueming Chen, Anbing Liu, Liqian Wang, Peisong Xu, Yunhui Liu, Lei Li, Fei Meng
Due to the low viral load of hepatitis B virus (HBV) in plasma samples, conventional techniques have limitations to the detection of antiviral resistance mutations. To solve the problem, we developed a fast, highly sensitive, and accurate method to sequence the HBV whole-genome sequencing in plasma samples which had various viral loads from very low to high.Twenty-one plasma samples were collected from patients who were carriers of HBV from the Hangzhou First People's Hospital. Two pairs of conserved, overlapping, nested primers were used to amplify and sequence the whole HBV genome in 8 plasma samples with different viral loads...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28746050/integration-of-alv-into-ctdspl-and-ctdspl2-genes-in-b-cell-lymphomas-promotes-cell-immortalization-migration-and-survival
#11
Shelby Winans, Alyssa Flynn, Sanandan Malhotra, Vidya Balagopal, Karen L Beemon
Avian leukosis virus induces tumors in chickens by integrating into the genome and altering expression of nearby genes. Thus, ALV can be used as an insertional mutagenesis tool to identify novel genes involved in tumorigenesis. Deep sequencing analysis of viral integration sites has identified CTDSPL and CTDSPL2 as common integration sites in ALV-induced B-cell lymphomas, suggesting a potential role in driving oncogenesis. We show that in tumors with integrations in these genes, the viral promoter is driving the expression of a truncated fusion transcript...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28745936/5-hydroxymethylcytosine-in-dna-repair-a-new-player-or-a-red-herring
#12
Omar L Kantidze, Sergey V Razin
Active DNA demethylation performed by ten-eleven translocation (TET) enzymes produces 5-hydroxymethylcytosines, 5-formylcytosines, and 5-carboxylcytosines. Recent observations suggest that 5-hydroxymethylcytosine is a stable epigenetic mark rather than merely an intermediate of DNA demethylation. However, the clear functional role of this new epigenetic player is elusive. The contribution of 5-hydroxymethylation to DNA repair is being discussed currently. Recently Jiang and colleagues have demonstrated that DNA damage response-activated ATR kinase phosphorylates TET3 in mammalian cells and promotes DNA demethylation and 5-hydroxymethylcytosine accumulation...
July 26, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28745585/maturation-of-selected-human-mitochondrial-trnas-requires-deadenylation
#13
Sarah F Pearce, Joanna Rorbach, Lindsey Van Haute, Aaron R D'Souza, Pedro Rebelo-Guiomar, Christopher A Powell, Ian Brierley, Andrew E Firth, Michal Minczuk
Human mitochondria contain a genome (mtDNA) that encodes essential subunits of the oxidative phosphorylation system. Expression of mtDNA entails multi-step maturation of precursor RNA. In other systems, the RNA life cycle involves surveillance mechanisms, however, the details of RNA quality control have not been extensively characterised in human mitochondria. Using a mitochondrial ribosome profiling and mitochondrial poly(A)-tail RNA sequencing (MPAT-Seq) assay we identify the poly(A)-specific exoribonuclease PDE12 as a major factor for the quality control of mitochondrial non-coding RNAs...
July 26, 2017: ELife
https://www.readbyqxmd.com/read/28744812/in-vivo-effects-of-dexamethasone-on-blood-gene-expression-in-ataxia-telangiectasia
#14
Michele Menotta, Sara Biagiotti, Sara Orazi, Luigia Rossi, Luciana Chessa, Vincenzo Leuzzi, Daniela D'Agnano, Alessandro Plebani, Annarosa Soresina, Mauro Magnani
Ataxia telangiectasia (AT) is a rare incurable genetic disease caused by biallelic mutations in the Ataxia telangiectasia-mutated gene. Intra-erythrocyte infusion of dexamethasone improves clinical outcomes in AT patients; however, the molecular mechanisms that lead to this improvement remain unknown. Hence, to gain a better understanding of these mechanisms, we assessed the effects of glucocorticoid administration on gene expression in the blood of AT patients. Whole blood was obtained from nine children enrolled in a phase two clinical trial, who were being treated with dexamethasone (AT Dexa), from six untreated AT patients (AT) and from six healthy volunteers (WT)...
July 25, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28743667/integrative-analysis-of-mrna-and-mirna-expression-profiles-in-oral-lichen-planus-preliminary-results
#15
Junjun Chen, Guanhuan Du, Yufeng Wang, Linjun Shi, Jun Mi, Guoyao Tang
OBJECTIVE: Oral lichen planus (OLP), a chronic inflammatory disease of unknown etiology, is considered a potentially malignant oral disorder. The aim of the present study was to analyze candidate microRNAs (miRNAs) and genes from patients with OLP and healthy controls (HCs). STUDY DESIGN: Biopsy specimens of the oral mucosa were collected from patients with OLP (n = 9) and from HCs (n = 4). Differentially expressed miRNAs and differentially expressed genes were screened by using next-generation sequencing with DESeq and edgeR software algorithms...
June 8, 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/28743172/modelling-nutritional-mutualisms-challenges-and-opportunities-for-data-integration
#16
REVIEW
Teresa J Clark, Colleen A Friel, Emily Grman, Yair Shachar-Hill, Maren L Friesen
Nutritional mutualisms are ancient, widespread, and profoundly influential in biological communities and ecosystems. Although much is known about these interactions, comprehensive answers to fundamental questions, such as how resource availability and structured interactions influence mutualism persistence, are still lacking. Mathematical modelling of nutritional mutualisms has great potential to facilitate the search for comprehensive answers to these and other fundamental questions by connecting the physiological and genomic underpinnings of mutualisms with ecological and evolutionary processes...
July 25, 2017: Ecology Letters
https://www.readbyqxmd.com/read/28743002/drosophila-histone-demethylase-kdm4a-has-enzymatic-and-non-enzymatic-roles-in-controlling-heterochromatin-integrity
#17
Serafin U Colmenares, Joel M Swenson, Sasha A Langley, Cameron Kennedy, Sylvain V Costes, Gary H Karpen
Eukaryotic genomes are broadly divided between gene-rich euchromatin and the highly repetitive heterochromatin domain, which is enriched for proteins critical for genome stability and transcriptional silencing. This study shows that Drosophila KDM4A (dKDM4A), previously characterized as a euchromatic histone H3 K36 demethylase and transcriptional regulator, predominantly localizes to heterochromatin and regulates heterochromatin position-effect variegation (PEV), organization of repetitive DNAs, and DNA repair...
July 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28742982/investigation-of-orthologous-pathogen-recognition-gene-rich-regions-in-solanaceous-species
#18
A Di Donato, Giuseppe Andolfo, A Ferrarini, M Delledonne, M R Ercolano
The genome architecture of pathogen receptor genes (PRGs) was extensively investigated in several plant species. However, we still know little about their elaborate reorganization arose during the plant speciation process. Using recently released pepper and eggplant genome sequences we were able to identify 1097 pathogen recognition genes in pepper Zunla-1 and 775 in eggplant Nakate-Shinkuro. The retrieved genes were analysed for their tendency to cluster, using different methods to infer the means of grouping...
July 25, 2017: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28742856/fit-for-genomic-and-proteomic-purposes-sampling-the-fitness-of-nucleic-acid-and-protein-derivatives-from-formalin-fixed-paraffin-embedded-tissue
#19
Anna Yakovleva, Jordan L Plieskatt, Sarah Jensen, Razan Humeida, Jonathan Lang, Guangzhao Li, Paige Bracci, Sylvia Silver, Jeffrey Michael Bethony
The demand for nucleic acid and protein derivatives from formalin-fixed paraffin-embedded (FFPE) tissue has greatly increased due to advances in extraction and purification methods, making these derivatives available for numerous genomic and proteomic platforms. Previously, DNA, RNA, microRNA (miRNA), or protein derived from FFPE tissue blocks were considered "unfit" for such platforms, as the process of tissue immobilization by FFPE resulted in cross-linked, fragmented, and chemically modified macromolecules...
2017: PloS One
https://www.readbyqxmd.com/read/28742119/doestrare-a-statistical-test-to-identify-local-enrichments-in-rare-genomic-variants-associated-with-disease
#20
Elodie Persyn, Matilde Karakachoff, Solena Le Scouarnec, Camille Le Clézio, Dominique Campion, French Exome Consortium, Jean-Jacques Schott, Richard Redon, Lise Bellanger, Christian Dina
Next-generation sequencing technologies made it possible to assay the effect of rare variants on complex diseases. As an extension of the "common disease-common variant" paradigm, rare variant studies are necessary to get a more complete insight into the genetic architecture of human traits. Association studies of these rare variations show new challenges in terms of statistical analysis. Due to their low frequency, rare variants must be tested by groups. This approach is then hindered by the fact that an unknown proportion of the variants could be neutral...
2017: PloS One
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