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Chromatin aging

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https://www.readbyqxmd.com/read/28289275/epigenetic-programming-by-stress-and-glucocorticoids-along-the-human-lifespan
#1
A S Zannas, G P Chrousos
Psychosocial stress triggers a set of behavioral, neural, hormonal, and molecular responses that can be a driving force for survival when adaptive and time-limited, but may also contribute to a host of disease states if dysregulated or chronic. The beneficial or detrimental effects of stress are largely mediated by the hypothalamic-pituitary axis, a highly conserved neurohormonal cascade that culminates in systemic secretion of glucocorticoids. Glucocorticoids activate the glucocorticoid receptor, a ubiquitous nuclear receptor that not only causes widespread changes in transcriptional programs, but also induces lasting epigenetic modifications in many target tissues...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28288000/age-associated-chromatin-relaxation-is-enhanced-in-huntington-s-disease-mice
#2
Myungsun Park, Byungkuk Min, Kyuheum Jeon, Sunwha Cho, Jung Sun Park, Jisun Kim, Jeha Jeon, Jinhoi Song, Seokho Kim, Sangkyun Jeong, Hyemyung Seo, Yong-Kook Kang
Expansion of polyglutamine stretch in the huntingtin (HTT) protein is a major cause of Huntington's disease (HD). The polyglutamine part in HTT interacts with various proteins implicated in epigenetic regulation of genes, suggesting that mutant HTT may disturb the integrity of the epigenetic system. Here, we used a PCRseq-based method to examine expression profile of 395 exonic segments from 260 "epi-driver" genes in splenic T lymphocytes from aged HD mice. We identified 67 exonic segments differentially expressed between young and aged HD mice, most of them upregulated in the aged...
March 12, 2017: Aging
https://www.readbyqxmd.com/read/28286338/integration-site-selection-by-retroviruses-and-transposable-elements-in-eukaryotes
#3
REVIEW
Tania Sultana, Alessia Zamborlini, Gael Cristofari, Pascale Lesage
Transposable elements and retroviruses are found in most genomes, can be pathogenic and are widely used as gene-delivery and functional genomics tools. Exploring whether these genetic elements target specific genomic sites for integration and how this preference is achieved is crucial to our understanding of genome evolution, somatic genome plasticity in cancer and ageing, host-parasite interactions and genome engineering applications. High-throughput profiling of integration sites by next-generation sequencing, combined with large-scale genomic data mining and cellular or biochemical approaches, has revealed that the insertions are usually non-random...
March 13, 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/28284043/the-histone-variant-h3-3-claims-its-place-in-the-crowded-scene-of-epigenetics
#4
Daniele Bano, Antonia Piazzesi, Paolo Salomoni, Pierluigi Nicotera
Histones are evolutionarily conserved DNA-binding proteins. As scaffolding molecules, they significantly regulate the DNA packaging into the nucleus of all eukaryotic cells. As docking units, they influence the recruitment of the transcriptional machinery, thus establishing unique gene expression patterns that ultimately promote different biological outcomes. While canonical histones H3.1 and H3.2 are synthetized and loaded during DNA replication, the histone variant H3.3 is expressed and deposited into the chromatin throughout the cell cycle...
March 10, 2017: Aging
https://www.readbyqxmd.com/read/28281664/genetic-interactions-and-functional-analyses-of-the-fission-yeast-gsk3-and-amk2-single-and-double-mutants-defective-in-torc1-dependent-processes
#5
Charalampos Rallis, StJohn Townsend, Jürg Bähler
The Target of Rapamycin (TOR) signalling network plays important roles in aging and disease. The AMP-activated protein kinase (AMPK) and the Gsk3 kinase inhibit TOR during stress. We performed genetic interaction screens using synthetic genetic arrays (SGA) with gsk3 and amk2 as query mutants, the latter encoding the regulatory subunit of AMPK. We identified 69 negative and 82 positive common genetic interactors, with functions related to cellular growth and stress. The 120 gsk3-specific negative interactors included genes functioning in translation and ribosomes...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28256572/clinicopathological-and-molecular-characterization-of-smarca4-deficient-thoracic-sarcomas-with-comparison-to-potentially-related-entities
#6
Akihiko Yoshida, Eisuke Kobayashi, Takashi Kubo, Makoto Kodaira, Toru Motoi, Noriko Motoi, Kan Yonemori, Yuichiro Ohe, Shun-Ichi Watanabe, Akira Kawai, Takashi Kohno, Hiroshi Kishimoto, Hitoshi Ichikawa, Nobuyoshi Hiraoka
A growing number of studies suggest critical tumor suppressor roles of the SWI/SNF chromatin remodeling complex in a variety of human cancers. The recent discovery of SMARCA4-deficient thoracic sarcomas has added to the list of tumor groups with the SMARCA4 inactivating mutation. To better characterize these tumors and establish their nosological status, we undertook a clinicopathological and molecular analysis of 12 SMARCA4-deficient thoracic sarcomas and compared them with three potentially related disease entities...
March 3, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28249716/conserved-effect-of-aging-on-dna-methylation-and-association-with-ezh2-polycomb-protein-in-mice-and-humans
#7
Khyobeni Mozhui, Ashutosh K Pandey
In humans, DNA methylation at specific CpG sites can be used to estimate the 'epigenetic clock', a biomarker of aging and health. The mechanisms that regulate the aging epigenome and level of conservation are not entirely clear. We performed affinity-based enrichment with methyl-CpG binding domain protein followed by high-throughput sequencing (MBD-seq) to assay DNA methylation in mouse samples. Consistent with previous reports, aging is associated with increase in methylation at CpG islands that likely overlap regulatory regions of genes that have been implicated in cancers (e...
February 27, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28249161/the-setd8-pr-set7-methyltransferase-functions-as-a-barrier-to-prevent-senescence-associated-metabolic-remodeling
#8
Hiroshi Tanaka, Shin-Ichiro Takebayashi, Akihisa Sakamoto, Tomoka Igata, Yuko Nakatsu, Noriko Saitoh, Shinjiro Hino, Mitsuyoshi Nakao
Cellular senescence is an irreversible growth arrest that contributes to development, tumor suppression, and age-related conditions. Senescent cells show active metabolism compared with proliferating cells, but the underlying mechanisms remain unclear. Here we show that the SETD8/PR-Set7 methyltransferase, which catalyzes mono-methylation of histone H4 at lysine 20 (H4K20me1), suppresses nucleolar and mitochondrial activities to prevent cellular senescence. SETD8 protein was selectively downregulated in both oncogene-induced and replicative senescence...
February 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28248055/-sperm-dna-fragmentation-association-with-semen-parameters-in-young-men
#9
L V Osadchuk, D A Tataru, N N Kuznetsova, M A Kleshev, E V Markova, A V Svetlakov
AIM: Abnormal sperm DNA integrity is an important risk factor for male infertility. The aim of this work was to examine sperm DNA fragmentation in a cohort of young male volunteers (n=111; age 21.0+/-0.2 years) from the general population and establish the association between the level of sperm DNA fragmentation and sperm functional parameters. MATERIALS AND METHODS: Sperm DNA fragmentation index (DFI) was determined by SCSA (sperm chromatin structure assay) using flow cytometry...
December 2016: Urologii︠a︡
https://www.readbyqxmd.com/read/28239474/predictive-value-of-sperm-deoxyribonucleic-acid-dna-fragmentation-index-in-male-infertility
#10
Budi Wiweko, Pramety Utami
BACKGROUND: Recently, damage to the sperm DNA has been studied as it is associated with reduced fertilization rates, embryo quality, and pregnancy rates, also higher rates of spontaneous miscarriage. OBJECTIVE: To develop a diagnostic method in predicting male infertility. MATERIAL AND METHODS: The design of this study is cross-sectional. Data were retrieved from medical records of Yasmin IVF Clinic Dr. Cipto Mangunkusumo General Hospital and Daya Medika Infertility Clinic from January to December 2015...
2017: Basic and Clinical Andrology
https://www.readbyqxmd.com/read/28229933/nuclear-lamins-and-progerin-are-dispensable-for-antioxidant-nrf2-response-to-arsenic-and-cadmium
#11
Kazunori Hashimoto, Rima Majumdar, Yoshiaki Tsuji
Lamins are important constituents of the nuclear inner membrane and provide a platform for transcription factors and chromatin. Progerin, a C-terminal truncated lamin A mutant, causes premature aging termed Hutchinson-Gilford Progeria Syndrome (HGPS). Oxidative stress appears to be involved in the pathogenesis of HGPS, although the mechanistic role of progerin remains elusive. Here we examined whether nuclear lamins are important for a cellular antioxidant mechanism, and whether progerin compromises it. We investigated the activation of nuclear factor-E2-related factor 2 (Nrf2) which regulates various antioxidant genes including heme oxygenase-1 (HMOX1), following exposure to sodium arsenite or cadmium chloride in lamin knockdown human cell lines and primary HGPS human fibroblasts...
February 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28228349/identification-of-prdm-genes-in-human-corneal-endothelium
#12
Kostadin Rolev, G O'Donovan Dominic, Christiana Georgiou, Rajan Madhavan, Alexandra Chittka
Corneal endothelial cells (CECs) are essential for maintaining corneal stromal hydration and ensuring its transparency, which is necessary for normal vision. Dysfunction of CECs leads to stromal decompensation, loss of transparency and corneal blindness. Corneal endothelium has low proliferative potential compared to surface epithelial cells leading to poor regeneration of CEC following injury or age related decline in cellular density. The mechanisms which control proliferation and differentiation of neural crest derived CEC progenitors are yet to be clearly elucidated...
February 19, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28211918/myotonic-dystrophy-type-1-patient-derived-ipscs-for-the-investigation-of-ctg-repeat-instability
#13
Junko Ueki, Masayuki Nakamori, Masahiro Nakamura, Misato Nishikawa, Yoshinori Yoshida, Azusa Tanaka, Asuka Morizane, Masayoshi Kamon, Toshiyuki Araki, Masanori P Takahashi, Akira Watanabe, Nobuya Inagaki, Hidetoshi Sakurai
Myotonic dystrophy type 1 (DM1) is an autosomal-dominant multi-system disease caused by expanded CTG repeats in dystrophia myotonica protein kinase (DMPK). The expanded CTG repeats are unstable and can increase the length of the gene with age, which worsens the symptoms. In order to establish a human stem cell system suitable for the investigation of repeat instability, DM1 patient-derived iPSCs were generated and differentiated into three cell types commonly affected in DM1, namely cardiomyocytes, neurons and myocytes...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196804/nipped-a-regulates-intestinal-stem-cell-proliferation-in-drosophila
#14
Helen Marie Tauc, Alpaslan Tasdogan, Patrick Meyer, Petra Pandur
Adult stem cells uphold a delicate balance between quiescent and active states, a deregulation of which can lead to age-associated diseases such as cancer. In Drosophila, intestinal stem cell (ISC) proliferation is tightly regulated and mis-regulation is detrimental to intestinal homeostasis. Various factors are known to govern ISC behavior; however, transcriptional changes in ISCs during aging are still unclear. RNA sequencing of young and old ISCs newly identified Nipped-A, a subunit of histone acetyltransferase complexes, as a regulator of ISC proliferation that is upregulated in old ISCs...
February 15, 2017: Development
https://www.readbyqxmd.com/read/28176655/epigenetics-in-clinical-management-of-children-and-adolescents-with-brain-tumors
#15
Andres Morales La Madrid, Mark W Kieran
Central nervous system (CNS) tumors represent the second most prevalent group of cancers in children and adolescents, yet account for the majority of childhood cancer-related deaths and considerable morbidity among survivors, due to high-intensity non-selective standard therapies delivered to immature nervous system structures undergoing development. These tumors arise at different ages -not infrequently very early in life-, in different locations and cellular contexts, have varied cell types of origin, and have heterogeneous responses to the "classic" current therapeutic approaches...
February 3, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28173669/-clinicopathologic-analysis-of-ewing-like-bcor-ccnb3-undifferentiated-sarcoma
#16
X J Wang, D H Zhao, Y M Wang, Y X Liu, X Li, M Y Li, W C Li, Z Wang
Objective: To investigate the morphologic, immunohistochemical, genetic, clinical features and prognosis of Ewing-like BCOR-CCNB3 gene fusion undifferentiated sarcoma (BCOR-CCNB3 fusion sarcoma). Method: Seventeen Ewing-like sarcoma cases were screened for CCNB3 expression and BCOR-CCNB3 fusion transcripts by immunohistochemistry and RT-PCR among 260 cases of Ewing-like sarcomas collected during Jan, 2006 to Dec, 2015. Three cases of BCOR-CCNB3 fusion sarcoma were found among 17 atypical Ewing sarcomas, and follow-up were conducted...
February 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28157704/overlooked-fancd2-variant-encodes-a-promising-portent-tumor-suppressor-and-alternative-polyadenylation-contributes-to-its-expression
#17
Bing Hang, Yihang Shen, Piyan Zhang, Panneerselvam Jayabal, Raymond Che, Jun Zhang, Herbert Yu, Peiwen Fei
Fanconi Anemia (FA) complementation group D2 protein (FANCD2) is the center of the FA tumor suppressor pathway, which has become an important field of investigation in human aging and cancer. Here we report an overlooked central player in the FA pathway, FANCD2 variant 2 (FANCD2-V2), which appears to perform more potent tumor suppressor-function compared to the known variant of FANCD2, namely, FANCD2-V1. Detailed analysis of the FANCD2 gene structure indicated a proximal and distal polyadenylation site (PAS), associated with V2 and V1 transcripts accordingly...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28153533/dysregulation-of-gene-expression-in-the-striatum-of-bachd-rats-expressing-full-length-mutant-huntingtin-and-associated-abnormalities-on-molecular-and-protein-levels
#18
Libo Yu-Taeger, Michael Bonin, Janice Stricker-Shaver, Olaf Riess, Hoa Huu Phuc Nguyen
Huntington disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for the huntingtin protein (HTT). Mutant HTT (mHTT) has been proposed to cause neuronal dysfunction and neuronal loss through multiple mechanisms. Transcriptional changes may be a core pathogenic feature of HD. Utilizing the Affymetrix platform we performed a genome-wide RNA expression analysis in two BACHD transgenic rat lines (TG5 and TG9) at 12 months of age, both of which carry full-length human mHTT but with different expression levels...
January 30, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28139645/visualization-of-aging-associated-chromatin-alterations-with-an-engineered-tale-system
#19
Ruotong Ren, Liping Deng, Yanhong Xue, Keiichiro Suzuki, Weiqi Zhang, Yang Yu, Jun Wu, Liang Sun, Xiaojun Gong, Huiqin Luan, Fan Yang, Zhenyu Ju, Xiaoqing Ren, Si Wang, Hong Tang, Lingling Geng, Weizhou Zhang, Jian Li, Jie Qiao, Tao Xu, Jing Qu, Guang-Hui Liu
Visualization of specific genomic loci in live cells is a prerequisite for the investigation of dynamic changes in chromatin architecture during diverse biological processes, such as cellular aging. However, current precision genomic imaging methods are hampered by the lack of fluorescent probes with high specificity and signal-to-noise contrast. We find that conventional transcription activator-like effectors (TALEs) tend to form protein aggregates, thereby compromising their performance in imaging applications...
January 31, 2017: Cell Research
https://www.readbyqxmd.com/read/28132833/nicotinamide-ameliorates-disease-phenotypes-in-a-human-ipsc-model-of-age-related-macular-degeneration
#20
Janmeet S Saini, Barbara Corneo, Justine D Miller, Thomas R Kiehl, Qingjie Wang, Nathan C Boles, Timothy A Blenkinsop, Jeffrey H Stern, Sally Temple
Age-related macular degeneration (AMD) affects the retinal pigment epithelium (RPE), a cell monolayer essential for photoreceptor survival, and is the leading cause of vision loss in the elderly. There are no disease-altering therapies for dry AMD, which is characterized by accumulation of subretinal drusen deposits and complement-driven inflammation. We report the derivation of human-induced pluripotent stem cells (hiPSCs) from patients with diagnosed AMD, including two donors with the rare ARMS2/HTRA1 homozygous genotype...
January 21, 2017: Cell Stem Cell
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