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Chromatin aging

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https://www.readbyqxmd.com/read/28211918/myotonic-dystrophy-type-1-patient-derived-ipscs-for-the-investigation-of-ctg-repeat-instability
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28129586/interaction-between-epigenetic-and-metabolism-in-aging-stem-cells
#9
REVIEW
Anne Brunet, Thomas A Rando
Aging is accompanied by a decline in tissue function, regeneration, and repair. A large part of this decline is caused by the deterioration of tissue stem cell function. Understanding the mechanisms that drive stem cell aging and how to counteract them is a critical step for enhancing tissue repair and maintenance during aging. Emerging evidence indicates that epigenetic modifiers and metabolism regulators interact to impact lifespan, suggesting that this mechanism may also affect stem cell function with age...
January 24, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28125586/a-novel-lamin-a-mutant-responsible-for-congenital-muscular-dystrophy-causes-distinct-abnormalities-of-the-cell-nucleus
#10
Alice Barateau, Nathalie Vadrot, Patrick Vicart, Ana Ferreiro, Michèle Mayer, Delphine Héron, Corinne Vigouroux, Brigitte Buendia
A-type lamins, the intermediate filament proteins participating in nuclear structure and function, are encoded by LMNA. LMNA mutations can lead to laminopathies such as lipodystrophies, premature aging syndromes (progeria) and muscular dystrophies. Here, we identified a novel heterozygous LMNA p.R388P de novo mutation in a patient with a non-previously described severe phenotype comprising congenital muscular dystrophy (L-CMD) and lipodystrophy. In culture, the patient's skin fibroblasts entered prematurely into senescence, and some nuclei showed a lamina honeycomb pattern...
2017: PloS One
https://www.readbyqxmd.com/read/28125036/regulation-of-replication-fork-advance-and-stability-by-nucleosome-assembly
#11
REVIEW
Felix Prado, Douglas Maya
The advance of replication forks to duplicate chromosomes in dividing cells requires the disassembly of nucleosomes ahead of the fork and the rapid assembly of parental and de novo histones at the newly synthesized strands behind the fork. Replication-coupled chromatin assembly provides a unique opportunity to regulate fork advance and stability. Through post-translational histone modifications and tightly regulated physical and genetic interactions between chromatin assembly factors and replisome components, chromatin assembly: (1) controls the rate of DNA synthesis and adjusts it to histone availability; (2) provides a mechanism to protect the integrity of the advancing fork; and (3) regulates the mechanisms of DNA damage tolerance in response to replication-blocking lesions...
January 24, 2017: Genes
https://www.readbyqxmd.com/read/28124509/a-novel-single-cell-method-provides-direct-evidence-of-persistent-dna-damage-in-senescent-cells-and-aged-mammalian-tissues
#12
Alessandro Galbiati, Christian Beauséjour, Fabrizio d'Adda di Fagagna
The DNA damage response (DDR) arrests cell cycle progression until DNA lesions, like DNA double-strand breaks (DSBs), are repaired. The presence of DSBs in cells is usually detected by indirect techniques that rely on the accumulation of proteins at DSBs, as part of the DDR. Such detection may be biased, as some factors and their modifications may not reflect physical DNA damage. The dependency on DDR markers of DSB detection tools has left questions unanswered. In particular, it is known that senescent cells display persistent DDR foci, that we and others have proposed to be persistent DSBs, resistant to endogenous DNA repair activities...
January 26, 2017: Aging Cell
https://www.readbyqxmd.com/read/28108335/tryptase-catalyzed-core-histone-truncation-a-novel-epigenetic-regulatory-mechanism-in-mast-cells
#13
Fabio R Melo, Ola Wallerman, Aida Paivandy, Gabriela Calounova, Ann-Marie Gustafson, Benjamin R Sabari, Giuliano Zabucchi, C David Allis, Gunnar Pejler
BACKGROUND: Mast cells are key effector cells in allergic reactions. When activated to degranulate, they release a plethora of bioactive compounds from their secretory granules, including mast cell-restricted proteases such as tryptase. In a previous study we showed that tryptase, in addition to its intragranular location, can be found within the nuclei of mast cells where it truncates core histones at their N-terminal ends. OBJECTIVE: Considering that the N-terminal portions of the core histones constitute sites for posttranslational modifications of major epigenetic impact, we here evaluated whether histone truncation by tryptase could have an impact on epigenetic events in mast cells...
January 17, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28104697/male-birthweight-semen-quality-and-birth-outcomes
#14
B W Whitcomb, M S Bloom, S Kim, Z Chen, G M Buck Louis
STUDY QUESTION: What are the relations among birthweight (BW), semen parameters and birth outcomes in a population-based sample? SUMMARY ANSWER: BW is unrelated to semen parameters, which are in turn unrelated to birth outcomes. WHAT IS KNOWN ALREADY: In clinical settings, there has been suggestion that semen parameters are related to BW when comparing fertile and infertile men; however, findings have been less clear in more general populations...
January 18, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28101820/insulin-insulin-like-growth-factor-1-signalling-iis-based-regulation-of-lifespan-across-species
#15
REVIEW
Rebecca Mathew, Manika Pal Bhadra, Utpal Bhadra
An organism's well-being is facilitated by numerous molecular and biochemical pathways that ensure homeostasis within cells and tissues. Aging causes a gradual let-down in the maintenance of homeostasis due to various endogenous and environmental challenges, leading to amassing of damages, functional deterioration of different tissues and vulnerability to ailments. Nutrient sensing pathways that maintain glucose homeostasis in body are involved in regulation of aging. Insulin/insulin-like growth factor-1 (IGF-1) signalling (IIS) pathway was the first nutrient sensing pathway discovered to affect the aging process...
January 18, 2017: Biogerontology
https://www.readbyqxmd.com/read/28081471/in-situ-morphological-assessment-of-apoptosis-induced-by-phaleria-macrocarpa-boerl-fruit-ethyl-acetate-fraction-pmeaf-in-mda-mb-231-cells-by-microscopy-observation
#16
Nowroji Kavitha, Yeng Chen, Jagat R Kanwar, Sreenivasan Sasidharan
Phaleria macrocarpa (Boerl.) is a well-known medicinal plant and have been extensively used as traditional medicine for ages in treatment of various diseases. The purpose of this study was to determine the in situ cytotoxicity effect P. macrocarpa fruit ethyl acetate fraction (PMEAF) by using various conventional and modern microscopy techniques. The cytotoxicity of PMEAF treated MDA-MB-231 cells was determined through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay and CyQuant Cell Proliferation Assay after 24h of treatment...
January 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28081156/generation-of-a-stable-transgenic-swine-model-expressing-a-porcine-histone-2b-egfp-fusion-protein-for-cell-tracking-and-chromosome-dynamics-studies
#17
Renan B Sper, Sehwon Koh, Xia Zhang, Sean Simpson, Bruce Collins, Jeff Sommer, Robert M Petters, Ignacio Caballero, Jeff L Platt, Jorge A Piedrahita
Transgenic pigs have become an attractive research model in the field of translational research, regenerative medicine, and stem cell therapy due to their anatomic, genetic and physiological similarities with humans. The development of fluorescent proteins as molecular tags has allowed investigators to track cell migration and engraftment levels after transplantation. Here we describe the development of two transgenic pig models via SCNT expressing a fusion protein composed of eGFP and porcine Histone 2B (pH2B)...
2017: PloS One
https://www.readbyqxmd.com/read/28064165/nutritional-control-of-chronological-aging-and-heterochromatin-in-saccharomyces-cerevisiae
#18
David F McCleary, Jasper Rine
Calorie restriction extends lifespan in organisms as diverse as yeast and mammals through incompletely understood mechanism(s). The role of NAD(+)-dependent deacetylases, known as Sirtuins, in this process, particularly in the yeast S. cerevisiae is controversial. We measured chronological lifespan of wild-type and sir2Δ strains over a higher glucose range than typically used for studying yeast calorie restriction. sir2Δ extended lifespan in high-glucose complete minimal medium, and had little effect in low glucose medium, revealing a partial role for Sir2 in the calorie restriction response under these conditions...
January 6, 2017: Genetics
https://www.readbyqxmd.com/read/28052107/ubiquitin-accumulation-on-disease-associated-protein-aggregates-is-correlated-with-nuclear-ubiquitin-depletion-histone-de-ubiquitination-and-impaired-dna-damage-response
#19
Adi Ben Yehuda, Marwa Risheq, Ofra Novoplansky, Kirill Bersuker, Ron R Kopito, Michal Goldberg, Michael Brandeis
Deposition of ubiquitin conjugates on inclusion bodies composed of protein aggregates is a definitive cytopathological hallmark of neurodegenerative diseases. We show that accumulation of ubiquitin on polyQ IB, associated with Huntington's disease, is correlated with extensive depletion of nuclear ubiquitin and histone de-ubiquitination. Histone ubiquitination plays major roles in chromatin regulation and DNA repair. Accordingly, we observe that cells expressing IB fail to respond to radiomimetic DNA damage, to induce gamma-H2AX phosphorylation and to recruit 53BP1 to damaged foci...
2017: PloS One
https://www.readbyqxmd.com/read/28049846/sir2-suppresses-replication-gaps-and-genome-instability-by-balancing-replication-between-repetitive-and-unique-sequences
#20
Eric J Foss, Uyen Lao, Emily Dalrymple, Robin L Adrianse, Taylor Loe, Antonio Bedalov
Replication gaps that persist into mitosis likely represent important threats to genome stability, but experimental identification of these gaps has proved challenging. We have developed a technique that allows us to explore the dynamics by which genome replication is completed before mitosis. Using this approach, we demonstrate that excessive allocation of replication resources to origins within repetitive regions, induced by SIR2 deletion, leads to persistent replication gaps and genome instability. Conversely, the weakening of replication origins in repetitive regions suppresses these gaps...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
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