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Chromatin aging

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https://www.readbyqxmd.com/read/28544616/biochemical-isolation-of-myonuclei-employed-to-define-changes-to-the-myonuclear-proteome-that-occur-with-aging
#1
Alicia A Cutler, Eric B Dammer, Duc M Doung, Nicholas T Seyfried, Anita H Corbett, Grace K Pavlath
Skeletal muscle aging is accompanied by loss of muscle mass and strength. Examining changes in myonuclear proteins with age would provide insight into molecular processes which regulate these profound changes in muscle physiology. However, muscle tissue is highly adapted for contraction and thus comprised largely of contractile proteins making the nuclear proteins difficult to identify from whole muscle samples. By developing a method to purify myonuclei from whole skeletal muscle, we were able to collect myonuclei for analysis by flow cytometry, biochemistry, and mass spectrometry...
May 23, 2017: Aging Cell
https://www.readbyqxmd.com/read/28533362/cgas-is-essential-for-cellular-senescence
#2
Hui Yang, Hanze Wang, Junyao Ren, Qi Chen, Zhijian J Chen
Cellular senescence is a natural barrier to tumorigenesis and it contributes to the antitumor effects of several therapies, including radiation and chemotherapeutic drugs. Senescence also plays an important role in aging, fibrosis, and tissue repair. The DNA damage response is a key event leading to senescence, which is characterized by the senescence-associated secretory phenotype (SASP) that includes expression of inflammatory cytokines. Here we show that cGMP-AMP (cGAMP) synthase (cGAS), a cytosolic DNA sensor that activates innate immunity, is essential for senescence...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533215/inhibition-of-hdac3-prevents-diabetic-cardiomyopathy-in-ove26-mice-via-epigenetic-regulation-of-dusp5-erk1-2-pathway
#3
Zheng Xu, Qian Tong, Zhiguo Zhang, Shudong Wang, Yang Zheng, Qiuju Liu, Lingbo Qian, Shao-Yu Chen, Jian Sun, Lu Cai
Inhibition of total histone deacetylases (HDACs) was phenomenally associated with the prevention of diabetic cardiomyopathy (DCM). However, which specific HDAC plays the key role in DCM remains unclear. The present study was designed to determine whether DCM can be prevented by specific inhibition of HDAC3 and to elucidate the mechanisms by which inhibition of HDAC3 prevent DCM. Type 1 diabetes OVE26 and age-matched wild-type mice were given the selective HDAC3 inhibitor RGFP966 or vehicle for 3 months. These mice were then sacrificed immediately or 3 months later for cardiac function and pathological examination...
May 22, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28500085/the-most-common-vices-of-men-can-damage-fertility-and-the-health-of-the-next-generation
#4
Tod Fullston, Nicole O McPherson, Deirdre Zander-Fox, Michelle Lane
There is growing evidence from animal and human studies that demonstrate that acquired paternal traits can impair both a male's fertility and the health of his offspring, including advanced age, smoking, stress, trauma, under-nutrition, infection, toxin exposure, and obesity. Curiously, many of these factors manifest as impaired neurological, behavioural, and/or metabolic functioning in offspring. The underlying molecular mechanisms that respond to the paternal environment and act as vectors of intergenerational transmission are beginning to emerge...
May 12, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28493873/modeling-of-a-negative-feedback-mechanism-explains-antagonistic-pleiotropy-in-reproduction-in-domesticated-caenorhabditis-elegans-strains
#5
Edward E Large, Raghavendra Padmanabhan, Kathie L Watkins, Richard F Campbell, Wen Xu, Patrick T McGrath
Most biological traits and common diseases have a strong but complex genetic basis, controlled by large numbers of genetic variants with small contributions to a trait or disease risk. The effect-size of most genetic variants is not absolute and is instead dependent upon multiple factors such as the age and genetic background of an organism. In order to understand the mechanistic basis of these changes, we characterized heritable trait differences between two domesticated strains of C. elegans. We previously identified a major effect locus, caused in part by a mutation in a component of the NURF chromatin remodeling complex, that regulates reproductive output in an age-dependent manner...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28484556/clear-cell-meningioma-intraoperative-diagnosis-by-squash-cytology-case-report-and-review-of-the-literature
#6
Vaishali Walke, Shantilal M Sisodia, Sanjay Bijwe, Purwa Patil
Clear-cell meningioma (CCM), an unusual subset of meningioma has prominent, clear-cell morphology. It is a wolf in sheep's clothing characterized by benign histologic attributes, but tendency for recurrence (61%) and metastasis. Therefore, WHO has classified it as grade II meningioma. Fine-needle aspiration cytology diagnosis is simple, rapid, cost-effective and reliable procedure primarily aimed at preoperative diagnosis of advanced and metastatic extracranial tumor. Preoperative and/or intraoperative cytodiagnosis of CCM demand expertise in the evaluation of cytology smears...
April 2017: Asian Journal of Neurosurgery
https://www.readbyqxmd.com/read/28476689/pax6-interacts-with-iba1-and-shows-age-associated-alterations-in-brain-of-aging-mice
#7
Shashank Kumar Maurya, Rajnikant Mishra
The Pax6, a transcriptional regulator and multifunctional protein, has been found critical for neurogenesis, neuro-degeneration, mental retardation, neuroendocrine tumors, glioblastoma and astrocytomas. The age-associated alteration in the expression of Pax6 in neuron and glia has also been observed in the immunologically privileged brain. Therefore, it is presumed that Pax6 may modulate brain immunity by activation of microglia either directly interacting with genes or proteins of microglia or indirectly though inflammation associated with neurodegeneration...
May 3, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28456919/genotoxic-risk-assessment-in-professionals-working-hairdressers-area-using-buccal-micronucleus-assay-in-ayd%C3%A4-n-city-turkey
#8
Özlem Sultan Aslantürk, Tülay Aşkin Çelik
The aim of this study was to determine the genotoxic risk of professional hairdressers in Aydın City, Turkey, through investigating the micronucleus frequencies in buccal mucosa epithelial cells. All the hairdresser working hairdresser area were included in the genotoxic risk group (GRG = 20) in Aydın City, Turkey. The control group (CG = 20) comprised healthy individuals matching the gender and age of the GRG. Buccal mucosal scraping from all the 40 subjects of GRG (10 women and 10 men) and CG (10 women and 10 men) was stained with Giemsa stain and observed under light microscope (×40) for the presence of micronuclei (M 10 N) and karyolysis, pyknosis, condensed chromatin, karyorrhexis, nuclear bud, and binucleates in the exfoliated epithelial cells...
April 29, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28451587/the-interplay-of-cofactor-interactions-and-post-translational-modifications-in-the-regulation-of-the-aaa-atpase-p97
#9
REVIEW
Petra Hänzelmann, Hermann Schindelin
The hexameric type II AAA ATPase (ATPase associated with various activities) p97 (also referred to as VCP, Cdc48, and Ter94) is critically involved in a variety of cellular activities including pathways such as DNA replication and repair which both involve chromatin remodeling, and is a key player in various protein quality control pathways mediated by the ubiquitin proteasome system as well as autophagy. Correspondingly, p97 has been linked to various pathophysiological states including cancer, neurodegeneration, and premature aging...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28439570/epigenomics-of-human-cd8-t-cell-differentiation-and-aging
#10
David M Moskowitz, David W Zhang, Bin Hu, Sabine Le Saux, Rolando E Yanes, Zhongde Ye, Jason D Buenrostro, Cornelia M Weyand, William J Greenleaf, Jörg J Goronzy
The efficacy of the adaptive immune response declines dramatically with age, but the cell-intrinsic mechanisms driving immune aging in humans remain poorly understood. Immune aging is characterized by a loss of self-renewing naïve cells and the accumulation of differentiated but dysfunctional cells within the CD8 T cell compartment. Using ATAC-seq, we inferred the transcription factor binding activities correlated with naive and central and effector memory CD8 T cell states in young adults. Integrating our results with RNA-seq, we identified transcription networks associated with CD8 T cell differentiation, with prominent roles implicated for BATF, ETS1, Eomes, and Sp1...
February 2017: Science Immunology
https://www.readbyqxmd.com/read/28427211/association-of-brm-promoter-polymorphisms-and-esophageal-adenocarcinoma-outcome
#11
Grzegorz J Korpanty, Lawson Eng, Xin Qiu, Olusola Olusesan Faluyi, Daniel J Renouf, Dangxiao Cheng, Devalben Patel, Zhuo Chen, Brandon C Tse, Jennifer J Knox, Lorin Dodbiba, Jennifer Teichman, Abul Kalam Azad, Rebecca Wong, Gail Darling, David Reisman, Sinead Cuffe, Geoffrey Liu, Wei Xu
PURPOSE: Brahma (BRM) is a critical catalytic subunit of the SWI/SNF chromatin remodeling complex; expression of BRM is commonly lost in various cancer types. BRM promoter polymorphisms (BRM-741; BRM-1321) are associated with loss of BRM expression, and with cancer risk/survival. We evaluated these two polymorphisms in the overall survival (OS) of esophageal adenocarcinoma (EAC) patients. RESULTS: Of 270 patients, 37% were stage IV. Minor allele frequencies were 47-49%; 15% were double-homozygotes...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420319/bcor-ccnb3-undifferentiated-sarcoma-does-immunohistochemistry-help-in-the-identification
#12
Kathrin Ludwig, Rita Alaggio, Angelica Zin, Marica Peron, Vincenza Guzzardo, Stefania Benini, Alberto Righi, Marco Gambarotti
Recent methodology has enabled the identification of some new genetic subgroups within the melting pot of lesions presently classified by the 2013 WHO classification as "undifferentiated/unclassified sarcomas". One of these subgroups is characterized by a paracentric inversion of the X chromosome with consequent formation of a BCOR-CCNB3 fusion. Clinical and pathological features of these tumors overlap with the Ewing sarcoma family as well as other soft tissue sarcomas, thus making them difficult to diagnose...
January 1, 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28415633/a-phase-2-study-of-vorinostat-in-locally-advanced-recurrent-or-metastatic-adenoid-cystic-carcinoma
#13
Priscila H Goncalves, Lance K Heilbrun, Michael T Barrett, Shivaani Kummar, Aaron R Hansen, Lillian L Siu, Richard L Piekarz, Ammar W Sukari, Joseph Chao, Mary Jo Pilat, Daryn W Smith, Lindsay Casetta, Scott A Boerner, Alice Chen, Elizabeth Lenkiewicz, Smriti Malasi, Patricia M LoRusso
PURPOSE: Vorinostat is a histone deacetylase inhibitor (HDACi). Based on a confirmed partial response (PR) in an adenoid cystic carcinoma (ACC) patient treated with vorinostat in a prior phase 1 trial, we initiated this phase 2 trial. METHODS: Vorinostat was administered orally 400 mg daily, 28 day cycles. The primary objective was to evaluate response rate (RR). Exploratory studies included whole exome sequencing (WES) of selected patients. RESULTS: Thirty patients were enrolled...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412438/torsional-stress-promotes-trinucleotidic-expansion-in-spermatids
#14
Olivier Simard, Seyedeh Raheleh Niavarani, Virginie Gaudreault, Guylain Boissonneault
Trinucleotide repeats are involved in various neurodegenerative diseases and are highly unstable both in dividing or non-dividing cells. In Huntington disease (HD), the age of onset of symptoms is inversely correlated to the number of CAG repeats within exon 1 of the HTT gene. HD shows paternal anticipation as CAG repeats are increased during spermatogenesis. CAG expansion were indeed found to be generated during the chromatin remodeling in spermatids where most histones are evicted and replaced by protamines...
April 9, 2017: Mutation Research
https://www.readbyqxmd.com/read/28408026/the-aging-cardiovascular-system-understanding-it-at-the-cellular-and-clinical-levels
#15
REVIEW
Francesco Paneni, Candela Diaz Cañestro, Peter Libby, Thomas F Lüscher, Giovanni G Camici
Cardiovascular disease (CVD) presents a great burden for elderly patients, their caregivers, and health systems. Structural and functional alterations of vessels accumulate throughout life, culminating in increased risk of developing CVD. The growing elderly population worldwide highlights the need to understand how aging promotes CVD in order to develop new strategies to confront this challenge. This review provides examples of some major unresolved clinical problems encountered in daily cardiovascular practice as we care for elderly patients...
April 18, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28407867/the-relationship-between-mitochondrial-dna-copy-number-and-stallion-sperm-function
#16
Christa R Darr, Luis E Moraes, Richard E Connon, Charles C Love, Sheila Teague, Dickson D Varner, Stuart A Meyers
Mitochondrial DNA (mtDNA) copy number has been utilized as a measure of sperm quality in several species including mice, dogs, and humans, and has been suggested as a potential biomarker of fertility in stallion sperm. The results of the present study extend this recent discovery using sperm samples from American Quarter Horse stallions of varying age. By determining copy number of three mitochondrial genes, cytochrome b (CYTB), NADH dehydrogenase 1 (ND1) and NADH dehydrogenase 4 (ND4), instead of a single gene, we demonstrate an improved understanding of mtDNA fate in stallion sperm mitochondria following spermatogenesis...
May 2017: Theriogenology
https://www.readbyqxmd.com/read/28406750/sirtuins-and-dna-damage-repair-sirt7-comes-to-play
#17
REVIEW
Berta N Vazquez, Joshua K Thackray, Lourdes Serrano
Aging is characterized by a cumulative loss of genome integrity, which involves chromatin reorganization, transcriptional dysregulation and the accumulation of DNA damage. Sirtuins participate in the protection against these aging processes by promoting genome homeostasis in response to cellular stress. We recently reported that SirT7(-/-) mice suffer from partial embryonic lethality and a progeroid like phenotype. At the cellular level, SIRT7 depletion results in the impaired repair of DNA double-strand breaks (DSBs), one the most dangerous DNA lesions, leading to genome instability...
March 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28400497/c57bl-6j-mice-as-a-polygenic-developmental-model-of-diet-induced-obesity
#18
Dinh-Toi Chu, Elzbieta Malinowska, Magdalena Jura, Leslie P Kozak
Susceptibility to obesity changes during the course of life. We utilized the C57BL/6J (B6) and 129S mouse as a genetic model for variation in diet-induced obesity to define the adiposity phenotypes from birth to maturity at 8 weeks-of-age. From birth to 8 weeks-of-age, both male and female 129S mice had significantly higher fat mass and adiposity index than B6 mice, although they were not obese. After 8 weeks-of-age, B6 had greater adiposity/obesity than 129S mice in response to a high fat (HF). We sought to determine the mechanism activating the fat accumulation in B6 mice at 8-weeks-of-age...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28398002/alpha-ketoglutarate-curbs-differentiation-and-induces-cell-death-in-mesenchymal-stromal-precursors-with-mitochondrial-dysfunction
#19
Karmveer Singh, Linda Krug, Abhijit Basu, Patrick Meyer, Nicolai Treiber, Seppe Vander Beken, Meinhard Wlaschek, Stefan Kochanek, Wilhelm Bloch, Hartmut Geiger, Pallab Maity, Karin Scharffetter-Kochanek
Increased concentrations of reactive oxygen species (ROS) originating from dysfunctional mitochondria contribute to diverse aging-related degenerative disorders. But so far little is known about the impact of distinct ROS on metabolism and fate of stromal precursor cells. Here, we demonstrate that an increase in superoxide anion radicals due to superoxide dismutase 2 (Sod2) deficiency in stromal precursor cells suppress osteogenic and adipogenic differentiation through fundamental changes in the global metabolite landscape...
April 11, 2017: Stem Cells
https://www.readbyqxmd.com/read/28393704/epigenetic-regulation-of-memory-therapeutic-potential-for-disorders
#20
Padmanabh Singh, Sweta Srivas, M K Thakur
Memory is a vital function which declines in different physiological and pathological conditions such as aging and neurodegenerative diseases. Research in the past has reported that memory formation and consolidation require the precise expression of synaptic plasticity genes. However, little is known about the regulation of these genes. Epigenetic modification is now a well established mechanism that regulates synaptic plasticity genes and neuronal functions including memory. Such modification includes mainly DNA methylation and hydroxymethylation, histone acetylation and methylation which involve chromatin modifying enzymes...
April 4, 2017: Current Neuropharmacology
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