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Epigenetics pathology

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https://www.readbyqxmd.com/read/28441426/identification-of-genes-associated-with-dissociation-of-cognitive-performance-and-neuropathological-burden-multistep-analysis-of-genetic-epigenetic-and-transcriptional-data
#1
Charles C White, Hyun-Sik Yang, Lei Yu, Lori B Chibnik, Robert J Dawe, Jingyun Yang, Hans-Ulrich Klein, Daniel Felsky, Alfredo Ramos-Miguel, Konstantinos Arfanakis, William G Honer, Reisa A Sperling, Julie A Schneider, David A Bennett, Philip L De Jager
INTRODUCTION: The molecular underpinnings of the dissociation of cognitive performance and neuropathological burden are poorly understood, and there are currently no known genetic or epigenetic determinants of the dissociation. METHODS AND FINDINGS: "Residual cognition" was quantified by regressing out the effects of cerebral pathologies and demographic characteristics on global cognitive performance proximate to death. To identify genes influencing residual cognition, we leveraged neuropathological, genetic, epigenetic, and transcriptional data available for deceased participants of the Religious Orders Study (n = 492) and the Rush Memory and Aging Project (n = 487)...
April 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28439935/neonatal-immune-challenge-followed-by-adult-immune-challenge-induces-epigenetic-susceptibility-to-aggravated-visceral-hypersensitivity
#2
J E Aguirre, J H Winston, S K Sarna
BACKGROUND: Abdominal pain is one of the major symptoms of inflammatory Bowel Disease (IBD). The inflammatory mediators released by colon inflammation are known to sensitize the afferent neurons, which is one of the contributors to abdominal pain. However, not all IBD patients have abdominal pain, and some patients report abdominal pain during remission, suggesting contributions of other pathological factors to abdominal pain in IBD. Epidemiological studies found early-life gastrointestinal infections a risk factor for IBD symptoms and adult-life gastrointestinal infections may trigger the onset of IBD...
April 25, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28439875/epigenetic-repression-of-mir-375-is-the-dominant-mechanism-for-constitutive-activation-of-the-pdpk1-rps6ka3-signalling-axis-in-multiple-myeloma
#3
Shotaro Tatekawa, Yoshiaki Chinen, Masaki Ri, Tomoko Narita, Yuji Shimura, Yayoi Matsumura-Kimoto, Taku Tsukamoto, Tsutomu Kobayashi, Eri Kawata, Nobuhiko Uoshima, Tomohiko Taki, Masafumi Taniwaki, Hiroshi Handa, Shinsuke Iida, Junya Kuroda
Cytogenetic/molecular heterogeneity is the hallmark of multiple myeloma (MM). However, we recently showed that the serine/threonine kinase PDPK1 and its substrate RPS6KA3 (also termed RSK2) are universally active in MM, and play pivotal roles in myeloma pathophysiology. In this study, we assessed involvement of aberrant miR-375 repression in PDPK1 overexpression in MM. An analysis of plasma cells from 30 pre-malignant monoclonal gammopathies of undetermined significance and 73 MM patients showed a significant decrease in miR-375 expression in patient-derived plasma cells regardless of the clinical stage, compared to normal plasma cells...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28431793/alcohol-effects-on-the-epigenome-in-the-germline-role-in-the-inheritance-of-alcohol-related-pathology
#4
REVIEW
Lucy G Chastain, Dipak K Sarkar
Excessive alcohol exposure has severe health consequences, and clinical and animal studies have demonstrated that disruptions in the epigenome of somatic cells, such as those in brain, are an important factor in the development of alcohol-related pathologies, such as alcohol-use disorders (AUDs) and fetal alcohol spectrum disorders (FASDs). It is also well known that alcohol-related health problems are passed down across generations in human populations, but the complete mechanisms for this phenomenon are currently unknown...
March 6, 2017: Alcohol
https://www.readbyqxmd.com/read/28428687/lysyl-oxidase-its-diversity-in-health-and-diseases
#5
REVIEW
Suchitra Kumari, Tarun Kumar Panda, Tapaswini Pradhan
The mechanical properties of extracellular matrix (ECM) and connective tissues is largely dependent on the collagen and elastin structure. Lysyl oxidase (LOX) plays a critical role in the formation and repair of the ECM by oxidizing lysine residues in elastin and collagen, thereby initiating the formation of covalent cross linkages which stabilize these fibrous proteins. Due to its multiple functions both extracellularly and intracellularly, lysyl oxidase is involved in several processes in the tumorigenic pathway, in many different cancer types and stages...
June 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28427903/atrial-fibrillation-is-associated-with-hypermethylation-in-human-left-atrium-and-treatment-with-decitabine-reduces-atrial-tachyarrhythmias-in-spontaneously-hypertensive-rats
#6
R Doñate Puertas, E Meugnier, C Romestaing, C Rey, E Morel, J Lachuer, N Gadot, A Scridon, C Julien, F Tronc, B Chapuis, C Valla, A Janin, L Pirola, A Méjat, S Rome, P Chevalier
Atrial fibrillation (AF) is the most common cardiac arrhythmia. As the molecular mechanisms underlying the pathology are largely unknown, this cardiac arrhythmia remains difficult to treat. To identify specific molecular actors involved in AF, we have performed a transcriptomic analysis on left atrium (LA) from patients with valvular heart disease with or without AF. We showed that 1627 genes had altered basal expression level in LA tissue of AF patients compared with the control group. The significantly enriched gene ontology biological process "anatomical structure morphogenesis" contained the highest number of genes in line with changes in structure that occur when the human heart remodels following AF development (ie, LA dilatation and interstitial fibrosis)...
March 30, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28424732/evidence-for-loss-in-identity-de-differentiation-and-trans-differentiation-of-islet-%C3%AE-cells-in-type-2-diabetes
#7
REVIEW
Chad S Hunter, Roland W Stein
The two main types of diabetes mellitus have distinct etiologies, yet a similar outcome: loss of islet β-cell function that is solely responsible for the secretion of the insulin hormone to reduce elevated plasma glucose toward euglycemic levels. Type 1 diabetes (T1D) has traditionally been characterized by autoimmune-mediated β-cell death leading to insulin-dependence, whereas type 2 diabetes (T2D) has hallmarks of peripheral insulin resistance, β-cell dysfunction, and cell death. However, a growing body of evidence suggests that, especially during T2D, key components of β-cell failure involves: (1) loss of cell identity, specifically proteins associated with mature cell function (e...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28423671/genome-wide-dna-methylation-analysis-reveals-molecular-subtypes-of-pancreatic-cancer
#8
Nitish Kumar Mishra, Chittibabu Guda
Pancreatic cancer (PC) is the fourth leading cause of cancer deaths in the United States with a five-year patient survival rate of only 6%. Early detection and treatment of this disease is hampered due to lack of reliable diagnostic and prognostic markers. Recent studies have shown that dynamic changes in the global DNA methylation and gene expression patterns play key roles in the PC development; hence, provide valuable insights for better understanding the initiation and progression of PC. In the current study, we used DNA methylation, gene expression, copy number, mutational and clinical data from pancreatic patients...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423572/acceleration-of-leukocytes-epigenetic-age-as-an-early-tumor-and-sex-specific-marker-of-breast-and-colorectal-cancer
#9
Danielle Fernandes Durso, Maria Giulia Bacalini, Claudia Sala, Chiara Pirazzini, Elena Marasco, Massimiliano Bonafé, Ítalo Faria do Valle, Davide Gentilini, Gastone Castellani, Ana Maria Caetano Faria, Claudio Franceschi, Paolo Garagnani, Christine Nardini
Changes in blood epigenetic age have been associated with several pathological conditions and have recently been described to anticipate cancer development. In this work, we analyze a publicly available leukocytes methylation dataset to evaluate the relation between DNA methylation age and the prospective development of specific types of cancer. We calculated DNA methylation age acceleration using five state-of-the-art estimators (three multi-site: Horvath, Hannum, Weidner; and two CpG specific: ELOV2 and FHL2) in a cohort including 845 subjects from the EPIC-Italy project and we compared 424 samples that remained cancer-free over the approximately ten years of follow-up with 235 and 166 subjects who developed breast and colorectal cancer, respectively...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421568/prions-prionoid-complexes-and-amyloids-the-bad-the-good-and-something-in-between
#10
Iva Hafner Bratkovič
Prions are infectious agents causing transmissible spongiform encephalopathies in humans and animals. These protein-based particles template conformational changes in a host-encoded prion protein to an insoluble self-like conformation. Prions are also present in yeast, where they support protein-based epigenetic inheritance. There is emerging evidence that prion-like (prionoid) particles can support a variety of pathological and beneficial functions. The recent data on the prionoid spread of other pathological amyloids are discussed in light of differences between prions and prion-like aggregates...
April 19, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28411854/the-molecular-revolution-in-cutaneous-biology-chromosomal-territories-higher-order-chromatin-remodeling-and-the-control-of%C3%A2-gene-expression-in-keratinocytes
#11
REVIEW
Vladimir A Botchkarev
Three-dimensional organization of transcription in the nucleus and mechanisms controlling the global chromatin folding, including spatial interactions between the genes, noncoding genome elements, and epigenetic and transcription machinery, are essential for establishing lineage-specific gene expression programs during cell differentiation. Spatial chromatin interactions in the nucleus involving gene promoters and distal regulatory elements are currently considered major forces that drive cell differentiation and genome evolution in general, and such interactions are substantially reorganized during many pathological conditions...
May 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28410601/the-diagnosis-and-management-of-nk-t-cell-lymphomas
#12
REVIEW
Eric Tse, Yok-Lam Kwong
Extranodal natural killer (NK)/T-cell lymphoma is an aggressive malignancy of putative NK-cell origin, with a minority deriving from the T-cell lineage. Pathologically, the malignancy occurs in two forms, extranodal NK/T-cell lymphoma, nasal type; and aggressive NK-cell leukaemia. Lymphoma occur most commonly (80%) in the nose and upper aerodigestive tract, less commonly (20%) in non-nasal areas (skin, gastrointestinal tract, testis, salivary gland), and rarely as disseminated disease with a leukemic phase...
April 14, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28409534/bifidobacterium-animalis-subsp-lactis-420-mitigates-the-pathological-impact-of-myocardial-infarction-in-the-mouse
#13
C A Danilo, E Constantopoulos, L A McKee, H Chen, J A Regan, Y Lipovka, S Lahtinen, L K Stenman, T-V V Nguyen, K P Doyle, M J Slepian, Z I Khalpey, J P Konhilas
There is a growing appreciation that our microbial environment in the gut plays a critical role in the maintenance of health and the pathogenesis of disease. Probiotic, beneficial gut microbes, administration can directly attenuate cardiac injury and post-myocardial infarction (MI) remodelling, yet the mechanisms of cardioprotection are unknown. We hypothesised that administration of Bifidobacterium animalis subsp. lactis 420 (B420), a probiotic with known anti-inflammatory properties, to mice will mitigate the pathological impact of MI, and that anti-inflammatory T regulatory (Treg) immune cells are necessary to impart protection against MI as a result of B420 administration...
April 14, 2017: Beneficial Microbes
https://www.readbyqxmd.com/read/28409176/systemic-analysis-of-osteoblast-specific-dna-methylation-marks-reveals-novel-epigenetic-basis-of-osteoblast-differentiation
#14
Fangtang Yu, Hui Shen, Hong-Wen Deng
DNA methylation is an important epigenetic modification that contributes to the lineage commitment and specific functions of different cell types. In this study, we compared ENCODE-generated genome-wide DNA methylation profiles of human osteoblast with 21 other types of human cells in order to identify osteoblast-specific methylation events. For most of the cell strains, data from two isogenic replicates were included, resulting in a total of 51 DNA methylation datasets. We identified 852 significant osteoblast-specific differentially methylated CpGs (DMCs) and 295 significant differentially methylated regions (DMRs)...
June 2017: Bone Reports
https://www.readbyqxmd.com/read/28408905/tet-methylcytosine-oxidases-in-t-cell-and-b-cell-development-and-function
#15
REVIEW
Ageliki Tsagaratou, Chan-Wang J Lio, Xiaojing Yue, Anjana Rao
DNA methylation is established by DNA methyltransferases and is a key epigenetic mark. Ten-eleven translocation (TET) proteins are enzymes that oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and further oxidization products (oxi-mCs), which indirectly promote DNA demethylation. Here, we provide an overview of the effect of TET proteins and altered DNA modification status in T and B cell development and function. We summarize current advances in our understanding of the role of TET proteins and 5hmC in T and B cells in both physiological and pathological contexts...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28408473/o-glcnacylation-and-chromatin-remodeling-in-mammals-an-up-to-date-overview
#16
REVIEW
Maïté Leturcq, Tony Lefebvre, Anne-Sophie Vercoutter-Edouart
Post-translational modifications of histones and the dynamic DNA methylation cycle are finely regulated by a myriad of chromatin-binding factors and chromatin-modifying enzymes. Epigenetic modifications ensure local changes in the architecture of chromatin, thus controlling in fine the accessibility of the machinery of transcription, replication or DNA repair to the chromatin. Over the past decade, the nutrient-sensor enzyme O-GlcNAc transferase (OGT) has emerged as a modulator of chromatin remodeling. In mammals, OGT acts either directly through dynamic and reversible O-GlcNAcylation of histones and chromatin effectors, or in an indirect manner through its recruitment into chromatin-bound multiprotein complexes...
April 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28401895/integrated-host-and-viral-transcriptome-analyses-reveal-pathology-and-inflammatory-response-mechanisms-to-alv-j-injection-in-spf-chickens
#17
Xi Lan, Yan Wang, Kai Tian, Fei Ye, Huadong Yin, Xiaoling Zhao, Hengyong Xu, Yong Huang, Haibo Liu, John C F Hsieh, Susan J Lamont, Qing Zhu
Avian leukosis virus (ALV) is detrimental to poultry health and causes substantial economic losses from mortality and decreased performance. Because tumorigenesis is a complex mechanism, the regulatory architecture of the immune system is likely to include the added dimensions of modulation by miRNAs and long-noncoding RNA (lncRNA). To characterize the response to ALV challenge, we developed a novel methodology that combines four datasets: mRNA expression and the associated regulatory factors of miRNA and lncRNA, and ALV gene expression...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28400482/epigenetic-programming-of-the-neuroendocrine-stress-response-by-adult-life-stress
#18
Bart Dirven, Judith Homberg, Tamas Kozicz, Marloes Henckens
The hypothalamic-pituitary adrenal (HPA) axis is critically involved in the neuroendocrine regulation of stress adaptation, and the restoration of homeostasis following stress exposure. Dysregulation of this axis is associated with stress-related pathologies like major depressive disorder, post-traumatic stress disorder, panic disorder, and chronic anxiety. It has long been understood that stress during early life can have a significant lasting influence on the development of the neuroendocrine system and its neural regulators, partially by modifying epigenetic regulation of gene expression, with implications for health and well-being in later life...
April 11, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28397115/neural-substrates-of-depression-and-resilience
#19
REVIEW
Ming-Hu Han, Eric J Nestler
There is an urgent need for more effective medications to treat major depressive disorder, as fewer than half of depressed patients achieve full remission and many are not responsive with currently available antidepressant medications or psychotherapy. It is known that prolonged stressful events are an important risk factor for major depressive disorder. However, there are prominent individual variations in response to stress: a relatively small proportion of people (10-20%) experiencing prolonged stress develop stress-related psychiatric disorders, including depression (susceptibility to stress), whereas most stress-exposed individuals maintain normal psychological functioning (resilience to stress)...
April 10, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
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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