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https://www.readbyqxmd.com/read/28102705/the-acetyl-code-in-rheumatoid-arthritis-and-other-rheumatic-diseases
#1
Chiara Angiolilli, Dominique L Baeten, Timothy R Radstake, Kris A Reedquist
Growing evidence supports the idea that aberrancies in epigenetic processes contribute to the onset and progression of human immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA). Epigenetic regulators of histone tail modifications play a role in chromatin accessibility and transcriptional responses to inflammatory stimuli. Among these, histone deacetylases (HDACs) regulate the acetylation status of histones and nonhistone proteins, essential for immune responses. Broad-spectrum HDAC inhibitors are well-known anti-inflammatory agents and reduce disease severity in animal models of arthritis; however, selective HDAC inhibitors remain poorly studied...
January 19, 2017: Epigenomics
https://www.readbyqxmd.com/read/28100676/gene-body-chromatin-modification-dynamics%C3%A2-mediate-epigenome-differentiation-in%C3%A2-arabidopsis
#2
Soichi Inagaki, Mayumi Takahashi, Aoi Hosaka, Tasuku Ito, Atsushi Toyoda, Asao Fujiyama, Yoshiaki Tarutani, Tetsuji Kakutani
Heterochromatin is marked by methylation of lysine 9 on histone H3 (H3K9me). A puzzling feature of H3K9me is that this modification localizes not only in promoters but also in internal regions (bodies) of silent transcription units. Despite its prevalence, the biological significance of gene-body H3K9me remains enigmatic. Here we show that H3K9me-associated removal of H3K4 monomethylation (H3K4me1) in gene bodies mediates transcriptional silencing. Mutations in an Arabidopsis H3K9 demethylase gene IBM1 induce ectopic H3K9me2 accumulation in gene bodies, with accompanying severe developmental defects...
January 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28100489/tale-induced-bhlh-transcription-factors-that-activate-a-pectate-lyase-contribute-to-water-soaking-in-bacterial-spot-of-tomato
#3
Allison R Schwartz, Robert Morbitzer, Thomas Lahaye, Brian J Staskawicz
AvrHah1 [avirulence (avr) gene homologous to avrBs3 and hax2, no. 1] is a transcription activator-like (TAL) effector (TALE) in Xanthomonas gardneri that induces water-soaked disease lesions on fruits and leaves during bacterial spot of tomato. We observe that water from outside the leaf is drawn into the apoplast in X. gardneri-infected, but not X. gardneriΔavrHah1 (XgΔavrHah1)-infected, plants, conferring a dark, water-soaked appearance. The pull of water can facilitate entry of additional bacterial cells into the apoplast...
January 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28100030/epigenetics-in-normal-and-malignant-hematopoiesis-an-overview-and-update-2017
#4
REVIEW
Susumu Goyama, Toshio Kitamura
Epigenetic regulation in hematopoiesis has been a field of rapid expansion. Genome-wide analyses have revealed, and will continue to identify genetic alterations in epigenetic genes that are present in various types of hematopoietic neoplasms. Development of new mouse models for individual epigenetic modifiers has revealed their novel, sometimes unexpected, functions. In this review, we provide an overview of genetic alterations within epigenetic genes in various types of hematopoietic neoplasms. We then summarize the physiologic roles of these epigenetic modifiers during hematopoiesis, and describe therapeutic approaches targeting the epigenetic modifications...
January 18, 2017: Cancer Science
https://www.readbyqxmd.com/read/28099154/vitamin-k-epoxide-reductase-regulation-of-androgen-receptor-activity
#5
Ben Yi Tew, Teresa B Hong, Maya Otto-Duessel, Catherine Elix, Egbert Castro, Miaoling He, Xiwei Wu, Sumanta K Pal, Markus Kalkum, Jeremy O Jones
Long-term use of warfarin has been shown to be associated with a reduced risk of prostate cancer. Warfarin belongs to the vitamin K antagonist class of anticoagulants, which inhibit vitamin K epoxide reductase (VKOR). The vitamin K cycle is primarily known for its role in γ-carboxylation, a rare post-translational modification important in blood coagulation. Here we show that warfarin inhibits the transcriptional activity of the androgen receptor (AR), an important driver of prostate cancer development and progression...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28096401/ornithine-decarboxylase-regulates-m1-macrophage-activation-and-mucosal-inflammation-via-histone-modifications
#6
Dana M Hardbower, Mohammad Asim, Paula B Luis, Kshipra Singh, Daniel P Barry, Chunying Yang, Meredith A Steeves, John L Cleveland, Claus Schneider, M Blanca Piazuelo, Alain P Gobert, Keith T Wilson
Macrophage activation is a critical step in host responses during bacterial infections. Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine metabolism, has been well studied in epithelial cells and is known to have essential roles in many different cellular functions. However, its role in regulating macrophage function during bacterial infections is not well characterized. We demonstrate that macrophage-derived ODC is a critical regulator of M1 macrophage activation during both Helicobacter pylori and Citrobacter rodentium infection...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096294/mouse-modeling-of-the-mdm2-mdmx-p53-signaling-axis
#7
REVIEW
Nicole R Tackmann, Yanping Zhang
It is evident that p53 activity is critical for tumor prevention and stress response through its transcriptional activation of genes affecting cellular senescence, apoptosis, cellular metabolism, and DNA repair. The regulation of p53 is highly complex, and MDM2 and MDMX are thought to be critical for deciding the fate of p53, both through inhibitory binding and posttranslational modification. Many mouse models have been generated to study the regulation of p53 in vivo, and they have altered our interpretations of how p53 is regulated by MDM2 and MDMX...
January 17, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28096221/efficient-crispr-cas9-assisted-gene-targeting-enables-rapid-and-precise-genetic-manipulation-of-mammalian-neural-stem-cells
#8
Raul Bardini Bressan, Pooran Singh Dewari, Maria Kalantzaki, Ester Gangoso, Mantas Matjusaitis, Claudia Garcia-Diaz, Carla Blin, Vivien Grant, Harry Bulstrode, Sabine Gogolok, William C Skarnes, Steven M Pollard
Mammalian neural stem (NS) cell lines provide a tractable model for discovery across stem cell and developmental biology, regenerative medicine and neuroscience. They can be derived from foetal or adult germinal tissues and continuously propagated in vitro as adherent monolayers. NS cells are clonally expandable, genetically stable, and easily transfectable - experimental attributes compatible with targeted genetic manipulations. However, gene targeting - so critical for functional studies of embryonic stem cells - has not been exploited to date in NS cells...
January 17, 2017: Development
https://www.readbyqxmd.com/read/28093214/the-upr-reduces-glucose-metabolism-via-ire1-signaling
#9
Judith M van der Harg, Jessica C van Heest, Fabian N Bangel, Sanne Patiwael, Jan R T van Weering, Wiep Scheper
Neurons are highly dependent on glucose. A disturbance in glucose homeostasis therefore poses a severe risk that is counteracted by activation of stress responses to limit damage and restore the energy balance. A major stress response that is activated under conditions of glucose deprivation is the unfolded protein response (UPR) that is aimed to restore proteostasis in the endoplasmic reticulum. The key signaling of the UPR involves the transient activation of a transcriptional program and an overall reduction of protein synthesis...
January 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28091569/epigenetic-regulation-of-plasmodium-falciparum-clonally-variant-gene-expression-during-development-in-anopheles-gambiae
#10
Elena Gómez-Díaz, Rakiswendé S Yerbanga, Thierry Lefèvre, Anna Cohuet, M Jordan Rowley, Jean Bosco Ouedraogo, Victor G Corces
P. falciparum phenotypic plasticity is linked to the variant expression of clonal multigene families such as the var genes. We have examined changes in transcription and histone modifications that occur during sporogonic development of P. falciparum in the mosquito host. All var genes are silenced or transcribed at low levels in blood stages (gametocyte/ring) of the parasite in the human host. After infection of mosquitoes, a single var gene is selected for expression in the oocyst, and transcription of this gene increases dramatically in the sporozoite...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28089822/micrornas-in-pituitary-tumors
#11
Anne Wierinckx, Magali Roche, Catherine Legras-Lachuer, Jacqueline Trouillas, Gérald Raverot, Joël Lachuer
Since the presence of microRNAs was first observed in normal pituitary, the majority of scientific publications addressing their role and the function of microRNAs in the pituitary have been based on pituitary tumor studies. In this review, we briefly describe the involvement of microRNAs in the synthesis of pituitary hormones and we present a comprehensive inventory of microRNA suppressors and inducers of pituitary tumors. Finally, we summarize the functional role of microRNAs in tumorigenesis, progression and aggressiveness of pituitary tumors, mechanisms contributing to the regulation (transcription factors, genomic modifications or epigenetic) or modulation (pharmacological treatment) of microRNAs in these tumors, and the interest of thoroughly studying the expression of miRNAs in body fluids...
January 12, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28089111/the-molecular-landscape-of-colitis-associated-carcinogenesis
#12
Deborah Saraggi, Matteo Fassan, Claudia Mescoli, Marco Scarpa, Nicola Valeri, Andrea Michielan, Renata D'Incá, Massimo Rugge
In spite of the well-established histopathological phenotyping of IBD-associated preneoplastic and neoplastic lesions, their molecular landscape remains to be fully elucidated. Several studies have pinpointed the initiating role of longstanding/relapsing inflammatory insult on the intestinal mucosa, with the activation of different pro-inflammatory cytokines (TNF-α, IL-6, IL-10, IFN-γ), chemokines and metabolites of arachidonic acid resulting in the activation of key transcription factors such as NF-κB. Longstanding inflammation may also modify the intestinal microbiota, prompting the overgrowth of genotoxic microorganisms, which may act as further cancer promoters...
December 21, 2016: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28088440/intersections-of-post-transcriptional-gene-regulatory-mechanisms-with-intermediary-metabolism
#13
REVIEW
Waqar Arif, Gandhar Datar, Auinash Kalsotra
Intermediary metabolism studies have typically concentrated on four major regulatory mechanisms-substrate availability, allosteric enzyme regulation, post-translational enzyme modification, and regulated enzyme synthesis. Although transcriptional control has been a big focus, it is becoming increasingly evident that many post-transcriptional events are deeply embedded within the core regulatory circuits of enzyme synthesis/breakdown that maintain metabolic homeostasis. The prominent post-transcriptional mechanisms affecting intermediary metabolism include alternative pre-mRNA processing, mRNA stability and translation control, and the more recently discovered regulation by noncoding RNAs...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28088184/anti-hepatitis-b-virus-hbv-response-of-imiquimod-based-toll-like-receptor-7-ligand-in-hbv-positive-human-hepatocelluar-carcinoma-cell-line
#14
Dipanwita Das, Isha Sengupta, Neelakshi Sarkar, Ananya Pal, Debraj Saha, Manikankana Bandopadhyay, Chandrima Das, Jimmy Narayan, Shivaram Prasad Singh, Sekhar Chakrabarti, Runu Chakravarty
BACKGROUND: Toll like receptors (TLRs) play an important role in innate immunity and various studies suggest that TLRs play a crucial role in pathogenesis of hepatitis B virus (HBV) infection. The present study aims in looking into the status of crucial host and viral gene expression on inciting TLR7. METHODS: The transcription of TLR7 pathway signaling molecules and HBV DNA viral load were quantified by Real Time-PCR after stimulation of TLR7 with its imiquimod based ligand, R837...
January 14, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28087593/norovirus-mediated-modification-of-the-translational-landscape-via-virus-and-host-induced-cleavage-of-translation-initiation-factors
#15
Edward Emmott, Frederic Sorgeloos, Sarah L Caddy, Surender Vashist, Stanislav Sosnovtsev, Richard Lloyd, Kate Heesom, Nicolas Locker, Ian Goodfellow
Noroviruses produce viral RNAs lacking a 5' cap structure and instead use a virus-encoded VPg protein covalently linked to viral RNA to interact with translation initiation factors and drive viral protein synthesis. Norovirus infection results in the induction of the innate response leading to interferon stimulated gene (ISG) transcription. However the translation of the induced ISG mRNAs is suppressed. A SILAC-based mass spectrometry approach was employed to analyse changes to protein abundance in both whole cell and m7GTP-enriched samples to demonstrate that diminished host mRNA translation correlates with changes to the composition of the eukaryotic initiation factor complex...
January 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28087189/assessment-of-gapdh-expression-by-quantitative-real-time-pcr-in-blood-of-moroccan-ad-cases
#16
REVIEW
Nadia El Kadmiri, Meryam El Khachibi, Ilham Slassi, Bouchra El Moutawakil, Sellama Nadifi, Abdelaziz Soukri
INTRODUCTION: Neuroproteomics studies have showed the high affinity interactions between GAPDH - β-amyloid in Alzheimer disease. The aim of our study is to complete our previous studies by assessing the mechanism responsible of decreased expression of GAPDH protein in the blood of Moroccan AD cases probably due to an alteration at the transcriptional level or at the post translational level. METHODS: The mRNA expression of GAPDH was assessed by quantitative real time PCR in AD cases and healthy controls...
January 10, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28086264/structural-insights-into-the-redox-sensing-mechanism-of-marr-type-regulator-abfr
#17
Guijie Liu, Xing Liu, Hongjiao Xu, Xichun Liu, Hu Zhou, Zhen Huang, Jianhua Gan, Hao Chen, Lefu Lan, Cai-Guang Yang
As a master redox-sensing MarR-family transcriptional regulator, AbfR participates in oxidative stress responses and virulence regulations in Staphylococcus epidermidis. Here, we present structural insights into the DNA-binding mechanism of AbfR in different oxidation states by determining the X-ray crystal structures of a reduced-AbfR/DNA complex, an overoxidized (Cys13-SO2H and Cys13-SO3H) AbfR/DNA, and 2-disulfide cross-linked AbfR dimer. Together with biochemical analyses, our results suggest that the redox regulation of AbfR-sensing displays two novel features: i) the reversible disulfide modification, but not the irreversible overoxidation, significantly abolishes the DNA-binding ability of the AbfR repressor; ii) either 1-disulfide cross-linked or 2-disulfide cross-linked AbfR dimer is biologically significant...
January 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28081126/a-pan-lyssavirus-taqman-real-time-rt-pcr-assay-for-the-detection-of-highly-variable-rabies-virus-and-other-lyssaviruses
#18
Ashutosh Wadhwa, Kimberly Wilkins, Jinxin Gao, Rene Edgar Condori Condori, Crystal M Gigante, Hui Zhao, Xiaoyue Ma, James A Ellison, Lauren Greenberg, Andres Velasco-Villa, Lillian Orciari, Yu Li
Rabies, resulting from infection by Rabies virus (RABV) and related lyssaviruses, is one of the most deadly zoonotic diseases and is responsible for up to 70,000 estimated human deaths worldwide each year. Rapid and accurate laboratory diagnosis of rabies is essential for timely administration of post-exposure prophylaxis in humans and control of the disease in animals. Currently, only the direct fluorescent antibody (DFA) test is recommended for routine rabies diagnosis. Reverse-transcription polymerase chain reaction (RT-PCR) based diagnostic methods have been widely adapted for the diagnosis of other viral pathogens, but there is currently no widely accepted rapid real-time RT-PCR assay for the detection of all lyssaviruses...
January 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28079188/proteome-response-of-chicken-embryo-fibroblast-cells-to-recombinant-h5n1-avian-influenza-viruses-with-different-neuraminidase-stalk-lengths
#19
Yongtao Li, Fan Ming, Huimin Huang, Kelei Guo, Huanchun Chen, Meilin Jin, Hongbo Zhou
The variation on neuraminidase (NA) stalk region of highly pathogenic avian influenza H5N1 virus results in virulence change in animals. In our previous studies, the special NA stalk-motif of H5N1 viruses has been demonstrated to play a significant role in the high virulence and pathogenicity in chickens. However, the molecular mechanisms underlying the pathogenicity of viruses with different NA stalk remain poorly understood. This study presents a comprehensive characterization of the proteome response of chicken cells to recombinant H5N1 virus with stalk-short NA (rNA-wt) and the stalkless NA mutant virus (rSD20)...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28079126/detecting-n-6-methyladenosine-sites-from-rna-transcriptomes-using-ensemble-support-vector-machines
#20
Wei Chen, Pengwei Xing, Quan Zou
As one of the most abundant RNA post-transcriptional modifications, N(6)-methyladenosine (m(6)A) involves in a broad spectrum of biological and physiological processes ranging from mRNA splicing and stability to cell differentiation and reprogramming. However, experimental identification of m(6)A sites is expensive and laborious. Therefore, it is urgent to develop computational methods for reliable prediction of m(6)A sites from primary RNA sequences. In the current study, a new method called RAM-ESVM was developed for detecting m(6)A sites from Saccharomyces cerevisiae transcriptome, which employed ensemble support vector machine classifiers and novel sequence features...
January 12, 2017: Scientific Reports
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