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https://www.readbyqxmd.com/read/28630893/a-d53-repression-motif-induces-oligomerization-of-topless-corepressors-and-promotes-assembly-of-a-corepressor-nucleosome-complex
#1
Honglei Ma, Jingbo Duan, Jiyuan Ke, Yuanzheng He, Xin Gu, Ting-Hai Xu, Hong Yu, Yonghong Wang, Joseph S Brunzelle, Yi Jiang, Scott B Rothbart, H Eric Xu, Jiayang Li, Karsten Melcher
TOPLESS are tetrameric plant corepressors of the conserved Tup1/Groucho/TLE (transducin-like enhancer of split) family. We show that they interact through their TOPLESS domains (TPDs) with two functionally important ethylene response factor-associated amphiphilic repression (EAR) motifs of the rice strigolactone signaling repressor D53: the universally conserved EAR-3 and the monocot-specific EAR-2. We present the crystal structure of the monocot-specific EAR-2 peptide in complex with the TOPLESS-related protein 2 (TPR2) TPD, in which the EAR-2 motif binds the same TPD groove as jasmonate and auxin signaling repressors but makes additional contacts with a second TPD site to mediate TPD tetramer-tetramer interaction...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28630323/role-of-the-cbp-catalytic-core-in-intramolecular-sumoylation-and-control-of-histone-h3-acetylation
#2
Sangho Park, Robyn L Stanfield, Maria A Martinez-Yamout, H Jane Dyson, Ian A Wilson, Peter E Wright
The histone acetyl transferases CREB-binding protein (CBP) and its paralog p300 play a critical role in numerous cellular processes. Dysregulation of their catalytic activity is associated with several human diseases. Previous work has elucidated the regulatory mechanisms of p300 acetyltransferase activity, but it is not known whether CBP activity is controlled similarly. Here, we present the crystal structure of the CBP catalytic core encompassing the bromodomain (BRD), CH2 (comprising PHD and RING), HAT, and ZZ domains at 2...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28627608/silencing-of-lsd1-gene-modulates-histone-methylation-and-acetylation-and-induces-the-apoptosis-of-jeko-1-and-molt-4-cells
#3
Zhong-Kai Zou, Yi-Qun Huang, Yong Zou, Xu-Ke Zheng, Xu-Dong Ma
Lysine-specific demethylase 1 (LSD1) has been identified and biochemically characterized in epigenetics; however, the pathological roles of its dysfunction in mantle cell lymphoma (MCL) and T-cell acute lymphoblastic leukemia remain to be elucidated. In this study, we evaluated LSD1, and histone H3 lysine 4 (H3K4)me1 and H3K4me2 expression in patients with MCL and silenced LSD1 in JeKo‑1 and MOLT‑4 cells, in order to define its role in JeKo‑1 and MOLT‑4 cell proliferation and apoptosis. We retrospectively analyzed the protein expression of LSD1, and mono- and dimethylated H3K4 (H3K4me1 and H3K4me2), and cyclin D1 and Ki67 in 30 cases of MCL by immunohistochemistry...
June 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28622575/protein-nanoparticle-vaccine-based-on-flagellin-carrier-fused-to-influenza-conserved-epitopes-confers-full-protection-against-influenza-a-virus-challenge
#4
Lei Deng, Jong R Kim, Timothy Z Chang, Han Zhang, Teena Mohan, Julie A Champion, Bao-Zhong Wang
Currently marketed influenza vaccines only confer protection against matching influenza virus strains. The influenza A composition of these vaccines needs to be annually updated. Vaccines that target conserved epitopes of influenza viruses would in principle offer broad cross-protection against influenza A viruses. In our study, we investigated the specific immune responses and protective efficacy of protein nanoparticles based on fusion proteins of flagellin carrier linked to conserved influenza epitopes. We designed fusion proteins by replacing the hyperimmunogenic region of flagellin (FliC) with four tandem copies of the ectodomain of matrix protein 2 (f4M2e), H1 HA2 domain (fHApr8) or H3 HA2 domain (fHAaichi)...
June 13, 2017: Virology
https://www.readbyqxmd.com/read/28620234/ezh2-mediated-epigenetic-silencing-of-timp2-promotes-ovarian-cancer-migration-and-invasion
#5
Xiaoqing Yi, Jianfeng Guo, Jing Guo, Si Sun, Ping Yang, Junjie Wang, Yuan Li, Lisha Xie, Jing Cai, Zehua Wang
Enhancer of zeste homolog 2 (EZH2) is often increased in malignant tumors and is involved in metastasis. EZH2 silences gene expression by tri-methylating the lysine 27 residue of histone H3 (H3K27me3). However, the mechanism underlying EZH2 promotion of ovarian cancer metastasis remains elusive. Here, we showed that EZH2 is up-regulated in ovarian cancer and is associated with tumor metastasis and poor survival by mRNA sequencing and microarray results from databases. Tissue microarray and immunohistochemistry results revealed that EZH2 was negatively correlated with the expression of tissue inhibitor of metalloproteinases 2 (TIMP2)...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28616911/-histone-deacetylation-down-regulates-the-expression-of-bnip3-in-renal-cell-carcinoma
#6
Jian-Bang Liu, Hai-Zhou Wang, Zhen-Hua Liu, Miao Xu, Xiang Li
OBJECTIVES: To investigate the down-regulation mechanism of (bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) expression in renal cell carcinoma (RCC). METHODS: RCC cell lines 786-O, ACHN and A498 were treated with different concentrations of histone deacetylase inhibitor TSA. Thereafter, the proliferation of RCC cells was determined with CCK-8 assay, cell apoptosis was observed by flow cytometry, and the expression levels of BNIP3 were determined by Q-PCR and Western blot, and the acetylation status of histone H3 in the promoter of BNIP3 was detected by ChIP...
May 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28611772/bovine-polymorphonuclear-neutrophils-cast-neutrophil-extracellular-traps-against-the-abortive-parasite-neospora-caninum
#7
Rodolfo Villagra-Blanco, Liliana M R Silva, Tamara Muñoz-Caro, Zhengtao Yang, Jianhua Li, Ulrich Gärtner, Anja Taubert, Xichen Zhang, Carlos Hermosilla
Neospora caninum represents a relevant apicomplexan parasite causing severe reproductive disorders in cattle worldwide. Neutrophil extracellular trap (NET) generation was recently described as an efficient defense mechanism of polymorphonuclear neutrophils (PMN) acting against different parasites. In vitro interactions of bovine PMN with N. caninum were analyzed at different ratios and time spans. Extracellular DNA staining was used to illustrate the typical molecules of NETs [i.e., histones (H3), neutrophil elastase (NE), myeloperoxidase (MPO), pentraxin] via antibody-based immunofluorescence analyses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28610789/comparative-study-of-genotypes-of-mycobacterium-tuberculosis-from-a-northern-indian-setting-with-strains-reported-from-other-parts-of-india-and-neighboring-countries
#8
Pragya Sharma, Kiran Katoch, Shilpi Chandra, Devendra Singh Chauhan, Vishnu Dutt Sharma, David Couvin, Nalin Rastogi, Vishwa Mohan Katoch
This study was carried out to characterize Mycobacterium tuberculosis population in Ghatampur, Kanpur, North India, by spoligotyping and Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTRs) typing. A total of 335 isolates were genotyped by spoligotyping and Central Asian (CAS) sub-lineage was the most prevalent, comprising 59.1% of all isolates. Other lineages were: East-African Indian (EAI) (19.10%), T (5.07%), Beijing (3.28%), Manu (2.98%), X (2.68%), S (0.89%), H3 (0...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28609344/phosphohistone-h3-and-ki67-useful-markers-in-differentiating-dermatofibroma-from-dermatofibrosarcoma-protuberans-and-atypical-fibrohistiocytic-lesions
#9
Atin Agarwal, Arun Gopinath, Michael T Tetzlaff, Victor G Prieto
Dermatofibromas (DF) are common, benign, skin tumors, usually easily differentiated from dermatofibrosarcoma protuberans (DFSP) by the presence of a relative low cellularity, lesser degree of infiltration of subcutaneous tissue, and immunohistochemical pattern (eg, FXIIIa in DF and CD34 in DFSP). Atypical fibrohistiocytic lesions (AFL) have features intermediate to DF and DFSP (trunk location, storiform pattern, infiltration of the subcutaneous tissue, and focal expression of both CD34 and Factor XIIIa). It is unclear if mitotic counts/degree of proliferation is helpful to distinguish DF from DFSP...
July 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28608634/molecular-basis-for-the-recognition-of-ccn1-by-monoclonal-antibody-093g9
#10
Chen Zhong, Rongfen Huo, Kuan Hu, Jinlong Shen, Dangsheng Li, Ningli Li, Jianping Ding
CCN1, also named Cyr61 (cysteine-rich protein 61), is the first identified member of the CCN family that is composed of 6 secreted extracellular matrix-associated glycoproteins. CCN1 has been demonstrated to participate in pathogenesis of rheumatoid arthritis through various pathways. A monoclonal antibody, namely, 093G9, is effective to antagonize the effects of CCN1 and hence has potential therapeutic benefits against rheumatoid arthritis. Here, we show that the epitope recognized by 093G9 is mapped to residues 77 to 80 of CCN1, and a cyclic peptide encompassing residues 75 to 81 of CCN1 displays high binding affinity for 093G9...
June 13, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28607149/polycomb-repressive-complex-2-in-an-autoinhibited-state
#11
Matthew Bratkowski, Xin Yang, Xin Liu
Polycomb-group proteins control many fundamental biological processes, such as anatomical development in mammals and vernalization in plants. Polycomb repressive complex 2 (PRC2) is responsible for methylation of histone H3 lysine 27 (H3K27), and trimethylated H3K27 (H3K27me3) is implicated in epigenetic gene silencing. Recent genomic, biochemical, and structural data indicate that PRC2 is broadly conserved from yeast to human in many aspects. Here, we determined the crystal structure of an apo PRC2 from the fungus Chaetomium thermophilum captured in a bona fide autoinhibited state, which represents a novel conformation of PRC2 associated with enzyme regulation in light of the basal and stimulated states that we reported previously...
June 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28600475/dual-inhibition-of-hdac-and-tyrosine-kinase-signaling-pathways-with-cudc-907-inhibits-thyroid-cancer-growth-and-metastases
#12
Shweta Kotian, Lisa Zhang, Myriem Boufraqech, Kelli Gaskins, Sudheer Kumar Gara, Martha M Quezado, Naris Nilubol, Electron Kebebew
PURPOSE: There is currently no standard therapy for anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC), which account for two-thirds of thyroid cancer deaths. Driver mutations in the PI3K/AKT and RAF/RAS/MEK/ERK pathways are common in ATC and PDTC. Histone deacetylases (HDACs) regulate cancer initiation and progression. Our aim was to determine the therapeutic efficacy of simultaneously targeting these pathways in thyroid cancer with a single agent, and to evaluate biomarkers of treatment response...
June 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28598772/implementation-of-a-novel-taxonomy-based-on-cognitive-work-analysis-in-the-assessment-of-safety-performance
#13
Toivo Niskanen
PURPOSE: The aim of this study was to examine how the developed taxonomy of cognitive work analysis (CWA) can be applied in combination with statistical analysis regarding different socio-technical categories. MATERIALS AND METHODS: This study applied a combination of quantitative and qualitative methodologies. Workers (n=120) and managers (n=85) in the chemical industry were asked in a questionnaire how different OSH measures were being implemented. The exploration of the qualitative CWA taxonomy consisted of an analysis of the following topics: (1) Work domain; (2) Control task; (3) Strategies; (4) Social organization and cooperation; and (5) Worker competencies...
June 9, 2017: International Journal of Occupational Safety and Ergonomics: JOSE
https://www.readbyqxmd.com/read/28596772/epigenetic-regulation-of-matrix-metalloproteinase-1-and-3-expression-in-mycobacterium-tuberculosis-infection
#14
Rachel C Moores, Sara Brilha, Frans Schutgens, Paul T Elkington, Jon S Friedland
In pulmonary tuberculosis (TB), the inflammatory immune response against Mycobacterium tuberculosis (Mtb) is associated with tissue destruction and cavitation, which drives disease transmission, chronic lung disease, and mortality. Matrix metalloproteinase (MMP)-1 is a host enzyme critical for the development of cavitation. MMP expression has been shown to be epigenetically regulated in other inflammatory diseases, but the importance of such mechanisms in Mtb-associated induction of MMP-1 is unknown. We investigated the role of changes in histone acetylation in Mtb-induced MMP expression using inhibitors of histone deacetylases (HDACs) and histone acetyltransferases (HAT), HDAC siRNA, promoter-reporter constructs, and chromatin immunoprecipitation assays...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28593137/msk1-regulates-transcriptional-induction-of-arc-arg3-1-in-response-to-neurotrophins
#15
Chris J Hunter, Judit Remenyi, Sonia A Correa, Lucia Privitera, Kathleen M S E Reyskens, Kirsty J Martin, Rachel Toth, Bruno G Frenguelli, J Simon C Arthur
The immediate early gene activity-regulated cytoskeletal protein (Arc)/Arg3.1 and the neurotrophin brain-derived neurotrophic factor (BDNF) play important roles in synaptic plasticity and learning and memory in the mammalian brain. However, the mechanisms by which BDNF regulates the expression of Arc/Arg3.1 are unclear. In this study, we show that BDNF acts via the ERK1/2 pathway to activate the nuclear kinase mitogen- and stress-activated protein kinase 1 (MSK1). MSK1 then induces Arc/Arg3.1 expression via the phosphorylation of histone H3 at the Arc/Arg3...
June 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28591604/g-protein-coupled-receptors-contain-two-conserved-packing-clusters
#16
Omar B Sanchez-Reyes, Aidan L G Cooke, Dale B Tranter, Dawood Rashid, Markus Eilers, Philip J Reeves, Steven O Smith
G protein-coupled receptors (GPCRs) have evolved a seven-transmembrane helix framework that is responsive to a wide range of extracellular signals. An analysis of the interior packing of family A GPCR crystal structures reveals two clusters of highly packed residues that facilitate tight transmembrane helix association. These clusters are centered on amino acid positions 2.47 and 4.53, which are highly conserved as alanine and serine, respectively. Ala2.47 mediates the interaction between helices H1 and H2, while Ser4...
June 6, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28590841/rapid-prediction-of-hematologic-acute-radiation-syndrome-in-radiation-injury-patients-using-peripheral-blood-cell-counts
#17
M Port, B Pieper, T Knie, H Dörr, A Ganser, D Graessle, V Meineke, M Abend
Rapid clinical triage of radiation injury patients is essential for determining appropriate diagnostic and therapeutic interventions. We examined the utility of blood cell counts (BCCs) in the first three days postirradiation to predict clinical outcome, specifically for hematologic acute radiation syndrome (HARS). We analyzed BCC test samples from radiation accident victims (n = 135) along with their clinical outcome HARS severity scores (H1-4) using the System for Evaluation and Archiving of Radiation Accidents based on Case Histories (SEARCH) database...
June 7, 2017: Radiation Research
https://www.readbyqxmd.com/read/28587626/evaluation-of-a-novel-antibody-to-define-histone-3-3-g34r-mutant-brain-tumours
#18
Farhana Haque, Pascale Varlet, Julien Puntonet, Lisa Storer, Aikaterini Bountali, Ruman Rahman, Jacques Grill, Angel M Carcaboso, Chris Jones, Robert Layfield, Richard G Grundy
Missense somatic mutations affecting histone H3.1 and H3.3 proteins are now accepted as the hallmark of paediatric diffuse intrinsic pontine gliomas (DIPG), non-brain stem paediatric high grade gliomas (pHGG) as well as a subset of adult glioblastoma multiforme (GBM). Different mutations give rise to one of three amino acid substitutions at two critical positions within the histone tails, K27M, G34R/V. Several studies have highlighted gene expression and epigenetic changes associated with histone H3 mutations; however their precise roles in tumourigenesis remain incompletely understood...
June 6, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28584723/selection-of-housekeeping-genes-as-internal-controls-for-quantitative-rt-pcr-analysis-of-the-veined-rapa-whelk-rapana-venosa
#19
Hao Song, Xin Dang, Yuan-Qiu He, Tao Zhang, Hai-Yan Wang
BACKGROUND: The veined rapa whelk Rapana venosa is an important commercial shellfish in China and quantitative real-time PCR (qRT-PCR) has become the standard method to study gene expression in R. venosa. For accurate and reliable gene expression results, qRT-PCR assays require housekeeping genes as internal controls, which display highly uniform expression in different tissues or stages of development. However, to date no studies have validated housekeeping genes in R. venosa for use as internal controls for qRT-PCR...
2017: PeerJ
https://www.readbyqxmd.com/read/28582417/genome-wide-alteration-in-dna-hydroxymethylation-in-the-sperm-from-bisphenol-a-exposed-men
#20
Huajun Zheng, Xiaoyu Zhou, De-Kun Li, Fen Yang, Hongjie Pan, Tianqi Li, Maohua Miao, Runsheng Li, Wei Yuan
Environmental BPA exposure has been shown to impact human sperm concentration and motility, as well as rodent spermatogenesis. However, it is unclear whether BPA exposure is associated with alteration in DNA hydroxymethylation, a marker for epigenetic modification, in human sperm. A genome-wide DNA hydroxymethylation study was performed using sperm samples of men who were occupationally exposed to BPA. Compared with controls who had no occupational BPA exposure, the total levels of 5-hydroxymethylcytosine (5hmc) increased significantly (19...
2017: PloS One
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