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https://www.readbyqxmd.com/read/28338656/focal-adhesion-kinase-depletion-reduces-human-hepatocellular-carcinoma-growth-by-repressing-enhancer-of-zeste-homolog-2
#1
Daniela Gnani, Ilaria Romito, Simona Artuso, Marco Chierici, Cristiano De Stefanis, Nadia Panera, Annalisa Crudele, Sara Ceccarelli, Elena Carcarino, Valentina D'Oria, Manuela Porru, Ezio Giorda, Karin Ferrari, Luca Miele, Erica Villa, Clara Balsano, Diego Pasini, Cesare Furlanello, Franco Locatelli, Valerio Nobili, Rossella Rota, Carlo Leonetti, Anna Alisi
Hepatocellular carcinoma (HCC) is the most common type of liver cancer in humans. The focal adhesion tyrosine kinase (FAK) is often over-expressed in human HCC and FAK inhibition may reduce HCC cell invasiveness. However, the anti-oncogenic effect of FAK knockdown in HCC cells remains to be clarified. We found that FAK depletion in HCC cells reduced in vitro and in vivo tumorigenicity, by inducing G2/M arrest and apoptosis, decreasing anchorage-independent growth, and modulating the expression of several cancer-related genes...
March 24, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28337120/antidyskinetic-effects-of-mek-inhibitor-are-associated-with-multiple-neurochemical-alterations-in-the-striatum-of-hemiparkinsonian-rats
#2
Guiqin Chen, Shuke Nie, Chao Han, Kai Ma, Yan Xu, Zhentao Zhang, Stella M Papa, Xuebing Cao
L-DOPA-induced dyskinesia (LID) represents one of the major problems of the long-term therapy of patients with Parkinson's disease (PD). Although, the pathophysiologic mechanisms underlying LID are not completely understood, activation of the extracellular signal regulated kinase (ERK) is recognized to play a key role. ERK is phosphorylated by mitogen-activated protein kinase kinase (MEK), and thus MEK inhibitor can prevent ERK activation. Here the effect of the MEK inhibitor PD98059 on LID and the associated molecular changes were examined...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28336670/pi3k-pathway-regulates-er-dependent-transcription-in-breast-cancer-through-the-epigenetic-regulator-kmt2d
#3
Eneda Toska, Hatice U Osmanbeyoglu, Pau Castel, Carmen Chan, Ronald C Hendrickson, Moshe Elkabets, Maura N Dickler, Maurizio Scaltriti, Christina S Leslie, Scott A Armstrong, José Baselga
Activating mutations in PIK3CA, the gene encoding phosphoinositide-(3)-kinase α (PI3Kα), are frequently found in estrogen receptor (ER)-positive breast cancer. PI3Kα inhibitors, now in late-stage clinical development, elicit a robust compensatory increase in ER-dependent transcription that limits therapeutic efficacy. We investigated the chromatin-based mechanisms leading to the activation of ER upon PI3Kα inhibition. We found that PI3Kα inhibition mediates an open chromatin state at the ER target loci in breast cancer models and clinical samples...
March 24, 2017: Science
https://www.readbyqxmd.com/read/28334966/structural-and-mechanistic-insights-into-regulation-of-hbo1-histone-acetyltransferase-activity-by-brpf2
#4
Ye Tao, Chen Zhong, Junjun Zhu, Shutong Xu, Jianping Ding
HBO1, a member of the MYST family of histone acetyltransferases (HATs), is required for global acetylation of histone H3K14 and embryonic development. It functions as a catalytic subunit in multisubunit complexes comprising a BRPF1/2/3 or JADE1/2/3 scaffold protein, and two accessory proteins. BRPF2 has been shown to be important for the HAT activity of HBO1 toward H3K14. Here we demonstrated that BRPF2 can regulate the HAT activity of HBO1 toward free H3 and H4, and nucleosomal H3. Particularly, a short N-terminal region of BRPF2 is sufficient for binding to HBO1 and can potentiate its activity toward H3K14...
February 24, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334823/h3-y-discriminates-between-hira-and-daxx-chaperone-complexes-and-reveals-unexpected-insights-into-human-daxx-h3-3-h4-binding-and-deposition-requirements
#5
Lisa-Maria Zink, Erwan Delbarre, H Christian Eberl, Eva C Keilhauer, Clemens Bönisch, Sebastian Pünzeler, Marek Bartkuhn, Philippe Collas, Matthias Mann, Sandra B Hake
Histone chaperones prevent promiscuous histone interactions before chromatin assembly. They guarantee faithful deposition of canonical histones and functionally specialized histone variants into chromatin in a spatial- and temporally-restricted manner. Here, we identify the binding partners of the primate-specific and H3.3-related histone variant H3.Y using several quantitative mass spectrometry approaches, and biochemical and cell biological assays. We find the HIRA, but not the DAXX/ATRX, complex to recognize H3...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28328154/a-symmetric-co-n5-2-h2-o-4-%C3%A2-4%C3%A2-h2-o-high-nitrogen-compound-formed-by-cobalt-ii-cation-trapping-of-a-cyclo-n5-anion
#6
Chong Zhang, Chen Yang, Bingcheng Hu, Chuanming Yu, Zhansheng Zheng, Chengguo Sun
The reactions of (N5 )6 (H3 O)3 (NH4 )4 Cl with Co(NO3 )2 ⋅6 H2 O at room temperature yielded Co(N5 )2 (H2 O)4 ⋅4 H2 O as an air-stable orange metal complex. The structure, as determined by single-crystal X-ray diffraction, has two planar cyclo-N5(-) rings and four bound water molecules symmetrically positioned around the central metal ion. Thermal analysis demonstrated the explosive properties of the material.
March 22, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28326943/analgesia-induced-by-the-epigenetic-drug-l-acetylcarnitine-outlasts-the-end-of-treatment-in-mouse-models-of-chronic-inflammatory-and-neuropathic-pain
#7
Serena Notartomaso, Giada Mascio, Matteo Bernabucci, Cristina Zappulla, Pamela Scarselli, Milena Cannella, Tiziana Imbriglio, Roberto Gradini, Giuseppe Battaglia, Valeria Bruno, Ferdinando Nicoletti
Background L-acetylcarnitine, a drug marketed for the treatment of chronic pain, causes analgesia by epigenetically up-regulating type-2 metabotropic glutamate (mGlu2) receptors in the spinal cord. Because the epigenetic mechanisms are typically long-lasting, we hypothesized that analgesia could outlast the duration of L-acetylcarnitine treatment in models of inflammatory and neuropathic pain. Results A seven-day treatment with L-acetylcarnitine (100 mg/kg, once a day, i.p.) produced an antiallodynic effect in the complete Freund adjuvant mouse model of chronic inflammatory pain...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28320872/the-drosophila-daxx-like-protein-dlp-cooperates-with-asf1-for-h3-3-deposition-and-heterochromatin-formation
#8
Catherine Fromental-Ramain, Philippe Ramain, Ali Hamiche
Histone variants are non-allelic isoforms of canonical histones and they are deposited, in contrast to canonical histones, in a replication-independent (RI) manner. RI deposition of H3.3, a histone variant from the H3.3 family, is mediated in mammals by distinct pathways involving either the histone regulator A (HIRA) complex or the death-associated protein (DAXX)/α-thalassemia X-linked mental retardation protein (ATRX) complex. Here, we investigated the function of Drosophila DAXX Like Protein (DLP) by using both fly genetics approaches and protein biochemistry...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28318771/cross-protection-to-new-drifted-influenza-a-h3-viruses-and-prevalence-of-protective-antibodies-to-seasonal-influenza-during-2014-in-portugal
#9
Raquel Guiomar, Susana Pereira da Silva, Patrícia Conde, Paula Cristóvão, Ana Carina Maia, Pedro Pechirra, Ana Paula Rodrigues, Baltazar Nunes, Luís Milho, Ana Paula Coelho, Aida Fernandes, Paula Caseiro, Fernando Rodrigues, Lurdes Correia, João Pereira-Vaz, Sofia Almeida, Paula Branquinho, Rita Côrte-Real, Regina Viseu, Maria João Peres, Raquel Sanches, Filipa Dantas, Ludovina Freitas, Graça Andrade, Manuel Maurílio, Filomena Caldeira, Rita Cabral Veloso, Luisa Mota-Vieira, Marta Soares, Ana Rita Couto, Jácome Bruges-Armas, Rita Mouro Pinto, Joana Sobrinho Simões, Maria do Rosário Costa, João Tiago Guimarães, Luís Martins, Mário Cunha
INTRODUCTION: Immune profile for influenza viruses is highly changeable over time. Serological studies can assess the prevalence of influenza, estimate the risk of infection, highlight asymptomatic infection rate and can also provide data on vaccine coverage. The aims of the study were to evaluate pre-existing cross-protection against influenza A(H3) drift viruses and to assess influenza immunity in the Portuguese population. MATERIALS AND METHODS: We developed a cross-sectional study based on a convenience sample of 626 sera collected during June 2014, covering all age groups, both gender and all administrative health regions of Portugal...
March 15, 2017: Vaccine
https://www.readbyqxmd.com/read/28317936/priming-of-transcriptional-memory-responses-via-the-chromatin-accessibility-landscape-in-t-cells
#10
Wen Juan Tu, Kristine Hardy, Christopher R Sutton, Robert McCuaig, Jasmine Li, Jenny Dunn, Abel Tan, Vedran Brezar, Melanie Morris, Gareth Denyer, Sau Kuen Lee, Stephen J Turner, Nabila Seddiki, Corey Smith, Rajiv Khanna, Sudha Rao
Memory T cells exhibit transcriptional memory and "remember" their previous pathogenic encounter to increase transcription on re-infection. However, how this transcriptional priming response is regulated is unknown. Here we performed global FAIRE-seq profiling of chromatin accessibility in a human T cell transcriptional memory model. Primary activation induced persistent accessibility changes, and secondary activation induced secondary-specific opening of previously less accessible regions associated with enhanced expression of memory-responsive genes...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315340/in-vivo-pharmacological-profile-of-s-38093-a-novel-histamine-h3-receptor-inverse-agonist
#11
Fany Panayi, Aurore Sors, Lionel Bert, Brigitte Martin, Gaelle Rollin-Jego, Rodolphe Billiras, Isabelle Carrié, Karine Albinet, Laurence Danober, Nathalie Rogez, Jean-Yves Thomas, Luigi Pira, Valérie Bertaina-Anglade, Pierre Lestage
S 38093, a novel histamine H3 receptor inverse agonist, was tested in a series of neurochemical and behavioral paradigms designed to evaluate its procognitive and arousal properties. In intracerebral microdialysis studies performed in rats, S 38093 dose-dependently increased histamine extracellular levels in the prefrontal cortex and facilitated cholinergic transmission in the prefrontal cortex and hippocampus of rats after acute and chronic administration (10mg/kg i.p.). Acute oral administration of S 38093 at 0...
March 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28301229/low-pathogenic-avian-influenza-viruses-in-wild-migratory-waterfowl-in-a-region-of-high-poultry-production-delmarva-maryland
#12
Diann J Prosser, Christine L Densmore, Larry J Hindman, Deborah D Iwanowicz, Chris A Ottinger, Luke R Iwanowicz, Cindy P Driscoll, Jessica L Nagel
Migratory waterfowl are natural reservoirs for low pathogenic avian influenza viruses (AIVs) and may contribute to the long-distance dispersal of these pathogens as well as spillover into domestic bird populations. Surveillance for AIVs is critical to assessing risks for potential spread of these viruses among wild and domestic bird populations. The Delmarva Peninsula on the east coast of the United States is both a key convergence point for migratory Atlantic waterfowl populations and a region with high poultry production (>4,700 poultry meat facilities)...
March 2017: Avian Diseases
https://www.readbyqxmd.com/read/28294989/a-flavone-constituent-from-myoporum-bontioides-induces-m-phase-cell-cycle-arrest-of-mcf-7-breast-cancer-cells
#13
Jing-Ru Weng, Li-Yuan Bai, Wei-Yu Lin, Chang-Fang Chiu, Yu-Chang Chen, Shi-Wei Chao, Chia-Hsien Feng
Myoporum bontioides is a traditional medicinal plant in Asia with various biological activities, including anti-inflammatory and anti-bacterial characteristics. To identify the bioactive constituents from M. bontioides, a newly-identified flavone, 3,4'-dimethoxy-3',5,7-trihydroxyflavone (compound 1), along with eight known compounds, were investigated in human MCF-7 breast cancer, SCC4 oral cancer, and THP-1 monocytic leukemia cells. Among these compounds, compound 1 exhibited the strongest antiproliferative activity with half-maximal inhibitory concentration (IC50) values ranging from 3...
March 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28294389/deciphering-the-molecular-effects-of-mutations-on-atrx-cause-atrx-syndrome-a-molecular-dynamics-study
#14
P Chandrasekaran, R Rajasekaran
α-thalassemia mental retardation X-linked (ATRX) syndrome is caused by the dysfunction of ATRX protein. The present study explored the structural consequences influenced by two observed mutations V194I and C220R on ADD domain of ATRX protein by applying all atom molecular dynamics (MD) simulation. MD result showed that both the mutants exhibited wide variations in their backbone dynamics, as a result, mutant V210I showed complete distortion on α3 and the mutant C220R displayed a biased disruption on α2-3...
March 10, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28291648/combining-stable-insect-cell-lines-with-baculovirus-mediated-expression-for-multi-ha-influenza-vlp-production
#15
Daniela P Sequeira, Ricardo Correia, Manuel J T Carrondo, António Roldão, Ana P Teixeira, Paula M Alves
Safer and broadly protective vaccines are needed to cope with the continuous evolution of circulating influenza virus strains and promising approaches based on the expression of multiple hemagglutinins (HA) in a virus-like particle (VLP) have been proposed. However, expression of multiple genes in the same vector can lead to its instability due to tandem repetition of similar sequences. By combining stable with transient expression systems we can rationally distribute the number of genes to be expressed per platform and thus mitigate this risk...
March 10, 2017: Vaccine
https://www.readbyqxmd.com/read/28288770/experimental-toxoplasma-gondii-infections-in-pigs-humoral-immune-response-estimation-of-specific-igg-avidity-and-the-challenges-of-reproducing-vertical-transmission-in-sows
#16
Walter Basso, Felix Grimm, Maja Ruetten, Vitomir Djokic, Radu Blaga, Xaver Sidler, Peter Deplazes
Ten pregnant sows were experimentally inoculated per os with T. gondii in order to investigate vertical and galactogenic transmission of the parasite and the evolution and maturation of the specific IgG humoral response in the sows and piglets. Five seronegative sows received 10(4)T. gondii (CZ isolate clone H3) sporulated oocysts during late-pregnancy (Exp. 1), three sows received 10(4) oocysts during mid-pregnancy (Exp. 2) and three sows from Exp. 1 (and two seronegative sows) were re-inoculated with 10(5) oocysts during a further pregnancy (late-pregnancy) (Exp...
March 15, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28284523/demethylase-kdm6a-epigenetically-promotes-il-6-and-ifn-%C3%AE-production-in-macrophages
#17
Xia Li, Qian Zhang, Qingzhu Shi, Yin Liu, Kai Zhao, Qicong Shen, Yang Shi, Xingguang Liu, Chunmei Wang, Nan Li, Yuanfang Ma, Xuetao Cao
Molecular regulation of innate signal-initiated proinflammatory cytokine production has been extensively investigated. However, the roles of epigenetic modifiers and their underlying mechanisms in regulating innate inflammatory response and development of autoimmune diseases need to be further understood. Demethylase Kdm6a promotes gene transcription in cell-lineage specification through demethylating histone H3 lysine di/tri-methylation (H3K27me2/3), and loss of Kdm6a results in developmental defects. However, the function of Kdm6a in innate immunity and inflammation remains largely unknown...
March 8, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28284043/the-histone-variant-h3-3-claims-its-place-in-the-crowded-scene-of-epigenetics
#18
Daniele Bano, Antonia Piazzesi, Paolo Salomoni, Pierluigi Nicotera
Histones are evolutionarily conserved DNA-binding proteins. As scaffolding molecules, they significantly regulate the DNA packaging into the nucleus of all eukaryotic cells. As docking units, they influence the recruitment of the transcriptional machinery, thus establishing unique gene expression patterns that ultimately promote different biological outcomes. While canonical histones H3.1 and H3.2 are synthetized and loaded during DNA replication, the histone variant H3.3 is expressed and deposited into the chromatin throughout the cell cycle...
March 10, 2017: Aging
https://www.readbyqxmd.com/read/28282440/h1n1-influenza-viruses-varying-widely-in-hemagglutinin-stability-transmit-efficiently-from-swine-to-swine-and-to-ferrets
#19
Marion Russier, Guohua Yang, Atanaska Marinova-Petkova, Peter Vogel, Bryan S Kaplan, Richard J Webby, Charles J Russell
A pandemic-capable influenza virus requires a hemagglutinin (HA) surface glycoprotein that is immunologically unseen by most people and is capable of supporting replication and transmission in humans. HA stabilization has been linked to 2009 pH1N1 pandemic potential in humans and H5N1 airborne transmissibility in the ferret model. Swine have served as an intermediate host for zoonotic influenza viruses, yet the evolutionary pressure exerted by this host on HA stability was unknown. For over 70 contemporary swine H1 and H3 isolates, we measured HA activation pH to range from pH 5...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28280610/investigation-of-the-human-h3-3b-h3f3b-gene-expression-as-a-novel-marker-in-patients-with-colorectal-cancer
#20
Habib Allah Ayoubi, Frouzandeh Mahjoubi, Rezvan Mirzaei
BACKGROUND: H3.3 histone is a replacement histone subtype that is express in entire cell cycle phases and overexpress in transcriptionally active regions, promoter regions, and intergenic or intragenic regulatory elements. This histone encoded by two genes termed H3.3A (H3F3A) and H3.3B (H3F3B). Mutations of these two genes lead to some human cancers such as chondroblastoma, osteosarcoma, and epithelial ovarian cancer. The aims of this study were to quantitatively examine the expression of H3...
February 2017: Journal of Gastrointestinal Oncology
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