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https://www.readbyqxmd.com/read/28214660/enhancer-of-zeste-homologue-2-plays-an-important-role-in-neuroblastoma-cell-survival-independent-of-its-histone-methyltransferase-activity
#1
Laurel T Bate-Eya, Hinco J Gierman, Marli E Ebus, Jan Koster, Huib N Caron, Rogier Versteeg, M Emmy M Dolman, Jan J Molenaar
Neuroblastoma is predominantly characterised by chromosomal rearrangements. Next to V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma Derived Homolog (MYCN) amplification, chromosome 7 and 17q gains are frequently observed. We identified a neuroblastoma patient with a regional 7q36 gain, encompassing the enhancer of zeste homologue 2 (EZH2) gene. EZH2 is the histone methyltransferase of lysine 27 of histone H3 (H3K27me3) that forms the catalytic subunit of the polycomb repressive complex 2. H3K27me3 is commonly associated with the silencing of genes involved in cellular processes such as cell cycle regulation, cellular differentiation and cancer...
February 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28209712/mycobacterium-tuberculosis-esxl-inhibit-mhc-ii-expression-by-promoting-hypermethylation-in-class-ii-transactivator-loci-in-macrophages
#2
Srabasti Sengupta, Saba Naz, Ishani Das, Abdul Ahad, Avinash Padhi, Sumanta Naik, Geetanjali Ganguli, Kaliprasad Patnaik, Sunil Kumar Raghav, Vinay Nandicoori, Avinash Sonawane
Mycobacterium tuberculosis (Mtb) is known to modulate the host immune responses to facilitate its persistence inside the host cells. One of the key mechanisms includes repression of class-II transactivator (CIITA) and MHC-II expression in infected macrophages. However, the precise mechanism of CIITA and MHC-II down-regulation is not well studied. Mtb 6-kDa early secretory antigenic target (ESAT-6) is a known potent virulence and antigenic determinant. Mtb genome encodes 23 such ESAT-6 family proteins. We herein report that Mtb and M...
February 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28192919/quantitative-mass-spectrometric-sequencing-of-chitosan-oligomers-revealing-cleavage-sites-of-chitosan-hydrolases
#3
Stefan Cord-Landwehr, Phillip Ihmor, Anna Niehues, Heinrich Luftmann, Bruno M Moerschbacher, Michael Mormann
Partially acetylated chito-oligosaccharides (paCOS) have diverse bioactivities that turn them into promising compounds especially for medical and agricultural applications. These properties likely arise from different acetylation patterns, but determining the sequences of paCOS and producing paCOS with patterns of interest have proven difficult. We present a novel method for sequencing submicrogram amounts of paCOS using quantitative mass spectrometry, allowing one to rapidly analyze the substrate specificities of chitosan hydrolases that can be used to produce paCOS...
February 13, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28188663/histamine-facilitates-gabaergic-transmission-in-the-rat-entorhinal-cortex-roles-of-h1-and-h2-receptors-na-permeable-cation-channels-and-inward-rectifier-k-channels
#4
Nicholas I Cilz, Saobo Lei
In the brain, histamine (HA) serves as a neuromodulator and a neurotransmitter released from the tuberomammillary nucleus (TMN). HA is involved in wakefulness, thermoregulation, energy homeostasis, nociception and learning and memory. The medial entorhinal cortex (MEC) receives inputs from the TMN and expresses HA receptors (H1 , H2 , and H3 ). We investigated the effects of HA on GABAergic transmission in the MEC and found that HA significantly increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) with an EC50 of 1...
February 11, 2017: Hippocampus
https://www.readbyqxmd.com/read/28186757/thieno-3-2-b-pyrrole-5-carboxamides-as-new-reversible-inhibitors-of-histone-lysine-demethylase-kdm1a-lsd1-part-2-structure-based-drug-design-and-structure-activity-relationship
#5
Paola Vianello, Luca Sartori, Federica Amigoni, Anna Cappa, Giovanni Fagá, Raimondo Fattori, Elena Legnaghi, Giuseppe Ciossani, Andrea Mattevi, Giuseppe Meroni, Loris Moretti, Valentina Cecatiello, Sebastiano Pasqualato, Alessia Romussi, Florian Thaler, Paolo Trifiró, Oronza A Botrugno, Manuela Villa, Paola Dessanti, Saverio Minucci, Stefania Vultaggio, Elisa Zagarrí, Mario Varasi, Ciro Mercurio
The balance of methylation levels at histone H3 lysine 4 (H3K4) is regulated by KDM1A (LSD1). KDM1A is overexpressed in several tumor types, thus representing an emerging target for the development of novel cancer therapeutics. We have previously described (Part 1) the identification of thieno[3,2-b]pyrrole-5-carboxamides, as novel reversible inhibitors of KDM1A, whose preliminary exploration resulted in compound 2 with biochemical IC50 = 160 nM. We now report the structure-guided optimization of this chemical series, based on multiple ligand/KDM1A-CoRest co-crystal structures, which led to several extremely potent inhibitors...
February 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28183840/imaging-characteristics-of-pediatric-diffuse-midline-gliomas-with-histone-h3-k27m-mutation
#6
M S Aboian, D A Solomon, E Felton, M C Mabray, J E Villanueva-Meyer, S Mueller, S Cha
BACKGROUND AND PURPOSE: The 2016 World Health Organization Classification of Tumors of the Central Nervous System includes "diffuse midline glioma with histone H3 K27M mutation" as a new diagnostic entity. We describe the MR imaging characteristics of this new tumor entity in pediatric patients. MATERIALS AND METHODS: We retrospectively reviewed imaging features of pediatric patients with midline gliomas with or without the histone H3 K27 mutation. We evaluated the imaging features of these tumors on the basis of location, enhancement pattern, and necrosis...
February 9, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28179535/a-bivalent-heterologous-dna-virus-like-particles-prime-boost-vaccine-elicits-broad-protection-against-both-groups-1-and-2-influenza-a-viruses
#7
Wenbo Jiang, Shuangshuang Wang, Honglin Chen, Huanhuan Ren, Xun Huang, Guiqin Wang, Ze Chen, Ling Chen, Zhiwei Chen, Paul Zhou
Current seasonal influenza vaccines are efficacious when vaccine strains are matched with circulating strains. But they do not protect antigenic variants and newly emerging pandemic and outbreak strains. Thus there is a critical need for developing so-called "universal" vaccines that protect against all influenza viruses. In the present study we developed a bivalent heterologous DNA-virus-like particles (VLP) prime-boost vaccine strategy. We show that mice immunized with this vaccine were broadly protected against lethal challenge of group 1 (H1, H5 and H9) and group 2 (H3 and H7) viruses with 94% aggregate survival...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28177835/analysis-of-the-histone-cluster-in-senegalese-sole-solea-senegalensis-evidence-for-a-divergent-evolution-of-two-canonical-histone-clusters
#8
Manuel Alejandro Merlo, Roger Iziga, Silvia Portela, Ismael Cross, Nadezda Kosyakova, Thomas Liehr, Manuel Manchado, Laureana Rebordinos
The Senegalese sole (Solea senegalensis) is commercially very important, and is a priority species for aquaculture product diversification. The main histone cluster was found in two BAC clones. However, two replacement histones (H1.0 and H3.3) were found in another BAC clone. Different types of canonical H2A and H2B have been found in one species for the first time. Phylogenetic analysis demonstrated that the different H1, H2A and H2B types were all more similar to each other than to canonical histones from other species...
December 10, 2016: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28177342/heterobimetallic-complexes-of-palladium-and-platinum-containing-a-redox-active-w-sns-2-metalloligand
#9
Kyle E Rosenkoetter, Joseph W Ziller, Alan F Heyduk
Complexes of the general formula W[SNS]2M(dppe) (M = Pd, Pt; [SNS]H3 = bis(2-mercapto-p-tolyl)amine; dppe = 1,2-bis(diphenylphosphino)ethane) were prepared by combining the corresponding (dppe)MCl2 synthon with W[SNS]2 under reducing conditions. X-ray diffraction studies revealed the formation of a heterobimetallic complex supported by a single thiolate bridging ligand and a short metal-metal bond between the tungsten and palladium or platinum. Electrochemical and computational results show that the frontier orbitals lie predominantly on the W[SNS]2 fragment suggesting that it behaves as a redox-active metalloligand in these complexes...
February 8, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28174273/h3k4me3-induces-allosteric-conformational-changes-in-the-dna-binding-and-catalytic-regions-of-the-v-d-j-recombinase
#10
John Bettridge, Chan Hyun Na, Akhilesh Pandey, Stephen Desiderio
V(D)J recombination is initiated by the recombination-activating gene (RAG) recombinase, consisting of RAG-1 and RAG-2 subunits. The susceptibility of gene segments to cleavage by RAG is associated with histone modifications characteristic of active chromatin, including trimethylation of histone H3 at lysine 4 (H3K4me3). Binding of H3K4me3 by a plant homeodomain (PHD) in RAG-2 stimulates substrate binding and catalysis, which are functions of RAG-1. This has suggested an allosteric mechanism in which information regarding occupancy of the RAG-2 PHD is transmitted to RAG-1...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28171866/selective-biological-responses-of-phagocytes-and-lungs-to-purified-histones
#11
Fatemeh Fattahi, Jamison J Grailer, Hope Lu, Rachel S Dick, Michella Parlett, Firas S Zetoune, Gabriel Nuñez, Peter A Ward
Histones invoke strong proinflammatory responses in many different organs and cells. We assessed biological responses to purified or recombinant histones, using human and murine phagocytes and mouse lungs. H1 had the strongest ability in vitro to induce cell swelling independent of requirements for toll-like receptors (TLRs) 2 or 4. These responses were also associated with lactate dehydrogenase release. H3 and H2B were the strongest inducers of [Ca2+]i elevations in phagocytes. Cytokine and chemokine release from mouse and human phagocytes was predominately a function of H2A and H2B...
February 8, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28171799/synergistic-antitumor-effect-of-histone-deacetylase-inhibitor-and-doxorubicin-in-peripheral-t-cell-lymphoma
#12
Huilai Zhang, Ling Dong, Qingqing Chen, Lingzhe Kong, Bin Meng, Huaqing Wang, Kai Fu, Xi Wang, Qiang Pan-Hammarström, Ping Wang, Xianhuo Wang
Chidamide (CS055) is a new and highly selective histone deacetylase inhibitor displaying significant single-agent activity in peripheral T-cell lymphoma (PTCL). But there is little known the synergistic effect between CS055 and chemotherapy. The purpose of this study is to explore the synergistic effect and molecular mechanisms of CS055 combination with Doxorubicin in PTCL cells. We found that CS055 showed dose- and time-dependent inhibition effects on PTCL cell. Meanwhile, the synergistic effect was significantly observed after combination treatment with lower drug-concentration of CS055 and Doxorubicin...
January 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28168839/histamine-h3-receptor-antagonist-prevents-memory-deficits-and-synaptic-plasticity-disruption-following-isoflurane-exposure
#13
Tao Luo, Ying Wang, Jian Qin, Zhi-Gang Liu, Min Liu
BACKGROUND: Exposure to pharmacological concentration of inhaled anesthetics such as isoflurane can cause short- or long-term cognitive impairments in preclinical studies. The selective antagonists of the histamine H3 receptors are considered as a promising group of novel therapeutic agents for the treatment of cognitive disorders. In this study, we investigated whether ciproxifan, a nonimidazole antagonist of H3 histamine receptors, could overcome the functional and electrophysiological sequela associated with isoflurane anesthesia...
February 6, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28165227/discovery-of-peptidomimetic-ligands-of-eed-as-allosteric-inhibitors-of-prc2
#14
Kimberly Diane Barnash, Juliana The, Jacqueline L Norris-Drouin, Stephanie H Cholensky, Beau M Worley, Fengling Li, Jacob I Stuckey, Peter J Brown, Masoud Vedadi, Cheryl H Arrowsmith, Stephen V Frye, Lindsey I James
The function of EED within Polycomb repressive complex 2 (PRC2) is mediated by a complex network of protein-protein interactions. Allosteric activation of PRC2 by binding of methylated proteins to EED's aromatic cage is essential for full catalytic activity, but details of this regulation are not fully understood. EED's recognition of the product of PRC2 activity, histone H3 lysine 27 trimethylation (H3K27me3), stimulates PRC2 methyltransferase activity at adjacent nucleosomes leading to H3K27me3 propagation and, ultimately, gene repression...
February 6, 2017: ACS Combinatorial Science
https://www.readbyqxmd.com/read/28164705/metal-organic-framework-chitosan-hybrid-materials-promote-nitric-oxide-release-from-s-nitrosoglutathione-in-aqueous-solution
#15
Megan J Neufeld, Alec Lutzke, Jesus B Tapia, Melissa M Reynolds
It has been previously demonstrated that copper-based metal-organic frameworks (MOFs) accelerate formation of the therapeutically active molecule nitric oxide (NO) from S-nitrosothiols (RSNOs). Because RSNOs are naturally present in blood, this function is hypothesized to permit the controlled production of NO through use of MOF-based blood-contacting materials. The practical implementation of MOFs in this application typically requires incorporation within a polymer support, yet this immobilization has been shown to impair the ability of the MOF to interact with the NO-forming RSNO substrate...
February 6, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28161762/validation-of-an-enzyme-linked-immunosorbent-assay-for-the-quantification-of-citrullinated-histone-h3-as-a-marker-for-neutrophil-extracellular-traps-in-human-plasma
#16
Charlotte Thålin, Maud Daleskog, Sophie Paues Göransson, Daphne Schatzberg, Julie Lasselin, Ann-Charlotte Laska, Anders Kallner, Thomas Helleday, Håkan Wallén, Mélanie Demers
There is an emerging interest in the diverse functions of neutrophil extracellular traps (NETs) in a variety of disease settings. However, data on circulating NETs rely largely upon surrogate NET markers such as cell-free DNA, nucleosomes, and NET-associated enzymes. Citrullination of histone H3 by peptidyl arginine deiminase 4 (PAD4) is central for NET formation, and citrullinated histone H3 (H3Cit) is considered a NET-specific biomarker. We therefore aimed to optimize and validate a new enzyme-linked immunosorbent assay (ELISA) to quantify the levels of H3Cit in human plasma...
February 4, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28155248/mutants-in-the-imprinted-pickle-related-2-gene-suppress-seed-abortion-of-fertilization-independent-seed-class-mutants-and-paternal-excess-interploidy-crosses-in-arabidopsis
#17
Fang Huang, Qian-Hao Zhu, Anyu Zhu, Xiaoba Wu, Liqiong Xie, Xianjun Wu, Chris Helliwell, Abed Chaudhury, E Jean Finnegan, Ming Luo
Endosperm cellularization is essential for embryo development and viable seed formation. Loss of function of the FERTILIZATION INDEPENDENT SEED (FIS) class Polycomb genes, which mediate histone H3 lysine27 trimethylation (H3K27me3), as well as imbalanced contributions of parental genomes interrupt this process. What causes the failure of cellularization is poorly understood. In this study, we identified PICKLE RELATED 2 (PKR2), mutations which suppress seed abortion in fis1/mea by restoring endosperm cellularization...
February 3, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28141907/a-cationic-unsaturated-platinum-ii-complex-that-promotes-the-tautomerization-of-acetylene-to-vinylidene
#18
Laura Ortega-Moreno, Riccardo Peloso, Joaquín López-Serrano, Javier Iglesias-Sigüenza, Celia Maya, Ernesto Carmona
Complex [PtMe2 (PMe2 ArDipp2 )] (1), which contains a tethered terphenyl phosphine (ArDipp2 =2,6-(2,6-(i) Pr2 C6 H3 )2 C6 H3 ), reacts with [H(Et2 O)2 ]BArF (BArF(-) =B[3,5-(CF3 )2 C6 H3 ]4(-) ) to give the solvent (S) complex [PtMe(S)(PMe2 ArDipp2 )](+) (2⋅S). Although the solvent molecule is easily displaced by a Lewis base (e.g., CO or C2 H4 ) to afford the corresponding adducts, treatment of 2⋅S with C2 H2 yielded instead the allyl complex [Pt(η(3) -C3 H5 )(PMe2 ArDipp2 )](+) (6) via the alkyne intermediate [PtMe(η(2) -C2 H2 )(PMe2 ArDipp2 )](+) (5)...
January 31, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28139057/synthesis-of-ubiquitylated-histone-h3-using-a-thiirane-linker-for-chemical-ligation
#19
Toru Kawakami, Yuichi Mishima, Hironobu Hojo, Isao Suetake
Post-translational modifications of histone proteins, which form nucleosome cores, play an important role in gene regulation. Ubiquitin modification is one such modification. We previously reported on the use of a thiirane linker to introduce a 1,2-aminothiol moiety at a cysteine residue for native chemical ligation with peptide thioesters, which permitted isopeptide mimetics to be produced. In this report, we describe the preparation of the ubiquitylated full length histone H3 at the 18 position and the construction of tetranucleosomes with recombinant histones H2A, H2B, H4, and DNA, which are slightly more stable than those that are prepared without ubiquitin modification...
January 31, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28138058/basic-pentacysteine-proteins-repress-abscisic-acid-insensitive4-expression-via-direct-recruitment-of-the-polycomb-repressive-complex-2-in-arabidopsis-root-development
#20
Ying Mu, Meijuan Zou, Xuwu Sun, Baoye He, Xiumei Xu, Yini Liu, Lixin Zhang, Wei Chi
Plant transcription factors generally act in complex regulatory networks that function at multiple levels to govern plant developmental programs. Dissection of the interconnections among different classes of transcription factors can elucidate these regulatory networks and thus improve our understanding of plant development. Here, we investigated the molecular and functional relationships of the transcription factors ABSCISIC ACID INSENSITIVE 4 (ABI4) and members of the BASIC PENTACYSTEINE (BPC) family in lateral root (LR) development of Arabidopsis thaliana Genetic analysis showed that BPCs promote LR development by repressing ABI4 expression...
January 30, 2017: Plant & Cell Physiology
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