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https://www.readbyqxmd.com/read/29352265/type-i-ifn-operates-pyroptosis-and-necroptosis-during-multidrug-resistant-a-baumannii-infection
#1
Yang Li, Xiaomin Guo, Chunmiao Hu, Yan Du, Chuansheng Guo, Di Wang, Weiheng Zhao, Gonghua Huang, Chunliang Li, Qiumin Lu, Ren Lai, Tao Xu, Xiaopeng Qi
Multidrug-resistant Acinetobacter baumannii, a common pathogen responsible for nosocomial infections, is the main cause for outbreaks of infectious diseases, such as pneumonia, meningitis, and bacteremia, especially among critically ill patients. Epidemic A. baumannii is a growing public health concern as it is resistant to all existing antimicrobial agents, thereby necessitating the development of new therapeutic approaches to mount an effective immune response against this bacterial pathogen. In this study, we identified a critical role for type I interferon (IFN) in epigenetic regulation during A...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352223/zeb1-confers-chemotherapeutic-resistance-to-breast-cancer-by-activating-atm
#2
Xiang Zhang, Zhen Zhang, Qing Zhang, Quansheng Zhang, Peiqing Sun, Rong Xiang, Guosheng Ren, Shuang Yang
Although zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in the regulation of breast cancer differentiation and metastasis, its potential role in modulating tumor chemoresistance has not been fully understood. Here, through the study of specimens from a large cohort of human breast cancer subjects, we showed that patients with tumors that expressed high levels of ZEB1 responded poorly to chemotherapy. Moreover, ZEB1 expression was positively correlated with expression of B-cell lymphoma-extra large (Bcl-xL) and cyclin D1, which are key components of tumor chemoresistant mechanisms...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29351919/high-yield-of-pathogenic-germline-mutations-causative-or-likely-causative-of-the-cancer-phenotype-in-selected-children-with-cancer
#3
Illja Diets, Esmé Waanders, Marjolijn J L Ligtenberg, Diede van Bladel, Eveline J Kamping, Peter M Hoogerbrugge, Saskia Hopman, Maran J W Olderode-Berends, Erica H Gerkes, David Koolen, Carlo Marcelis, Gijs We Santen, Martine van Belzen, Dylan Mordaunt, Lesley McGregor, Elizabeth Thompson, Antonis Kattamis, Agata Pastorczak, Wojciech Mlynarski, Denisa Ilencikova, Anneke Vulto-van Silfhout, Thatjana Gardeitchik, E S J M de Bont, Jan Loeffen, Anja Wagner, Arjen R Mensenkamp, Roland P Kuiper, Nicoline Hoogerbrugge, Marjolijn Jongmans
PURPOSE: In many children with cancer and characteristics suggestive of a genetic predisposition syndrome, the genetic cause is still unknown. We studied the yield of pathogenic mutations by applying whole exome sequencing on a selected cohort of children with cancer. EXPERIMENTAL DESIGN: To identify mutations in known and novel cancer predisposing genes, we performed trio-based whole exome sequencing on germline DNA of 40 selected children and their parents. These children were diagnosed with cancer and had at least one of the following features: (1) intellectual disability and/or congenital anomalies, (2) multiple malignancies, (3) family history of cancer or (4) an adult type of cancer...
January 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29348807/discovery-of-spiro-oxazolidinediones-as-selective-orally-bioavailable-inhibitors-of-p300-cbp-histone-acetyltransferases
#4
Michael R Michaelides, Arthur Kluge, Michael Patane, John H Van Drie, Ce Wang, T Matthew Hansen, Roberto M Risi, Robert Mantei, Carmen Hertel, Kannan Karukurichi, Alexandre Nesterov, David McElligott, Peter de Vries, J William Langston, Philip A Cole, Ronen Marmorstein, Hong Liu, Loren Lasko, Kenneth D Bromberg, Albert Lai, Edward A Kesicki
p300 and its paralog CBP can acetylate histones and other proteins and have been implicated in a number of diseases characterized by aberrant gene activation, such as cancer. A novel, highly selective, orally bioavailable histone acetyltransferase (HAT) domain inhibitor has been identified through virtual ligand screening and subsequent optimization of a unique hydantoin screening hit. Conformational restraint in the form of a spirocyclization followed by substitution with a urea led to a significant improvement in potency...
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29343662/cost-benefit-performance-simulation-of-robot-assisted-thoracic-surgery-as-required-for-financiall-viability-under-the-2016-revised-reimbursement-paradigm-of-the-japanese-national-health-insurance-system
#5
Naohiro Kajiwara, Yasufumi Kato, Masaru Hagiwara, Masatoshi Kakihana, Tatsuo Ohira, Norihiko Kawate, Norihiko Ikeda
PURPOSE: To discuss the cost-benefit performance (CBP) and establish a medical fee system for robotic-assisted thoracic surgery (RATS) under the Japanese National Health Insurance System (JNHIS), which is a system not yet firmly established. METHODS: All management steps for RATS are identical, such as preoperative and postoperative management. This study examines the CBP based on medical fees of RATS under the JNHIS introduced in 2016. RESULTS: Robotic-assisted laparoscopic prostatectomy (RALP) and robotic-assisted partial nephrectomy (RAPN) now receive insurance reimbursement under the category of use of support devices for endoscopic surgery ($5420 and $3485, respectively)...
January 17, 2018: Annals of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/29343442/the-transcription-factor-stat6-mediates-direct-repression-of-inflammatory-enhancers-and-limits-activation-of-alternatively-polarized-macrophages
#6
Zsolt Czimmerer, Bence Daniel, Attila Horvath, Dominik Rückerl, Gergely Nagy, Mate Kiss, Matthew Peloquin, Marietta M Budai, Ixchelt Cuaranta-Monroy, Zoltan Simandi, Laszlo Steiner, Bela Nagy, Szilard Poliska, Csaba Banko, Zsolt Bacso, Ira G Schulman, Sascha Sauer, Jean-Francois Deleuze, Judith E Allen, Szilvia Benko, Laszlo Nagy
The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, but our understanding remains limited regarding the molecular determinants of repression. Here we show that IL-4-activated STAT6 transcription factor is required for the direct transcriptional repression of a large number of genes during in vitro and in vivo alternative macrophage polarization. Repression results in decreased lineage-determining transcription factor, p300, and RNA polymerase II binding followed by reduced enhancer RNA expression, H3K27 acetylation, and chromatin accessibility...
January 16, 2018: Immunity
https://www.readbyqxmd.com/read/29341830/pregnancy-related-hormones-progesterone-and-human-chorionic-gonadotrophin-upregulate-expression-of-maternal-plasma-gelsolin
#7
Renu Garg, Nagesh Peddada, Kunzes Dolma, Neeraj Khatri, Ashish Ashish
Plasma gelsolin (pGSN), a protein primarily involved in clearance of circulating actin filaments, is an upcoming novel biomarker. Its level changes in multiple disease and injury conditions, attributable mainly to its consumption during actin clearance, the endogenous regulation of its expression, however, remains elusive as well as unexplored. Here, we are reporting first isolation of the promoter region of pGSN gene and investigation of its transcriptional regulation during pregnancy (a natural process associated with a well programmed injury course of parturition)...
January 17, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29340061/analysis-of-the-mutational-landscape-of-classic-hodgkin-lymphoma-identifies-disease-heterogeneity-and-potential-therapeutic-targets
#8
Elena Mata, Antonio Díaz-López, Ana M Martín-Moreno, Margarita Sánchez-Beato, Ignacio Varela, María J Mestre, Carlos Santonja, Fernando Burgos, Javier Menárguez, Mónica Estévez, Mariano Provencio, Beatriz Sánchez-Espiridión, Eva Díaz, Carlos Montalbán, Miguel A Piris, Juan F García
Defining the mutational landscape of classic Hodgkin lymphoma is still a major research goal. New targeted next-generation sequencing (NGS) techniques may identify pathogenic mechanisms and new therapeutic opportunities related to this disease. We describe the mutational profile of a series of 57 cHL cases, enriched in Hodgkin and Reed-Sternberg (HRS) cells. Overall, the results confirm the presence of strong genomic heterogeneity. However, several variants were consistently detected in genes related to relevant signaling pathways, such as GM-CSF/IL-3, CBP/EP300, JAK/STAT, NF-kappaB, and numerous variants of genes affecting the B-cell receptor (BCR) pathway, such as BTK, CARD11, BCL10, among others...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339447/guidance-of-super-enhancers-in-regulation-of-il-9-induction-and-airway-inflammation
#9
Xiang Xiao, Yihui Fan, Junhui Li, Xiaolong Zhang, Xiaohua Lou, Yaling Dou, Xiaomin Shi, Peixiang Lan, Yue Xiao, Laurie Minze, Xian Chang Li
Th9 cells are prominently featured in allergic lung inflammation, but the mechanism that regulates IL-9 induction in T helper cells remains poorly defined. Here we demonstrate that formation of super-enhancers (SEs) is critical in robust induction of IL-9 and that assembly of the Il9 SEs in Th cells requires OX40-triggered chromatin acetylation. Mechanistically, we found that OX40 costimulation induces RelB expression, which recruits the histone acetyltransferase p300 to the Il9 locus to catalyze H3K27 acetylation...
January 16, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29339118/aerobic-and-anaerobic-cellulose-utilization-by-paenibacillus-sp-caa11-and-enhancement-of-its-cellulolytic-ability-by-expressing-a-heterologous-endoglucanase
#10
Eun Sook Kim, Byeong-Soo Kim, Ki-Yeon Kim, Han-Min Woo, Sun-Mi Lee, Youngsoon Um
For cost-effective lignocellulosic biofuel/chemical production, consolidated bioprocessing (CBP)-enabling microorganisms utilizing cellulose as well as producing biofuel/chemical are required. A novel strain Paenibacillus sp. CAA11 isolated from sediment was found to be not only as a cellulose degrader under both aerobic and strict anaerobic conditions but also as a producer of cellulosic biofuel/chemicals. Paenibacillus sp. CAA11 secreted cellulolytic enzymes by its own secretion system and produced ethanol as well as short-chain organic acids (formic acid, acetic acid, lactic acid) from cellulose...
January 12, 2018: Journal of Biotechnology
https://www.readbyqxmd.com/read/29338479/graphene-oxide-regulates-cox2-in-human-embryonic-kidney-293t-cells-via-epigenetic-mechanisms-dynamic-chromosomal-interactions
#11
Yuxiang Sun, Hui Dai, Shaopeng Chen, Ming Xu, Xuanyu Wang, Yajun Zhang, Shengmin Xu, An Xu, Jian Weng, Sijin Liu, Lijun Wu
To extend the applications of engineered nanomaterials, such as graphene oxide (GO), it is necessary to minimize cytotoxicity. However, the mechanisms underlying this cytotoxicity are unclear. Dynamic chromosomal interactions have been used to illustrate the molecular bases of gene expression, which offers a more sensitive and cutting-edge technology to elucidate complex biological processes associated with epigenetic regulations. In this study, the role of GO-triggered chromatin interactions in the activation of cox2, a hallmark of inflammation, was investigated in normal human cells...
January 16, 2018: Nanotoxicology
https://www.readbyqxmd.com/read/29337239/background-suppression-and-its-relation-to-foreground-processing-of-speech-versus-non-speech-streams
#12
Xiaochen Zhang, Xiaolin Li, Jingjing Chen, Qin Gong
Since sound perception takes place against a background with a certain amount of noise, both speech and non-speech processing involve extraction of target signals and suppression of background noise. Previous works on early processing of speech phonemes largely neglected how background noise is encoded and suppressed. This study aimed to fill in this gap. We adopted an oddball paradigm where speech (vowels) or non-speech stimuli (complex tones) were presented with or without a background of amplitude-modulated noise and analyzed cortical responses related to foreground stimulus processing, including mismatch negativity (MMN), N2b, and P300, as well as neural representations of the background noise, i...
January 11, 2018: Neuroscience
https://www.readbyqxmd.com/read/29331689/baicalin-inhibits-pressure-overload-induced-cardiac-fibrosis-through-regulating-ampk-tgf-%C3%AE-smads-signaling-pathway
#13
Yichuan Xiao, Jiantao Ye, Ying Zhou, Junjun Huang, Xiawen Liu, Biyun Huang, Liu Zhu, Bo Wu, Genshui Zhang, Yi Cai
AMP-activated protein kinase (AMPK) is a central regulator of multiple metabolic pathways. It has been shown that activation of AMPK could inhibit fibroblast proliferation and extracellular matrix (ECM) accumulation, thereby suppressing cardiac fibrosis. Baicalin, the major component found in skullcap, possesses multiple protective effects on the cardiovascular system. However, little is known about the effect of baicalin on cardiac fibrosis and the molecular mechanism by which baicalin exerts its anti-fibrotic effects has not been investigated...
January 10, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29329830/theoretical-research-in-structure-characteristics-of-different-inhibitors-and-differences-of-binding-modes-with-cbp-bromodomain
#14
Xue-Song Wang, Qing-Chuan Zheng
The CBP (CREB (cAMP responsive element binding protein) binding protein) bromodomain (BRD) could recognize and bind with acetyl K382 of human tumor suppressor protein p53 which the mutation of encoding gene might cause human cancers. CBP-BRD serves as a promising drug target for several disease pathways and a series of effective drug have been discovered. In this study, molecular dynamics (MD) simulations and molecular mechanics generalized born surface area (MM-GB/SA) approaches were performed to investigate the different binding modes between five inhibitors with CBP-BRD...
December 26, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29328447/high-mobility-group-protein%C3%A2-b1-silencing-promotes-susceptibility-of-retinoblastoma-cells-to-chemotherapeutic-drugs-through-downregulating-nuclear-factor-%C3%AE%C2%BAb
#15
Yong Chai, Juhua Xiao, Shouhua Zhang, Yunyan Du, Zhipeng Luo, Xin Zhou, Kai Huang
The aim of the present study was to investigate the effects of high-mobility group protein B1 (HMGB1) silencing on the susceptibility of retinoblastoma (RB) cells to chemotherapeutic drugs and the underlying molecular mechanisms. Western blot analysis revealed that vincristine (VCR), etoposide (ETO) and carboplatin (CBP) significantly increased the expression of HMGB1 in Weri‑Rb-1 and Y79 cells compared with the untreated control (P<0.01). siRNA HMGB1 and siRNA negative control (NC) were transfected to Y79 cells by Lipofectamine™ 2000 and, following VCR treatment, the expression of HMGB1 and nuclear factor-κB (NF-κB) was analyzed...
January 10, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29322983/auditory-p300-event-related-potential-normative-data-in-the-indian-population
#16
N A Uvais, S Haque Nizamie, Basudeb Das, Samir K Praharaj, Mohammad Zia Ul Haq Katshu
OBJECTIVE: To generate the normative data of auditory P300 event-related potential for various age groups in the Indian population. MATERIALS AND METHODS: Auditory P300 event-related potentials, using the oddball paradigm, of healthy control participants in studies carried out at our institute were included to generate normative data in the age range of 10-50 years. The amplitude and latency of P300 for Fz, Cz, and Pz were selected for analysis. RESULTS: For P300 amplitude, overall multivariate analysis of variance (MANOVA) was significant [Pillai's Trace F (9/453) = 3...
January 2018: Neurology India
https://www.readbyqxmd.com/read/29322263/comparative-transcriptomic-analysis-of-skeletal-muscle-tissue-during-prenatal-stages-in-tongcheng-and-yorkshire-pig-using-rna-seq
#17
Huijing Liu, Yu Xi, Guorong Liu, Yuqiang Zhao, Ji Li, Minggang Lei
Myogenesis is accompanied by a number of changes in gene expression in mammals, and the transcriptional events that underlie these processes have not been yet fully elucidated. In this study, RNA-seq was used to comprehensively compare the transcription profiles of skeletal muscle between Tongcheng (TC) and Yorkshire (YK) pigs at 40, 55, 63, 70, and 90 days of gestation. One thousand three hundred seventeen and 691 differentially expressed genes (DEGs) were detected in TC and YK, respectively, among which 321 DEGs were shown to be common in TC and YK...
January 10, 2018: Functional & Integrative Genomics
https://www.readbyqxmd.com/read/29321817/enhanced-myc-association-with-the-nua4-histone-acetyltransferase-complex-mediated-by-the-adenovirus-e1a-n-terminal-domain-activates-a-subset-of-myc-target-genes-highly-expressed-in-cancer-cells
#18
Ling-Jun Zhao, Paul M Loewenstein, Maurice Green
The proto-oncogene MYC is a transcription factor over-expressed in many cancers and required for cell survival. Its function is regulated by histone acetyltransferase (HAT) complexes, such as the GCN5 complex and the NuA4/Tip60 complex. However, the roles of the HAT complexes during MYC function in cancer have not been well characterized. We recently showed that adenovirus E1A and its N-terminal 80 aa region, E1A 1-80, interact with the NuA4 complex, through the E1A TRRAP-targeting (ET) domain, and enhance MYC association with the NuA4 complex...
November 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29320743/a-p300-and-sirt1-regulated-acetylation-switch-of-c-ebp%C3%AE-controls-mitochondrial-function
#19
Mohamad A Zaini, Christine Müller, Tristan V de Jong, Tobias Ackermann, Götz Hartleben, Gertrud Kortman, Karl-Heinz Gührs, Fabrizia Fusetti, Oliver H Krämer, Victor Guryev, Cornelis F Calkhoven
Cellular metabolism is a tightly controlled process in which the cell adapts fluxes through metabolic pathways in response to changes in nutrient supply. Among the transcription factors that regulate gene expression and thereby cause changes in cellular metabolism is the basic leucine-zipper (bZIP) transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα). Protein lysine acetylation is a key post-translational modification (PTM) that integrates cellular metabolic cues with other physiological processes...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29317678/peptidomimetic-blockade-of-myb-in-acute-myeloid-leukemia
#20
Kavitha Ramaswamy, Lauren Forbes, Gerard Minuesa, Tatyana Gindin, Fiona Brown, Michael G Kharas, Andrei V Krivtsov, Scott A Armstrong, Eric Still, Elisa de Stanchina, Birgit Knoechel, Richard Koche, Alex Kentsis
Aberrant gene expression is a hallmark of acute leukemias. MYB-driven transcriptional coactivation with CREB-binding protein (CBP)/P300 is required for acute lymphoblastic and myeloid leukemias, including refractory MLL-rearranged leukemias. Using structure-guided molecular design, we developed a peptidomimetic inhibitor MYBMIM that interferes with the assembly of the molecular MYB:CBP/P300 complex and rapidly accumulates in the nuclei of AML cells. Treatment of AML cells with MYBMIM led to the dissociation of the MYB:CBP/P300 complex in cells, its displacement from oncogenic enhancers enriched for MYB binding sites, and downregulation of MYB-dependent gene expression, including of MYC and BCL2 oncogenes...
January 9, 2018: Nature Communications
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