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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/29348807/discovery-of-spiro-oxazolidinediones-as-selective-orally-bioavailable-inhibitors-of-p300-cbp-histone-acetyltransferases
#3
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/29343442/the-transcription-factor-stat6-mediates-direct-repression-of-inflammatory-enhancers-and-limits-activation-of-alternatively-polarized-macrophages
#4
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
#5
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/29339447/guidance-of-super-enhancers-in-regulation-of-il-9-induction-and-airway-inflammation
#6
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/29338479/graphene-oxide-regulates-cox2-in-human-embryonic-kidney-293t-cells-via-epigenetic-mechanisms-dynamic-chromosomal-interactions
#7
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
#8
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
#9
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/29322983/auditory-p300-event-related-potential-normative-data-in-the-indian-population
#10
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/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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/29309117/chemical-control-of-a-crispr-cas9-acetyltransferase
#14
Jonathan H Shrimp, Carissa Grose, Stephanie R T Widmeyer, Abigail L Thorpe, Ajit Jadhav, Jordan L Meier
Lysine acetyltransferases (KATs) play a critical role in the regulation of transcription and other genomic functions. However, a persistent challenge is the development of assays capable of defining KAT activity directly in living cells. Towards this goal, here we report the application of a previously reported dCas9-p300 fusion as a transcriptional reporter of KAT activity. First we benchmark the activity of dCas9-p300 relative to other dCas9-based transcriptional activators, and demonstrate its compatibility with second generation short guide RNA architectures...
January 8, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29308984/control-changes-the-way-we-look-at-the-world
#15
Wen Wen, Patrick Haggard
The feeling of control is a fundamental aspect of human experience and accompanies our voluntary actions all the time. However, it remains poorly understood how the sense of control interacts with wider perception, cognition, and behavior. This study focused on how controlling an external object influences the allocation of attention. Experiment 1 examined attention to an object that is under a different level of control from the others. Participants searched for a target among multiple distractors on screen...
January 8, 2018: Journal of Cognitive Neuroscience
https://www.readbyqxmd.com/read/29305663/investigation-of-auditory-potentials-and-cognitive-impairment-in-premenstrual-syndrome
#16
Ceyda Hayretdag Ors, Handan Işin Ozisik Karaman
Premenstrual syndrome is a term which is used for describing of somatic, cognitive, emotional, and behavioral symptoms that occur during the luteal phase of menstrual cycle in women of reproductive age; symptoms rapidly improve at the onset of menstruation. In this study, we aimed to reveal if cognitive functions are affected or not in PMS and if the subjects are affected, we try to explain this situation by an objective diagnostic test. Ethical committee approval was taken for this project on 09.03.2012 and numbered 050...
January 5, 2018: Neurological Sciences
https://www.readbyqxmd.com/read/29304065/bilateral-theta-burst-magnetic-stimulation-influence-on-event-related-brain-potentials
#17
Nuno Pinto, Marta Duarte, Helena Gonçalves, Ricardo Silva, Jorge Gama, Maria Vaz Pato
Theta-burst stimulation (TBS) can be a non-invasive technique to modulate cognitive functions, with promising therapeutic potential, but with some contradictory results. Event related potentials are used as a marker of brain deterioration and can be used to evaluate TBS-related cognitive performance, but its use remains scant. This study aimed to study bilateral inhibitory and excitatory TBS effects upon neurocognitive performance of young healthy volunteers, using the auditory P300' results. Using a double-blind sham-controlled study, 51 healthy volunteers were randomly assigned to five different groups, two submitted to either excitatory (iTBS) or inhibitory (cTBS) stimulation over the left dorsolateral pre-frontal cortex (DLPFC), two other actively stimulated the right DLPFC and finally a sham stimulation group...
2018: PloS One
https://www.readbyqxmd.com/read/29302713/psilocybin-disrupts-sensory-and-higher-order-cognitive-processing-but-not-pre-attentive-cognitive-processing-study-on-p300-and-mismatch-negativity-in-healthy-volunteers
#18
Anna Bravermanová, Michaela Viktorinová, Filip Tylš, Tomáš Novák, Renáta Androvičová, Jakub Korčák, Jiří Horáček, Marie Balíková, Inga Griškova-Bulanova, Dominika Danielová, Přemysl Vlček, Pavel Mohr, Martin Brunovský, Vlastimil Koudelka, Tomáš Páleníček
RATIONALE: Disruption of auditory event-related evoked potentials (ERPs) P300 and mismatch negativity (MMN), electrophysiological markers of attentive and pre-attentive cognitive processing, is repeatedly described in psychosis and schizophrenia. Similar findings were observed in a glutamatergic model of psychosis, but the role of serotonergic 5-HT2A receptors in information processing is less clear. OBJECTIVES: We studied ERPs in a serotonergic model of psychosis, induced by psilocybin, a psychedelic with 5-HT2A/C agonistic properties, in healthy volunteers...
January 5, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29291580/the-effect-of-panic-disorder-versus-anxiety-sensitivity-on-event-related-potentials-during-anticipation-of-threat
#19
Elizabeth S Stevens, Anna Weinberg, Brady D Nelson, Emily E E Meissel, Stewart A Shankman
Attention-related abnormalities are key components of the abnormal defensive responding observed in panic disorder (PD). Although behavioral studies have found aberrant attentional biases towards threat in PD, psychophysiological studies have been mixed. Predictability of threat, an important feature of threat processing, may have contributed to these mixed findings. Additionally, anxiety sensitivity, a dimensional trait associated with PD, may yield stronger associations with cognitive processes than categorical diagnoses of PD...
December 15, 2017: Journal of Anxiety Disorders
https://www.readbyqxmd.com/read/29286496/evoked-bioelectrical-brain-activity-following-exposure-to-ionizing-radiation
#20
K Loganovsky, K Kuts
The article provides an overview of modern physiological evidence to support the hypothesis on cortico limbic sys tem dysfunction due to the hippocampal neurogenesis impairment as a basis of the brain interhemispheric asym metry and neurocognitive deficit after radiation exposure. The importance of the research of both evoked poten tials and fields as a highly sensitive and informative method is emphasized.Particular attention is paid to cerebral sensor systems dysfunction as a typical effect of ionizing radiation...
December 2017: Problemy Radiat︠s︡iĭnoï Medyt︠s︡yny Ta Radiobiolohiï
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