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Sanjay Singh, Sarfraj Ahmad Siddiqui, Sukanya Tripathy, Shiv Kumar, Sudipta Saha, Rajesh Ugale, Dinesh Raj Modi, Anand Prakash
In the last few decades, there has been exponential increase in studies aiming to trace the molecular mechanism of fear extinction with a hope to minimize the return of fear after exposure therapy required for operational treatment of anxiety disorders. The present study explored how the timing of extinction training after developing a specific fear, affects the consequent return of the extinguished fear and the role of histone acetylation in controlling the circuitry, thereof. It was found that rats undergone extinction training 10 min...
June 14, 2018: Brain Research Bulletin
Maria E Ramirez-Roman, Carlos E Billini, Alfredo Ghezzi
Alcohol addiction is a serious condition perpetuated by enduring physiological and behavioral adaptations. An important component of these adaptations is the long-term rearrangement of neuronal gene expression in the brain of the addicted individual. Epigenetic histone modifications have recently surfaced as important modulators of the transcriptional adaptation to alcohol as these are thought to represent a form of transcriptional memory that is directly imprinted on the chromosome. Some histone modifications affect transcription by modulating the accessibility of the underlying DNA, whereas others have been proposed to serve as marks read by transcription factors as a "histone code" that helps to specify the expression level of a gene...
2018: Journal of Experimental Neuroscience
Lan Ling, Qian-Kuan Wen, Shan-Hong Zhang, Li-Da Zhi, Hong Li, Gang Li, Wen-Jia Zhang
BACKGROUND/AIMS: Multiple organ failure (MOF) is a primary threat to the survival of patients with systemic inflammation. Blood purification is employed in the treatment of MOF, as an artificial kidney or artificial liver. This study focuses on the effects of continuous blood purification (CBP) on ameliorating MOF through regulating the p38 mitogen-activated protein kinase (MAPK) signaling pathway in a rat model. METHODS: A rat model of MOF was successfully established by endotoxin injection after hemorrhagic shock resuscitation...
June 7, 2018: Kidney & Blood Pressure Research
Angeles C Tecalco-Cruz, Diana G Ríos-López, Genaro Vázquez-Victorio, Reyna E Rosales-Alvarez, Marina Macías-Silva
The transforming growth factor-β (TGF-β) family plays major pleiotropic roles by regulating many physiological processes in development and tissue homeostasis. The TGF-β signaling pathway outcome relies on the control of the spatial and temporal expression of >500 genes, which depend on the functions of the Smad protein along with those of diverse modulators of this signaling pathway, such as transcriptional factors and cofactors. Ski (Sloan-Kettering Institute) and SnoN (Ski novel) are Smad-interacting proteins that negatively regulate the TGF-β signaling pathway by disrupting the formation of R-Smad/Smad4 complexes, as well as by inhibiting Smad association with the p300/CBP coactivators...
2018: Signal Transduction and Targeted Therapy
Valentina Alari, Silvia Russo, Benedetta Terragni, Paola Francesca Ajmone, Alessandra Sironi, Ilaria Catusi, Luciano Calzari, Daniela Concolino, Rosa Marotta, Donatella Milani, Daniela Giardino, Massimo Mantegazza, Cristina Gervasini, Palma Finelli, Lidia Larizza
Rubinstein-Taybi syndrome (RSTS) is a rare neurodevelopmental disorder characterized by distinctive facial features, growth retardation, broad thumbs and toes and mild to severe intellectual disability, caused by heterozygous mutations in either CREBBP or EP300 genes, encoding the homologous CBP and p300 lysine-acetyltransferases and transcriptional coactivators. No RSTS in vitro induced Pluripotent Stem Cell (iPSC)-neuronal model is available yet to achieve mechanistic insights on cognitive impairment of RSTS patients...
May 30, 2018: Stem Cell Research
Faten A Al-Aqil, Maria J Monte, Ana Peleteiro-Vigil, Oscar Briz, Ruben Rosales, Raquel Gonzalez, Carlos J Aranda, Borja Ocon, Iker Uriarte, Fermin Sanchez de Medina, Olga Martinez-Augustin, Matias A Avila, Jose J G Marin, Marta R Romero
At high doses, glucocorticoids (GC) have been associated with enhanced serum bile acids and liver injury. We have evaluated the effect of GC, in the absence of hepatotoxicity, on FXR/Fgf15/Fgf21-mediated ileum-liver crosstalk. Rats and mice (wild type and Fxr-/- , Fgf15-/- and int-Gr-/- strains; the latter with GC receptor (Gr) knockout selective for intestinal epithelial cells), were treated (i.p.) with dexamethasone, prednisolone or budesonide. In both species, high doses of GC caused hepatotoxicity. At a non-hepatotoxic dose, GC induced ileal Fgf15 down-regulation and liver Fgf21 up-regulation, without affecting Fxr expression...
June 5, 2018: Biochimica et Biophysica Acta
Ornella M Ontañon, Silvina Ghio, Rubén Marrero Díaz de Villegas, Florencia E Piccinni, Paola M Talia, María L Cerutti, Eleonora Campos
Biomass hydrolysis constitutes a bottleneck for the biotransformation of lignocellulosic residues into bioethanol and high-value products. The efficient deconstruction of polysaccharides to fermentable sugars requires multiple enzymes acting concertedly. GH43 β-xylosidases are among the most interesting enzymes involved in hemicellulose deconstruction into xylose. In this work, the structural and functional properties of β-xylosidase EcXyl43 from Enterobacter sp. were thoroughly characterized. Molecular modeling suggested a 3D structure formed by a conserved N-terminal catalytic domain linked to an ancillary C-terminal domain...
June 6, 2018: Applied Microbiology and Biotechnology
Stephen L Thorp, Thomas Suchy, Nalini Vadivelu, Erik M Helander, Richard D Urman, Alan D Kaye
BACKGROUND: Chronic pain is a major public health problem resulting in physical and emotional pain for individuals and families, loss of productivity, and an annual cost of billions of dollars. The lack of objective measures available to aid in diagnosis and evaluation of therapies for chronic pain continues to be a challenge for the clinician. OBJECTIVES: Functional magnetic resonance imaging (fMRI) is an imaging technique that can establish regional areas of interest and examine synchronous neuronal activity in functionally related but anatomically distinct regions of the brain, known as functional connectivity...
May 2018: Pain Physician
Weilei Yao, Tongxin Wang, Feiruo Huang
The overwhelming frequency of metabolic diseases such as obesity and diabetes are closely related to liver diseases, which might share common pathogenic signaling processes. These metabolic disorders in the presence of inflammatory response seem to be triggered by and to reside in the liver, which is the central metabolic organ that plays primary roles in regulating lipid and glucose homeostasis upon alterations of metabolic conditions. Recently, abundant emerging researches suggested that p300 and CREB binding protein (CBP) are crucial regulators of energy homeostasis and liver fibrosis through both their acetyltransferase activities and transcriptional coactivators...
2018: BioMed Research International
Pedro J Torres, John Thompson, Jeffrey S McLean, Scott T Kelley, Anna Edlund
One of the world's most common infectious disease, periodontitis (PD), derives from largely uncharacterized communities of oral bacteria growing as biofilms (a.k.a. plaque) on teeth and gum surfaces in periodontal pockets. Bacteria associated with periodontal disease trigger inflammatory responses in immune cells, which in later stages of the disease cause loss of both soft and hard tissue structures supporting teeth. Thus far, only a handful of bacteria have been characterized as infectious agents of PD. Although deep sequencing technologies, such as whole community shotgun sequencing have the potential to capture a detailed picture of highly complex bacterial communities in any given environment, we still lack major reference genomes for the oral microbiome associated with PD and other diseases...
June 2, 2018: Microbial Ecology
Omanma Adighibe, Francesco Pezzella
Following the event of DNA damage, the level of tumour suppressor protein p53 increases inducing either cell cycle arrest or apoptosis. Junctional Mediating and Regulating Y protein (JMY) is a transcription co-factor involved in p53 regulation. In event of DNA damage, JMY levels also upregulate in the nucleus where JMY forms a co-activator complex with p300/CREB-binding protein (p300/CBP), Apoptosis-stimulating protein of p53 (ASPP) and Stress responsive activator of p53 (Strap). This co-activator complex then binds to and increases the ability of p53 to induce transcription of proteins triggering apoptosis but not cell cycle arrest...
May 31, 2018: Cancers
Volkan Korkmaz, Abbas Güngördü, Murat Ozmen
This study evaluated the toxic effects and recovery patterns in zebrafish (Danio rerio) after exposure to phosalone-based (PBP) and cypermethrin-based (CBP) pesticides. Initially, the 96 h LC50 values of the pesticides were calculated as being 5.35 µg of active ingredient (AI) L-1 for CBP and 217 µg AI L-1 for PBP based on measured concentrations. Accordingly, experimental groups were exposed to three sublethal concentrations of pesticides for 96 h, separately, and then zebrafish were transferred to pesticide-free conditions for 10 and 20 days recovery periods...
September 30, 2018: Ecotoxicology and Environmental Safety
Brian T Weinert, Takeo Narita, Shankha Satpathy, Balaji Srinivasan, Bogi K Hansen, Christian Schölz, William B Hamilton, Beth E Zucconi, Wesley W Wang, Wenshe R Liu, Joshua M Brickman, Edward A Kesicki, Albert Lai, Kenneth D Bromberg, Philip A Cole, Chunaram Choudhary
The acetyltransferases CBP and p300 are multifunctional transcriptional co-activators. Here, we combined quantitative proteomics with CBP/p300-specific catalytic inhibitors, bromodomain inhibitor, and gene knockout to reveal a comprehensive map of regulated acetylation sites and their dynamic turnover rates. CBP/p300 acetylates thousands of sites, including signature histone sites and a multitude of sites on signaling effectors and enhancer-associated transcriptional regulators. Time-resolved acetylome analyses identified a subset of CBP/p300-regulated sites with very rapid (<30 min) acetylation turnover, revealing a dynamic balance between acetylation and deacetylation...
May 14, 2018: Cell
Rebecca L Ambrose, Yu Chih Liu, Timothy E Adams, Andrew G D Bean, Cameron R Stewart
The host recognition of intracellular viral RNA and subsequent induction of cytokine signalling is tightly regulated at the cellular level and is a target for manipulation by viruses and therapeutics alike. Here we characterise C6orf106 as an evolutionarily-conserved inhibitor of the innate antiviral response. C6orf106 suppresses the synthesis of IFN-α/β and the pro-inflammatory TNF-α in response to the double-stranded RNA mimic poly(I:C) and to Sendai virus infection. Unlike canonical inhibitors of antiviral signalling, C6orf106 blocks IRF3 and, to a lesser extent, NF-κB activity without modulating their activation, nuclear translocation, cellular expression or degradation...
May 25, 2018: Journal of Biological Chemistry
Andrew N Rouble, Liam J Hawkins, Kenneth B Storey
The thirteen-lined ground squirrel (Ictidomys tridecemlineatus) is a well-known model for studying hibernation. While in a torpid state, these animals globally suppress energy expensive processes, while supporting specialized pathways necessary for survival. Lysine acetyltransferases (KATs) play a crucial role in modulating the expression and activity of a wide-variety of cellular pathways and processes, and therefore, may play a role during hibernation when the cell is shifting to an energy conservative, cytoprotective state...
May 2018: Journal of Thermal Biology
Yujia Jiang, Jiasheng Lu, Tianpeng Chen, Wei Yan, Weiliang Dong, Jie Zhou, Wenming Zhang, Jiangfeng Ma, Min Jiang, Fengxue Xin
A novel butanogenic Clostridium sp. NJ4 was successfully isolated and characterized, which could directly produce relatively high titer of butanol from inulin through consolidated bioprocessing (CBP). The assembled draft genome of strain NJ4 is 4.09 Mp, containing 3891 encoded protein sequences with G+C content of 30.73%. Among these annotated genes, a levanase, a hypothetical inulinase, and two bifunctional alcohol/aldehyde dehydrogenases (AdhE) were found to play key roles in the achievement of ABE production from inulin through CBP...
May 23, 2018: Current Microbiology
Lama Alabdi, Ming He, Qianyi Yang, Allison B Norvil, Humaira Gowher
Formation of the vasculature by angiogenesis is critical for proper development, but angiogenesis also contributes to the pathogenesis of various disorders, including cancer and cardiovascular diseases. Vascular endothelial zinc finger 1 (Vezf1), is a Krüppel-like zinc finger protein that plays a vital role in vascular development. However, the mechanism by which Vezf1 regulates this process is not fully understood. Here, we show that Vezf1-/- mouse embryonic stem cells (ESC) have significantly increased expression of a stem cell factor, Cbp/p300-interacting transactivator 2 (Cited2)...
May 24, 2018: Journal of Biological Chemistry
Junichi Taniguchi, Yihong Feng, Ganesh N Pandian, Fumitaka Hashiya, Takuya Hidaka, Kaori Hashiya, Soyoung Park, Toshikazu Bando, Shinji Ito, Hiroshi Sugiyama
While the central role of locus-specific acetylation of histone proteins in eukaryotic gene expression is well established, the availability of designer tools to regulate acetylation at particular nucleosome sites remains limited. Here, we develop a unique strategy to introduce acetylation by constructing a bifunctional molecule designated Bi-PIP. Bi-PIP has a P300/CBP-selective bromodomain inhibitor (Bi) as a P300/CBP recruiter and a pyrrole-imidazole polyamide (PIP) as a sequence-selective DNA binder. Biochemical assays verified that Bi-PIPs recruit P300 to the nucleosomes having their target DNA sequences and extensively accelerate acetylation...
May 24, 2018: Journal of the American Chemical Society
Zoran Culig, Frédéric R Santer
High expression of several androgen receptor coactivators is frequently reported in prostate cancer. Coactivators such as p300/CBP are involved in modulation of androgen receptor activity by increasing the effects of androgenic hormones and enhancing agonistic activity of antiandrogens. Studies in the field of prostate cancer frequently examined the role of p300/CBP and SRC-1 (NCOA1). In addition to their effects on steroid receptor activity, coactivators may influence other cellular functions such as migration and invasion...
2018: Methods in Molecular Biology
Masaru Katoh
β‑catenin/CTNNB1 is an intracellular scaffold protein that interacts with adhesion molecules (E‑cadherin/CDH1, N‑cadherin/CDH2, VE‑cadherin/CDH5 and α‑catenins), transmembrane‑type mucins (MUC1/CD227 and MUC16/CA125), signaling regulators (APC, AXIN1, AXIN2 and NHERF1/EBP50) and epigenetic or transcriptional regulators (BCL9, BCL9L, CREBBP/CBP, EP300/p300, FOXM1, MED12, SMARCA4/BRG1 and TCF/LEF). Gain‑of‑function CTTNB1 mutations are detected in bladder cancer, colorectal cancer, gastric cancer, liver cancer, lung cancer, pancreatic cancer, prostate cancer and uterine cancer, whereas loss‑of‑function CTNNB1 mutations are also detected in human cancer...
May 17, 2018: International Journal of Molecular Medicine
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