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https://www.readbyqxmd.com/read/28817838/pharmacogenetic-determinants-of-outcomes-on-triplet-hepatic-artery-infusion-and-intravenous-cetuximab-for-liver-metastases-from-colorectal-cancer-european-trial-optiliv-nct00852228
#1
Francis Lévi, Abdoulaye Karaboué, Raphaël Saffroy, Christophe Desterke, Valerie Boige, Denis Smith, Mohamed Hebbar, Pasquale Innominato, Julien Taieb, Carlos Carvalho, Rosine Guimbaud, Christian Focan, Mohamed Bouchahda, René Adam, Michel Ducreux, Gérard Milano, Antoinette Lemoine
BACKGROUND: The hepatic artery infusion (HAI) of irinotecan, oxaliplatin and 5-fluorouracil with intravenous cetuximab achieved outstanding efficacy in previously treated patients with initially unresectable liver metastases from colorectal cancer. This planned study aimed at the identification of pharmacogenetic predictors of outcomes. METHODS: Circulating mononuclear cells were analysed for 207 single-nucleotide polymorphisms (SNPs) from 34 pharmacology genes...
August 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28815970/structural-insight-into-cbp-bromodomain-mediated-recognition-of-acetylated-histone-h3k56ac
#2
Li Xu, Aimin Cheng, Min Huang, Jiahai Zhang, Yiyang Jiang, Chongyuan Wang, Fudong Li, Hongyu Bao, Jia Gao, Na Wang, Jiuyang Liu, Jihui Wu, Catherine C L Wong, Ke Ruan
The acetylation of lysine 56 of histone H3 (H3K56ac) enhances the binding affinity of histone chaperones to H3-H4 dimers. CREB binding protein (CBP) possesses a bromodomain that recognizes H3K56 acetylation. CBP also possesses a histone acetyltransferase (HAT) domain, which has been shown to promote H3K56 acetylation of free histones to facilitate delivery of replication-dependent chaperones to acetylated histones for chromatin assembly. However, the mechanism by which the CBP bromodomain recognizes H3K56ac, and thecontext in which such recognition occurs remains elusive...
August 16, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28814961/compound-schisandra-ginseng-notoginseng-lycium-extract-ameliorates-scopolamine-induced-learning-and-memory-disorders-in-mice
#3
Ning Li, Cong Liu, Shu Jing, Mengyang Wang, Han Wang, Jinghui Sun, Chunmei Wang, Jianguang Chen, He Li
Schisandra, Ginseng, Notoginseng, and Lycium barbarum are traditional Chinese medicinal plants sharing cognitive-enhancing properties. To design a functional food to improve memory, we prepared a compound Schisandra-Ginseng-Notoginseng-Lycium (CSGNL) extract and investigated its effect on scopolamine-induced learning and memory loss in mice. To optimize the dose ratios of the four herbal extracts in CSGNL, orthogonal experiments were performed. Mice were administered CSGNL by gavage once a day for 30 days and then mouse learning and memory were evaluated by Morris water maze and step-through tests...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28814955/characterization-of-carbapenem-resistant-acinetobacter-baumannii-strains-isolated-from-hospitalized-patients-in-palestine
#4
Regeen Handal, Lulu Qunibi, Ibrahim Sahouri, Maha Juhari, Rula Dawodi, Hiyam Marzouqa, Musa Hindiyeh
The American Centers for Disease Control and Prevention (CDC) recognizes Acinetobacter baumannii as a source of global outbreaks and epidemics especially due to its increasing resistance to commercially available antibiotics. In this study, 69 single patient multidrug resistant isolates collected from all over Palestine, except Gaza, were studied. All the isolates were resistant to all the β-lactam antibiotics including the carbapenems. Of the 69 isolates, 82.6% were positive for blaOXA-23, 14.5% were positive for blaOXA-24, and 3% were positive for blaOXA-58...
2017: International Journal of Microbiology
https://www.readbyqxmd.com/read/28813510/construction-of-novel-pjrd215-derived-plasmids-using-chloramphenicol-acetyltransferase-cat-gene-as-a-selection-marker-for-acidithiobacillus-caldus
#5
Rui Wang, Chunmao Lin, Jianqiang Lin, Xin Pang, Xiangmei Liu, Chengjia Zhang, Jianqun Lin, Linxu Chen
BACKGROUND: Acidithiobacillus caldus, a Gram-negative, chemolithotrophic sulfur-oxidizing bacterium, is widely applied in bioleaching. The absence of an ideal selection marker has become a major obstacle to achieve high efficiency of the gene transfer system for A. caldus. Plasmid pJRD215, widely used in Acidithiobacillus spp., has severe drawbacks in molecular manipulations and potential biosafety issues due to its mobility. Therefore, finding a new selection marker and constructing new plasmids have become an urgent and fundamental work for A...
2017: PloS One
https://www.readbyqxmd.com/read/28811661/myst2-kat7-histone-acetyltransferase-interaction-proteomics-reveals-tumour-suppressor-niam-as-a-novel-binding-partner-in-embryonic-stem-cells
#6
Mercedes Pardo, Lu Yu, Shihpei Shen, Peri Tate, Daniel Bode, Blake L Letney, Dawn E Quelle, William Skarnes, Jyoti S Choudhary
MYST histone acetyltransferases have crucial functions in transcription, replication and DNA repair and are hence implicated in development and cancer. Here we characterise Myst2/Kat7/Hbo1 protein interactions in mouse embryonic stem cells by affinity purification coupled to mass spectrometry. This study confirms that in embryonic stem cells Myst2 is part of H3 and H4 histone acetylation complexes similar to those described in somatic cells. We identify a novel Myst2-associated protein, the tumour suppressor protein Niam (Nuclear Interactor of ARF and Mdm2)...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808424/acetylation-of-hmof-modulates-h4k16ac-to-regulate-dna-repair-genes-in-response-to-oxidative-stress
#7
Jianing Zhong, Liying Ji, Huiqian Chen, Xianfeng Li, Jian'an Zhang, Xingxing Wang, Weilin Wu, Ying Xu, Fei Huang, Wanshi Cai, Zhong Sheng Sun
Oxidative stress is considered to be a key risk state for a variety of human diseases. In response to oxidative stress, the regulation of transcriptional expression of DNA repair genes would be important to DNA repair and genomic stability. However, the overall pattern of transcriptional expression of DNA repair genes and the underlying molecular response mechanism to oxidative stress remain unclear. Here, by employing colorectal cancer cell lines following exposure to hydrogen peroxide, we generated expression profiles of DNA repair genes via RNA-seq and identified gene subsets that are induced or repressed following oxidative stress exposure...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28807788/adolescent-binge-ethanol-exposure-alters-specific-forebrain-cholinergic-cell-populations-and-leads-to-selective-functional-deficits-in-the-prefrontal-cortex
#8
Gina M Fernandez, Lisa M Savage
Adolescence has been identified as a vulnerable developmental time period during which exposure to drugs can have long-lasting, detrimental effects. Although adolescent binge-like ethanol (EtOH) exposure leads to a significant reduction of forebrain cholinergic neurons, EtOH's functional effect on acetylcholine (ACh) release during behavior has yet to be examined. Using an adolescent intermittent ethanol exposure model (AIE), rats were exposed to binge-like levels of EtOH from postnatal day (PD) 25-55. Three weeks following the final EtOH exposure, cholinergic functioning was assessed during a spontaneous alternation protocol...
August 11, 2017: Neuroscience
https://www.readbyqxmd.com/read/28805482/cyclophilin-20-3-is-positioned-as-a-regulatory-hub-between-light-dependent-redox-and-12-oxo-phytodienoic-acid-signaling
#9
Hoon Cheong, Izailda Barbosa Dos Santos, Wenshan Liu, Heather N Gosse, Sang-Wook Park
The jasmonate family of phytohormones plays central roles in plant development and stress acclimation. However, the regulatory modes of their signaling circuitry remain largely unknown. Here we describe that cyclophilin 20-3 (CYP20-3), a binding protein of (+)-12-oxo-phytodienoic acid (OPDA), crisscrosses stress responses with light-dependent redox reactions, which fine-tunes the activity of key enzymes in the plastid photosynthetic carbon assimilation and sulfur assimilation pathways. Under stressed states, OPDA - accumulated in the chloroplasts - binds and promotes CYP20-3 to transfer electron (e(-)) from thioredoxins (i...
August 14, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28805060/substrate-induced-facilitated-dissociation-of-competitive-inhibitor-from-the-active-site-of-o-acetyl-serine-sulfhydrylase-reveal-a-competitive-allostery-mechanism
#10
Appu Kumar Singh, Mary Krishna Ekka, Abhishek Kaushik, Vaibhav Kumar Pandya, Ravi Pratap Singh, Srijita Banerjee, Monica Mittal, Vijay Singh, Sangaralingam Kumaran
By classical competitive-antagonism, substrate and competitive-inhibitor must bind mutually exclusively to the active site. The competitive inhibition of O-acetyl serine sulfhydrylase (OASS) by C-terminal of serine acetyltransferase (SAT) presents a paradox, because the C-terminal of SAT binds to the active site of OASS with 4-6 log fold (104 -106) more affinity than that of the substrate. Therefore, we employed multiple approaches to understand how substrate gains access to OASS active site under physiological conditions...
August 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/28799976/effect-of-gene-gene-and-gene-environment-interactions-associated-with-antituberculosis-drug-induced-hepatotoxicity
#11
Julián G Chamorro, Jorge P Castagnino, Omar Aidar, Rosa M Musella, Ana Frías, Mabel Visca, Mabel Nogueras, Lucas Costa, Alessandro Perez, Fabio Caradonna, Gabriela F de Larrañaga
OBJECTIVES: This study evaluated the association between environmental factors and genetic variations in enzymes that metabolize antituberculosis (anti-TB) drugs [arylamine N-acetyltransferase 2, cytochrome P450 2E1 (CYP2E1), glutathione S-transferase theta 1 (GSTT1), and glutathione S-transferase mu 1] with antituberculosis drug-induced hepatotoxicity (ATDH). We also investigated the potential gene-gene and gene-environment interactions as well as their association with ATDH development in a population of hospitalized TB patients from Buenos Aires...
August 9, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28798030/ethanol-exposure-regulates-gabra1-expression-via-histone-deacetylation-at-the-promoter-in-cultured-cortical-neurons
#12
John Peyton Bohnsack, Vraj K Patel, A Leslie Morrow
GABAA-Rs mediate the majority of inhibitory neurotransmission in the adult brain. α1-containing GABAA-Rs are the most prominent subtype in the adult brain, and are important in both homeostatic function and several disease pathologies including alcohol dependence, epilepsy, and stress. Ethanol exposure causes a decrease of α1 transcription and peptide expression both in vivo and in vitro, but the mechanism that controls the transcriptional regulation is unknown. Since ethanol is known to activate epigenetic regulation of gene expression, we tested the hypothesis that ethanol regulates α1 expression through histone modifications in cerebral cortical cultured neurons...
August 10, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28796367/hbo1-promotes-cell-proliferation-in-bladder-cancer-via-activation-of-wnt-%C3%AE-catenin-signaling
#13
Zhaohui Chen, Lijie Zhou, Longwang Wang, Gallina Kazobinka, Xiaoping Zhang, Xiaomin Han, Bin Li, Teng Hou
Histone acetyltransferase binding to ORC1 (HBO1), a histone acetyltransferase, was recently identified as an oncoprotein; however, its role in bladder cancer remains unknown. In this study, we showed that HBO1 was highly expressed at both the mRNA and the protein levels in bladder cancer. HBO1 expression was associated with the clinical features of human bladder cancer, including tumor size (p = 0.018) and T (p = 0.007) classifications. Patients with higher HBO1 expression had shorter recurrence-free survival time, whereas patients with lower HBO1 expression had better survival time...
August 10, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28794203/the-myst-family-histone-acetyltransferase-complex-regulates-stress-resistance-and-longevity-through-transcriptional-control-of-daf-16-foxo-transcription-factors
#14
Takako Ikeda, Masaharu Uno, Sakiko Honjoh, Eisuke Nishida
The well-known link between longevity and the Sir2 histone deacetylase family suggests that histone deacetylation, a modification associated with repressed chromatin, is beneficial to longevity. However, the molecular links between histone acetylation and longevity remain unclear. Here, we report an unexpected finding that the MYST family histone acetyltransferase complex (MYS-1/TRR-1 complex) promotes rather than inhibits stress resistance and longevity in Caenorhabditis elegans Our results show that these beneficial effects are largely mediated through transcriptional up-regulation of the FOXO transcription factor DAF-16...
August 9, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28793366/cadmium-induced-melatonin-synthesis-in-rice-requires-light-hydrogen-peroxide-and-nitric-oxide-key-regulatory-roles-for-tryptophan-decarboxylase-and-caffeic-acid-o-methyltransferase
#15
Kyungjin Lee, Geun-Hee Choi, Kyoungwhan Back
In plants, melatonin production is induced by stimuli such as cold and drought, and cadmium (Cd) is the best elicitor of melatonin production in rice. However, the mechanism by which Cd induces melatonin synthesis in plants remains unknown. We challenged rice seedlings with Cd under different light conditions and found that continuous light produced the highest levels of melatonin, while continuous dark failed to induce melatonin production. Transcriptional and translational induction of tryptophan decarboxylase contributed to the light induction of melatonin during Cd treatment, whereas the protein level of light-induced caffeic acid O-methyltransferase (COMT) was decreased by Cd treatment...
August 9, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28792629/alteration-of-cell-wall-xylan-acetylation-trigger-defense-responses-that-counterbalance-the-immune-deficiencies-of-plants-impaired-in-the-%C3%AE-subunit-of-the-heterotrimeric-g-protein
#16
Viviana Escudero, Lucía Jordá, Sara Sopeña-Torres, Hugo Mélida, Eva Miedes, Antonio Muñoz-Barrios, Sanjay Swami, Danny Alexander, Lauren S McKee, Andrea Sánchez-Vallet, Vincent Bulone, Alan M Jones, Antonio Molina
Arabidopsis heterotrimeric G protein complex modulates Pathogen Associated Molecular Pattern-triggered immunity (PTI) and disease resistance responses to different type of pathogens. It also plays a role in plant cell wall integrity as mutants impaired in the Gβ (agb1-2) or Gγ subunits have an altered wall composition compared to wild-type plants. Here we performed a mutant screen to identify suppressors of agb1-2 (sgb) that restore susceptibility to pathogens to wild-type levels. Out of the four sgb mutants (sgb10-sgb13) identified, sgb11 is a new mutant allele of ESKIMO1 (ESK1), which encodes a plant-specific polysaccharide O-acetyltransferase involved in xylan acetylation...
August 9, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28783662/suppression-by-human-foxp3-regulatory-t-cells-requires-foxp3-tip60-interactions
#17
Khalid Bin Dhuban, Eva d'Hennezel, Yasuhiro Nagai, Yan Xiao, Steven Shao, Roman Istomine, Fernando Alvarez, Moshe Ben-Shoshan, Hans Ochs, Bruce Mazer, Bin Li, Chiyoko Sekine, Alan Berezov, Wayne Hancock, Troy R Torgerson, Mark I Greene, Ciriaco A Piccirillo
CD4(+)FOXP3(+) regulatory T (Treg) cells are critical mediators of immune tolerance, and their deficiency owing to FOXP3 mutations in immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) patients results in severe autoimmunity. Different FOXP3 mutations result in a wide range of disease severity, reflecting the relative importance of the affected residues in the integrity of the FOXP3 protein and its various molecular interactions. We characterized the cellular and molecular impact of the most common IPEX mutation, p...
June 16, 2017: Science Immunology
https://www.readbyqxmd.com/read/28782640/effect-of-melatonin-on-neuronal-differentiation-requires-cbp-p300-mediated-acetylation-of-histone-h3-lysine-14
#18
Xian Li, Xueran Chen, Wenjuan Zhou, Shufang Ji, Xinyue Li, Guanchong Li, Guowei Liu, Fuwu Wang, Aijun Hao
The transition from multipotent neural stem cells (NSCs) to terminally differentiated neurons is a multistep process, and the transition is finely regulated by transcription factors with basic helix-loop-helix (bHLH) motifs. Melatonin is an endogenous neurohormone with profound neurotrophic and neuroprotective effects both during the embryonic developmental stage and adulthood. The effects of melatonin on the differentiation of NSCs have been reported, and these effects may be responsible for its neuroprotective properties...
August 3, 2017: Neuroscience
https://www.readbyqxmd.com/read/28776755/maternal-administration-of-melatonin-exerts-short-and-long-term-neuroprotective-effects-on-the-offspring-from-lipopolysaccharide-treated-mice
#19
Ana Paula Domínguez Rubio, Fernando Correa, Julieta Aisemberg, Damián Dorfman, María Victoria Bariani, Ruth Rosenstein, María Zorrilla Zubilete, Ana María Franchi
Preterm birth is a major contributor to early and delayed physical and cognitive impairment. Epidemiological and experimental data indicate that maternal infections are a significant and preventable cause of preterm birth. Recently, melatonin has been suggested to exert neuroprotective effects in several models of brain injury. Here we sought to investigate whether the administration of melatonin is able to prevent LPS-induced fetal brain damage in a model of lipopolysaccharide (LPS)-induced preterm labor. For this purpose, 15-days pregnant BALB/c mice received intraperitoneally two doses of lipopolysaccharide (LPS) or vehicle, the first one at 10:00 h (0...
August 4, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28771443/ard1-mediated-aurora-kinase-a%C3%A2-acetylation-promotes-cell-proliferation-and-migration
#20
Tam Thuy Lu Vo, Ji-Hyeon Park, Ji Hae Seo, Eun Ji Lee, Hoon Choi, Sung-Jin Bae, Hoang Le, Sunho An, Hye Shin Lee, Hee-Jun Wee, Kyu-Won Kim
Aurora kinase A (AuA) is a prerequisite for centrosome maturation, separation, and mitotic spindle assembly, thus, it is essential for cell cycle regulation. Overexpression of AuA is implicated in poor prognosis of many types of cancer. However, the regulatory mechanisms underlying the functions of AuA are still not fully understood. Here, we report that AuA colocalizes with arrest defective protein 1 (ARD1) acetyltransferase during cell division and cell migration. Additionally, AuA is acetylated by ARD1 at lysine residues at positions 75 and 125...
July 18, 2017: Oncotarget
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