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https://www.readbyqxmd.com/read/29165700/epigenetic-therapy-novel-translational-implications-for-arrest-of-environmental-dioxin-induced-disease-in-females
#1
Zaraq Khan, Ye Zheng, Tiffanny L Jones, Abigail A Delaney, Luiz F Correa, Chandra C Shenoy, Khashayarsha Khazaie, Gaurang S Daftary
Increased toxicant exposure and resultant environmentally-induced diseases are a tradeoff of industrial productivity. Dioxin (TCDD: 2,3,7,8 tetrachlorodibenzo-p-dioxin), a ubiquitous by-product is associated with a spectrum of diseases including endometriosis, a common, chronic disease in women. TCDD activates cytochrome p450 (CYP) metabolic enzymes, which alters organ function to cause disease. In contrast, the transcription factor, Krüppel-Like Factor (KLF) 11 represses these enzymes via epigenetic mechanisms...
November 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/29163825/maternal-histone-acetyltransferase-kat8-is-required-for-porcine-preimplantation-embryo-development
#2
Zubing Cao, Ronghua Wu, Di Gao, Tengteng Xu, Lei Luo, Yunsheng Li, Jianyong Han, Yunhai Zhang
K (lysine) acetyltransferase 8 (KAT8), an acetyltransferase that specifically catalyzes histone H4 lysine 16 acetylation, is critical for key biological processes including cell proliferation and maintenance of genome stability. However, the role of KAT8 during preimplantation development in pigs remains unclear. Results herein showed that KAT8 mRNA is maternally derived and it is required for successful development of early embryos. An abundance of KAT8 transcripts are expressed in oocytes and its abundance continuously decreases throughout meiotic maturation and preimplantation development...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163803/hat1-induces-lung-cancer-cell-apoptosis-via-up-regulating-fas
#3
Na Han, Lei Shi, Qiuyun Guo, Wei Sun, Yang Yu, Li Yang, Xiaoxi Zhang, Mengxian Zhang
The dysfunction of apoptosis is one of the factors contributing to lung cancer (LC) growth. Histone acetyltransferase HAT1 can up regulate cell apoptosis. This study aims to investigate the mechanism by which HAT1 induces LC cell (LCC) apoptosis via up regulating the expression of Fas. In this study, the surgically removed human LC tissues were collected. LCCs were isolated from the LC tissues and analyzed for the expression of HAT1 and Fas by RT-qPCR and Western blotting. We observed that the expression of Fas was negatively correlated with PAR2 in LCCs...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163768/inhibitor-of-growth-protein-4-interacts-with-beclin-1-and-represses-autophagy
#4
Valentina Sica, José Manuel Bravo-San Pedro, Guo Chen, Guillermo Mariño, Sylvie Lachkar, Valentina Izzo, Maria Chiara Maiuri, Mireia Niso-Santano, Guido Kroemer
Beclin 1 (BECN1) is a multifunctional protein that activates the pro-autophagic class III phosphatidylinositol 3-kinase (PIK3C3, best known as VPS34), yet also interacts with multiple negative regulators. Here we report that BECN1 interacts with inhibitor of growth family member 4 (ING4), a tumor suppressor protein that is best known for its capacity to interact with the tumor suppressor protein p53 (TP53) and the acetyltransferase E1A binding protein p300 (EP300). Removal of TP53 or EP300 did not affect the BECN1/ING4 interaction, which however was lost upon culture of cells in autophagy-inducing, nutrient free conditions...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163618/the-ralstonia-solanacearum-type-iii-effector-ripay-is-phosphorylated-in-plant-cells-to-modulate-its-enzymatic-activity
#5
Yali Wei, Yuying Sang, Alberto P Macho
Most bacterial pathogens subvert plant cellular functions using effector proteins delivered inside plant cells. In the plant pathogen Ralstonia solanacearum, several of these effectors contain domains with predicted enzymatic activities, including acetyltransferases, phosphatases, and proteases, among others. How these enzymatic activities get activated inside plant cells, but not in the bacterial cell, remains unknown in most cases. In this work, we found that the R. solanacearum effector RipAY is phosphorylated in plant cells...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29163129/biomarkers-of-presbycusis-and-tinnitus-in-a-portuguese-older-population
#6
Haúla F Haider, Marisa Flook, Mariana Aparicio, Diogo Ribeiro, Marilia Antunes, Agnieszka J Szczepek, Derek J Hoare, Graça Fialho, João C Paço, Helena Caria
Introduction: Presbycusis or age-related hearing loss (ARHL) is a ubiquitous health problem. It is estimated that it will affect up to 1.5 billion people by 2025. In addition, tinnitus occurs in a large majority of cases with presbycusis. Glutamate metabotropic receptor 7 (GRM7) and N-acetyltransferase 2 (NAT2) are some of the genetic markers for presbycusis. Objectives: To explore patterns of hearing loss and the role of GRM7 and NAT2 as possible markers of presbycusis and tinnitus in a Portuguese population sample...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29163051/young-human-cholinergic-neurons-respond-to-physiological-regulators-and-improve-cognitive-symptoms-in-an-animal-model-of-alzheimer-s-disease
#7
Annamaria Morelli, Erica Sarchielli, Giulia Guarnieri, Elisabetta Coppi, Daniela Pantano, Paolo Comeglio, Pamela Nardiello, Anna M Pugliese, Lara Ballerini, Rosanna Matucci, Stefano Ambrosini, Giuseppe Castronovo, Rosa Valente, Benedetta Mazzanti, Sandra Bucciantini, Mario Maggi, Fiorella Casamenti, Pasquale Gallina, Gabriella B Vannelli
The degeneration of cholinergic neurons of the nucleus basalis of Meynert (NBM) in the basal forebrain (BF) is associated to the cognitive decline of Alzheimer's disease (AD) patients. To date no resolutive therapies exist. Cell-based replacement therapy is a strategy currently under consideration, although the mechanisms underlying the generation of stem cell-derived NBM cholinergic neurons able of functional integration remain to be clarified. Since fetal brain is an optimal source of neuronal cells committed towards a specific phenotype, this study is aimed at isolating cholinergic neurons from the human fetal NBM (hfNBMs) in order to study their phenotypic, maturational and functional properties...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29162816/impairments-of-spatial-memory-in-an-alzheimer-s-disease-model-via-degeneration-of-hippocampal-cholinergic-synapses
#8
Houze Zhu, Huanhuan Yan, Na Tang, Xinyan Li, Pei Pang, Hao Li, Wenting Chen, Yu Guo, Shu Shu, You Cai, Lei Pei, Dan Liu, Min-Hua Luo, Hengye Man, Qing Tian, Yangling Mu, Ling-Qiang Zhu, Youming Lu
Choline acetyltransferase neurons in the vertical diagonal band of Broca (vChATs) degenerate in the early stage of Alzheimer's disease (AD). Here, we report that vChATs directly innervate newly generated immature neurons (NGIs) in the dorsal hippocampus (dNGIs) of adult mice and regulate both the dNGIs survival and spatial pattern separation. In a mouse model that exhibits amyloid-β plaques similar to AD patients, cholinergic synaptic transmission, dNGI survival and spatial pattern separation are impaired...
November 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29155171/manganese-chloride-induces-histone-acetylation-changes-in-neuronal-cells-its-role-in-manganese-induced-damage
#9
Zhenkun Guo, Zhipeng Zhang, Qingqing Wang, Jie Zhang, Lijin Wang, Qunwei Zhang, Huangyuan Li, Siying Wu
Manganese neurotoxicity presents with Parkinson-like symptoms, with degeneration of dopaminergic neurons in the basal ganglia as the principal pathological feature. Manganese neurotoxicity studies may contribute to a better understanding of the mechanism of Parkinson's disease. Here, we examined the effects of manganese on histone acetylation, a major epigenetic change in chromatin that can regulate gene expression, chromatin remodelling, cell cycle progression, DNA repair and apoptosis. In this study, we found that manganese chloride (MnCl2) may significantly suppress the acetylation of histone H3 and H4 in PC12 cells and SHSY5Y cells in a time-dependent manner...
November 16, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/29154281/gradual-cerebral-hypoperfusion-impairs-fear-conditioning-and-object-recognition-learning-and-memory-in-mice-potential-roles-of-neurodegeneration-and-cholinergic-dysfunction
#10
Jogender Mehla, Sean Lacoursiere, Emily Stuart, Robert J McDonald, Majid H Mohajerani
In the present study, male C57BL/6J mice were subjected to gradual cerebral hypoperfusion by implanting an ameroid constrictor (AC) on the left common carotid artery (CCA) and a stenosis on the right CCA. In the sham group, all surgical procedures were kept the same except no AC was implanted and stenosis was not performed. One month following the surgical procedures, fear conditioning and object recognition tests were conducted to evaluate learning and memory functions and motor functions were assessed using a balance beam test...
November 14, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29150924/comprehensive-profiling-of-lysine-acetylome-in-baculovirus-infected-silkworm-bombyx-mori-cells
#11
Dongbing Hu, Shengjie Xue, Cui Zhao, Ming Wei, Huihui Yan, Yanping Quan, Wei Yu
Bombyx mori is one of the key lepidopteran model species, and is economically important for silk production and proteinaceous drug expression. Baculovirus and insect host are important natural biological models for studying host-pathogen interactions. The impact of Bombyx mori nucleopolyhedrovirus (BmNPV) infection on the proteome and acetylome of Bombyx mori ovarian (BmN) cells were explored to facilitate a better understanding of infection-driven interactions between BmNPV and host in vitro. The proteome and acetylome were profiled through 6-plex Tandem mass tag (TMT) labelling-based quantitative proteomics...
November 18, 2017: Proteomics
https://www.readbyqxmd.com/read/29147966/polyamine-concentration-is-increased-in-thoracic-ascending-aorta-of-patients-with-bicuspid-aortic-valve
#12
Amalia Forte, Mario Grossi, Ciro Bancone, Marilena Cipollaro, Marisa De Feo, Per Hellstrand, Lo Persson, Bengt-Olof Nilsson, Alessandro Della Corte
Polyamines are cationic molecules synthesized via a highly regulated pathway, obtained from the diet or produced by the gut microbiota. They are involved in general molecular and cellular phenomena that play a role also in vascular disease. Bicuspid aortic valve (BAV) is a congenital malformation associated to a greater risk of thoracic ascending aorta (TAA) aneurysm, whose pathogenesis is not yet well understood. We focused on differential analysis of key members of polyamine pathway and on polyamine concentration in non-dilated TAA samples from patients with either stenotic tricuspid aortic valve (TAV) or BAV (diameter ≤ 45 mm), vs...
November 17, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/29145630/yaf9-subunit-of-the-nua4-and-swr1-complexes-targets-histone-h3k27ac-through-its-yeats-domain
#13
Brianna J Klein, Salar Ahmad, Kendra R Vann, Forest H Andrews, Zachary A Mayo, Gaelle Bourriquen, Joseph B Bridgers, Jinyong Zhang, Brian D Strahl, Jacques Côté, Tatiana G Kutateladze
Yaf9 is an integral part of the NuA4 acetyltransferase and the SWR1 chromatin remodeling complexes. Here, we show that Yaf9 associates with acetylated histone H3 with high preference for H3K27ac. The crystal structure of the Yaf9 YEATS domain bound to the H3K27ac peptide reveals that the sequence C-terminal to K27ac stabilizes the complex. The side chain of K27ac inserts between two aromatic residues, mutation of which abrogates the interaction in vitro and leads in vivo to phenotypes similar to YAF9 deletion, including loss of SWR1-dependent incorporation of variant histone H2A...
November 14, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29143350/dna-variants-and-organophosphate-neurotoxicity-among-emerging-farmers-in-the-western-cape-of-south-africa
#14
Tracy Glass, Mohamed A Dalvie, Zelda Holtman, Anna A Vorster, Rajkumar S Ramesar, Leslie London
BACKGROUND: Previous epidemiological studies investigating modification of organophosphate (OP) neurotoxicity by xenobiotic metabolizing enzymes (XMEs) polymorphisms have produced inconsistent results. METHODS: A cross-sectional study of 301 emerging farmers was conducted. Neurotoxicity testing included forward and backward recall, digit span, and vibration sensitivity testing. Questionnaire data included demography, potential confounders, and work history of pesticide exposures...
November 16, 2017: American Journal of Industrial Medicine
https://www.readbyqxmd.com/read/29142305/assay-interference-and-off-target-liabilities-of-reported-histone-acetyltransferase-inhibitors
#15
Jayme L Dahlin, Kathryn M Nelson, Jessica M Strasser, Dalia Barsyte-Lovejoy, Magdalena M Szewczyk, Shawna Organ, Matthew Cuellar, Gurpreet Singh, Jonathan H Shrimp, Nghi Nguyen, Jordan L Meier, Cheryl H Arrowsmith, Peter J Brown, Jonathan B Baell, Michael A Walters
Many compounds with potentially reactive chemical motifs and poor physicochemical properties are published as selective modulators of biomolecules without sufficient validation and then propagated in the scientific literature as useful chemical probes. Several histone acetyltransferase (HAT) inhibitors with these liabilities are now routinely used to probe epigenetic pathways. We profile the most commonly used HAT inhibitors and confirm that the majority of them are nonselective interference compounds. Most (15 out of 23, 65%) of the inhibitors are flagged by ALARM NMR, an industry-developed counter-screen for promiscuous compounds...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29142304/maternal-exposure-to-iodine-excess-throughout-pregnancy-and-lactation-induces-hypothyroidism-in-adult-male-rat-offspring
#16
Caroline Serrano-Nascimento, Rafael Barrera Salgueiro, Thiago Pantaleão, Vânia Maria Corrêa da Costa, Maria Tereza Nunes
This study aimed to investigate the consequences of maternal exposure to iodine excess (IE; 0.6 mg NaI/L) throughout pregnancy and lactation on the hypothalamus-pituitary-thyroid axis of the male offspring in adulthood. Maternal IE exposure increased hypothalamic Trh mRNA expression and pituitary Tsh expression and secretion in the adult male offspring. Moreover, the IE-exposed offspring rats presented reduced thyroid hormones levels, morphological alterations in the thyroid follicles, increased thyroid oxidative stress and decreased expression of thyroid differentiation markers (Tshr, Nis, Tg, Tpo, Mct8) and thyroid transcription factors (Nkx2...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142277/genetic-metabolomic-and-transcriptomic-analyses-of-the-de-novo-l-cysteine-biosynthetic-pathway-in-the-enteric-protozoan-parasite-entamoeba-histolytica
#17
Ghulam Jeelani, Dan Sato, Tomoyoshi Soga, Tomoyoshi Nozaki
The de novo L-cysteine biosynthetic pathway is critical for the growth, antioxidative stress defenses, and pathogenesis of bacterial and protozoan pathogens, such as Salmonella typhimurium and Entamoeba histolytica. This pathway involves two key enzymes, serine acetyltransferase (SAT) and cysteine synthase (CS), which are absent in mammals and therefore represent rational drug targets. The human parasite E. histolytica possesses three SAT and CS isozymes; however, the specific roles of individual isoforms and significance of such apparent redundancy remains unclear...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142164/bacterial-degradation-of-spermine-and-expression-of-spermidine-spermine-acetyltransferase-in-bacillus-subtilis-natto-under-liquid-cultivation
#18
Kazuya Kobayashi, Yuji Kubo, Yuichiro Horii, Toshikazu Nishiwaki, Shin Kamiyama, Hideyuki Sone, Satoshi Watanabe
No abstract text is available yet for this article.
November 15, 2017: Journal of General and Applied Microbiology
https://www.readbyqxmd.com/read/29141908/two-distinct-regulatory-mechanisms-of-transcriptional-initiation-in-response-to-nutrient-signaling
#19
Jannatul Ferdoush, Rwik Sen, Amala Kaja, Priyanka Barman, Sukesh R Bhaumik
SAGA (Spt-Ada-Gcn5-Acetyltransferase) and TFIID (transcription factor IID) have been previously shown to facilitate the PIC (pre-initiation complex) formation at the promoters of two distinct sets of genes. Here, we demonstrate that TFIID and SAGA differentially participate in stimulation of the PIC formation (and hence transcriptional initiation) at the promoter of PHO84, a gene for high affinity inorganic phosphate (Pi) transporter for crucial cellular functions, in response to nutrient signaling. We show that transcriptional initiation of PHO84 occurs predominantly in the TFIID-dependent manner in the absence of Pi in the growth medium...
November 15, 2017: Genetics
https://www.readbyqxmd.com/read/29138297/mafb-enhances-oncogenic-notch-signaling-in-t-cell-acute-lymphoblastic-leukemia
#20
Kostandin V Pajcini, Lanwei Xu, Lijian Shao, Jelena Petrovic, Karol Palasiewicz, Yumi Ohtani, Will Bailis, Curtis Lee, Gerald B Wertheim, Rajeswaran Mani, Natarajan Musuthamy, Yunlei Li, Jules P P Meijerink, Stephen C Blacklow, Robert B Faryabi, Sara Cherry, Warren S Pear
Activating mutations in the gene encoding the cell-cell contact signaling protein Notch1 are common in human T cell acute lymphoblastic leukemias (T-ALLs). However, expressing Notch1 mutant alleles in mice fails to efficiently induce the development of leukemia. We performed a gain-of-function screen to identify proteins that enhanced signaling by leukemia-associated Notch1 mutants. The transcription factors MAFB and ETS2 emerged as candidates that individually enhanced Notch1 signaling, and when coexpressed, they synergistically increased signaling to an extent similar to that induced by core components of the Notch transcriptional complex...
November 14, 2017: Science Signaling
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