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https://www.readbyqxmd.com/read/28533215/inhibition-of-hdac3-prevents-diabetic-cardiomyopathy-in-ove26-mice-via-epigenetic-regulation-of-dusp5-erk1-2-pathway
#1
Zheng Xu, Qian Tong, Zhiguo Zhang, Shudong Wang, Yang Zheng, Qiuju Liu, Lingbo Qian, Shao-Yu Chen, Jian Sun, Lu Cai
Inhibition of total histone deacetylases (HDACs) was phenomenally associated with the prevention of diabetic cardiomyopathy (DCM). However, which specific HDAC plays the key role in DCM remains unclear. The present study was designed to determine whether DCM can be prevented by specific inhibition of HDAC3 and to elucidate the mechanisms by which inhibition of HDAC3 prevent DCM. Type 1 diabetes OVE26 and age-matched wild-type mice were given the selective HDAC3 inhibitor RGFP966 or vehicle for 3 months. These mice were then sacrificed immediately or 3 months later for cardiac function and pathological examination...
May 22, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28523558/epigenome-editing-in-the-brain
#2
Pavel Bashtrykov, Albert Jeltsch
Epigenome editing aims for an introduction or removal of chromatin marks at a defined genomic region using artificial EpiEffectors resulting in a modulation of the activity of the targeted functional DNA elements. Rationally designed EpiEffectors consist of a targeting DNA-binding module (such as a zinc finger protein, TAL effector, or CRISPR/Cas complex) and usually, but not exclusively, a catalytic domain of a chromatin-modifying enzyme. Epigenome editing opens a completely new strategy for basic research of the central nervous system and causal treatment of psychiatric and neurological diseases, because rewriting of epigenetic information can lead to the direct and durable control of the expression of disease-associated genes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28516124/bioinformatic-analysis-for-profiling-drug-induced-chromatin-modification-landscapes-in-mouse-brain-using-chlp-seq-data
#3
Yong-Hwee Eddie Loh, Jian Feng, Eric Nestler, Li Shen
Chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq) is a powerful technology to profile genome-wide chromatin modification patterns and is increasingly being used to study the molecular mechanisms of brain diseases such as drug addiction. This protocol discusses the typical procedures involved in ChIP-seq data generation, bioinformatic analysis, and interpretation of results, using a chronic cocaine treatment study as a template. We describe an experimental design that induces significant chromatin modifications in mouse brain, and the use of ChIP-seq to derive novel information about the chromatin regulatory mechanisms involved...
February 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28506839/evolutionary-relationships-among-protein-lysine-deacetylases-of-parasites-causing-neglected-diseases
#4
Larissa L S Scholte, Marina M Mourão, Fabiano Sviatopolk-Mirsky Pais, Jelena Melesina, Dina Robaa, Angela C Volpini, Wolfgang Sippl, Raymond J Pierce, Guilherme Oliveira, Laila A Nahum
The availability of the genomic data of diverse parasites provides an opportunity to identify new drug candidates against neglected tropical diseases affecting people worldwide. Histone modifying enzymes (HMEs) are potential candidates since they play key roles in the regulation of chromatin modifications, thus globally regulating gene expression. Furthermore, aberrant epigenetic states are often associated with human diseases, leading to great interest in HMEs as therapeutic targets. Our work focused on two families of protein lysine deacetylases (HDACs and sirtuins)...
May 13, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28502712/ligation-mediated-pcr-with-a-back-to-back-adapter-reduces-amplification-bias-resulting-from-variations-in-gc-content
#5
Satoru Ishihara, Naoe Kotomura, Naoki Yamamoto, Hiroshi Ochiai
Ligation-mediated polymerase chain reaction (LM-PCR) is a common technique for amplification of a pool of DNA fragments. Here, a double-stranded oligonucleotide consisting of two primer sequences in back-to-back orientation was designed as an adapter for LM-PCR. When DNA fragments were ligated with this adapter, the fragments were sandwiched between two adapters in random orientations. In the ensuing PCR, ligation products linked at each end to an opposite side of the adapter, i.e. to a distinct primer sequence, were preferentially amplified compared with products linked at each end to an identical primer sequence...
May 11, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28500085/the-most-common-vices-of-men-can-damage-fertility-and-the-health-of-the-next-generation
#6
Tod Fullston, Nicole O McPherson, Deirdre Zander-Fox, Michelle Lane
There is growing evidence from animal and human studies that demonstrate that acquired paternal traits can impair both a male's fertility and the health of his offspring, including advanced age, smoking, stress, trauma, under-nutrition, infection, toxin exposure, and obesity. Curiously, many of these factors manifest as impaired neurological, behavioural, and/or metabolic functioning in offspring. The underlying molecular mechanisms that respond to the paternal environment and act as vectors of intergenerational transmission are beginning to emerge...
May 12, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28497787/locus-specific-histone-deacetylation-using-a-synthetic-crispr-cas9-based-hdac
#7
Deborah Y Kwon, Ying-Tao Zhao, Janine M Lamonica, Zhaolan Zhou
Efforts to manipulate locus-specific histone acetylation to assess their causal role in gene expression and cellular and behavioural phenotypes have been impeded by a lack of experimental tools. The Cas9 nuclease has been adapted to target epigenomic modifications, but a detailed description of the parameters of such synthetic epigenome remodellers is still lacking. Here we describe a Cas9-based histone deacetylase (HDAC) and the design principles required to achieve locus-specific histone deacetylation. We assess its range of activity and specificity, and analyse target gene expression in two different cell types to investigate cellular context-dependent effects...
May 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28497199/arachidonic-acid-induces-are-nrf2-dependent-heme-oxygenase-1-transcription-in-rat-brain-astrocytes
#8
Chih-Chung Lin, Chien-Chung Yang, Yu-Wen Chen, Li-Der Hsiao, Chuen-Mao Yang
Arachidonic acid (AA) is a major product of phospholipid hydrolysis catalyzed by phospholipase A2 during neurodegenerative diseases. AA exerts as a second messenger to regulate various signaling components which may be involved in different pathophysiological processes. Astrocytes are the main types of CNS resident cells which maintain and support the physiological function of brain. AA has been shown to induce ROS generation through activation of NADPH oxidases (Noxs) which may play a key role in the expression of heme oxygenase-1 (HO-1)...
May 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28486547/hat2-mediates-histone-h4k4-acetylation-and-affects-micrococcal-nuclease-sensitivity-of-chromatin-in-leishmania-donovani
#9
Pravin K Jha, Mohd Imran Khan, Anshul Mishra, Pradeep Das, Kislay K Sinha
Histone post-translational modifications (PTMs) such as acetylation and methylation are known to affect chromatin higher order structures. Primary targets of these modifications include basic residues present at N-terminus tail region of core histones. Four histone acetyltransferase (HAT) genes have been identified in trypanosomatids. HAT1, HAT3 and HAT4 of Leishmania donovani have been partially characterized. However, there is no report about HAT2 of Leishmania donovani. Lysine residues present on the N-terminal tail of Leishmania donovani histone H4 are conserved in other trypanosomatids and humans...
2017: PloS One
https://www.readbyqxmd.com/read/28481278/combining-low-temperature-fluorescence-dna-hybridization-immunostaining-and-super-resolution-localization-microscopy-for-nano-structure-analysis-of-alu-elements-and-their-influence-on-chromatin-structure
#10
Matthias Krufczik, Aaron Sievers, Annkathrin Hausmann, Jin-Ho Lee, Georg Hildenbrand, Wladimir Schaufler, Michael Hausmann
Immunostaining and fluorescence in situ hybridization (FISH) are well established methods for specific labelling of chromatin in the cell nucleus. COMBO-FISH (combinatorial oligonucleotide fluorescence in situ hybridization) is a FISH method using computer designed oligonucleotide probes specifically co-localizing at given target sites. In combination with super resolution microscopy which achieves spatial resolution far beyond the Abbe Limit, it allows new insights into the nano-scaled structure and organization of the chromatin of the nucleus...
May 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28463515/rational-design-of-bisubstrate-type-analogues-as-inhibitors-of-dna-methyltransferases-in-cancer-cells
#11
Ludovic Halby, Yoann Menon, Elodie Rilova, Dany Pechalrieu, Véronique Masson, Celine Faux, Mohamed Amine Bouhlel, Marie-Hélène David-Cordonnier, Natacha Novosad, Yannick Aussagues, Arnaud Samson, Laurent Lacroix, Fréderic Ausseil, Laurence Fleury, Dominique Guianvarc'h, Clotilde Ferroud, Paola B Arimondo
Aberrant DNA hypermethylation of promoter of tumor suppressor genes is commonly observed in cancer, and its inhibition by small molecules is promising for their reactivation. Here we designed bisubstrate analogues-based inhibitors, by mimicking each substrate, the S-adenosyl-l-methionine and the deoxycytidine, and linking them together. This approach resulted in quinazoline-quinoline derivatives as potent inhibitors of DNMT3A and DNMT1, some showing certain isoform selectivity. We highlighted the importance of (i) the nature and rigidity of the linker between the two moieties for inhibition, as (ii) the presence of the nitrogen on the quinoline group, and (iii) of a hydrophobic group on the quinazoline...
May 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28440495/relationship-between-epigenetic-changes-in-wnt-antagonists-and-acute-leukemia
#12
Hua-Rong Zhou, Hai-Ying Fu, Dan-Sen Wu, Yuan-Yuan Zhang, Si-Han Huang, Cong-Jie Chen, Jian-Guo Yan, Jin-Long Huang, Jian-Zhen Shen
The present study was designed to investigate the relationship among epigenetic changes in Wnt antagonists, histone H4K20me1 and the expression of tumor-suppressor genes in acute leukemia (AL) to better understand the pathogenesis of leukemia. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to detect messenger RNA (mRNA) expression levels of Wnt antagonists (Wnt5a, HDPR1, DKK1 and DKK3) in patients with AL and in normal controls; pyrophosphate sequencing was performed to detect the methylation status of the Wnt5a promoter; and western blotting was performed to detect the overall expression levels of Wnt5a protein and histone H4K20me1 in patients with acute myeloid leukemia (AML) and in normal controls...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28438565/improvements-in-oocyte-competence-in-superovulated-mice-following-treatment-with-cilostazol-ovulation-of-immature-oocytes-with-high-developmental-rates
#13
Ahmed M Taiyeb, Saeeda A Muhsen-Alanssari, William L Dees, Jill Hiney, Michael E Kjelland, Duane C Kraemer, Mundhir T Ridha-Albarzanchi
Exogenous administration of superovulatory hormones negatively affects oocyte competence in mammals. Phosphodiesterase 3A inhibitors were found to improve competence of oocytes matured in vitro in several species, including humans. This study was therefore designed to define oocyte maturation synchronization and competence, in vivo, using superovulated mice treated with cilostazol, a selective phosphodiesterase 3A inhibitor. Swiss Webster mice were superovulated and treated orally with 7.5mg cilostazol once or twice to result in ovulation of immature oocytes at the metaphase I (MI) or germinal vesicle (GV) stage, respectively...
April 22, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28426098/targeting-chromatin-defects-in-selected-solid-tumors-based-on-oncogene-addiction-synthetic-lethality-and-epigenetic-antagonism
#14
D Morel, G Almouzni, J-C Soria, S Postel-Vinay
Background: Although the role of epigenetic abnormalities has been studied for several years in cancer genesis and development, epigenetic-targeting drugs have historically failed to demonstrate efficacy in solid malignancies. However, successful targeting of chromatin remodeling deficiencies, histone writers and histone reader alterations has been achieved very recently using biomarker-driven and mechanism-based approaches. Epigenetic targeting is now one of the most active areas in drug development and could represent novel therapeutic opportunity for up to 25% of all solid tumors...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28404792/toxoplasma-effectors-targeting-host-signaling-and-transcription
#15
REVIEW
Mohamed-Ali Hakimi, Philipp Olias, L David Sibley
Early electron microscopy studies revealed the elaborate cellular features that define the unique adaptations of apicomplexan parasites. Among these were bulbous rhoptry (ROP) organelles and small, dense granules (GRAs), both of which are secreted during invasion of host cells. These early morphological studies were followed by the exploration of the cellular contents of these secretory organelles, revealing them to be comprised of highly divergent protein families with few conserved domains or predicted functions...
July 2017: Clinical Microbiology Reviews
https://www.readbyqxmd.com/read/28399532/metastatic-pituitary-carcinoma-to-cervical-lymph-node-diagnosis-by-fine-needle-aspiration-and-review-of-the-literature
#16
Huiying Wang, Jiancong Liang, William H Yong, Peggy Sullivan
BACKGROUND: Pituitary carcinomas are rare neoplasms whose designation requires demonstration of metastatic disease. No specific morphologic features can reliably distinguish pituitary carcinomas from pituitary adenomas, rendering the diagnosis particularly challenging. Furthermore, as reports of pituitary carcinoma on fine needle aspiration (FNA) biopsy are exceedingly rare in the literature, the cytological features of pituitary carcinoma are poorly characterized. CASE REPORT: Here we describe a case of pituitary carcinoma in a 67-year-old woman with history of recurrent adrenocorticotropic hormone (ACTH)-producing pituitary adenoma who presented with a persistent left cervical nodule for 2 years...
April 12, 2017: Acta Cytologica
https://www.readbyqxmd.com/read/28398344/induction-of-functional-dopamine-neurons-from-human-astrocytes-in-vitro-and-mouse-astrocytes-in-a-parkinson-s-disease-model
#17
Pia Rivetti di Val Cervo, Roman A Romanov, Giada Spigolon, Débora Masini, Elisa Martín-Montañez, Enrique M Toledo, Gioele La Manno, Michael Feyder, Christian Pifl, Yi-Han Ng, Sara Padrell Sánchez, Sten Linnarsson, Marius Wernig, Tibor Harkany, Gilberto Fisone, Ernest Arenas
Cell replacement therapies for neurodegenerative disease have focused on transplantation of the cell types affected by the pathological process. Here we describe an alternative strategy for Parkinson's disease in which dopamine neurons are generated by direct conversion of astrocytes. Using three transcription factors, NEUROD1, ASCL1 and LMX1A, and the microRNA miR218, collectively designated NeAL218, we reprogram human astrocytes in vitro, and mouse astrocytes in vivo, into induced dopamine neurons (iDANs)...
May 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28369277/genogam-genome-wide-generalized-additive-models-for-chip-seq-analysis
#18
Georg Stricker, Alexander Engelhardt, Daniel Schulz, Matthias Schmid, Achim Tresch, Julien Gagneur
Motivation: Chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) is a widely used approach to study protein-DNA interactions. Often, the quantities of interest are the differential occupancies relative to controls, between genetic backgrounds, treatments, or combinations thereof. Current methods for differential occupancy of ChIP-seq data rely however on binning or sliding window techniques, for which the choice of the window and bin sizes are subjective. Results: Here, we present GenoGAM (Genome-wide Generalized Additive Model), which brings the well-established and flexible generalized additive models framework to genomic applications using a data parallelism strategy...
March 22, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28359304/determination-of-the-cell-permissiveness-spectrum-mode-of-rna-replication-and-rna-protein-interaction-of-zika-virus
#19
Wangheng Hou, Najealicka Armstrong, Lilian Akello Obwolo, Michael Thomas, Xiaowu Pang, Kevin S Jones, Qiyi Tang
BACKGROUND: Two lineages of Zika virus (ZIKV) have been classified according to the phylogenetic analysis: African and Asian lineages. It is unclear whether differences exist between the two strains in host cell permissiveness, this information is important for understanding viral pathogenesis and designing anti-viral strategies. METHODS: In the present study, we comparatively studied the permissive spectrum of human cells for both the African (MR766) and Asian strains (PRVABC59) using an RNA in situ hybridization (RISH) to visualize RNA replication, an immunofluorescence technology, and a western blot assay to determine viral protein production, and a real-time RT-PCR to examine viral RNA multiplication level...
March 31, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28358847/alpha-1-antitrypsin-suppresses-oxidative-stress-in-preeclampsia-by-inhibiting-the-p38mapk-signaling-pathway-an-in-vivo-and-in-vitro-study
#20
Ya-Ling Feng, Yong-Xiang Yin, Jian Ding, Hua Yuan, Lan Yang, Jian-Juan Xu, Ling-Qin Hu
This present study was designed to investigate the effects of alpha-1-antitrypsin (AAT) on oxidative stress in preeclampsia (PE) by regulating p38 mitogen-activated protein kinase (p38MAPK) signaling pathway. HTR8/SVneo cells were randomly assigned into normal, hypoxia/reoxygenation (H/R), HR + AAT and HR + siRNA-AAT groups. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to detect the mRNA and protein expressions of p-p38MAPK, AAT, signal transducer and activator of transcription 1 (STAT1) and activating transcription factor2 (ATF2)...
2017: PloS One
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