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https://www.readbyqxmd.com/read/28339163/next-generation-sequencing-of-urine-specimens-a-novel-platform-for-genomic-analysis-in-patients-with-non-muscle-invasive-urothelial-carcinoma-treated-with-bacille-calmette-gu%C3%A3-rin
#1
Sasinya N Scott, Irina Ostrovnaya, Caroline M Lin, Nancy Bouvier, Bernard H Bochner, Gopakumar Iyer, David Solit, Michael F Berger, Oscar Lin
BACKGROUND: Biopsies from patients with high-risk (HR) non-muscle-invasive urothelial carcinoma (NMIUC), especially flat urothelial carcinoma in situ, frequently contain scant diagnostic material or denuded mucosa only, and this precludes further extensive genomic analysis. This study evaluated the use of next-generation sequencing (NGS) analysis of urine cytology material from patients with HR NMIUC in an attempt to identify genetic alterations that might correlate with clinical features and responses to bacille Calmette-Guérin (BCG) treatment...
March 24, 2017: Cancer
https://www.readbyqxmd.com/read/28338398/dexamethasone-suppresses-jmjd3-gene-activation-via-a-putative-negative-glucocorticoid-response-element-and-maintains-integrity-of-tight-junctions-in-brain-microvascular-endothelial-cells
#2
Wonho Na, Jee Y Shin, Jee Y Lee, Sangyun Jeong, Won-Sun Kim, Tae Y Yune, Bong-Gun Ju
The blood-brain barrier (BBB) exhibits a highly selective permeability to support the homeostasis of the central nervous system (CNS). The tight junctions in the BBB microvascular endothelial cells seal the paracellular space to prevent diffusion. Thus, disruption of tight junctions results in harmful effects in CNS diseases and injuries. It has recently been demonstrated that glucocorticoids have beneficial effects on maintaining tight junctions in both in vitro cell and in vivo animal models. In the present study, we found that dexamethasone suppresses the expression of JMJD3, a histone H3K27 demethylase, via the recruitment of glucocorticoid receptor α (GRα) and nuclear receptor co-repressor (N-CoR) to the negative glucocorticoid response element (nGRE) in the upstream region of JMJD3 gene in brain microvascular endothelial cells subjected to TNFα treatment...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28338320/inhibitors-of-protein-methyltransferases-and-demethylases
#3
H Ümit Kaniskan, Michael L Martini, Jian Jin
Post-translational modifications of histones by protein methyltransferases (PMTs) and histone demethylases (KDMs) play an important role in the regulation of gene expression and transcription and are implicated in cancer and many other diseases. Many of these enzymes also target various nonhistone proteins impacting numerous crucial biological pathways. Given their key biological functions and implications in human diseases, there has been a growing interest in assessing these enzymes as potential therapeutic targets...
March 24, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28336409/development-and-crystallographic-evaluation-of-histone-h3-peptide-with-n-terminal-serine-substitution-as-a-potent-inhibitor-of-lysine-specific-demethylase-1
#4
Yuichi Amano, Masaki Kikuchi, Shin Sato, Shigeyuki Yokoyama, Takashi Umehara, Naoki Umezawa, Tsunehiko Higuchi
Lysine-specific demethylase 1 (LSD1/KDM1A) is a flavoenzyme demethylase, which removes mono- and dimethyl groups from histone H3 Lys4 (H3K4) or Lys9 (H3K9) in complexes with several nuclear proteins. Since LSD1 is implicated in the tumorigenesis and progression of various cancers, LSD1-specific inhibitors are considered as potential anti-cancer agents. A modified H3 peptide with substitution of Lys4 to Met [H3K4M] is already known to be a potent competitive inhibitor of LSD1. In this study, we synthesized a series of H3K4M peptide derivatives and evaluated their LSD1-inhibitory activities in vitro...
March 9, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28336172/curcuma-longa-linn-extract-and-curcumin-protect-cyp-2e1-enzymatic-activity-against-mercuric-chloride-induced-hepatotoxicity-and-oxidative-stress-a-protective-approach
#5
Deepmala Joshi, Deepak Kumar Mittal, Sangeeta Shukla, Sunil Kumar Srivastav, Vaibhav A Dixit
The present investigation has been conducted to evaluate the therapeutic potential of Curcuma longa (200mgkg(-1), po) and curcumin (80mgkg(-1), po) for their hepatoprotective efficacy against mercuric chloride (HgCl2: 12μmolkg(-1), ip; once only) hepatotoxicity. The HgCl2 administration altered various biochemical parameters, including transaminases, alkaline phosphatase, lactate dehydrogenase, bilirubin, gamma-glutamyl transferase, triglycerides and cholesterol contents with a concomitant decline in protein and albumin concentration in serum which were restored towards control by therapy of Curcuma longa or curcumin...
March 20, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28334124/a-newly-identified-amino-acid-substitution-t123i-in-the-14%C3%AE-demethylase-erg11p-of-candida-albicans-confers-azole-resistance
#6
YongQin Wu, Ning Gao, Cui Li, Jing Gao, ChunMei Ying
The increasing prevalence of azole resistance in Candida albicans poses a growing problem for clinical treatment. Amino acid substitution of the 14α-demethylase (Erg11p) encoded by the ERG11 gene is one of the most common mechanisms involved in azole resistance. Although amino acid substitutions of Erg11p have been observed in many clinical isolates, only a few amino acid substitutions have been confirmed to be related to azole resistance. In this study, by amplifying and sequencing the open reading frame of the ERG11 gene from 55 clinical isolates, we identified 27 fluconazole-resistant isolates that harbor a novel amino acid substitution, T123I, in Erg11p, in addition to the previously described homozygous substitution Y132H...
February 25, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28333151/fto-is-required-for-myogenesis-by-positively-regulating-mtor-pgc-1%C3%AE-pathway-mediated-mitochondria-biogenesis
#7
Xiaobo Wang, Ning Huang, Min Yang, Dandan Wei, Haoran Tai, Xiaojuan Han, Hui Gong, Jiao Zhou, Jianqiong Qin, Xiawei Wei, Honghan Chen, Tingting Fang, Hengyi Xiao
Global germ line loss of fat mass- and obesity-associated (FTO) gene results in both the reduction of fat mass and lean mass in mice. The role of FTO in adipogenesis has been proposed, however, that in myogenesis has not. Skeletal muscle is the main component of body lean mass, so its connection with FTO physiologic significance need to be clarified. Here, we assessed the impact of FTO on murine skeletal muscle differentiation by in vitro and in vivo experiments. We found that FTO expression increased during myoblasts differentiation, while the silence of FTO inhibited the differentiation; in addition, skeletal muscle development was impaired in skeletal muscle FTO-deficient mice...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28327608/kdm4b-histone-demethylase-and-g9a-regulate-expression-of-vascular-adhesion-proteins-in-cerebral-microvessels
#8
Ji-Young Choi, Sang-Sun Yoon, Sang-Eun Kim, Sangmee Ahn Jo
Intercellular adhesion molecule 1 (ICAM1) mediates the adhesion and transmigration of leukocytes across the endothelium, promoting inflammation. We investigated the epigenetic mechanism regulating ICAM1 expression. The pro-inflammatory cytokine TNF-α dramatically increased ICAM1 mRNA and protein levels in human brain microvascular endothelial cells and mouse brain microvessels. Chromatin immunoprecipitation revealed that TNF-α reduced methylation of histone H3 at lysines 9 and 27 (H3K9 and H3K27), well-known residues involved in gene suppression...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28323958/jmjd3-is-crucial-for-female-avpv-rip-cre-neuron-controlled-kisspeptin-estrogen-feedback-loop-and-reproductive-function
#9
Anying Song, Shujun Jiang, Qinghua Wang, Jianghuan Zou, Zhaoyu Lin, Xiang Gao
The hypothalamic-pituitary-gonadal axis controls development, reproduction, and metabolism. While most studies were focusing on the hierarch from brain to gonad, many questions remain unresolved concerning the feedback from gonad to the central nervous system, especially on the potential epigenetic modification in hypothalamic neurons. In this report, we generated genetically modified mice lacking histone H3 lysine 27 demethylase JMJD3 in hypothalamic RIP-Cre neurons. The female mutant mice display late-onset obesity due to reduced locomotor activity and decreased energy expenditure...
March 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/28322580/macrophage-kdm6b-controls-the-pro-fibrotic-transcriptome-signature-of-foam-cells
#10
Annette E Neele, Koen Hm Prange, Marten A Hoeksema, Saskia van der Velden, Tina Lucas, Stefanie Dimmeler, Esther Lutgens, Jan Van den Bossche, Menno Pj de Winther
AIM: In order to identify regulators of foam cells, we studied the H3K27 demethylase Kdm6b (also known as Jmjd3), a known regulator of macrophages, in controlling the transcriptional profile of foam cells. MATERIALS & METHODS: Foam cells from Kdm6b-deleted or Kdm6b wild-type mice were isolated and used for RNA-sequencing analysis. RESULTS: Pathway analysis revealed that pro-fibrotic pathways were strongly suppressed in Kdm6b-deleted foam cells...
March 21, 2017: Epigenomics
https://www.readbyqxmd.com/read/28319137/the-h3k27-demethylase-utx-regulates-adipogenesis-in-a-differentiation-stage-dependent-manner
#11
Kazushige Ota, Kit I Tong, Kouichiro Goto, Shuta Tomida, Akiyoshi Komuro, Zhong Wang, Kazuto Nishio, Hitoshi Okada
Understanding the molecular mechanisms that drive adipogenesis is important in developing new treatments for obesity and diabetes. Epigenetic regulations determine the capacity of adipogenesis. In this study, we examined the role of a histone H3 lysine 27 demethylase, the ubiquitously transcribed tetratricopeptide repeat protein on the X chromosome (Utx), in the differentiation of mouse embryonic stem cells (mESCs) to adipocytes. Using gene trapping, we examined Utx-deficient male mESCs to determine whether loss of Utx would enhance or inhibit the differentiation of mESCs to adipocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28319067/the-histone-demethylase-kdm3a-and-its-downstream-target-mcam-promote-ewing-sarcoma-cell-migration-and-metastasis
#12
M Sechler, J K Parrish, D K Birks, P Jedlicka
Ewing Sarcoma is the second most common solid pediatric malignant neoplasm of bone and soft tissue. Driven by EWS/Ets, or rarely variant, oncogenic fusions, Ewing Sarcoma is a biologically and clinically aggressive disease with a high propensity for metastasis. However, the mechanisms underpinning Ewing Sarcoma metastasis are currently not well understood. In the present study, we identify and characterize a novel metastasis-promotional pathway in Ewing Sarcoma, involving the histone demethylase KDM3A, previously identified by our laboratory as a new cancer-promoting gene in this disease...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28316154/-the-influence-and-mechanisms-of-lysine-specific-demethylase-1-lsd1-on-invasion-and-metastasis-of-colon-cancer-cells
#13
J Ding, Z M Zhang, Q Dong, R Mi, K S Xu, X F Yang, G Q Liao
Objective: To investigate the effect and molecular mechanisms of LSD1 on proliferation and metastasis of colon cancer. Methods: The influence of down-regulated LSD1 expression on proliferation, invasion and apoptosis of colon cancer cells were detected by transwell invasion assay, cell proliferation assay and apoptosis assay, respectively. Results: Three independent siRNAs targeting LSD1 (siRNA-1554, siRNA-705, and siRNA-1973) were transfected to SW620 cells to detect gene-silencing efficiency, and the result showed that the knockdown effect of siRNA-705 were better than the other two siRNAs at both mRNA and protein levels...
March 14, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28314754/kdm6b-regulates-cartilage-development-and-homeostasis-through-anabolic-metabolism
#14
Jun Dai, Dongsheng Yu, Yafei Wang, Yishan Chen, Heng Sun, Xiaolei Zhang, Shouan Zhu, Zongyou Pan, Boon Chin Heng, Shufang Zhang, Hongwei Ouyang
OBJECTIVES: Epigenetic mechanisms have been reported to play key roles in chondrogenesis and osteoarthritis (OA) development. Here, we sought to identify specific histone demethylases that are involved and delineate the underlying mechanisms. METHODS: We screened the expression of 17 distinct histone demethylases by quantitative real time PCR (qRT-PCR) during chondrogenic differentiation of C3H10T1/2 cells. The role of Kdm6b in cartilage development was then analysed with transgenic Col2a1-CreER(T2);Kdm6b(f/f) ...
March 17, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28314201/inhibition-of-mirna-212-132-improves-the-reprogramming-of-fibroblasts-into-induced-pluripotent-stem-cells-by-de-repressing-important-epigenetic-remodelling-factors
#15
Nils Pfaff, Steffi Liebhaber, Selina Möbus, Abbas Beh-Pajooh, Jan Fiedler, Angelika Pfanne, Axel Schambach, Thomas Thum, Tobias Cantz, Thomas Moritz
MicroRNAs (miRNAs) repeatedly have been demonstrated to play important roles in the generation of induced pluripotent stem cells (iPSCs). To further elucidate the molecular mechanisms underlying transcription factor-mediated reprogramming we have established a model, which allows for the efficient screening of whole libraries of miRNAs modulating the generation of iPSCs from murine embryonic fibroblasts. Applying this model, we identified 14 miRNAs effectively inhibiting iPSC generation, including miR-132 and miR-212...
March 7, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28304334/kdm2-family-members-are-regulated-by-hif-1-in-hypoxia
#16
Michael Batie, Jimena Druker, Laura D'Ignazio, Sonia Rocha
Hypoxia is not only a developmental cue but also a stress and pathological stimulus in many human diseases. The response to hypoxia at the cellular level relies on the activity of the transcription factor family, hypoxia inducible factor (HIF). HIF-1 is responsible for the acute response and transactivates a variety of genes involved in cellular metabolism, cell death, and cell growth. Here, we show that hypoxia results in increased mRNA levels for human lysine (K)-specific demethylase 2 (KDM2) family members, KDM2A and KDM2B, and also for Drosophila melanogaster KDM2, a histone and protein demethylase...
March 17, 2017: Cells
https://www.readbyqxmd.com/read/28302961/getting-to-the-heart-of-the-matter-in-cancer-novel-approaches-to-targeting-cancer-stem-cells
#17
Hugh Colvin, Masaki Mori
Cancer is one of the leading causes of deaths worldwide. While cancers may initially show good response to chemotherapy or radiotherapy, it is not uncommon for them to recur at a later date. This phenomenon may be explained by the existence of a small population of cancer stem cells, which are inherently resistant to anti-cancer treatment as well as being capable of self-renewal. Therefore, while most of the tumour bulk consisting of cells that are not cancer stem cells respond to treatment, the cancer stem cells remain, leading to disease recurrence...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28297716/rna-m-6-a-methylation-regulates-the-ultraviolet-induced-dna-damage-response
#18
Yang Xiang, Benoit Laurent, Chih-Hung Hsu, Sigrid Nachtergaele, Zhike Lu, Wanqiang Sheng, Chuanyun Xu, Hao Chen, Jian Ouyang, Siqing Wang, Dominic Ling, Pang-Hung Hsu, Lee Zou, Ashwini Jambhekar, Chuan He, Yang Shi
Cell proliferation and survival require the faithful maintenance and propagation of genetic information, which are threatened by the ubiquitous sources of DNA damage present intracellularly and in the external environment. A system of DNA repair, called the DNA damage response, detects and repairs damaged DNA and prevents cell division until the repair is complete. Here we report that methylation at the 6 position of adenosine (m(6)A) in RNA is rapidly (within 2 min) and transiently induced at DNA damage sites in response to ultraviolet irradiation...
March 15, 2017: Nature
https://www.readbyqxmd.com/read/28297667/m-6-a-rna-methylation-regulates-the-self-renewal-and-tumorigenesis-of-glioblastoma-stem-cells
#19
Qi Cui, Hailing Shi, Peng Ye, Li Li, Qiuhao Qu, Guoqiang Sun, Guihua Sun, Zhike Lu, Yue Huang, Cai-Guang Yang, Arthur D Riggs, Chuan He, Yanhong Shi
RNA modifications play critical roles in important biological processes. However, the functions of N(6)-methyladenosine (m(6)A) mRNA modification in cancer biology and cancer stem cells remain largely unknown. Here, we show that m(6)A mRNA modification is critical for glioblastoma stem cell (GSC) self-renewal and tumorigenesis. Knockdown of METTL3 or METTL14, key components of the RNA methyltransferase complex, dramatically promotes human GSC growth, self-renewal, and tumorigenesis. In contrast, overexpression of METTL3 or inhibition of the RNA demethylase FTO suppresses GSC growth and self-renewal...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28291760/gentle-fast-and-effective-crystal-soaking-by-acoustic-dispensing
#20
Patrick M Collins, Jia Tsing Ng, Romain Talon, Karolina Nekrosiute, Tobias Krojer, Alice Douangamath, Jose Brandao-Neto, Nathan Wright, Nicholas M Pearce, Frank von Delft
The steady expansion in the capacity of modern beamlines for high-throughput data collection, enabled by increasing X-ray brightness, capacity of robotics and detector speeds, has pushed the bottleneck upstream towards sample preparation. Even in ligand-binding studies using crystal soaking, the experiment best able to exploit beamline capacity, a primary limitation is the need for gentle and nontrivial soaking regimens such as stepwise concentration increases, even for robust and well characterized crystals...
March 1, 2017: Acta Crystallographica. Section D, Structural Biology
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