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https://www.readbyqxmd.com/read/28529687/histone-demethylases-utx-and-jmjd3-are-required-for-nkt-cell-development-in-mice
#1
Daniel Northrup, Ryoji Yagi, Kairong Cui, William R Proctor, Chaochen Wang, Katarzyna Placek, Lance R Pohl, Rongfu Wang, Kai Ge, Jinfang Zhu, Keji Zhao
BACKGROUND: Natural killer (NK)T cells and conventional T cells share phenotypic characteristic however they differ in transcription factor requirements and functional properties. The role of histone modifying enzymes in conventional T cell development has been extensively studied, little is known about the function of enzymes regulating histone methylation in NKT cells. RESULTS: We show that conditional deletion of histone demethylases UTX and JMJD3 by CD4-Cre leads to near complete loss of liver NKT cells, while conventional T cells are less affected...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28528318/metabolic-profiling-of-goldfish-carassius-auratis-after-long-term-glyphosate-based-herbicide-exposure
#2
Ming-Hui Li, Ling-Yu Ruan, Jin-Wei Zhou, Yong-Hong Fu, Lei Jiang, He Zhao, Jun-Song Wang
Glyphosate is an efficient herbicide widely used worldwide. However, its toxicity to non-targeted organisms has not been fully elucidated. In this study, the toxicity of glyphosate-based herbicide was evaluated on goldfish (Carassius auratus) after long-term exposure. Tissues of brains, kidneys and livers were collected and submitted to NMR-based metabolomics analysis and histopathological inspection. Plasma was collected and the blood biochemical indexes of AST, ALT, BUN, CRE, LDH, SOD, GSH-Px, GR and MDA were measured...
May 13, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28527696/essential-roles-of-g9a-in-cell-proliferation-and-differentiation-during-tooth-development
#3
Taichi Kamiunten, Hisashi Ideno, Akemi Shimada, Yoshinori Arai, Tatsuo Terashima, Yasuhiro Tomooka, Yoshiki Nakamura, Kazuhisa Nakashima, Hiroshi Kimura, Yoichi Shinkai, Makoto Tachibana, Akira Nifuji
Teeth develop through interactions between epithelial and mesenchymal tissues mediated by a signaling network comprised of growth factors and transcription factors However, little is known about how epigenetic modifiers affect signaling pathways and thereby regulate tooth formation. We previously reported that the histone 3 lysine 9 (H3K9) methyltransferase (MTase) G9a is specifically enriched in the tooth mesenchyme during mouse development. In this study, we investigated the functions of G9a in tooth development using G9a conditional knockout (KO) mice...
May 17, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28526298/regulation-of-the-glycerol-transporter-aquaporin-3-by-histone-deacetylase-3-and-p53-in-keratinocytes
#4
Vivek Choudhary, Lawrence O Olala, Karen Kagha, Zhi-Qiang Pan, Xunsheng Chen, Rong Yang, Abigail Cline, Inas Helwa, Lauren Marshall, Ismail Kaddour-Djebbar, Meghan E McGee-Lawrence, Wendy B Bollag
Aquaporin-3 (AQP3), a water and glycerol channel, plays an important role in epidermal function, with studies demonstrating its involvement in keratinocyte proliferation, differentiation and migration and epidermal wound healing and barrier repair. Increasing speculation about the use of histone deacetylase (HDAC) inhibitors to treat skin diseases led us to investigate HDAC's role in the regulation of AQP3. The broad-spectrum HDAC inhibitor, suberolyanilide hydroxamic acid (SAHA) induced AQP3 mRNA and protein expression in a dose- and time-dependent manner in normal keratinocytes...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28525381/the-cell-of-origin-dictates-the-temporal-course-of-neurofibromatosis-1-nf1-low-grade-glioma-formation
#5
Anne C Solga, Joseph A Toonen, Yuan Pan, Patrick J Cimino, Yu Ma, Guillaume A Castillon, Scott M Gianino, Mark H Ellisman, Da Yong Lee, David H Gutmann
Low-grade gliomas are one of the most common brain tumors in children, where they frequently form within the optic pathway (optic pathway gliomas; OPGs). Since many OPGs occur in the context of the Neurofibromatosis Type 1 (NF1) cancer predisposition syndrome, we have previously employed Nf1 genetically-engineered mouse (GEM) strains to study the pathogenesis of these low-grade glial neoplasms. In the light of the finding that human and mouse low-grade gliomas are composed of Olig2+ cells and that Olig2+ oligodendrocyte precursor cells (OPCs) give rise to murine high-grade gliomas, we sought to determine whether Olig2+ OPCs could be tumor-initiating cells for Nf1 optic glioma...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28523568/role-of-dopamine-projections-from-ventral-tegmental-area-to-nucleus-accumbens-and-medial-prefrontal-cortex-in-reinforcement-behaviors-assessed-using-optogenetic-manipulation
#6
Xiao Han, Man-Yi Jing, Tai-Yun Zhao, Ning Wu, Rui Song, Jin Li
Dopamine (DA) neurons in the ventral tegmental area (VTA) are predicted to play important roles in reward. In pharmacological studies, the rewarding effects of methamphetamine are mediated by DA neurons localized in the VTA. The nucleus accumbens (NAc) and medial prefrontal cortices (mPFC) are the main projections from the VTA. However, the role of these projections remains unclear, particularly the mPFC projections. In the present study, DAT-Cre transgenic mice received an injection of adeno-associated viral vectors encoding channelrhodopsin2 (ChR2) or control vector into the VTA resulting in the selective expression of these opsins in DA neurons...
May 19, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28522730/11%C3%AE-hsd1-suppresses-cardiac-fibroblast-cxcl2-cxcl5-and-neutrophil-recruitment-to-the-heart-post-mi
#7
Katie J Mylonas, Neil A Turner, Sumia A Bageghni, Christopher J Kenyon, Christopher I White, Kieran McGregor, Robert A Kimmitt, Richard Sulston, Valerie Kelly, Brian R Walker, Karen E Porter, Karen E Chapman, Gillian A Gray
We have previously demonstrated that neutrophil recruitment to the heart following myocardial infarction (MI) is enhanced in mice lacking 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) that regenerates active glucocorticoid within cells from intrinsically inert metabolites. The present study aimed to identify the mechanism of regulation. In a mouse model of MI, neutrophil mobilization to blood and recruitment to the heart were higher in 11β-HSD1-deficient (Hsd11b1(-)(/)(-) ) relative to wild-type (WT) mice, despite similar initial injury and circulating glucocorticoid...
June 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28522687/integrin-linked-kinase-signaling-promotes-cyst-growth-and-fibrosis-in-polycystic-kidney-disease
#8
Archana Raman, Gail A Reif, Yuqiao Dai, Aditi Khanna, Xiaogang Li, Lindsay Astleford, Stephen C Parnell, James P Calvet, Darren P Wallace
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by innumerous fluid-filled cysts and progressive deterioration of renal function. Previously, we showed that periostin, a matricellular protein involved in tissue repair, is markedly overexpressed by cyst epithelial cells. Periostin promotes cell proliferation, cyst growth, interstitial fibrosis, and the decline in renal function in PKD mice. Here, we investigated the regulation of these processes by the integrin-linked kinase (ILK), a scaffold protein that links the extracellular matrix to the actin cytoskeleton and is stimulated by periostin...
May 18, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28522308/development-of-a-ssdna-aptamer-for-detection-of-residual-benzylpenicillin
#9
A-Young Lee, Na-Reum Ha, In-Pil Jung, Sang-Heon Kim, A-Ru Kim, Moon-Young Yoon
Antibiotics are useful for improving the living conditions of livestock. However, residual antibiotics induce several human diseases such as food-borne illness and infection of carbapenem-resistant Enterobacteriaceae (CRE). In this study, the identification of a benzylpenicillin-specific aptamer was selected by rGO-SELEX (reduced Graphene Oxide-Systematic Evolution of Ligands by EXponential enrichment). A random ssDNA library was incubated with rGO for adsorption and eluted with benzylpenicillin. As a result of the selection process, a DNA aptamer was found that specifically bound to benzylpenicillin with high binding affinity, Kd = 383...
May 15, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28521937/using-drosophila-pigmentation-traits-to-study-the-mechanisms-of-cis-regulatory-evolution
#10
REVIEW
Mark Rebeiz, Thomas M Williams
One primary agenda of the developmental evolution field is to elucidate molecular mechanisms governing differences in animal form. While mounting evidence has established an important role for mutations in transcription controlling cis-regulatory elements (CREs), the underlying mechanisms that translate these alterations into differences in gene expression are poorly understood. Emerging studies focused on pigmentation differences among closely related Drosophila species have provided many examples of phenotypically relevant CRE changes, and have begun to illuminate how this process works at the level of regulatory sequence function and transcription factor binding...
February 2017: Current Opinion in Insect Science
https://www.readbyqxmd.com/read/28520915/ovary-specific-depletion-of-the-nuclear-receptor-nr5a2-compromises-expansion-of-the-cumulus-oophorus-but-not-fertilization-by-icsi
#11
Kalyne Bertolin, Marie-Charlotte Meinsohn, João Suzuki, Jan Gossen, Kristina Schoonjans, Rajesha Duggavathi, Bruce D Murphy
The orphan nuclear receptor, liver receptor homolog-1 (Nr5a2) is widely expressed in mammalian tissues, its ovarian expression is restricted to granulosa cells of activated follicles. We employed the floxed Nr5a2 (Nr5a2f/f) mutant mouse line and two granulosa-specific Cre lines, Amhr2Cre and tgCyp19Cre, to develop two tissue- and time-specific Nr5a2 depletion models, Nr5a2Amhr2-/- and Nr5a2Cyp19-/-. In the Nr5a2Cyp19-/- ovaries, Nr5a2 was depleted in mural granulosa, but not cumulus cells. We induced follicular development in mutant and wild type (control, CON) mice with equine chorionic gonadotropin (eCG) followed 44h later treatment with human chorionic gonadotropin (hCG) to induce ovulation...
May 18, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28520872/glucocerebrosidase-deficiency-in-dopaminergic-neurons-induces-microglial-activation-without-neurodegeneration
#12
Federico N Soria, Michel Engeln, Marta Martinez-Vicente, Christelle Glangetas, María José López-González, Sandra Dovero, Benjamin Dehay, Elisabeth Normand, Miquel Vila, Alexandre Favereaux, François Georges, Christophe Lo Bianco, Erwan Bezard, Pierre-Olivier Fernagut
Mutations in the GBA1 gene encoding the lysosomal enzyme glucocerebrosidase (GBA1) are important risk factors for Parkinson's disease (PD). In vitro, altered GBA1 activity promotes alpha-synuclein accumulation while elevated levels of alpha-synuclein compromise GBA1 function, thus supporting a pathogenic mechanism in PD. However, the mechanisms by which GBA1 deficiency is linked to increased risk of PD remains elusive, partially because of lack of aged models of GBA1 deficiency. Since knocking-out GBA1 in the entire brain induces massive neurodegeneration and early death, we generated a mouse model of GBA1 deficiency amenable to investigate the long-term consequences of compromised GBA1 function in dopaminergic neurons...
May 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28520214/mtorc1-inhibits-nf-%C3%AE%C2%BAb-nfatc1-signaling-and-prevents-osteoclast-precursor-differentiation-in-vitro-and-in-mice
#13
Yue Zhang, Song Xu, Kai Li, Kang Tan, Kangyan Liang, Jian Wang, Junhui Shen, Wenchong Zou, Le Hu, Daozhang Cai, Changhai Ding, Mangmang Li, Guozhi Xiao, Bin Liu, Anling Liu, Xiaochun Bai
The mechanistic target of rapamycin complex 1 (mTORC1) is a critical sensor for bone homeostasis and bone formation; however, the role of mTORC1 in osteoclast development and the underlying mechanisms have not yet been fully established. Here, we found that mTORC1 activity declined during osteoclast precursors differentiation in vitro and in vivo. We further targeted deletion of Raptor (mTORC1 key component) or Tsc1 (mTORC1 negative regulator) to constitutively inhibit or activate mTORC1 in osteoclast precursors (monocytes/macrophages), using LyzM-cre mice...
May 18, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28515282/talin-plays-a-critical-role-in-the-maintenance-of-the-regulatory-t-cell-pool
#14
Jane E Klann, Kelly A Remedios, Stephanie H Kim, Patrick J Metz, Justine Lopez, Lauren A Mack, Ye Zheng, Mark H Ginsberg, Brian G Petrich, John T Chang
Talin, a cytoskeletal protein essential in mediating integrin activation, has been previously shown to be involved in the regulation of T cell proliferation and function. In this study, we describe a role for talin in maintaining the homeostasis and survival of the regulatory T (Treg) cell pool. T cell-specific deletion of talin in Tln1(fl/fl)Cd4(Cre) mice resulted in spontaneous lymphocyte activation, primarily due to numerical and functional deficiencies of Treg cells in the periphery. Peripheral talin-deficient Treg cells were unable to maintain high expression of IL-2Rα, resulting in impaired IL-2 signaling and ultimately leading to increased apoptosis through downregulation of prosurvival proteins Bcl-2 and Mcl-1...
May 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28513431/dissection-of-zebrafish-shha-function-using-site-specific-targeting-with-a-cre-dependent-genetic-switch
#15
Kotaro Sugimoto, Subhra P Hui, Delicia Z Sheng, Kazu Kikuchi
Despite the extensive use of zebrafish as a model organism in developmental biology and regeneration research, genetic techniques enabling conditional analysis of gene function are limited. In this study, we generated Zwitch, a Cre-dependent invertible gene-trap cassette, enabling the establishment of conditional alleles in zebrafish by generating intronic insertions via in vivo homologous recombination. To demonstrate the utility of Zwitch, we generated a conditional sonic hedgehog a (shha) allele. Homozygous shha mutants developed normally; however, shha mutant embryos globally expressing Cre exhibited strong reductions in endogenous shha and shha target gene mRNA levels and developmental defects associated with null shha mutations...
May 17, 2017: ELife
https://www.readbyqxmd.com/read/28512198/novel-role-of-rac-mid1-signaling-in-medial-cerebellar-development
#16
Takashi Nakamura, Takehiko Ueyama, Yuzuru Ninoyu, Hirofumi Sakaguchi, Narantsog Choijookhuu, Yoshitaka Hishikawa, Hiroshi Kiyonari, Masaaki Kohta, Mizuho Sakahara, Ivan de Curtis, Eiji Kohmura, Yasuo Hisa, Atsu Aiba, Naoaki Saito
Rac signaling impacts a relatively large number of downstream targets; however, few studies have established an association between Rac pathways and pathological conditions. In the present study, we generated mice with double knockout of Rac1 and Rac3 (Atoh1-Cre;Rac1(flox/flox);Rac3(-/-) ) in cerebellar granule neurons (CGNs). We observed impaired tangential migration at E16.5, as well as numerous apoptotic CGNs at the deepest layer of the external granule layer (EGL) in the medial cerebellum of Atoh1-Cre;Rac1(flox/flox);Rac3(-/-) mice at P8...
May 15, 2017: Development
https://www.readbyqxmd.com/read/28512117/the-interaction-of-mc3r-and-mc4r-with-mrap2-acth-%C3%AE-msh-and-agrp-in-chickens
#17
Jiannan Zhang, Xin Li, Yawei Zhou, Lin Cui, Jing Li, Chenlei Wu, Yiping Wan, Juan Li, Yajun Wang
The interaction of melanocortin-4 (MC4R) and melanocortin-3 (MC3R) receptors with proopiomelanocortin (POMC)-derived peptides (e.g. α-MSH), agouti-related protein (AgRP), and melanocortin-2 receptor accessory protein 2 (MRAP2) is suggested to play critical roles in energy balance of vertebrates. However, evidence on their interaction in birds remains scarce. Our study aims to reveal their interaction in chickens and the results showed that: 1) chicken (c-)MC3R and cMC4R expressed in CHO cells can be activated by α-MSH and ACTH1-39 equipotently, monitored by a pGL3-CRE-luciferase reporter system; 2) cMC3R and cMC4R, when co-expressed with cMRAP2 (or cMRAP, a cMRAP2 homolog), show increased sensitivity to ACTH treatment and thus likely act as ACTH-preferring receptors, and the interaction between cMC3R/cMC4R and cMRAP2 was demonstrated by co-immunoprecipitation assay; 3) both cMC3R and cMC4R display constitutive activity when expressed in CHO cells, as monitored by Dual-luciferase reporter assay, and cMRAP2 (and cMRAP) can modulate their constitutive activity; 4) AgRP inhibits the constitutive activity of cMC3R/cMC4R, and it also antagonizes ACTH/α-MSH action on cMC4R/cMC3R, indicating that AgRP functions as the inverse agonist and antagonist for both receptors...
May 16, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28512107/divergent-requirements-for-ezh1-in-heart-development-versus-regeneration
#18
Shanshan Ai, Xianhong Yu, Yumei Li, Yong Peng, Chen Li, Yanzhu Yue, Ge Tao, Chuan-Yun Li, William T Pu, Aibin He
Rationale: Polycomb repressive complex 2 (PRC2) is a major epigenetic repressor that deposits methylation on histone H3 on lysine 27 (H3K27me) and controls differentiation and function of many cells, including cardiac myocytes. EZH1 and EZH2 are two alternative catalytic subunits with partial functional redundancy. The relative roles of EZH1 and EZH2 in heart development and regeneration are unknown. Objective: We compared the roles of EZH1 versus EZH2 in heart development and neonatal heart regeneration. Methods and Results: Heart development was normal in Ezh1(-/-) (E1KO) and Ezh2(f/f)::cTNT(-Cre) (E2KO) embryos...
May 16, 2017: Circulation Research
https://www.readbyqxmd.com/read/28511701/easi-crispr-a-robust-method-for-one-step-generation-of-mice-carrying-conditional-and-insertion-alleles-using-long-ssdna-donors-and-crispr-ribonucleoproteins
#19
Rolen M Quadros, Hiromi Miura, Donald W Harms, Hisako Akatsuka, Takehito Sato, Tomomi Aida, Ronald Redder, Guy P Richardson, Yutaka Inagaki, Daisuke Sakai, Shannon M Buckley, Parthasarathy Seshacharyulu, Surinder K Batra, Mark A Behlke, Sarah A Zeiner, Ashley M Jacobi, Yayoi Izu, Wallace B Thoreson, Lisa D Urness, Suzanne L Mansour, Masato Ohtsuka, Channabasavaiah B Gurumurthy
BACKGROUND: Conditional knockout mice and transgenic mice expressing recombinases, reporters, and inducible transcriptional activators are key for many genetic studies and comprise over 90% of mouse models created. Conditional knockout mice are generated using labor-intensive methods of homologous recombination in embryonic stem cells and are available for only ~25% of all mouse genes. Transgenic mice generated by random genomic insertion approaches pose problems of unreliable expression, and thus there is a need for targeted-insertion models...
May 17, 2017: Genome Biology
https://www.readbyqxmd.com/read/28511405/evaluation-of-acute-oral-toxicity-of-ethanol-leaves-extract-of-catharanthus-roseus-in-wistar-albino-rats
#20
Venkateswar Rao Vutukuri, M C Das, Muralidhar Reddy, Siva Prabodh, Padma Sunethri
INTRODUCTION: Herbal drugs have gained importance globally in the treatment of various diseases. Catharanthus roseus is traditionally used as an anti diabetic and anti cancer drug. To the best of our knowledge limited data are available on acute and sub acute toxicity of C. roseus extract despite its wide spread use in traditional medicine. The present study was under taken to evaluate the acute oral toxicity of the ethanol leaves extract of C. roseus. AIM: To investigate the acute oral toxic effects of ethanol leaves extract of C...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
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