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Bo Jiang, Lin Gao, Dawei Lei, Jiannan Liu, Zhengbo Shao, Xinrong Zhou, Renke Li, Donglai Wu, Fei Xue, Yuanmao Zhu, Huiping Yuan
The aims of the present study were to investigate the effect of E50K optineurin (OPTN) mutation on RGC‑5 cells and to define the role of microRNA‑9 (miR‑9) in this system. Transfected RGC‑5 cells were used to evaluate the effects of E50K OPTN on the expression of miR‑9 and subsequent disruption of RGC‑5 cell apoptosis was analyzed using western blotting. The results showed that the expression of E50K OPTN was associated with a marked reduction in the levels of miR‑9 in the E50K OPTN‑transfected RGC‑5 cells...
October 6, 2016: Molecular Medicine Reports
Musteyde Yucebas, Sunde Yilmaz Susluer, Hasan Onur Caglar, Tugce Balci, Z Ozlem Dogan Sigva, Taner Akalin, Nezih Oktar, Tayfun Dalbasti, Cigir Biray Avci, Cumhur Gunduz
PURPOSE: The repressor element 1 (RE-1) silencing transcription factor (REST) is a transcription factor which represses the expression of neuronal differentiation-related genes including SYN1 gene. CoREST, encoded by RCOR1 gene, binds to the REST protein for remodeling of chromatin structure. Although there is a relation among REST, RCOR1, and SYN1 genes, the role of these genes in glioma tumors is still unclear. In this study, expressions of REST, RCOR1, and SYN1 genes were detected in primary cultures derived from tumor samples of diffuse astrocytoma (DA), anaplastic oligodendroglioma (AO), and glioblastoma multiforme (GBM) cases...
July 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Hitomi Aoki, Hajime Ogino, Hiroyuki Tomita, Akira Hara, Takahiro Kunisada
REST (RE1-silencing transcription factor, also called Nrsf) is involved in the maintenance of the undifferentiated state of neuronal stem/progenitor cells in vitro by preventing precocious expression of neuronal genes. REST expression was then decreased in developing neurons to down-regulate neuronal genes which allow their maturation. However, the function of REST during neurogenesis in vivo remains to be elucidated because of the early embryonic lethal phenotype of conventional Rest knockout mice. In order to investigate the role of REST in ocular tissues, we generated and examined the mice evoking genetic ablation to Rest specifically to neural tissues including ocular tissue...
2016: PloS One
Cara E Moravec, John Samuel, Wei Weng, Ian C Wood, Howard I Sirotkin
UNLABELLED: During embryonic development, regulation of gene expression is key to creating the many subtypes of cells that an organism needs throughout its lifetime. Recent work has shown that maternal genetics and environmental factors have lifelong consequences on diverse processes ranging from immune function to stress responses. The RE1-silencing transcription factor (Rest) is a transcriptional repressor that interacts with chromatin-modifying complexes to repress transcription of neural-specific genes during early development...
September 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Xiaorui Sun, Ruirui Yang, Rixiang Song, Song Leng, Pengfei Jiang, Wenliang Gao, Rihong Cong, Tao Yang
There emerge great interests in the syntheses of metastable polyborates; however, most are involved with the high-pressure technique. A facile method to synthesize metastable rare earth borates at ambient pressure is eagerly required for the large-scale production and property investigation. Here we demonstrate the critical role of Bi(3+) substitutions in the stabilization of metastable β-REB3O6 (RE = Sm, Eu, Gd, Tb, Dy, Ho, Er, and Y) at ambient pressure, where the Bi(3+)-to-RE(3+) substitutions would efficiently reduce the synthetic temperatures to 735-820 °C, well below the upper limit of thermodynamically stable window (840-980 °C)...
September 19, 2016: Inorganic Chemistry
Lutz Menzel, Magdalena Paterka, Stefan Bittner, Robin White, Wiesia Bobkiewicz, Jack van Horssen, Melitta Schachner, Esther Witsch, Tanja Kuhlmann, Frauke Zipp, Michael K E Schäfer
In multiple sclerosis (MS), the immune cell attack leads to axonal injury as a major cause for neurological disability. Here, we report a novel role of the cell adhesion molecule L1 in the crosstalk between the immune and nervous systems. L1 was found to be expressed by CNS axons of MS patients and human T cells. In MOG35-55-induced murine experimental neuroinflammation, CD4(+) T cells were associated with degenerating axons in the spinal cord, both expressing L1. However, neuronal L1 expression in the spinal cord was reduced, while levels of the transcriptional repressor REST (RE1-Silencing Transcription Factor) were up-regulated...
November 2016: Acta Neuropathologica
Karine Mathilde Campestrini Dallagnol, Aline Pertile Remor, Rodrigo Augusto da Silva, Rui Daniel Prediger, Alexandra Latini, Aderbal Silva Aguiar
Exercise improves mental health and synaptic function in the aged brain. However, the molecular mechanisms involved in exercise-induced healthy brain aging are not well understood. Evidence supports the role of neurogenesis and neuroplasticity in exercise-induced neuroplasticity. The gene silencing transcription factor neuronal RE1-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) and an anti-inflammatory role of exercise are also candidate mechanisms. We evaluate the effect of 8 weeks of physical activity on running wheels (RW) on motor and depressive-like behavior and hippocampal gene expression of brain-derived neurotrophic factor (BDNF), REST, and interleukins IL-1β and IL-10 of adult and aged C57BL/6 mice...
July 29, 2016: Brain, Behavior, and Immunity
Jonas Thelin, Pär Halje, Jacob Nielsen, Michael Didriksen, Per Petersson, Jesper F Bastlund
AIM: To date, the understanding and development of novel treatments for mental illness is hampered by inadequate animal models. For instance, it is unclear to what extent commonly used behavioural tests in animals can inform us on the mental and affective aspects of schizophrenia. METHODS: In order to link pathophysiological processes in an animal model to clinical findings, we have here utilized the recently developed Df(h15q13)/+ mouse model for detailed investigations of cortical neuronal engagement during pre-attentive processing of auditory information from two back-translational auditory paradigms...
July 1, 2016: Acta Physiologica
Jing-Jing Liu, Cui-Mei Zhao, Zhi-Gang Li, Yu-Mei Wang, Wei Miao, Xiu-Juan Wu, Wen-Jing Wang, Chang Liu, Duo Wang, Kang Wang, Li Li, Lu-Ying Peng
MicroRNAs (miRNAs) have been identified as key players in cardiomyocyte hypertrophy, which is associated with significant risks of heart failure. However, many microRNAs are still not recognized for their functions in pathophysiological processes. In this study, we evaluated effects of miR-218 in cardiomyocyte hypertrophy using both in vitro and in vivo models. We found that miR-218 was evidently downregulated in a transverse aortic constriction (TAC) mouse model. Overexpression of miR-218 is sufficient to reduce hypertrophy, whereas the suppression of miR-218 aggravates hypertrophy in primary cardiomyocytes induced by isoprenaline (ISO)...
2016: International Journal of Molecular Sciences
Yinan Li, Nilgun Donmez, Cenk Sahinalp, Ning Xie, Yuwei Wang, Hui Xue, Fan Mo, Himisha Beltran, Martin Gleave, Yuzhuo Wang, Colin Collins, Xuesen Dong
BACKGROUND: Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of castration-resistant prostate cancer that typically does not respond to androgen receptor pathway inhibition (ARPI), and its diagnosis is increasing. OBJECTIVE: To understand how NEPC develops and to identify driver genes to inform therapy for NEPC prevention. DESIGN, SETTING, AND PARTICIPANTS: Whole-transcriptome sequencing data were extracted from prostate tumors from two independent cohorts: The Beltran cohort contained 27 adenocarcinoma and five NEPC patient samples, and the Vancouver Prostate Centre cohort contained three patient samples and nine patient-derived xenografts...
May 11, 2016: European Urology
Thorsten R Doeppner, Britta Kaltwasser, Eduardo H Sanchez-Mendoza, Ahmet B Caglayan, Mathias Bähr, Dirk M Hermann
Lithium promotes acute poststroke neuronal survival, which includes mechanisms that are not limited to GSK3β inhibition. However, whether lithium induces long-term neuroprotection and enhanced brain remodeling is unclear. Therefore, mice were exposed to transient middle cerebral artery occlusion and lithium (1 mg/kg bolus followed by 2 mg/kg/day over up to 7 days) was intraperitoneally administered starting 0-9 h after reperfusion onset. Delivery of lithium no later than 6 h reduced infarct volume on day 2 and decreased brain edema, leukocyte infiltration, and microglial activation, as shown by histochemistry and flow cytometry...
April 28, 2016: Journal of Cerebral Blood Flow and Metabolism
Rui-Rong Ye, Cai-Ping Tan, Mu-He Chen, Liang Hao, Liang-Nian Ji, Zong-Wan Mao
Elucidation of relationship among chemical structure, cellular uptake, localization, and biological activity of anticancer metal complexes is important for the understanding of their mechanisms of action. Organometallic rhenium(I) tricarbonyl compounds have emerged as potential multifunctional anticancer drug candidates that can integrate therapeutic and imaging capabilities in a single molecule. Herein, two mononuclear phosphorescent rhenium(I) complexes (Re1 and Re2), along with their corresponding dinuclear complexes (Re3 and Re4), were designed and synthesized as potent anticancer agents...
June 1, 2016: Chemistry: a European Journal
Carmen Rios, Gianluca D'Ippolito, Kevin M Curtis, Gaëtan J-R Delcroix, Lourdes A Gomez, Jimmy El Hokayem, Megan Rieger, Ricardo Parrondo, Alicia de Las Pozas, Carlos Perez-Stable, Guy A Howard, Paul C Schiller
Human bone marrow multipotent mesenchymal stromal cell (hMSC) number decreases with aging. Subpopulations of hMSCs can differentiate into cells found in bone, vasculature, cartilage, gut, and other tissues and participate in their repair. Maintaining throughout adult life such cell subpopulations should help prevent or delay the onset of age-related degenerative conditions. Low oxygen tension, the physiological environment in progenitor cell-rich regions of the bone marrow microarchitecture, stimulates the self-renewal of marrow-isolated adult multilineage inducible (MIAMI) cells and expression of Sox2, Nanog, Oct4a nuclear accumulation, Notch intracellular domain, notch target genes, neuronal transcriptional repressor element 1 (RE1)-silencing transcription factor (REST), and hypoxia-inducible factor-1 alpha (HIF-1α), and additionally, by decreasing the expression of (i) the proapoptotic proteins, apoptosis-inducing factor (AIF) and Bak, and (ii) senescence-associated p53 expression and β-galactosidase activity...
June 1, 2016: Stem Cells and Development
Rakhi P Jattani, Julia M Tritapoe, Joel L Pomerantz
The CARD11 signaling scaffold transmits signaling between antigen receptors on B and T lymphocytes and the transcription factor NF-κB during the adaptive immune response. CARD11 activity is controlled by an inhibitory domain (ID), which participates in intramolecular interactions and prevents cofactor binding prior to receptor triggering. Oncogenic CARD11 mutations associated with the activated B cell-like subtype of diffuse large B cell lymphoma somehow perturb ID-mediated autoinhibition to confer CARD11 with the dysregulated spontaneous signaling to NF-κB that is required for the proliferation and survival of the lymphoma...
April 15, 2016: Journal of Biological Chemistry
Irene Aksoy, Guillaume Marcy, Jiaxuan Chen, Ushashree Divakar, Vibhor Kumar, Daniel John-Sanchez, Mehran Rahmani, Noel J Buckley, Lawrence W Stanton
During development, lineage specification is controlled by several signaling pathways involving various transcription factors (TFs). Here, we studied the RE-1-silencing transcription factor (REST) and identified an important role of this TF in cardiac differentiation. Using mouse embryonic stem cells (ESC) to model development, we found that REST knockout cells lost the ability to differentiate into the cardiac lineage. Detailed analysis of specific lineage markers expression showed selective downregulation of endoderm markers in REST-null cells, thus contributing to a loss of cardiogenic signals...
April 2016: Stem Cells
Jun Ishii, Takuya Yazawa, Tomohiro Chiba, Yukiko Shishido-Hara, Yuu Arimasu, Hanako Sato, Hiroshi Kamma
Mechanisms of endocrine secretory granule (SG) formation in thyroid C cells and medullary thyroid cancer (MTC) cells have not been fully elucidated. Here we directly demonstrated that PROX1, a developmental homeobox gene, is transcriptionally involved in SG formation in MTC, which is derived from C cells. Analyses using gene expression databases on web sites revealed that, among thyroid cancer cells, MTC cells specifically and highly express PROX1 as well as several SG-forming molecule genes. Immunohistochemical analyses showed that in vivo MTC and C cells expressed PROX1, although follicular thyroid cancer and papillary thyroid cancer cells, normal follicular cells did not...
March 2016: Endocrinology
Francesco Paonessa, Stefania Criscuolo, Silvio Sacchetti, Davide Amoroso, Helena Scarongella, Federico Pecoraro Bisogni, Emanuele Carminati, Giacomo Pruzzo, Luca Maragliano, Fabrizia Cesca, Fabio Benfenati
Optogenetics provides new ways to activate gene transcription; however, no attempts have been made as yet to modulate mammalian transcription factors. We report the light-mediated regulation of the repressor element 1 (RE1)-silencing transcription factor (REST), a master regulator of neural genes. To tune REST activity, we selected two protein domains that impair REST-DNA binding or recruitment of the cofactor mSin3a. Computational modeling guided the fusion of the inhibitory domains to the light-sensitive Avena sativa light-oxygen-voltage-sensing (LOV) 2-phototrophin 1 (AsLOV2)...
January 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
Kaushali Thakore-Shah, Tasneem Koleilat, Majib Jan, Alan John, April D Pyle
REST (RE1 silencing transcription factor), also known as NRSF (neuron-restrictive silencer factor), is a well-known transcriptional repressor of neural genes in non-neural tissues and stem cells. Dysregulation of REST activity is thought to play a role in diverse diseases including epilepsy, cancer, Down's syndrome and Huntington's disease. The role of REST/NRSF in control of human embryonic stem cell (hESC) fate has never been examined. To evaluate the role of REST in hESCs we developed an inducible REST knockdown system and examined both growth and differentiation over short and long term culture...
2015: PloS One
Shazia S Mahamdallie, Sandra Hanks, Kristen L Karlin, Anna Zachariou, Elizabeth R Perdeaux, Elise Ruark, Chad A Shaw, Alexander Renwick, Emma Ramsay, Shawn Yost, Anna Elliott, Jillian Birch, Michael Capra, Juliet Gray, Juliet Hale, Judith Kingston, Gill Levitt, Thomas McLean, Eamonn Sheridan, Anthony Renwick, Sheila Seal, Charles Stiller, Neil Sebire, Thomas F Westbrook, Nazneen Rahman
Wilms tumor is the most common childhood renal cancer. To identify mutations that predispose to Wilms tumor, we are conducting exome sequencing studies. Here we describe 11 different inactivating mutations in the REST gene (encoding RE1-silencing transcription factor) in four familial Wilms tumor pedigrees and nine non-familial cases. Notably, no similar mutations were identified in the ICR1000 control series (13/558 versus 0/993; P < 0.0001) or in the ExAC series (13/558 versus 0/61,312; P < 0.0001)...
December 2015: Nature Genetics
Pietro Baldelli, Jacopo Meldolesi
REST [RE1-silencing transcription factor (also called neuron-restrictive silencer factor)] is known to repress thousands of possible target genes, many of which are neuron specific. To date, REST repression has been investigated mostly in stem cells and differentiating neurons. Current evidence demonstrates its importance in adult neurons as well. Low levels of REST, which are acquired during differentiation, govern the expression of specific neuronal phenotypes. REST-dependent genes encode important targets, including transcription factors, transmitter release proteins, voltage-dependent and receptor channels, and signaling proteins...
July 2015: ENeuro
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