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notch gene

Jennifer Jurkin, Corinna Krump, René Köffel, Christina Fieber, Christopher Schuster, Patrick M Brunner, Izabela Borek, Gregor Eisenwort, Clarice Lim, Jörg Mages, Roland Lang, Wolfgang Bauer, Diana Mechtcheriakova, Anastasia Meshcheryakova, Adelheid Elbe-Bürger, Georg Stingl, Herbert Strobl
BACKGROUND: Langerhans cell (LC) networks play key roles in immunity and tolerance at body surfaces. LCs are established prenatally and can be replenished from blood monocytes. Unlike skin-resident dermal/interstitial-type DCs (d/intDCs) and inflammatory dendritic epidermal cells (IDECs) appearing in dermatitis/eczema lesions, LCs lack key monocyte-affiliated markers. Inversely, LCs express various epithelial genes critical for their long-term peripheral tissue residency. OBJECTIVE: DCs are functionally involved in inflammatory diseases; however, mechanisms remained poorly understood...
October 11, 2016: Journal of Allergy and Clinical Immunology
Alon Peled, Ofer Sarig, Liat Samuelov, Marta Bertolini, Limor Ziv, Daphna Weissglas-Volkov, Marina Eskin-Schwartz, Christopher A Adase, Natalia Malchin, Ron Bochner, Gilad Fainberg, Ilan Goldberg, Koji Sugawara, Avital Baniel, Daisuke Tsuruta, Chen Luxenburg, Noam Adir, Olivier Duverger, Maria Morasso, Stavit Shalev, Richard L Gallo, Noam Shomron, Ralf Paus, Eli Sprecher
Despite recent advances in our understanding of the pathogenesis of ectodermal dysplasias (EDs), the molecular basis of many of these disorders remains unknown. In the present study, we aimed at elucidating the genetic basis of a new form of ED featuring facial dysmorphism, scalp hypotrichosis and hypodontia. Using whole exome sequencing, we identified 2 frameshift and 2 missense mutations in TSPEAR segregating with the disease phenotype in 3 families. TSPEAR encodes the thrombospondin-type laminin G domain and EAR repeats (TSPEAR) protein, whose function is poorly understood...
October 2016: PLoS Genetics
J Philippe York, Yi Athena Ren, Jie Zeng, Bin Zhang, Fang Wang, Rui Chen, Jianqiao Liu, Xuefeng Xia, Pumin Zhang
In the mouse ovary, the primordial follicle pool is established through a diverse array of signaling pathways and tissue remodeling events. Growth arrest specific gene two (GAS2) is a highly conserved cytoskeleton-associated protein whose in vivo function remains unclear. In Drosophila, loss of the GAS2 homolog, Pigs, results in infertility. We demonstrate herein that, in the mouse ovary, GAS2 is expressed in the stromal cells surrounding the oocyte cysts on 16.5 dpc, and in stromal cells surrounding growing follicles during juvenile and adult life...
October 13, 2016: Scientific Reports
Shanmugam Muruganandan, Rajgopal Govindarajan, Nichole M McMullen, Christopher J Sinal
Bone remodelling is a dynamic process requiring the coordinated action of formative (osteoblast) and resorptive (osteoclast) cell populations. An imbalance of the development and function of these cell types underlies several chronic bone loss disorders such as osteoporosis. Increased bone marrow adipocyte numbers commonly occur with bone loss disorders and numerous studies have documented an inverse relationship between bone marrow fat and bone formation. Osteoblasts and adipocytes derive in a competitive fashion from a common mesenchymal stem cell (MSC) precursor...
October 12, 2016: Stem Cells
Riikka Kivelä, Ida Salmela, Yen Hoang Nguyen, Tatiana V Petrova, Heikki A Koistinen, Zoltan Wiener, Kari Alitalo
The remarkable adaptive and regenerative capacity of skeletal muscle is regulated by several transcription factors and pathways. Here we show that the transcription factor Prox1 is an important regulator of myoblast differentiation and of slow muscle fibre type. In both rodent and human skeletal muscles Prox1 is specifically expressed in slow muscle fibres and in muscle stem cells called satellite cells. Prox1 activates the NFAT signalling pathway and is necessary and sufficient for the maintenance of the gene program of slow muscle fibre type...
October 12, 2016: Nature Communications
Areerat Kunanopparat, Ingorn Kimkong, Tanapat Palaga, Pisit Tangkijvanich, Boonchoo Sirichindakul, Nattiya Hirankarn
AIM: To investigate autophagy-related genes, particularly ATG12, in apoptosis and cell cycle in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and non-HBV-HCC cell lines. METHODS: The expression of autophagy-related genes in HBV-associated hepatocellular carcinoma and non-HBV-HCC cell lines and human liver tissues was examined by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blotting. The silencing of target genes was used to examine the function of various genes in apoptosis and cell cycle progression...
October 7, 2016: World Journal of Gastroenterology: WJG
Yu-Hui Yan, Shao-Heng Li, Zhong Gao, Sa-Feng Zou, Hong-Yan Li, Zhen-Yu Tao, Jie Song, Jing-Xian Yang
AIMS: Recently, the potential for neural stem cells (NSCs) to be used in the treatment of Alzheimer's disease (AD) has been reported; however, the therapeutic effects are modest by virtue of the low neural differentiation rate. In our study, we transfected bone marrow-derived NSCs (BM-NSCs) with Neurotrophin-3 (NT-3), a superactive neurotrophic factor that promotes neuronal survival, differentiation, and migration of neuronal cells, to investigate the effects of NT-3 gene overexpression on the proliferation and differentiation into cholinergic neuron of BM-NSCs in vitro and its possible molecular mechanism...
October 6, 2016: Life Sciences
Wenwen Zhou, Qiuping He, Chunxia Zhang, Xin He, Zongbin Cui, Feng Liu, Wei Li
Notch signaling plays a crucial role in the control of proliferation and differentiation of stem and progenitor cells during embryogenesis or organogenesis, but its regulation is incompletely understood. BLOS2, encoded by the Bloc1s2 gene, is a shared subunit of two lysosomal trafficking complexes, biogenesis of lysosome-related organelles complex-1 (BLOC-1) and BLOC-1 related complex. Bloc1s2(-/-) mice were embryonic lethal and exhibited defects in cortical development and hematopoiesis. Loss of BLOS2 resulted in elevated Notch signaling, which consequently increased the proliferation of neural progenitor cells and inhibited neuronal differentiation in cortices...
October 10, 2016: ELife
Yi-Hong Zhou, Yuanjie Hu, Liping Yu, Chao Ke, Christopher Vo, Hao Hsu, Zhenzhi Li, Anne T Di Donato, Abhishek Chaturbedi, Ji Won Hwang, Eric R Siegel, Mark E Linskey
De-regulated EFEMP1 gene expression in solid tumors has been widely reported with conflicting roles. We dissected EFEMP1 to identify domains responsible for its cell context-dependent dual functions, with the goal being to construct an EFEMP1-derived tumor-suppressor protein (ETSP) that lacked tumor-promoting function. Exon/intron boundaries of EFEMP1 were used as boundaries of functional modules in constructing EFEMP1 variants, with removal of various module(s), and/or mutating an amino acid residue to convert a weak integrin binding-site into a strong one...
2016: Oncoscience
Thomas K Smylla, Anette Preiss, Dieter Maier
Cell communication in metazoans requires the highly conserved Notch signaling pathway, which is subjected to strict regulation of both activation and silencing. In Drosophila melanogaster, silencing involves the assembly of a repressor complex by Hairless (H) on Notch target gene promoters. We previously found an in-frame internal ribosome entry site in the full length H transcript resulting in two H protein isoforms (H(p120) and H(p150)). Hence, H may repress Notch signalling activity in situations where cap-dependent translation is inhibited...
October 7, 2016: Scientific Reports
Zhenhao Qi, Lisu Wang, Aiqing He, Manling Ma-Edmonds, John Cogswell
AIM: Formalin-fixed, paraffin-embedded (FFPE) clinical tissue samples have the potential to provide valuable gene-expression data for the development of cancer biomarkers. However, FFPE RNA is extensively fragmented, presenting a significant challenge for reliably detecting gene expression using traditional qPCR methods. RESULTS: We evaluated three novel methodologies along with the traditional qPCR method for their ability to detect Notch pathway gene expression in colorectal cancer FFPE tissue RNAs...
October 7, 2016: Bioanalysis
Amal Al-Garawi, Vincent J Carey, Divya Chhabra, Hooman Mirzakhani, Jarrett Morrow, Jessica Lasky-Su, Weiliang Qiu, Nancy Laranjo, Augusto A Litonjua, Scott T Weiss
BACKGROUND: Patterns of gene expression of human pregnancy are poorly understood. In a trial of vitamin D supplementation in pregnant women, peripheral blood transcriptomes were measured longitudinally on 30 women and used to characterize gene co-expression networks. OBJECTIVE: Studies suggest that increased maternal Vitamin D levels may reduce the risk of asthma in early life, yet the underlying mechanisms have not been examined. In this study, we used a network-based approach to examine changes in gene expression profiles during the course of normal pregnancy and evaluated their association with maternal Vitamin D levels...
2016: PloS One
M A E Nieuwenhuis, J M Vonk, B E Himes, C Sarnowski, C Minelli, D Jarvis, E Bouzigon, D C Nickle, M Laviolette, D Sin, S T Weiss, M van den Berge, G H Koppelman, D S Postma
BACKGROUND: The severity of bronchial hyperresponsiveness (BHR) is a fundamental feature of asthma. The severity of BHR varies between asthmatics and is associated with lack of asthma control. The mechanisms underlying this trait are still unclear. This study aims to identify genes associated with BHR severity, using a genome wide association study (GWAS) on the slope of BHR in adult asthmatics. METHODS: We performed a GWAS on BHR severity in adult asthmatics from the Dutch Asthma GWAS cohort (n=650), adjusting for smoking and inhaled corticosteroid use, and verified results in 3 other cohorts...
October 6, 2016: Allergy
Humberto Contreras-Cornejo, Germán Saucedo-Correa, Javier Oviedo-Boyso, Juan José Valdez-Alarcón, Víctor Manuel Baizabal-Aguirre, Marcos Cajero-Juárez, Alejandro Bravo-Patiño
The Notch signaling pathway is a reiteratively used cell to cell communication pathway that triggers pleiotropic effects. The correct regulation of the pathway permits the efficient regulation of genes involved in cell fate decision throughout development. This activity relies notably on the CSL proteins, (an acronym for CBF-1/RBPJ-κ in Homo sapiens/Mus musculus respectively, Suppressor of Hairless in Drosophila melanogaster, Lag-1 in Caenorhabditis elegans) which is the unique transcription factor and DNA binding protein involved in this pathway...
2016: Cell Division
Peng Shen, Xiaoxi Li, Guoming Xie, Xiaoqiao Huangfu, Jinzhong Zhao
PURPOSE: To assess time-dependent effects of arthroscopic conditions on human articular cartilage in vivo. METHODS: From each of 10 patients undergoing multiligament reconstruction of the knee under our routine arthroscopic conditions (gravity irrigation of 0.9% normal saline solution at room temperature with 150 cm H2O [110 mm Hg] pressure and pneumatic tourniquet under 270 mm Hg pressure), cartilage specimens were harvested from the lateral edge of the femoral notch at the beginning of the operation (baseline) and at 15-, 30-, 45-, and 60-minute time points during the operation...
October 1, 2016: Arthroscopy: the Journal of Arthroscopic & related Surgery
Francisca F Vasconcelos, Alessandro Sessa, Cátia Laranjeira, Alexandre A S F Raposo, Vera Teixeira, Daniel W Hagey, Diogo M Tomaz, Jonas Muhr, Vania Broccoli, Diogo S Castro
The generation of neurons from neural stem cells requires large-scale changes in gene expression that are controlled to a large extent by proneural transcription factors, such as Ascl1. While recent studies have characterized the differentiation genes activated by proneural factors, less is known on the mechanisms that suppress progenitor cell identity. Here, we show that Ascl1 induces the transcription factor MyT1 while promoting neuronal differentiation. We combined functional studies of MyT1 during neurogenesis with the characterization of its transcriptional program...
October 4, 2016: Cell Reports
Fernanda Silva, Ana Félix, Jacinta Serpa
Epithelial ovarian cancer is the most lethal gynecologic malignancy, despite advances in treatment. The most common histological type, high-grade ovarian serous carcinoma (OSC) is usually diagnosed at an advanced stage, and although these types of tumors frequently respond to surgery and platinum-based chemotherapy, they usually recur. Ovarian clear cell carcinoma (OCCC) is an unusual histological type, which is known to be intrinsically chemoresistant and is associated with poor prognosis in advanced stages...
October 2016: Oncology Letters
Keren Gueta, Ahuvit David, Tsadok Cohen, Yotam Menuchin-Lasowski, Hila Nobel, Ginat Narkis, LiQi Li, Paul Love, Jimmy de Melo, Seth Blackshaw, Heiner Westphal, Ruth Ashery-Padan
The Lim domain binding proteins (Ldbs) are key cofactor proteins that assemble with LIM domains of the LMO/LIM-HD family to form functional complexes that regulate cell proliferation and differentiation throughout the CNS. Here, using conditional mutagenesis and comparative phenotypic analysis, we analyze the function of Ldb1 and Ldb2 in mouse retinal development, and demonstrate overlapping and specific functions of both genes. We show that Ldb1 interacts with Lhx2 in the embryonic retina and that both Ldb1 and Ldb2, probably functioning with Lhx2 in a complex, play a key role in maintaining the pool of retinal progenitor cells...
October 3, 2016: Development
Aditi Khandekar, Steven Springer, Wei Wang, Stephanie Hicks, Carla J Weinheimer, Ramon Diaz-Trelles, Jeanne M Nerbonne, Stacey Rentschler
RATIONALE: Ventricular arrhythmias often arise from the Purkinje-myocyte junction and are a leading cause of sudden cardiac death. Notch activation reprograms cardiac myocytes to an "induced Purkinje-like" state characterized by prolonged action potential duration and expression of Purkinje enriched genes. OBJECTIVE: To understand the mechanism by which canonical Notch signaling causes action potential prolongation. METHODS AND RESULTS: We find that endogenous Purkinje cells have reduced peak K(+) current, Ito and IK,slow when compared with ventricular myocytes...
October 3, 2016: Circulation Research
Zhong-Bao Ruan, Xing-Li Fu, Wei Li, Jun Ye, Ru-Zhu Wang, Li Zhu
BACKGROUND: Notch and NF-κB signaling pathways both play important roles in the regulation of atherosclerosis (AS). However, the mechanisms of notch and NF-κB signaling pathways on AS are still unclear. In this study, we aimed to investigate the effects of notch1,2,3 genes silicing by siRNA on notch and NF-κB signaling pathways of macrophages in patients with atherosclerosis (AS), so as to seek the treatment of AS from genetic perspective. METHODS: Peripheral blood mononuclears of 31 patients with AS were isolated by density gradient centrifugation and transformed by PMA to macrophages...
September 30, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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