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https://www.readbyqxmd.com/read/29242286/hop-1-presenilin-deficiency-causes-a-late-onset-notch-signaling-phenotype-that-affects-adult-germline-function-in-c-elegans
#1
Ipsita Agarwal, Cassandra Farnow, Joshua Jiang, Kyung-Sik Kim, Donna E Leet, Ruth Z Solomon, Valerie A Hale, Caroline Goutte
Functionally redundant genes present a puzzle as to their evolutionary preservation, and offer an interesting opportunity for molecular specialization. In Caenorhabditis elegans, either one of two presenilin genes (sel-12 or hop-1) facilitate Notch activation, providing the catalytic subunit for the gamma secretase proteolytic enzyme complex.  For all known Notch signaling events, sel-12 can mediate Notch activation, so the conservation of hop-1 remains a mystery. Here, we uncover a novel "late-onset" germline Notch phenotype in which HOP-1-deficient worms fail to maintain proliferating germline stem cells during adulthood...
December 14, 2017: Genetics
https://www.readbyqxmd.com/read/29241683/notch-pathway-signaling-in-the-skin-antagonizes-merkel-cell-development
#2
Gregory J Logan, Margaret C Wright, Adam C Kubicki, Stephen M Maricich
Merkel cells are mechanosensitive skin cells derived from the epidermal lineage whose development requires expression of the basic helix-loop-helix transcription factor Atoh1. The genes and pathways involved in regulating Merkel cell development during embryogenesis are poorly understood. Notch pathway signaling antagonizes Atoh1 expression in many developing body regions, so we hypothesized that Notch signaling might inhibit Merkel cell development. We found that conditional, constitutive overexpression of the Notch intracellular domain (NICD) in mouse epidermis significantly decreased Merkel cell numbers in whisker follicles and touch domes of hairy skin...
December 11, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29239031/molecular-alterations-of-neuroendocrine-tumours-of-the-lung
#3
REVIEW
Giulio Rossi, Luca Bertero, Caterina Marchiò, Mauro Papotti
Neuroendocrine tumours of the lung comprise low [typical carcinoid (TC)], intermediate [atypical carcinoid (AC)] and high-grade [small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC)] malignancies, while a pre-invasive lesion [diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH)] may generate a subset of peripheral carcinoid tumours. These neoplasms are differentiated conventionally based on mitotic rate, presence of necrosis and cytological details, according to the 2015 World Health Organisation (WHO) classification...
January 2018: Histopathology
https://www.readbyqxmd.com/read/29238898/comprehensive-bioinformation-analysis-of-the-mirna-of-plce1-knockdown-in-esophageal-squamous-cell-carcinoma
#4
Xiaobin Cui, Kaige Wang, Xinqian Yang, Hao Peng, Xi Chen, Huahua Xin, Yanxia Tian, Yunzhao Chen, Feng Li
Phospholipase C epsilon 1 (PLCE1) has been recognized as a novel susceptibility marker for esophageal squamous cell carcinoma (ESCC). The purpose of our study is to investigate its effect on the regulation of miRNA expression so as to translating the data into a novel strategy in control of ESCC. In this study, PLCE1 siRNA and vector-only plasmid were stably transfected into Eca109 and EC9706 cells and then subjected to miRNA array analysis, and quantitative real-time PCR was applied to validate miRNA array data...
December 13, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29235987/gene-free-methodology-for-cell-fate-dynamics-during-development
#5
Francis Corson, Eric D Siggia
Models of cell function that assign a variable to each gene frequently lead to systems of equations with many parameters whose behavior is obscure. Geometric models reduce dynamics to intuitive pictorial elements that provide compact representations for sparse in-vivo data and transparent descriptions of developmental transitions. To illustrate, a geometric model fit to vulval development in C. elegans, implies a phase diagram where cell-fate choices are displayed in a plane defined by EGF and Notch signaling levels...
December 13, 2017: ELife
https://www.readbyqxmd.com/read/29230705/crosstalk-between-tlr4-and-notch1-signaling-in-the-iga-nephropathy-during-inflammatory-response
#6
Xuxiang Sheng, Xiaoyan Zuo, Xihui Liu, Yang Zhou, Xia Sun
PURPOSE: IgA nephropathy (IgAN) is an immune complex-mediated disease involved in the kidney disease. Recent studies have revealed that Notch signaling-related genes are aberrantly expressed in various cell types and maybe associate with inflammation-induced carcinogenesis. The aim of our study was to investigate the function of Notch1 in the inflammatory response of IgAN. METHODS: The expression of Notch1, Jagged1 and NICD1 in 52 IgAN renal tissues and 20 control renal tissues was first determined using quantitative real-time PCR and Western blot...
December 11, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/29228002/comparative-cell-cycle-transcriptomics-reveals-synchronization-of-developmental-transcription-factor-networks-in-cancer-cells
#7
Johan Boström, Zuzana Sramkova, Alena Salašová, Helena Johard, Diana Mahdessian, Radek Fedr, Carolyn Marks, Jiřina Medalová, Karel Souček, Emma Lundberg, Sten Linnarsson, Vítězslav Bryja, Petra Sekyrova, Mikael Altun, Michael Andäng
The cell cycle coordinates core functions such as replication and cell division. However, cell-cycle-regulated transcription in the control of non-core functions, such as cell identity maintenance through specific transcription factors (TFs) and signalling pathways remains unclear. Here, we provide a resource consisting of mapped transcriptomes in unsynchronized HeLa and U2OS cancer cells sorted for cell cycle phase by Fucci reporter expression. We developed a novel algorithm for data analysis that enables efficient visualization and data comparisons and identified cell cycle synchronization of Notch signalling and TFs associated with development...
2017: PloS One
https://www.readbyqxmd.com/read/29227558/rna-sequencing-identifies-gene-regulatory-networks-controlling-extracellular-matrix-synthesis-in-intervertebral-disk-tissues
#8
Scott M Riester, Yang Lin, Wei Wang, Lin Cong, Abdel-Moneim Mohamed Ali, Sun H Peck, Lachlan J Smith, Bradford L Currier, Michelle Clark, Paul Huddleston, William Krauss, Michael J Yaszemski, Mark E Morrey, Matthew P Abdel, Mohamad Bydon, Wenchun Qu, A Noelle Larson, Andre J van Wijnen, Ahmad Nassr
Degenerative disk disease of the spine is a major cause of back pain and disability. Optimization of regenerative medical therapies for degenerative disk disease requires a deep mechanistic understanding of the factors controlling the structural integrity of spinal tissues. In this investigation, we sought to identify candidate regulatory genes controlling extracellular matrix synthesis in spinal tissues. To achieve this goal we performed high throughput next generation RNA sequencing on 39 annulus fibrosus and 21 nucleus pulposus human tissue samples...
December 11, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/29226075/prediction-of-target-genes-for-mir-140-5p-in-pulmonary-arterial-hypertension-using-bioinformatics-methods
#9
Fangwei Li, Wenhua Shi, Yixin Wan, Qingting Wang, Wei Feng, Xin Yan, Jian Wang, Limin Chai, Qianqian Zhang, Manxiang Li
The expression of microRNA (miR)-140-5p is known to be reduced in both pulmonary arterial hypertension (PAH) patients and monocrotaline-induced PAH models in rat. Identification of target genes for miR-140-5p with bioinformatics analysis may reveal new pathways and connections in PAH. This study aimed to explore downstream target genes and relevant signaling pathways regulated by miR-140-5p to provide theoretical evidences for further researches on role of miR-140-5p in PAH. Multiple downstream target genes and upstream transcription factors (TFs) of miR-140-5p were predicted in the analysis...
December 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/29218101/delta-notch-like-epidermal-growth-factor-related-receptor-dner-orchestrates-stemness-and-cancer-progression-in-prostate-cancer
#10
Lijun Wang, Qi Wu, Shan Zhu, Zhiyu Li, Jingping Yuan, Dehua Yu, Zhiliang Xu, Juanjuan Li, Shengrong Sun, Changhua Wang
DNER, Delta/Notch-like epidermal growth factor (EGF)-related receptor, is a neuron-specific transmembrane protein carrying extracellular EGF-like repeats. The function of DNER in prostate cancer has not been evaluated. Here, we showed that the upregulation of DNER is observed in various cancers, including prostate cancer. Knockdown of DNER in PC-3 cells inhibited cell proliferation, migration and invasion as well as tumorigenesis in PC-3 xenografts. DNER knockdown specifically inhibited cell growth in spheroids...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29215066/pharmacological-inhibition-of-rev-erb-stimulates-differentiation-inhibits-turnover-and-reduces-fibrosis-in-dystrophic-muscle
#11
Ryan D Welch, Cyrielle Billon, Aurore-Cecile Valfort, Thomas P Burris, Colin A Flaveny
Duchenne muscular dystrophy (DMD) is a debilitating X-linked disorder that is fatal. DMD patients lack the expression of the structural protein dystrophin caused by mutations within the DMD gene. The absence of functional dystrophin protein results in excessive damage from normal muscle use due to the compromised structural integrity of the dystrophin associated glycoprotein complex. As a result, DMD patients exhibit ongoing cycles of muscle destruction and regeneration that promote inflammation, fibrosis, mitochondrial dysfunction, satellite cell (SC) exhaustion and loss of skeletal and cardiac muscle function...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29212792/differential-effects-of-alcohol-and-its-metabolite-acetaldehyde-on-vascular-smooth-muscle-cell-notch-signaling-and-growth
#12
Ekaterina Hatch, David Morrow, Weimin Liu, Paul A Cahill, Eileen M Redmond
Alcohol (EtOH) consumption can variously affect cardiovascular disease (CVD). Our aim was to compare the effects of EtOH and its primary metabolite acetaldehyde (ACT) on vascular smooth muscle Notch signaling and cell growth that are important for atherogenesis. Human coronary artery smooth muscle cells (HCASMC) were treated with EtOH (25 mM) or ACT (10 μM, 25 μM). As previously reported, EtOH inhibited Notch signaling and growth of HCASMC. In contrast, ACT treatment stimulated HCASMC proliferation (cell counts) and increased proliferating cell nuclear antigen (PCNA) expression, concomitant with stimulation of Notch signaling as determined by increased Notch receptor (N1, N3) and target gene (HRT 1-3) mRNA levels...
December 6, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29210315/expression-of-lamina-proteins-lamin-and-kugelkern-suppresses-stem-cell-proliferation
#13
Roman Petrovsky, Jörg Großhans
The nuclear lamina is involved in numerous cellular functions, such as gene expression, nuclear organization, nuclear stability, and cell proliferation. The mechanism underlying the involvement of lamina is often not clear, especially in physiological or developmental contexts. Here we investigate the role and activity of farnesylated lamina proteins Lamin (Lam) and Kugelkern (Kuk) in proliferation control of intestinal stem cells (ISCs) in adult Drosophila flies. We found that ISCs mutant for Lam or kuk proliferate, whereas overexpression of Lam or Kuk strongly suppressed proliferation...
December 6, 2017: Nucleus
https://www.readbyqxmd.com/read/29208636/homeodomain-interacting-protein-kinase-promotes-tumorigenesis-and-metastatic-cell-behavior
#14
Jessica A Blaquiere, Kenneth Kin Lam Wong, Stephen D Kinsey, Jin Wu, Esther M Verheyen
Aberrations in signaling pathways that regulate tissue growth often lead to tumorigenesis. Homeodomain interacting protein kinase (Hipk) family members are reported to have distinct and contradictory effects on cell proliferation and tissue growth. From these studies it is clear that much remains to be learned about the roles of Hipk family protein kinases in proliferation and cell behaviour. Previous work has shown that Drosophila Hipk is a potent growth regulator, thus we predicted that it could have a role in tumorigenesis...
November 20, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29208631/the-drosophila-junctophilin-gene-is-functionally-equivalent-to-its-four-mammalian-counterparts-and-is-a-modifier-of-a-huntingtin-poly-q-expansion-and-the-notch-pathway
#15
Eduardo Calpena, Víctor López Del Amo, Mouli Chakraborty, Beatriz Llamusí, Rubén Artero, Carmen Espinós, Máximo I Galindo
Members of the Junctophilin (JPH) protein family have emerged as key actors in all excitable cells with critical implications for human pathophysiology. In mammals this family consists in four members (JPH1-4) that are differentially expressed throughout excitable cells. The analysis of knockout mice lacking JPH subtypes has demonstrated their essential contribution to physiological functions in skeletal and cardiac muscles, and neurons. Moreover, mutations in the human JPH2 gene are associated with hypertrophic and dilated cardiomyopathies; mutations in JPH3 are responsible for the neurodegenerative Huntington's disease-like-2 (HDL2), whereas JPH1 acts as a genetic modifier in CMT2K peripheral neuropathy...
November 20, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29206900/cbx3-inhibits-vascular-smooth-muscle-cell-proliferation-migration-and-neointima-formation
#16
Cheng Zhang, Dan Chen, Eithne Margaret Maguire, Shiping He, Jiangyong Chen, Weiwei An, Mei Yang, Tayyab Adeel Afzal, Le Anh Luong, Li Zhang, Han Lei, Qingchen Wu, Qingzhong Xiao
Objective: To investigate the role of chromobox protein homolog 3 (Cbx3) in vascular smooth muscle cell (VSMC) proliferation, migration and neointima formation following vascular injury. Methods and Results: Overexpression of Cbx3 led to a significant increase in VSMC contractile gene expression and VSMC apoptosis, as well as a dramatic decrease in collagen gene expression, VSMC proliferation and migration. Meanwhile the opposite was observed following inhibition of endogenous Cbx3...
November 30, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29206808/extrinsic-calcitonin-gene-related-peptide-inhibits-hyperoxia-induced-alveolar-epithelial-type-ii-cells-apoptosis-oxidative-stress-and-reactive-oxygen-species-ros-production-by-enhancing-notch-1-and-homocysteine-induced-endoplasmic-reticulum-protein-herp-expression
#17
Yu-Xin Bai, Fang Fang, Jia-Ling Jiang, Feng Xu
BACKGROUND Lung alveolar epithelial type II cells (AEC II) are the most important stem cells in lung tissues, which are critical for wound repair of bronchopulmonary dysplasia (BPD). This study investigated the effects of calcitonin gene-related peptide (CGRP) on AEC II cells exposed to hyperoxia. MATERIAL AND METHODS Neonatal rat AEC II cells were isolated and identified by detecting surfactant protein C (SP-C). Three small interfering RNAs targeting Notch 1 were synthesized and transfected into AEC II. A hyperoxia-exposed AEC II cell injury model was established and was divided into 8 groups...
December 5, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29205612/homeodomain-interacting-protein-kinase-phosphorylates-the-drosophila-paired-box-protein-6-pax6-homologues-twin-of-eyeless-and-eyeless
#18
E L Steinmetz, D N Dewald, U Walldorf
Homeodomain-interacting protein kinase (Hipk), the Drosophila homologue of mammalian HIPK2, plays several important roles in regulating differentiation, proliferation, apoptosis, and stress responses and acts as a mediator for signals of diverse pathways, such as Notch or Wingless signalling. The Paired box protein 6 (Pax6) has two Drosophila homologues, Twin of eyeless (Toy) and Eyeless (Ey). Both stand atop the retinal determination gene network (RDGN), which is essential for proper eye development in Drosophila...
December 4, 2017: Insect Molecular Biology
https://www.readbyqxmd.com/read/29198823/microrna-184-induces-a-commitment-switch-to-epidermal-differentiation
#19
Sara Nagosa, Friederike Leesch, Daria Putin, Swarnabh Bhattacharya, Anna Altshuler, Laura Serror, Aya Amitai-Lange, Waseem Nasser, Edith Aberdam, Matthieu Rouleau, Sudhir G Tattikota, Matthew N Poy, Daniel Aberdam, Ruby Shalom-Feuerstein
miR-184 is a highly evolutionary conserved microRNA (miRNA) from fly to human. The importance of miR-184 was underscored by the discovery that point mutations in miR-184 gene led to corneal/lens blinding disease. However, miR-184-related function in vivo remained unclear. Here, we report that the miR-184 knockout mouse model displayed increased p63 expression in line with epidermal hyperplasia, while forced expression of miR-184 by stem/progenitor cells enhanced the Notch pathway and induced epidermal hypoplasia...
November 23, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29196606/control-of-endothelial-cell-tube-formation-by-notch-ligand-intracellular-domain-interactions-with-activator-protein-1-ap-1
#20
Zary Forghany, Francesca Robertson, Alicia Lundby, Jesper V Olsen, David A Baker
Notch signaling is a ubiquitous signal transduction pathway found in most if not all metazoan cell types characterized to date. It is indispensable for cell differentiation as well as tissue growth, tissue remodelling and apoptosis. Although the canonical Notch signaling pathway is well characterized, accumulating evidence points to the existence of multiple, less well-defined, layers of regulation. In this study, we investigated the function of the intracellular domain (ICD) of the Notch ligand Delta-like 4 (DLL4)...
December 1, 2017: Journal of Biological Chemistry
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