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Notch signaling

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https://www.readbyqxmd.com/read/28098823/integrative-mirna-gene-expression-analysis-enables-refinement-of-associated-biology-and-prediction-of-response-to-cetuximab-in-head-and-neck-squamous-cell-cancer
#1
Loris De Cecco, Marco Giannoccaro, Edoardo Marchesi, Paolo Bossi, Federica Favales, Laura D Locati, Lisa Licitra, Silvana Pilotti, Silvana Canevari
This paper documents the process by which we, through gene and miRNA expression profiling of the same samples of head and neck squamous cell carcinomas (HNSCC) and an integrative miRNA-mRNA expression analysis, were able to identify candidate biomarkers of progression-free survival (PFS) in patients treated with cetuximab-based approaches. Through sparse partial least square-discriminant analysis (sPLS-DA) and supervised analysis, 36 miRNAs were identified in two components that clearly separated long- and short-PFS patients...
January 14, 2017: Genes
https://www.readbyqxmd.com/read/28098794/ftr82-is-critical-for-vascular-patterning-during-zebrafish-development
#2
Hsueh-Wei Chang, Wen-Der Wang, Chien-Chih Chiu, Chiou-Hua Chen, Yi-Shan Wang, Zih-Ying Chen, Wangta Liu, Ming-Hong Tai, Zhi-Hong Wen, Chang-Yi Wu
Cellular components and signaling pathways are required for the proper growth of blood vessels. Here, we report for the first time that a teleost-specific gene ftr82 (finTRIM family, member 82) plays a critical role in vasculature during zebrafish development. To date, there has been no description of tripartite motif proteins (TRIM) in vascular development, and the role of ftr82 is unknown. In this study, we found that ftr82 mRNA is expressed during the development of vessels, and loss of ftr82 by morpholino (MO) knockdown impairs the growth of intersegmental vessels (ISV) and caudal vein plexus (CVP), suggesting that ftr82 plays a critical role in promoting ISV and CVP growth...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28098310/a-computational-model-predicts-genetic-nodes-that-allow-switching-between-species-specific-responses-in-a-conserved-signaling-network
#3
Adriana T Dawes, David Wu, Karley K Mahalak, Edward M Zitnik, Natalia Kravtsova, Haiwei Su, Helen M Chamberlin
Cell signaling networks regulate a variety of developmental and physiological processes, and changes in their response to external stimuli are often implicated in disease initiation and progression. To elucidate how different responses can arise from conserved signaling networks, we have developed a mathematical model of the well-characterized Caenorhabditis vulval development network involving EGF, Wnt and Notch signaling that recapitulates biologically observed behaviors. We experimentally block a specific element of the EGF pathway (MEK), and find different behaviors in vulval development in two Caenorhabditis species, C...
January 18, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28097825/signalling-pathways-involved-in-hypoxia-induced-renal-fibrosis
#4
REVIEW
Minna Liu, Xiaoxuan Ning, Rong Li, Zhen Yang, Xiaoxia Yang, Shiren Sun, Qi Qian
Renal fibrosis is the common pathological hallmark of progressive chronic kidney disease (CKD) with diverse aetiologies. Recent researches have highlighted the critical role of hypoxia during the development of renal fibrosis as a final common pathway in end-stage kidney disease (ESKD), which joints the scientist's attention recently to exploit the molecular mechanism underlying hypoxia-induced renal fibrogenesis. The scaring formation is a multilayered cellular response and involves the regulation of multiple hypoxia-inducible signalling pathways and complex interactive networks...
January 18, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28095743/adult-murine-pancreatic-progenitors-require-egf-and-nicotinamide-for-self-renewal-and-differentiation-in-a-serum-and-conditioned-medium-free-culture
#5
Lena Wedeken, Angela Luo, Jacob R Tremblay, Jeffrey Rawson, Liang Jin, Dan Gao, Janine Quijano, Hsun Teresa Ku
Adult pancreatic stem and progenitor cells may serve as an alternative source of insulin-secreting endocrine cells in cell replacement therapy for type 1 diabetes, but much remained unknown about these cells. We previously identified adult murine pancreatic progenitor-like cells that displayed in vitro self-renewal and tri-lineage differentiation activities in a 3-dimensional colony/organoid assay containing 1% methylcellulose and 5% Matrigel. However, the presence of other undefined culture components, such as serum and conditioned medium, has prevented a complete understanding of the signals required for progenitor cell growth...
January 17, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28094257/pten-is-necessary-for-the-quiescence-and-maintenance-of-adult-muscle-stem-cells
#6
Feng Yue, Pengpeng Bi, Chao Wang, Tizhong Shan, Yaohui Nie, Timothy L Ratliff, Timothy P Gavin, Shihuan Kuang
Satellite cells (SCs) are myogenic stem cells required for regeneration of adult skeletal muscles. A proper balance among quiescence, activation and differentiation is essential for long-term maintenance of SCs and their regenerative function. Here we show a function of Pten (phosphatase and tensin homologue) in quiescent SCs. Deletion of Pten in quiescent SCs leads to their spontaneous activation and premature differentiation without proliferation, resulting in depletion of SC pool and regenerative failure...
January 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28092987/emerging-treatment-approaches-for-myeloma-related-bone-disease
#7
Maria Gavriatopoulou, Meletios A Dimopoulos, Efstathios Kastritis, Evangelos Terpos
Multiple myeloma is characterized by the presence of osteolytic lesions that leads to devastating skeletal-related events in the majority of patients. Myeloma bone disease is attributed to increased osteoclastic and suppressed osteoblastic activity. Areas covered: Bisphosphonates remain the main treatment option, however they have limitations on their own. Understanding the pathogenesis of myeloma bone disease may provide a roadmap for new therapeutic approaches. The pathway of RANKRANKLOPG pathway has revealed denosumab, a monoclonal antibody targeting RANKL as a novel emerging therapy for myeloma-related bone disease...
January 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28090565/thbs2-is-a-candidate-modifier-of-liver-disease-severity-in-alagille-syndrome
#8
Ellen A Tsai, Melissa A Gilbert, Christopher M Grochowski, Lara A Underkoffler, He Meng, Xiaojie Zhang, Michael M Wang, Hailu Shitaye, Kurt D Hankenson, David Piccoli, Henry Lin, Binita M Kamath, Marcella Devoto, Nancy B Spinner, Kathleen M Loomes
BACKGROUND & AIMS: Alagille syndrome is an autosomal-dominant, multisystem disorder caused primarily by mutations in JAG1, resulting in bile duct paucity, cholestasis, cardiac disease, and other features. Liver disease severity in Alagille syndrome is highly variable, however, factors influencing the hepatic phenotype are unknown. We hypothesized that genetic modifiers may contribute to the variable expressivity of this disorder. METHODS: We performed a genome-wide association study in a cohort of Caucasian subjects with known pathogenic JAG1 mutations, comparing patients with mild vs severe liver disease, followed by functional characterization of a candidate locus...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28089430/high-variability-of-expression-profiles-of-homeologous-genes-for-wnt-hh-notch-and-hippo-signaling-pathways-in-xenopus-laevis
#9
Tatsuo Michiue, Takayoshi Yamamoto, Yuuri Yasuoka, Toshiyasu Goto, Takafumi Ikeda, Kei Nagura, Takuya Nakayama, Masanori Taira, Tsutomu Kinoshita
Cell signaling pathways, such as Wnt, Hedgehog (Hh), Notch, and Hippo, are essential for embryogenesis, organogenesis, and tissue homeostasis. In this study, we analyzed 415 genes involved in these pathways in the allotetraploid frog, Xenopus laevis. Most genes are retained in two subgenomes called L and S (193 homeologous gene pairs and 29 singletons). This conservation rate of homeologs is much higher than that of all genes in the X. laevis genome (86.9% vs 60.2%). Among singletons, 24 genes are retained in the L subgenome, a rate similar to the average for all genes (82...
January 12, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28089369/deciphering-the-fringe-mediated-notch-code-identification-of-activating-and-inhibiting-sites-allowing-discrimination-between-ligands
#10
Shinako Kakuda, Robert S Haltiwanger
Fringe proteins are β3-N-acetylglucosaminyltransferases that modulate Notch activity by modifying O-fucose residues on epidermal growth factor-like (EGF) repeats of Notch. Mammals have three Fringes: Lunatic, Manic, and Radical. While Lunatic and Manic Fringe inhibit Notch1 activation from Jagged1 and enhance activation from Delta-like 1, Radical Fringe enhances signaling from both. We used a mass spectrometry approach to determine whether the variable effects of Fringes on Notch1 result from generation of unique glycosylation patterns on Notch1...
December 29, 2016: Developmental Cell
https://www.readbyqxmd.com/read/28087636/r-spondin-1-is-required-for-specification-of-hematopoietic-stem-cells-through-wnt16-and-vegfa-signaling-pathways
#11
Jamie R Genthe, Wilson K Clements
Hematopoietic stem cells (HSCs) are the therapeutic component of bone marrow transplants, but finding immune-compatible donors limits treatment availability and efficacy. Recapitulation of endogenous specification during development is a promising approach to directing HSC specification in vitro, but current protocols are not capable of generating authentic HSCs with high efficiency. Across phyla, HSCs arise from hemogenic endothelium in the ventral floor of the dorsal aorta concurrent with arteriovenous specification and intersegmental vessel (ISV) sprouting, processes regulated by Notch and Wnt...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28086833/delta-like-4-notch-signaling-promotes-apc-min-tumor-initiation-through-angiogenic-and-non-angiogenic-related-mechanisms
#12
Marina Badenes, Alexandre Trindade, Hugo Pissarra, Luís Lopes-da-Costa, António Duarte
BACKGROUND: Delta like 4 (Dll4)/Notch signaling is a key regulator of tumor angiogenesis. Additionally, the role of Dll4 has been studied on tumor stem cells. However, as these cells are implicated in tumor angiogenesis, it is conceivable that the effect of Dll4 on these cells may be a consequence of its angiogenic function. Our aim was to evaluate the expression and dissect the functions of Dll4 in the Apc (Min/+) model of colorectal cancer. METHODS: We evaluated the protein expression pattern of Dll4 and other Notch members in the Apc (Min/+) tumors relatively to the normal gut and compared endothelial-specific with ubiquitous Dll4 knockout mice on an Apc (Min/+) background...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28081466/long-non-coding-rna-zfas1-is-an-unfavourable-prognostic-factor-and-promotes-glioma-cell-progression-by-activation-of-the-notch-signaling-pathway
#13
Kai Gao, Zhiwu Ji, Kun She, Qingyan Yang, Lianbin Shao
Survival of patients with glioma remains poor, which is largely attributed to active carcinogenesis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play key roles in tumor initiation and progression. However, the function of lncRNA ZFAS1 in glioma is still unclear. In the current study, we found that ZFAS1 was upregulated in glioma tissues and cell lines. High ZFAS1 expression in glioma tissues was significantly correlated with advanced tumor stage and poor overall survival. Furthermore, in vitro assays demonstrated that ZFAS1 inhibition significantly suppressed glioma cell proliferation, migration and invasion...
January 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28077657/lmp1-and-lmp2a-collaborate-to-promote-epstein-barr-virus-ebv-induced-b-cell-lymphomas-in-a-cord-blood-humanized-mouse-model-but-are-not-essential
#14
Shi-Dong Ma, Ming-Han Tsai, James C Romero-Masters, Erik A Ranheim, Shane M Huebner, Jillian Bristol, Henri-Jacques Delecluse, Shannon C Kenney
: Epstein-Barr virus (EBV) infection is associated with B cell lymphomas in humans. The ability of EBV to convert human B cells into long-lived lymphoblastoid cell lines (LCLs) in vitro requires the collaborative effects of EBNA2 (which hijacks notch signaling), LMP1 (which mimics CD40 signaling), and EBNA 3A/3C (which inhibit oncogene-induced senescence and apoptosis). However, we recently showed that an LMP1-deleted EBV mutant induces B cell lymphomas in a newly developed cord blood-humanized mouse model that allows EBV-infected B cells to interact with CD4 T cells (the major source of CD40 ligand)...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28071661/neuronal-sflt1-and-vegfaa-determine-venous-sprouting-and-spinal-cord-vascularization
#15
Raphael Wild, Alina Klems, Masanari Takamiya, Yuya Hayashi, Uwe Strähle, Koji Ando, Naoki Mochizuki, Andreas van Impel, Stefan Schulte-Merker, Janna Krueger, Laetitia Preau, Ferdinand le Noble
Formation of organ-specific vasculatures requires cross-talk between developing tissue and specialized endothelial cells. Here we show how developing zebrafish spinal cord neurons coordinate vessel growth through balancing of neuron-derived Vegfaa, with neuronal sFlt1 restricting Vegfaa-Kdrl mediated angiogenesis at the neurovascular interface. Neuron-specific loss of flt1 or increased neuronal vegfaa expression promotes angiogenesis and peri-neural tube vascular network formation. Combining loss of neuronal flt1 with gain of vegfaa promotes sprout invasion into the neural tube...
January 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28069038/motility-of-glioblastoma-cells-is-driven-by-netrin-1-induced-gain-of-stemness
#16
Irene Ylivinkka, Harri Sihto, Olli Tynninen, Yizhou Hu, Aki Laakso, Riku Kivisaari, Pirjo Laakkonen, Jorma Keski-Oja, Marko Hyytiäinen
BACKGROUND: Glioblastoma is an untreatable brain cancer. The tumors contain a population of stem-like cells which are highly invasive and resistant to therapies. These cells are the main reason for the lethality of glioblastoma. Extracellular guidance molecule netrin-1 promotes the invasiveness and survival of various cancer cell types. We have previously found that netrin-1 activates Notch signaling, and Notch signaling associates with cell stemness. Therefore, we have here investigated the effects of netrin-1 on glioblastoma pathogenesis and glioblastoma cell stemness...
January 9, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28068481/micrornas-and-periodontal-homeostasis
#17
X Luan, X Zhou, J Trombetta-eSilva, M Francis, A K Gaharwar, P Atsawasuwan, T G H Diekwisch
MicroRNAs (miRNAs) are a group of small RNAs that control gene expression in all aspects of eukaryotic life, primarily through RNA silencing mechanisms. The purpose of the present review is to introduce key miRNAs involved in periodontal homeostasis, summarize the mechanisms by which they affect downstream genes and tissues, and provide an introduction into the therapeutic potential of periodontal miRNAs. In general, miRNAs function synergistically to fine-tune the regulation of biological processes and to remove expression noise rather than by causing drastic changes in expression levels...
January 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28068334/two-paralogous-tetraspanins-tsp-12-and-tsp-14-function-with-the-adam10-metalloprotease-sup-17-to-promote-bmp-signaling-in-caenorhabditis-elegans
#18
Lin Wang, Zhiyu Liu, Herong Shi, Jun Liu
The highly conserved bone morphogenetic protein (BMP) signaling pathway regulates many developmental and homeostatic processes. While the core components of the BMP pathway have been well studied, much research is needed for understanding the mechanisms involved in the precise spatiotemporal control of BMP signaling in vivo. Here, we provide evidence that two paralogous and evolutionarily conserved tetraspanins, TSP-12 and TSP-14, function redundantly to promote BMP signaling in C. elegans. We further show that the ADAM10 (a disintegrin and metalloprotease 10) ortholog SUP-17 also functions to promote BMP signaling, and that TSP-12 can bind to and promote the cell surface localization of SUP-17...
January 9, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28068307/transitional-b-cells-commit-to-marginal-zone-b-cell-fate-by-taok3-mediated-surface-expression-of-adam10
#19
Hamida Hammad, Matthias Vanderkerken, Philippe Pouliot, Kim Deswarte, Wendy Toussaint, Karl Vergote, Lana Vandersarren, Sophie Janssens, Ioanna Ramou, Savvas N Savvides, Jody J Haigh, Rudi Hendriks, Manfred Kopf, Katleen Craessaerts, Bart de Strooper, John F Kearney, Daniel H Conrad, Bart N Lambrecht
Notch2 and B cell antigen receptor (BCR) signaling determine whether transitional B cells become marginal zone B (MZB) or follicular B (FoB) cells in the spleen, but it is unknown how these pathways are related. We generated Taok3(-/-) mice, lacking the serine/threonine kinase Taok3, and found cell-intrinsic defects in the development of MZB but not FoB cells. Type 1 transitional (T1) B cells required Taok3 to rapidly respond to ligation by the Notch ligand Delta-like 1. BCR ligation by endogenous or exogenous ligands induced the surface expression of the metalloproteinase ADAM10 on T1 B cells in a Taok3-dependent manner...
January 9, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28067332/photonic-crystal-nanocavity-assisted-rejection-ratio-tunable-notch-microwave-photonic-filter
#20
Yun Long, Jinsong Xia, Yong Zhang, Jianji Dong, Jian Wang
Driven by the increasing demand on handing microwave signals with compact device, low power consumption, high efficiency and high reliability, it is highly desired to generate, distribute, and process microwave signals using photonic integrated circuits. Silicon photonics offers a promising platform facilitating ultracompact microwave photonic signal processing assisted by silicon nanophotonic devices. In this paper, we propose, theoretically analyze and experimentally demonstrate a simple scheme to realize ultracompact rejection ratio tunable notch microwave photonic filter (MPF) based on a silicon photonic crystal (PhC) nanocavity with fixed extinction ratio...
January 9, 2017: Scientific Reports
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