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Notch signaling

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https://www.readbyqxmd.com/read/27926871/in%C3%A2-vivo-visualization-of-cardiomyocyte-apicobasal-polarity-reveals-epithelial-to-mesenchymal-like-transition-during-cardiac-trabeculation
#1
Vanesa Jiménez-Amilburu, S Javad Rasouli, David W Staudt, Hiroyuki Nakajima, Ayano Chiba, Naoki Mochizuki, Didier Y R Stainier
Despite great strides in understanding cardiac trabeculation, many mechanistic aspects remain unclear. To elucidate how cardiomyocyte shape changes are regulated during this process, we engineered transgenes to label their apical and basolateral membranes. Using these tools, we observed that compact-layer cardiomyocytes are clearly polarized while delaminating cardiomyocytes have lost their polarity. The apical transgene also enabled the imaging of cardiomyocyte apical constriction in real time. Furthermore, we found that Neuregulin signaling and blood flow/cardiac contractility are required for cardiomyocyte apical constriction and depolarization...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926858/g-protein-coupled-receptor-2-interacting-protein-1-controls-stalk-cell-fate-by-inhibiting-delta-like-4-notch1-signaling
#2
Syamantak Majumder, GuoFu Zhu, Xiangbin Xu, Sharon Senchanthisai, Dongyang Jiang, Hao Liu, Chao Xue, Xiaoqun Wang, Heidi Coia, Zhaoqiang Cui, Elaine M Smolock, Richard T Libby, Bradford C Berk, Jinjiang Pang
The spatiotemporal localization and expression of Dll4 are critical for sprouting angiogenesis. However, the related mechanisms are poorly understood. Here, we show that G-protein-coupled receptor-kinase interacting protein-1 (GIT1) is a robust endogenous inhibitor of Dll4-Notch1 signaling that specifically controls stalk cell fate. GIT1 is highly expressed in stalk cells but not in tip cells. GIT1 deficiency remarkably enhances Dll4 expression and Notch1 signaling, resulting in impaired retinal sprouting angiogenesis, which can be rescued by treatment with the Notch inhibitor or Dll4 neutralizing antibody...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27925454/rap1a-promotes-ovarian-cancer-metastasis-via-activation-of-erk-p38-and-notch-signaling
#3
Lili Lu, Jingshu Wang, Yougen Wu, Ping Wan, Gong Yang
As one of the Ras-associated proteins, Rap1A has been linked to cancer initiation and development. However, the precise function of Rap1A in ovarian cancer is still not understood. Here, we show that Rap1A promotes ovarian cancer tumorigenesis and metastasis via stimulating cell proliferation, migration and invasion both in vivo and in vitro. Mechanistic study showed that Rap1A activates extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK) and Notch pathways, leading to the enhanced expression of several epithelial-mesenchymal transition (EMT) markers such as slug, zeb1, vimentin, fibronectin, and MMP9...
December 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27924447/associations-between-polymorphisms-in-the-nicd-domain-of-bovine-notch1-gene-and-growth-traits-in-chinese-qinchuan-cattle
#4
Mei Liu, Chenge Zhang, Xinsheng Lai, Jing Xue, Xianyong Lan, Chuzhao Lei, Yutang Jia, Hong Chen
NOTCH1 is one of the four mammalian Notch receptors, which is involved in the Notch signaling pathway. Specifically, NOTCH1 promotes the proliferation of myogenic precursor cells, and the NICD domain of NOTCH1 can impair regeneration of skeletal muscles. However, similar research on the bovine NOTCH1 gene is lacking. In this study, we detected the polymorphisms of the bovine NOTCH1 gene in a total of 448 individuals from Chinese Qinchuan cattle with DNA pooling, forced PCR-RFLP, and DNA sequencing methods. Five novel SNPs were identified within the NICD domain, and eight haplotypes comprising combinations of these five SNPs were studied as well...
December 6, 2016: Journal of Applied Genetics
https://www.readbyqxmd.com/read/27924063/%C3%AE-np63%C3%AE-and-micrornas-leveraging-the-epithelial-mesenchymal-transition
#5
REVIEW
Andrew J Stacy, Michael P Craig, Suraj Sakaram, Madhavi Kadakia
The epithelial-mesenchymal transition (EMT) is a cellular reprogramming mechanism that is an underlying cause of cancer metastasis. Recent investigations have uncovered an intricate network of regulation involving the TGFβ, Wnt, and Notch signaling pathways and small regulatory RNA species called microRNAs (miRNAs). The activity of a transcription factor vital to the maintenance of epithelial stemness, ΔNp63α, has been shown to modulate the activity of these EMT pathways to either repress or promote EMT...
December 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27923836/the-swi-snf-complex-protein-snr1-is-a-tumor-suppressor-in-drosophila-imaginal-tissues
#6
Gengqiang Xie, Hanqing Chen, Dongyu Jia, Zhiqiang Shu, William Hunt Palmer, Yi-Chun Huang, Xiankun Zeng, Steven X Hou, Renjie Jiao, Wu-Min Deng
Components of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in various human cancers, yet only SMARCB1/hSNF5, a core member of the SWI/SNF complex, is mutated in malignant rhabdoid tumors (MRT). How SMARCB1/hSNF5 functions differently from other members of the SWI/SNF complex remains unclear. Here we use Drosophila imaginal epithelial tissues to demonstrate that Snr1, the conserved homolog of human SMARCB1/hSNF5, prevents tumorigenesis by maintaining normal endosomal trafficking-mediated signaling cascades...
December 6, 2016: Cancer Research
https://www.readbyqxmd.com/read/27923595/vitamin-d-compounds-inhibit-cancer-stem-like-cells-and-induce-differentiation-in-triple-negative-breast-cancer
#7
REVIEW
Naing Lin Shan, Joseph Wahler, Hong Jin Lee, Min Ji Bak, Soumyasri Das Gupta, Hubert Maehr, Nanjoo Suh
Triple-negative breast cancer is one of the least responsive breast cancer subtypes to available targeted therapies due to the absence of hormonal receptors, aggressive phenotypes, and the high rate of relapse. Early breast cancer prevention may therefore play an important role in delaying the progression of triple-negative breast cancer. Cancer stem cells are a subset of cancer cells that are thought to be responsible for tumor progression, treatment resistance, and metastasis. We have previously shown that vitamin D compounds, including a Gemini vitamin D analog BXL0124, suppress progression of ductal carcinoma in situ in vivo and inhibit cancer stem-like cells in MCF10DCIS mammosphere cultures...
December 3, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27923395/regulation-of-downstream-neuronal-genes-by-proneural-transcription-factors-during-initial-neurogenesis-in-the-vertebrate-brain
#8
Michelle Ware, Houda Hamdi-Rozé, Julien Le Friec, Véronique David, Valérie Dupé
BACKGROUND: Neurons arise in very specific regions of the neural tube, controlled by components of the Notch signalling pathway, proneural genes, and other bHLH transcription factors. How these specific neuronal areas in the brain are generated during development is just beginning to be elucidated. Notably, the critical role of proneural genes during differentiation of the neuronal populations that give rise to the early axon scaffold in the developing brain is not understood. The regulation of their downstream effectors remains poorly defined...
December 7, 2016: Neural Development
https://www.readbyqxmd.com/read/27922338/pathophysiology-of-aortic-aneurysm-insights-from-human-genetics-and-mouse-models
#9
Nicole K Wilson, Russell A Gould, Elena Gallo MacFarlane, Mibava Leducq Consortium
Aneurysms are local dilations of an artery that predispose the vessel to sudden rupture. They are often asymptomatic and undiagnosed, resulting in a high mortality rate. The predisposition to develop thoracic aortic aneurysms is often genetically inherited and associated with syndromes affecting connective tissue homeostasis. This review discusses how elucidation of the genetic causes of syndromic forms of thoracic aortic aneurysm has helped identify pathways that contribute to disease progression, including those activated by TGF-β, angiotensin II and Notch ligands...
December 6, 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27922122/identification-of-critical-paralog-groups-with-indispensable-roles-in-the-regulation-of-signaling-flow
#10
Dezso Modos, Johanne Brooks, David Fazekas, Eszter Ari, Tibor Vellai, Peter Csermely, Tamas Korcsmaros, Katalin Lenti
Extensive cross-talk between signaling pathways is required to integrate the myriad of extracellular signal combinations at the cellular level. Gene duplication events may lead to the emergence of novel functions, leaving groups of similar genes - termed paralogs - in the genome. To distinguish critical paralog groups (CPGs) from other paralogs in human signaling networks, we developed a signaling network-based method using cross-talk annotation and tissue-specific signaling flow analysis. 75 CPGs were found with higher degree, betweenness centrality, closeness, and 'bowtieness' when compared to other paralogs or other proteins in the signaling network...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922003/blood-flow-controls-bone-vascular-function-and-osteogenesis
#11
Saravana K Ramasamy, Anjali P Kusumbe, Maria Schiller, Dagmar Zeuschner, M Gabriele Bixel, Carlo Milia, Jaba Gamrekelashvili, Anne Limbourg, Alexander Medvinsky, Massimo M Santoro, Florian P Limbourg, Ralf H Adams
While blood vessels play important roles in bone homeostasis and repair, fundamental aspects of vascular function in the skeletal system remain poorly understood. Here we show that the long bone vasculature generates a peculiar flow pattern, which is important for proper angiogenesis. Intravital imaging reveals that vessel growth in murine long bone involves the extension and anastomotic fusion of endothelial buds. Impaired blood flow leads to defective angiogenesis and osteogenesis, and downregulation of Notch signalling in endothelial cells...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27922002/targeting-the-notch-regulated-non-coding-rna-tug1-for-glioma-treatment
#12
Keisuke Katsushima, Atsushi Natsume, Fumiharu Ohka, Keiko Shinjo, Akira Hatanaka, Norihisa Ichimura, Shinya Sato, Satoru Takahashi, Hiroshi Kimura, Yasushi Totoki, Tatsuhiro Shibata, Mitsuru Naito, Hyun Jin Kim, Kanjiro Miyata, Kazunori Kataoka, Yutaka Kondo
Targeting self-renewal is an important goal in cancer therapy and recent studies have focused on Notch signalling in the maintenance of stemness of glioma stem cells (GSCs). Understanding cancer-specific Notch regulation would improve specificity of targeting this pathway. In this study, we find that Notch1 activation in GSCs specifically induces expression of the lncRNA, TUG1. TUG1 coordinately promotes self-renewal by sponging miR-145 in the cytoplasm and recruiting polycomb to repress differentiation genes by locus-specific methylation of histone H3K27 via YY1-binding activity in the nucleus...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27918591/transcriptomic-analysis-of-mouse-cochlear-supporting-cell-maturation-reveals-large-scale-changes-in-notch-responsiveness-prior-to-the-onset-of-hearing
#13
Juan C Maass, Rende Gu, Tiantian Cai, Ying-Wooi Wan, Silvia C Cantellano, Joanna S T Asprer, Hongyuan Zhang, Hsin-I Jen, Renée K Edlund, Zhandong Liu, Andrew K Groves
Neonatal mouse cochlear supporting cells have a limited ability to divide and trans-differentiate into hair cells, but this ability declines rapidly in the two weeks after birth. This decline is concomitant with the morphological and functional maturation of the organ of Corti prior to the onset of hearing. However, despite this association between maturation and loss of regenerative potential, little is known of the molecular changes that underlie these events. To identify these changes, we used RNA-seq to generate transcriptional profiles of purified cochlear supporting cells from 1- and 6-day-old mice...
2016: PloS One
https://www.readbyqxmd.com/read/27918553/jagged-1-is-a-major-notch-ligand-along-cholangiocarcinoma-development-in-mice-and-humans
#14
L Che, B Fan, M G Pilo, Z Xu, Y Liu, A Cigliano, A Cossu, G Palmieri, R M Pascale, A Porcu, G Vidili, M Serra, F Dombrowski, S Ribback, D F Calvisi, X Chen
Intrahepatic cholangiocarcinoma (ICC) is a rare yet deadly malignancy with limited treatment options. Activation of the Notch signalling cascade has been implicated in cholangiocarcinogenesis. However, while several studies focused on the Notch receptors required for ICC development, little is known about the upstream inducers responsible for their activation. Here, we show that the Jagged 1 (Jag1) ligand is almost ubiquitously upregulated in human ICC samples when compared with corresponding non-tumorous counterparts...
December 5, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27917547/pituitary-stalk-interruption-syndrome-from-clinical-findings-to-pathogenesis
#15
REVIEW
Cheng-Zhi Wang, Ling-Ling Guo, Bai-Yu Han, Xing Su, Qing-Hua Guo, Yi-Ming Mu
Pituitary stalk interruption syndrome is a rare congenital defect manifesting with varying degrees of pituitary hormone deficiency. The signs and symptoms of PSIS during the neonatal period and infancy are often overlooked and therefore diagnosis is delayed. The typical manifestations of PSIS can be detected by magnetic resonance imaging. Several genes in Wnt, Notch and Shh signaling pathways related to hypothalamic-pituitary development, such as PIT1, PROP1, LHX3/LHX4, PROKR2, OTX2, TGIF and HESX1, have been found to be associated with PSIS...
December 5, 2016: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/27916094/-knockdown-of-runx3-inhibits-hypoxia-induced-endothelial-to-mesenchymal-transition-of-human-cardiac-microvascular-endothelial-cells
#16
Yanhua Liu, Bingong Li, Yuqin Wang, Delong Wang, Jin Zou, Xuan Ke, Yanqin Hao
Objective To investigate the effects of Runt-related transcription factor 3 (RUNX3) knockdown on hypoxia-induced endothelial-to-mesenchymal transition (EndoMT) of human cardiac microvascular endothelial cells (HCMECs), and elucidate the underlying molecular mechanism. Methods HCMECs were cultured in hypoxic conditions and infected with RUNX3-RNAi lentivirus to knock-down the expression of RUNX3. Reverse transcription PCR was performed to detect the mRNA expressions of RUNX3 and EndoMT related genes such as CD31, vascular endothelial cadherin (VE-cadherin), α-smooth muscle actin (α-SMA) and fibroblast-specific protein-1 (FSP-1); Western blotting was used to determine the protein expressions of RUNX3, CD31, α-SMA and another molecules involved in EndoMT; and immunofluorescence cytochemistry was applied to observe the colocalization of CD31 and α-SMA...
December 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27913625/absence-of-mir-146a-in-podocytes-increases-risk-of-diabetic-glomerulopathy-via-upregulation-of-erbb4-and-notch-1
#17
Ha Won Lee, Samia Q Khan, Shehryar Khaliqdina, Mehmet M Altintas, Florian Grahammer, Jimmy L Zhao, Kwihey Koh, Nicholas J Tardi, Mohd Hafeez Faridi, Terese Geraghty, David J Cimbaluk, Katalin Susztak, Luis F Moita, David Baltimore, Pierre-Louis Tharaux, Tobias B Huber, Matthias Kretzler, Markus Bitzer, Jochen Reiser, Vineet Gupta
Podocyte injury is an early event in diabetic kidney disease and is a hallmark of glomerulopathy. MicroRNA-146a (miR-146a) is highly expressed in many cell types under homeostatic conditions, and plays an important anti-inflammatory role in myeloid cells. However, its role in podocytes is unclear. Here, we show that miR-146a expression levels decrease in the glomeruli of patients with type 2 diabetes (T2D), which correlates with increased albuminuria and glomerular damage. MiR-146a levels are also significantly reduced in the glomeruli of albuminuric BTBR ob/ob mice, indicating its significant role in maintaining podocyte health...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27913341/quantification-of-shear-wave-scattering-from-far-surface-defects-via-ultrasonic-wavefield-measurements
#18
Alexander J Dawson, Jennifer E Michaels, Joseph W Kummer, Thomas E Michaels
Nondestructive evaluation methods rely on prior knowledge of the expected interaction of ultrasonic waves with defects to inform detection and characterization decisions. Wavefield imaging, which refers to the measurement of signals originating from a spatially fixed source on a two-dimensional rectilinear grid, can be applied to visualize the effect of a subsurface scatterer on surface-measured wave motion. Here, obliquely-incident shear waves are directed at the far surface of a plate containing a through-hole using the well-known angle-beam ultrasonic inspection method...
December 1, 2016: IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
https://www.readbyqxmd.com/read/27909729/self-renewal-molecular-mechanisms-of-colorectal-cancer-stem-cells
#19
Tianhui Pan, Jinghong Xu, Yongliang Zhu
Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) and Hedgehog-Gli (HH-GLI), specific roles mediated by cell surface markers and micro-environmental factors are involved in the regulation of self-renewal...
November 30, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27909410/mechanosensitive-molecular-networks-involved-in-transducing-resistance-exercise-signals-into-muscle-protein-accretion
#20
REVIEW
Emil Rindom, Kristian Vissing
Loss of skeletal muscle myofibrillar protein with disease and/or inactivity can severely deteriorate muscle strength and function. Strategies to counteract wasting of muscle myofibrillar protein are therefore desirable and invite for considerations on the potential superiority of specific modes of resistance exercise and/or the adequacy of low load resistance exercise regimens as well as underlying mechanisms. In this regard, delineation of the potentially mechanosensitive molecular mechanisms underlying muscle protein synthesis (MPS), may contribute to an understanding on how differentiated resistance exercise can transduce a mechanical signal into stimulation of muscle accretion...
2016: Frontiers in Physiology
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