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Notch pathway

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https://www.readbyqxmd.com/read/28549153/chippi-a-novel-method-for-mapping-chimeric-protein-protein-interactions-uncovers-selection-principles-of-protein-fusion-events-in-cancer
#1
Milana Frenkel-Morgenstern, Alessandro Gorohovski, Somnath Tagore, Vaishnovi Sekar, Miguel Vazquez, Alfonso Valencia
Fusion proteins, comprising peptides deriving from the translation of two parental genes, are produced in cancer by chromosomal aberrations. The expressed fusion protein incorporates domains of both parental proteins. Using a methodology that treats discrete protein domains as binding sites for specific domains of interacting proteins, we have cataloged the protein interaction networks for 11 528 cancer fusions (ChiTaRS-3.1). Here, we present our novel method, chimeric protein-protein interactions (ChiPPI) that uses the domain-domain co-occurrence scores in order to identify preserved interactors of chimeric proteins...
May 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28542953/zebrafish-tmem230a-cooperates-with-the-delta-notch-signaling-pathway-to-modulate-endothelial-cell-number-in-angiogenic-vessels
#2
Silvia Carra, Lorenzo Sangiorgio, Paride Pelucchi, Solei Cermenati, Alessandra Mezzelani, Valentina Martino, Mira Palizban, Alberto Albertini, Martin Götte, James Kehler, Gianluca Deflorian, Monica Beltrame, Antonio Giordano, Rolland Reinbold, Franco Cotelli, Gianfranco Bellipanni, Ileana Zucchi
During embryonic development, new arteries and veins form from preexisting vessels in response to specific angiogenic signals. Angiogenic signaling is complex since not all endothelial cells exposed to angiogenic signals respond equally. Some cells will be selected to become tip cells and acquire migration and proliferation capacity necessary for vessel growth while others, the stalk cells become trailer cells that stay connected with pre-existing vessels and act as a linkage to new forming vessels. Additionally, stalk and tip cells have the capacity to interchange their roles...
May 25, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28542174/specification-and-spatial-arrangement-of-cells-in-the-germline-stem-cell-niche-of-the-drosophila-ovary-depend-on-the-maf-transcription-factor-traffic-jam
#3
Trupti Panchal, Xi Chen, Ekaterina Alchits, Youjin Oh, James Poon, Jane Kouptsova, Frank A Laski, Dorothea Godt
Germline stem cells in the Drosophila ovary are maintained by a somatic niche. The niche is structurally and functionally complex and contains four cell types, the escort, cap, and terminal filament cells and the newly identified transition cell. We find that the large Maf transcription factor Traffic jam (Tj) is essential for determining niche cell fates and architecture, enabling each niche in the ovary to support a normal complement of 2-3 germline stem cells. In particular, we focused on the question of how cap cells form...
May 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28539263/nutrients-neurogenesis-and-brain-ageing-from-disease-mechanisms-to-therapeutic-opportunities
#4
REVIEW
Marco Fidaleo, Virve Cavallucci, Giovambattista Pani
Appreciation of the physiological relevance of mammalian adult neurogenesis has in recent years rapidly expanded from a phenomenon of homeostatic cell replacement and brain repair to the current view of a complex process involved in high order cognitive functions. In parallel, an array of endogenous or exogenous triggers of neurogenesis have also been identified, among which metabolic and nutritional cues have drawn significant attention. Converging evidence from animal and in vitro studies point to nutrient sensing and energy metabolism as major physiological determinants of neural stem cell fate, and modulators of the whole neurogenic process...
May 21, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28536097/dynamic-regulation-of-vegf-inducible-genes-by-an-erk-erg-p300-transcriptional-network
#5
Jason E Fish, Manuel Cantu Gutierrez, Lan T Dang, Nadiya Khyzha, Zhiqi Chen, Shawn Veitch, Henry S Cheng, Melvin Khor, Lina Antounians, Makon-Sébastien Njock, Emilie Boudreau, Alexander M Herman, Alexander M Rhyner, Oscar E Ruiz, George T Eisenhoffer, Alejandra Medina-Rivera, Michael D Wilson, Joshua D Wythe
The transcriptional pathways activated downstream of Vascular Endothelial Growth Factor (VEGF) signaling during angiogenesis remain incompletely characterized. By assessing the signals responsible for induction of the Notch ligand, Delta-Like 4 (DLL4) in endothelial cells we find that activation of the MAPK/ERK pathway mirrors the rapid and dynamic induction of DLL4 transcription and that this pathway is required for DLL4 expression. Furthermore, VEGF/ERK signaling induces phosphorylation and activation of the ETS transcription factor ERG, a prerequisite for DLL4 induction...
May 23, 2017: Development
https://www.readbyqxmd.com/read/28534077/white-matter-injury-in-the-preterm-infant-pathology-and-mechanisms
#6
REVIEW
Stephen A Back
The human preterm brain is particularly susceptible to cerebral white matter injury (WMI) that disrupts the normal progression of developmental myelination. Advances in the care of preterm infants have resulted in a sustained reduction in the severity of WMI that has shifted from more severe focal necrotic lesions to milder diffuse WMI. Nevertheless, WMI remains a global health problem and the most common cause of chronic neurological morbidity from cerebral palsy and diverse neurobehavioral disabilities. Diffuse WMI involves maturation-dependent vulnerability of the oligodendrocyte (OL) lineage with selective degeneration of late oligodendrocyte progenitors (preOLs) triggered by oxidative stress and other insults...
May 22, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28533486/galectin-3-acts-as-an-angiogenic-switch-to-induce-tumor-angiogenesis-via-jagged-1-notch-activation
#7
Sofia Nascimento Dos Santos, Helen Sheldon, Jonathas Xavier Pereira, Christopher Paluch, Esther M Bridges, Márcia Curry El-Cheikh, Adrian L Harris, Emerson Soares Bernardes
Angiogenesis is a coordinated process tightly regulated by the balance between Delta-like-4 (DLL4) and Jagged-1 (JAG1) in endothelial cells. Here we show that galectin-3 (gal-3), a glycan-binding protein secreted by cancer cells under hypoxic conditions, triggers sprouting angiogenesis, assisted by hypoxic changes in the glycosylation status of endothelial cells that enhance binding to gal-3. Galectin-3's proangiogenic functions were found to be predominantly dependent on the Notch ligand JAG1. Differential direct binding to JAG1 was shown by surface plasmon resonance assay...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28526588/adam10-and-%C3%AE-secretase-regulate-sensory-regeneration-in-the-avian-vestibular-organs
#8
Mark E Warchol, Jennifer Stone, Matthew Barton, Jeffrey Ku, Rose Veile, Nicolas Daudet, Michael Lovett
The loss of sensory hair cells from the inner ear is a leading cause of hearing and balance disorders. The mammalian ear has a very limited ability to replace lost hair cells, but the inner ears of non-mammalian vertebrates can spontaneously regenerate hair cells after injury. Prior studies have shown that replacement hair cells are derived from epithelial supporting cells and that the differentiation of new hair cells is regulated by the Notch signaling pathway. The present study examined molecular influences on regeneration in the avian utricle, which has a particularly robust regenerative ability...
May 16, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28525978/notch-ligand-delta-like-1-as-a-novel-molecular-target-in-childhood-neuroblastoma
#9
P Bettinsoli, G Ferrari-Toninelli, S A Bonini, C Prandelli, M Memo
BACKGROUND: Neuroblastoma is the most common extracranial solid malignancy in childhood, responsible for 15% of all pediatric cancer deaths. It is an heterogeneous disease that does not always respond to classical therapy; so the identification of new and specific molecular targets to improve existing therapy is needed. We have previously demonstrated the involvement of the Notch pathway in the onset and progression of neuroblastoma. In this study we further investigated the role of Notch signaling and identified Delta-like 1 (DLL1) as a novel molecular target in neuroblastoma cells with a high degree of MYCN amplification, which is a major oncogenic driver in neuroblastoma...
May 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28523980/diverse-endometrial-mrna-signatures-during-the-window-of-implantation-in-patients-with-repeated-implantation-failure
#10
Cheng Shi, Hong Jing Han, Li Juan Fan, Jing Guan, Xing Bang Zheng, Xi Chen, Rong Liang, Xiao Wei Zhang, Kun Kun Sun, Qing Hua Cui, Huan Shen
High endometrial receptivity in the window of implantation (WOI) is essential for successful implantation. However, a diagnostic tool with high specificity for impaired endometrial receptivity remains to be developed. We collected endometrium specimens during the WOI from patients with RIF and women who conceived after one IVF/ICSI attempt. We conducted mRNA microarray on the samples followed by relevant comparative and functional analysis. Microarray analysis revealed 357 dysregulated mRNAs between the two groups...
May 19, 2017: Human Fertility: Journal of the British Fertility Society
https://www.readbyqxmd.com/read/28522590/notch-inhibitor-pf-03084014-inhibits-hepatocellular-carcinoma-growth-and-metastasis-via-suppression-of-cancer-stemness-due-to-reduced-activation-of-notch1-stat3
#11
Chuan Xing Wu, Aimin Xu, Cathy C Zhang, Peter Olson, Lin Chen, Terence K Lee, Tan To Cheung, Chung Mau Lo, Xiao Qi Wang
Aberrant activation of the Notch signaling pathway is implicated in many solid tumors, including hepatocellular carcinoma (HCC), indicating a potential use of Notch inhibitors for treatment. In this study, we investigated the antitumor and antimetastasis efficacy of the novel Notch inhibitor (γ-secretase inhibitor) PF-03084014 in HCC. HCC spherical cells (stem-like cancer cells), a sphere-derived orthotopic tumor model and one patient-derived xenograft (PDX) model were used in our experiment. We demonstrated that PF-03084014 inhibited the self-renewal and proliferation of cancer stem cells...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28521042/induced-pluripotent-stem-cell-modelling-of-hlhs-underlines-the-contribution-of-dysfunctional-notch-signalling-to-impaired-cardiogenesis
#12
Chunbo Yang, Yaobo Xu, Min Yu, David Lee, Sameer Alharti, Nicola Hellen, Noor Ahmad Shaik, Babajan Banaganapalli, Hussein Ali Mohamoud Sheikh, Elango Ramu, Stefan Przyborski, Gennadiy Tenin, Simon Williams, John O'Sullivan, Osman O Al-Radi, Jameel Atta, Sian E Harding, Bernard Keavney, Majlinda Lako, Lyle Armstrong
Hypoplastic left heart syndrome (HLHS) is among the most severe forms of congenital heart disease. Although the consensus view is that reduced flow through the left heart during development is a key factor in the development of the condition, the molecular mechanisms leading to hypoplasia of left heart structures are unknown. We have generated induced pluripotent stem cells (iPSC) from five HLHS patients and two unaffected controls, differentiated these to cardiomyocytes and identified reproducible in vitro cellular and functional correlates of the HLHS phenotype...
May 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28520516/mesenchymal-stem-cell-migration-and-proliferation-are-mediated-by-hypoxia-inducible-factor-1%C3%AE-upstream-of-notch-and-sumo-pathways
#13
María Ciria, Nahuel A García, Imelda Ontoria-Oviedo, Hernán González-King, Rubén Carrero, José Luis De La Pompa, José Anastasio Montero, Pilar Sepúlveda
Mesenchymal stem cells (MSCs) are effective in treating several pathologies. We and others have demonstrated that hypoxia or hypoxia-inducible factor 1 alpha (HIF-1α) stabilization improves several MSC functions, including cell adhesion, migration, and proliferation, thereby increasing their therapeutic potential. To further explore the mechanisms induced by HIF-1α in MSCs, we studied its relationship with Notch signaling and observed that overexpression of HIF-1α in MSCs increased protein levels of the Notch ligands Jagged 1-2 and Delta-like (Dll)1, Dll3, and Dll4 and potentiated Notch signaling only when this pathway was activated...
May 18, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28513901/transcriptomic-profiling-reveals-disordered-regulation-of-surfactant-homeostasis-in-neonatal-cloned-bovines-with-collapsed-lungs-and-respiratory-distress
#14
Yan Liu, Yifan Rao, Xiaojing Jiang, Fanyi Zhang, Linhua Huang, Weihua Du, Haisheng Hao, Xueming Zhao, Dong Wang, Qiuling Jiang, Huabin Zhu, Xiuzhu Sun
Respiratory distress is a major cause of mortality in cloned neonatal animals, but its pathogenesis remains poorly understood. Here, we used necropsy and histology procedures to evaluate the lungs of cloned neonatal bovines dying of respiratory distress, finding incomplete lung dilation, alveolar collapse, and thickened alveolar walls. Comparison of the transcriptomes between collapsed lungs of cloned bovines and their normal counterparts revealed 1373 differentially expressed genes in collapsed lungs (p < 0...
May 17, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28513598/yap-taz-link-cell-mechanics-to-notch-signalling-to-control-epidermal-stem-cell-fate
#15
Antonio Totaro, Martina Castellan, Giusy Battilana, Francesca Zanconato, Luca Azzolin, Stefano Giulitti, Michelangelo Cordenonsi, Stefano Piccolo
How the behaviour of somatic stem cells (SCs) is influenced by mechanical signals remains a black-box in cell biology. Here we show that YAP/TAZ regulation by cell shape and rigidity of the extracellular matrix (ECM) dictates a pivotal SC decision: to remain undifferentiated and grow, or to activate a terminal differentiation programme. Notably, mechano-activation of YAP/TAZ promotes epidermal stemness by inhibition of Notch signalling, a key factor for epidermal differentiation. Conversely, YAP/TAZ inhibition by low mechanical forces induces Notch signalling and loss of SC traits...
May 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28512190/hematopoietic-origin-of-langerhans-cell-histiocytosis-and-erdheim-chester-disease-in-adults
#16
Paul Milne, Venetia Bigley, Chris M Bacon, Antoine Néel, Naomi McGovern, Simon Bomken, Muzlifah Haniffa, Eli L Diamond, Benjamin H Durham, Johannes Visser, David Hunt, Harsha Gunawardena, Mac Macheta, Kenneth L McClain, Carl Allen, Omar Abdel-Wahab, Matthew Collin
Langerhans cell histiocytosis (LCH) and Erdheim Chester Disease (ECD) are rare histiocytic disorders induced by somatic mutation of MAP kinase pathway genes. BRAF(V600E) mutation is the most common mutation in both conditions and also occurs in the hematopoietic neoplasm hairy cell leukemia (HCL). It is not known if adult LCH or ECD arise from hematopoietic stem cells (HSC) nor which potential blood borne precursors lead to the formation of histiocytic lesions. In this study, BRAF V600E allele-specific PCR was used to map the neoplastic clone in 20 adults with LCH ECD and HCL...
May 16, 2017: Blood
https://www.readbyqxmd.com/read/28507201/sensitivity-of-non-small-cell-lung-cancer-to-erlotinib-is-regulated-by-the-notch-mir-223-fbxw7-pathway
#17
Haiwei Zhang, Fanglin Chen, Yongpeng He, Lin Yi, Chuang Ge, Xiaolong Shi, Chao Tang, Donglin Wang, Yongzhong Wu, Weiqi Nian
Recent evidence supports a role for microRNA-223 (miR-223) in modulating tumor cell sensitivity to chemotherapeutic drugs; however, its role in cellular resistance to the effects of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) used in treatment of non-small cell lung cancer (NSCLC) remains to be elucidated. The levels of miR-223 in parental cell line (HCC827) and erlotinib resistant HCC827 cell line (HCC827/ER)  were detected by qRT-PCR. HCC827/ER cells were treated with MK-2206 to block the Akt signaling pathway or RO4929097 to block the Notch signaling pathway, and then transfected with a miR-223 inhibitor or interference expression plasmid of F-Box/WD repeat-containing protein 7 (FBXW7) or insulin-like growth factor 1 receptor (IGF1R)...
May 15, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28506315/molecular-mechanisms-underlying-osteoarthritis-development-notch-and-nf-%C3%AE%C2%BAb
#18
REVIEW
Taku Saito, Sakae Tanaka
Osteoarthritis (OA) is a multi-factorial and highly prevalent joint disorder worldwide. Since the establishment of murine surgical knee OA models in 2005, many of the key molecules and signalling pathways responsible for OA development have been identified. Here we review the roles of two multi-functional signalling pathways in OA development: Notch and nuclear factor kappa-light-chain-enhancer of activated B cells. Previous studies have identified various aspects of articular chondrocyte regulation by these pathways...
May 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28501774/tuning-of-major-signaling-networks-tgf-%C3%AE-wnt-notch-and-hedgehog-by-mirnas-in-human-stem-cells-commitment-to-different-lineages-possible-clinical-application
#19
REVIEW
Sedigheh Fekri Aval, Hajie Lotfi, Roghayeh Sheervalilou, Nosratollah Zarghami
Two distinguishing characteristics of stem cells, their continuous division in the undifferentiated state and growth into any cell types, are orchestrated by a number of cell signaling pathways. These pathways act as a niche factor in controlling variety of stem cells. The core stem cell signaling pathways include Wingless-type (Wnt), Hedgehog (HH), and Notch. Additionally, they critically regulate the self-renewal and survival of cancer stem cells. Conversely, stem cells' main properties, lineage commitment and stemness, are tightly controlled by epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNA-mediated regulatory events...
May 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28499720/t-follicular-helper-and-th2-cells-in-allergic-responses
#20
REVIEW
Masato Kubo
IL-4 is a cytokine commonly secreted by TH2 and follicular helper T (TFH) cells after antigenic sensitization. TH2 cells have been thought to be the major contributor of B cell help as a source of IL-4 responsible for class switch recombination to Immunoglobulin G1 (IgG1) and Immunoglobulin E (IgE). Importantly, there are some differences in transcriptional regulation between these two T cell subsets. The IL-4 production by TH2 and TFH cells is distinctively regulated by two pathways, GATA-3-mediated Il4-HS2 enhancer and Notch mediated Il4-CNS-2 enhancer...
May 9, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
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