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EphA4

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https://www.readbyqxmd.com/read/28425198/the-cell-adhesion-molecule-epha4-is-involved-in-circadian-clock-functions
#1
Silke Kiessling, Emma K O'Callaghan, Marlène Freyburger, Nicolas Cermakian, Valérie Mongrain
Circadian (~24 h) rhythms of cellular network plasticity in the central circadian clock, the suprachiasmatic nucleus (SCN), have been described. The neuronal network in the SCN regulates photic resetting of the circadian clock as well as stability of the circadian system during both entrained and constant conditions. EphA4, a cell adhesion molecule regulating synaptic plasticity by controlling connections of neurons and astrocytes, is expressed in the SCN. To address whether EphA4 plays a role in circadian photoreception and influences the neuronal network of the SCN, we have analysed circadian wheel-running behavior of EphA4 knockout (EphA4(-/-) ) mice under different light conditions and upon photic resetting, as well as their light-induced protein response in the SCN...
April 20, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28424425/ephrin-b3-supports-glioblastoma-growth-by-inhibiting-apoptosis-induced-by-the-dependence-receptor-epha4
#2
Amélie Royet, Laura Broutier, Marie-May Coissieux, Céline Malleval, Nicolas Gadot, Denis Maillet, Lise Gratadou-Hupon, Agnès Bernet, Pascale Nony, Isabelle Treilleux, Jérôme Honnorat, Daniel Liebl, Laurent Pelletier, François Berger, David Meyronet, Marie Castets, Patrick Mehlen
EphA4, an Ephrins tyrosine kinase receptor, behaves as a dependence receptor (DR) by triggering cell apoptosis in the absence of its ligand Ephrin-B3. DRs act as conditional tumor suppressors, engaging cell death based on ligand availability; this mechanism is bypassed by overexpression of DRs ligands in some aggressive cancers. The pair EphA4/Ephrin-B3 favors survival of neuronal progenitors of the brain subventricular zone, an area where glioblastoma multiform (GBM) are thought to originate. Here, we report that Ephrin-B3 is highly expressed in human biopsies and that it inhibits EphA4 pro-apoptotic activity in tumor cells...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423606/ephrin-b3-supports-glioblastoma-growth-by-inhibiting-apoptosis-induced-by-the-dependence-receptor-epha4
#3
Amélie Royet, Laura Broutier, Marie-May Coissieux, Céline Malleval, Nicolas Gadot, Denis Maillet, Lise Gratadou-Hupon, Agnès Bernet, Pascale Nony, Isabelle Treilleux, Jérôme Honnorat, Daniel Liebl, Laurent Pelletier, François Berger, David Meyronet, Marie Castets, Patrick Mehlen
EphA4, an Ephrins tyrosine kinase receptor, behaves as a dependence receptor (DR) by triggering cell apoptosis in the absence of its ligand Ephrin-B3. DRs act as conditional tumor suppressors, engaging cell death based on ligand availability; this mechanism is bypassed by overexpression of DRs ligands in some aggressive cancers. The pair EphA4/Ephrin-B3 favors survival of neuronal progenitors of the brain subventricular zone, an area where glioblastoma multiform (GBM) are thought to originate. Here, we report that Ephrin-B3 is highly expressed in human biopsies and that it inhibits EphA4 pro-apoptotic activity in tumor cells...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28361918/single-cell-rna-sequencing-identifies-distinct-mouse-medial-ganglionic-eminence-cell-types
#4
Ying-Jiun J Chen, Brad A Friedman, Connie Ha, Steffen Durinck, Jinfeng Liu, John L Rubenstein, Somasekar Seshagiri, Zora Modrusan
Many subtypes of cortical interneurons (CINs) are found in adult mouse cortices, but the mechanism generating their diversity remains elusive. We performed single-cell RNA sequencing on the mouse embryonic medial ganglionic eminence (MGE), the major birthplace for CINs, and on MGE-like cells differentiated from embryonic stem cells. Two distinct cell types were identified as proliferating neural progenitors and immature neurons, both of which comprised sub-populations. Although lineage development of MGE progenitors was reconstructed and immature neurons were characterized as GABAergic, cells that might correspond to precursors of different CINs were not identified...
March 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28351297/epha4-promotes-cell-proliferation-and-cell-adhesion-mediated-drug-resistance-via-the-akt-pathway-in-multiple-myeloma
#5
Linlin Ding, Yaodong Shen, Jing Ni, Yiqing Ou, Yangyu Ou, Hong Liu
Eph receptor A4 (EphA4), a member of the erythropoietin-producing hepatocellular (Eph) family, has been reported to upregulate in several tumors. However, the role of EphA4 in multiple myeloma has not been clarified yet. In this study, we found that EphA4 promoted proliferation of multiple myeloma cells via the regulation of cell cycle. Besides, EphA4 was closely related to cell adhesion of multiple myeloma cells and promoted cell adhesion-mediated drug resistance by enhancing the phosphorylation levels of Akt (p-AKT) expression in multiple myeloma...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28346224/mutant-%C3%AE-2-chimaerin-signals-via-bidirectional-ephrin-pathways-in-duane-retraction-syndrome
#6
Alicia A Nugent, Jong G Park, Yan Wei, Alan P Tenney, Nicole M Gilette, Michelle M DeLisle, Wai-Man Chan, Long Cheng, Elizabeth C Engle
Duane retraction syndrome (DRS) is the most common form of congenital paralytic strabismus in humans and can result from α2-chimaerin (CHN1) missense mutations. We report a knockin α2-chimaerin mouse (Chn1KI/KI) that models DRS. Whole embryo imaging of Chn1KI/KI mice revealed stalled abducens nerve growth and selective trochlear and first cervical spinal nerve guidance abnormalities. Stalled abducens nerve bundles did not reach the orbit, resulting in secondary aberrant misinnervation of the lateral rectus muscle by the oculomotor nerve...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28320388/exploring-the-fgfr3-related-oncogenic-mechanism-in-bladder-cancer-using-bioinformatics-strategy
#7
Wei Cao, Enguang Ma, Li Zhou, Tan Yuan, Chunying Zhang
BACKGROUND: Aberrant activation of fibroblast growth factor receptor 3 (FGFR3) is frequently observed in bladder cancer, but how it involved in carcinogenesis is not well understood. The current study was aimed to investigate the underlying mechanism on the progression of bladder cancer. METHODS: The GSE41035 dataset downloaded from Gene Expression Omnibus was used to identify the differentially expressed genes (DEGs) between bladder cancer cell line RT112 with or without depletion of FGFR3, and gene ontology enrichment analysis was performed...
March 20, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28258169/epha4-regulates-neuroblast-and-astrocyte-organization-in-a-neurogenic-niche
#8
Krysti L Todd, Kasey L Baker, Matthew B Eastman, Frederick W Kolling, Alexandra G Trausch, Craig E Nelson, Joanne C Conover
Significant migration cues are required to guide and contain newly generated rodent subventricular zone (SVZ) neuroblasts as they transit along the lateral ventricles and then through the anterior forebrain to their ultimate site of differentiation in the olfactory bulbs (OBs). These cues enforce strict neuroblast spatial boundaries within the dense astroglial meshwork of the SVZ and rostral migratory stream (RMS), yet are permissive to large-scale neuroblast migration. Therefore, the molecular mechanisms that define these cues and control dynamic interactions between migratory neuroblasts and surrounding astrocytes are of particular interest...
March 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28196613/potent-and-selective-epha4-agonists-for-the-treatment-of-als
#9
Bainan Wu, Surya K De, Anna Kulinich, Ahmed F Salem, Jordan Koeppen, Rengang Wang, Elisa Barile, Si Wang, Dongxiang Zhang, Iryna Ethell, Maurizio Pellecchia
Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease that affects motor neurons. Recent studies identified the receptor tyrosine kinase EphA4 as a disease-modifying gene that is critical for the progression of motor neuron degeneration. We report on the design and characterization of a family of EphA4 targeting agents that bind to its ligand binding domain with nanomolar affinity. The molecules exhibit excellent selectivity and display efficacy in a SOD1 mutant mouse model of ALS. Interestingly, the molecules appear to act as agonists for the receptor in certain surrogate cellular assays...
March 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28153688/the-identification-of-a-novel-isoform-of-epha4-and-its-expression-in-sod1-g93a-mice
#10
Jing Zhao, Andrew W Boyd, Perry F Bartlett
Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of motor neurons, leading to progressive muscle atrophy and fatal paralysis. Mutations in more than 20 genes, including full-length EphA4 (EphA4-FL), have been implicated in this pathogenesis. The present study aimed to identify novel isoforms of EphA4-FL and to investigate the expression of EphA4-FL and its isoforms in the superoxide dismutase 1 (SOD1) mutant mouse model of ALS. Two novel transcripts were verified in mouse and humans...
April 7, 2017: Neuroscience
https://www.readbyqxmd.com/read/28130310/reestablishment-of-glucose-inhibition-of-glucagon-secretion-in-small-pseudoislets
#11
Christopher A Reissaus, David W Piston
Misregulated hormone secretion from the islet of Langerhans is central to the pathophysiology of diabetes. Although insulin plays a key role in glucose regulation, the importance of glucagon is increasingly acknowledged. However, the mechanisms that regulate glucagon secretion from α-cells are still unclear. We used pseudoislets reconstituted from dispersed islet cells to study α-cells with and without various indirect effects from other islet cells. Dispersed islet cells secrete aberrant levels of glucagon and insulin at basal and elevated glucose levels...
April 2017: Diabetes
https://www.readbyqxmd.com/read/27994470/identification-of-feature-genes-for-smoking-related-lung-adenocarcinoma-based-on-gene-expression-profile-data
#12
Ying Liu, Ran Ni, Hui Zhang, Lijun Miao, Jing Wang, Wenqing Jia, Yuanyuan Wang
This study aimed to identify the genes and pathways associated with smoking-related lung adenocarcinoma. Three lung adenocarcinoma associated datasets (GSE43458, GSE10072, and GSE50081), the subjects of which included smokers and nonsmokers, were downloaded to screen the differentially expressed feature genes between smokers and nonsmokers. Based on the identified feature genes, we constructed the protein-protein interaction (PPI) network and optimized feature genes using closeness centrality (CC) algorithm...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27993984/an-epha4-sipa1l3-wnt-pathway-regulates-eye-development-and-lens-maturation
#13
Melanie Rothe, Noreen Kanwal, Petra Dietmann, Franziska A Seigfried, Annemarie Hempel, Desiree Schütz, Dominik Reim, Rebecca Engels, Alexander Linnemann, Michael J Schmeisser, Juergen Bockmann, Michael Kühl, Tobias M Boeckers, Susanne J Kühl
The signal-induced proliferation-associated family of proteins comprises four members, SIPA1 and SIPA1L1-3. Mutations of the human SIPA1L3 gene result in congenital cataracts. In Xenopus, loss of Sipa1l3 function led to a severe eye phenotype that was distinguished by smaller eyes and lenses including lens fiber cell maturation defects. We found a direct interaction between Sipa1l3 and Epha4, building a functional platform for proper ocular development. Epha4 deficiency phenocopied loss of Sipa1l3 and rescue experiments demonstrated that Epha4 acts upstream of Sipa1l3 during eye development, with both Sipa1l3 and Epha4 required for early eye specification...
January 15, 2017: Development
https://www.readbyqxmd.com/read/27993871/flt3-internal-tandem-duplication-mutation-cmpl-and-cd34-expressions-predict-low-survival-in-acute-myeloid-leukemia-patients
#14
Eman K Ebrahim, Magda M Assem, Ahmed I Amin, Mahmoud M Kamel, Yomna M El Meligui, Ayman M Metwally
OBJECTIVES: To detect FMS-like tyrosine kinase-3 internal tandem duplicate (FLT3 ITD) mutation, Myeloproliferative leukemia virus oncogene (cMPL) and Ephrin A 4 receptor (EphA4) expressions in Acute myeloid leukemia (AML) and their correlation to patient's clinicopathological characteristics and survival. METHODS: RNA was extracted from blood samples of 58 AML patients (39 adults and 19 children) and 20 age and sex matched controls. FLT3 ITD mutation, cMPL and EphA4 expression was studied using RT-PCR and correlated to the clinical and survival data of the patients...
December 2016: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/27959424/epha4-may-contribute-to-microvessel-remodeling-in-the-hippocampal-ca1-and-ca3-areas-in-a-mouse-model-of-temporal-lobe-epilepsy
#15
Li Feng, Yi Shu, Qian Wu, Tiantian Liu, Hongyu Long, Huan Yang, Yi Li, Bo Xiao
Unclustered and pre-clustered ephrin-A5-Fc have identical anti-epileptic effects in the dentate gyrus of hippocampus in a mouse model of temporal lobe epilepsy (TLE), and act through alleviating ephrin receptor A4 (EphA4)‑mediated neurogenesis and angiogenesis. However, the effects of ephrin‑A5‑Fcs on EphA4 and angiogenesis in Cornu Ammonis (CA)1 and CA3 areas remain unclear. In the present study, male C57BL/6 mice underwent pilocarpine‑induced TLE. The expression of EphA4 and ephrin‑A5 proteins was analyzed by immunohistochemistry, and the mean density and diameter of platelet endothelial cell adhesion molecule‑1‑labeled microvessels in CA1 and CA3 were calculated in the absence or presence of two types of ephrin‑A5‑Fc intrahippocampal infusion...
January 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27935866/hic1-hypermethylated-in-cancer-1-sumoylation-is-dispensable-for-dna-repair-but-is-essential-for-the-apoptotic-dna-damage-response-ddr-to-irreparable-dna-double-strand-breaks-dsbs
#16
Sonia Paget, Marion Dubuissez, Vanessa Dehennaut, Joe Nassour, Brennan T Harmon, Nathalie Spruyt, Ingrid Loison, Corinne Abbadie, Brian R Rood, Dominique Leprince
The tumor suppressor gene HIC1 (Hypermethylated In Cancer 1) encodes a transcriptional repressor mediating the p53-dependent apoptotic response to irreparable DNA double-strand breaks (DSBs) through direct transcriptional repression of SIRT1. HIC1 is also essential for DSB repair as silencing of endogenous HIC1 in BJ-hTERT fibroblasts significantly delays DNA repair in functional Comet assays. HIC1 SUMOylation favours its interaction with MTA1, a component of NuRD complexes. In contrast with irreparable DSBs induced by 16-hours of etoposide treatment, we show that repairable DSBs induced by 1 h etoposide treatment do not increase HIC1 SUMOylation or its interaction with MTA1...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27847705/a-model-of-glial-scarring-analogous-to-the-environment-of-a-traumatically-injured-spinal-cord-using-kainate
#17
Jong Yoon Yoo, Chang Ho Hwang, Hea Nam Hong
OBJECTIVE: To develop an in vitro model analogous to the environment of traumatic spinal cord injury (SCI), the authors evaluated change of astrogliosis following treatments with kainate and/or scratch, and degree of neurite outgrowth after treatment with a kainate inhibitor. METHODS: Astrocytes were obtained from the rat spinal cord. Then, 99% of the cells were confirmed to be GFAP-positive astrocytes. For chemical injury, the cells were treated with kainate at different concentrations (10, 50 or 100 µM)...
October 2016: Annals of Rehabilitation Medicine
https://www.readbyqxmd.com/read/27826286/transcriptomic-biomarkers-for-tuberculosis-evaluation-of-dock9-epha4-and-npc2-mrna-expression-in-peripheral-blood
#18
Leonardo S de Araujo, Lea A I Vaas, Marcelo Ribeiro-Alves, Robert Geffers, Fernanda C Q Mello, Alexandre S de Almeida, Adriana da S R Moreira, Afrânio L Kritski, José R Lapa E Silva, Milton O Moraes, Frank Pessler, Maria H F Saad
Lately, much effort has been made to find mRNA biomarkers for tuberculosis (TB) disease/infection with microarray-based approaches. In a pilot investigation, through RNA sequencing technology, we observed a prominent modulation of DOCK9, EPHA4, and NPC2 mRNA abundance in the blood of TB patients. To corroborate these findings, independent validations were performed in cohorts from different areas. Gene expression levels in blood were evaluated by quantitative real-time PCR (Brazil, n = 129) or reanalysis of public microarray data (UK: n = 96; South Africa: n = 51; Germany: n = 26; and UK/France: n = 63)...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27804940/-estimation-of-the-diagnostic-potential-of-apod-ptov1-and-epha4-for-prostatic-neoplasms
#19
D O Allina, Yu Yu Andreeva, L E Zavalishina, L V Moskvina, G A Frank
Prostate cancer is one of the most frequently detected malignancies in men. The gold standard for its diagnosis is morphological examination; at the same time the differential diagnosis of adenocarcinoma, high-grade prostatic intraepithelial neoplasia (HGPIN), and benign conditions that are able to mimic the malignancies is tremendously difficult in a number of cases, this being so, the hyperdiagnosis rate of HGPIN requiring mandatory repeat biopsy is as high as 24%. The currently available differential diagnostic panel of antibodies is imperfect, which necessitates a search for novel markers...
2016: Arkhiv Patologii
https://www.readbyqxmd.com/read/27673329/motor-experience-reprograms-development-of-a-genetically-altered-bilateral-corticospinal-motor-circuit
#20
Najet Serradj, John H Martin
Evidence suggests that motor experience plays a role in shaping development of the corticospinal system and voluntary motor control, which is a key motor function of the system. Here we used a mouse model with conditional forebrain deletion of the gene for EphA4 (Emx1-Cre:EphA4tm2Kldr), which regulates development of the laterality of corticospinal tract (CST). We combined study of Emx1-Cre:EphA4tm2Kldr with unilateral forelimb constraint during development to expand our understanding of experience-dependent CST development from both basic and translational perspectives...
2016: PloS One
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