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https://www.readbyqxmd.com/read/28642575/reactive-astrocytes-function-as-phagocytes-after-brain-ischemia-via-abca1-mediated-pathway
#1
Yosuke M Morizawa, Yuri Hirayama, Noubuhiko Ohno, Shinsuke Shibata, Eiji Shigetomi, Yang Sui, Junichi Nabekura, Koichi Sato, Fumikazu Okajima, Hirohide Takebayashi, Hideyuki Okano, Schuichi Koizumi
Astrocytes become reactive following various brain insults; however, the functions of reactive astrocytes are poorly understood. Here, we show that reactive astrocytes function as phagocytes after transient ischemic injury and appear in a limited spatiotemporal pattern. Following transient brain ischemia, phagocytic astrocytes are observed within the ischemic penumbra region during the later stage of ischemia. However, phagocytic microglia are mainly observed within the ischemic core region during the earlier stage of ischemia...
June 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28536440/genetic-variants-in-the-transcription-regulatory-region-of-megf10-are-associated-with-autism-in-chinese-han-population
#2
Zhiliu Wu, Jian Qin, Yang You, Yuanlin Ma, Meixiang Jia, Linyan Wang, Tianlan Lu, Weihua Yue, Yanyan Ruan, Dai Zhang, Jun Li, Lifang Wang
Multiple epidermal growth factor-like-domains 10 (MEGF10), a critical member of the apoptotic engulfment pathway, mediates axon pruning and synapse elimination during brain development. Previous studies indicated that synaptic pruning deficit was associated with autism-related phenotypes. However, the relationship between MEGF10 and autism remains poorly understood. Disease-associated variants are significantly enriched in the transcription regulatory regions. These include the transcription start site (TSS) and its cis-regulatory elements...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526325/expression-of-megf10-in-cholinergic-and-glutamatergic-neurons
#3
Yu Fujita, Tomoji Maeda, Koji Kamaishi, Rui Saito, Koyo Chiba, Xuefeng Shen, Kun Zou, Hiroto Komano
Multiple-EGF like domains 10 (MEGF10) is the mammalian homologue of Draper, a Drosophila phagocytosis receptor that plays an important role in synapse elimination and cell type-specific recognition. However, the expression and function of MEGF10 in the brain remain to be elucidated. Therefore, we aimed to clarify the regions and types of neurons that express MEGF10 in the brain, and to determine whether cells expressing MEGF10 possess phagocytic abilities. Our results indicated that MEGF10 is expressed in cholinergic and glutamatergic neurons of the cortex, hippocampus, and substantia nigra...
July 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28498977/consequences-of-megf10-deficiency-on-myoblast-function-and-notch1-interactions
#4
Madhurima Saha, Satomi Mitsuhashi, Michael D Jones, Kelsey Manko, Hemakumar M Reddy, Christine Bruels, Kyung-Ah Cho, Christina A Pacak, Isabelle Draper, Peter B Kang
Mutations in MEGF10 cause early onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD), a rare congenital muscle disease, but the pathogenic mechanisms remain largely unknown. We demonstrate that short hairpin RNA (shRNA)-mediated knockdown of Megf10, as well as overexpression of the pathogenic human p.C774R mutation, leads to impaired proliferation and migration of C2C12 cells. Myoblasts from Megf10-/- mice and Megf10-/-/mdx double knockout (dko) mice also show impaired proliferation and migration compared to myoblasts from wild type and mdx mice, whereas the dko mice show histological abnormalities that are not observed in either single mutant mouse...
May 11, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/27974694/hormophysa-triquerta-polyphenol-an-elixir-that-deters-cxcr4-and-cox2-dependent-dissemination-destiny-of-treatment-resistant-pancreatic-cancer-cells
#5
Sheeja Aravindan, Satishkumar Ramraj, Kathiresan Kandasamy, Somasundaram S Thirugnanasambandan, Dinesh Babu Somasundaram, Terence S Herman, Natarajan Aravindan
Therapy-resistant pancreatic cancer (PC) cells play a crucial role in tumor relapse, recurrence, and metastasis. Recently, we showed the anti-PC potential of an array of seaweed polyphenols and identified efficient drug deliverables. Herein, we investigated the benefit of one such deliverable, Hormophysa triquerta polyphenol (HT-EA), in regulating the dissemination physiognomy of therapy-resistant PC cells in vitro,and residual PC in vivo. Human PC cells exposed to ionizing radiation (IR), with/without HT-EA pre-treatment were examined for the alterations in the tumor invasion/metastasis (TIM) transcriptome (93 genes, QPCR-profiling)...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/27862318/genome-wide-dna-methylation-analysis-identifies-megf10-as-a-novel-epigenetically-repressed-candidate-tumor-suppressor-gene-in-neuroblastoma
#6
Jessica Charlet, Ayumi Tomari, Anthony R Dallosso, Marianna Szemes, Martina Kaselova, Thomas J Curry, Bader Almutairi, Heather C Etchevers, Carmel McConville, Karim T A Malik, Keith W Brown
Neuroblastoma is a childhood cancer in which many children still have poor outcomes, emphasising the need to better understand its pathogenesis. Despite recent genome-wide mutation analyses, many primary neuroblastomas do not contain recognizable driver mutations, implicating alternate molecular pathologies such as epigenetic alterations. To discover genes that become epigenetically deregulated during neuroblastoma tumorigenesis, we took the novel approach of comparing neuroblastomas to neural crest precursor cells, using genome-wide DNA methylation analysis...
April 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27822178/loss-of-cpeb3-upregulates-megf10-to-impair-mosaic-development-of-on-starburst-amacrine-cells
#7
Yin-Peng Chen, Geng-Shuo Bai, Meng-Fang Wu, Chuan-Chin Chiao, Yi-Shuian Huang
Cytoplasmic polyadenylation element binding protein 3 (CPEB3) regulates target RNA translation in neurons. Here, we examined CPEB3 distribution and function in the mouse retina. CPEB3 is expressed in retinal neurons, including those located in the inner nuclear layer (INL) and ganglion cell layer (GCL) but not in cone and rod photoreceptors in the outer nuclear layer (ONL). A previous study found CPEB3 expressed in cholinergic starburst amacrine cells (SACs). We first examined these cells and observed aberrant SAC mosaicism in CPEB3-knockout (KO) retinas...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27717089/chromosomal-microarray-in-a-highly-consanguineous-population-diagnostic-yield-utility-of-regions-of-homozygosity-and-novel-mutations
#8
M A Alabdullatif, M A Al Dhaibani, M Y Khassawneh, A W El-Hattab
Chromosomal microarray (CMA) has significantly improved diagnosing copy number variations (CNVs). Single nucleotide polymorphism (SNP) arrays confer additional utility in detecting regions of homozygosity (ROH). Investigating ROH for genes associated with recessive disorders for follow-up sequencing can aid in diagnosis. In this study, we performed a retrospective review of clinical and molecular data for 227 individuals from a highly consanguineous population who previously had a CMA. Pathogenic CNVs were identified in 32 (14%) cases; ROH suggesting uniparental disomy (UPD) in three (1%) cases, and an additional 25 (11%) individuals were diagnosed with recessive disorders caused by mutations in ROH candidate genes, thereby increasing the CMA diagnostic yield to 26%...
April 2017: Clinical Genetics
https://www.readbyqxmd.com/read/27647497/delayed-glial-clearance-of-degenerating-axons-in-aged-drosophila-is-due-to-reduced-pi3k-draper-activity
#9
Maria D Purice, Sean D Speese, Mary A Logan
Advanced age is the greatest risk factor for neurodegenerative disorders, but the mechanisms that render the senescent brain vulnerable to disease are unclear. Glial immune responses provide neuroprotection in a variety of contexts. Thus, we explored how glial responses to neurodegeneration are altered with age. Here we show that glia-axon phagocytic interactions change dramatically in the aged Drosophila brain. Aged glia clear degenerating axons slowly due to low phosphoinositide-3-kinase (PI3K) signalling and, subsequently, reduced expression of the conserved phagocytic receptor Draper/MEGF10...
September 20, 2016: Nature Communications
https://www.readbyqxmd.com/read/27460346/japanese-multiple-epidermal-growth-factor-10-megf10-myopathy-with-novel-mutations-a-phenotype-genotype-correlation
#10
Kazuko Takayama, Satomi Mitsuhashi, Je-Young Shin, Rieko Tanaka, Tatsuya Fujii, Rie Tsuburaya, Souichi Mukaida, Satoru Noguchi, Ikuya Nonaka, Ichizo Nishino
Mutations in the multiple epidermal growth factor-like domains 10 (MEGF10: NM_032446.2) gene are known to cause early-onset myopathy characterized by areflexia, respiratory distress, and dysphagia (EMARDD: OMIM 614399), and a milder phenotype of minicore myopathy. To date, there have been reports of six families with EMARDD and one with a milder disorder. Cysteine mutations in the extracellular EGF-like domain may be responsible for the milder phenotype, but the relationship is not conclusive because of the few reports of this disorder...
September 2016: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/27254118/rna-seq-reveals-10-novel-promising-candidate-genes-affecting-milk-protein-concentration-in-the-chinese-holstein-population
#11
Cong Li, Wentao Cai, Chenghao Zhou, Hongwei Yin, Ziqi Zhang, Juan J Loor, Dongxiao Sun, Qin Zhang, Jianfeng Liu, Shengli Zhang
Paired-end RNA sequencing (RNA-Seq) was used to explore the bovine transcriptome from the mammary tissue of 12 Chinese Holstein cows with 6 extremely high and 6 low phenotypic values for milk protein percentage. We defined the differentially expressed transcripts between the two comparison groups, extremely high and low milk protein percentage during the peak lactation (HP vs LP) and during the non-lactating period (HD vs LD), respectively. Within the differentially expressed genes (DEGs), we detected 157 at peak lactation and 497 in the non-lactating period with a highly significant correlation with milk protein concentration...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27170117/megf10-is-a-receptor-for-c1q-that-mediates-clearance-of-apoptotic-cells-by-astrocytes
#12
Tal Iram, Zaida Ramirez-Ortiz, Michael H Byrne, Uwanda A Coleman, Nathan D Kingery, Terry K Means, Dan Frenkel, Joseph El Khoury
UNLABELLED: Multiple EGF-like domains 10 (Megf10) is a class F scavenger receptor (SR-F3) expressed on astrocytes and myosatellite cells, and recessive mutations in humans result in early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD). Here we report that Megf10-deficient mice have increased apoptotic cells in the developing cerebellum and have impaired phagocytosis of apoptotic cells by astrocytes ex vivo We also report that cells transfected with Megf10 gain the ability to phagocytose apoptotic neurons and that Megf10 binds with high affinity to C1q, an eat-me signal for apoptotic cells...
May 11, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/26802438/adult-onset-respiratory-insufficiency-scoliosis-and-distal-joint-hyperlaxity-in-patients-with-multiminicore-disease-due-to-novel-megf10-mutations
#13
Teerin Liewluck, Margherita Milone, Xia Tian, Andrew G Engel, Nathan P Staff, Lee-Jun Wong
INTRODUCTION: Multiminicore disease is a congenital myopathy characterized pathologically by the presence of multiple minicore structures in the sarcoplasm. Mutations in the selenoprotein N1-encoding gene (SEPN1) and ryanodine receptor 1-encoding gene (RYR1) are responsible for half of the reported cases. Mutations in multiple epidermal growth factor-like domains 10-encoding gene (MEGF10) have been identified only recently in a few patients with antenatal to infantile-onset myopathy, with and without minicore pathology...
June 2016: Muscle & Nerve
https://www.readbyqxmd.com/read/26657541/engulfment-pathways-promote-programmed-cell-death-by-enhancing-the-unequal-segregation-of-apoptotic-potential
#14
Sayantan Chakraborty, Eric J Lambie, Samik Bindu, Tamara Mikeladze-Dvali, Barbara Conradt
Components of the conserved engulfment pathways promote programmed cell death in Caenorhabditis elegans (C. elegans) through an unknown mechanism. Here we report that the phagocytic receptor CED-1 mEGF10 is required for the formation of a dorsal-ventral gradient of CED-3 caspase activity within the mother of a cell programmed to die and an increase in the level of CED-3 protein within its dying daughter. Furthermore, CED-1 becomes enriched on plasma membrane regions of neighbouring cells that appose the dorsal side of the mother, which later forms the dying daughter...
December 10, 2015: Nature Communications
https://www.readbyqxmd.com/read/26148557/reorganization-of-metastamirs-in-the-evolution-of-metastatic-aggressive-neuroblastoma-cells
#15
Faizan H Khan, Vijayabaskar Pandian, Satishkumar Ramraj, Sheeja Aravindan, Terence S Herman, Natarajan Aravindan
BACKGROUND: MetastamiRs have momentous clinical relevance and have been correlated with disease progression in many tumors. In this study, we identified neuroblastoma metastamiRs exploiting unique mouse models of favorable and high-risk metastatic human neuroblastoma. Further, we related their deregulation to the modulation of target proteins and established their association with clinical outcomes. RESULTS: Whole genome miRNA microarray analysis identified 74 metastamiRs across the manifold of metastatic tumors...
2015: BMC Genomics
https://www.readbyqxmd.com/read/25111228/silencing-of-drpr-leads-to-muscle-and-brain-degeneration-in-adult-drosophila
#16
Isabelle Draper, Lane J Mahoney, Satomi Mitsuhashi, Christina A Pacak, Robert N Salomon, Peter B Kang
Mutations in the gene encoding the single transmembrane receptor multiple epidermal growth factor-like domain 10 (MEGF10) cause an autosomal recessive congenital muscle disease in humans. Although mammalian MEGF10 is expressed in the central nervous system as well as in skeletal muscle, patients carrying mutations in MEGF10 do not show symptoms of central nervous system dysfunction. drpr is the sole Drosophila homolog of the human genes MEGF10, MEGF11, and MEGF12 (JEDI, PEAR). The functional domains of MEGF10 and drpr bear striking similarities, and residues affected by MEGF10 mutations in humans are conserved in drpr...
October 2014: American Journal of Pathology
https://www.readbyqxmd.com/read/25044114/myogenin-is-a-positive-regulator-of-megf10-expression-in-skeletal-muscle
#17
Seung-Yoon Park, Youngeun Yun, Mi-Jin Kim, In-San Kim
MEGF10 is known to function as a myogenic regulator of satellite cells in skeletal muscle. Mutations in MEGF10 gene cause a congenital myopathy called early onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD). Despite its biological importance in muscle physiology, transcriptional regulation of the MEGF10 gene is unknown. Here, we characterized the 5' flanking region of the human MEGF10 gene and showed that the role of myogenic basic helix-loop-helix factor (bHLH) myogenin in MEGF10 transcription in muscle cells...
August 8, 2014: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/24270812/astrocytes-mediate-synapse-elimination-through-megf10-and-mertk-pathways
#18
Won-Suk Chung, Laura E Clarke, Gordon X Wang, Benjamin K Stafford, Alexander Sher, Chandrani Chakraborty, Julia Joung, Lynette C Foo, Andrew Thompson, Chinfei Chen, Stephen J Smith, Ben A Barres
To achieve its precise neural connectivity, the developing mammalian nervous system undergoes extensive activity-dependent synapse remodelling. Recently, microglial cells have been shown to be responsible for a portion of synaptic pruning, but the remaining mechanisms remain unknown. Here we report a new role for astrocytes in actively engulfing central nervous system synapses. This process helps to mediate synapse elimination, requires the MEGF10 and MERTK phagocytic pathways, and is strongly dependent on neuronal activity...
December 19, 2013: Nature
https://www.readbyqxmd.com/read/23954233/cysteine-mutations-cause-defective-tyrosine-phosphorylation-in-megf10-myopathy
#19
Satomi Mitsuhashi, Hiroaki Mitsuhashi, Matthew S Alexander, Hiroyuki Sugimoto, Peter B Kang
Recessive mutations in MEGF10 are known to cause a congenital myopathy in humans. Two mutations in the extracellular EGF-like domains of MEGF10, C326R and C774R, were associated with decreased tyrosine phosphorylation of MEGF10 in vitro. Y1030 was identified to be the major tyrosine phosphorylation site in MEGF10 and is phosphorylated at least in part by c-Src. Overexpression of wild-type MEGF10 enhanced C2C12 myoblast proliferation, while overexpression of Y1030F mutated MEGF10 did not. We conclude that MEGF10-mediated signaling via tyrosine phosphorylation helps to regulate myoblast proliferation...
September 17, 2013: FEBS Letters
https://www.readbyqxmd.com/read/23580569/the-absence-of-er-%C3%AE-results-in-altered-gene-expression-in-ovarian-granulosa-cells-isolated-from-in-vivo-preovulatory-follicles
#20
April K Binder, Karina F Rodriguez, Katherine J Hamilton, Patricia S Stockton, Casey E Reed, Kenneth S Korach
Determining the spatial and temporal expression of genes involved in the ovulatory pathway is critical for the understanding of the role of each estrogen receptor in the modulation of folliculogenesis and ovulation. Estrogen receptor (ER)-β is highly expressed in ovarian granulosa cells, and mice lacking ER-β are subfertile due to inefficient ovulation. Previous work has focused on isolated granulosa cells or cultured follicles and, although informative, provides confounding results due to the heterogeneous cell types present including granulosa and theca cells and oocytes and exposure to in vitro conditions...
June 2013: Endocrinology
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