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https://www.readbyqxmd.com/read/29720978/pathogen-specific-binding-soluble-down-syndrome-cell-adhesion-molecule-dscam-regulates-phagocytosis-via-membrane-bound-dscam-in-crab
#1
Xue-Jie Li, Lei Yang, Dan Li, You-Ting Zhu, Qun Wang, Wei-Wei Li
The Down syndrome cell adhesion molecule (Dscam) gene is an extraordinary example of diversity that can produce thousands of isoforms and has so far been found only in insects and crustaceans. Cumulative evidence indicates that Dscam may contribute to the mechanistic foundations of specific immune responses in insects. However, the mechanism and functions of Dscam in relation to pathogens and immunity remain largely unknown. In this study, we identified the genome organization and alternative Dscam exons from Chinese mitten crab, Eriocheir sinensis ...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29718256/dscam-mutation-impairs-motor-cortex-network-dynamic-and-voluntary-motor-functions
#2
Olivier D Laflamme, Maxime Lemieux, Louise Thiry, Frédéric Bretzner
While it is well known that netrin-1 and its receptors UNC5 and UNC40 family members are involved in the normal establishment of the motor cortex and its corticospinal tract, less is known about its other receptor Down syndrome cell adherence molecule (DSCAM). DSCAM is expressed in the developing motor cortex, regulates axonal outgrowth of cortical neurons, and its mutation impairs the dendritic arborization of cortical neurons, thus suggesting that it might be involved in the normal development and functioning of the motor cortex...
April 27, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29462945/luminal-lncrnas-regulation-by-er%C3%AE-controlled-enhancers-in-a-ligand-independent-manner-in-breast-cancer-cells
#3
Valentina Miano, Giulio Ferrero, Valentina Rosti, Eleonora Manitta, Jamal Elhasnaoui, Giulia Basile, Michele De Bortoli
Estrogen receptor-α (ERα) is a ligand-inducible protein which mediates estrogenic hormones signaling and defines the luminal BC phenotype. Recently, we demonstrated that even in absence of ligands ERα (apoERα) binds chromatin sites where it regulates transcription of several protein-coding and lncRNA genes. Noteworthy, apoERα-regulated lncRNAs marginally overlap estrogen-induced transcripts, thus representing a new signature of luminal BC genes. By the analysis of H3K27ac enrichment in hormone-deprived MCF-7 cells, we defined a set of Super Enhancers (SEs) occupied by apoERα, including one mapped in proximity of the DSCAM-AS1 lncRNA gene...
February 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29423937/mutually-exclusive-alternative-splicing-of-pre-mrnas
#4
REVIEW
Yongfeng Jin, Haiyang Dong, Yang Shi, Lina Bian
Pre-mRNA alternative splicing is an important mechanism used to expand protein diversity in higher eukaryotes, and mutually exclusive splicing is a specific type of alternative splicing in which only one of the exons in a cluster is included in functional transcripts. The most extraordinary example of this is the Drosophila melanogaster Down's syndrome cell adhesion molecule gene (Dscam), which potentially encodes 38,016 different isoforms through mutually exclusive splicing. Mutually exclusive splicing is a unique and challenging model that can be used to elucidate the evolution, regulatory mechanism, and function of alternative splicing...
May 2018: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/29351731/a-chelicerate-specific-burst-of-nonclassical-dscam-diversity
#5
Guozheng Cao, Yang Shi, Jian Zhang, Hongru Ma, Shouqing Hou, Haiyang Dong, Weiling Hong, Shuo Chen, Hao Li, Yandan Wu, Pengjuan Guo, Xu Shao, Bingbing Xu, Feng Shi, Yijun Meng, Yongfeng Jin
BACKGROUND: The immunoglobulin (Ig) superfamily receptor Down syndrome cell adhesion molecule (Dscam) gene can generate tens of thousands of isoforms via alternative splicing, which is essential for both nervous and immune systems in insects. However, further information is required to develop a comprehensive view of Dscam diversification across the broad spectrum of Chelicerata clades, a basal branch of arthropods and the second largest group of terrestrial animals. RESULTS: In this study, a genome-wide comprehensive analysis of Dscam genes across Chelicerata species revealed a burst of nonclassical Dscams, categorised into four types-mDscam, sDscamα, sDscamβ, and sDscamγ-based on their size and structure...
January 19, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29196216/a-third-copy-of-the-down-syndrome-cell-adhesion-molecule-dscam-causes-synaptic-and-locomotor-dysfunction-in-drosophila
#6
Simon A Lowe, James J L Hodge, Maria M Usowicz
Down syndrome (DS) is caused by triplication of chromosome 21 (HSA21). It is characterised by intellectual disability and impaired motor coordination that arise from changes in brain volume, structure and function. However, the contribution of each HSA21 gene to these various phenotypes and to the causal alterations in neuronal and synaptic structure and function are largely unknown. Here we have investigated the effect of overexpression of the HSA21 gene DSCAM (Down syndrome cell adhesion molecule), on glutamatergic synaptic transmission and motor coordination, using Drosophila expressing three copies of Dscam1...
February 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29114051/dscam-mediated-control-of-dendritic-and-axonal-arbor-outgrowth-enforces-tiling-and-inhibits-synaptic-plasticity
#7
Aaron B Simmons, Samuel J Bloomsburg, Joshua M Sukeena, Calvin J Miller, Yohaniz Ortega-Burgos, Bart G Borghuis, Peter G Fuerst
Mature mammalian neurons have a limited ability to extend neurites and make new synaptic connections, but the mechanisms that inhibit such plasticity remain poorly understood. Here, we report that OFF-type retinal bipolar cells in mice are an exception to this rule, as they form new anatomical connections within their tiled dendritic fields well after retinal maturity. The Down syndrome cell-adhesion molecule ( Dscam ) confines these anatomical rearrangements within the normal tiled fields, as conditional deletion of the gene permits extension of dendrite and axon arbors beyond these borders...
November 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29093169/age-and-speed-dependent-modulation-of-gaits-in-dscam-2j-mutant-mice
#8
Louise Thiry, Maxime Lemieux, Frédéric Bretzner
Gaits depend on the interplay between distributed spinal neural networks, termed central pattern generators, generating rhythmic and coordinated movements, primary afferents, and descending supraspinal inputs. Recent studies demonstrated that the mouse displays a rich repertoire of gaits. Changes in gaits occur in mutant mice lacking particular neurons or molecular signaling pathways implicated in the normal establishment of these neural networks. Given the role of the Down syndrome cell adherence molecule (DSCAM) to the formation and maintenance of spinal interneuronal circuits and sensorimotor integration, we have investigated its functional contribution to gaits over a wide range of locomotor speeds using freely walking mice...
February 1, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29078722/local-translation-of-the-down-syndrome-cell-adhesion-molecule-dscam-mrna-in-the-vertebrate-central-nervous-system
#9
María Luz Montesinos
Local translation of synaptic mRNAs is an important process related to key aspects of central nervous system development and physiology, including dendritogenesis, axonal growth cone morphology and guidance and synaptic plasticity. Accordingly, local translation is compromised in several intellectual disabilities, including Fragile X syndrome, tuberous sclerosis and Down syndrome. Down Syndrome Cell Adhesion Molecule (DSCAM) is a gene with ascribed functions in neuronal wiring that belongs to the Down Syndrome Critical Region (DSCR) of chromosome 21...
December 2017: Journal of Neurogenetics
https://www.readbyqxmd.com/read/29042325/characterize-a-typically-dscam-with-alternative-splicing-in-mud-crab-scylla-paramamosain
#10
Wenshi Li, Xixiang Tang, Yan Chen, Wanwei Sun, Yan Liu, Yi Gong, Xiaobo Wen, Shengkang Li
As a member of the immunoglobulin superfamily, Down syndrome cell adhesion molecule (Dscam) could function in the innate immunity of invertebrates. Recently, it is shown that arthropod Dscams play similar functions as antibodies in the adaptive immune system. Dscam could produce thousands of isoforms by alternative splicing and specifically bind to various pathogens. In the present study, we cloned the first Dscam from mud crab Scylla paramamosain (SpDscam), with full-length cDNA 7363 bp containing an open reading frame (ORF) of 6069bp and encoding 2022 amino acids, which had typical domain architecture as other arthropods, i...
October 16, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28738804/oncogenic-long-noncoding-rna-landscape-in-breast-cancer
#11
Shouping Xu, Dejia Kong, Qianlin Chen, Yanyan Ping, Da Pang
BACKGROUND: Few long noncoding RNAs (lncRNAs) that act as oncogenic genes in breast cancer have been identified. METHODS: Oncogenic lncRNAs associated with tumourigenesis and worse survival outcomes were examined and validated in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), respectively. Then, the potential biological functions and expression regulation of these lncRNAs were studied via bioinformatics and genome data analysis. Moreover, progressive breast cancer subtype-specific lncRNAs were investigated via high-throughput sequencing in our cohort and TCGA validation...
July 24, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28659724/identification-of-sets-of-cytoskeletal-related-and-adhesion-related-coding-region-mutations-in-the-tcga-melanoma-dataset-that-correlate-with-a-negative-outcome
#12
John M Yavorski, Rebecca J Stoll, Mohammad D Samy, James A Mauro, George Blanck
BACKGROUND: Relatively little cancer genome atlas data has been associated with clinically relevant stratifications of individual cancers. RESULTS: Mutations in two subsets of a cytoskeletal related and adhesion-related protein coding region set (CAPCRs) were determined to have strong associations with a negative outcome for melanoma, in-cluding a subset constituted by: DSCAM, FAT3, MUC17 and PCDHGC5 (p < 0.0001). CONCLUSION: Roles for CAPCR mutations in cancer progression raise a question about the potential dominant negative impact of these mutations for multi-meric subcellular and extra-cellular protein struc-tures...
June 2017: Current Genomics
https://www.readbyqxmd.com/read/28648597/genotype-phenotype-correlation-for-congenital-heart-disease-in-down-syndrome-through-analysis-of-partial-trisomy-21-cases
#13
Maria Chiara Pelleri, Elena Gennari, Chiara Locatelli, Allison Piovesan, Maria Caracausi, Francesca Antonaros, Alessandro Rocca, Costanza Maria Donati, Letizia Conti, Pierluigi Strippoli, Marco Seri, Lorenza Vitale, Guido Cocchi
Among Down syndrome (DS) children, 40-50% have congenital heart disease (CHD). Although trisomy 21 is not sufficient to cause CHD, three copies of at least part of chromosome 21 (Hsa21) increases the risk for CHD. In order to establish a genotype-phenotype correlation for CHD in DS, we built an integrated Hsa21 map of all described partial trisomy 21 (PT21) cases with sufficient indications regarding presence or absence of CHD (n=107), focusing on DS PT21 cases. We suggest a DS CHD candidate region on 21q22...
October 2017: Genomics
https://www.readbyqxmd.com/read/28621421/roles-of-dscam-in-axonal-decussation-and-fasciculation-of-chick-spinal-interneurons
#14
Oksana Cohen, Lilach Vald, Masahito Yamagata, Joshua R Sanes, Avihu Klar
The ventral midline of the embryonic neural tube, the floor plate, has a profound role in guiding axons during embryonic development. Floor plate-derived guidance cues attract or repel axons, depending on the neuronal subtype and developmental stage. Netrin-1 and its receptor, Deleted in Colon Carcinoma (DCC), are the key constituents of commissurral axons guidance cues toward the floor plate. Recent studies have implicated Down Syndrome Cell Adhesion Molecule (Dscam) as an additional Netrin-1 receptor. In this study, we examined the role of Dscam in guiding defined spinal dorsal interneuron populations...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28600779/the-landscape-of-genetic-diseases-in-saudi-arabia-based-on-the-first-1000-diagnostic-panels-and-exomes
#15
Dorota Monies, Mohamed Abouelhoda, Moeenaldeen AlSayed, Zuhair Alhassnan, Maha Alotaibi, Husam Kayyali, Mohammed Al-Owain, Ayaz Shah, Zuhair Rahbeeni, Mohammad A Al-Muhaizea, Hamad I Alzaidan, Edward Cupler, Saeed Bohlega, Eissa Faqeih, Maha Faden, Banan Alyounes, Dyala Jaroudi, Ewa Goljan, Hadeel Elbardisy, Asma Akilan, Renad Albar, Hesham Aldhalaan, Shamshad Gulab, Aziza Chedrawi, Bandar K Al Saud, Wesam Kurdi, Nawal Makhseed, Tahani Alqasim, Heba Y El Khashab, Hamoud Al-Mousa, Amal Alhashem, Imaduddin Kanaan, Talal Algoufi, Khalid Alsaleem, Talal A Basha, Fathiya Al-Murshedi, Sameena Khan, Adila Al-Kindy, Maha Alnemer, Sami Al-Hajjar, Suad Alyamani, Hasan Aldhekri, Ali Al-Mehaidib, Rand Arnaout, Omar Dabbagh, Mohammad Shagrani, Dieter Broering, Maha Tulbah, Amal Alqassmi, Maisoon Almugbel, Mohammed AlQuaiz, Abdulaziz Alsaman, Khalid Al-Thihli, Raashda A Sulaiman, Wajeeh Al-Dekhail, Abeer Alsaegh, Fahad A Bashiri, Alya Qari, Suzan Alhomadi, Hisham Alkuraya, Mohammed Alsebayel, Muddathir H Hamad, Laszlo Szonyi, Faisal Abaalkhail, Sulaiman M Al-Mayouf, Hamad Almojalli, Khalid S Alqadi, Hussien Elsiesy, Taghreed M Shuaib, Mohammed Zain Seidahmed, Ibraheem Abosoudah, Hana Akleh, Abdulaziz AlGhonaium, Turki M Alkharfy, Fuad Al Mutairi, Wafa Eyaid, Abdullah Alshanbary, Farrukh R Sheikh, Fahad I Alsohaibani, Abdullah Alsonbul, Saeed Al Tala, Soher Balkhy, Randa Bassiouni, Ahmed S Alenizi, Maged H Hussein, Saeed Hassan, Mohamed Khalil, Brahim Tabarki, Saad Alshahwan, Amira Oshi, Yasser Sabr, Saad Alsaadoun, Mustafa A Salih, Sarar Mohamed, Habiba Sultana, Abdullah Tamim, Moayad El-Haj, Saif Alshahrani, Dalal K Bubshait, Majid Alfadhel, Tariq Faquih, Mohamed El-Kalioby, Shazia Subhani, Zeeshan Shah, Nabil Moghrabi, Brian F Meyer, Fowzan S Alkuraya
In this study, we report the experience of the only reference clinical next-generation sequencing lab in Saudi Arabia with the first 1000 families who span a wide-range of suspected Mendelian phenotypes. A total of 1019 tests were performed in the period of March 2016-December 2016 comprising 972 solo (index only), 14 duo (parents or affected siblings only), and 33 trio (index and parents). Multigene panels accounted for 672 tests, while whole exome sequencing (WES) represented the remaining 347 tests. Pathogenic or likely pathogenic variants that explain the clinical indications were identified in 34% (27% in panels and 43% in exomes), spanning 279 genes and including 165 novel variants...
August 2017: Human Genetics
https://www.readbyqxmd.com/read/28584888/autism-spectrum-disorder-neuropathology-and-animal-models
#16
REVIEW
Merina Varghese, Neha Keshav, Sarah Jacot-Descombes, Tahia Warda, Bridget Wicinski, Dara L Dickstein, Hala Harony-Nicolas, Silvia De Rubeis, Elodie Drapeau, Joseph D Buxbaum, Patrick R Hof
Autism spectrum disorder (ASD) has a major impact on the development and social integration of affected individuals and is the most heritable of psychiatric disorders. An increase in the incidence of ASD cases has prompted a surge in research efforts on the underlying neuropathologic processes. We present an overview of current findings in neuropathology studies of ASD using two investigational approaches, postmortem human brains and ASD animal models, and discuss the overlap, limitations, and significance of each...
October 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28513774/hippocampal-overexpression-of-down-syndrome-cell-adhesion-molecule-in-amyloid-precursor-protein-transgenic-mice
#17
Y L Jia, Z X Fu, B H Zhang, Y J Jia
Down syndrome cell adhesion molecule (DSCAM) is located within the Down syndrome critical region of chromosome 21. DSCAM is a broadly expressed neurodevelopmental protein involved in synaptogenesis, neurite outgrowth, and axon guidance. We previously demonstrated DSCAM overexpression in the cortex of amyloid precursor protein (APP) transgenic mice, suggesting possible regulatory interactions between APP and DSCAM. APP mice exhibit deficits in hippocampus-dependent learning and memory. In this preliminary study, we examined age-related changes in DSCAM expression within the hippocampus in 16 APP transgenic mice (1, 3, 6 and 12 months old)...
May 15, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28483977/uncoupling-of-unc5c-with-polymerized-tubb3-in-microtubules-mediates-netrin-1-repulsion
#18
Qiangqiang Shao, Tao Yang, Huai Huang, Farrah Alarmanazi, Guofa Liu
Modulation of microtubule (MT) dynamics is a key event of cytoskeleton remodeling in the growth cone (GC) during axon outgrowth and pathfinding. Our previous studies have shown that the direct interaction of netrin receptor DCC and DSCAM with polymerized TUBB3, a neuron-specific MT subunit in the brain, is required for netrin-1-mediated axon outgrowth, branching, and attraction. Here, we show that uncoupling of polymerized TUBB3 with netrin-1-repulsive receptor UNC5C is involved in netrin-1-mediated axonal repulsion...
June 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28422838/opposite-chromosome-constitutions-due-to-a-familial-translocation-t-1-21-q43-q22-in-2-cousins-with-development-delay-and-congenital-anomalies-a-case-report
#19
Beata Aleksiūnienė, Rugilė Matulevičiūtė, Aušra Matulevičienė, Birutė Burnytė, Natalija Krasovskaja, Laima Ambrozaitytė, Violeta Mikštienė, Vaidas Dirsė, Algirdas Utkus, Vaidutis Kučinskas
RATIONALE: Chromosomal rearrangements are the major cause of multiple congenital abnormalities and intellectual disability. PATIENT CONCERNS AND DIAGNOSIS: We report 2 first cousins with unbalanced chromosomal aberrations of chromosomes 1 and 21, resulting from balanced familial translocation. Chromosome microarray analysis revealed 8.5 Mb1q43q44 duplication/21q22.2q22.3 deletion and 6.8 Mb 1q43q44 deletion/21q22.2q22.3 duplication. Among other features, cognitive and motor development delay and craniofacial anomalies are present in both patients, whereas congenital heart defect and hearing impairment is only present in patient carrying 1q43q44 duplication/21q22...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28202568/developmental-role-of-dscam-in-spinal-locomotor-circuits
#20
REVIEW
Carl Farah
Studying the development of spinal circuitry is essential in understanding the motor behaviors that arise from them. In their study, Thiry et al. ( J Neurophysiol 115: 1338-1354, 2016) show that loss of Down syndrome cell adhesion molecule (DSCAM) leads to locomotor impairments that may stem from specific changes in spinal connectivity altering the balance of central and peripheral excitatory drive onto spinal motoneurons. These findings as well as additional insights and future directions are discussed in the context of the recent literature...
June 1, 2017: Journal of Neurophysiology
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