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Down's syndrome cell adhesion molecule

Olga Villarroya, Raúl Ballestín, Rosa López-Hidalgo, Maria Mulet, José Miguel Blasco-Ibáñez, Carlos Crespo, Juan Nacher, Javier Gilabert-Juan, Emilio Varea
Down syndrome (DS) is the most common chromosomal aneuploidy. Although trisomy on chromosome 21 can display variable phenotypes, there is a common feature among all DS individuals: the presence of intellectual disability. This condition is partially attributed to abnormalities found in the hippocampus of individuals with DS and in the murine model for DS, Ts65Dn. To check if all hippocampal areas were equally affected in 4-5 month adult Ts65Dn mice, we analysed the morphology of dentate gyrus granule cells and cornu ammonis pyramidal neurons using Sholl method on Golgi-Cox impregnated neurons...
April 4, 2017: Histology and Histopathology
Freyja M Bruce, Samantha Brown, Jonathan N Smith, Peter G Fuerst, Lynda Erskine
Although many aspects of optic pathway development are beginning to be understood, the mechanisms promoting the growth of retinal ganglion cell (RGC) axons toward visual targets remain largely unknown. Down syndrome cell adhesion molecule (Dscam) is expressed by mouse RGCs shortly after they differentiate at embryonic day 12 and is essential for multiple aspects of postnatal visual system development. Here we show that Dscam is also required during embryonic development for the fasciculation and growth of RGC axons...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
Linna Cheng, Shu Ang Li, Jia Huai Wang, Yamei Yu, Qiang Chen
An extra author is added to the article by Chen et al. [(2015), Acta Cryst. F71, 775-778].
December 1, 2016: Acta Crystallographica. Section F, Structural Biology Communications
Jianping Zhao, Zhengguo Zhang, Shumin Ren, Yanan Zong, Xiangdong Kong
Down's syndrome (DS) is a type of chromosome disease. The present study aimed to explore the underlying molecular mechanisms of DS. GSE5390 microarray data downloaded from the gene expression omnibus database was used to identify differentially expressed genes (DEGs) in DS. Pathway enrichment analysis of the DEGs was performed, followed by co-expression network construction. Significant differential modules were mined by mutual information, followed by functional analysis. The accuracy of sample classification for the significant differential modules of DEGs was evaluated by leave-one-out cross-validation...
September 2016: Experimental and Therapeutic Medicine
Shu-Ang Li, Linna Cheng, Yamei Yu, Qiang Chen
The Drosophila neural receptor Dscam1 (Down syndrome cell adhesion molecule 1) plays an essential role in neuronal wiring and self-avoidance. Dscam1 potentially encodes 19,008 ectodomains through alternative RNA splicing and exhibits exquisite isoform-specific homophilic binding, which makes it an exceptional example for studying protein binding specificity. However, structural information on Dscam1 is limited, which hinders illumination of the mechanism of Dscam1 isoform-specific recognition. Whether different Dscam1 isoforms adopt the same dimerization mode remains a subject of debate...
May 2016: Science Advances
Larisa C Kruger, Heather A O'Malley, Jacob M Hull, Amanda Kleeman, Gustavo A Patino, Lori L Isom
UNLABELLED: Voltage-gated sodium channel (VGSC) β subunits signal through multiple pathways on multiple time scales. In addition to modulating sodium and potassium currents, β subunits play nonconducting roles as cell adhesion molecules, which allow them to function in cell-cell communication, neuronal migration, neurite outgrowth, neuronal pathfinding, and axonal fasciculation. Mutations in SCN1B, encoding VGSC β1 and β1B, are associated with epilepsy. Autosomal-dominant SCN1B-C121W, the first epilepsy-associated VGSC mutation identified, results in genetic epilepsy with febrile seizures plus (GEFS+)...
June 8, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Myung-Sun Kim, Ji Hea Yu, Min-Young Lee, Ah Leum Kim, Mi Hyun Jo, MinGi Kim, Sung-Rae Cho, Young-Han Kim
Preeclampsia is a common disease that can occur during human pregnancy and is a leading cause of both maternal and neonatal morbidity and mortality. Inadequate trophoblast invasion and deficient remodeling of uterine spiral arteries are associated with preeclampsia (PE). The development of this syndrome is thought to be related to multiple factors. Recently, we isolated patient-specific human amniotic epithelial cells (AECs) from the placentas of 3 women with normal pregnancy and 3 with preeclamptic pregnancy...
2016: PloS One
Hung-Chang Shen, Jia-Yi Wei, Sao-Yu Chu, Pei-Chi Chung, Tsai-Chi Hsu, Hung-Hsiang Yu
In the Drosophila olfactory system, odorant information is sensed by olfactory sensory neurons and relayed from the primary olfactory center, the antennal lobe (AL), to higher olfactory centers via olfactory projection neurons (PNs). A major portion of the AL is constituted with dendrites of four groups of PNs, anterodorsal PNs (adPNs), lateral PNs (lPNs), lateroventral PNs (lvPNs) and ventral PNs (vPNs). Previous studies have been focused on the development and function of adPNs and lPNs, while the investigation on those of lvPNs and vPNs received less attention...
2016: PloS One
Robert Peuß, Kristina U Wensing, Luisa Woestmann, Hendrik Eggert, Barbara Milutinović, Marlene G U Sroka, Jörn P Scharsack, Joachim Kurtz, Sophie A O Armitage
Down syndrome cell adhesion molecule 1 (Dscam1) has wide-reaching and vital neuronal functions although the role it plays in insect and crustacean immunity is less well understood. In this study, we combine different approaches to understand the roles that Dscam1 plays in fitness-related contexts in two model insect species. Contrary to our expectations, we found no short-term modulation of Dscam1 gene expression after haemocoelic or oral bacterial exposure in Tribolium castaneum, or after haemocoelic bacterial exposure in Drosophila melanogaster...
April 2016: Royal Society Open Science
Yuan Yue, Yijun Meng, Hongru Ma, Shouqing Hou, Guozheng Cao, Weiling Hong, Yang Shi, Pengjuan Guo, Baoping Liu, Feng Shi, Yun Yang, Yongfeng Jin
Drosophila Dscam1 (Down Syndrome Cell Adhesion Molecules) and vertebrate clustered protocadherins (Pcdhs) are two classic examples of the extraordinary isoform diversity from a single genomic locus. Dscam1 encodes 38,016 distinct isoforms via mutually exclusive splicing in D. melanogaster, while the vertebrate clustered Pcdhs utilize alternative promoters to generate isoform diversity. Here we reveal a shortened Dscam gene family with tandemly arrayed 5' cassettes in Chelicerata. These cassette repeats generally comprise two or four exons, corresponding to variable Immunoglobulin 7 (Ig7) or Ig7-8 domains of Drosophila Dscam1...
2016: Nature Communications
Aaron B Simmons, Morgan M Merrill, Justin C Reed, Michael R Deans, Malia M Edwards, Peter G Fuerst
PURPOSE: Abnormal retinal angiogenesis leads to visual impairment and blindness. Understanding how retinal vessels develop normally has dramatically improved treatments for people with retinal vasculopathies, but additional information about development is required. Abnormal neuron patterning in the outer retina has been shown to result in abnormal vessel development and blindness, for example, in people and mouse models with Crumbs homologue 1 (CRB1) mutations. In this study, we report and characterize a mouse model of inner retinal lamination disruption and bleeding, the Down syndrome cell adhesion molecule (Dscam) mutant, and test how neuron-neurite placement within the inner retina guides development of intraretinal vessels...
April 2016: Investigative Ophthalmology & Visual Science
F Zhang, Q Li, X Chen, Y Huo, H Guo, Z Song, F Cui, L Zhang, R Fang
The arthropod Down syndrome cell adhesion molecule (Dscam) mediates pathogen-specific recognition via an extensive protein isoform repertoire produced by alternative splicing. To date, most studies have focused on the subsequent pathogen-specific immune response, and few have investigated the entry into cells of viruses or endosymbionts. In the present study, we cloned and characterized the cDNA of Laodelphax striatellus Dscam (LsDscam) and investigated the function of LsDscam in rice stripe virus (RSV) infection and the influence on the endosymbiont Wolbachia...
August 2016: Insect Molecular Biology
Ramón Pérez-Núñez, Natalia Barraza, Arlek Gonzalez-Jamett, Ana Maria Cárdenas, Jean-Vianney Barnier, Pablo Caviedes
In humans, Down syndrome (DS) is caused by the presence of an extra copy of autosome 21. The most striking finding in DS patients is intellectual disability and the onset of Alzheimer's disease (AD)-like neuropathology in adulthood. Gene overdose is most likely to underlie both developmental impairments, as well as altered neuronal function in DS. Lately, the disruption of cellular signaling and regulatory pathways has been implicated in DS pathophysiology, and many of such pathways may represent common targets for diverse DS-related genes, which could in turn represent attractive therapeutical targets...
July 2016: Neurotoxicity Research
Shuai Li, Joe Mitchell, Deidrie J Briggs, Jaime K Young, Samuel S Long, Peter G Fuerst
PURPOSE: Rod spherules are the site of the first synaptic contact in the retina's rod pathway, linking rods to horizontal and bipolar cells. Rod spherules have been described and characterized through electron micrograph (EM) and other studies, but their morphological diversity related to retinal circuitry and their intracellular structures have not been quantified. Most rod spherules are connected to their soma by an axon, but spherules of rods on the surface of the Mus musculus outer plexiform layer often lack an axon and have a spherule structure that is morphologically distinct from rod spherules connected to their soma by an axon...
2016: PloS One
K A Fernandes, S J Bloomsburg, C J Miller, S A Billingslea, M M Merrill, R W Burgess, R T Libby, P G Fuerst
The Down syndrome cell adhesion molecule gene (Dscam) is required for normal dendrite patterning and promotes developmental cell death in the mouse retina. Loss-of-function studies indicate that Dscam is required for refinement of retinal ganglion cell (RGC) axons in the lateral geniculate nucleus, and in this study we report and describe a requirement for Dscam in the maintenance of RGC axon projections within the retina. Mouse Dscam loss of function phenotypes related to retinal ganglion cell axon outgrowth and targeting have not been previously reported, despite the abundance of axon phenotypes reported in Drosophila Dscam1 loss and gain of function models...
March 2016: Molecular and Cellular Neurosciences
Louise Thiry, Maxime Lemieux, Olivier D Laflamme, Frédéric Bretzner
Locomotion is controlled by spinal circuits that generate rhythm and coordinate left-right and flexor-extensor motoneuronal activities. The outputs of motoneurons and spinal interneuronal circuits are shaped by sensory feedback, relaying peripheral signals that are critical to the locomotor and postural control. Several studies in invertebrates and vertebrates have argued that the Down syndrome cell adhesion molecule (DSCAM) would play an important role in the normal development of neural circuits through cell spacing and targeting, axonal and dendritic branching, and synapse establishment and maintenance...
March 2016: Journal of Neurophysiology
Chisako Sakuma, Misako Okumura, Tomoki Umehara, Masayuki Miura, Takahiro Chihara
During neural development, regulation of microtubule stability is essential for proper morphogenesis of neurons. Recently, the striatin-interacting phosphatase and kinase (STRIPAK) complex was revealed to be involved in diverse cellular processes. However, there is little evidence that STRIPAK components regulate microtubule dynamics, especially in vivo. Here, we show that one of the core STRIPAK components, Strip, is required for microtubule organization during neuronal morphogenesis. Knockdown of Strip causes a decrease in the level of acetylated α-tubulin in Drosophila S2 cells, suggesting that Strip influences the stability of microtubules...
December 8, 2015: Scientific Reports
Yuan Yue, Yun Yang, Lanzhi Dai, Guozheng Cao, Ran Chen, Weiling Hong, Baoping Liu, Yang Shi, Yijun Meng, Feng Shi, Mu Xiao, Yongfeng Jin
Mutually exclusive splicing is an important means of increasing the protein repertoire, by which the Down's syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 different isoforms in Drosophila melanogaster. However, the regulatory mechanisms remain obscure due to the complexity of the Dscam exon cluster. Here, we reveal a molecular model for the regulation of the mutually exclusive splicing of the serpent pre-mRNA based on competition between upstream and downstream RNA pairings. Such dual RNA pairings confer fine tuning of the inclusion of alternative exons...
January 2016: RNA
Daniela Brites, Louis Du Pasquier
Arthropod Dscam, the homologue of the human Down Syndrome cell adhesion molecule, is a receptor used by the nervous and immune systems. Unlike in vertebrates, evolutionary pressure has selected and maintained a vast Dscam diversity of isoforms, known to specifying neuronal identity during the nervous system differentiation. This chapter examines the different modes of Dscam diversification in the context of arthropods' evolution and that of their immune system, where its role is controversial. In the single Dscam gene of insects and crustaceans, mutually exclusive alternative splicing affects three clusters of duplicated exons encoding the variable parts of the receptor...
2015: Results and Problems in Cell Differentiation
Susan J Fisher
The causes of preeclampsia remain one of the great medical mysteries of our time. This syndrome is thought to occur in 2 stages with abnormal placentation leading to a maternal inflammatory response. Specific regions of the placenta have distinct pathologic features. During normal pregnancy, cytotrophoblasts emigrate from the chorionic villi and invade the uterus, reaching the inner third of the myometrium. This unusual process is made even more exceptional by the fact that the placental cells are hemiallogeneic, coexpressing maternal and paternal genomes...
October 2015: American Journal of Obstetrics and Gynecology
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