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https://www.readbyqxmd.com/read/29048670/suppression-of-tumor-derived-semaphorin%C3%A2-7a-and-genetic-ablation-of-host-derived-semaphorin%C3%A2-7a-impairs-tumor-progression-in-a-murine-model-of-advanced-breast-carcinoma
#1
R Garcia-Areas, S Libreros, M Simoes, C Castro-Silva, N Gazaniga, S Amat, J Jaczewska, P Keating, K Schilling, M Brito, E P Wojcikiewicz, V Iragavarpu-Charyulu
Solid tumors can generate a plethora of neurogenesis-related molecules that enhance their growth and metastasis. Among them, we have identified axonal guidance molecule Semaphorin 7A (SEMA7A) in breast cancer. The goal of this study was to determine the therapeutic effect of suppressing SEMA7A levels in the 4T1 murine model of advanced breast carcinoma. We used anti-SEMA7A short hairpin RNA (shRNA) to gene silence SEMA7A in 4T1 mammary tumor cells. When implanted into the mammary fat pads of syngeneic mice, SEMA7A shRNA-expressing 4T1 tumors exhibited decreased growth rates, deferred metastasis and reduced mortality...
October 3, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29044418/friedreich-ataxia-developmental-failure-of-the-dorsal-root-entry-zone
#2
Arnulf H Koeppen, Alyssa B Becker, Jiang Qian, Benjamin B Gelman, Joseph E Mazurkiewicz
Dorsal root ganglia, dorsal roots (DR), and dorsal root entry zones (DREZ) are vulnerable to frataxin deficiency in Friedreich ataxia (FA). A previously unrecognized abnormality is the intrusion of astroglial tissue into DR. Segments of formalin-fixed upper lumbar spinal cord of 13 homozygous and 2 compound heterozygous FA patients were sectioned longitudinally to represent DREZ and stained for glial fibrillary acidic protein (GFAP), S100, vimentin, the central nervous system (CNS)-specific myelin protein proteolipid protein, the peripheral nervous system (PNS) myelin proteins PMP-22 and P0, and the Schwann cell proteins laminin, alpha-dystroglycan, and periaxin...
November 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29041904/shift-in-the-function-of-netrin-1-from-axon-outgrowth-to-axon-branching-in-developing-cerebral-cortical-neurons
#3
Hideko Matsumoto, Masabumi Nagashima
BACKGROUND: Netrin-1, a multifunctional axon guidance cue, elicits axon outgrowth via one of its receptors deleted in colorectal cancer (DCC) in several types of neurons, including cerebral cortical neurons of embryonic mice. However, we and others have observed de novo formation of axon branches without axon outgrowth induced by netrin-1 in cortical culture of neonatal hamsters. These previous reports suggested the possibility that netrin-1 function might alter during development, which we here investigated using dissociated culture prepared from cerebral cortices of embryonic mice...
October 17, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/29039486/analysis-of-mirna-expression-profiling-in-human-umbilical-vein-endothelial-cells-affected-by-heat-stress
#4
Jie Liu, Guoguo Zhu, Siya Xu, Shixin Liu, Qiping Lu, Zhongzhi Tang
To investigate the regulation of endothelial cell (EC) microRNAs (miRNAs) altered by heat stress, miRNA microarrays and bioinformatics methods were used to determine changes in miRNA profiles and the pathophysiological characteristics of differentially expressed miRNAs. A total of 31 differentially expressed miRNAs were identified, including 20 downregulated and 11 upregulated miRNAs. Gene Ontology (GO) enrichment analysis revealed that the validated targets of the differentially expressed miRNAs were significantly enriched in gene transcription regulation...
October 5, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29038581/transcriptional-repression-of-plxnc1-by-lmx1a-and-lmx1b-directs-topographic-dopaminergic-circuit-formation
#5
Audrey Chabrat, Guillaume Brisson, Hélène Doucet-Beaupré, Charleen Salesse, Marcos Schaan Profes, Axelle Dovonou, Cléophace Akitegetse, Julien Charest, Suzanne Lemstra, Daniel Côté, R Jeroen Pasterkamp, Monica I Abrudan, Emmanouil Metzakopian, Siew-Lan Ang, Martin Lévesque
Mesodiencephalic dopamine neurons play central roles in the regulation of a wide range of brain functions, including voluntary movement and behavioral processes. These functions are served by distinct subtypes of mesodiencephalic dopamine neurons located in the substantia nigra pars compacta and the ventral tegmental area, which form the nigrostriatal, mesolimbic, and mesocortical pathways. Until now, mechanisms involved in dopaminergic circuit formation remained largely unknown. Here, we show that Lmx1a, Lmx1b, and Otx2 transcription factors control subtype-specific mesodiencephalic dopamine neurons and their appropriate axon innervation...
October 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29032842/making-dopamine-connections-in-adolescence
#6
REVIEW
Daniel Hoops, Cecilia Flores
A dramatic maturational process ongoing in adolescence is prefrontal cortex development, including its dopamine innervation. Dopamine axons grow from the striatum to the prefrontal cortex, the only known case of long-distance axon growth during adolescence. This is coordinated by the Netrin-1 guidance cue receptor DCC (deleted in colorectal cancer), which in turn controls the intrinsic development of the prefrontal cortex itself. Stimulant drugs in adolescence alter DCC in dopamine neurons and, in turn prefrontal cortex maturation, impacting cognitive abilities...
October 9, 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/29029846/identification-of-novel-risk-loci-for-restless-legs-syndrome-in-genome-wide-association-studies-in-individuals-of-european-ancestry-a-meta-analysis
#7
REVIEW
Barbara Schormair, Chen Zhao, Steven Bell, Erik Tilch, Aaro V Salminen, Benno Pütz, Yves Dauvilliers, Ambra Stefani, Birgit Högl, Werner Poewe, David Kemlink, Karel Sonka, Cornelius G Bachmann, Walter Paulus, Claudia Trenkwalder, Wolfgang H Oertel, Magdolna Hornyak, Maris Teder-Laving, Andres Metspalu, Georgios M Hadjigeorgiou, Olli Polo, Ingo Fietze, Owen A Ross, Zbigniew Wszolek, Adam S Butterworth, Nicole Soranzo, Willem H Ouwehand, David J Roberts, John Danesh, Richard P Allen, Christopher J Earley, William G Ondo, Lan Xiong, Jacques Montplaisir, Ziv Gan-Or, Markus Perola, Pavel Vodicka, Christian Dina, Andre Franke, Lukas Tittmann, Alexandre F R Stewart, Svati H Shah, Christian Gieger, Annette Peters, Guy A Rouleau, Klaus Berger, Konrad Oexle, Emanuele Di Angelantonio, David A Hinds, Bertram Müller-Myhsok, Juliane Winkelmann
BACKGROUND: Restless legs syndrome is a prevalent chronic neurological disorder with potentially severe mental and physical health consequences. Clearer understanding of the underlying pathophysiology is needed to improve treatment options. We did a meta-analysis of genome-wide association studies (GWASs) to identify potential molecular targets. METHODS: In the discovery stage, we combined three GWAS datasets (EU-RLS GENE, INTERVAL, and 23andMe) with diagnosis data collected from 2003 to 2017, in face-to-face interviews or via questionnaires, and involving 15 126 cases and 95 725 controls of European ancestry...
November 2017: Lancet Neurology
https://www.readbyqxmd.com/read/29025592/significantly-mutated-genes-and-regulatory-pathways-in-sclc-a-meta-analysis
#8
Varsha Sundaresan, Victor T Lin, Faming Liang, Frederic J Kaye, Reika Kawabata-Iwakawa, Kouya Shiraishi, Takashi Kohno, Jun Yokota, Lei Zhou
Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers and demands effective targeted therapeutic strategies. In this meta-analysis study, we aim to identify significantly mutated genes and regulatory pathways to help us better understand the progression of SCLC and to identify potential biomarkers. Besides ranking genes based on their mutation frequencies, we sought to identify statistically significant mutations in SCLC with the MutSigCV software. Our analysis identified several genes with relatively low mutation frequency, including PTEN, as highly significant (p < 0...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29017837/robo-ig4-is-a-dimerization-domain
#9
Galit Yom-Tov, Reut Barak, Omri Matalon, Mira Barda-Saad, Julia Guez-Haddad, Yarden Opatowsky
Robo receptors play pivotal roles in axonal guidance as well as in neurogenesis, angiogenesis, cell migration, and cancer progression and invasiveness. They are considered to be attractive drug targets for the treatment of cancer, ocular neovascular disorders, chronic kidney diseases, and more. Despite their great importance, the mechanisms by which Robo receptors switch from their "off" to "on" states remain obscure. One possibility involves a monomer-to-dimer or dimer-to-monomer transition that facilitates the recruitment and activation of enzymatic effectors to instigate intracellular signaling...
October 7, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29016853/metalloprotease-mediated-cleavage-of-plexind1-and-its-sequestration-to-actin-rods-in-the-motoneuron-disease-spinal-muscular-atrophy-sma
#10
Sebastian Rademacher, Bert M Verheijen, Niko Hensel, Miriam Peters, Gamze Bora, Gudrun Brandes, Renata Vieira de Sá, Natascha Heidrich, Silke Fischer, Hella Brinkmann, W Ludo van der Pol, Brunhilde Wirth, R Jeroen Pasterkamp, Peter Claus
Cytoskeletal rearrangement during axon growth is mediated by guidance receptors and their ligands which act either as repellent, attractant or both. Regulation of the actin cytoskeleton is disturbed in Spinal Muscular Atrophy (SMA), a devastating neurodegenerative disease affecting mainly motoneurons, but receptor-ligand interactions leading to the dysregulation causing SMA are poorly understood. In this study, we analysed the role of the guidance receptor PlexinD1 in SMA pathogenesis. We showed that PlexinD1 is cleaved by metalloproteases in SMA and that this cleavage switches its function from an attractant to repellent...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28993416/regulation-of-axon-guidance-by-the-wnt-receptor-ror-cam-1-in-the-pvt-guidepost-cell-in%C3%A2-caenorhabditis-elegans
#11
Jason Chien, Ranjan Devkota, Nebeyu Yosef, Catarina Mörck
The Caenorhabditis elegans ventral nerve cord (VNC) consists of two asymmetric bundles of neurons and axons that are separated by the midline. How the axons are guided to stay on the correct sides of the midline remains poorly understood. Here we provide evidence that the conserved Wnt signaling pathway along with the Netrin and Robo pathways constitute a combinatorial code for midline guidance of PVP and PVQ axons that extend into the VNC. Combined loss of the Wnts CWN-1, CWN-2 and EGL-20 or loss of the Wnt receptor CAM-1 caused more than 70 % of PVP and PVQ axons to inappropriately cross over from the left side to the right side...
October 9, 2017: Genetics
https://www.readbyqxmd.com/read/28990762/multichanneled-nerve-guidance-conduit-with-spatial-gradients-of-neurotrophic-factors-and-oriented-nanotopography-for-repairing-the-peripheral-nervous-system
#12
Yo-Cheng Chang, Ming-Hong Chen, Shih-Yung Liao, Hsi-Chin Wu, Chen-Hsiang Kuan, Jui-Sheng Sun, Tzu-Wei Wang
Peripheral nerve injuries, causing sensory and motor impairment, affect a great number of patients annually. It is therefore important to incorporate different strategies to promote nerve healing. Among the treatment options, however, the efficacy of nerve conduits is often compromised by their lack of living cells, insufficient growth factors, and absence of the extracellular matrix (ECM)-like structure. To improve the functional recovery, we aimed to develop a natural biodegradable multichanneled scaffold characterized with aligned electrospun nanofibers and neurotrophic gradient (MC/AN/NG) to guide axon outgrowth...
October 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28986946/effect-of-decellularized-spinal-scaffolds-on-spinal-axon-regeneration-in-rats
#13
Junyi Zhu, Yingfeng Lu, Fangzheng Yu, Lebin Zhou, Jiawei Shi, Qihui Chen, Weili Ding, Xin Wen, Yu-Qiang Ding, Jin Mei, Jian Wang
A series of complex influencing factors lead to failure of neural regeneration after spinal cord injury (SCI). Up to now, there is no robust treatment that can restore the loss of function caused by injury. Because damaged spinal axons do not spontaneously regenerate in their naturally inhibitory microenvironments, biomaterials that induce neural regeneration to appear as attractive treatments to improve the microenvironmental conditions after SCI. In this study, we report the novel use of decellularized (DC) scaffolds to provide contact guidance for axonal regrowth in vivo...
October 7, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28986144/motor-axons-are-guided-to-exit-points-in-the-spinal-cord-by-slit-and-netrin-signals
#14
Minkyung Kim, Tatiana M Fontelonga, Clare H Lee, Sarah J Barnum, Grant S Mastick
In the spinal cord, motor axons project out the neural tube at specific exit points, then bundle together to project toward target muscles. The molecular signals that guide motor axons to and out of their exit points remain undefined. Since motor axons and their exit points are located near the floor plate, guidance signals produced by the floor plate and adjacent ventral tissues could influence motor axons as they project toward and out of exit points. The secreted Slit proteins are major floor plate repellents, and motor neurons express two Slit receptors, Robo1 and Robo2...
October 3, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28979185/the-membrane-glycoprotein-m6a-endocytic-recycling-pathway-involves-clathrin-mediated-endocytosis-and-affects-neuronal-synapses
#15
Micaela D Garcia, Karina Formoso, Gabriela I Aparicio, Alberto C C Frasch, Camila Scorticati
Single point mutations or variations in the expression of the gene encoding the neuronal glycoprotein M6a have been associated with psychiatric disorders such as Alzheimer's disease, depression and schizophrenia. In cultured neurons, M6a positively contributes to neurite extension, axon guidance, filopodia/spine outgrowth, and synapse formation. The endocytic processes of neuronal membrane proteins are linked to the differentiation, growth, signaling and plasticity of neurons. However, the roles of M6a and the precise mechanisms through which M6a internalizes and recycles back to the neuronal membrane are unknown...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28975768/a-physicochemically-optimized-and-neuroconductive-biphasic-nerve-guidance-conduit-for-peripheral-nerve-repair
#16
Alan J Ryan, William A Lackington, Alan J Hibbitts, Austyn Matheson, Tijna Alekseeva, Anna Stejskalova, Phoebe Roche, Fergal J O'Brien
Clinically available hollow nerve guidance conduits (NGCs) have had limited success in treating large peripheral nerve injuries. This study aims to develop a biphasic NGC combining a physicochemically optimized collagen outer conduit to bridge the transected nerve, and a neuroconductive hyaluronic acid-based luminal filler to support regeneration. The outer conduit is mechanically optimized by manipulating crosslinking and collagen density, allowing the engineering of a high wall permeability to mitigate the risk of neuroma formation, while also maintaining physiologically relevant stiffness and enzymatic degradation tuned to coincide with regeneration rates...
October 4, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28975140/patient-derived-hipsc-neurons-with-heterozygous-cntnap2-deletions-display-altered-neuronal-gene-expression-and-network-activity
#17
Erin Flaherty, Rania M Deranieh, Elena Artimovich, Inkyu S Lee, Arthur J Siegel, Deborah L Levy, Michael W Nestor, Kristen J Brennand
Variants in CNTNAP2, a member of the neurexin family of genes that function as cell adhesion molecules, have been associated with multiple neuropsychiatric conditions such as schizophrenia, autism spectrum disorder and intellectual disability; animal studies indicate a role for CNTNAP2 in axon guidance, dendritic arborization and synaptogenesis. We previously reprogrammed fibroblasts from a family trio consisting of two carriers of heterozygous intragenic CNTNAP2 deletions into human induced pluripotent stem cells (hiPSCs) and described decreased migration in the neural progenitor cells (NPCs) differentiated from the affected CNTNAP2 carrier in this trio...
2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28974727/timing-and-localization-of-human-dystrophin-isoform-expression-provide-insights-into-the-cognitive-phenotype-of-duchenne-muscular-dystrophy
#18
Nathalie Doorenweerd, Ahmed Mahfouz, Maaike van Putten, Rajaram Kaliyaperumal, Peter A C T' Hoen, Jos G M Hendriksen, Annemieke M Aartsma-Rus, Jan J G M Verschuuren, Erik H Niks, Marcel J T Reinders, Hermien E Kan, Boudewijn P F Lelieveldt
Duchenne muscular dystrophy (DMD) is a muscular dystrophy with high incidence of learning and behavioural problems and is associated with neurodevelopmental disorders. To gain more insights into the role of dystrophin in this cognitive phenotype, we performed a comprehensive analysis of the expression patterns of dystrophin isoforms across human brain development, using unique transcriptomic data from Allen Human Brain and BrainSpan atlases. Dystrophin isoforms show large changes in expression through life with pronounced differences between the foetal and adult human brain...
October 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28970473/patient-derived-hipsc-neurons-with-heterozygous-cntnap2-deletions-display-altered-neuronal-gene-expression-and-network-activity
#19
Erin Flaherty, Rania M Deranieh, Elena Artimovich, Inkyu S Lee, Arthur J Siegel, Deborah L Levy, Michael W Nestor, Kristen J Brennand
Variants in CNTNAP2, a member of the neurexin family of genes that function as cell adhesion molecules, have been associated with multiple neuropsychiatric conditions such as schizophrenia, autism spectrum disorder and intellectual disability; animal studies indicate a role for CNTNAP2 in axon guidance, dendritic arborization and synaptogenesis. We previously reprogrammed fibroblasts from a family trio consisting of two carriers of heterozygous intragenic CNTNAP2 deletions into human induced pluripotent stem cells (hiPSCs) and described decreased migration in the neural progenitor cells (NPCs) differentiated from the affected CNTNAP2 carrier in this trio...
October 2, 2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28970231/the-terminal-nerve-plays-a-prominent-role-in-gnrh-1-neuronal-migration-independent-from-proper-olfactory-and-vomeronasal-connections-to-the-olfactory-bulbs
#20
Ed Zandro M Taroc, Aparna Prasad, Jennifer M Lin, Paolo E Forni
Gonadotropin-releasing hormone-1 (GnRH-1) neurons (GnRH-1 ns) migrate from the developing olfactory pit into the hypothalamus during embryonic development. Migration of the GnRH-1 neurons is required for mammalian reproduction as these cells control release of gonadotropins from the anterior pituitary gland. Disturbances in GnRH-1 ns migration, GnRH-1 synthesis, secretion or signaling lead to varying degrees of hypogonadotropic hypogonadism (HH), which impairs pubertal onset and fertility. HH associated with congenital olfactory defects is clinically defined as Kallmann Syndrome (KS)...
October 15, 2017: Biology Open
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