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https://www.readbyqxmd.com/read/28387217/defective-gpsm2-g%C3%AE-i3-signalling-disrupts-stereocilia-development-and-growth-cone-actin-dynamics-in-chudley-mccullough-syndrome
#1
Stephanie A Mauriac, Yeri E Hien, Jonathan E Bird, Steve Dos-Santos Carvalho, Ronan Peyroutou, Sze Chim Lee, Maite M Moreau, Jean-Michel Blanc, Aysegul Geyser, Chantal Medina, Olivier Thoumine, Sandra Beer-Hammer, Thomas B Friedman, Lukas Rüttiger, Andrew Forge, Bernd Nürnberg, Nathalie Sans, Mireille Montcouquiol
Mutations in GPSM2 cause Chudley-McCullough syndrome (CMCS), an autosomal recessive neurological disorder characterized by early-onset sensorineural deafness and brain anomalies. Here, we show that mutation of the mouse orthologue of GPSM2 affects actin-rich stereocilia elongation in auditory and vestibular hair cells, causing deafness and balance defects. The G-protein subunit Gαi3, a well-documented partner of Gpsm2, participates in the elongation process, and its absence also causes hearing deficits. We show that Gpsm2 defines an ∼200 nm nanodomain at the tips of stereocilia and this localization requires the presence of Gαi3, myosin 15 and whirlin...
April 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28373358/neurofilaments-and-neurofilament-proteins-in-health-and-disease
#2
REVIEW
Aidong Yuan, Mala V Rao, Veeranna, Ralph A Nixon
SUMMARYNeurofilaments (NFs) are unique among tissue-specific classes of intermediate filaments (IFs) in being heteropolymers composed of four subunits (NF-L [neurofilament light]; NF-M [neurofilament middle]; NF-H [neurofilament heavy]; and α-internexin or peripherin), each having different domain structures and functions. Here, we review how NFs provide structural support for the highly asymmetric geometries of neurons and, especially, for the marked radial expansion of myelinated axons crucial for effective nerve conduction velocity...
April 3, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28224388/ocular-safety-of-intravitreal-clindamycin-hydrochloride-released-by-plga-implants
#3
Gabriella M Fernandes-Cunha, Silvia Ligório Fialho, Gisele Rodrigues da Silva, Armando Silva-Cunha, Min Zhao, Francine Behar-Cohen
BACKGROUND: Drug ocular toxicity is a field that requires attention. Clindamycin has been injected intravitreally to treat ocular toxoplasmosis, the most common cause of eye posterior segment infection worldwide. However, little is known about the toxicity of clindamycin to ocular tissues. We have previously showed non intraocular toxicity in rabbit eyes of poly(lactic-co-glycolic acid) (PLGA) implants containing clindamycin hydrochloride (CLH) using only clinical macroscotopic observation...
February 21, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28199839/the-survival-of-motor-neuron-protein-acts-as-a-molecular-chaperone-for-mrnp-assembly
#4
Paul G Donlin-Asp, Claudia Fallini, Jazmin Campos, Ching-Chieh Chou, Megan E Merritt, Han C Phan, Gary J Bassell, Wilfried Rossoll
Spinal muscular atrophy (SMA) is a motor neuron disease caused by reduced levels of the survival of motor neuron (SMN) protein. SMN is part of a multiprotein complex that facilitates the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs). SMN has also been found to associate with mRNA-binding proteins, but the nature of this association was unknown. Here, we have employed a combination of biochemical and advanced imaging methods to demonstrate that SMN promotes the molecular interaction between IMP1 protein and the 3' UTR zipcode region of β-actin mRNA, leading to assembly of messenger ribonucleoprotein (mRNP) complexes that associate with the cytoskeleton to facilitate trafficking...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28194647/cofilin-mediates-lps-induced-microglial-cell-activation-and-associated-neurotoxicity-through-activation-of-nf-%C3%AE%C2%BAb-and-jak-stat-pathway
#5
Qasim Alhadidi, Zahoor A Shah
Microglial cells are activated in response to different types of injuries or stress in the CNS. Such activation is necessary to get rid of the injurious agents and restore tissue homeostasis. However, excessive activation of microglial cells is harmful and contributes to secondary injury. Pertinently, microglial cell activity was targeted in many preclinical and clinical studies but such strategy failed in clinical trials. The main reason behind the failed attempts is the complexity of the injury mechanisms which needs either a combination therapy or targeting a process that is involved in multiple pathways...
February 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28107513/the-zebrafish-anillin-egfp-reporter-marks-late-dividing-retinal-precursors-and-stem-cells-entering-neuronal-lineages
#6
Meret Cepero Malo, Anne-Laure Duchemin, Luca Guglielmi, Eva Patzel, Saadettin Sel, Gerd U Auffarth, Matthias Carl, Lucia Poggi
Monitoring cycling behaviours of stem and somatic cells in the living animal is a powerful tool to better understand tissue development and homeostasis. The tg(anillin:anillin-eGFP) transgenic line carries the full-length zebrafish F-actin binding protein Anillin fused to eGFP from a bacterial artificial chromosome (BAC) containing Anillin cis-regulatory sequences. Here we report the suitability of the Anillin-eGFP reporter as a direct indicator of cycling cells in the late embryonic and post-embryonic retina...
2017: PloS One
https://www.readbyqxmd.com/read/28077579/neuron-enriched-rna-binding-proteins-regulate-pancreatic-beta-cell-function-and-survival
#7
Jonàs Juan-Mateu, Tatiana H Rech, Olatz Villate, Esther Lizarraga-Mollinedo, Anna Wendt, Jean-Valery Turatsinze, Letícia A Brondani, Tarlliza R Nardelli, Tatiane C Nogueira, Jonathan L S Esguerra, Maria Inês Alvelos, Piero Marchetti, Lena Eliasson, Décio L Eizirik
Pancreatic beta cell failure is the central event leading to diabetes. Beta cells share many phenotypic traits with neurons, and proper beta cell function relies on the activation of several neuron-like transcription programs. Regulation of gene expression by alternative splicing plays a pivotal role in brain, where it affects neuronal development, function, and disease. The role of alternative splicing in beta cells remains unclear, but recent data indicate that splicing alterations modulated by both inflammation and susceptibility genes for diabetes contribute to beta cell dysfunction and death...
February 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28062917/the-enteric-nervous-system-and-the-musculature-of-the-colon-are-altered-in-patients-with-spina-bifida-and-spinal-cord-injury
#8
Marjanne den Braber-Ymker, Martin Lammens, Michel J A M van Putten, Iris D Nagtegaal
Neurogenic bowel dysfunction occurs in a large percentage of adult patients with spina bifida (SB) and spinal cord injury (SCI), significantly affecting their quality of life. Although bowel motility is autonomously regulated by the enteric nervous system (ENS), disruption of the modulation of the ENS by extrinsic innervation as present in many patients with SB and SCI might lead to motility disorders. In order to gain insight in the pathophysiology, we studied histological changes of the neuromuscular structures in the colon of SB and SCI patients...
February 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28005071/rab8a-rab11a-regulate-intercellular-communications-between-neural-cells-via-tunneling-nanotubes
#9
Hui Zhu, Chengbin Xue, Xi Xu, Yibing Guo, Xiaohong Li, Jingjing Lu, Shaoqing Ju, Yongjun Wang, Zheng Cao, Xiaosong Gu
Tunneling nanotubes (TNTs) are F-actin-based membrane tubes, and can form between cultured cells and within vital tissues. TNTs mediate intercellular communications that range from electrical signaling to the transfer of organelles. Following peripheral nerve injury, the orchestrated intercellular communications among neural and non-neural cells are required for effective nerve regeneration. It remains unknown whether TNTs exist between neural cells in the peripheral nerve system and how TNTs affect neural regeneration...
December 22, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27964758/expression-of-acid-sensing-ion-channels-and-selection-of-reference-genes-in-mouse-and-naked-mole-rat
#10
Laura-Nadine Schuhmacher, Ewan St John Smith
Acid-sensing ion channels (ASICs) are a family of ion channels comprised of six subunits encoded by four genes and they are expressed throughout the peripheral and central nervous systems. ASICs have been implicated in a wide range of physiological and pathophysiological processes: pain, breathing, synaptic plasticity and excitotoxicity. Unlike mice and humans, naked mole-rats do not perceive acid as a noxious stimulus, even though their sensory neurons express functional ASICs, likely an adaptation to living in a hypercapnic subterranean environment...
December 13, 2016: Molecular Brain
https://www.readbyqxmd.com/read/27942867/thymosin-%C3%AE-4-overexpression-regulates-neuron-production-and-spatial-distribution-in-the-developing-avian-optic-tectum
#11
Mael Lever, Carsten Theiss, Gabriela Morosan-Puopolo, Beate Brand-Saberi
Thymosin β4 (Tβ4), the principal G-actin regulating entity in eukaryotic cells, has also multiple intra- and extracellular functions related to tissue regeneration and healing. While its effect in adult organs is being widely investigated, currently, little is known about its influence on embryonic tissues, i.e., in the developing nervous system. The importance of Tβ4 for neural stem cell proliferation in the embryonic chicken optic tectum (OT) has previously been shown by us for the first time. In the present study, using in ovo electroporation, we carried out a quantification of the effects of the Tβ4-overexpression on the developing chicken OT between E4 and E6 at the hemisphere as well as cellular level...
December 10, 2016: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/27881869/netrin-1-induced-stem-cell-bioactivity-contributes-to-the-regeneration-of-injured-tissues-via-the-lipid-raft-dependent-integrin-%C3%AE-6%C3%AE-4-signaling-pathway
#12
Soo Sang Lee, Sei-Jung Lee, Sang Hun Lee, Jung Min Ryu, Hyeon Su Lim, Jun Sung Kim, Eun Ju Song, Young Hyun Jung, Hyun Jik Lee, Chung Hun Kim, Ho Jae Han
Netrin-1 (Ntn-1) is a multifunctional neuronal signaling molecule; however, its physiological significance, which improves the tissue-regeneration capacity of stem cells, has not been characterized. In the present study, we investigate the mechanism by which Ntn-1 promotes the proliferation of hUCB-MSCs with regard to the regeneration of injured tissues. We found that Ntn-1 induces the proliferation of hUCB-MSCs mainly via Inα6β4 coupled with c-Src. Ntn-1 induced the recruitment of NADPH oxidases and Rac1 into membrane lipid rafts to facilitate ROS production...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27867348/better-targeting-better-efficiency-for-wide-scale-neuronal-transduction-with-the-synapsin-promoter-and-aav-php-b
#13
Kasey L Jackson, Robert D Dayton, Benjamin E Deverman, Ronald L Klein
Widespread genetic modification of cells in the central nervous system (CNS) with a viral vector has become possible and increasingly more efficient. We previously applied an AAV9 vector with the cytomegalovirus/chicken beta-actin (CBA) hybrid promoter and achieved wide-scale CNS transduction in neonatal and adult rats. However, this method transduces a variety of tissues in addition to the CNS. Thus we studied intravenous AAV9 gene transfer with a synapsin promoter to better target the neurons. We noted in systematic comparisons that the synapsin promoter drives lower level expression than does the CBA promoter...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27843073/off-target-effect-of-sildenafil-on-postsurgical-erectile-dysfunction-alternate-pathways-and-localized-delivery-system
#14
Amirali Salmasi, Geun Taek Lee, Neal Patel, Ritu Goyal, Michael Dinizo, Young Suk Kwon, Part K Modi, Izak Faiena, Hee-Jin Kim, Nara Lee, Johanna L Hannan, Joachim Kohn, Isaac Yi Kim
INTRODUCTION: There is no consensus on the best oral phosphodiesterase type 5 inhibitor (PDE5I) for patients undergoing penile rehabilitation after surgical nerve injury. AIM: To determine the mechanism of PDE5I on cultured neuronal cells and the effectiveness of local drug delivery using nanospheres (NSPs) to sites of nerve injury in a rat model of bilateral cavernous nerve injury (BCNI). METHODS: The effects of sildenafil, tadalafil, and vardenafil on cyclic adenosine monophosphate, cyclic guanosine monophosphate, and cell survival after exposure to hypoxia and H2O2 were measured in PC12, SH-SY5Y, and NTERA-2 (NT2) cell cultures...
December 2016: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/27825441/neurotrophin-signaling-is-required-for-glucose-induced-insulin-secretion
#15
Jessica Houtz, Philip Borden, Alexis Ceasrine, Liliana Minichiello, Rejji Kuruvilla
Insulin secretion by pancreatic islet β cells is critical for glucose homeostasis, and a blunted β cell secretory response is an early deficit in type 2 diabetes. Here, we uncover a regulatory mechanism by which glucose recruits vascular-derived neurotrophins to control insulin secretion. Nerve growth factor (NGF), a classical trophic factor for nerve cells, is expressed in pancreatic vasculature while its TrkA receptor is localized to islet β cells. High glucose rapidly enhances NGF secretion and increases TrkA phosphorylation in mouse and human islets...
November 7, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27756615/cytoskeletal-dynamics-during-in-vitro-neurogenesis-of-induced-pluripotent-stem-cells-ipscs
#16
Claudia Compagnucci, Emanuela Piermarini, Antonella Sferra, Rossella Borghi, Alessia Niceforo, Stefania Petrini, Fiorella Piemonte, Enrico Bertini
Patient-derived induced pluripotent stem cells (iPSCs) provide a novel tool to investigate the pathophysiology of poorly known diseases, in particular those affecting the nervous system, which has been difficult to study for its lack of accessibility. In this emerging and promising field, recent iPSCs studies are mostly used as "proof-of-principle" experiments that are confirmatory of previous findings obtained from animal models and postmortem human studies; its promise as a discovery tool is just beginning to be realized...
December 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27725917/human-somatic-cells-acquire-the-plasticity-to-generate-embryoid-like-metamorphosis-via-the-actin-cytoskeleton-in-injured-tissues
#17
Jairo A Diaz, Mauricio F Murillo, Jhonan A Mendoza, Ana M Barreto, Lina S Poveda, Lina K Sanchez, Laura C Poveda, Katherine T Mora
Emergent biological responses develop via unknown processes dependent on physical collision. In hypoxia, when the tissue architecture collapses but the geometric core is stable, actin cytoskeleton filament components emerge, revealing a hidden internal order that identifies how each molecule is reassembled into the original mold, using one common connection, i.e., a fractal self-similarity that guides the system from the beginning in reverse metamorphosis, with spontaneous self-assembly of past forms that mimics an embryoid phenotype...
2016: American Journal of Stem Cells
https://www.readbyqxmd.com/read/27720798/blast-waves-from-detonated-military-explosive-reduce-glur1-and-synaptophysin-levels-in-hippocampal-slice-cultures
#18
Marquitta Smith, Thuvan Piehler, Richard Benjamin, Karen L Farizatto, Morgan C Pait, Michael F Almeida, Vladimir V Ghukasyan, Ben A Bahr
Explosives create shockwaves that cause blast-induced neurotrauma, one of the most common types of traumatic brain injury (TBI) linked to military service. Blast-induced TBIs are often associated with reduced cognitive and behavioral functions due to a variety of factors. To study the direct effects of military explosive blasts on brain tissue, we removed systemic factors by utilizing rat hippocampal slice cultures. The long-term slice cultures were briefly sealed air-tight in serum-free medium, lowered into a 37°C water-filled tank, and small 1...
October 5, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27645771/pak1-regulates-inhibitory-synaptic-function-via-a-novel-mechanism-mediated-by-endocannabinoids
#19
Shuting Xia, Zikai Zhou, Zhengping Jia
The Rho family small GTPases and their effectors, including PAKs, are extensively studied in the context of the actin cytoskeleton, excitatory synaptic function, spine morphology and memory formation. However, their roles in inhibitory synaptic function remain poorly understood. We have recently shown that PAK1 is a potent regulator of GABAergic synaptic transmission. Thus, disruption of PAK1 leads to significant impairments in inhibitory postsynaptic currents which are manifested as reduced GABA presynaptic releases...
September 20, 2016: Small GTPases
https://www.readbyqxmd.com/read/27524794/alzheimer-related-decrease-in-cyfip2-links-amyloid-production-to-tau-hyperphosphorylation-and-memory-loss
#20
Sachin Suresh Tiwari, Keiko Mizuno, Anshua Ghosh, Wajeeha Aziz, Claire Troakes, Jason Daoud, Vidushi Golash, Wendy Noble, Tibor Hortobágyi, Karl Peter Giese
Characteristic features of Alzheimer's disease are memory loss, plaques resulting from abnormal processing of amyloid precursor protein (APP), and presence of neurofibrillary tangles and dystrophic neurites containing hyperphosphorylated tau. Currently, it is not known what links these abnormalities together. Cytoplasmic FMR1 interacting protein 2 (CYFIP2) has been suggested to regulate mRNA translation at synapses and this may include local synthesis of APP and alpha-calcium/calmodulin-dependent kinase II, a kinase that can phosphorylate tau...
October 2016: Brain: a Journal of Neurology
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