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Neuromuscular junction

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https://www.readbyqxmd.com/read/29231975/the-precise-subcellular-localization-of-dlg-in-the-drosophila-larva-body-wall-using-improved-pre-embedding-immuno-em
#1
Guangming Gan, Chenchen Zhang
Discs-large (Dlg) plays important roles in nerve tissue and epithelial tissue in Drosophila. However, the precise positioning of Dlg in the neuromuscular junction remains to be confirmed using an optimized labeling method. In this study, we improved the method of pre-embedding immunogold electron microscopy without the osmic tetroxide procedure, and we found that Lowicryl K4 M resin and low temperature helped to preserve the authenticity of the labeling signal with relatively good contrast. Dlg was strongly expressed in the entire subsynaptic reticulum (SSR) membrane of type Ib boutons, expressed in parts of the SSR membrane of type Is boutons, weakly expressed in axon terminals and axons, and not expressed in pre- or postsynaptic membranes of type Is boutons...
December 12, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29230271/the-role-of-oxidative-stress-in-decreased-acetylcholinesterase-activity-at-the-neuromuscular-junction-of-the-diaphragm-during-sepsis
#2
Hua Liu, Jin Wu, Jun-Yan Yao, Hong Wang, Shi-Tong Li
Our recent study demonstrated that acetylcholinesterase (AChE) activity at the neuromuscular junction (NMJ) of the diaphragm decreased during sepsis. However, the mechanisms were not clearly identified. In this study, we aimed to investigate whether the decreased AChE activity was related to oxidative stress by observing AChE activity in different grades of sepsis induced by caecal ligation and puncture (CLP). At 24 h after surgery, an assay of thiobarbituric acid reactive species (TBARS) and protein carbonyls, as well as the myeloperoxidase (MPO), superoxide dismutase (SOD), and catalase (CAT) activity, was conducted...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29226485/immunohistologic-analysis-of-spontaneous-recurrent-laryngeal-nerve-reinnervation-in-a-rat-model
#3
Andrew J Rosko, Robbi A Kupfer, Sang S Oh, Catherine T Haring, Eva L Feldman, Norman D Hogikyan
OBJECTIVE: After recurrent laryngeal nerve injury (RLN), spontaneous reinnervation of the larynx occurs with input from multiple sources. The purpose of this study was to determine the timing and efficiency of reinnervation across a resected RLN segment in a rat model of RLN injury. STUDY DESIGN: Animal study. METHODS: Twelve male 60-day-old Sprague Dawley rats underwent resection of a 5-mm segment of the right RLN. Rats were sacrificed at 1, 2, 4, and 12 weeks after nerve injury to harvest the larynx and trachea for immunohistologic analysis...
December 11, 2017: Laryngoscope
https://www.readbyqxmd.com/read/29221906/presynaptic-active-zones-of-mammalian-neuromuscular-junctions-nanoarchitecture-and-selective-impairments-in-aging
#4
REVIEW
Yomna Badawi, Hiroshi Nishimune
Neurotransmitter release occurs at active zones, which are specialized regions of the presynaptic membrane. A dense collection of proteins at the active zone provides a platform for molecular interactions that promote recruitment, docking, and priming of synaptic vesicles. At mammalian neuromuscular junctions (NMJs), muscle-derived laminin β2 interacts with presynaptic voltage-gated calcium channels to organize active zones. The molecular architecture of presynaptic active zones has been revealed using super-resolution microscopy techniques that combine nanoscale resolution and multiple molecular identification...
December 5, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/29221139/epstein-barr-virus-in-tumor-infiltrating-b-cells-of-myasthenia-gravis-thymoma-an-innocent-bystander-or-an-autoimmunity-mediator
#5
Paola Cavalcante, Stefania Marcuzzo, Sara Franzi, Barbara Galbardi, Lorenzo Maggi, Teresio Motta, Raffaella Ghislandi, Antonella Buzzi, Luisella Spinelli, Lorenzo Novellino, Fulvio Baggi, Carlo Antozzi, Fabio Conforti, Tommaso Martino De Pas, Massimo Barberis, Pia Bernasconi, Renato Mantegazza
The thymus plays a key role in myasthenia gravis (MG), a B cell-mediated autoimmune disorder affecting neuromuscular junction. Most MG patients have thymic abnormalities, including hyperplasia and thymoma, a neoplasm of thymic epithelial cells. Epstein-Barr virus (EBV) is associated with autoimmune diseases and tumors. Recently, we showed EBV persistence and reactivation in hyperplastic MG thymuses, suggesting that EBV might contribute to intra-thymic B cell dysregulation in MG patients. Here, we investigated EBV involvement in thymoma-associated MG, by searching for EBV markers in MG (n=26) and non-MG (n=14) thymomas...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29217522/drosophila-syd-1-has-rhogap-activity-that-is-required-for-presynaptic-clustering-of-bruchpilot-elks-but-not-neurexin-1
#6
Michael A Spinner, David A Walla, Tory G Herman
Syd-1 proteins are required for presynaptic development in worm, fly, and mouse. Syd-1s in all three species contain a Rho GTPase activating protein (GAP)-like domain of unclear significance. Invertebrate Syd-1s are thought to lack GAP activity, and mouse mSYD1A has GAP activity that is thought to be dispensible for its function. Here we show that Drosophila melanogaster Syd-1 can interact with all six fly Rhos and has GAP activity toward Rac1 and Cdc42. During development, fly Syd-1 clusters multiple presynaptic proteins at the neuromuscular junction (NMJ), including the cell adhesion molecule Neurexin (Nrx-1) and the active zone (AZ) component Bruchpilot (Brp), both of which Syd-1 binds directly...
December 7, 2017: Genetics
https://www.readbyqxmd.com/read/29217407/can-we-predict-intermediate-syndrome-a-review
#7
REVIEW
Chanika Alahakoon, Tharaka Lagath Dassanayake, Indika Bandara Gawarammana, Vajira Senaka Weerasinghe
INTRODUCTION: Ingestion of organophosphorus insecticides (OPI) is a common method of deliberate self harm in the developing world. Deaths mainly follow as a result of the respiratory failure associated with both cholinergic crisis and the intermediate syndrome. Even though death can be prevented by early mechanical ventilation of these patients, limited studies are available regarding the prediction of intermediate syndrome and subsequent respiratory failure. OBJECTIVE: To systematically review articles that are published with regard to possible prediction of intermediate syndrome using clinical, biochemical and electrophysiological parameters...
December 4, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/29215185/potential-of-autologous-adipose-derived-stem-cells-to-regenerate-atrophied-muscle-in-a-rat-model
#8
Ji Ung Park, Sung Tack Kwon
Muscle atrophy results in severe functional impairment and is a significant clinical problem. We examined and characterized the therapeutic effects of autologous adipose-derived stem cells (ADCSs) using an in vivo muscle atrophy rat model. To identify the effect of injected ADSCs into muscle, we developed the following two models of muscle atrophy in rats: induction of denervation by sciatic nerve defects; and nerve repair after severing the sciatic nerve. The inguinal fat pads were harvested from each rat and autologous ADSCs were cultured and ADSCs were injected in the right hind limbs as the experimental group, while normal saline was injected in the left hind limbs, which served as the control group...
December 7, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/29209388/a-genome-wide-association-study-identifies-utrn-gene-polymorphism-for-restless-legs-syndrome-in-a-korean-population
#9
Chul-Hyun Cho, Ji-Hye Choi, Seung-Gul Kang, Ho-Kyoung Yoon, Young-Min Park, Joung-Ho Moon, Ki-Young Jung, Jin-Kyu Han, Hong-Bum Shin, Hyun Ji Noh, Yong Seo Koo, Leen Kim, Hyun Goo Woo, Heon-Jeong Lee
Objective: Restless legs syndrome (RLS) is a highly heritable and common neurological sensorimotor disease disturbing sleep. The objective of study was to investigate significant gene for RLS by performing GWA and replication study in a Korean population. Methods: We performed a GWA study for RLS symptom group (n=325) and non-RLS group (n=2,603) from the Korea Genome Epidemiology Study. We subsequently performed a replication study in RLS and normal controls (227 RLS and 229 controls) to confirm the present GWA study findings as well as previous GWA study results...
November 2017: Psychiatry Investigation
https://www.readbyqxmd.com/read/29209177/a-new-behavioral-test-and-associated-genetic-tools-highlight-the-function-of-ventral-abdominal-muscles-in-adult-drosophila
#10
Marine Pons, Claire Soulard, Laurent Soustelle, Marie-Laure Parmentier, Yves Grau, Sophie Layalle
The function of the nervous system in complex animals is reflected by the achievement of specific behaviors. For years in Drosophila, both simple and complex behaviors have been studied and their genetic bases have emerged. The neuromuscular junction is maybe one of the prototypal simplest examples. A motor neuron establishes synaptic connections on its muscle cell target and elicits behavior: the muscle contraction. Different muscles in adult fly are related to specific behaviors. For example, the thoracic muscles are associated with flight and the leg muscles are associated with locomotion...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29205338/s1p-receptor-antagonists-fingolimod-and-siponimod-do-not-improve-the-outcome-of-experimental-autoimmune-myasthenia-gravis-mice-after-disease-onset
#11
Andreas Pelz, Hanne Schaffert, Radharani Diallo, Falk Hiepe, Andreas Meisel, Siegfried Kohler
Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and fatigue in the presence of circulating antibodies against components of the neuromuscular junction. Most patients have a good prognosis, but some are refractory to standard-of-care immunosuppressive treatment and suffer from recurrent myasthenic crises. Functional sphingosine-1-phosphate (S1P) antagonists like fingolimod and siponimod (BAF312) are successfully used for the treatment of multiple sclerosis, and fingolimod was shown to prevent the development of myasthenic symptoms in experimental autoimmune myasthenia gravis (EAMG), the standard model of MG...
December 4, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29205096/anatomical-and-functional-changes-to-the-colonic-neuromuscular-compartment-after-experimental-spinal-cord-injury
#12
Amanda White, Gregory M Holmes
A profound reduction in colorectal transit time accompanies spinal cord injury (SCI), yet the colonic alterations after SCI have yet to be fully understood. The loss of descending supraspinal input to lumbosacral neural circuits innervating the colon is recognized as one causal mechanism. However, remodeling of the colonic enteric nervous system/smooth muscle junction in response to inflammation is recognized as one factor leading to colonic dysmotility in other pathophysiological models. We investigated the alterations to the neuromuscular junction in rats with experimental high-thoracic (T3) SCI...
December 5, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29202456/neuroleptics-as-therapeutic-compounds-stabilizing-neuromuscular-transmission-in-amyotrophic-lateral-sclerosis
#13
Shunmoogum A Patten, Dina Aggad, Jose Martinez, Elsa Tremblay, Janet Petrillo, Gary Ab Armstrong, Alexandre La Fontaine, Claudia Maios, Meijiang Liao, Sorana Ciura, Xiao-Yan Wen, Victor Rafuse, Justin Ichida, Lorne Zinman, Jean-Pierre Julien, Edor Kabashi, Richard Robitaille, Lawrence Korngut, J Alexander Parker, Pierre Drapeau
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice...
November 16, 2017: JCI Insight
https://www.readbyqxmd.com/read/29201547/decremental-responses-in-patients-with-motor-neuron-disease
#14
Mohammed H Alanazy, Janka Hegedus, Chris White, Lawrence Korngut
Objective: Involvement of the neuromuscular junction (NMJ) in amyotrophic lateral sclerosis (ALS) has been reported and is increasingly recognized as an important pathophysiological aspect. The relationship between decrement and clinical measures for possible application as a biomarker has not been comprehensively explored. Methods: We performed routine repetitive nerve stimulation (RNS) of three nerves on patients with ALS. We captured measures of muscle strength, grip strength, fatigability, and calculated slow vital capacity (SVC) rates of change assessing for associations...
November 2017: Brain and Behavior
https://www.readbyqxmd.com/read/29196274/neuromuscular-diseases-diagnosis-and-management
#15
REVIEW
P Mary, L Servais, R Vialle
Neuromuscular diseases (NMDs) affect the peripheral nervous system, which includes the motor neurons and sensory neurons; the muscle itself; or the neuromuscular junction. Thus, the term NMDs encompasses a vast array of different syndromes. Some of these syndromes are of direct relevance to paediatric orthopaedic surgeons, either because the presenting manifestation is a functional sign (e.g., toe walking) or deformity (e.g., pes cavus or scoliosis) suggesting a need for orthopaedic attention or because orthopaedic abnormalities requiring treatment develop during the course of a known NMD...
November 28, 2017: Orthopaedics & Traumatology, Surgery & Research: OTSR
https://www.readbyqxmd.com/read/29196216/a-third-copy-of-the-down-syndrome-cell-adhesion-molecule-dscam-causes-synaptic-and-locomotor-dysfunction-in-drosophila
#16
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...
November 28, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29195055/neuromuscular-junction-formation-aging-and-disorders
#17
Lei Li, Wen-Cheng Xiong, Lin Mei
Synapses, the fundamental unit in neuronal circuits, are critical for learning and memory, perception, thinking, and reaction. The neuromuscular junction (NMJ) is a synapse formed between motoneurons and skeletal muscle fibers that is wrapped by Schwann cells (SCs). It is essential for controlling muscle contraction. NMJ formation requires intimate interactions among motoneurons, muscles, and SCs. Deficits in NMJ formation and maintenance cause neuromuscular disorders, including congenital myasthenic syndrome and myasthenia gravis...
December 1, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/29194538/mitochondrial-abnormalities-and-disruption-of-the-neuromuscular-junction-precede-the-clinical-phenotype-and-motor-neuron-loss-in-hfuswt-transgenic-mice
#18
Eva So, Jacqueline C Mitchell, Caroline Memmi, George Chennell, Gema Vizcay-Barrena, Leanne Allison, Christopher E Shaw, Caroline Vance
FUS mislocalisation and cytoplasmic aggregation are hallmark pathologies in FUS-related amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Many of the mechanistic hypotheses have focused on a loss of nuclear function in the FUS-opathies, implicating dysregulated RNA transcription and splicing in driving neurodegeneration. Recent studies describe an additional somato-dendritic localisation for FUS in the cerebral cortex implying a regulatory role in mRNA transport and local translation at the synapse...
November 28, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29194454/development-of-a-tissue-specific-ribosome-profiling-approach-in-drosophila-enables-genome-wide-evaluation-of-translational-adaptations
#19
Xun Chen, Dion Dickman
Recent advances in next-generation sequencing approaches have revolutionized our understanding of transcriptional expression in diverse systems. However, measurements of transcription do not necessarily reflect gene translation, the process of ultimate importance in understanding cellular function. To circumvent this limitation, biochemical tagging of ribosome subunits to isolate ribosome-associated mRNA has been developed. However, this approach, called TRAP, lacks quantitative resolution compared to a superior technology, ribosome profiling...
December 1, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29193204/engineered-agrin-attenuates-the-severity-of-experimental-autoimmune-myasthenia-gravis
#20
Zhiguo Li, Minshu Li, Kristofer Wood, Steffan Hettwer, Suraj A Muley, Fu-Dong Shi, Qiang Liu, Shafeeq S Ladha
Introduction-Agrin is essential for the formation and maintenance of neuromuscular junctions (NMJs). NT-1654 is a C-terminal fragment of mouse neural agrin. In this study, we determined the effects of NT-1654 on the severity of experimental autoimmune myasthenia gravis (EAMG). Methods-EAMG was induced in female Lewis rats by immunization with the Torpedo acetylcholine receptor (tAChR) and complete Freund's adjuvant. NT-1654 was dissolved in PBS and injected daily s.c. into tAChR immunized rats during the first 10 days after immunization, and then every other day for the following 20 days...
November 28, 2017: Muscle & Nerve
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