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https://www.readbyqxmd.com/read/28072465/splicing-regulation-and-dysregulation-of-cholinergic-genes-expressed-at-the-neuromuscular-junction
#1
REVIEW
Kinji Ohno, Mohammad Alinoor Rahman, Mohammad Nazim, Farhana Nasrin, Yingni Lin, Jun-Ichi Takeda, Akio Masuda
We humans have evolved by acquiring diversity of alternative RNA metabolisms including alternative means of splicing and transcribing non-coding genes, and not by acquiring new coding genes. Tissue-specific and developmental stage-specific alternative RNA splicing is achieved by tightly regulated spatiotemporal regulation of expressions and activations of RNA-binding proteins that recognize their cognate splicing cis-elements on nascent RNA transcripts. Genes expressed at the neuromuscular junction (NMJ) are also alternatively spliced...
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28069562/effect-of-electroacupuncture-on-the-expression-of-agrin-and-acetylcholine-receptor-subtypes-in-rats-with-tibialis-anterior-muscular-atrophy-induced-by-sciatic-nerve-injection-injury
#2
Jianqi Yu, Meng Wang, Junying Liu, Xiaoming Zhang, Shengbo Yang
OBJECTIVE: To investigate the effects of electroacupuncture (EA) on mRNA and protein expression of agrin, acetylcholine receptor (AChR)-ε and AChR-γ in a rat model of tibialis anterior muscle atrophy induced by sciatic nerve injection injury, and to examine the underlying mechanism of action. METHODS: Fifty-four adult Sprague-Dawley rats were divided into four groups: healthy control group (CON, n=6); sciatic nerve injury group (SNI, n=24), comprising rats euthanased at 1, 2, 4 and 6 weeks, respectively, after penicillin injection-induced SNI (n=6 each); CON+EA group (n=12), comprising healthy rats euthanased at 4 and 6 weeks (after 2 and 4 weeks, respectively, of EA at GB30 and ST36); and SNI+EA group, comprising rats euthanased at 4 and 6 weeks (after 2 and 4 weeks, respectively, of EA)...
January 9, 2017: Acupuncture in Medicine: Journal of the British Medical Acupuncture Society
https://www.readbyqxmd.com/read/27977898/expansion-of-divergent-sea-domains-in-cell-surface-proteins-and-nucleoporin-54
#3
Jimin Pei, Nick V Grishin
SEA (sea urchin sperm protein, enterokinase, agrin) domains, many of which possess autoproteolysis activity, have been found in a number of cell surface and secreted proteins. Despite high sequence divergence, SEA domains were also proposed to be present in dystroglycan based on a conserved autoproteolysis motif and receptor-type protein phosphatase IA-2 based on structural similarity. The presence of a SEA domain adjacent to the transmembrane segment appears to be a recurring scheme in quite a number of type I transmembrane proteins on the cell surface, such as MUC1, dystroglycan, IA-2, and Notch receptors...
December 15, 2016: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/27965060/igg4-autoantibodies-against-muscle-specific-kinase-undergo-fab-arm-exchange-in-myasthenia-gravis-patients
#4
Inga Koneczny, Jo A A Stevens, Anna De Rosa, Saif Huda, Maartje G Huijbers, Abhishek Saxena, Michelangelo Maestri, Konstantinos Lazaridis, Paraskevi Zisimopoulou, Socrates Tzartos, Jan Verschuuren, Silvère M van der Maarel, Philip van Damme, Marc H De Baets, Peter C Molenaar, Angela Vincent, Roberta Ricciardi, Pilar Martinez-Martinez, Mario Losen
Autoimmunity mediated by IgG4 subclass autoantibodies is an expanding field of research. Due to their structural characteristics a key feature of IgG4 antibodies is the ability to exchange Fab-arms with other, unrelated, IgG4 molecules, making the IgG4 molecule potentially monovalent for the specific antigen. However, whether those disease-associated antigen-specific IgG4 are mono- or divalent for their antigens is unknown. Myasthenia gravis (MG) with antibodies to muscle specific kinase (MuSK-MG) is a well-recognized disease in which the predominant pathogenic IgG4 antibody binds to extracellular epitopes on MuSK at the neuromuscular junction; this inhibits a pathway that clusters the acetylcholine (neurotransmitter) receptors and leads to failure of neuromuscular transmission...
December 10, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27964993/laminin-is-instructive-and-calmodulin-dependent-kinase-ii-is-non-permissive-for-the-formation-of-complex-aggregates-of-acetylcholine-receptors-on-myotubes-in-culture
#5
Raphael Vezina-Audette, Mathieu Tremblay, Salvatore Carbonetto
Previous work has shown that myotubes cultured on laminin-coated substrates form complex aggregates of synaptic proteins that are similar in shape and composition to neuromuscular junctions (NMJs). Here we show that laminin instructs the location of complex aggregates which form only on the lower surface when laminin is coated onto culture dishes but over the entire cell when laminin is added in solution. Silencing of myotubes by agents that block electrical activity (tetrodotoxin, verapamil) or by inhibitors of calmodulin dependent kinase (CaMKII) render the myotube permissive for the formation of complex aggregates...
December 10, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27956075/natural-product-htp-screening-for-attenuation-of-cytokine-induced-neutrophil-chemo-attractants-cincs-and-no2-in-lps-ifn%C3%AE-activated-glioma-cells
#6
Elizabeth A Mazzio, David Bauer, Patricia Mendonca, Equar Taka, Karam F A Soliman
Chronic and acute central nervous system (CNS) inflammation are contributors toward neurological injury associated with head trauma, stroke, infection, Parkinsons or Alzheimers disease. CNS inflammatory illnesses can also contribute toward risk of developing glioblastoma multiforme (GBM). With growing public interest in complementary and alternative medicines (CAMs), we conduct a high throughput (HTP) screening of >1400 natural herbs, plants and over the counter (OTC) products for anti-inflammatory effects on lipopolysaccharide (LPS)/interferon gamma (IFNγ) activated C6 glioma cells...
January 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27943179/a-cell-culture-system-to-investigate-the-presynaptic-control-of-subsynaptic-membrane-differentiation-at-the-neuromuscular-junction
#7
Nadine Schmidt, Sreya Basu, Stephan Kröger, Hans Rudolf Brenner
For decades the neuromuscular junction (NMJ) has been a favorite preparation to investigate basic mechanisms of synaptic function and development. As its function is to transmit action potentials in a 1:1 ratio from motor neurons to muscle fibers, the NMJ shows little or no functional plasticity, a property that makes it poorly suited to investigate mechanisms of use-dependent adaptations of synaptic function, which are thought to underlie learning and memory formation in the brain. On the other hand, the NMJ is unique in that the differentiation of the subsynaptic membrane is regulated by one major factor secreted from motor neurons, agrin...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27756107/agrin-and-lrp4-antibodies-in-amyotrophic-lateral-sclerosis-patients
#8
Michael H Rivner, Siyang Liu, Brandy Quarles, Brandi Fleenor, Chengyong Shen, Jinxiu Pan, Lin Mei
INTRODUCTION: The prevalence and characteristics of Agrin and LRP4 antibody positive amyotrophic lateral sclerosis (ALS) patients were studied. METHODS: We tested 82 ALS patients and 59 controls for Agrin and LRP4 antibodies using ELISA. RESULTS: We found that 13.8% of ALS patients had Agrin antibodies, and 9.8% had LRP4 antibodies. Women ALS patients are twice as likely as men to have antibodies. Agrin-positive ALS patients are younger than Agrin-negative ALS patients...
October 18, 2016: Muscle & Nerve
https://www.readbyqxmd.com/read/27753903/os-02-03-effect-of-high-glucose-exposure-on-endothelial-microparticle-formation-and-composition
#9
Maddison Turner, Larissa Reid, Mercedes Munkonda, Dylan Burger
OBJECTIVE: Diabetes and hypertension are cognate diseases that often coexist, potentiating one's risk for cardiovascular complications. Both diseases are typified by the development of endothelial dysfunction and are accompanied by increased circulating endothelial microparticles (eMPs). Microparticles are small membrane-derived vesicles that are secreted ubiquitously following cell stress. We have previously shown that eMPs are sensitive markers of vascular injury in hypertension and identified eMP-mediated signaling pathways that lead to endothelial injury...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27704496/myasthenia-gravis
#10
Daniel B Drachman
The basic abnormality in myasthenia gravis (MG) is a reduction in acetylcholine receptors (AChRs) at neuromuscular junctions due to the effects of autoantibodies that are directed against the AChRs in most patients, or against neighboring proteins involved in the clustering of AChRs (MuSK, LRP-4, or agrin). Clinically, MG is characterized by muscle weakness and fatigue, often in typical patterns. The diagnosis may be missed early, and depends on the recognition of clinical manifestations, the measurement of autoantibodies, and/or electrophysiological features...
October 2016: Seminars in Neurology
https://www.readbyqxmd.com/read/27666825/musk-kinase-activity-is-modulated-by-a-serine-phosphorylation-site-in-the-kinase-loop
#11
B Z Camurdanoglu, C Hrovat, G Dürnberger, M Madalinski, K Mechtler, R Herbst
The neuromuscular junction (NMJ) forms when a motor neuron contacts a muscle fibre. A reciprocal exchange of signals initiates a cascade of signalling events that result in pre- and postsynaptic differentiation. At the centre of these signalling events stands muscle specific kinase (MuSK). MuSK activation, kinase activity and subsequent downstream signalling are crucial for NMJ formation as well as maintenance. Therefore MuSK kinase activity is tightly regulated to ensure proper NMJ development. We have identified a novel serine phosphorylation site at position 751 in MuSK that is increasingly phosphorylated upon agrin stimulation...
September 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27643249/os-02-03-effect-of-high-glucose-exposure-on-endothelial-microparticle-formation-and-composition
#12
Maddison Turner, Larissa Reid, Mercedes Munkonda, Dylan Burger
OBJECTIVE: Diabetes and hypertension are cognate diseases that often coexist, potentiating one's risk for cardiovascular complications. Both diseases are typified by the development of endothelial dysfunction and are accompanied by increased circulating endothelial microparticles (eMPs). Microparticles are small membrane-derived vesicles that are secreted ubiquitously following cell stress. We have previously shown that eMPs are sensitive markers of vascular injury in hypertension and identified eMP-mediated signaling pathways that lead to endothelial injury...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27638235/the-reference-intervals-for-serum-c-terminal-agrin-fragment-in-healthy-individuals-and-as-a-biomarker-for-renal-function-in-kidney-transplant-recipients
#13
Dan Yu, Hai-Xia Li, Yi Liu, Ze-Wei Ying, Jing-Jing Guo, Chen-Ying Cao, Jia Wang, Yuan-Fang Li, Hui-Rong Yang
BACKGROUND: C-terminal agrin fragment (CAF) has been shown to be a promising new biomarker for kidney function. The aim of this study was to verify the reference intervals for CAF in Chinese healthy adults and to assess the efficiency of CAF for monitoring renal function after transplantation. METHODS: Serum samples were collected from 200 healthy adult subjects and 60 living donor kidney recipients before and on day 1, day 2 and at 6 months after transplantation...
September 17, 2016: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/27614046/igf2-is-up-regulated-by-epigenetic-mechanisms-in-hepatocellular-carcinomas-and-is-an-actionable-oncogene-product-in-experimental-models
#14
Iris Martinez-Quetglas, Roser Pinyol, Daniel Dauch, Sara Torrecilla, Victoria Tovar, Agrin Moeini, Clara Alsinet, Anna Portela, Leonardo Rodriguez-Carunchio, Manel Solé, Amaia Lujambio, Augusto Villanueva, Swan Thung, Manel Esteller, Lars Zender, Josep M Llovet
BACKGROUND & AIMS: Effective treatments are urgently needed for hepatocellular carcinoma (HCC), which is usually diagnosed at advanced stages. Signaling via the insulin-like growth factor (IGF) pathway is aberrantly activated in HCC by IGF2 overexpression. We aimed to elucidate the mechanism of IGF2 overexpression and its oncogenic activities and evaluate the anti-tumor effects of reducing IGF2 signaling. METHODS: We obtained 228 HCC samples from patients who underwent liver resection, 168 paired non-tumor adjacent cirrhotic liver samples, and 10 non-tumor liver tissues from patients undergoing resection for hepatic hemangioma...
December 2016: Gastroenterology
https://www.readbyqxmd.com/read/27609404/glomerular-basement-membrane-heparan-sulfate-in-health-and-disease-a-regulator-of-local-complement-activation
#15
Dorin-Bogdan Borza
The glomerular basement membrane (GBM) is an essential component of the glomerular filtration barrier. Heparan sulfate proteoglycans such as agrin are major components of the GBM, along with α345(IV) collagen, laminin-521 and nidogen. A loss of GBM heparan sulfate chains is associated with proteinuria in several glomerular diseases and may contribute to the underlying pathology. As the major determinants of the anionic charge of the GBM, heparan sulfate chains have been thought to impart charge selectivity to the glomerular filtration, a view challenged by the negligible albuminuria in mice that lack heparan sulfate in the GBM...
September 6, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27598865/the-different-binding-properties-of-cultured-human-corneal-endothelial-cell-subpopulations-to-descemet-s-membrane-components
#16
Munetoyo Toda, Morio Ueno, Jun Yamada, Asako Hiraga, Hiroshi Tanaka, Ursula Schlötzer-Schrehardt, Chie Sotozono, Shigeru Kinoshita, Junji Hamuro
PURPOSE: To clarify the adherent properties of cultured human corneal endothelial cell (cHCEC) subpopulations (SPs). METHODS: Each SP was prepared by controlling the culture conditions or by using magnetic cell separation, and then confirmed by staining with several cell-surface markers. Binding abilities of HCEC SPs were examined by adding the cells to culture plates immobilized with collagens, laminins, or proteoglycans, and then centrifuging the plates. Adhered cells were then evaluated by phase-contrast microscopy...
September 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27529631/3d-cell-printing-of-functional-skeletal-muscle-constructs-using-skeletal-muscle-derived-bioink
#17
Yeong-Jin Choi, Taek Gyoung Kim, Jonghyeon Jeong, Hee-Gyeong Yi, Ji Won Park, Woonbong Hwang, Dong-Woo Cho
Engineered skeletal muscle tissues that mimic the structure and function of native muscle have been considered as an alternative strategy for the treatment of various muscular diseases and injuries. Here, it is demonstrated that 3D cell-printing of decellularized skeletal muscle extracellular matrix (mdECM)-based bioink facilitates the fabrication of functional skeletal muscle constructs. The cellular alignment and the shape of the tissue constructs are controlled by 3D cell-printing technology. mdECM bioink provides the 3D cell-printed muscle constructs with a myogenic environment that supports high viability and contractility as well as myotube formation, differentiation, and maturation...
August 16, 2016: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/27471561/proteomic-upregulation-of-fatty-acid-synthase-and-fatty-acid-binding-protein-5-and-identification-of-cancer-and-race-specific-pathway-associations-in-human-prostate-cancer-tissues
#18
Jennifer S Myers, Ariana K von Lersner, Qing-Xiang Amy Sang
Protein profiling studies of prostate cancer have been widely used to characterize molecular differences between diseased and non-diseased tissues. When combined with pathway analysis, profiling approaches are able to identify molecular mechanisms of prostate cancer, group patients by cancer subtype, and predict prognosis. This strategy can also be implemented to study prostate cancer in very specific populations, such as African Americans who have higher rates of prostate cancer incidence and mortality than other racial groups in the United States...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27456748/synthesis-and-deposition-of-basement-membrane-proteins-by-primary-brain-capillary-endothelial-cells-in-a-murine-model-of-the-blood-brain-barrier
#19
Maj Schneider Thomsen, Svend Birkelund, Annette Burkhart, Allan Stensballe, Torben Moos
The brain vascular basement membrane is important for both blood-brain barrier (BBB) development, stability, and barrier integrity and the contribution hereto from brain capillary endothelial cells (BCECs), pericytes, and astrocytes of the BBB is probably significant. The aim of the present study was to analyse four different in vitro models of the murine BBB for expression and possible secretion of major basement membrane proteins from murine BCECs (mBCECs). mBCECs, pericytes, and glial cells (mainly astrocytes and microglia) were prepared from brains of C57BL/6 mice...
July 26, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27439268/rehabilitation-of-an-edentulous-maxilla-in-a-patient-with-isolated-cleft-palate
#20
Bardia Valizadeh, S Agrin Barzanji, Mital Patel, Shakeel Shahdad
This article aims to discuss the use of short dental implants in cleft patients, the construction of an implant-retained obturator and the use of a Createch milled titanium bar with three Locator overdenture attachments incorporated within the bar. CPD/Clinical Relevance: Implant-retained obturators offer a possible solution for treating patients with isolated cleft palate who are struggling with dentures due to the unfavourable soft and hard tissue profile. This paper demonstrates how to manage such patients and shows all the clinical and laboratory stages involved...
April 2016: Dental Update
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