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https://www.readbyqxmd.com/read/28728573/splicing-arrays-reveal-novel-rbm10-targets-including-smn2-pre-mrna
#1
Leslie C Sutherland, Philippe Thibault, Mathieu Durand, Elvy Lapointe, Jose M Knee, Ariane Beauvais, Irina Kalatskaya, Sarah C Hunt, Julie J Loiselle, Justin G Roy, Sarah J Tessier, Gustavo Ybazeta, Lincoln Stein, Rashmi Kothary, Roscoe Klinck, Benoit Chabot
BACKGROUND: RBM10 is an RNA binding protein involved in message stabilization and alternative splicing regulation. The objective of the research described herein was to identify novel targets of RBM10-regulated splicing. To accomplish this, we downregulated RBM10 in human cell lines, using small interfering RNAs, then monitored alternative splicing, using a reverse transcription-PCR screening platform. RESULTS: RBM10 knockdown (KD) provoked alterations in splicing events in 10-20% of the pre-mRNAs, most of which had not been previously identified as RBM10 targets...
July 20, 2017: BMC Molecular Biology
https://www.readbyqxmd.com/read/28709001/ciliary-hedgehog-signaling-restricts-injury-induced-adipogenesis
#2
Daniel Kopinke, Elle C Roberson, Jeremy F Reiter
Injured skeletal muscle regenerates, but with age or in muscular dystrophies, muscle is replaced by fat. Upon injury, muscle-resident fibro/adipogenic progenitors (FAPs) proliferated and gave rise to adipocytes. These FAPs dynamically produced primary cilia, structures that transduce intercellular cues such as Hedgehog (Hh) signals. Genetically removing cilia from FAPs inhibited intramuscular adipogenesis, both after injury and in a mouse model of Duchenne muscular dystrophy. Blocking FAP ciliation also enhanced myofiber regeneration after injury and reduced myofiber size decline in the muscular dystrophy model...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28706936/impact-of-the-host-on-toxoplasma-stage-differentiation
#3
REVIEW
Carsten G K Lüder, Taibur Rahman
The unicellular parasite Toxoplasma gondii infects warm-blooded animals and humans, and it is highly prevalent throughout the world. Infection of immunocompetent hosts is usually asymptomatic or benign but leads to long-term parasite persistence mainly within neural and muscular tissues. The transition from acute primary infection towards chronic toxoplasmosis is accompanied by a developmental switch from fast replicating and metabolically highly active tachyzoites to slow replicating and largely dormant bradyzoites within tissue cysts...
June 22, 2017: Microbial Cell
https://www.readbyqxmd.com/read/28702326/rev-erb-co-regulates-muscle-regeneration-via-tethered-interaction-with-the-nf-y-cistrome
#4
Ryan D Welch, Chun Guo, Monideepa Sengupta, Katherine J Carpenter, Natalie A Stephens, Stacy A Arnett, Marvin J Meyers, Lauren M Sparks, Steven R Smith, Jinsong Zhang, Thomas P Burris, Colin A Flaveny
OBJECTIVE: The loss of skeletal muscle mass and strength are a central feature of traumatic injury and degenerative myopathies. Unfortunately, pharmacological interventions typically fail to stem the long-term decline in quality of life. Reduced Rev-Erb-mediated gene suppression in cultured C2C12 myoblasts has been shown to stimulate myoblast differentiation. Yet the mechanisms that allow Rev-Erb to pleiotropically inhibit muscle differentiation are not well understood. In this study, we sought to elucidate the role of Rev-Erb in the regulation of muscle differentiation and regeneration in vivo...
July 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28687588/the-carotid-baroreflex-modifies-the-pressor-threshold-of-the-muscle-metaboreflex-in-humans
#5
Masashi Ichinose, Tomoko K Ichinose-Kuwahara, Kazuhito Watanabe, Narihiko Kondo, Takeshi Nishiyasu
The purpose of present study was to test our hypothesis that unloading the carotid baroreceptors alters the threshold and gain of the muscle metaboreflex in humans. Ten healthy subjects performed a static handgrip exercise at 50% of maximum voluntary contraction. Contraction was sustained for 15, 30, 45 and 60 s, and was followed by 3 min of forearm circulatory arrest, during which forearm muscular pH is known to decrease linearly with increasing contraction time. The carotid baroreceptors were unloaded by applying 0...
July 7, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28680390/the-role-of-the-heat-shock-protein-b8-hspb8-in-motoneuron-diseases
#6
REVIEW
Paola Rusmini, Riccardo Cristofani, Mariarita Galbiati, Maria E Cicardi, Marco Meroni, Veronica Ferrari, Giulia Vezzoli, Barbara Tedesco, Elio Messi, Margherita Piccolella, Serena Carra, Valeria Crippa, Angelo Poletti
Amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA) are two motoneuron diseases (MNDs) characterized by aberrant protein behavior in affected cells. In familial ALS (fALS) and in SBMA specific gene mutations lead to the production of neurotoxic proteins or peptides prone to misfold, which then accumulate in form of aggregates. Notably, some of these proteins accumulate into aggregates also in sporadic ALS (sALS) even if not mutated. To prevent proteotoxic stresses detrimental to cells, misfolded and/or aggregated proteins must be rapidly removed by the protein quality control (PQC) system...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28649046/transgenerational-endocrine-disruption-and-neurotoxicity-in-zebrafish-larvae-after-parental-exposure-to-binary-mixtures-of-decabromodiphenyl-ether-bde-209-and-lead
#7
Lianguo Chen, Xianfeng Wang, Xiaohua Zhang, Paul K S Lam, Yongyong Guo, James C W Lam, Bingsheng Zhou
Polybrominated diphenyl ethers (PBDEs) and heavy metals are two key groups of electric and electronic equipment contaminants. Despite their co-occurrence in aquatic environments, their combined effects remain largely unknown, particularly under a chronic exposure regime. In the present study, adult zebrafish (Danio rerio) were exposed to environmentally relevant concentrations of BDE-209 and lead (Pb), or their binary mixtures, for 3 months. After chronic parental exposure, increased transfer of BDE-209 and Pb to the offspring eggs was activated in the coexposure groups, with BDE-197 being the predominant PBDE congener, indicating the dynamic metabolism of BDE-209 in parental zebrafish...
June 22, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28639365/vascular-calcification-vitamin-k-and-warfarin-therapy-possible-or-plausible-connection
#8
Aino Siltari, Heikki Vapaatalo
Atherosclerosis is a pathological process underpinning many cardiovascular diseases; it is the main cause of global mortality. Atherosclerosis is characterized by an invasion of inflammatory cells, accumulation of lipids and the formation of fatty streaks (plaques) which subsequently allow accumulation of calcium and other minerals leading to a disturbance in the vascular endothelium and its regulatory role in arterial function. Vascular calcification is a different process, stringently regulated mainly by local factors, in which osteoblast-like cells accumulate in the muscular layer of arteries ultimately taking on the physiological appearance of bone...
June 21, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28638346/micrornas-in-muscle-characterizing-the-powerlifter-phenotype
#9
Randall F D'Souza, Thomas Bjørnsen, Nina Zeng, Kirsten M M Aasen, Truls Raastad, David Cameron-Smith, Cameron J Mitchell
Powerlifters are the epitome of muscular adaptation and are able to generate extreme forces. The molecular mechanisms underpinning the significant capacity for force generation and hypertrophy are not fully elucidated. MicroRNAs (miRs) are short non-coding RNA sequences that control gene expression via promotion of transcript breakdown and/or translational inhibition. Differences in basal miR expression may partially account for phenotypic differences in muscle mass and function between powerlifters and untrained age-matched controls...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28637335/astrocyte-produced-mir-146a-as-a-mediator-of-motor-neuron-loss-in-spinal-muscular-atrophy
#10
Samantha L Sison, Teresa N Patitucci, Emily R Seminary, Eric Villalon, Christian L Lorson, Allison D Ebert
Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, is caused by loss of the survival motor neuron-1 (SMN1) gene, which leads to motor neuron loss, muscle atrophy, respiratory distress, and death. Motor neurons exhibit the most profound loss, but the mechanisms underlying disease pathogenesis are not fully understood. Recent evidence suggests that motor neuron extrinsic influences, such as those arising from astrocytes, contribute to motor neuron malfunction and loss. Here we investigated both loss-of-function and toxic gain-of-function astrocyte mechanisms that could play a role in SMA pathology...
June 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28623958/knockdown-of-subunit-3-of-the-cop9-signalosome-inhibits-c2c12-myoblast-differentiation-via-nf-kappab-signaling-pathway
#11
Mariam A Ba, Jeffrey Surina, Cherie A Singer, Maria L Valencik
BACKGROUND: The COP9 signalosome (CSN) is a conserved protein complex composed of 8 subunits designated CSN1-CSN8. CSN3 represents the third subunit of the CSN and maintains the integrity of the complex. CSN3 binds to the striated muscle-specific β1D integrin tail, and its subcellular localization is altered in differentiated skeletal muscle cells. However, the role of CSN3 in skeletal muscle differentiation is unknown. The main goal of this study was to identify whether CSN3 participates in myoblast differentiation and the signalling mechanisms involved using C2C12 cells as a skeletal muscle cell model...
June 17, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28615015/the-gastroprotective-effect-of-ethyl-acetate-fraction-of-hot-water-extract-of-trichosanthes-cucumerina-linn-and-its-underlying-mechanisms
#12
Ramani Karunakaran, M Ira Thabrew, G Mayuri Thammitiyagodage, B Prasanna Galhena, L D A Menuka Arawwawala
BACKGROUND: Antacids, anticholinergic drugs, histamine H2- receptor antagonists and irreversible proton pump inhibitors have been used for the treatment of gastric ulcers. However, prolonged use of these drugs may lead to series of adverse effects such as diarrhea, headache, rash, hypertension, muscular and joint pain. Therefore, there is an urgent need of more effective and safer treatments with fewer side effects. The aim of the present study was to scientifically evaluate the gastroprotective activity of fractions of the hot water extract of Trichosanthes cucumerina Linn (Family: Cucurbitaceae) aerial parts with a view to identifying the fraction with the best gastroprotective activity and the possible mechanism/s by which this fraction exert gastroprotection...
June 14, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28608457/potential-therapeutic-interventions-for-chronic-kidney-disease-associated-sarcopenia-via-indoxyl-sulfate-induced-mitochondrial-dysfunction
#13
Yuki Enoki, Hiroshi Watanabe, Riho Arake, Rui Fujimura, Kana Ishiodori, Tadashi Imafuku, Kento Nishida, Ryusei Sugimoto, Saori Nagao, Shigeyuki Miyamura, Yu Ishima, Motoko Tanaka, Kazutaka Matsushita, Hirotaka Komaba, Masafumi Fukagawa, Masaki Otagiri, Toru Maruyama
BACKGROUND: Chronic kidney disease (CKD) patients experience skeletal muscle wasting and decreased exercise endurance. Our previous study demonstrated that indoxyl sulfate (IS), a uremic toxin, accelerates skeletal muscle atrophy. The purpose of this study was to examine the issue of whether IS causes mitochondria dysfunction and IS-targeted intervention using AST-120, which inhibits IS accumulation, or mitochondria-targeted intervention using L-carnitine or teneligliptin, a dipeptidyl peptidase-4 inhibitor which retains mitochondria function and alleviates skeletal muscle atrophy and muscle endurance in chronic kidney disease mice...
June 12, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/28607086/specific-targeting-of-tgf-%C3%AE-family-ligands-demonstrates-distinct-roles-in-the-regulation-of-muscle-mass-in-health-and-disease
#14
Justin L Chen, Kelly L Walton, Adam Hagg, Timothy D Colgan, Katharine Johnson, Hongwei Qian, Paul Gregorevic, Craig A Harrison
The transforming growth factor-β (TGF-β) network of ligands and intracellular signaling proteins is a subject of intense interest within the field of skeletal muscle biology. To define the relative contribution of endogenous TGF-β proteins to the negative regulation of muscle mass via their activation of the Smad2/3 signaling axis, we used local injection of adeno-associated viral vectors (AAVs) encoding ligand-specific antagonists into the tibialis anterior (TA) muscles of C57BL/6 mice. Eight weeks after AAV injection, inhibition of activin A and activin B signaling produced moderate (∼20%), but significant, increases in TA mass, indicating that endogenous activins repress muscle growth...
June 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28591280/keratoconus-progression-is-not-inhibited-by-reducing-eyelid-muscular-force-with-botulinum-toxin-a-treatment-a-randomized-trial
#15
Adimara da Candelaria Renesto, Teissy Hentona Osaki, Midori Hentona Osaki, Flávio E Hirai, Mauro Campos
Purpose: To evaluate whether reducing eyelid muscular force through the administration of botulinum toxin type A (BTX-A) to the orbicularis oculi muscles of patients with keratoconus affected corneal parameters indicative of disease progression. Methods: In this prospective parallel randomized clinical trial, 40 eyes of 40 patients with keratoconus were randomized into equally sized control and BTX-A groups. Patients in the BTX-A group received subcutaneous BTX-A injections into the orbicularis muscle...
March 2017: Arquivos Brasileiros de Oftalmologia
https://www.readbyqxmd.com/read/28588757/identification-of-neuron-selective-androgen-receptor-inhibitors
#16
Maya Otto-Duessel, Ben Yi Tew, Steven Vonderfecht, Roger Moore, Jeremy O Jones
AIM: To identify neuron-selective androgen receptor (AR) signaling inhibitors, which could be useful in the treatment of spinal and bulbar muscular atrophy (SBMA), or Kennedy's disease, a neuromuscular disorder in which deterioration of motor neurons leads to progressive muscle weakness. METHODS: Cell lines representing prostate, kidney, neuron, adipose, and muscle tissue were developed that stably expressed the CFP-AR-YFP FRET reporter. We used these cells to screen a library of small molecules for cell type-selective AR inhibitors...
May 26, 2017: World Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28581498/dystrophin-glycoprotein-complex-sequesters-yap-to-inhibit-cardiomyocyte-proliferation
#17
Yuka Morikawa, Todd Heallen, John Leach, Yang Xiao, James F Martin
The regenerative capacity of the adult mammalian heart is limited, because of the reduced ability of cardiomyocytes to progress through mitosis. Endogenous cardiomyocytes have regenerative capacity at birth but this capacity is lost postnatally, with subsequent organ growth occurring through cardiomyocyte hypertrophy. The Hippo pathway, a conserved kinase cascade, inhibits cardiomyocyte proliferation in the developing heart to control heart size and prevents regeneration in the adult heart. The dystrophin-glycoprotein complex (DGC), a multicomponent transmembrane complex linking the actin cytoskeleton to extracellular matrix, is essential for cardiomyocyte homeostasis...
July 13, 2017: Nature
https://www.readbyqxmd.com/read/28576407/rp5063-a-novel-multimodal-serotonin-receptor-modulator-prevents-sugen-5416-hypoxia-induced-pulmonary-arterial-hypertension-in-rats
#18
Laxminarayan Bhat, Jon Hawkinson, Marc Cantillon, Dasharatha G Reddy, Seema R Bhat, Charles E Laurent, Annie Bouchard, Marzena Biernat, Dany Salvail
RP5063, a multimodal dopamine (DA) and serotonin (5-HT) modulator with high affinity for DA2/3/4 and 5-HT2A/2B/7 receptors and moderate affinity for SERT, is a novel therapeutic of special interest in the treatment of pulmonary arterial hypertension (PAH). Evidence indicates that therapeutics targeting the 5-HT2A/2B receptors can influence the pathogenesis of PAH. However, the therapeutic effect of RP5063 in humans has yet to be investigated. A Sugen 5416-hypoxia (SuHx)-induced PAH model was used to evaluate twice-daily (b...
May 31, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28576350/cannabinoids-in-attention-deficit-hyperactivity-disorder-a-randomised-controlled-trial
#19
Ruth E Cooper, Emma Williams, Seth Seegobin, Charlotte Tye, Jonna Kuntsi, Philip Asherson
Adults with ADHD describe self-medicating with cannabis, with some reporting a preference for cannabis over ADHD medications. A small number of psychiatrists in the US prescribe cannabis medication for ADHD, despite there being no evidence from randomised controlled studies. The EMA-C trial (Experimental Medicine in ADHD-Cannabinoids) was a pilot randomised placebo-controlled experimental study of a cannabinoid medication, Sativex Oromucosal Spray, in 30 adults with ADHD. The primary outcome was cognitive performance and activity level using the QbTest...
May 30, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28572004/%C3%AE-dystroglycan-hypoglycosylation-affects-cell-migration-by-influencing-%C3%AE-dystroglycan-membrane-clustering-and-filopodia-length-a-multiscale-confocal-microscopy-analysis
#20
V Palmieri, M Bozzi, G Signorino, M Papi, M De Spirito, A Brancaccio, G Maulucci, F Sciandra
Dystroglycan (DG) serves as an adhesion complex linking the actin cytoskeleton to the extracellular matrix. DG is encoded by a single gene as a precursor, which is constitutively cleaved to form the α- and β-DG subunits. α-DG is a peripheral protein characterized by an extensive glycosylation that is essential to bind laminin and other extracellular matrix proteins, while β-DG binds the cytoskeleton proteins. The functional properties of DG depend on the correct glycosylation of α-DG and on the cross-talk between the two subunits...
May 29, 2017: Biochimica et Biophysica Acta
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