Muscle Cell News 4.19 June 3, 2019 | |
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TOP STORYOligogenic Inheritance of a Human Heart Disease Involving a Genetic Modifier Scienists used CRISPR-Cas9 to generate mice encoding the orthologous variants of the MKL2, MYH7, and NKX2-5 genes and found that compound heterozygosity for all three variants recapitulated the human disease phenotype. Analysis of murine hearts and human induced pluripotent stem cell-derived cardiomyocytes provided histologic and molecular evidence for the NKX2-5 variant’s contribution as a genetic modifier. [Science] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)CARDIAC MUSCLE CELLSThe Translational Landscape of the Human Heart Researchers showed extensive translational control of cardiac gene expression, which was orchestrated in a process-specific manner. Translation downstream of predicted disease-causing protein-truncating variants appeared to be frequent, suggesting inefficient translation termination. [Cell] Abstract | Press Release | Graphical Abstract A Single-Cell Transcriptional Roadmap for Cardiopharyngeal Fate Diversification The authors used single-cell genomics in the simple chordate model Ciona to reconstruct developmental trajectories forming first and second heart lineages and pharyngeal muscle precursors and characterized the molecular underpinnings of cardiopharyngeal fate choices. [Nat Cell Biol] Abstract Using RLM-RACE, investigators identified distinct Gja1 transcripts differing only in 5′ UTR length, of which two were upregulated during TGF-β exposure and hypoxia. Introduction of these transcripts into Gja1−/− cells phenocopied the response of Gja1 to TGF-β with reduced internal translation initiation. [Cell Rep] Full Article | Press Release | Graphical Abstract Scientists showed that impairment of the autophagy-lysosome pathway dysregulated degradation of connexin 43, either by inhibiting lysosomal activity or suppressing the level of Bcl2-associated athanogene 3, a stress-induced pleiotropic protein that was involved in protein quality control via the autophagy pathway. [Sci Rep] Full Article SKELETAL MUSCLE CELLSDissecting Cell Diversity and Connectivity in Skeletal Muscle for Myogenesis Investigators explored the function of rapidly adhering cells (RACs) by co-culturing them with myogenic progenitor cells (MPCs) in a biomimetic skeletal muscle organoid system. Results showed that RACs promoted the myogenic potential of MPCs in the organoid. Single-cell RNA-Seq was also performed, classifying RACs into seven cell subtypes, including one newly described cell subtype: teno-muscular cells. [Cell Death Dis] Full Article Scientists demonstrated that human induced pluripotent stem cell-derived myogenic progenitors formed highly-aligned myotubes and contracted when seeded on two-dimensional micropatterned platforms. The differentiated cells showed clear nuclear alignment and formed elongated myotubes dependent on the width of the micropatterned lanes. [Biotechnol Bioeng] Abstract SMOOTH MUSCLE CELLSUsing a transwell co-culture system, the authors demonstrated that M1 macrophages (M1M) contributed to functional change of vascular smooth muscle cells (VSMCs). They further stimulated VSMCs with exosomes isolated from M1M. Their results demonstrated that these exosomes could be taken up by VSMCs through macropinocytosis. [Cell Death Dis] Full Article Researchers investigated the effects of arginase (Arg) II activity on mitochondrial Ca2+ uptake through mitochondrial p32 protein and on CaMKII-dependent vascular smooth muscle cell (SMC) contraction. Native low-density lipoprotein stimulation induced an increase in [Ca2+]m as measured by CoCl2-quenched calcein-AM fluorescence, which was prevented by Arg inhibition in hAoSMCs and reduced in mAoSMCs from ArgII−/− mice. [Exp Mol Med] Full Article Medial Artery Calcification Increases Neointimal Hyperplasia after Balloon Injury In vascular smooth muscle cells grown under calcifying conditions, stimulation with bone morphogenetic protein 2 significantly increased cell proliferation. However, this did not occur in those grown under non-calcifying conditions. [Sci Rep] Full Article Subscribe to one of our other 19 science newsletters such as Extracellular Matrix News & ESC & iPSC News. | |
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REVIEWSTherapeutic Developments for Duchenne Muscular Dystrophy Gene-addition, exon-skipping, stop codon readthrough and genome-editing therapies can restore the expression of partially functional dystrophin protein, whereas other therapeutic approaches aim to improve muscle function and quality by targeting pathways involved in the pathogenesis of Duchenne Muscular Dystrophy. The authors outline important developments in these research areas and specifically focus on new therapies that are in the clinical trial phase or have already been approved. [Nat Rev Neurol] Abstract Endothelial Cell-Derived Angiocrines Elicit Physiological Cardiomyocyte Hypertrophy Pathological hypertrophy is associated with contractile/diastolic dysfunction and interstitial fibrosis leading to irreversible cardiac remodeling and heart failure. Elucidating the factors that determine the difference between physiological and pathological cardiac hypertrophy could offer insights into novel therapeutic strategies for the treatment of heart failure. [Circulation] Full Article Visit our reviews page to see a complete list of reviews in the muscle cell research field. | |
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SCIENCE NEWSMyoKardia Presents Results from Phase Ia Clinical Trial of MYK-491 MyoKardia, Inc. presented data from its Phase Ia single-ascending dose study of MYK-491 in healthy volunteers. MYK-491 is MyoKardia’s most advanced activator molecule, designed to increase contractility of the heart with minimal effects on myocardial relaxation. [Press release from “MyoKardia, Inc. discussing research presented at the European Society of Cardiology Heart Failure Congress, Athens] Press Release | |
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INDUSTRY NEWSAmarin Corporation plc announced that its supplemental new drug application for Vascepa® capsules has been accepted for filing and granted Priority Review designation by the FDA. [Amarin Corporation plc] Press Release FDA Approves Gene Therapy for Spinal Muscular Atrophy The US FDA has approved a new treatment for a rare childhood disorder that costs $2.125 million for single dose—the most expensive medicine on the market. The medicine is designed to treat spinal muscular atrophy, a condition driven by defects in the SMN1 gene, which causes afflicted babies to lose muscle control. [The Scientist] Press Release Santhera Pharmaceuticals announced that it has submitted a marketing authorization application for Puldysa® for the treatment of respiratory dysfunction in patients with Duchenne muscular dystrophy to the European Medicines Agency. Santhera is seeking conditional marketing authorization. [Santhera Pharmaceuticals] Press Release | |
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POLICY NEWSJust last week, the FDA gave Jaci Hermstad, a 25-year old Iowan who is dying from a rare form of ALS, an early sign that she will receive the first dose of an experimental drug never before tested in humans. The FDA’s move, which was confirmed to STAT by Jaci’s family and doctor, is a breakthrough for the Hermstads. [STAT News] Editorial US Science Academy Approves Plan to Oust Sexual Harassers The US National Academy of Sciences has approved an amendment to its by-laws that allows its governing council to expel members for misconduct, including proven cases of sexual harassment. [Nature News] Editorial No Paper, No PhD? India Rethinks Graduate Student Policy PhD students in India will no longer be required to publish articles in academic journals before they are awarded their doctorates, if the country’s higher-education regulator adopts recommendations from a committee of researchers. [Nature News] Editorial Bipartisan Bill Would Create Forum for Discussing How to Counter US Academic Espionage Academic leaders say more dialogue is urgently needed on one issue now bedeviling the US research community: how to best protect the country against its economic and military competitors without choking off international scientific collaborations and the free flow of people and ideas. [ScienceInsider] Editorial MD Anderson Clears Researcher Flagged by NIH for Not Disclosing Foreign Ties MD Anderson Cancer Center in Houston, Texas, says it has concluded an investigation of the last of five researchers flagged by the US National Institutes of Health (NIH) for potential violations of agency rules. The investigation “confirmed non-compliance with NIH and MD Anderson rules and policies, but such violations were not in our view serious or indicative of willful malfeasance,” the center said in a statement. [ScienceInsider] Editorial
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EVENTSNEW 5th Ottawa International Conference on Neuromuscular Disease and Biology Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Fellow – Pathogenesis in Heart Failure (Oslo University Hospital) NEW Postdoctoral – Proteomics of Muscles and Aging (Oklahoma Medical Research Foundation) Postdoctoral Fellow – Facioscapulohumeral Muscular Dystrophy Research (Pfizer) Postdoctoral Fellow – Muscular Growth, Wasting, and Dystrophy (University of Louisville) Postdoctoral Fellow – Cardiovascular Epidemiology (Boston University School of Medicine) Postdoctoral Fellow – Molecular Cardiology (University of Illinois at Chicago) Senior Research Investigator – Multiple Sclerosis Research (Thomas Jefferson University) Assistant Professor – Sarcoma or Skeletal Related Malignancies (University of California, Davis) Assistant Specialist – Cardiovascular Research (University of California, Davis) Assistant/Associate Adjunct Professor – Cardiovascular Medicine (University of California, Davis) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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