Muscle Cell News 4.16 May 6, 2019 | |
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TOP STORYExternalized Histone H4 Orchestrates Chronic Inflammation by Inducing Lytic Cell Death Investigators used mouse models of atherosclerosis—a major underlying cause of mortality worldwide—to demonstrate that extracellular histone H4-mediated membrane lysis of smooth muscle cells (SMCs) triggered arterial tissue damage and inflammation. They showed that activated lesional SMCs attracted neutrophils, triggering the ejection of neutrophil extracellular traps that contain nuclear proteins. [Nature] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)CARDIAC MUSCLE CELLSScientists describe engineered heart slices (EHS), preparations of decellularized porcine myocardium repopulated with human induced pluripotent stem cell-derived cardiomyocytes (CMs) that exhibited structural and functional improvements over standard culture. EHS exhibited multicellular, aligned bundles of elongated CMs with organized sarcomeres, positive inotropic responses to isoproterenol, anisotropic conduction of action potentials, and electrophysiological functionality for more than 200 days. [Stem Cell Reports] Full Article | Graphical Abstract Researchers tested human induced pluripotent stem cell-derived cardiomyocytes’ (hESC-CMs) capacity to stably engraft in a translationally relevant preclinical model, the infarcted pig heart. Transplantation of immature hESC-CMs resulted in substantial myocardial implants within the infarct scar that matured over time, formed vascular networks with the host, and evoked minimal cellular rejection. [Stem Cell Reports] Full Article The contractile properties of patient-specific human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs), with no detectable dystrophin, were compared to CMs containing a CRISPR-Cas9 mediated deletion of a single G base at position 263 of the dystrophin gene isogenic to the parental line of hiPSC-CMs from a healthy individual. Investigators hypothesized that the absence of a dystrophin-actin linkage would adversely affect myofibril and cardiomyocyte structure and function. [Cardiovasc Res] Abstract Irisin Exerts a Therapeutic Effect against Myocardial Infarction via Promoting Angiogenesis The authors investigated the therapeutic effects of irisin in an acute myocardial infarction model (MI) and its underlying mechanisms. Adult C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery and treated with irisin for two weeks after MI. Cardiac function was assessed using echocardiography. [Acta Pharmacol Sin] Abstract SKELETAL MUSCLE CELLSnNOS/GSNOR Interaction Contributes to Skeletal Muscle Differentiation and Homeostasis The authors demonstrated that nitric oxide synthase(NO) and denitrosylase S-nitrosoglutathione reductase (GSNOR) were concomitantly expressed during C1C12. They colocalized at the sarcolemma and co-immunoprecipitated in cells and in myofibers. They also provide evidence that GSNOR expression decreased in mouse models of muscular dystrophies and of muscle atrophy and wasting, suggesting a more general regulatory role of GSNOR in skeletal muscle homeostasis. [Cell Death Dis] Full Article To determine the effect of physical activity on the skeletal muscle proteome, researchers utilized liquid-chromatography mass spectrometry to obtain quantitative proteomics data on human skeletal muscle biopsies from 60 well-characterized healthy individuals who reported heterogeneous levels of physical activity. [Front Physiol] Full Article SMOOTH MUSCLE CELLSIt was found that NRG-1 expression was down-regulated via the circNRG-1/miR-193b-5p-mediated post-transcriptional mechanism in response to Angiotensin II (Ang II). In addition, NRG-1 overexpression reversed the inhibitory effect of Ang II on apoptosis in aortic smooth muscle cells (MAMCs). The data may have provided a molecular basis for further understanding the mechanism of Ang II in suppressing the apoptosis of MASMCs by decreasing NRG-1 expression at circular RNA and micro RNA levels. [Cell Death Dis] Full Article To determine the pathogenesis of aging-associated decreased in internal anal sphincter tone, the authors investigated the effect of aging on GPCR activation and related downstream signaling. They particularly investigated two GPCRs that characterize IAS smooth muscle cells: thromboxane A2 and angiotensin II type 1. [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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REVIEWSThe authors review cardiac differentiation protocols and their molecular machinery, closing with a discussion of the future challenges for producing human induced pluripotent stem cell-derived cardiomyocytes. [Stem Cells] Abstract | Full Article Visit our reviews page to see a complete list of reviews in the muscle cell research field. | |
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SCIENCE NEWSAmicus Therapeutics Presents Positive Preclinical Pompe Disease Gene Therapy Data Amicus Therapeutics announced initial preclinical data from its investigational adeno-associated viral gene therapy program for Pompe disease in mice. These data will be highlighted in a poster entitled “Development of a Novel Gene Therapy for Pompe Disease: Engineered Acid Alpha-Glucosidase Transgene for Improved Expression and Muscle Targeting.” [Press release from Amicus Therapeutics discussing research presented at the American Society of Gene & Cell Therapy (ASGCT) 22nd Annual Meeting, Washington, DC] Press Release Catabasis Pharmaceuticals, Inc. announced that it will present data on edasalonexent treatment in boys affected by Duchenne muscular dystrophy from the MoveDMD trial open-label extension. [Press release from Catabasis Pharmaceuticals discussing research to be presented at the American Academy of Neurology 71st Annual Meeting, Philadelphia] Press Release Rocket Pharmaceuticals Presents Preclinical Data of RP-A501 for Danon Disease Rocket Pharmaceuticals, Inc. presented preclinical data of RP-A501. RP-A501 is the company’s adeno-associated viral vector (AAV)-based gene therapy for the treatment of Danon disease. The data is included in an oral presentation by Annahita Keravala, PhD, Associate Vice President, AAV Platform, entitled, “Systemic Delivery of AAV9.LAMP2B for the Treatment of Danon Disease: Toxicology Studies in Mice and Cynomolgus Monkeys.” [Press release from Rocket Pharmaceuticals, Inc. discussing research presented at the American Society of Gene & Cell Therapy (ASGCT) 22nd Annual Meeting, Washington, DC, Washington, DC] Press Release Biogen Inc. announced new data affirming the safety and durability of SPINRAZA® and highlighting its clinically meaningful benefits for individuals with spinal muscular atrophy. Data from the SHINE extension study, with patients followed for up to four years, the NURTURE study of pre-symptomatic infants and an evaluation of phosphorylated neurofilament heavy chain as a biomarker. [Press release from Biogen Inc. discussing research to be presented at the 71st Annual Meeting of the American Academy of Neurology (AAN), Philadelphia] Press Release Cytokinetics, Incorporated announced that results of FORTITUDE-ALS (Functional Outcomes in a Randomized Trial of Investigational Treatment with CK-2127107 to Understand Decline in Endpoints – in ALS) were presented by Jeremy Shefner, MD, PhD, Lead Investigator of FORTITUDE-ALS, Professor and Chair of Neurology at Barrow Neurological Institute, and Professor and Executive Chair of Neurology at the University of Arizona, Phoenix. [Press release from Cytokinetics, Incorporated discussing research presented at the 71st Annual Meeting of the American Academy of Neurology (AAN), Philadelphia] Press Release AveXis announced interim data from ongoing trials of the investigational product Zolgensma® that showed positive results across a broad spectrum of patients with spinal muscular atrophy (SMA). These included the first presentation of data from the Phase I STRONG trial, which showed motor function gains and milestone achievements in patients with SMA Type II via intrathecal delivery. [Press release from AveXis discussing research presented at the 71st Annual Meeting of the American Academy of Neurology (AAN), Philadelphia] Press Release | |
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INDUSTRY NEWSCytRx Corporation highlighted that arimoclomol licensee Orphazyme A/S has completed enrollment in its Phase II/III clinical trial evaluating arimoclomol for the treatment of sporadic Inclusion Body Myositis (sIBM). Orphazyme is currently developing arimoclomol in four different indications, including amyotrophic lateral sclerosis, Niemann-Pick disease Type C, Gaucher disease and sIBM. [CytRx Corporation (PR Newswire Association LLC.)] Press Release FDA Approves Initiation of STEMI DTU Pivotal Randomized Controlled Trial Abiomed announced that, on April 26, the FDA approved initiation of the ST-Elevation Myocardial Infarction Door-to-Unloading Pivotal Randomized Controlled Trial. The prospective, multi-center, two-arm trial plans to enroll 668 patients undergoing treatment for a STEMI heart attack. Half the patients will be randomized to receive delayed reperfusion after 30 minutes of left ventricular unloading with the Impella CP. The other half will receive immediate reperfusion, the current standard of care. [Abiomed] Press Release Translarna™ (Ataluren) Is the First Therapy Approved in Brazil for Duchenne Muscular Dystrophy PTC Therapeutics, Inc. announced that Translarna™ has been granted marketing approval from the Brazilian National Health Surveillance Agency under rare diseases procedure, for the treatment of ambulatory children five years and older with Duchenne muscular dystrophy caused by a nonsense mutation. [PTC Therapeutics] Press Release Pfizer Inc. announced that the FDA has approved both VYNDAQEL® and VYNDAMAX™ for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. VYNDAQEL and VYNDAMAX are two oral formulations of the first-in-class transthyretin stabilizer tafamidis, and the first and only medicines approved by the FDA to treat ATTR-CM. [Pfizer Inc. (Business Wire, Inc.)] Press Release $150,000 Grant Will Help Finance Research on Spinal Muscular Atrophy Cure SMA awarded a $150,000 research grant to Laxman Gangwani, PhD, associate professor of Molecular and Translational Medicine, Center of Emphasis in Neurosciences, at TTUHSC El Paso’s Paul L. Foster School of Medicine. The grant will support Gangwani’s research on a genetic disorder known as spinal muscular atrophy (SMA). [Cure SMA (Newswise, Inc.)] Press Release The Muscular Dystrophy Association (MDA) launched an extensive campaign to raise awareness about amyotrophic lateral sclerosis, with a focus on how innovative research and technology are bringing researchers one step closer to the next breakthrough and how MDA’s multidisciplinary Care Center network is extending patients’ lives. [The Muscular Dystrophy Association (Newswire Association LLC.)] Press Release | |
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POLICY NEWSNIH Imposes Term Limits for Lab Chiefs The National Institutes of Health’s intramural research program will begin imposing 12-year term limits on laboratory leaders, Science reports. The policy, which goes into effect next year, aims to expand the diversity of those in management positions who oversee research groups, most of which are currently held by white men. [The Scientist] Editorial German Research Promised a Decade of Budget Increases German research organizations cheered a decision announced by state and federal ministers to increase research budgets by 3% a year for the next decade—a total boost of €17 billion over that time. [ScienceInsider] Editorial
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EVENTSNEW 3rd Annual HEART iN DIABETES (HiD) Conference Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESPostdoctoral Fellow – Cardiovascular Epidemiology (Boston University School of Medicine) Postdoctoral Fellow – Molecular Cardiology (University of Illinois at Chicago) Postdoctoral Researcher – Proliferative Responses in Cardiac Disease (University of Cambridge) Senior Research Investigator – Multiple Sclerosis Research (Thomas Jefferson University) Postdoctoral Scholar – Cardiovascular Genomics (Stanford Medicine) 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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