Muscle Cell News Volume 3.41 | Dec 10 2018

TOP STORY

Scientists Cut Main Heart Disease Risk Locus Out of DNA by Genome Editing

Researchers report that a large block of DNA, known as the 9p21.3 cardiovascular risk haplotype, causes abnormalities in vascular smooth muscular cells—the cells in blood vessel walls that normally allow them to expand and contract. [Press release from Scripps Research discussing online prepublication in Cell] Press Release | Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

Histone Lysine Dimethyl-Demethylase KDM3A Controls Pathological Cardiac Hypertrophy and Fibrosis

The authors investigated gain and loss of function of an H3K9me2 specific demethylase, lysine demethylase (Kdm) 3a, and showed it promoted left ventricular hypertrophy and fibrosis in response to pressure-overload. Cardiomyocyte KDM3A activated Timp1 transcription with pro-fibrotic activity. [Nat Commun] Full Article

Profiling Proliferative Cells and Their Progeny in Damaged Murine Hearts

Scientists applied the most direct definition of stem cell function to interrogate the existence of cardiac stem cells. By single-cell mRNA sequencing and genetic lineage tracing using two Ki67 knockin mouse models, they mapped all proliferating cells and their progeny in homoeostatic and regenerating murine hearts. [Proc Natl Acad Sci USA] Full Article | Press Release | Editorial

Effect of Atorvastatin on Cardiomyocyte Hypertrophy through Suppressing MURC Induced by Volume Overload and Cyclic Stretch

Researchers investigated the hypothesis that muscle-restricted coiled-coil protein (MURC) mediates hypertrophy in cardiomyocytes under mechanical stress. They used the in vitro model of cyclic stretch in rat neonatal cardiomyocytes to clarify MURC expression and the molecular regulation mechanism. [J Cell Mol Med] Full Article

Effect of Gpx3 Gene Silencing by siRNA on Apoptosis and Autophagy in Chicken Cardiomyocytes

Investigators revealed that glutathione peroxidase 3 (Gpx3) suppression could increase ROS levels, which induced apoptosis through the upregulated expression of Caspase-3 in cardiomyocytes. They also found that the whole process was accompanied by the occurrence of autophagy, which was promoted by inhibiting mTOR, and increasing the expression of ATG-7, ATG-10, and ATG-12. [J Cell Physiol] Abstract

SKELETAL MUSCLE CELLS

Lipin1 Is Required for Skeletal Muscle Development by Regulating MEF2c and MyoD Expression

Restoration of diacylglycerol-mediated signaling in lipin1 deficient myoblasts by phorbol 12-myristate 13-acetate transiently activated protein kinase C and histone deacetylase 5, and upregulated myocyte-specific enhancer factor 2C (MEF2c) expression. [J Physiol] Abstract

Involvement of Natriuretic Peptide System in C2C12 Myocytes

Scientists investigated the role of the natriuretic peptide system in C2C12 myocytes. All three natriuretic peptide receptors were expressed by cells differentiating from myoblasts to myotubes, and natriuretic peptide receptor B transcripts were detected at the highest levels. [Mol Cell Biochem] Abstract

SMOOTH MUSCLE CELLS

Engineered Microenvironment for Manufacturing Human Pluripotent Stem Cell-Derived Vascular Smooth Muscle Cells

Investigators report a scalable method for manufacturing human pluripotent stem cell-derived vascular smooth muscle cells in alginate hydrogel microtubes, which protect cells from hydrodynamic stresses and limit cell mass to <400 μm to ensure efficient mass transport. The tubes provided cells a friendly microenvironment, leading to extremely high culture efficiency. [Stem Cell Reports] Full Article | Graphical Abstract

miR-92b-3p-TSC1 Axis Is Critical for mTOR Signaling-Mediated Vascular Smooth Muscle Cell Proliferation Induced by Hypoxia

Mammalian target of rapamycin (mTOR) signaling and consequent cell proliferation were promoted by enforced expression of miR-92b-3p but inhibited by knocking down endogenous miR-92b-3p. Furthermore, inhibition of miR-92b-3p attenuated hypoxia-induced proliferation of vascular smooth muscle cells. [Cell Death Differ] Full Article

Hyperoxia-Induced Cellular Senescence in Fetal Airway Smooth Muscle Cells

Using human fetal airway smooth muscle (ASM) cells as a model of prematurity, researchers ascertained the effects of clinically-relevant moderate hyperoxia on cellular senescence. Fetal ASM exposed to 40% O₂ for seven days exhibited elevated levels of senescence-associated markers including β-galactosidase, cell cycle checkpoint proteins p16, p21 and p-p53, and the DNA damage marker p-γH2A.X. [Am J Respir Cell Mol Biol] Abstract

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Titin as a Force Generating Muscle Protein under Regulatory Control

The authors focus on the mechanisms shown to modulate titin-based viscoelastic forces in skeletal muscle cells, including chaperone binding, titin oxidation, phosphorylation, Ca²⁺-binding, and interaction with actin filaments. They discuss which of these modulatory mechanisms might contribute to the phenomenon of residual force enhancement relevant for eccentric muscle contractions. [J Appl Physiol] Abstract

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Cytokinetics Announces New Data Presented

Cytokinetics, Incorporated announced that new data was presented, including patient baseline characteristics and demographics from FORTITUDE-ALS, the Phase II clinical trial of reldesemtiv in patients with ALS. [Press release from Cytokinetics, Inc. discussing research presented at the 29^th International Symposium on ALS/MND, Glasgow] Press Release

BIOPHYTIS Announces One Oral Presentation and Two Poster Presentations

BIOPHYTIS announced that abstracts highlighting the company’s lead candidate, SARCONEOS will be presented. BIOPHYTIS’s lead candidate, SARCONEOS, is a first-in-class drug candidate formulated to activate the MAS receptor for the treatment of neuromuscular diseases. [Press release from Biophytis discussing research presented at the 11^th International Conference on Cachexia, Sarcopenia and Muscle Wasting, Maastricht] Press Release

Mitsubishi Tanabe Pharma America Announces Collaborative Study to Identify and Measure Biomarkers in People with ALS

Mitsubishi Tanabe Pharma America, Inc. announced it will conduct a study to identify and measure specific biomarkers in people with ALS. The findings may assist researchers and clinicians in starting the process of validation and the use of biomarkers as quantifiable, biological, non-clinical measures for disease progression and treatment effect of edaravone in people with ALS. [Mitsubishi Tanabe Pharma America, Inc.] Press Release

Biogen Exercises Option with Ionis to Develop and Commercialize Investigational Treatment BIIB067 for a Subtype of Familial Amyotrophic Lateral Sclerosis (ALS) Based on Positive Phase I Data

Biogen Inc. and Ionis Pharmaceuticals, Inc. announced that Biogen exercised its option to obtain from Ionis a worldwide, exclusive, royalty-bearing license to develop and commercialize BIIB067, an investigational treatment for ALS with superoxide dismutase 1 mutations. [Biogen Inc.] Press Release

Ra Pharmaceuticals Announces Positive Top-Line Data from Phase II Trial of Zilucoplan in Patients with Generalized Myasthenia Gravis

Ra Pharmaceuticals, Inc. announced positive top-line results from the company’s Phase II clinical trial evaluating zilucoplan for the treatment of generalized myasthenia gravis, achieving clinically meaningful and statistically significant reductions in both the primary and key secondary endpoints for both zilucoplan dose groups tested versus placebo at 12 weeks. [Ra Pharmaceuticals, Inc.] Press Release

Wave Life Sciences Announces Positive Phase I Results for WVE-210201 in Duchenne Muscular Dystrophy (DMD)

Wave Life Sciences Ltd. announced that the safety and tolerability data from the WVE-210201 Phase I clinical trial in boys with DMD who are amenable to exon 51 skipping support initiation of a Phase II/III clinical trial. [Wave Life Sciences Ltd.] Press Release

Cytokinetics Announces Initiation of Phase I Clinical Trial of CK-3773274, a Cardiac Myosin Inhibitor

Cytokinetics, Incorporated announced the first subject has been dosed in a Phase I double-blind, randomized, placebo-controlled, multi-part, single and multiple ascending dose clinical trial of CK-3773274 in healthy adult subjects. [Cytokinetics, Inc.] Press Release

Innovus Pharma Announces Initiation of a Clinical Study to Evaluate the Tolerance and the Effect of Musclin^™ on Muscle Health in Adults in the United States

Innovus Pharmaceuticals, Inc. announced the enrollment of the first participant in the clinical study to evaluate the effect and tolerance of Musclin^™ dietary supplement. [Innovus Pharmaceuticals, Inc.] Press Release

South Africa’s Science Academy Urges Update to Nation’s Genetics Laws

South Africa needs to overhaul the laws and ethical guidelines that govern its genetics research, testing and databases, says its national science academy — especially given the country’s troubled history of race-based discrimination. [Nature News] Editorial

Despite Growing Budget, U.S. Cancer Institute Slashes Operating Budget by 5%

A good year for biomedical research funding has turned sour at the National Cancer Institute (NCI) in Bethesda, Maryland, where the director is cutting operating budgets by 5% across the agency. Despite a rising overall budget, NCI’s funds are being stretched thin by various priorities and a ballooning number of funding applications, explains NCI Director Norman “Ned” Sharpless. [ScienceInsider] Editorial

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NEW Postdoctoral Researcher – Muscle Regeneration & Muscular Dystrophy Research (Carnegie Institution of Science)

Postdoctoral Research Fellow – Sarcopenia (Lee Kong Chian School of Medicine)

Assistant Professor – Skeletal Muscle Biology (University of Alabama at Birmingham)

Tenure Track Assistant Professor – Muscle Biology (University of Zurich)

Assistant/Associate Adjunct Professor – Cardiovascular Medicine (UC Davis)

Postdoctoral Research Fellow – Cardiac RNA Biology (University of Illinois at Chicago)

Postdoctoral Fellow – Muscle Degeneration (Rice University)

Assistant/Associate Professor – Exercise Science (Syracuse University)

Postdoctoral Research Scientist – Integrative Cardiac Pathophysiology (Columbia University)

Postdoctoral Fellow – Cardiovascular Tissue Engineering (Stanford University)

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