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Alexander Kushnir, Gaetano Santulli, Steven R Reiken, Ellie Coromilas, Sarah J Godfrey, Danielle L Brunjes, Paolo C Colombo, Melana Yuzefpolskaya, Seth I Sokol, Richard N Kitsis, Andrew R Marks
Background -Advances in congestive heart failure (CHF) management depend on biomarkers for monitoring disease progression and therapeutic response. During systole, intracellular Ca2+ is released from the sarcoplasmic reticulum (SR) into the cytoplasm through type 2 ryanodine receptor/Ca2+ release channels (RyR2). In CHF, chronically elevated circulating catecholamine levels cause pathologic remodeling of RyR2 resulting in diastolic SR Ca2+ leak, and decreased myocardial contractility. Similarly, skeletal muscle contraction requires SR Ca2+ release through type-1 ryanodine receptors (RyR1), and chronically elevated catecholamine levels in CHF cause RyR1 mediated SR Ca2+ leak, contributing to myopathy and weakness...
March 28, 2018: Circulation
Elisabeth Fischer, Alexander Gottschalk, Christina Schüler
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a condition of abnormal heart rhythm (arrhythmia), induced by physical activity or stress. Mutations in ryanodine receptor 2 (RyR2), a Ca2+ release channel located in the sarcoplasmic reticulum (SR), or calsequestrin 2 (CASQ2), a SR Ca2+ binding protein, are linked to CPVT. For specific drug development and to study distinct arrhythmias, simple models are required to implement and analyze such mutations. Here, we introduced CPVT inducing mutations into the pharynx of Caenorhabditis elegans, which we previously established as an optogenetically paced heart model...
December 13, 2017: Scientific Reports
Dongkyoon Kim, Christian Schmidt, Mark A Brown, Haley Tucker
Arid3a/Bright/Dril1 is a B cell-specific transactivator that regulates immunoglobulin heavy chain (IgH) gene transcription by binding promoter and enhancer-associated matrix attachment regions (MARs) within the IgH gene locus. Promoter MAR-mediated Arid3a transactivation is antagonized by direct competition of MAR binding by Cux1/CDP-a ubiquitously expressed repressor originally termed NF-μNR. We report that the NF-μNR complex includes Arid3a in B cells but not in non-B cells through mobility shift assays...
December 10, 2017: Diseases (Basel)
Cat Chenal, M R Gunner
The ubiquitously expressed CLC chloride transporters are involved in a great variety of physiological functions. The CLC protein fold is shared by Cl- channels and 2Cl- :1H+ antiporters. The antiporters pump three charges per cycle across the membrane with two Cl ions moving in the opposite direction of one proton. Multiconformational continuum electrostatics was used to calculate the coupled thermodynamics of the protonation of the extracellular-facing gating Glu (Ex ) and Cl- binding to the external (Sx ) and central (Sc ) sites in CLC-ec1, the Escherichia coli exchanger...
September 5, 2017: Biophysical Journal
Valeriy Lukyanenko, Joaquin M Muriel, Robert J Bloch
KEY POINTS: Dysferlin, the protein missing in limb girdle muscular dystrophy 2B and Miyoshi myopathy, concentrates in transverse tubules of skeletal muscle, where it stabilizes voltage-induced Ca2+ transients against loss after osmotic shock injury (OSI). Local expression of dysferlin in dysferlin-null myofibres increases transient amplitude to control levels and protects them from loss after OSI. Inhibitors of ryanodine receptors (RyR1) and L-type Ca2+ channels protect voltage-induced Ca2+ transients from loss; thus both proteins play a role in injury in dysferlin's absence...
August 1, 2017: Journal of Physiology
Kyrylo Bessonov, Kenrick A Vassall, George Harauz
The molecular details of the association between the human Fyn-SH3 domain, and the fragment of 18.5-kDa myelin basic protein (MBP) spanning residues S38-S107 (denoted as xα2-peptide, murine sequence numbering), were studied in silico via docking and molecular dynamics over 50-ns trajectories. The results show that interaction between the two proteins is energetically favorable and heavily dependent on the MBP proline-rich region (P93-P98) in both aqueous and membrane environments. In aqueous conditions, the xα2-peptide/Fyn-SH3 complex adopts a "sandwich"-like structure...
July 2017: Proteins
Tabita Kreko-Pierce, Jorge Azpurua, Rebekah E Mahoney, Benjamin A Eaton
The accumulation of oxidative damage is strongly linked to age-dependent declines in cell function, but the contribution of oxidative damage to morbidity is still debated. Many organisms seem to tolerate oxidative damage, and the extension of health span and life span by augmenting antioxidant activity has been inconsistent. Here we use the Drosophila model system to investigate the relationship among oxidative stress, health span, and life span. The oxidation-dependent dissociation of the Calstabin protein from the ryanodine receptor has been shown to result in reduced muscle function in mammals...
December 9, 2016: Journal of Biological Chemistry
Kenichi Sasaki, Takeru Makiyama, Yoshinori Yoshida, Yimin Wuriyanghai, Tsukasa Kamakura, Suguru Nishiuchi, Mamoru Hayano, Takeshi Harita, Yuta Yamamoto, Hirohiko Kohjitani, Sayako Hirose, Jiarong Chen, Mihoko Kawamura, Seiko Ohno, Hideki Itoh, Ayako Takeuchi, Satoshi Matsuoka, Masaru Miura, Naokata Sumitomo, Minoru Horie, Shinya Yamanaka, Takeshi Kimura
INTRODUCTION: Human induced pluripotent stem cells (hiPSCs) offer a unique opportunity for disease modeling. However, it is not invariably successful to recapitulate the disease phenotype because of the immaturity of hiPSC-derived cardiomyocytes (hiPSC-CMs). The purpose of this study was to establish and analyze iPSC-based model of catecholaminergic polymorphic ventricular tachycardia (CPVT), which is characterized by adrenergically mediated lethal arrhythmias, more precisely using electrical pacing that could promote the development of new pharmacotherapies...
2016: PloS One
Joseph F Fowler
Rosacea is a chronic skin disorder associated with flushing, erythema, dryness, burning and stinging, and inflammatory papules and pustules. New treatments available or in development target the inflammatory and erythematous components of the disease. These agents include the selective α2 receptor agonist brimonidine, the topical agents ivermectin cream 1% and azelaic acid foam 15%, and use of tetracyclinetype antibiotics, which affect the cathelicidin pathway. Semin Cutan Med Surg 35(supp6):S107-S109.
June 2016: Seminars in Cutaneous Medicine and Surgery
Stefan Matecki, Haikel Dridi, Boris Jung, Nathalie Saint, Steven R Reiken, Valérie Scheuermann, Ségolène Mrozek, Gaetano Santulli, Alisa Umanskaya, Basil J Petrof, Samir Jaber, Andrew R Marks, Alain Lacampagne
Ventilator-induced diaphragmatic dysfunction (VIDD) refers to the diaphragm muscle weakness that occurs following prolonged controlled mechanical ventilation (MV). The presence of VIDD impedes recovery from respiratory failure. However, the pathophysiological mechanisms accounting for VIDD are still not fully understood. Here, we show in human subjects and a mouse model of VIDD that MV is associated with rapid remodeling of the sarcoplasmic reticulum (SR) Ca(2+) release channel/ryanodine receptor (RyR1) in the diaphragm...
August 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
Yoram Epstein, Chen Fleischmann, Ran Yanovich, Yuval Heled
Anthropometric and physiological factors place female soldiers at a disadvantage relative to male soldiers in most aspects of physical performance. Average aerobic and anaerobic fitness levels are lower in women than in men. Thus, women have a lower overall work capacity and must exert themselves more than men to achieve the same output. The lower weight and fat-free mass and the higher body fat of women are associated with lower muscle strength and endurance, placing them at a disadvantage compared with men in performing military tasks such as lifting and carrying weights, or marching with a load...
November 2015: Journal of Strength and Conditioning Research
Yvonne Ford
BACKGROUND: Positive nurse self-concept has been shown to increase job productivity, retention, and job satisfaction. Student participation in peer-mentoring experiences has been shown to increase self-confidence and understanding of the role of the nurse leader. METHOD: The Nurse Self-Concept Questionnaire (NSCQ) was used to measure the nurse self-concept of senior baccalaureate nursing students before and after completion of a peer-mentoring experience. RESULTS: Female students scored significantly higher on two subscales of the NSCQ than male students prior to the peer-mentoring experience...
September 2015: Journal of Nursing Education
James Q Del Rosso, Leon H Kircik
Azelaic acid (AzA) 15% gel has been available in the United States for slightly over a decade, approved for treatment of the inflammatory lesions (papules and pustules) of rosacea. Efficacy and safety have been established in multiple studies both as monotherapy and in combination with oral doxycycline. Azelaic acid 15% gel has been shown not to induce epidermal permeability barrier impairment, and proper skin care reduces the likelihood of neurosensory adverse effects of stinging and burning that can affect a subset of patients with rosacea...
December 2014: Journal of Drugs in Dermatology: JDD
Jirayut Euanorasetr, Bungonsiri Intra, Phayungsak Mongkol, Surang Chankhamhaengdecha, Patoomratana Tuchinda, Mihoko Mori, Kazuro Shiomi, Takuya Nihira, Watanalai Panbangred
The rare actinomycetes strain 2EPS was isolated from soil and analysis of cultural, morphological characteristics, diaminopimelic acid content of its cell wall, and 16S rRNA gene sequence indicates that 2EPS belongs to genus Actinomadura. In addition, neighbor-joining phylogenetic tree also confirmed the relationships of this strain to other members of Actinomadura. A butanol extract with antibacterial activity was purified by reversed-phase chromatography to obtain three bioactive compounds, designated as compounds 1, 2 and 3...
February 2015: World Journal of Microbiology & Biotechnology
Yibo Jiang, Faheem Ahmed Khan, Nuruliarizki Shinta Pandupuspitasari, Ishwari Kadariya, Zhangrui Cheng, Yuwei Ren, Xing Chen, Ao Zhou, Liguo Yang, Dexin Kong, Shujun Zhang
Porcine reproductive and respiratory syndrome virus (PRRSV) can infect pigs and cause enormous economic losses to the pig industry worldwide. Porcine sialoadhesin (pSN) and CD163 have been identified as key viral receptors on porcine alveolar macrophages (PAM), a main target cell infected by PRRSV. In this study, the protein structures of amino acids 1-119 from the pSN and cSN (cattle sialoadhesin) N-termini (excluding the 19-amino acid signal peptide) were modeled via homology modeling based on mSN (mouse sialoadhesin) template structures using bioinformatics tools...
2013: International Journal of Molecular Sciences
Wenjun Xie, Gaetano Santulli, Xiaoxiao Guo, Melanie Gao, Bi-Xing Chen, Andrew R Marks
Abnormalities in intracellular Ca(2+) signaling have been proposed to play an essential role in the pathophysiology of atrial arrhythmias. However, a direct observation of intracellular Ca(2+) in atrial myocytes during atrial arrhythmias is lacking. Here, we have developed an ex vivo model of simultaneous Ca(2+) imaging and electrocardiographic recording in cardiac atria. Using this system we were able to record atrial arrhythmic intracellular Ca(2+) activities. Our results indicate that atrial arrhythmias can be tightly linked to intracellular Ca(2+) waves and Ca(2+) alternans...
November 2013: Journal of Molecular and Cellular Cardiology
Kenrick A Vassall, Kyrylo Bessonov, Miguel De Avila, Eugenia Polverini, George Harauz
The classic isoforms of myelin basic protein (MBP) are essential for the formation and maintenance of myelin in the central nervous system of higher vertebrates. The protein is involved in all facets of the development, compaction, and stabilization of the multilamellar myelin sheath, and also interacts with cytoskeletal and signaling proteins. The predominant 18.5-kDa isoform of MBP is an intrinsically-disordered protein that is a candidate auto-antigen in the human demyelinating disease multiple sclerosis...
2013: PloS One
Yingwu Mei, Le Xu, Henning F Kramer, Ginger H Tomberlin, Claire Townsend, Gerhard Meissner
Activation of the skeletal muscle ryanodine receptor (RyR1) complex results in the rapid release of Ca(2+) from the sarcoplasmic reticulum and muscle contraction. Dissociation of the small FK506 binding protein 12 subunit (FKBP12) increases RyR1 activity and impairs muscle function. The 1,4-benzothiazepine derivative JTV519, and the more specific derivative S107 (2,3,4,5,-tetrahydro-7-methoxy-4-methyl-1,4-benzothiazepine), are thought to improve skeletal muscle function by stabilizing the RyR1-FKBP12 complex...
2013: PloS One
Kam H To, Jill Dewey, Jeremy Weaver, Taehyun Park, Ry Young
Y is the putative holin gene of the paradigm coliphage P2 and encodes a 93-amino-acid protein. Y is predicted to be an integral membrane protein that adopts an N-out C-in membrane topology with 3 transmembrane domains (TMDs) and a highly charged C-terminal cytoplasmic tail. The same features are observed in the canonical class I lambda holin, the S105 protein of phage lambda, which controls lysis by forming holes in the plasma membrane at a programmed time. S105 has been the subject of intensive genetic, cellular, and biochemical analyses...
March 2013: Journal of Bacteriology
Genevieve C Kendall, Ekaterina I Mokhonova, Miriana Moran, Natalia E Sejbuk, Derek W Wang, Oscar Silva, Richard T Wang, Leonel Martinez, Qi L Lu, Robert Damoiseaux, Melissa J Spencer, Stanley F Nelson, M Carrie Miceli
Duchenne muscular dystrophy (DMD) causes profound and progressive muscle weakness and loss, resulting in early death. DMD is usually caused by frameshifting deletions in the gene DMD, which leads to absence of dystrophin protein. Dystrophin binds to F-actin and components of the dystrophin-associated glycoprotein complex and protects the sarcolemma from contraction-induced injury. Antisense oligonucleotide-mediated exon skipping is a promising therapeutic approach aimed at restoring the DMD reading frame and allowing expression of an intact dystrophin glycoprotein complex...
December 12, 2012: Science Translational Medicine
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