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https://www.readbyqxmd.com/read/28635959/optogenetic-activation-of-plexin-b1-reveals-contact-repulsion-between-osteoclasts-and-osteoblasts
#1
Abhijit Deb Roy, Taofei Yin, Shilpa Choudhary, Vladimir Rodionov, Carol C Pilbeam, Yi I Wu
During bone remodelling, osteoclasts induce chemotaxis of osteoblasts and yet maintain spatial segregation. We show that osteoclasts express the repulsive guidance factor Semaphorin 4D and induce contact inhibition of locomotion (CIL) in osteoblasts through its receptor Plexin-B1. To examine causality and elucidate how localized Plexin-B1 stimulation may spatiotemporally coordinate its downstream targets in guiding cell migration, we develop an optogenetic tool for Plexin-B1 designated optoPlexin. Precise optoPlexin activation at the leading edge of migrating osteoblasts readily induces local retraction and, unexpectedly, distal protrusions to steer cells away...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28633918/traction-force-and-its-regulation-during-cytokinesis-in-dictyostelium-cells
#2
Md Golam Sarowar Jahan, Shigehiko Yumura
Cytokinesis is the final stage of cell division. Dictyostelium cells have multiple modes of cytokinesis, including cytokinesis A, B and C. Cytokinesis A is a conventional mode, which depends on myosin II in the contractile ring. Myosin II null cells divide depending on substratum-attachment (cytokinesis B) or in a multi-polar fashion independent of the cell cycle (cytokinesis C). We investigated the traction stress exerted by dividing cells in the three different modes using traction force microscopy. In all cases, the traction forces were directed inward from both poles...
June 12, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28629674/cystinosis-distal-myopathy-novel-clinical-pathological-and-genetic-features
#3
Macarena Cabrera-Serrano, Reimar C Junckerstorff, Ali Alisheri, Alan Pestronk, Nigel G Laing, Conrad C Weihl, Phillipa J Lamont
Nephropathic cystinosis is an autosomal recessive lysosomal disease in which cystine cannot exit the lysosome to complete its degradation in the cytoplasm, thus accumulating in tissues. Some patients develop a distal myopathy involving mainly hand muscles. Myopathology descriptions from only 5 patients are available in the literature. We present a comprehensive clinical, pathological and genetic description of 3 patients from 2 families with nephropathic cystinosis. Intrafamiliar variability was detected in one family in which one sibling developed a severe distal myopathy while the other sibling did not show any signs of skeletal muscle involvement...
May 15, 2017: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28627341/-protective-effects-of-valproic-acid-on-gut-barrier-function-after-major-burn-injury-and-its-mechanism
#4
Hongmin Luo, Sen Hu, Huining Bian, Shaoyi Zheng, Bing Xiong, Zhifeng Huang, Zuan Liu, Chuanwei Sun, Lianghua Ma, Hanhua Li, Wen Yu, Minghua Du, Huade Chen, Wen Lai
OBJECTIVE: To investigate the potential protective effects of valproic acid (VPA) on gut barrier function after major burn injury in rats and its mechanism. METHODS: Forty male Sprague-Dawley (SD) rats were divided into sham + normal saline (NS), sham + VPA, scald + NS, and scald + VPA groups, with 10 rats in each group. Rat with 55% total body surface area (TBSA) third-degree severe-burns model was reproduced by immersing into 80 °C water, and the rats in sham groups were given sham-burns by immersing into 37 °C water...
March 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28624465/muscle-pathology-in-vici-syndrome-a-case-study-with-a-novel-mutation-in-epg5-and-a-summary-of-the-literature
#5
Carola Hedberg-Oldfors, Niklas Darin, Anders Oldfors
Vici syndrome is a disorder characterized by myopathy, cardiomyopathy, agenesis of the corpus callosum, immunodeficiency, cataracts, hypopigmentation, microcephaly, gross developmental delay and failure to thrive. It is caused by mutations in EPG5, which encodes a protein involved in the autophagy pathway. Although myopathy is part of the syndrome, few publications have described the muscle pathology. We present a detailed morphological analysis in a boy with Vici syndrome due to a novel homozygous one-base deletion in EPG5 (c...
May 8, 2017: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28624424/fusaric-acid-fa-protects-heart-failure-induced-by-isoproterenol-isp-in-mice-through-fibrosis-prevention-via-tgf-%C3%AE-1-smads-and-pi3k-akt-signaling-pathways
#6
Xin Li, Zhou-Long Zhang, Hui-Fen Wang
Fusaric acid (FA) is a novel compound derived from a class of nicotinic acid derivatives, exhibiting activity against cancers. However, its role in regulating cardiac injury is limited. Our study was aimed to investigate the role and the underlying molecular mechanism of FA in heart fibrosis and hypertrophy. Isoproterenol (ISP) was used to induce cardiac fibrosis and hypertrophy in vitro and in vivo. FA administration ameliorated hypertrophy by reducing atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β -myosin heavy chain (β-MHC) in vitro and in vivo...
June 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28624223/evaluation-of-mybpc3-trans-splicing-and-gene-replacement-as-therapeutic-options-in-human-ipsc-derived-cardiomyocytes
#7
Maksymilian Prondzynski, Elisabeth Krämer, Sandra D Laufer, Aya Shibamiya, Ole Pless, Frederik Flenner, Oliver J Müller, Julia Münch, Charles Redwood, Arne Hansen, Monica Patten, Thomas Eschenhagen, Giulia Mearini, Lucie Carrier
Gene therapy is a promising option for severe forms of genetic diseases. We previously provided evidence for the feasibility of trans-splicing, exon skipping, and gene replacement in a mouse model of hypertrophic cardiomyopathy (HCM) carrying a mutation in MYBPC3, encoding cardiac myosin-binding protein C (cMyBP-C). Here we used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from an HCM patient carrying a heterozygous c.1358-1359insC MYBPC3 mutation and from a healthy donor. HCM hiPSC-CMs exhibited ∼50% lower MYBPC3 mRNA and cMyBP-C protein levels than control, no truncated cMyBP-C, larger cell size, and altered gene expression, thus reproducing human HCM features...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28618428/the-impact-of-circulating-mitochondrial-dna-on-cardiomyocyte-apoptosis-and-myocardial-injury-after-tlr4-activation-in-experimental-autoimmune-myocarditis
#8
Bangwei Wu, Huanchun Ni, Jian Li, Xinyu Zhuang, Jinjin Zhang, Zhiyong Qi, Qiying Chen, Zhichao Wen, Haiming Shi, Xinping Luo, Bo Jin
BACKGROUND/AIMS: Mitochondrial DNA (mtDNA), acting as a newly found 'danger-associated molecular patterns' (DAMPs), is released into circulation upon tissue injury and performs as a considerable activator of inflammation and immune response. However, the role of circulating mtDNA in experimental autoimmune myocarditis (EAM) as well as Toll like receptor4 (TLR4) mediated cardiac inflammation and injury remains unknown. METHODS: A model of EAM was established in BALB/c mice by immunization with porcine cardiac myosin...
June 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28615630/non-muscle-myosin-ii-is-required-for-correct-fate-specification-in-the-caenorhabditis-elegans-seam-cell-divisions
#9
Siyu Serena Ding, Alison Woollard
During development, cell division often generates two daughters with different developmental fates. Distinct daughter identities can result from the physical polarity and size asymmetry itself, as well as the subsequent activation of distinct fate programmes in each daughter. Asymmetric divisions are a feature of the C. elegans seam lineage, in which a series of post-embryonic, stem-like asymmetric divisions give rise to an anterior daughter that differentiates and a posterior daughter that continues to divide...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615321/par-proteins-regulate-maintenance-phase-myosin-dynamics-during-c-elegans-zygote-polarization
#10
Lawrence E Small, Adriana T Dawes
Establishment of anterior-posterior polarity in the C. elegans zygote requires two different processes: mechanical activity of the actin-myosin cortex and biochemical activity of partitioning defective (PAR) proteins. Here, we have analyzed how PARs regulate the behavior of the cortical motor protein non-muscle myosin (NMY-2) to complement recent efforts that investigate how PARs regulate the Rho GTPase CDC-42, which in turn regulates the actin-myosin cortex. We found that PAR-3 and PAR-6 concentrate CDC-42-dependent NMY-2 in the anterior cortex, while PAR-2 inhibits CDC-42-dependent NMY-2 in the posterior by inhibiting PAR-3 and PAR-6...
June 14, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28615295/burden-of-recurrent-and-ancestral-mutations-in-families-with-hypertrophic-cardiomyopathy
#11
Samantha Barratt Ross, Richard D Bagnall, Jodie Ingles, J Peter Van Tintelen, Christopher Semsarian
BACKGROUND: Hypertrophic cardiomyopathy is a genetically heterogeneous myocardial disease with >1000 causal variants identified. Nonunique variants account for disease in many families. We sought to characterize nonunique variants in Australian families and determine whether they arise from common ancestral mutations or recurrent mutation events. METHODS AND RESULTS: Genetic test results of 467 index patients from apparently unrelated families with hypertrophic cardiomyopathy were evaluated...
June 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28611654/age-related-gene-expression-in-the-frontal-cortex-suggests-synaptic-function-changes-in-specific-inhibitory-neuron-subtypes
#12
Leon French, TianZhou Ma, Hyunjung Oh, George C Tseng, Etienne Sibille
Genome-wide expression profiling of the human brain has revealed genes that are differentially expressed across the lifespan. Characterizing these genes adds to our understanding of both normal functions and pathological conditions. Additionally, the specific cell-types that contribute to the motor, sensory and cognitive declines during aging are unclear. Here we test if age-related genes show higher expression in specific neural cell types. Our study leverages data from two sources of murine single-cell expression data and two sources of age-associations from large gene expression studies of postmortem human brain...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28611128/decreased-kcne2-expression-participates-in-the-development-of-cardiac-hypertrophy-by-regulation-of-calcineurin-nfat-nuclear-factor-of-activated-t-cells-and-mitogen-activated-protein-kinase-pathways
#13
Wenjuan Liu, Jianxin Deng, Wenwen Ding, Gang Wang, Yuanyuan Shen, Junmeng Zheng, Xiaoming Zhang, Yizhi Luo, Chifei Lv, Yonghui Wang, Liqing Chen, Dewen Yan, Ryan L Boudreau, Long-Sheng Song, Jie Liu
BACKGROUND: KCNE2 is a promiscuous auxiliary subunit of voltage-gated cation channels. A recent work demonstrated that KCNE2 regulates L-type Ca(2+) channels. Given the important roles of altered Ca(2+) signaling in structural and functional remodeling in diseased hearts, this study investigated whether KCNE2 participates in the development of pathological hypertrophy. METHODS AND RESULTS: We found that cardiac KCNE2 expression was significantly decreased in phenylephrine-induced cardiomyocyte hypertrophy in neonatal rat ventricular myocytes and in transverse aortic constriction-induced cardiac hypertrophy in mice, as well as in dilated cardiomyopathy in human...
June 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28610850/dietary-myo-inositol-deficiency-decreased-the-growth-performances-and-impaired-intestinal-physical-barrier-function-partly-relating-to-nrf2-jnk-e2f4-and-mlck-signaling-in-young-grass-carp-ctenopharyngodon-idella
#14
Shuang-An Li, Wei-Dan Jiang, Lin Feng, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou
In this study, we investigated the effects of dietary myo-inositol on the growth and intestinal physical barrier functions of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp (221.83 ± 0.84 g) were fed six diets containing graded levels of myo-inositol (27.0, 137.9, 286.8, 438.6, 587.7 and 737.3 mg/kg) for 10 weeks. After the growth trial, fish were challenged with Aeromonas hydrophila for 14 days. The results indicated that compared with optimal myo-inositol levels, myo-inositol deficiency (27...
June 10, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28606474/regulation-of-intracellular-trafficking-and-secretion-of-adiponectin-by-myosin-ii
#15
Deepa Bedi, John C Dennis, Edward E Morrison, Tim D Braden, Robert L Judd
Adiponectin is a protein secreted by white adipocytes that plays an important role in insulin action, energy homeostasis and the development of atherosclerosis. The intracellular localization and trafficking of GLUT4 and leptin in adipocytes has been well studied, but little is known regarding the intracellular trafficking of adiponectin. Recent studies have demonstrated that constitutive adiponectin secretion is dependent on PIP2 levels and the integrity of cortical F-actin. Non-muscle myosin II is an actin-based motor that is associated with membrane vesicles and participates in vesicular trafficking in mammalian cells...
June 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28604953/-genetic-analysis-of-a-pedigree-affected-with-inherited-thrombocytopenia-caused-by-a-novel-mutation-of-myh9-gene
#16
Wenjun Liao, Xiaocheng Luo, Xue Zhang, Ping Chen, Huayu Wu, Wei Shu, Zhigang Yuan
OBJECTIVE: To study genetic mutations and clinical features of a pedigree affected with MYH9-related disorders from Guangxi. METHODS: Blood platelets were counted with a hemocytometer. Blood smear was carried out to detect the inclusion body in peripheral blood neutrophils. DNA and mRNA samples were extracted from blood samples from the members of the pedigree. Fragments of the MYH9 gene were amplified with PCR and directly sequenced. RESULTS: The affected individuals presented with a triad of giant platelets, decreased platelet count and inclusion bodies in the neutrophils with variable expressivity...
June 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28602422/loss-of-function-variants-in-mylk-cause-recessive-megacystis-microcolon-intestinal-hypoperistalsis-syndrome
#17
Danny Halim, Erwin Brosens, Françoise Muller, Michael F Wangler, Arthur L Beaudet, James R Lupski, Zeynep H Coban Akdemir, Michael Doukas, Hans J Stoop, Bianca M de Graaf, Rutger W W Brouwer, Wilfred F J van Ijcken, Jean-François Oury, Jonathan Rosenblatt, Alan J Burns, Dick Tibboel, Robert M W Hofstra, Maria M Alves
Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a congenital disorder characterized by loss of smooth muscle contraction in the bladder and intestine. To date, three genes are known to be involved in MMIHS pathogenesis: ACTG2, MYH11, and LMOD1. However, for approximately 10% of affected individuals, the genetic cause of the disease is unknown, suggesting that other loci are most likely involved. Here, we report on three MMIHS-affected subjects from two consanguineous families with no variants in the known MMIHS-associated genes...
June 7, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28598488/myosin-light-chain-kinase-knockout-improves-gut-barrier-function-and-confers-a-survival-advantage-in-polymicrobial-sepsis
#18
C Adam Lorentz, Zhe Liang, Mei Meng, Ching-Wen Chen, Benyam P Yoseph, Elise R Breed, Rohit Mittal, Nathan J Klingensmith, Alton B Farris, Eileen M Burd, Michael Koval, Mandy L Ford, Craig M Coopersmith
Sepsis-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the peri-junctional actin-myosin ring. Myosin light chain kinase (MLCK) phosphorylates the myosin regulatory light chain, resulting in increased permeability. The purpose of this study was to determine whether genetic deletion of MLCK would alter gut barrier function and survival from sepsis. MLCK(-/-) and wild type (WT) mice were subjected to cecal ligation and puncture and assayed for both survival and mechanistic studies...
June 7, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28596995/cardiac-myosin-binding-protein-c-autoantibodies-are-potential-early-indicators-of-cardiac-dysfunction-and-patient-outcome-in-acute-coronary-syndrome
#19
Thomas L Lynch, Diederik W D Kuster, Beverly Gonzalez, Neelam Balasubramanian, Nandini Nair, Sharlene Day, Jenna E Calvino, Yanli Tan, Christoph Liebetrau, Christian Troidl, Christian W Hamm, Ahmet Güçlü, Barbara McDonough, Ali J Marian, Jolanda van der Velden, Christine E Seidman, Gordon S Huggins, Sakthivel Sadayappan
The degradation and release of cardiac myosin binding protein-C (cMyBP-C) upon cardiac damage may stimulate an inflammatory response and autoantibody (AAb) production. We determined whether the presence of cMyBP-C-AAbs associated with adverse cardiac function in CVD patients. Importantly, cMyBP-C-AAbs were significantly detected in ACS patient sera upon arrival to the emergency department, particularly in STEMI patients. Patients positive for cMyBP-C-AAbs had a reduced LVEF and elevated levels of clinical biomarkers of MI...
April 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28596275/skeletal-muscle-morphology-protein-synthesis-and-gene-expression-in-ehlers-danlos-syndrome
#20
Rie H Nygaard, Jacob K Jensen, Nicol C Voermans, Katja Maria Heinemeier, Peter Schjerling, Lars Holm, Jakob Agergaard, Abigail Louise Mackey, Jesper Løvind Andersen, Lars Remvig, Michael Kjaer
INTRODUCTION: Patients with Ehlers Danlos Syndrome are known to have genetically impaired connective tissue and skeletal muscle symptoms in form of pain, fatigue and cramps, however earlier studies have not been able to link these symptoms to morphological muscle changes. METHODS: We obtained skeletal muscle biopsies in patients with classic EDS (cEDS, n=5 (Denmark)+ 8 (The Netherlands)) and vascular EDS (vEDS, n=3) and analyzed muscle fiber morphology and content (Western blotting and muscle fiber type/area distributions) and muscle mRNA expression and protein synthesis rate (RT-PCR and stable isotope technique)...
June 8, 2017: Journal of Applied Physiology
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