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https://www.readbyqxmd.com/read/28431892/a-humanized-hla-dr4-mouse-model-for-autoimmune-myocarditis
#1
M Emrah Şelli, Anita C Thomas, David C Wraith, Andrew C Newby
Myocarditis, the principal cause of dilated cardiomyopathy and heart failure in young adults, is associated with autoimmunity to human cardiac α-myosin (hCAM) and the DR4 allele of human major histocompatibility II (MHCII). We developed an hCAM-induced myocarditis model in human HLA-DR4 transgenic mice that lack all mouse MHCII genes, demonstrating that immunization for 3weeks significantly increased splenic T-cell proliferative responses and titres of IgG1 and IgG2c antibodies, abolished weight gain, provoked cardiac inflammation and significantly impaired cardiac output and fractional shortening, by echocardiography, compared to adjuvant-injected mice...
April 18, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28423519/vitamin-d-and-vdr-in-cancer-cachexia-and-muscle-regeneration
#2
Andrea Camperi, Fabrizio Pin, Domiziana Costamagna, Fabio Penna, Maria Lopez Menduina, Zaira Aversa, Teresa Zimmers, Roberto Verzaro, Raffaella Fittipaldi, Giuseppina Caretti, Francesco Maria Baccino, Maurizio Muscaritoli, Paola Costelli
Low circulating levels of vitamin D were associated with decreased muscle strength and physical performance. Along this line, the present study was aimed to investigate: i) the therapeutic potential of vitamin D in cancer-induced muscle wasting; ii) the mechanisms by which vitamin D affects muscle phenotype in tumor-bearing animals.Rats bearing the AH130 hepatoma showed decreased circulating vitamin D compared to control rats, while muscle vitamin D receptor (VDR) mRNA was up-regulated. Both circulating vitamin D and muscle VDR expression increased after vitamin D administration, without exerting appreciable effects on body weight and muscle mass...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411398/bud-detachment-in-hydra-requires-activation-of-fgfr-and-a-rho-rock-myosin-ii-signaling-pathway-to-ensure-formation-of-a-basal-constriction
#3
Oliver Holz, David Apel, Patrick Steinmetz, Ellen Lange, Simon Hopfenmüller, Kerstin Ohler, Stefanie Sudhop, Monika Hassel
BACKGROUND: Hydra propagates asexually by exporting tissue into a bud, which detaches four days later as a fully differentiated young polyp. Prerequisite for detachment is activation of fibroblast growth factor receptor (FGFR) signaling. The mechanism which enables constriction and tissue separation within the monolayered ecto- and endodermal epithelia is unknown. RESULTS: Histological sections and staining of F-actin by phalloidin revealed conspicuous cell shape changes at the bud detachment site indicating a localized generation of mechanical forces and the potential enhancement of secretory functions in ectodermal cells...
April 15, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28406994/neisseria-gonorrhoeae-infects-the-human-endocervix-by-activating-non-muscle-myosin-ii-mediated-epithelial-exfoliation
#4
Liang-Chun Wang, Qian Yu, Vonetta Edwards, Brian Lin, Jessica Qiu, Jerrold R Turner, Daniel C Stein, Wenxia Song
Colonization and disruption of the epithelium is a major infection mechanism of mucosal pathogens. The epithelium counteracts infection by exfoliating damaged cells while maintaining the mucosal barrier function. The sexually transmitted bacterium Neisseria gonorrhoeae (GC) infects the female reproductive tract primarily from the endocervix, causing gonorrhea. However, the mechanism by which GC overcome the mucosal barrier remains elusive. Using a new human tissue model, we demonstrate that GC can penetrate into the human endocervix by inducing the exfoliation of columnar epithelial cells...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28404582/histone-deacetylase-activity-modulates-exercise-induced-skeletal-muscle-plasticity-in-zebrafish-danio-rerio
#5
Alec Izaac Marcus Simmonds, Frank Seebacher
Aerobic exercise has a positive impact on animals by enhancing skeletal muscle function and locomotor performance. Responses of skeletal muscle to exercise involve changes in energy metabolism, calcium handling, and the composition of contractile protein isoforms, which together influence contractile properties. Histone deacetylases (HDAC) can cause short-term changes in gene expression, and may thereby mediate plasticity in contractile properties of skeletal muscle in response to exercise. The aim of this project was to determine (in zebrafish, Danio rerio) the traits that mediate inter-individual differences in sustained and sprint performance, and to determine whether inhibiting class I and II HDACs mediates exercise-induced changes in these traits...
April 12, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28400443/plastin-increases-cortical-connectivity-to-facilitate-robust-polarization-and-timely-cytokinesis
#6
Wei Yung Ding, Hui Ting Ong, Yusuke Hara, Jantana Wongsantichon, Yusuke Toyama, Robert C Robinson, François Nédélec, Ronen Zaidel-Bar
The cell cortex is essential to maintain animal cell shape, and contractile forces generated within it by nonmuscle myosin II (NMY-2) drive cellular morphogenetic processes such as cytokinesis. The role of actin cross-linking proteins in cortical dynamics is still incompletely understood. Here, we show that the evolutionarily conserved actin bundling/cross-linking protein plastin is instrumental for the generation of potent cortical actomyosin contractility in the Caenorhabditis elegans zygote. PLST-1 was enriched in contractile structures and was required for effective coalescence of NMY-2 filaments into large contractile foci and for long-range coordinated contractility in the cortex...
April 11, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28378710/calcium-oscillations-in-wounded-fibroblast-monolayers-are-spatially-regulated-through-substrate-mechanics
#7
Josephine Lembong, Benedikt Sabass, Howard Stone
The maintenance of tissue integrity is essential for the life of multicellular organisms. Healing of a skin wound is a paradigm for how various cell types localize and repair tissue perturbations in an orchestrated fashion. To investigate biophysical mechanisms associated with wound localization, we focus on a model system consisting of a fibroblast monolayer on an elastic substrate. We find that the creation of an edge in the monolayer causes cytosolic calcium oscillations throughout the monolayer. The oscillation frequency increases with cell density, which shows that wound-induced calcium oscillations occur collectively...
April 5, 2017: Physical Biology
https://www.readbyqxmd.com/read/28367863/ginsenoside-rb1-improves-cardiac-function-and-remodeling-in-heart-failure
#8
Xian Zheng, Shuai Wang, Xiaoming Zou, Yating Jing, Ronglai Yang, Siqi Li, Fengrong Wang
We investigated the effect of ginsenoside Rb1 on cardiac function and remodeling in heart failure (HF). Four weeks after HF induction, the rats were administrated with ginsenoside Rb1 (35 and 70 mg/kg) and losartan (4.5 mg/kg) for 8 weeks. Losartan was used as a positive control. Cardiac function was assessed by measuring hemodynamic parameters. Histological changes were analyzed by HE and Masson's trichrome staining. Cardiac hypertrophy, fibrosis, mitochondrial membrane potential and glucose transporter type 4 (GLUT4) levels were evaluated...
March 30, 2017: Experimental Animals
https://www.readbyqxmd.com/read/28363972/myosin-ii-promotes-the-anisotropic-loss-of-the-apical-domain-during-drosophila-neuroblast-ingression
#9
Sérgio Simões, Youjin Oh, Michael F Z Wang, Rodrigo Fernandez-Gonzalez, Ulrich Tepass
Epithelial-mesenchymal transitions play key roles in development and cancer and entail the loss of epithelial polarity and cell adhesion. In this study, we use quantitative live imaging of ingressing neuroblasts (NBs) in Drosophila melanogaster embryos to assess apical domain loss and junctional disassembly. Ingression is independent of the Snail family of transcriptional repressors and down-regulation of Drosophila E-cadherin (DEcad) transcription. Instead, the posttranscriptionally regulated decrease in DEcad coincides with the reduction of cell contact length and depends on tension anisotropy between NBs and their neighbors...
March 31, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28361956/role-for-formin-like-1-dependent-acto-myosin-assembly-in-lipid-droplet-dynamics-and-lipid-storage
#10
Simon G Pfisterer, Gergana Gateva, Peter Horvath, Juho Pirhonen, Veijo T Salo, Leena Karhinen, Markku Varjosalo, Samppa J Ryhänen, Pekka Lappalainen, Elina Ikonen
Lipid droplets (LDs) are cellular organelles specialized in triacylglycerol (TG) storage undergoing homotypic clustering and fusion. In non-adipocytic cells with numerous LDs this is balanced by poorly understood droplet dissociation mechanisms. We identify non-muscle myosin IIa (NMIIa/MYH-9) and formin-like 1 (FMNL1) in the LD proteome. NMIIa and actin filaments concentrate around LDs, and form transient foci between dissociating LDs. NMIIa depletion results in decreased LD dissociations, enlarged LDs, decreased hydrolysis and increased storage of TGs...
March 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28352215/myosin-iia-related-actomyosin-contractility-mediates-oxidative-stress-induced-neuronal-apoptosis
#11
Yan Wang, Yingqiong Xu, Qian Liu, Yuanyuan Zhang, Zhen Gao, Mingzhu Yin, Nan Jiang, Guosheng Cao, Boyang Yu, Zhengyu Cao, Junping Kou
Oxidative stress-induced neuronal apoptosis plays an important role in the progression of central nervous system (CNS) diseases. In our study, when neuronal cells were exposed to hydrogen peroxide (H2O2), an exogenous oxidant, cell apoptosis was observed with typical morphological changes including membrane blebbing, neurite retraction and cell contraction. The actomyosin system is considered to be responsible for the morphological changes, but how exactly it regulates oxidative stress-induced neuronal apoptosis and the distinctive functions of different myosin II isoforms remain unclear...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28346813/protein-supplementation-does-not-affect-myogenic-adaptations-to-resistance-training
#12
Paul T Reidy, Christopher S Fry, Sherry Igbinigie, Rachel R Deer, Kristofer Jennings, Mark B Cope, Ratna Mukherjea, Elena Volpi, Blake B Rasmussen
It has been proposed that protein supplementation during resistance exercise training enhances muscle hypertrophy. The degree of hypertrophy during training is controlled in part through activation of satellite cells and myonuclear accretion. PURPOSE: To determine the efficacy of protein supplementation (and the type of protein) during traditional resistance training on myofiber cross-sectional-area, satellite cell content and myonuclear addition. METHODS: Healthy young men participated in supervised whole body progressive resistance training 3d/wk for 12 weeks...
February 14, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28346438/basolateral-protrusion-and-apical-contraction-cooperatively-drive-drosophila-germ-band-extension
#13
Zijun Sun, Christopher Amourda, Murat Shagirov, Yusuke Hara, Timothy E Saunders, Yusuke Toyama
Throughout development, tissues undergo complex morphological changes, resulting from cellular mechanics that evolve over time and in three-dimensional space. During Drosophila germ-band extension (GBE), cell intercalation is the key mechanism for tissue extension, and the associated apical junction remodelling is driven by polarized myosin-II-dependent contraction. However, the contribution of the basolateral cellular mechanics to GBE remains poorly understood. Here, we characterize how cells coordinate their shape from the apical to the basal side during rosette formation, a hallmark of cell intercalation...
March 27, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28338991/mir-30e-is-negatively-regulated-by-myostatin-in-skeletal-muscle-and-is-functionally-related-to-fiber-type-composition
#14
Haixue Jia, Yixia Zhao, Tingting Li, Yong Zhang, Dahai Zhu
Myostatin (MSTN) negatively regulates skeletal myogenesis in which microRNAs (miRNAs) also play critical roles. Using miRNA microarrays of skeletal muscle from MSTN-knockout (MSTN-/-) mice, we recently showed that miR-431 is regulated by MSTN signaling. To identify additional miRNAs regulated by MSTN, we re-analyzed these miRNA arrays and validated their expression by quantitative RT-PCR. Herein, we demonstrated that miR-30e was significantly upregulated in skeletal muscle of MSTN-/- mice compared with that of the wild-type littermates...
March 17, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28333953/involvement-of-%C3%AE-and-%C3%AE-actin-isoforms-in-actin-cytoskeleton-organization-and-migration-abilities-of-bleb-forming-human-colon-cancer-cells
#15
Aleksandra Simiczyjew, Antonina Joanna Mazur, Ewelina Dratkiewicz, Dorota Nowak
Amoeboid movement is characteristic for rounded cells, which do not form strong adhesion contacts with the ECM and use blebs as migratory protrusions. It is well known that actin is the main component of mature forms of these structures, but the exact role fulfilled by non-muscle actin isoforms β- and γ- in bleb formation and migration of these cells is still not fully understood. The aim of this study was to establish the role of β- and γ-actin in migration of bleb-forming cancer cells using isoform-specific antibodies and expression of fluorescently tagged actin isoforms...
2017: PloS One
https://www.readbyqxmd.com/read/28328100/smart-mechanosensing-machineries-enable-migration-of-vascular-smooth-muscle-cells-in-atherosclerosis-relevant-3d-matrices
#16
REVIEW
Qingjia Chi, Jieling Shan, Xiaorong Ding, Tieying Yin, Yazhou Wang, Dongyu Jia, Guixue Wang
At the early stage of atherosclerosis, neointima is formed due to the migration of vascular smooth muscle cells (VSMCs) from the media to the intima. VSMCs are surrounded by highly adhesive 3D matrices. They take specific strategies to cross various 3D matrices in the media, including heterogeneous collagen and mechanically-strong basement membrane. Migration of VSMCs is potentially caused by biomechanical mechanism. Most in vitro studies focus on cell migration on 2D substrates in response to biochemical factors...
March 22, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28315297/paxillin-genes-and-actomyosin-contractility-regulate-myotome-morphogenesis-in-zebrafish
#17
Andrew E Jacob, Jeffrey D Amack, Christopher E Turner
Paxillin (Pxn) is a key adapter protein and signaling regulator at sites of cell-extracellular matrix (ECM) adhesion. Here, we investigated the role of Pxn during vertebrate development using the zebrafish embryo as a model system. We have characterized two Pxn genes, pxna and pxnb, in zebrafish that are maternally supplied and expressed in multiple tissues. Gene editing and antisense gene knockdown approaches were used to uncover Pxn functions during zebrafish development. While mutation of either pxna or pxnb alone did not cause gross embryonic phenotypes, double mutants lacking maternally supplied pxna or pxnb displayed defects in cardiovascular, axial, and skeletal muscle development...
March 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28303576/nonmuscle-nm-myosin-heavy-chain-phosphorylation-regulates-the-formation-of-nm-myosin-filaments-adhesome-assembly-and-smooth-muscle-contraction
#18
Wenwu Zhang, Susan J Gunst
The molecular function of nonmuscle (NM) isoforms of myosin II in smooth muscle (SM) tissues, and their possible role in contraction are largely unknown. We evaluated the function of NM myosin during contractile stimulation of canine tracheal SM tissues. Stimulation with ACh caused NM myosin filament assembly, as assessed by a Triton solubility assay and a proximity ligation assay to measure interactions between NM myosin monomers. ACh stimulated the phosphorylation of NM myosin heavy chain (HC) on Ser1943 in tracheal SM tissues, which can regulate NM myosin IIA filament assembly in vitro...
March 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28302447/dcebio-facilitates-myogenic-differentiation-via-intermediate-conductance-ca-2-activated-k-channel-activation-in-c2c12-myoblasts
#19
Shoko Tanaka, Yuko Ono, Kazuho Sakamoto
Membrane hyperpolarization is suggested to be a trigger for skeletal muscle differentiation. We investigated whether DCEBIO, an opener of the small/intermediate conductance Ca(2+) activated K(+) (SKCa/IKCa) channels, increase myogenic differentiation in C2C12 skeletal myoblasts. DCEBIO significantly increased myotube formation, protein expression level of myosin heavy chain II, and mRNA expression level of myogenin in C2C12 myoblasts cultured in differentiation medium. DCEBIO induced myotube formation and hyperpolarization were reduced by the IKCa channel blocker TRAM-34, but not by the SKCa channel blocker apamin...
February 17, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28300193/interplay-of-myosin-phosphatase-and-protein-phosphatase-2a-in-the-regulation-of-endothelial-nitric-oxide-synthase-phosphorylation-and-nitric-oxide-production
#20
Róbert Bátori, Bálint Bécsi, Dénes Nagy, Zoltán Kónya, Csaba Hegedűs, Zsuzsanna Bordán, Alexander Verin, Beáta Lontay, Ferenc Erdődi
The inhibitory phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) at Thr497 (eNOS(pThr497)) by protein kinase C or RhoA-activated kinase is a major regulatory determinant of eNOS activity. The signalling mechanisms involved in the dephosphorylation of eNOS(pThr497) have not yet been clarified. This study identifies myosin phosphatase (MP) holoenzyme consisting of protein phosphatase-1 catalytic subunit (PP1c) and MP target subunit-1 (MYPT1) as an eNOS(pThr497) phosphatase. In support of this finding are: (i) eNOS and MYPT1 interacts in various endothelial cells (ECs) and in in vitro binding assays (ii) MYPT1 targets and stimulates PP1c toward eNOS(pThr497) substrate (iii) phosphorylation of MYPT1 at Thr696 (MYPT1(pThr696)) controls the activity of MP on eNOS(pThr497)...
March 16, 2017: Scientific Reports
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