Myosin content of single muscle fibers following short-term disuse and active recovery in young and old healthy men

DEFF Research Database (Denmark)

Hvid, Lars G; Brocca, Lorenza; Ørtenblad, Niels

2017-01-01

healthy men. Following disuse, myosin content decreased (p... young and old in both fiber types, with MHC 2a fibers demonstrating an overshooting in young (+31%, pStrong correlations were observed between myosin content and single fiber SF in both young and old, with greater slope steepness in MHC 2a vs 1 fibers indicating an enhanced intrinsic...

CHARACTERIZATION OF TIGHTLY-ASSOCIATED SMOOTH MUSCLE MYOSIN-MYOSIN LIGHT CHAIN KINASE-CALMODULIN COMPLEXES*

OpenAIRE

Hong, Feng; Haldeman, Brian D.; John, Olivia A.; Brewer, Paul D.; Wu, Yi-Ying; Ni, Shaowei; Wilson, David P.; Walsh, Michael P.; Baker, Jonathan E.; Cremo, Christine R.

2009-01-01

A current popular model to explain phosphorylation of smooth muscle myosin (SMM) by smooth muscle myosin light chain kinase (MLCK) proposes that MLCK is bound tightly to actin but weakly to SMM. We found that MLCK and calmodulin (CaM) co-purify with unphosphorylated SMM (up-SMM) from chicken gizzard, suggesting that they are tightly bound. Although the MLCK:SMM molar ratio in SMM preparations was well below stoichiometric (1:73 ± 9), the ratio was ~ 23–37% of that in gizzard tissue. Fifteen t...

Preparation of human cardiac anti-myosin: a review

International Nuclear Information System (INIS)

Okada, H.; Souza, I.T.T.

1990-01-01

The present communication is a review of the physicochemical characterization and immunological properties of myosin isolated from the cardiac muscle, the production of monoclonal antibody anti-myosin, the radiolabeling of this antibody and its applications as radiopharmaceuticals to imaging myocardial infarcts. The classical example of radioimmunologic diagnosis of non malignant tissues is the detection of myocardial infarction by radiolabeled antibodies to myosin. (author)

Myosin II dynamics are regulated by tension in intercalating cells.

Science.gov (United States)

Fernandez-Gonzalez, Rodrigo; Simoes, Sérgio de Matos; Röper, Jens-Christian; Eaton, Suzanne; Zallen, Jennifer A

2009-11-01

Axis elongation in Drosophila occurs through polarized cell rearrangements driven by actomyosin contractility. Myosin II promotes neighbor exchange through the contraction of single cell boundaries, while the contraction of myosin II structures spanning multiple pairs of cells leads to rosette formation. Here we show that multicellular actomyosin cables form at a higher frequency than expected by chance, indicating that cable assembly is an active process. Multicellular cables are sites of increased mechanical tension as measured by laser ablation. Fluorescence recovery after photobleaching experiments show that myosin II is stabilized at the cortex in regions of increased tension. Myosin II is recruited in response to an ectopic force and relieving tension leads to a rapid loss of myosin, indicating that tension is necessary and sufficient for cortical myosin localization. These results demonstrate that myosin II dynamics are regulated by tension in a positive feedback loop that leads to multicellular actomyosin cable formation and efficient tissue elongation.

Myosin Light Chain Kinase and the Role of Myosin Light Chain Phosphorylation in Skeletal Muscle

OpenAIRE

Stull, James T.; Kamm, Kristine E.; Vandenboom, Rene

2011-01-01

Skeletal muscle myosin light chain kinase (skMLCK) is a dedicated Ca2+/calmodulin-dependent serine-threonine protein kinase that phosphorylates the regulatory light chain (RLC) of sarcomeric myosin. It is expressed from the MYLK2 gene specifically in skeletal muscle fibers with most abundance in fast contracting muscles. Biochemically, activation occurs with Ca2+ binding to calmodulin forming a (Ca2+)4•calmodulin complex sufficient for activation with a diffusion limited, stoichiometic bindin...

Characterization of myosin light chain in shrimp hemocytic phagocytosis.

Science.gov (United States)

Han, Fang; Wang, Zhiyong; Wang, Xiaoqing

2010-11-01

Myosin light chain, a well-known cytoskeleton gene, regulates multiple processes that are involved in material transport, muscle shrink and cell division. However, its function in phagocytosis against invading pathogens in crustacean remains unknown. In this investigation, a myosin light chain gene was obtained from Marsupenaeus japonicus shrimp. The full-length cDNA of this gene was of 766 bp and an open reading frame (ORF) of 462 bp encoding a polypeptide of 153 amino acids. The myosin light chain protein was expressed in Escherichia coli and purified. Subsequently the specific antibody was raised using the purified GST fusion protein. As revealed by immuno-electron microscopy, the myosin light chain protein was only expressed in the dark bands of muscle. In the present study, the myosin light chain gene was up-regulated in the WSSV-resistant shrimp as revealed by real-time PCR and western blot. And the phagocytic percentage and phagocytic index using FITC-labeled Vibrio parahemolyticus were remarkably increased in the WSSV-resistant shrimp, suggesting that the myosin light chain protein was essential in hemocytic phagocytosis. On the other hand, RNAi assays indicated that the phagocytic percentage and phagocytic index were significantly decreased when the myosin light chain gene was silenced by sequence-specific siRNA. These findings suggested that myosin light chain protein was involved in the regulation of hemocytic phagocytosis of shrimp. Copyright 2010 Elsevier Ltd. All rights reserved.

Diverse functions of myosin VI elucidated by an isoform-specific α-helix domain.

Science.gov (United States)

Wollscheid, Hans-Peter; Biancospino, Matteo; He, Fahu; Magistrati, Elisa; Molteni, Erika; Lupia, Michela; Soffientini, Paolo; Rottner, Klemens; Cavallaro, Ugo; Pozzoli, Uberto; Mapelli, Marina; Walters, Kylie J; Polo, Simona

2016-04-01

Myosin VI functions in endocytosis and cell motility. Alternative splicing of myosin VI mRNA generates two distinct isoform types, myosin VI(short) and myosin VI(long), which differ in the C-terminal region. Their physiological and pathological roles remain unknown. Here we identified an isoform-specific regulatory helix, named the α2-linker, that defines specific conformations and hence determines the target selectivity of human myosin VI. The presence of the α2-linker structurally defines a new clathrin-binding domain that is unique to myosin VI(long) and masks the known RRL interaction motif. This finding is relevant to ovarian cancer, in which alternative myosin VI splicing is aberrantly regulated, and exon skipping dictates cell addiction to myosin VI(short) in tumor-cell migration. The RRL interactor optineurin contributes to this process by selectively binding myosin VI(short). Thus, the α2-linker acts like a molecular switch that assigns myosin VI to distinct endocytic (myosin VI(long)) or migratory (myosin VI(short)) functional roles.

Life without double-headed non-muscle myosin II motor proteins

Science.gov (United States)

Betapudi, Venkaiah

2014-07-01

Non-muscle myosin II motor proteins (myosin IIA, myosin IIB, and myosin IIC) belong to a class of molecular motor proteins that are known to transduce cellular free-energy into biological work more efficiently than man-made combustion engines. Nature has given a single myosin II motor protein for lower eukaryotes and multiple for mammals but none for plants in order to provide impetus for their life. These specialized nanomachines drive cellular activities necessary for embryogenesis, organogenesis, and immunity. However, these multifunctional myosin II motor proteins are believed to go awry due to unknown reasons and contribute for the onset and progression of many autosomal-dominant disorders, cataract, deafness, infertility, cancer, kidney, neuronal, and inflammatory diseases. Many pathogens like HIV, Dengue, hepatitis C, and Lymphoma viruses as well as Salmonella and Mycobacteria are now known to take hostage of these dedicated myosin II motor proteins for their efficient pathogenesis. Even after four decades since their discovery, we still have a limited knowledge of how these motor proteins drive cell migration and cytokinesis. We need to enrich our current knowledge on these fundamental cellular processes and develop novel therapeutic strategies to fix mutated myosin II motor proteins in pathological conditions. This is the time to think how to relieve the hijacked myosins from pathogens in order to provide a renewed impetus for patients’ life. Understanding how to steer these molecular motors in proliferating and differentiating stem cells will improve stem cell based-therapeutics development. Given the plethora of cellular activities non-muscle myosin motor proteins are involved in, their importance is apparent for human life.

Life without double-headed non-muscle myosin II motor proteins

Directory of Open Access Journals (Sweden)

Venkaiah eBetapudi

2014-07-01

Full Text Available Non-muscle myosin II motor proteins (myosin IIA, myosin IIB, and myosin IIC belong to a class of molecular motor proteins that are known to transduce cellular free-energy into biological work more efficiently than man-made combustion engines. Nature has given a single myosin II motor protein for lower eukaryotes and multiple for mammals but none for plants in order to provide impetus for their life. These specialized nanomachines drive cellular activities necessary for embryogenesis, organogenesis, and immunity. However, these multifunctional myosin II motor proteins are believed to go awry due to unknown reasons and contribute for the onset and progression of many autosomal-dominant disorders, cataract, deafness, infertility, cancer, kidney, neuronal, and inflammatory diseases. Many pathogens like HIV, Dengue, hepatitis C, and Lymphoma viruses as well as Salmonella and Mycobacteria are now known to take hostage of these dedicated myosin II motor proteins for their efficient pathogenesis. Even after four decades since their discovery, we still have a limited knowledge of how these motor proteins drive cell migration and cytokinesis. We need to enrich our current knowledge on these fundamental cellular processes and develop novel therapeutic strategies to fix mutated myosin II motor proteins in pathological conditions. This is the time to think how to relieve the hijacked myosins from pathogens in order to provide a renewed impetus for patients’ life. Understanding how to steer these molecular motors in proliferating and differentiating stem cells will improve stem cell based-therapeutics development. Given the plethora of cellular activities non-muscle myosin motor proteins are involved in, their importance is apparent for human life.

N-terminus of Cardiac Myosin Essential Light Chain Modulates Myosin Step-Size

Science.gov (United States)

Wang, Yihua; Ajtai, Katalin; Kazmierczak, Katarzyna; Szczesna-Cordary, Danuta; Burghardt, Thomas P.

2016-01-01

Muscle myosin cyclically hydrolyzes ATP to translate actin. Ventricular cardiac myosin (βmys) moves actin with three distinct unitary step-sizes resulting from its lever-arm rotation and with step-frequencies that are modulated in a myosin regulation mechanism. The lever-arm associated essential light chain (vELC) binds actin by its 43 residue N-terminal extension. Unitary steps were proposed to involve the vELC N-terminal extension with the 8 nm step engaging the vELC/actin bond facilitating an extra ~19 degrees of lever-arm rotation while the predominant 5 nm step forgoes vELC/actin binding. A minor 3 nm step is the unlikely conversion of the completed 5 to the 8 nm step. This hypothesis was tested using a 17 residue N-terminal truncated vELC in porcine βmys (Δ17βmys) and a 43 residue N-terminal truncated human vELC expressed in transgenic mouse heart (Δ43αmys). Step-size and step-frequency were measured using the Qdot motility assay. Both Δ17βmys and Δ43αmys had significantly increased 5 nm step-frequency and coincident loss in the 8 nm step-frequency compared to native proteins suggesting the vELC/actin interaction drives step-size preference. Step-size and step-frequency probability densities depend on the relative fraction of truncated vELC and relate linearly to pure myosin species concentrations in a mixture containing native vELC homodimer, two truncated vELCs in the modified homodimer, and one native and one truncated vELC in the heterodimer. Step-size and step-frequency, measured for native homodimer and at two or more known relative fractions of truncated vELC, are surmised for each pure species by using a new analytical method. PMID:26671638

Topology of interaction between titin and myosin thick filaments.

Science.gov (United States)

Kellermayer, Miklós; Sziklai, Dominik; Papp, Zsombor; Decker, Brennan; Lakatos, Eszter; Mártonfalvi, Zsolt

2018-05-05

Titin is a giant protein spanning between the Z- and M-lines of the sarcomere. In the A-band titin is associated with the myosin thick filament. It has been speculated that titin may serve as a blueprint for thick-filament formation due to the super-repeat structure of its A-band domains. Accordingly, titin might provide a template that determines the length and structural periodicity of the thick filament. Here we tested the titin ruler hypothesis by mixing titin and myosin at in situ stoichiometric ratios (300 myosins per 12 titins) in buffers of different ionic strength (KCl concentration range 100-300 mM). The topology of the filamentous complexes was investigated with atomic force microscopy. We found that the samples contained distinct, segregated populations of titin molecules and myosin thick filaments. We were unable to identify complexes in which myosin molecules were regularly associated to either mono- or oligomeric titin in either relaxed or stretched states of the titin filaments. Thus, the electrostatically driven self-association is stronger in both myosin and titin than their binding to each other, and it is unlikely that titin functions as a geometrical template for thick-filament formation. However, when allowed to equilibrate configurationally, long myosin thick filaments appeared with titin oligomers attached to their surface. The titin meshwork formed on the thick-filament surface may play a role in controlling thick-filament length by regulating the structural dynamics of myosin molecules and placing a mechanical limit on the filament length. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of proteolysis on the adenosinetriphosphatase activities of thymus myosin

International Nuclear Information System (INIS)

Vu, N.D.; Wagner, P.D.

1987-01-01

Limited proteolysis was used to identify regions on the heavy chains of calf thymus myosin which may be involved in ATP and actin binding. Assignments of the various proteolytic fragments to different parts of the myosin heavy chain were based on solubility, gel filtration, electron microscopy, and binding of 32 P-labeled regulatory light chains. Chymotrypsin rapidly cleaved within the head of thymus myosin to give a 70,000-dalton N-terminal fragment and a 140,000-dalton C-terminal fragment. These two fragments did not dissociate under nondenaturing conditions. Cleavage within the myosin tail to give heavy meromyosin occurred more slowly. Cleavage at the site 70,000 daltons from the N-terminus of the heavy chain caused about a 30-fold decrease in the actin concentration required to achieve half-maximal stimulation of the magnesium-adenosinetriphosphatase (Mg-ATPase) activity of unphosphorylated thymus myosin. The actin-activated ATPase activity of this digested myosin was only slightly affected by light chain phosphorylation. Actin inhibited the cleavage at this site by chymotrypsin. In the presence of ATP, chymotrypsin rapidly cleaved the thymus myosin heavy chain at an additional site about 4000 daltons from the N-terminus. Cleavage at this site caused a 2-fold increase in the ethylenediaminetetraacetic acid-ATPase activity and 3-fold decreases in the Ca 2+ - and Mg-ATPase activities of thymus myosin. Thus, cleavage at the N-terminus of thymus myosin was affected by ATP, and this cleavage altered ATPase activity. Papain cleaved the thymus myosin heavy chain about 94,000 daltons from the N-terminus to give subfragment 1. Although this subfragment 1 contained intact light chains, its actin-activated ATPase activity was not affected by light chain phosphorylation

Functions of myosin motors tailored for parasitism

DEFF Research Database (Denmark)

Mueller, Christina; Graindorge, Arnault; Soldati-Favre, Dominique

2017-01-01

Myosin motors are one of the largest protein families in eukaryotes that exhibit divergent cellular functions. Their roles in protozoans, a diverse group of anciently diverged, single celled organisms with many prominent members known to be parasitic and to cause diseases in human and livestock......, are largely unknown. In the recent years many different approaches, among them whole genome sequencing, phylogenetic analyses and functional studies have increased our understanding on the distribution, protein architecture and function of unconventional myosin motors in protozoan parasites. In Apicomplexa......, myosins turn out to be highly specialized and to exhibit unique functions tailored to accommodate the lifestyle of these parasites....

Increased expression of Myosin binding protein H in the skeletal muscle of amyotrophic lateral sclerosis patients

KAUST Repository

Conti, Antonio

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a severe and fatal neurodegenerative disease of still unknown pathogenesis. Recent findings suggest that the skeletal muscle may play an active pathogenetic role. To investigate ALS\\'s pathogenesis and to seek diagnostic markers, we analyzed skeletal muscle biopsies with the differential expression proteomic approach. We studied skeletal muscle biopsies from healthy controls (CN), sporadic ALS (sALS), motor neuropathies (MN) and myopathies (M). Pre-eminently among several differentially expressed proteins, Myosin binding protein H (MyBP-H) expression in ALS samples was anomalously high. MyBP-H is a component of the thick filaments of the skeletal muscle and has strong affinity for myosin, but its function is still unclear. High MyBP-H expression level was associated with abnormal expression of Rho kinase 2 (ROCK2), LIM domain kinase 1 (LIMK1) and cofilin2, that might affect the actin-myosin interaction. We propose that MyBP-H expression level serves, as a putative biomarker in the skeletal muscle, to discriminate ALS from motor neuropathies, and that it signals the onset of dysregulation in actin-myosin interaction; this in turn might contribute to the pathogenesis of ALS. © 2013 Elsevier B.V.

Allosteric communication in myosin V: from small conformational changes to large directed movements.

Directory of Open Access Journals (Sweden)

M Cecchini

Full Text Available The rigor to post-rigor transition in myosin, a consequence of ATP binding, plays an essential role in the Lymn-Taylor functional cycle because it results in the dissociation of the actomyosin complex after the powerstroke. On the basis of the X-ray structures of myosin V, we have developed a new normal mode superposition model for the transition path between the two states. Rigid-body motions of the various subdomains and specific residues at the subdomain interfaces are key elements in the transition. The allosteric communication between the nucleotide binding site and the U50/L50 cleft is shown to result from local changes due to ATP binding, which induce large amplitude motions that are encoded in the structure of the protein. The triggering event is the change in the interaction of switch I and the P-loop, which is stabilized by ATP binding. The motion of switch I, which is a relatively rigid element of the U50 subdomain, leads directly to a partial opening of the U50/L50 cleft; the latter is expected to weaken the binding of myosin to actin. The calculated transition path demonstrates the nature of the subdomain coupling and offers an explanation for the mutual exclusion of ATP and actin binding. The mechanism of the uncoupling of the converter from the motor head, an essential part of the transition, is elucidated. The origin of the partial untwisting of the central beta-sheet in the rigor to post-rigor transition is described.

Design considerations in coiled-coil fusion constructs for the structural determination of a problematic region of the human cardiac myosin rod

Energy Technology Data Exchange (ETDEWEB)

Andreas, Michael P.; Ajay, Gautam; Gellings, Jaclyn A.; Rayment, Ivan (UW)

2017-12-01

X-ray structural determination of segments of the myosin rod has proved difficult because of the strong salt-dependent aggregation properties and repeating pattern of charges on the surface of the coiled-coil that lead to the formation of paracrystals. This problem has been resolved in part through the use of globular assembly domains that improve protein folding and prevent aggregation. The primary consideration now in designing coiled-coil fusion constructs for myosin is deciding where to truncate the coiled-coil and which amino acid residues to include from the folding domain. This is especially important for myosin that contains numerous regions of low predicted coiled-coil propensity. Here we describe the strategy adopted to determine the structure of the region that extends from Arg1677 – Leu1797 that included two areas that do not show a strong sequence signature of a conventional left-handed coiled coil or canonical heptad repeat. This demonstrates again that, with careful choice of fusion constructs, overlapping structures exhibit very similar conformations for the myosin rod fragments in the canonical regions. However, conformational variability is seen around Leu1706 which is a hot spot for cardiomyopathy mutations suggesting that this might be important for function.

Evolutionary traces decode molecular mechanism behind fast pace of myosin XI

Directory of Open Access Journals (Sweden)

Syamaladevi Divya P

2011-09-01

Full Text Available Abstract Background Cytoplasmic class XI myosins are the fastest processive motors known. This class functions in high-velocity cytoplasmic streaming in various plant cells from algae to angiosperms. The velocities at which they process are ten times faster than its closest class V homologues. Results To provide sequence determinants and structural rationale for the molecular mechanism of this fast pace myosin, we have compared the sequences from myosin class V and XI through Evolutionary Trace (ET analysis. The current study identifies class-specific residues of myosin XI spread over the actin binding site, ATP binding site and light chain binding neck region. Sequences for ET analysis were accumulated from six plant genomes, using literature based text search and sequence searches, followed by triple validation viz. CDD search, string-based searches and phylogenetic clustering. We have identified nine myosin XI genes in sorghum and seven in grape by sequence searches. Both the plants possess one gene product each belonging to myosin type VIII as well. During this process, we have re-defined the gene boundaries for three sorghum myosin XI genes using fgenesh program. Conclusion Molecular modelling and subsequent analysis of putative interactions involving these class-specific residues suggest a structural basis for the molecular mechanism behind high velocity of plant myosin XI. We propose a model of a more flexible switch I region that contributes to faster ADP release leading to high velocity movement of the algal myosin XI.

Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus

Czech Academy of Sciences Publication Activity Database

Venit, Tomáš; Dzijak, Rastislav; Kalendová, Alžběta; Kahle, Michal; Rohožková, Jana; Schmidt, V.; Rülicke, T.; Rathkolb, B.; Hans, W.; Bohla, A.; Eickelberg, O.; Stoeger, T.; Wolf, E.; Yildirim, A.Ö.; Gailus-Durner, V.; Fuchs, H.; de Angelis, M.H.; Hozák, Pavel

2013-01-01

Roč. 8, č. 4 (2013), e61406 E-ISSN 1932-6203 R&D Projects: GA ČR GAP305/11/2232; GA TA ČR TE01020022; GA MŠk LH12143; GA ČR(CZ) GD204/09/H084 Institutional research plan: CEZ:AV0Z50520514 Institutional support: RVO:68378050 Keywords : nuclear myosin * myosin isoforms * cell nucleus Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.534, year: 2013

Phosphorylation of human skeletal muscle myosin

International Nuclear Information System (INIS)

Houston, M.E.; Lingley, M.D.; Stuart, D.S.; Hoffman-Goetz, L.

1986-01-01

Phosphorylation of the P-light chains (phosphorylatable light chains) in human skeletal muscle myosin was studied in vitro and in vivo under resting an d contracted conditions. biopsy samples from rested vastus lateralis muscle of male and female subjects were incubated in oxygenated physiological solution at 30 0 C. Samples frozen following a quiescent period showed the presence of only unphosphorylated P-light chains designated LC2f (light chain two of fast myosin) CL2s and LC2s'(light chains two of slow myosin). Treatment with caffeine (10 mM) or direct electrical stimulation resulted in the appearance of three additional bands which were identified as the phosphorylated forms of the P-light chains i.e. LC2f-P, LC2s-P and LC2s'-P. The presence of phosphate was confirmed by prior incubation with ( 30 P) orthophosphate. Muscle samples rapidly frozen from resting vastus lateralis muscle revealed the presence of unphosphorylated and phosphorylated P-light chains in approximately equal ratios. Muscle samples rapidly frozen following a maximal 10 second isometric contraction showed virtually only phosphorylated fast and slow P-light chains. These results reveal that the P-light chains in human fast and slow myosin may be rapidly phosphorylated, but the basal level of phosphorylation in rested human muscle considerably exceeds that observed in animal muscles studied in vitro or in situ

Increased expression of Myosin binding protein H in the skeletal muscle of amyotrophic lateral sclerosis patients.

Science.gov (United States)

Conti, Antonio; Riva, Nilo; Pesca, Mariasabina; Iannaccone, Sandro; Cannistraci, Carlo V; Corbo, Massimo; Previtali, Stefano C; Quattrini, Angelo; Alessio, Massimo

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a severe and fatal neurodegenerative disease of still unknown pathogenesis. Recent findings suggest that the skeletal muscle may play an active pathogenetic role. To investigate ALS's pathogenesis and to seek diagnostic markers, we analyzed skeletal muscle biopsies with the differential expression proteomic approach. We studied skeletal muscle biopsies from healthy controls (CN), sporadic ALS (sALS), motor neuropathies (MN) and myopathies (M). Pre-eminently among several differentially expressed proteins, Myosin binding protein H (MyBP-H) expression in ALS samples was anomalously high. MyBP-H is a component of the thick filaments of the skeletal muscle and has strong affinity for myosin, but its function is still unclear. High MyBP-H expression level was associated with abnormal expression of Rho kinase 2 (ROCK2), LIM domain kinase 1 (LIMK1) and cofilin2, that might affect the actin-myosin interaction. We propose that MyBP-H expression level serves, as a putative biomarker in the skeletal muscle, to discriminate ALS from motor neuropathies, and that it signals the onset of dysregulation in actin-myosin interaction; this in turn might contribute to the pathogenesis of ALS. © 2013 Elsevier B.V. All rights reserved.

Myosin heavy chain expression in rabbit masseter muscle during postnatal development

NARCIS (Netherlands)

Bredman, J. J.; Weijs, W. A.; Korfage, H. A.; Brugman, P.; Moorman, A. F.

1992-01-01

The expression of isoforms of myosin heavy chain (MHC) during postnatal development was studied in the masseter muscle of the rabbit. Evidence is presented that in addition to adult fast and slow myosin, the rabbit masseter contains neonatal and 'cardiac' alpha-MHC. During postnatal growth myosin

Identification of signals that facilitate isoform specific nucleolar localization of myosin IC

Energy Technology Data Exchange (ETDEWEB)

Schwab, Ryan S.; Ihnatovych, Ivanna; Yunus, Sharifah Z.S.A.; Domaradzki, Tera [Department of Physiology and Biophysics, University at Buffalo—State University of New York, Buffalo, NY (United States); Hofmann, Wilma A., E-mail: whofmann@buffalo.edu [Department of Physiology and Biophysics, University at Buffalo—State University of New York, Buffalo, NY (United States)

2013-05-01

Myosin IC is a single headed member of the myosin superfamily that localizes to the cytoplasm and the nucleus, where it is involved in transcription by RNA polymerases I and II, intranuclear transport, and nuclear export. In mammalian cells, three isoforms of myosin IC are expressed that differ only in the addition of short isoform-specific N-terminal peptides. Despite the high sequence homology, the isoforms show differences in cellular distribution, in localization to nuclear substructures, and in their interaction with nuclear proteins through yet unknown mechanisms. In this study, we used EGFP-fusion constructs that express truncated or mutated versions of myosin IC isoforms to detect regions that are involved in isoform-specific localization. We identified two nucleolar localization signals (NoLS). One NoLS is located in the myosin IC isoform B specific N-terminal peptide, the second NoLS is located upstream of the neck region within the head domain. We demonstrate that both NoLS are functional and necessary for nucleolar localization of specifically myosin IC isoform B. Our data provide a first mechanistic explanation for the observed functional differences between the myosin IC isoforms and are an important step toward our understanding of the underlying mechanisms that regulate the various and distinct functions of myosin IC isoforms. - Highlights: ► Two NoLS have been identified in the myosin IC isoform B sequence. ► Both NoLS are necessary for myosin IC isoform B specific nucleolar localization. ► First mechanistic explanation of functional differences between the isoforms.

Myosin VIIa as a common component of cilia and microvilli.

Science.gov (United States)

Wolfrum, U; Liu, X; Schmitt, A; Udovichenko, I P; Williams, D S

1998-01-01

The distribution of myosin VIIa, which is defective or absent in Usher syndrome 1B, was studied in a variety of tissues by immunomicroscopy. The primary aim was to determine whether this putative actin-based mechanoenzyme is a common component of cilia. Previously, it has been proposed that defective ciliary function might be the basis of some forms of Usher syndrome. Myosin VIIa was detected in cilia from cochlear hair cells, olfactory neurons, kidney distal tubules, and lung bronchi. It was also found to cofractionate with the axonemal fraction of retinal photoreceptor cells. Immunolabeling appeared most concentrated in the periphery of the transition zone of the cilia. This general presence of a myosin in cilia is surprising, given that cilia are dominated by microtubules, and not actin filaments. In addition to cilia, myosin VIIa was also found in actin-rich microvilli of different types of cell. We conclude that myosin VIIa is a common component of cilia and microvilli.

Fast and slow myosins as markers of muscle injury.

Science.gov (United States)

Guerrero, M; Guiu-Comadevall, M; Cadefau, J A; Parra, J; Balius, R; Estruch, A; Rodas, G; Bedini, J L; Cussó, R

2008-07-01

The diagnosis of muscular lesions suffered by athletes is usually made by clinical criteria combined with imaging of the lesion (ultrasonography and/or magnetic resonance) and blood tests to detect the presence of non-specific muscle markers. This study was undertaken to evaluate injury to fast and slow-twitch fibres using specific muscle markers for these fibres. Blood samples were obtained from 51 non-sports people and 38 sportsmen with skeletal muscle injury. Western blood analysis was performed to determine fast and slow myosin and creatine kinase (CK) levels. Skeletal muscle damage was diagnosed by physical examination, ultrasonography and magnetic resonance and biochemical markers. The imaging tests were found to be excellent for detecting and confirming grade II and III lesions. However, grade I lesions were often unconfirmed by these techniques. Grade I lesions have higher levels of fast myosin than slow myosin with a very small increase in CK levels. Grade II and III lesions have high values of both fast and slow myosin. The evaluation of fast and slow myosin in the blood 48 h after the lesion occurs is a useful aid for the detection of type I lesions in particular, since fast myosin is an exclusive skeletal muscle marker. The correct diagnosis of grade I lesions can prevent progression of the injury in athletes undergoing continual training sessions and competitions, thus aiding sports physicians in their decision making.

Biased Brownian motion mechanism for processivity and directionality of single-headed myosin-VI.

Science.gov (United States)

Iwaki, Mitsuhiro; Iwane, Atsuko Hikikoshi; Ikebe, Mitsuo; Yanagida, Toshio

2008-01-01

Conventional form to function as a vesicle transporter is not a 'single molecule' but a coordinated 'two molecules'. The coordinated two molecules make it complicated to reveal its mechanism. To overcome the difficulty, we adopted a single-headed myosin-VI as a model protein. Myosin-VI is an intracellular vesicle and organelle transporter that moves along actin filaments in a direction opposite to most other known myosin classes. The myosin-VI was expected to form a dimer to move processively along actin filaments with a hand-over-hand mechanism like other myosin organelle transporters. However, wild-type myosin-VI was demonstrated to be monomer and single-headed, casting doubt on its processivity. Using single molecule techniques, we show that green fluorescent protein (GFP)-fused single-headed myosin-VI does not move processively. However, when coupled to a 200 nm polystyrene bead (comparable to an intracellular vesicle in size) at a ratio of one head per bead, single-headed myosin-VI moves processively with large (40 nm) steps. Furthermore, we found that a single-headed myosin-VI-bead complex moved more processively in a high-viscous solution (40-fold higher than water) similar to cellular environment. Because diffusion of the bead is 60-fold slower than myosin-VI heads alone in water, we propose a model in which the bead acts as a diffusional anchor for the myosin-VI, enhancing the head's rebinding following detachment and supporting processive movement of the bead-monomer complex. This investigation will help us understand how molecular motors utilize Brownian motion in cells.

The Kinetics of Myosin Light Chain Kinase Activation of Smooth Muscle Myosin in an In Vitro Model System

OpenAIRE

Hong, Feng; Facemyer, Kevin C.; Carter, Michael S.; Jackson, Del R.; Haldeman, Brian D.; Ruana, Nick; Sutherland, Cindy; Walsh, Michael P.; Cremo, Christine R.; Baker, Josh E.

2013-01-01

During activation of smooth muscle contraction, one myosin light chain kinase (MLCK) molecule rapidly phosphorylates many smooth muscle myosin (SMM) molecules, suggesting that muscle activation rates are influenced by the kinetics of MLCK-SMM interactions. To determine the rate-limiting step underlying activation of SMM by MLCK, we measured the kinetics of calcium-calmodulin (Ca2+-CaM)-MLCK-mediated SMM phosphorylation and the corresponding initiation of SMM-based F-actin motility in an in vi...

A Role for Myosin Va in Human Cytomegalovirus Nuclear Egress.

Science.gov (United States)

Wilkie, Adrian R; Sharma, Mayuri; Pesola, Jean M; Ericsson, Maria; Fernandez, Rosio; Coen, Donald M

2018-03-15

Herpesviruses replicate and package their genomes into capsids in replication compartments within the nuclear interior. Capsids then move to the inner nuclear membrane for envelopment and release into the cytoplasm in a process called nuclear egress. We previously found that nuclear F-actin is induced upon infection with the betaherpesvirus human cytomegalovirus (HCMV) and is important for nuclear egress and capsid localization away from replication compartment-like inclusions toward the nuclear rim. Despite these and related findings, it has not been shown that any specific motor protein is involved in herpesvirus nuclear egress. In this study, we have investigated whether the host motor protein, myosin Va, could be fulfilling this role. Using immunofluorescence microscopy and coimmunoprecipitation, we observed associations between a nuclear population of myosin Va and the viral major capsid protein, with both concentrating at the periphery of replication compartments. Immunoelectron microscopy showed that nearly 40% of assembled nuclear capsids associate with myosin Va. We also found that myosin Va and major capsid protein colocalize with nuclear F-actin. Importantly, antagonism of myosin Va with RNA interference or a dominant negative mutant revealed that myosin Va is important for the efficient production of infectious virus, capsid accumulation in the cytoplasm, and capsid localization away from replication compartment-like inclusions toward the nuclear rim. Our results lead us to suggest a working model whereby human cytomegalovirus capsids associate with myosin Va for movement from replication compartments to the nuclear periphery during nuclear egress. IMPORTANCE Little is known regarding how newly assembled and packaged herpesvirus capsids move from the nuclear interior to the periphery during nuclear egress. While it has been proposed that an actomyosin-based mechanism facilitates intranuclear movement of alphaherpesvirus capsids, a functional role for

Dynamics of myosin II organization into cortical contractile networks and fibers

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Nie, Wei; Wei, Ming-Tzo; Ou-Yang, Daniel; Jedlicka, Sabrina; Vavylonis, Dimitrios

2014-03-01

The morphology of adhered cells critically depends on the formation of a contractile meshwork of parallel and cross-linked stress fibers along the contacting surface. The motor activity and mini-filament assembly of non-muscle myosin II is an important component of cell-level cytoskeletal remodeling during mechanosensing. To monitor the dynamics of myosin II, we used confocal microscopy to image cultured HeLa cells that stably express myosin regulatory light chain tagged with GFP (MRLC-GFP). MRLC-GFP was monitored in time-lapse movies at steady state and during the response of cells to varying concentrations of blebbistatin which disrupts actomyosin stress fibers. Using image correlation spectroscopy analysis, we quantified the kinetics of disassembly and reassembly of actomyosin networks and compared them to studies by other groups. This analysis suggested that the following processes contribute to the assembly of cortical actomyosin into fibers: random myosin mini-filament assembly and disassembly along the cortex; myosin mini-filament aligning and contraction; stabilization of cortical myosin upon increasing contractile tension. We developed simple numerical simulations that include those processes. The results of simulations of cells at steady state and in response to blebbistatin capture some of the main features observed in the experiments. This study provides a framework to help interpret how different cortical myosin remodeling kinetics may contribute to different cell shape and rigidity depending on substrate stiffness.

Unconstrained steps of myosin VI appear longest among known molecular motors.

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Ali, M Yusuf; Homma, Kazuaki; Iwane, Atsuko Hikikoshi; Adachi, Kengo; Itoh, Hiroyasu; Kinosita, Kazuhiko; Yanagida, Toshio; Ikebe, Mitsuo

2004-06-01

Myosin VI is a two-headed molecular motor that moves along an actin filament in the direction opposite to most other myosins. Previously, a single myosin VI molecule has been shown to proceed with steps that are large compared to its neck size: either it walks by somehow extending its neck or one head slides along actin for a long distance before the other head lands. To inquire into these and other possible mechanism of motility, we suspended an actin filament between two plastic beads, and let a single myosin VI molecule carrying a bead duplex move along the actin. This configuration, unlike previous studies, allows unconstrained rotation of myosin VI around the right-handed double helix of actin. Myosin VI moved almost straight or as a right-handed spiral with a pitch of several micrometers, indicating that the molecule walks with strides slightly longer than the actin helical repeat of 36 nm. The large steps without much rotation suggest kinesin-type walking with extended and flexible necks, but how to move forward with flexible necks, even under a backward load, is not clear. As an answer, we propose that a conformational change in the lifted head would facilitate landing on a forward, rather than backward, site. This mechanism may underlie stepping of all two-headed molecular motors including kinesin and myosin V.

Distribution and evolution of stable single α-helices (SAH domains in myosin motor proteins.

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Dominic Simm

Full Text Available Stable single-alpha helices (SAHs are versatile structural elements in many prokaryotic and eukaryotic proteins acting as semi-flexible linkers and constant force springs. This way SAH-domains function as part of the lever of many different myosins. Canonical myosin levers consist of one or several IQ-motifs to which light chains such as calmodulin bind. SAH-domains provide flexibility in length and stiffness to the myosin levers, and may be particularly suited for myosins working in crowded cellular environments. Although the function of the SAH-domains in human class-6 and class-10 myosins has well been characterised, the distribution of the SAH-domain in all myosin subfamilies and across the eukaryotic tree of life remained elusive. Here, we analysed the largest available myosin sequence dataset consisting of 7919 manually annotated myosin sequences from 938 species representing all major eukaryotic branches using the SAH-prediction algorithm of Waggawagga, a recently developed tool for the identification of SAH-domains. With this approach we identified SAH-domains in more than one third of the supposed 79 myosin subfamilies. Depending on the myosin class, the presence of SAH-domains can range from a few to almost all class members indicating complex patterns of independent and taxon-specific SAH-domain gain and loss.

Myosin light chain kinase phosphorylation in tracheal smooth muscle

International Nuclear Information System (INIS)

Stull, J.T.; Hsu, L.C.; Tansey, M.G.; Kamm, K.E.

1990-01-01

Purified myosin light chain kinase from smooth muscle is phosphorylated by cyclic AMP-dependent protein kinase, protein kinase C, and the multifunctional calmodulin-dependent protein kinase II. Because phosphorylation in a specific site (site A) by any one of these kinases desensitizes myosin light chain kinase to activation by Ca2+/calmodulin, kinase phosphorylation could play an important role in regulating smooth muscle contractility. This possibility was investigated in 32 P-labeled bovine tracheal smooth muscle. Treatment of tissues with carbachol, KCl, isoproterenol, or phorbol 12,13-dibutyrate increased the extent of kinase phosphorylation. Six primary phosphopeptides (A-F) of myosin light chain kinase were identified. Site A was phosphorylated to an appreciable extent only with carbachol or KCl, agents which contract tracheal smooth muscle. The extent of site A phosphorylation correlated to increases in the concentration of Ca2+/calmodulin required for activation. These results show that cyclic AMP-dependent protein kinase and protein kinase C do not affect smooth muscle contractility by phosphorylating site A in myosin light chain kinase. It is proposed that phosphorylation of myosin light chain kinase in site A in contracting tracheal smooth muscle may play a role in the reported desensitization of contractile elements to activation by Ca2+

Actin-myosin network is required for proper assembly of influenza virus particles

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Kumakura, Michiko; Kawaguchi, Atsushi, E-mail: ats-kawaguchi@md.tsukuba.ac.jp; Nagata, Kyosuke, E-mail: knagata@md.tsukuba.ac.jp

2015-02-15

Actin filaments are known to play a central role in cellular dynamics. After polymerization of actin, various actin-crosslinking proteins including non-muscle myosin II facilitate the formation of spatially organized actin filament networks. The actin-myosin network is highly expanded beneath plasma membrane. The genome of influenza virus (vRNA) replicates in the cell nucleus. Then, newly synthesized vRNAs are nuclear-exported to the cytoplasm as ribonucleoprotein complexes (vRNPs), followed by transport to the beneath plasma membrane where virus particles assemble. Here, we found that, by inhibiting actin-myosin network formation, the virus titer tends to be reduced and HA viral spike protein is aggregated on the plasma membrane. These results indicate that the actin-myosin network plays an important role in the virus formation. - Highlights: • Actin-myosin network is important for the influenza virus production. • HA forms aggregations at the plasma membrane in the presence of blebbistatin. • M1 is recruited to the budding site through the actin-myosin network.

Actin-myosin network is required for proper assembly of influenza virus particles

International Nuclear Information System (INIS)

Kumakura, Michiko; Kawaguchi, Atsushi; Nagata, Kyosuke

2015-01-01

Actin filaments are known to play a central role in cellular dynamics. After polymerization of actin, various actin-crosslinking proteins including non-muscle myosin II facilitate the formation of spatially organized actin filament networks. The actin-myosin network is highly expanded beneath plasma membrane. The genome of influenza virus (vRNA) replicates in the cell nucleus. Then, newly synthesized vRNAs are nuclear-exported to the cytoplasm as ribonucleoprotein complexes (vRNPs), followed by transport to the beneath plasma membrane where virus particles assemble. Here, we found that, by inhibiting actin-myosin network formation, the virus titer tends to be reduced and HA viral spike protein is aggregated on the plasma membrane. These results indicate that the actin-myosin network plays an important role in the virus formation. - Highlights: • Actin-myosin network is important for the influenza virus production. • HA forms aggregations at the plasma membrane in the presence of blebbistatin. • M1 is recruited to the budding site through the actin-myosin network

Myosin phosphatase Fine-tunes Zebrafish Motoneuron Position during Axonogenesis.

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Juliane Bremer

2016-11-01

Full Text Available During embryogenesis the spinal cord shifts position along the anterior-posterior axis relative to adjacent tissues. How motor neurons whose cell bodies are located in the spinal cord while their axons reside in adjacent tissues compensate for such tissue shift is not well understood. Using live cell imaging in zebrafish, we show that as motor axons exit from the spinal cord and extend through extracellular matrix produced by adjacent notochord cells, these cells shift several cell diameters caudally. Despite this pronounced shift, individual motoneuron cell bodies stay aligned with their extending axons. We find that this alignment requires myosin phosphatase activity within motoneurons, and that mutations in the myosin phosphatase subunit mypt1 increase myosin phosphorylation causing a displacement between motoneuron cell bodies and their axons. Thus, we demonstrate that spinal motoneurons fine-tune their position during axonogenesis and we identify the myosin II regulatory network as a key regulator.

Myosin content of individual human muscle fibers isolated by laser capture microdissection.

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Stuart, Charles A; Stone, William L; Howell, Mary E A; Brannon, Marianne F; Hall, H Kenton; Gibson, Andrew L; Stone, Michael H

2016-03-01

Muscle fiber composition correlates with insulin resistance, and exercise training can increase slow-twitch (type I) fibers and, thereby, mitigate diabetes risk. Human skeletal muscle is made up of three distinct fiber types, but muscle contains many more isoforms of myosin heavy and light chains, which are coded by 15 and 11 different genes, respectively. Laser capture microdissection techniques allow assessment of mRNA and protein content in individual fibers. We found that specific human fiber types contain different mixtures of myosin heavy and light chains. Fast-twitch (type IIx) fibers consistently contained myosin heavy chains 1, 2, and 4 and myosin light chain 1. Type I fibers always contained myosin heavy chains 6 and 7 (MYH6 and MYH7) and myosin light chain 3 (MYL3), whereas MYH6, MYH7, and MYL3 were nearly absent from type IIx fibers. In contrast to cardiomyocytes, where MYH6 (also known as α-myosin heavy chain) is seen solely in fast-twitch cells, only slow-twitch fibers of skeletal muscle contained MYH6. Classical fast myosin heavy chains (MHC1, MHC2, and MHC4) were present in variable proportions in all fiber types, but significant MYH6 and MYH7 expression indicated slow-twitch phenotype, and the absence of these two isoforms determined a fast-twitch phenotype. The mixed myosin heavy and light chain content of type IIa fibers was consistent with its role as a transition between fast and slow phenotypes. These new observations suggest that the presence or absence of MYH6 and MYH7 proteins dictates the slow- or fast-twitch phenotype in skeletal muscle. Copyright © 2016 the American Physiological Society.

Myosin VIII regulates protonemal patterning and developmental timing in the moss Physcomitrella patens.

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Wu, Shu-Zon; Ritchie, Julie A; Pan, Ai-Hong; Quatrano, Ralph S; Bezanilla, Magdalena

2011-09-01

Plants have two classes of myosins. While recent work has focused on class XI myosins showing that myosin XI is responsible for organelle motility and cytoplasmic streaming, much less is known about the role of myosin VIII in plant growth and development. We have used a combination of RNAi and insertional knockouts to probe myosin VIII function in the moss Physcomitrella patens. We isolated Δmyo8ABCDE plants demonstrating that myosin VIII is not required for plant viability. However, myosin VIII mutants are smaller than wild-type plants in part due to a defect in cell size. Additionally, Δmyo8ABCDE plants produce more side branches and form gametophores much earlier than wild-type plants. In the absence of nutrient media, Δmyo8ABCDE plants exhibit significant protonemal patterning defects, including highly curved protonemal filaments, morphologically defective side branches, as well as an increase in the number of branches. Exogenous auxin partially rescues protonemal defects in Δmyo8ABCDE plants grown in the absence of nutrients. This result, together with defects in protonemal branching, smaller caulonemal cells, and accelerated development in the Δmyo8ABCDE plants, suggests that myosin VIII is involved in hormone homeostasis in P. patens.

Structural insight into the UNC-45–myosin complex

DEFF Research Database (Denmark)

Fratev, Filip; Jonsdottir, Svava Osk; Pajeva, Ilza

2013-01-01

The UNC-45 chaperone protein interacts with and affects the folding, stability, and the ATPase activity of myosins. It plays a critical role in the cardiomyopathy development and in the breast cancer tumor growth. Here we propose the first structural model of the UNC-45–myosin complex using various...... is mainly stabilized by electrostatic interactions. Remarkably, the contact surface area is similar to that of the myosinactin complex. A significant interspecies difference in the myosin binding epitope is observed. Our results reveal the structural basis of MYH7 exons 15–16 hypertrophic cardiomyopathy...... mutations and provide directions for drug targeting. © 2013 Wiley Periodicals, Inc....

Three-dimensional stochastic model of actin–myosin binding in the sarcomere lattice

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Mijailovich, Srboljub M.; Kayser-Herold, Oliver; Stojanovic, Boban; Nedic, Djordje; Irving, Thomas C.; Geeves, MA (Harvard); (IIT); (U. Kent); (Kragujevac)

2016-11-18

The effect of molecule tethering in three-dimensional (3-D) space on bimolecular binding kinetics is rarely addressed and only occasionally incorporated into models of cell motility. The simplest system that can quantitatively determine this effect is the 3-D sarcomere lattice of the striated muscle, where tethered myosin in thick filaments can only bind to a relatively small number of available sites on the actin filament, positioned within a limited range of thermal movement of the myosin head. Here we implement spatially explicit actomyosin interactions into the multiscale Monte Carlo platform MUSICO, specifically defining how geometrical constraints on tethered myosins can modulate state transition rates in the actomyosin cycle. The simulations provide the distribution of myosin bound to sites on actin, ensure conservation of the number of interacting myosins and actin monomers, and most importantly, the departure in behavior of tethered myosin molecules from unconstrained myosin interactions with actin. In addition, MUSICO determines the number of cross-bridges in each actomyosin cycle state, the force and number of attached cross-bridges per myosin filament, the range of cross-bridge forces and accounts for energy consumption. At the macroscopic scale, MUSICO simulations show large differences in predicted force-velocity curves and in the response during early force recovery phase after a step change in length comparing to the two simplest mass action kinetic models. The origin of these differences is rooted in the different fluxes of myosin binding and corresponding instantaneous cross-bridge distributions and quantitatively reflects a major flaw of the mathematical description in all mass action kinetic models. Consequently, this new approach shows that accurate recapitulation of experimental data requires significantly different binding rates, number of actomyosin states, and cross-bridge elasticity than typically used in mass action kinetic models to

The expression of myosin genes in developing skeletal muscle in the mouse embryo

International Nuclear Information System (INIS)

Lyons, G.E.; Ontell, M.; Cox, R.; Sassoon, D.; Buckingham, M.

1990-01-01

Using in situ hybridization, we have investigated the temporal sequence of myosin gene expression in the developing skeletal muscle masses of mouse embryos. The probes used were isoform-specific, 35S-labeled antisense cRNAs to the known sarcomeric myosin heavy chain and myosin alkali light chain gene transcripts. Results showed that both cardiac and skeletal myosin heavy chain and myosin light chain mRNAs were first detected between 9 and 10 d post coitum (p.c.) in the myotomes of the most rostral somites. Myosin transcripts appeared in more caudal somites at later stages in a developmental gradient. The earliest myosin heavy chain transcripts detected code for the embryonic skeletal (MHCemb) and beta-cardiac (MHC beta) isoforms. Perinatal myosin heavy chain (MHCpn) transcripts begin to accumulate at 10.5 d p.c., which is much earlier than previously reported. At this stage, MHCemb is the major MHC transcript. By 12.5 d p.c., MHCpn and MHCemb mRNAs are present to an equal extent, and by 15.5 d p.c. the MHCpn transcript is the major MHC mRNA detected. Cardiac MHC beta transcripts are always present as a minor component. In contrast, the cardiac MLC1A mRNA is initially more abundant than that encoding the skeletal MLC1F isoform. By 12.5 d p.c. the two MLC mRNAs are present at similar levels, and by 15.5 d p.c., MLC1F is the predominant MLC transcript detected. Transcripts for the ventricular/slow (MLC1V) and another fast skeletal myosin light chain (MLC3F) are not detected in skeletal muscle before 15 d p.c., which marks the beginning of the fetal stage of muscle development. This is the first stage at which we can detect differences in expression of myosin genes between developing muscle fibers. We conclude that, during the development of the myotome and body wall muscles, different myosin genes follow independent patterns of activation and acculumation

A Drosophila model of dominant inclusion body myopathy type 3 shows diminished myosin kinetics that reduce muscle power and yield myofibrillar defects.

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Suggs, Jennifer A; Melkani, Girish C; Glasheen, Bernadette M; Detor, Mia M; Melkani, Anju; Marsan, Nathan P; Swank, Douglas M; Bernstein, Sanford I

2017-06-01

Individuals with inclusion body myopathy type 3 (IBM3) display congenital joint contractures with early-onset muscle weakness that becomes more severe in adulthood. The disease arises from an autosomal dominant point mutation causing an E706K substitution in myosin heavy chain type IIa. We have previously expressed the corresponding myosin mutation (E701K) in homozygous Drosophila indirect flight muscles and recapitulated the myofibrillar degeneration and inclusion bodies observed in the human disease. We have also found that purified E701K myosin has dramatically reduced actin-sliding velocity and ATPase levels. Since IBM3 is a dominant condition, we now examine the disease state in heterozygote Drosophila in order to gain a mechanistic understanding of E701K pathogenicity. Myosin ATPase activities in heterozygotes suggest that approximately equimolar levels of myosin accumulate from each allele. In vitro actin sliding velocity rates for myosin isolated from the heterozygotes were lower than the control, but higher than for the pure mutant isoform. Although sarcomeric ultrastructure was nearly wild type in young adults, mechanical analysis of skinned indirect flight muscle fibers revealed a 59% decrease in maximum oscillatory power generation and an approximately 20% reduction in the frequency at which maximum power was produced. Rate constant analyses suggest a decrease in the rate of myosin attachment to actin, with myosin spending decreased time in the strongly bound state. These mechanical alterations result in a one-third decrease in wing beat frequency and marginal flight ability. With aging, muscle ultrastructure and function progressively declined. Aged myofibrils showed Z-line streaming, consistent with the human heterozygote phenotype. Based upon the mechanical studies, we hypothesize that the mutation decreases the probability of the power stroke occurring and/or alters the degree of movement of the myosin lever arm, resulting in decreased in vitro

A Drosophila model of dominant inclusion body myopathy type 3 shows diminished myosin kinetics that reduce muscle power and yield myofibrillar defects

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Jennifer A. Suggs

2017-06-01

Full Text Available Individuals with inclusion body myopathy type 3 (IBM3 display congenital joint contractures with early-onset muscle weakness that becomes more severe in adulthood. The disease arises from an autosomal dominant point mutation causing an E706K substitution in myosin heavy chain type IIa. We have previously expressed the corresponding myosin mutation (E701K in homozygous Drosophila indirect flight muscles and recapitulated the myofibrillar degeneration and inclusion bodies observed in the human disease. We have also found that purified E701K myosin has dramatically reduced actin-sliding velocity and ATPase levels. Since IBM3 is a dominant condition, we now examine the disease state in heterozygote Drosophila in order to gain a mechanistic understanding of E701K pathogenicity. Myosin ATPase activities in heterozygotes suggest that approximately equimolar levels of myosin accumulate from each allele. In vitro actin sliding velocity rates for myosin isolated from the heterozygotes were lower than the control, but higher than for the pure mutant isoform. Although sarcomeric ultrastructure was nearly wild type in young adults, mechanical analysis of skinned indirect flight muscle fibers revealed a 59% decrease in maximum oscillatory power generation and an approximately 20% reduction in the frequency at which maximum power was produced. Rate constant analyses suggest a decrease in the rate of myosin attachment to actin, with myosin spending decreased time in the strongly bound state. These mechanical alterations result in a one-third decrease in wing beat frequency and marginal flight ability. With aging, muscle ultrastructure and function progressively declined. Aged myofibrils showed Z-line streaming, consistent with the human heterozygote phenotype. Based upon the mechanical studies, we hypothesize that the mutation decreases the probability of the power stroke occurring and/or alters the degree of movement of the myosin lever arm, resulting in

The structure of the actin-smooth muscle myosin motor domain complex in the rigor state.

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Banerjee, Chaity; Hu, Zhongjun; Huang, Zhong; Warrington, J Anthony; Taylor, Dianne W; Trybus, Kathleen M; Lowey, Susan; Taylor, Kenneth A

2017-12-01

Myosin-based motility utilizes catalysis of ATP to drive the relative sliding of F-actin and myosin. The earliest detailed model based on cryo-electron microscopy (cryoEM) and X-ray crystallography postulated that higher actin affinity and lever arm movement were coupled to closure of a feature of the myosin head dubbed the actin-binding cleft. Several studies since then using crystallography of myosin-V and cryoEM structures of F-actin bound myosin-I, -II and -V have provided details of this model. The smooth muscle myosin II interaction with F-actin may differ from those for striated and non-muscle myosin II due in part to different lengths of important surface loops. Here we report a ∼6 Å resolution reconstruction of F-actin decorated with the nucleotide-free recombinant smooth muscle myosin-II motor domain (MD) from images recorded using a direct electron detector. Resolution is highest for F-actin and the actin-myosin interface (3.5-4 Å) and lowest (∼6-7 Å) for those parts of the MD at the highest radius. Atomic models built into the F-actin density are quite comparable to those previously reported for rabbit muscle actin and show density from the bound ADP. The atomic model of the MD, is quite similar to a recently published structure of vertebrate non-muscle myosin II bound to F-actin and a crystal structure of nucleotide free myosin-V. Larger differences are observed when compared to the cryoEM structure of F-actin decorated with rabbit skeletal muscle myosin subfragment 1. The differences suggest less closure of the 50 kDa domain in the actin bound skeletal muscle myosin structure. Copyright © 2017 Elsevier Inc. All rights reserved.

Nonmuscle myosin IIB as a therapeutic target for the prevention of relapse to methamphetamine use

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Young, Erica J.; Blouin, Ashley M.; Briggs, Sherri B.; Sillivan, Stephanie E.; Lin, Li; Cameron, Michael D.; Rumbaugh, Gavin; Miller, Courtney A.

2015-01-01

Memories associated with drug use increase vulnerability to relapse in substance use disorder (SUD) and there are no pharmacotherapies for the prevention of relapse. Previously, we reported a promising finding that storage of memories associated with methamphetamine (METH), but not memories for fear or food reward, is vulnerable to disruption by actin depolymerization in the basolateral amygdala complex (BLC). However, actin is not a viable therapeutic target because of its numerous functions throughout the body. Here we report the discovery of a viable therapeutic target, nonmuscle myosin II (NMIIB), a molecular motor that supports memory by directly driving synaptic actin polymerization. A single intra-BLC treatment with Blebbistatin, a small molecule inhibitor of class II myosin isoforms, including NMIIB, produced a long-lasting disruption of context-induced drug seeking (at least 30 days). Further, post-consolidation genetic knockdown of Myh10, the heavy chain of the most highly expressed NMII in the BLC, was sufficient to produce METH-associated memory loss. Blebbistatin was found to be highly brain penetrant. A single systemic injection of the compound selectively disrupted the storage of METH-associated memory and reversed the accompanying increase in BLC spine density. This effect was specific to METH-associated memory, as it had no effect on an auditory fear memory. The effect was also independent of retrieval, as METH-associated memory was disrupted twenty-four hours after a single systemic injection of Blebbistatin delivered in the home cage. Together, these results argue for the further development of small molecule inhibitors of nonmuscle myosin II as potential therapeutics for the prevention of SUD relapse triggered by drug associations. PMID:26239291

Oxidation of myosin by haem proteins generates myosin radicals and protein cross-links

DEFF Research Database (Denmark)

Lametsch, Marianne Lund; Luxford, Catherine; Skibsted, Leif Horsfelt

2008-01-01

of thiyl and tyrosyl radicals is consistent with the observed consumption of cysteine and tyrosine residues, the detection of di-tyrosine by HPLC and the detection of both reducible (disulfide bond) and non-reducible cross-links between myosin molecules by SDS/PAGE. The time course of radical formation...

Slit and Netrin-1 guide cranial motor axon pathfinding via Rho-kinase, myosin light chain kinase and myosin II

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Drescher Uwe

2010-06-01

Full Text Available Abstract Background In the developing hindbrain, cranial motor axon guidance depends on diffusible repellent factors produced by the floor plate. Our previous studies have suggested that candidate molecules for mediating this effect are Slits, Netrin-1 and Semaphorin3A (Sema3A. It is unknown to what extent these factors contribute to floor plate-derived chemorepulsion of motor axons, and the downstream signalling pathways are largely unclear. Results In this study, we have used a combination of in vitro and in vivo approaches to identify the components of floor plate chemorepulsion and their downstream signalling pathways. Using in vitro motor axon deflection assays, we demonstrate that Slits and Netrin-1, but not Sema3A, contribute to floor plate repulsion. We also find that the axon pathways of dorsally projecting branchiomotor neurons are disrupted in Netrin-1 mutant mice and in chick embryos expressing dominant-negative Unc5a receptors, indicating an in vivo role for Netrin-1. We further demonstrate that Slit and Netrin-1 signalling are mediated by Rho-kinase (ROCK and myosin light chain kinase (MLCK, which regulate myosin II activity, controlling actin retrograde flow in the growth cone. We show that MLCK, ROCK and myosin II are required for Slit and Netrin-1-mediated growth cone collapse of cranial motor axons. Inhibition of these molecules in explant cultures, or genetic manipulation of RhoA or myosin II function in vivo causes characteristic cranial motor axon pathfinding errors, including the inability to exit the midline, and loss of turning towards exit points. Conclusions Our findings suggest that both Slits and Netrin-1 contribute to floor plate-derived chemorepulsion of cranial motor axons. They further indicate that RhoA/ROCK, MLCK and myosin II are components of Slit and Netrin-1 signalling pathways, and suggest that these pathways are of key importance in cranial motor axon navigation.

Adult fast myosin pattern and Ca2+-induced slow myosin pattern in primary skeletal muscle culture

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Kubis, Hans-Peter; Haller, Ernst-August; Wetzel, Petra; Gros, Gerolf

1997-01-01

A primary muscle cell culture derived from newborn rabbit muscle and growing on microcarriers in suspension was established. When cultured for several weeks, the myotubes in this model develop the completely adult pattern of fast myosin light and heavy chains. When Ca2+ ionophore is added to the culture medium on day 11, raising intracellular [Ca2+] about 10-fold, the myotubes develop to exhibit properties of an adult slow muscle by day 30, expressing slow myosin light as well as heavy chains, elevated citrate synthase, and reduced lactate dehydrogenase. The remarkable plasticity of these myotubes becomes apparent, when 8 days after withdrawal of the ionophore a marked slow-to-fast transition, as judged from the expression of isomyosins and metabolic enzymes, occurs. PMID:9108130

Acceleration of the sliding movement of actin filaments with the use of a non-motile mutant myosin in in vitro motility assays driven by skeletal muscle heavy meromyosin.

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Kohei Iwase

Full Text Available We examined the movement of an actin filament sliding on a mixture of normal and genetically modified myosin molecules that were attached to a glass surface. For this purpose, we used a Dictyostelium G680V mutant myosin II whose release rates of Pi and ADP were highly suppressed relative to normal myosin, leading to a significantly extended life-time of the strongly bound state with actin and virtually no motility. When the mixing ratio of G680V mutant myosin II to skeletal muscle HMM (heavy myosin was 0.01%, the actin filaments moved intermittently. When they moved, their sliding velocities were about two-fold faster than the velocity of skeletal HMM alone. Furthermore, sliding movements were also faster when the actin filaments were allowed to slide on skeletal muscle HMM-coated glass surfaces in the motility buffer solution containing G680V HMM. In this case no intermittent movement was observed. When the actin filaments used were copolymerized with a fusion protein consisting of Dictyostelium actin and Dictyostelium G680V myosin II motor domain, similar faster sliding movements were observed on skeletal muscle HMM-coated surfaces. The filament sliding velocities were about two-fold greater than the velocities of normal actin filaments. We found that the velocity of actin filaments sliding on skeletal muscle myosin molecules increased in the presence of a non-motile G680V mutant myosin motor.

Catalytic strategy used by the myosin motor to hydrolyze ATP.

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Kiani, Farooq Ahmad; Fischer, Stefan

2014-07-22

Myosin is a molecular motor responsible for biological motions such as muscle contraction and intracellular cargo transport, for which it hydrolyzes adenosine 5'-triphosphate (ATP). Early steps of the mechanism by which myosin catalyzes ATP hydrolysis have been investigated, but still missing are the structure of the final ADP·inorganic phosphate (Pi) product and the complete pathway leading to it. Here, a comprehensive description of the catalytic strategy of myosin is formulated, based on combined quantum-classical molecular mechanics calculations. A full exploration of catalytic pathways was performed and a final product structure was found that is consistent with all experiments. Molecular movies of the relevant pathways show the different reorganizations of the H-bond network that lead to the final product, whose γ-phosphate is not in the previously reported HPγO4(2-) state, but in the H2PγO4(-) state. The simulations reveal that the catalytic strategy of myosin employs a three-pronged tactic: (i) Stabilization of the γ-phosphate of ATP in a dissociated metaphosphate (PγO3(-)) state. (ii) Polarization of the attacking water molecule, to abstract a proton from that water. (iii) Formation of multiple proton wires in the active site, for efficient transfer of the abstracted proton to various product precursors. The specific role played in this strategy by each of the three loops enclosing ATP is identified unambiguously. It explains how the precise timing of the ATPase activation during the force generating cycle is achieved in myosin. The catalytic strategy described here for myosin is likely to be very similar in most nucleotide hydrolyzing enzymes.

The role of the myosin ATPase activity in adaptive thermogenesis by skeletal muscle.

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Cooke, Roger

2011-03-01

Resting skeletal muscle is a major contributor to adaptive thermogenesis, i.e., the thermogenesis that changes in response to exposure to cold or to overfeeding. The identification of the "furnace" that is responsible for increased heat generation in resting muscle has been the subject of a number of investigations. A new state of myosin, the super relaxed state (SRX), with a very slow ATP turnover rate has recently been observed in skeletal muscle (Stewart et al. in Proc Natl Acad Sci USA 107:430-435, 2010). Inhibition of the myosin ATPase activity in the SRX was suggested to be caused by binding of the myosin head to the core of the thick filament in a structural motif identified earlier by electron microscopy. To be compatible with the basal metabolic rate observed in vivo for resting muscle, most myosin heads would have to be in the SRX. Modulation of the population of this state, relative to the normal relaxed state, was proposed to be a major contributor to adaptive thermogenesis in resting muscle. Transfer of only 20% of myosin heads from the SRX into the normal relaxed state would cause muscle thermogenesis to double. Phosphorylation of the myosin regulatory light chain was shown to transfer myosin heads from the SRX into the relaxed state, which would increase thermogenesis. In particular, thermogenesis by myosin has been proposed to play a role in the dissipation of calories during overfeeding. Up-regulation of muscle thermogenesis by pharmaceuticals that target the SRX would provide new approaches to the treatment of obesity or high blood sugar levels.

Modulation of neutrophil superoxide generation by inhibitors of protein kinase C, calmodulin, diacylglycerol and myosin light chain kinases, and peptidyl prolyl cis-trans isomerase.

Science.gov (United States)

Bergstrand, H; Eriksson, T; Hallberg, A; Johansson, B; Karabelas, K; Michelsen, P; Nybom, A

1992-12-01

To assess the role of protein kinase C (PKC) in the respiratory burst of adherent human polymorphonuclear leukocytes (PMNL), reduction of ferricytochrome C by cells triggered with a phorbol ester (PMA), ionophore A23187, serum-treated zymosan (STZ) or three lipid derivatives, 3-decanoyl-sn-glycerol (G-3-OCOC9), (R,R)-1,4-diethyl-2-O-decyl-L-tartrate (Tt-2-OC10) and 3-decyloxy-5-hydroxymethylphenol (DHP) was examined in a microtiter plate procedure in the presence of inhibitors of PKC and, for comparison, inhibitors of calmodulin, diacylglycerol and myosin light chain kinases and the peptidyl-prolyl cis-trans isomerase activity of fujiphilin. 1) Of the protein kinase inhibitors examined, Ro 31-7549 and staurosporine reduced responses to all stimuli except possibly STZ; in contrast, K252a and the myosin light chain kinase inhibitors ML-7 and ML-9 blocked responses to A23187 and STZ better than those triggered by PMA. H-7 reduced responses to A23187, DHP and G-3-OCOC9, and calphostin, palmitoyl carnitine, sphingosine and the multifunctional drugs TMB-8 and W-7 reduced A23187; they also, when examined, reduced decane derivative-induced O2- production more effectively than PMA- and STZ-triggered responses. Polymyxin B, 4 alpha-PMA and retinal displayed no inhibitory capacity. 2) Of the selective calmodulin antagonists, CGS 9343B, Ro 22-4839 and calmidazolium did not inhibit the oxidative response irrespective of the stimulus used, whereas metofenazate reduced those evoked by A23187, DHP, G-3-OCOC9 and STZ.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracellular matrix-dependent myosin dynamics during G1-S phase cell cycle progression in hepatocytes

International Nuclear Information System (INIS)

Bhadriraju, Kiran; Hansen, Linda K.

2004-01-01

Cell spreading and proliferation are tightly coupled in anchorage-dependent cells. While adhesion-dependent proliferation signals require an intact actin cytoskeleton, and some of these signals such as ERK activation have been characterized, the role of myosin in spreading and cell cycle progression under different extracellular matrix (ECM) conditions is not known. Studies presented here examine changes in myosin activity in freshly isolated hepatocytes under ECM conditions that promote either proliferation (high fibronectin density) or growth arrest (low fibronectin density). Three different measures were obtained and related to both spreading and cell cycle progression: myosin protein levels and association with cytoskeleton, myosin light chain phosphorylation, and its ATPase activity. During the first 48 h in culture, corresponding with transit through G1 phase, there was a six-fold increase in both myosin protein levels and myosin association with actin cytoskeleton. There was also a steady increase in myosin light chain phosphorylation and ATPase activity with spreading, which did not occur in non-spread, growth-arrested cells on low density of fibronectin. Myosin-inhibiting drugs blocked ERK activation, cyclin D1 expression, and S phase entry. Overexpression of the cell cycle protein cyclin D1 overcame both ECM-dependent and actomyosin-dependent inhibition of DNA synthesis, suggesting that cyclin D1 is a key event downstream of myosin-dependent cell cycle regulation

TRIGGER

CERN Multimedia

W. Smith, from contributions of D. Acosta

2012-01-01

  The L1 Trigger group deployed several major improvements this year. Compared to 2011, the single-muon trigger rate has been reduced by a factor of 2 and the η coverage has been restored to 2.4, with high efficiency. During the current technical stop, a higher jet seed threshold will be applied in the Global Calorimeter Trigger in order to significantly reduce the strong pile-up dependence of the HT and multi-jet triggers. The currently deployed L1 menu, with the “6E33” prescales, has a total rate of less than 100 kHz and operates with detector readout dead time of less than 3% for luminosities up to 6.5 × 1033 cm–2s–1. Further prescale sets have been created for 7 and 8 × 1033 cm–2s–1 luminosities. The L1 DPG is evaluating the performance of the Trigger for upcoming conferences and publication. Progress on the Trigger upgrade was reviewed during the May Upgrade Week. We are investigating scenarios for stagin...

Localization of Myosin and Actin in the Pelage and Whisker Hair Follicles of Rat

International Nuclear Information System (INIS)

Morioka, Kiyokazu; Matsuzaki, Toshiyuki; Takata, Kuniaki

2006-01-01

The combined effects of myosin II and actin enable muscle and nonmuscle cells to generate forces required for muscle contraction, cell division, cell migration, cellular morphological changes, the maintenance of cellular tension and polarity, and so on. However, except for the case of muscle contraction, the details are poorly understood. We focus on nonmuscle myosin and actin in the formation and maintenance of hair and skin, which include highly active processes in mammalian life with respect to the cellular proliferation, differentiation, and movement. The localization of nonmuscle myosin II and actin in neonatal rat dorsal skin, mystacial pad, hair follicles, and vibrissal follicles was studied by immunohistochemical technique to provide the basis for the elucidation of the roles of these proteins. Specificities of the antibodies were verified by using samples from the relevant tissues and subjecting them to immunoblotting test prior to morphological analyses. The myosin and actin were abundant and colocalized in the spinous and granular layers but scarce in the basal layer of the dorsal and mystacial epidermis. In hair and vibrissal follicles, nonmuscle myosin and actin were colocalized in the outer root sheath and some hair matrix cells adjoining dermal papillae. In contrast, most areas of the inner root sheath and hair matrix appeared to comprise very small amounts of myosin and actin. Hair shaft may comprise significant myosin during the course of its keratinization. These results suggest that the actin-myosin system plays a part in cell movement, differentiation, protection and other key functions of skin and hair cells

Reduction in beta-myosin heavy chains in stunned myocardium as assessed by nondenaturing gel electrophoresis.

Science.gov (United States)

Garcia, S C; Pomblum, V J; Gams, E; Rupp, H; Schipke, J D

2007-09-01

Myosin plays a key role in the structure and function of cardiac muscle. Three myosin isoenzymes (V(1), V(2), and V(3)) with different ATPase activities have been identified in mammalian ventricles based on their heavy chain constituents. The relative amount of myosin isoenzymes changes under physiological and pathological conditions. Until now, myosin isoenzymes have frequently been determined using either tube gel (nondenaturing) polyacrylamide gel electrophoresis (PAGE), or gradient or uniform sodium dodecyl sulfate (denaturing) PAGE. Both methods have disadvantages, e.g., a long running time. We developed, therefore, a uniform, nondenaturing PAGE with slab minigel format for analyzing the myosin isoenzymes in normoxic and stunned rabbit hearts. In normoxic hearts of adult rabbits, V(3) predominated over V(1) (46 vs 41%). In turn, in the stunned hearts, V(1) predominated over V(3) (70 vs 30%), and the heterodimeric V(2) was not anymore detectable. This alteration appears to result from a selective loss of myosin heavy chain (MHC)-beta. In parallel, the biochemical markers troponin I and creatine kinase were increased in the stunned hearts. We suggest that alterations of myosin isoenzymes in stunned myocardium can be monitored with native PAGE. The present analysis of myosin isoenzyme appears thus as a new tool for evaluating defects in MHC dimer formation in postischemic hearts.

Myosins 1 and 6, myosin light chain kinase, actin and microtubules cooperate during antibody-mediated internalisation and trafficking of membrane-expressed viral antigens in feline infectious peritonitis virus infected monocytes.

Science.gov (United States)

Dewerchin, Hannah L; Desmarets, Lowiese M; Noppe, Ytse; Nauwynck, Hans J

2014-02-12

Monocytes infected with feline infectious peritonitis virus, a coronavirus, express viral proteins in their plasma membranes. Upon binding of antibodies, these proteins are quickly internalised through a new clathrin- and caveolae-independent internalisation pathway. By doing so, the infected monocytes can escape antibody-dependent cell lysis. In the present study, we investigated which kinases and cytoskeletal proteins are of importance during internalisation and subsequent intracellular transport. The experiments showed that myosin light chain kinase (MLCK) and myosin 1 are crucial for the initiation of the internalisation. With co-localisation stainings, it was found that MLCK and myosin 1 co-localise with antigens even before internalisation started. Myosin 6 co-localised with the internalising complexes during passage through the cortical actin, were it might play a role in moving or disintegrating actin filaments, to overcome the actin barrier. One minute after internalisation started, vesicles had passed the cortical actin, co-localised with microtubules and association with myosin 6 was lost. The vesicles were further transported over the microtubules and accumulated at the microtubule organising centre after 10 to 30 min. Intracellular trafficking over microtubules was mediated by MLCK, myosin 1 and a small actin tail. Since inhibiting MLCK with ML-7 was so efficient in blocking the internalisation pathway, this target can be used for the development of a new treatment for FIPV.

Actin-myosin contractility is responsible for the reduced viability of dissociated human embryonic stem cells.

Science.gov (United States)

Chen, Guokai; Hou, Zhonggang; Gulbranson, Daniel R; Thomson, James A

2010-08-06

Human ESCs are the pluripotent precursor of the three embryonic germ layers. Human ESCs exhibit basal-apical polarity, junctional complexes, integrin-dependent matrix adhesion, and E-cadherin-dependent cell-cell adhesion, all characteristics shared by the epiblast epithelium of the intact mammalian embryo. After disruption of epithelial structures, programmed cell death is commonly observed. If individualized human ESCs are prevented from reattaching and forming colonies, their viability is significantly reduced. Here, we show that actin-myosin contraction is a critical effector of the cell death response to human ESC dissociation. Inhibition of myosin heavy chain ATPase, downregulation of myosin heavy chain, and downregulation of myosin light chain all increase survival and cloning efficiency of individualized human ESCs. ROCK inhibition decreases phosphorylation of myosin light chain, suggesting that inhibition of actin-myosin contraction is also the mechanism through which ROCK inhibitors increase cloning efficiency of human ESCs. Copyright 2010 Elsevier Inc. All rights reserved.

An isoform of myosin XI is responsible for the translocation of endoplasmic reticulum in tobacco cultured BY-2 cells.

Science.gov (United States)

Yokota, Etsuo; Ueda, Shunpei; Tamura, Kentaro; Orii, Hidefumi; Uchi, Satoko; Sonobe, Seiji; Hara-Nishimura, Ikuko; Shimmen, Teruo

2009-01-01

The involvement of myosin XI in generating the motive force for cytoplasmic streaming in plant cells is becoming evident. For a comprehensive understanding of the physiological roles of myosin XI isoforms, it is necessary to elucidate the properties and functions of each isoform individually. In tobacco cultured BY-2 cells, two types of myosins, one composed of 175 kDa heavy chain (175 kDa myosin) and the other of 170 kDa heavy chain (170 kDa myosin), have been identified biochemically and immunocytochemically. From sequence analyses of cDNA clones encoding heavy chains of 175 kDa and 170 kDa myosin, both myosins have been classified as myosin XI. Immunocytochemical studies using a polyclonal antibody against purified 175 kDa myosin heavy chain showed that the 175 kDa myosin is distributed throughout the cytoplasm as fine dots in interphase BY-2 cells. During mitosis, some parts of 175 kDa myosin were found to accumulate in the pre-prophase band (PPB), spindle, the equatorial plane of a phragmoplast and on the circumference of daughter nuclei. In transgenic BY-2 cells, in which an endoplasmic reticulum (ER)-specific retention signal, HDEL, tagged with green fluorescent protein (GFP) was stably expressed, ER showed a similar behaviour to that of 175 kDa myosin. Furthermore, this myosin was co-fractionated with GFP-ER by sucrose density gradient centrifugation. From these findings, it was suggested that the 175 kDa myosin is a molecular motor responsible for translocating ER in BY-2 cells.

Mathematical modeling of Myosin induced bistability of Lamellipodial fragments.

Science.gov (United States)

Hirsch, S; Manhart, A; Schmeiser, C

2017-01-01

For various cell types and for lamellipodial fragments on flat surfaces, externally induced and spontaneous transitions between symmetric nonmoving states and polarized migration have been observed. This behavior is indicative of bistability of the cytoskeleton dynamics. In this work, the Filament Based Lamellipodium Model (FBLM), a two-dimensional, anisotropic, two-phase continuum model for the dynamics of the actin filament network in lamellipodia, is extended by a new description of actin-myosin interaction. For appropriately chosen parameter values, the resulting model has bistable dynamics with stable states showing the qualitative features observed in experiments. This is demonstrated by numerical simulations and by an analysis of a strongly simplified version of the FBLM with rigid filaments and planar lamellipodia at the cell front and rear.

The non-resonant kink modes triggering strong sawtooth-like crashes in the EAST tokamak

Science.gov (United States)

Li, Erzhong; Igochine, V.; Dumbrajs, O.; Xu, L.; Chen, K.; Shi, T.; Hu, L.

2014-12-01

Evolution of the safety factor (q) profile during L-H transitions in the Experimental Advanced Superconducting Tokamak (EAST) was accompanied by strong core crashes prior to regular sawtooth behavior. These crashes appeared in the absence of q = 1 (q is the safety factor) rational surface inside the plasma. Analysis indicates that the m/n = 2/1 tearing mode is destabilized and phase-locked with the m/n = 1/1 non-resonant kink mode (the q = 1 rational surface is absent) due to the self-consistent evolution of plasma profiles as the L-H transition occurs (m and n are the poloidal and toroidal mode numbers, respectively). The growing m/n = 1/1 mode destabilizes the m/n = 2/2 kink mode which eventually triggers the strong crash due to an anomalous heat conductivity, as predicted by the transport model of stochastic magnetic fields using experimental parameters. It is also shown that the magnetic topology changes with the amplitude of m/n = 2/2 mode and the value of center safety factor in a reasonable range.

The non-resonant kink modes triggering strong sawtooth-like crashes in the EAST tokamak

International Nuclear Information System (INIS)

Li, Erzhong; Xu, L; Chen, K; Shi, T; Hu, L; Igochine, V; Dumbrajs, O

2014-01-01

Evolution of the safety factor (q) profile during L–H transitions in the Experimental Advanced Superconducting Tokamak (EAST) was accompanied by strong core crashes prior to regular sawtooth behavior. These crashes appeared in the absence of q = 1 (q is the safety factor) rational surface inside the plasma. Analysis indicates that the m/n = 2/1 tearing mode is destabilized and phase-locked with the m/n = 1/1 non-resonant kink mode (the q = 1 rational surface is absent) due to the self-consistent evolution of plasma profiles as the L–H transition occurs (m and n are the poloidal and toroidal mode numbers, respectively). The growing m/n = 1/1 mode destabilizes the m/n = 2/2 kink mode which eventually triggers the strong crash due to an anomalous heat conductivity, as predicted by the transport model of stochastic magnetic fields using experimental parameters. It is also shown that the magnetic topology changes with the amplitude of m/n = 2/2 mode and the value of center safety factor in a reasonable range. (paper)

Exploration of flexible phenylpropylurea scaffold as novel cardiac myosin activators for the treatment of systolic heart failure.

Science.gov (United States)

Manickam, Manoj; Jalani, Hitesh B; Pillaiyar, Thanigaimalai; Sharma, Niti; Boggu, Pulla Reddy; Venkateswararao, Eeda; Lee, You-Jung; Jeon, Eun-Seok; Jung, Sang-Hun

2017-07-07

A series of flexible urea derivatives have been synthesized and demonstrated as selective cardiac myosin ATPase activator. Among them 1-phenethyl-3-(3-phenylpropyl)urea (1, cardiac myosin ATPase activation at 10 μM = 51.1%; FS = 18.90; EF = 12.15) and 1-benzyl-3-(3-phenylpropyl)urea (9, cardiac myosin ATPase activation = 53.3%; FS = 30.04; EF = 18.27) showed significant activity in vitro and in vivo. The change of phenyl ring with tetrahydropyran-4-yl moiety viz., 1-(3-phenylpropyl)-3-((tetrahydro-2H-pyran-4-yl)methyl)urea (14, cardiac myosin ATPase activation = 81.4%; FS = 20.50; EF = 13.10), and morpholine moiety viz., 1-(2-morpholinoethyl)-3-(3-phenylpropyl)urea (21, cardiac myosin ATPase activation = 44.0%; FS = 24.79; EF = 15.65), proved to be efficient to activate the cardiac myosin. The potent compounds 1, 9, 14 and 21 were found to be selective for cardiac myosin over skeletal and smooth myosins. Thus, these urea derivatives are potent scaffold to develop as a newer cardiac myosin activator for the treatment of systolic heart failure. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Dynamics of myosin II organization into contractile networks and fibers at the medial cell cortex

Science.gov (United States)

Nie, Wei

The cellular morphology of adhered cells depends crucially on the formation of a contractile meshwork of parallel and cross-linked stress fibers along the contacting surface. The motor activity and mini-filament assembly of non-muscle myosin II is an important component of cell-level cytoskeletal remodeling during mechanosensing. To monitor the dynamics of non-muscle myosin II, we used confocal microscopy to image cultured HeLa cells that stably express myosin regulatory light chain tagged with GFP (MRLC-GFP). MRLC-GFP was monitored in time-lapse movies at steady state and during the response of cells to varying concentrations of blebbistatin (which disrupts actomyosin stress fibers). Using image correlation spectroscopy analysis, we quantified the kinetics of disassembly and reassembly of actomyosin networks and compared to studies by other groups. This analysis suggested the following processes: myosin minifilament assembly and disassembly; aligning and contraction; myosin filament stabilization upon increasing contractile tension. Numerical simulations that include those processes capture some of the main features observed in the experiments. This study provides a framework to help interpret how different cortical myosin remodeling kinetics may contribute to different cell shape and rigidity depending on substrate stiffness. We discuss methods to monitor myosin reorganization using non-linear imaging methods.

Native myosin from adult rabbit skeletal muscle: isoenzymes and states of aggregation.

Science.gov (United States)

Morel, J E; D'hahan, N; Taouil, K; Francin, M; Aguilar, A; Dalbiez, J P; Merah, Z; Grussaute, H; Hilbert, B; Ollagnon, F; Selva, G; Piot, F

1998-04-21

The globular heads of skeletal muscle myosin have been shown to exist as isoenzymes S1 (A1) and S1 (A2), and there are also isoforms of the heavy chains. Using capillary electrophoresis, we found two dominant isoenzymes of the whole native myosin molecule, in agreement with what has previously been found by various techniques for native and nondenatured myosin from adult rabbits. Findings about possible states of aggregation of myosin and its heads are contradictory. By analytical ultracentrifugation, we confirmed the existence of a tail-tail dimer. By laser light scattering, we found a head-head dimer in the presence of MgATP. Capillary electrophoresis coupled with analytical ultracentrifugation and laser light scattering led us to refine these results. We found tail-tail dimers in a conventional buffer. We found tail-tail and head-head dimers in the presence of 0.5 mM MgATP and pure head-head dimers in the presence of 6 mM MgATP. All the dimers were homodimers. Naming the dominant isoenzymes of myosin a and b, we observed tail-tail dimers with isoenzyme a (TaTa) and with isoenzyme b (TbTb) and also head-head dimers with isoenzyme a (HaHa) and with isoenzyme b (HbHb).

Excessive Myosin Activity in Mbs Mutants Causes Photoreceptor Movement Out of the Drosophila Eye Disc Epithelium

OpenAIRE

Lee, Arnold; Treisman, Jessica E.

2004-01-01

Neuronal cells must extend a motile growth cone while maintaining the cell body in its original position. In migrating cells, myosin contraction provides the driving force that pulls the rear of the cell toward the leading edge. We have characterized the function of myosin light chain phosphatase, which down-regulates myosin activity, in Drosophila photoreceptor neurons. Mutations in the gene encoding the myosin binding subunit of this enzyme cause photoreceptors to drop out of the eye disc e...

Myosin light chain kinase regulates synaptic plasticity and fear learning in the lateral amygdala.

Science.gov (United States)

Lamprecht, R; Margulies, D S; Farb, C R; Hou, M; Johnson, L R; LeDoux, J E

2006-01-01

Learning and memory depend on signaling molecules that affect synaptic efficacy. The cytoskeleton has been implicated in regulating synaptic transmission but its role in learning and memory is poorly understood. Fear learning depends on plasticity in the lateral nucleus of the amygdala. We therefore examined whether the cytoskeletal-regulatory protein, myosin light chain kinase, might contribute to fear learning in the rat lateral amygdala. Microinjection of ML-7, a specific inhibitor of myosin light chain kinase, into the lateral nucleus of the amygdala before fear conditioning, but not immediately afterward, enhanced both short-term memory and long-term memory, suggesting that myosin light chain kinase is involved specifically in memory acquisition rather than in posttraining consolidation of memory. Myosin light chain kinase inhibitor had no effect on memory retrieval. Furthermore, ML-7 had no effect on behavior when the training stimuli were presented in a non-associative manner. Anatomical studies showed that myosin light chain kinase is present in cells throughout lateral nucleus of the amygdala and is localized to dendritic shafts and spines that are postsynaptic to the projections from the auditory thalamus to lateral nucleus of the amygdala, a pathway specifically implicated in fear learning. Inhibition of myosin light chain kinase enhanced long-term potentiation, a physiological model of learning, in the auditory thalamic pathway to the lateral nucleus of the amygdala. When ML-7 was applied without associative tetanic stimulation it had no effect on synaptic responses in lateral nucleus of the amygdala. Thus, myosin light chain kinase activity in lateral nucleus of the amygdala appears to normally suppress synaptic plasticity in the circuits underlying fear learning, suggesting that myosin light chain kinase may help prevent the acquisition of irrelevant fears. Impairment of this mechanism could contribute to pathological fear learning.

Calcium and cargoes as regulators of myosin 5a activity

International Nuclear Information System (INIS)

Sellers, James R.; Thirumurugan, Kavitha; Sakamoto, Takeshi; Hammer, John A.; Knight, Peter J.

2008-01-01

Myosin 5a is a two-headed actin-dependent motor that transports various cargoes in cells. Its enzymology and mechanochemistry have been extensively studied in vitro. It is a processive motor that takes multiple 36 nm steps on actin. The enzymatic activity of myosin 5 is regulated by an intramolecular folding mechanism whereby its lever arms fold back against the coiled-coil tail such that the motor domains directly bind the globular tail domains. We show that the structure seen in individual folded molecules is consistent with electron density map of two-dimensional crystals of the molecule. In this compact state, the actin-activated MgATPase activity of the molecule is markedly inhibited and the molecule cannot move processively on surface bound actin filaments. The actin-activated MgATPase activity of myosin 5a is activated by increasing the calcium concentration or by binding of a cargo-receptor molecule, melanophilin, in vitro. However, calcium binding to the calmodulin light chains results in dissociation of some of the calmodulin which disrupts the ability of myosin 5a to move on actin filaments in vitro. Thus we propose that the physiologically relevant activation pathway in vivo involves binding of cargo-receptor proteins

Smitin, a novel smooth muscle titin-like protein, interacts with myosin filaments in vivo and in vitro.

Science.gov (United States)

Kim, Kyoungtae; Keller, Thomas C S

2002-01-07

Smooth muscle cells use an actin-myosin II-based contractile apparatus to produce force for a variety of physiological functions, including blood pressure regulation and gut peristalsis. The organization of the smooth muscle contractile apparatus resembles that of striated skeletal and cardiac muscle, but remains much more poorly understood. We have found that avian vascular and visceral smooth muscles contain a novel, megadalton protein, smitin, that is similar to striated muscle titin in molecular morphology, localization in a contractile apparatus, and ability to interact with myosin filaments. Smitin, like titin, is a long fibrous molecule with a globular domain on one end. Specific reactivities of an anti-smitin polyclonal antibody and an anti-titin monoclonal antibody suggest that smitin and titin are distinct proteins rather than differentially spliced isoforms encoded by the same gene. Smitin immunofluorescently colocalizes with myosin in chicken gizzard smooth muscle, and interacts with two configurations of smooth muscle myosin filaments in vitro. In physiological ionic strength conditions, smitin and smooth muscle myosin coassemble into irregular aggregates containing large sidepolar myosin filaments. In low ionic strength conditions, smitin and smooth muscle myosin form highly ordered structures containing linear and polygonal end-to-end and side-by-side arrays of small bipolar myosin filaments. We have used immunogold localization and sucrose density gradient cosedimentation analyses to confirm association of smitin with both the sidepolar and bipolar smooth muscle myosin filaments. These findings suggest that the titin-like protein smitin may play a central role in organizing myosin filaments in the contractile apparatus and perhaps in other structures in smooth muscle cells.

Interaction of Myosin Phosphatase Target Subunit (MYPT1) with Myosin Phosphatase-RhoA Interacting Protein (MRIP): A Role of Glutamic Acids in the Interaction.

Science.gov (United States)

Lee, Eunhee; Stafford, Walter F

2015-01-01

Scaffold proteins bind to and functionally link protein members of signaling pathways. Interaction of the scaffold proteins, myosin phosphatase target subunit (MYPT1) and myosin phosphatase-RhoA interacting protein (MRIP), causes co-localization of myosin phosphatase and RhoA to actomyosin. To examine biophysical properties of interaction of MYPT1 with MRIP, we employed analytical ultracentrifugation and surface plasmon resonance. In regard to MRIP, its residues 724-837 are sufficient for the MYPT1/MRIP interaction. Moreover, MRIP binds to MYPT1 as either a monomer or a dimer. With respect to MYPT1, its leucine repeat region, LR (residues 991-1030) is sufficient to account for the MYPT1/MRIP interaction. Furthermore, point mutations that replace glutamic acids 998-1000 within LR reduced the binding affinity toward MRIP. This suggests that the glutamic acids of MYPT1 play an important role in the interaction.

Myosin-Powered Membrane Compartment Drives Cytoplasmic Streaming, Cell Expansion and Plant Development.

Science.gov (United States)

Peremyslov, Valera V; Cole, Rex A; Fowler, John E; Dolja, Valerian V

2015-01-01

Using genetic approaches, particle image velocimetry and an inert tracer of cytoplasmic streaming, we have made a mechanistic connection between the motor proteins (myosins XI), cargo transported by these motors (distinct endomembrane compartment defined by membrane-anchored MyoB receptors) and the process of cytoplasmic streaming in plant cells. It is shown that the MyoB compartment in Nicotiana benthamiana is highly dynamic moving with the mean velocity of ~3 μm/sec. In contrast, Golgi, mitochondria, peroxisomes, carrier vesicles and a cytosol flow tracer share distinct velocity profile with mean velocities of 0.6-1.5 μm/sec. Dominant negative inhibition of the myosins XI or MyoB receptors using overexpression of the N. benthamiana myosin cargo-binding domain or MyoB myosin-binding domain, respectively, resulted in velocity reduction for not only the MyoB compartment, but also each of the tested organelles, vesicles and cytoplasmic streaming. Furthermore, the extents of this reduction were similar for each of these compartments suggesting that MyoB compartment plays primary role in cytosol dynamics. Using gene knockout analysis in Arabidopsis thaliana, it is demonstrated that inactivation of MyoB1-4 results in reduced velocity of mitochondria implying slower cytoplasmic streaming. It is also shown that myosins XI and MyoB receptors genetically interact to contribute to cell expansion, plant growth, morphogenesis and proper onset of flowering. These results support a model according to which myosin-dependent, MyoB receptor-mediated transport of a specialized membrane compartment that is conserved in all land plants drives cytoplasmic streaming that carries organelles and vesicles and facilitates cell growth and plant development.

Finding the Cell Center by a Balance of Dynein and Myosin Pulling and Microtubule Pushing: A Computational Study

Science.gov (United States)

Zhu, Jie; Burakov, Anton; Rodionov, Vladimir

2010-01-01

The centrosome position in many types of interphase cells is actively maintained in the cell center. Our previous work indicated that the centrosome is kept at the center by pulling force generated by dynein and actin flow produced by myosin contraction and that an unidentified factor that depends on microtubule dynamics destabilizes position of the centrosome. Here, we use modeling to simulate the centrosome positioning based on the idea that the balance of three forces—dyneins pulling along microtubule length, myosin-powered centripetal drag, and microtubules pushing on organelles—is responsible for the centrosome displacement. By comparing numerical predictions with centrosome behavior in wild-type and perturbed interphase cells, we rule out several plausible hypotheses about the nature of the microtubule-based force. We conclude that strong dynein- and weaker myosin-generated forces pull the microtubules inward competing with microtubule plus-ends pushing the microtubule aster outward and that the balance of these forces positions the centrosome at the cell center. The model also predicts that kinesin action could be another outward-pushing force. Simulations demonstrate that the force-balance centering mechanism is robust yet versatile. We use the experimental observations to reverse engineer the characteristic forces and centrosome mobility. PMID:20980619

Electron Microscopic Recording of the Power and Recovery Strokes of Individual Myosin Heads Coupled with ATP Hydrolysis: Facts and Implications

Directory of Open Access Journals (Sweden)

Haruo Sugi

2018-05-01

Full Text Available The most straightforward way to get information on the performance of individual myosin heads producing muscle contraction may be to record their movement, coupled with ATP hydrolysis, electron-microscopically using the gas environmental chamber (EC. The EC enables us to visualize and record ATP-induced myosin head movement in hydrated skeletal muscle myosin filaments. When actin filaments are absent, myosin heads fluctuate around a definite neutral position, so that their time-averaged mean position remains unchanged. On application of ATP, myosin heads are found to move away from, but not towards, the bare region, indicating that myosin heads perform a recovery stroke (average amplitude, 6 nm. After exhaustion of ATP, myosin heads return to their neutral position. In the actin–myosin filament mixture, myosin heads form rigor actin myosin linkages, and on application of ATP, they perform a power stroke by stretching adjacent elastic structures because of a limited amount of applied ATP ≤ 10 µM. The average amplitude of the power stroke is 3.3 nm and 2.5 nm at the distal and the proximal regions of the myosin head catalytic domain (CAD, respectively. The power stroke amplitude increases appreciably at low ionic strength, which is known to enhance Ca2+-activated force in muscle. In both the power and recovery strokes, myosin heads return to their neutral position after exhaustion of ATP.

[Myosin B ATPase activity of the intestinal smooth muscle in intestinal obstruction].

Science.gov (United States)

Takamatsu, H

1983-06-01

Intestinal smooth myosin B was prepared from muscle layers around the lesion in dogs with experimental colonic stenosis and in patients with congenital intestinal obstruction. Mg2+-ATPase activity of the myosin B was compared between the proximal dilated segment and distal segment to obstruction. Experimental colonic stenosis: In early period after surgery, proximal colons showed higher activity of myosin B ATPase than distal colons, decreasing to less than distal colon as time passed. Congenital intestinal obstruction: In three cases, whose atresia might have occurred at earlier period of gestation, proximal bowels showed less activity of myosin B ATPase than distal bowels. However, in two cases, whose atresia might have occurred at later period of gestation, and two cases with intestinal stenosis, proximal bowels indicated higher activity of myosin B ATPase than distal bowels. These data suggested that the contractibility of the proximal intestine was depending on the duration of obstruction, and it was depressed in the former patients and was accelerated in the latter patients. These results suggested that the extensive resection of dilated proximal bowel in the congenital atresia is not always necessary to obtain good postoperative intestinal dynamics at the operation of the atresial lesions which may be induced at later period of gestation. They also suggested that surgery for intestinal obstruction should be performed before the depression of intestinal contractibility to get good bowel function.

Preparation and Characterization of Myosin Proteins.

Science.gov (United States)

Caldwell, Elizabeth; Eftink, Maurice R.

1985-01-01

Students complete five experimental projects at the end of a senior-level biochemistry course which involves the isolation and characterization of myosin and its water-soluble subfragments. Procedures used and results obtained are provided for such projects as viscosity and ATPase measurements and gel electrophoresis experiments. (JN)

The Role of a Novel Myosin Isoform in Prostate Cancer Metastasis

Science.gov (United States)

2013-10-01

2013 Accepted 14 February 2013 Available online 21 February 2013 Keywords: Myosin IC Isoforms Nucleolar localization signal Nucleolus Nucleus RNA...polymerase I Fibrillarinnt matter & 2013 Elsevier 1016/j.yexcr.2013.02.008 S, nucleolar localization ; No, nucleolus ; N, nucle bovine serum albumin; S...the nucleus, and the nucleolus . In the cytoplasm, myosin IC associ- ates with membranes and is involved in vesicle transport of membrane proteins [2

Response of slow and fast muscle to hypothyroidism: maximal shortening velocity and myosin isoforms

Science.gov (United States)

Caiozzo, V. J.; Herrick, R. E.; Baldwin, K. M.

1992-01-01

This study examined both the shortening velocity and myosin isoform distribution of slow- (soleus) and fast-twitch (plantaris) skeletal muscles under hypothyroid conditions. Adult female Sprague-Dawley rats were randomly assigned to one of two groups: control (n = 7) or hypothyroid (n = 7). In both muscles, the relative contents of native slow myosin (SM) and type I myosin heavy chain (MHC) increased in response to the hypothyroid treatment. The effects were such that the hypothyroid soleus muscle expressed only the native SM and type I MHC isoforms while repressing native intermediate myosin and type IIA MHC. In the plantaris, the relative content of native SM and type I MHC isoforms increased from 5 to 13% and from 4 to 10% of the total myosin pool, respectively. Maximal shortening velocity of the soleus and plantaris as measured by the slack test decreased by 32 and 19%, respectively, in response to hypothyroidism. In contrast, maximal shortening velocity as estimated by force-velocity data decreased only in the soleus (-19%). No significant change was observed for the plantaris.

Auxotonic to isometric contraction transitioning in a beating heart causes myosin step-size to down shift.

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Thomas P Burghardt

Full Text Available Myosin motors in cardiac ventriculum convert ATP free energy to the work of moving blood volume under pressure. The actin bound motor cyclically rotates its lever-arm/light-chain complex linking motor generated torque to the myosin filament backbone and translating actin against resisting force. Previous research showed that the unloaded in vitro motor is described with high precision by single molecule mechanical characteristics including unitary step-sizes of approximately 3, 5, and 8 nm and their relative step-frequencies of approximately 13, 50, and 37%. The 3 and 8 nm unitary step-sizes are dependent on myosin essential light chain (ELC N-terminus actin binding. Step-size and step-frequency quantitation specifies in vitro motor function including duty-ratio, power, and strain sensitivity metrics. In vivo, motors integrated into the muscle sarcomere form the more complex and hierarchically functioning muscle machine. The goal of the research reported here is to measure single myosin step-size and step-frequency in vivo to assess how tissue integration impacts motor function. A photoactivatable GFP tags the ventriculum myosin lever-arm/light-chain complex in the beating heart of a live zebrafish embryo. Detected single GFP emission reports time-resolved myosin lever-arm orientation interpreted as step-size and step-frequency providing single myosin mechanical characteristics over the active cycle. Following step-frequency of cardiac ventriculum myosin transitioning from low to high force in relaxed to auxotonic to isometric contraction phases indicates that the imposition of resisting force during contraction causes the motor to down-shift to the 3 nm step-size accounting for >80% of all the steps in the near-isometric phase. At peak force, the ATP initiated actomyosin dissociation is the predominant strain inhibited transition in the native myosin contraction cycle. The proposed model for motor down-shifting and strain sensing involves ELC N

Preparation of monoclonal antibodies against cardiac myosin and some radiolabelling studies

International Nuclear Information System (INIS)

Bapat, K.; Venkatesh, M.; Pillai, M.R.A.; Sarma, H.D.; Sainis, K.B.

1998-01-01

Monoclonal antibodies were raised against myosin, a specific indicator of myocardial infarction and labelled with 125 I and 99m Tc. Human cardiac myosin was isolated from normal human heart and was used for raising the monoclonal antibodies by the hybridoma technique. Antibody producing clones were identified by ELISA and cloning was done by the limiting dilution technique. Of the 13 clones obtained, 4 were deemed suitable for further studies. The antibodies were grown in ascites, purified, isotyped and their cross reactions with other forms of myosin were estimated. All the clones showed negligible cross reaction with rabbit myosin, but reacted to different extents with bovine skeletal myosin. The most avid antibody Mab-4G4 was chosen for further labelling studies. Mab-4G4 was labelled with 125 I using different oxidising agents such as iodogen, chloramine-T and lactoperoxidase. Purified radioiodinated antibody with radiochemical purity >95% could be obtained by gel filtration. Immunoreactivity was retained as tested by binding to myosin immobilised on a solid support. Mab-4G4 was also labelled with 99m Tc using stannous tartrate as the reducing agent. Radiolabelling yield was ∼60%, the purity was >95% and the immunoreactivity was retained. Both the labelled preparations were tested for bio-distribution in normal and infarcted rats. The activity accumulation in the infarcted region was ∼ 1.5 and 3.5 times as that in normal heart muscle for 125 I and 99m Tc labelled Mab-4G4 respectively. The major problem with the iodinated antibody was the in vivo deiodination resulting in very high percentage of activity in the thyroid. Although the fraction of the total activity associated with the infarcted heart is not very impressive, the fact that the activities with the infarcted and normal hearths are significantly different is heartening. With further optimisation of labelling and use of F(ab)'2 fragments, better delineation of the infarct sites is aspired. (author)

Metal cation controls phosphate release in the myosin ATPase.

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Ge, Jinghua; Huang, Furong; Nesmelov, Yuri E

2017-11-01

Myosin is an enzyme that utilizes ATP to produce a conformational change generating a force. The kinetics of the myosin reverse recovery stroke depends on the metal cation complexed with ATP. The reverse recovery stroke is slow for MgATP and fast for MnATP. The metal ion coordinates the γ phosphate of ATP in the myosin active site. It is accepted that the reverse recovery stroke is correlated with the phosphate release; therefore, magnesium "holds" phosphate tighter than manganese. Magnesium and manganese are similar ions in terms of their chemical properties and the shell complexation; hence, we propose to use these ions to study the mechanism of the phosphate release. Analysis of octahedral complexes of magnesium and manganese show that the partial charge of magnesium is higher than that of manganese and the slightly larger size of manganese ion makes its ionic potential smaller. We hypothesize that electrostatics play a role in keeping and releasing the abstracted γ phosphate in the active site, and the stronger electric charge of magnesium ion holds γ phosphate tighter. We used stable myosin-nucleotide analog complex and Raman spectroscopy to examine the effect of the metal cation on the relative position of γ phosphate analog in the active site. We found that in the manganese complex, the γ phosphate analog is 0.01 nm further away from ADP than in the magnesium complex. We conclude that the ionic potential of the metal cation plays a role in the retention of the abstracted phosphate. © 2017 The Protein Society.

K-252a, a novel microbial product, inhibits smooth muscle myosin light chain kinase

International Nuclear Information System (INIS)

Nakanishi, S.; Yamada, K.; Kase, H.; Nakamura, S.; Nonomura, Y.

1988-01-01

Effects of K-252a, purified from the culture broth of Nocardiopsis sp., on the activity of myosin (light chain kinase were investigated. 1) K-252a affected three characteristic properties of chicken gizzard myosin-B, natural actomyosin, to a similar degree: the Ca 2+ -dependent activity of ATPase, superprecipitation, and the phosphorylation of the myosin light chain. 2) K-252a inhibited the activities of the purified myosin light chain kinase and a Ca 2+ -independent form of the enzyme which was constructed by cross-linking of myosin light chain kinase and calmodulin using glutaraldehyde. The degrees of inhibition by 3 x 10 -6 M K-252a were 69 and 48% of the control activities with the purified enzyme and the cross-linked complex, respectively. Chlorpromazine (3 x 10 -4 M), a calmodulin antagonist, inhibited the native enzyme, but not the cross-linked one. These results suggested that K-252a inhibited myosin light chain kinase by direct interaction with the enzyme, whereas chlorpromazine suppressed the enzyme activation by interacting with calmodulin. 3) The inhibition by K-252a of the cross-linked kinase was affected by the concentration of ATP, a phosphate donor. The concentration causing 50% inhibition was two orders magnitude lowere in the presence of 100 μM ATP than in the presence of 2 mM ATP. 4) Kinetic analyses using [γ- 32 P]ATP indicated that the inhibitory mode of K-252a was competitive with respect to ATP. These results suggest that K-252a interacts at the ATP-binding domain of myosin light chain kinase

The Effects of Hsp90α1 Mutations on Myosin Thick Filament Organization.

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He, Qiuxia; Liu, Kechun; Tian, Zhenjun; Du, Shao Jun

2015-01-01

Heat shock protein 90α plays a key role in myosin folding and thick filament assembly in muscle cells. To assess the structure and function of Hsp90α and its potential regulation by post-translational modification, we developed a combined knockdown and rescue assay in zebrafish embryos to systematically analyze the effects of various mutations on Hsp90α function in myosin thick filament organization. DNA constructs expressing the Hsp90α1 mutants with altered putative ATP binding, phosphorylation, acetylation or methylation sites were co-injected with Hsp90α1 specific morpholino into zebrafish embryos. Myosin thick filament organization was analyzed in skeletal muscles of the injected embryos by immunostaining. The results showed that mutating the conserved D90 residue in the Hsp90α1 ATP binding domain abolished its function in thick filament organization. In addition, phosphorylation mimicking mutations of T33D, T33E and T87E compromised Hsp90α1 function in myosin thick filament organization. Similarly, K287Q acetylation mimicking mutation repressed Hsp90α1 function in myosin thick filament organization. In contrast, K206R and K608R hypomethylation mimicking mutations had not effect on Hsp90α1 function in thick filament organization. Given that T33 and T87 are highly conserved residues involved post-translational modification (PTM) in yeast, mouse and human Hsp90 proteins, data from this study could indicate that Hsp90α1 function in myosin thick filament organization is potentially regulated by PTMs involving phosphorylation and acetylation.

Human myosin VIIa is a very slow processive motor protein on various cellular actin structures.

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Sato, Osamu; Komatsu, Satoshi; Sakai, Tsuyoshi; Tsukasaki, Yoshikazu; Tanaka, Ryosuke; Mizutani, Takeomi; Watanabe, Tomonobu M; Ikebe, Reiko; Ikebe, Mitsuo

2017-06-30

Human myosin VIIa (MYO7A) is an actin-linked motor protein associated with human Usher syndrome (USH) type 1B, which causes human congenital hearing and visual loss. Although it has been thought that the role of human myosin VIIa is critical for USH1 protein tethering with actin and transportation along actin bundles in inner-ear hair cells, myosin VIIa's motor function remains unclear. Here, we studied the motor function of the tail-truncated human myosin VIIa dimer (HM7AΔTail/LZ) at the single-molecule level. We found that the HM7AΔTail/LZ moves processively on single actin filaments with a step size of 35 nm. Dwell-time distribution analysis indicated an average waiting time of 3.4 s, yielding ∼0.3 s -1 for the mechanical turnover rate; hence, the velocity of HM7AΔTail/LZ was extremely slow, at 11 nm·s -1 We also examined HM7AΔTail/LZ movement on various actin structures in demembranated cells. HM7AΔTail/LZ showed unidirectional movement on actin structures at cell edges, such as lamellipodia and filopodia. However, HM7AΔTail/LZ frequently missed steps on actin tracks and exhibited bidirectional movement at stress fibers, which was not observed with tail-truncated myosin Va. These results suggest that the movement of the human myosin VIIa motor protein is more efficient on lamellipodial and filopodial actin tracks than on stress fibers, which are composed of actin filaments with different polarity, and that the actin structures influence the characteristics of cargo transportation by human myosin VIIa. In conclusion, myosin VIIa movement appears to be suitable for translocating USH1 proteins on stereocilia actin bundles in inner-ear hair cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Stretch activates myosin light chain kinase in arterial smooth muscle

International Nuclear Information System (INIS)

Barany, K.; Rokolya, A.; Barany, M.

1990-01-01

Stretching of porcine carotid arterial muscle increased the phosphorylation of the 20 kDa myosin light chain from 0.23 to 0.68 mol [32P]phosphate/mol light chain, whereas stretching of phorbol dibutyrate treated muscle increased the phosphorylation from 0.30 to 0.91 mol/mol. Two-dimensional gel electrophoresis followed by two-dimensional tryptic phosphopeptide mapping was used to identify the enzyme involved in the stretch-induced phosphorylation. Quantitation of the [32P]phosphate content of the peptides revealed considerable light chain phosphorylation by protein kinase C only in the phorbol dibutyrate treated arterial muscle, whereas most of the light chain phosphorylation was attributable to myosin light chain kinase. Upon stretch of either the untreated or treated muscle, the total increment in [32P]phosphate incorporation into the light chain could be accounted for by peptides characteristic for myosin light chain kinase catalyzed phosphorylation, demonstrating that the stretch-induced phosphorylation is caused by this enzyme exclusively

Head-head interactions of resting myosin crossbridges in intact frog skeletal muscles, revealed by synchrotron x-ray fiber diffraction.

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Kanji Oshima

Full Text Available The intensities of the myosin-based layer lines in the x-ray diffraction patterns from live resting frog skeletal muscles with full thick-thin filament overlap from which partial lattice sampling effects had been removed were analyzed to elucidate the configurations of myosin crossbridges around the thick filament backbone to nanometer resolution. The repeat of myosin binding protein C (C-protein molecules on the thick filaments was determined to be 45.33 nm, slightly longer than that of myosin crossbridges. With the inclusion of structural information for C-proteins and a pre-powerstroke head shape, modeling in terms of a mixed population of regular and perturbed regions of myosin crown repeats along the filament revealed that the myosin filament had azimuthal perturbations of crossbridges in addition to axial perturbations in the perturbed region, producing pseudo-six-fold rotational symmetry in the structure projected down the filament axis. Myosin crossbridges had a different organization about the filament axis in each of the regular and perturbed regions. In the regular region that lacks C-proteins, there were inter-molecular interactions between the myosin heads in axially adjacent crown levels. In the perturbed region that contains C-proteins, in addition to inter-molecular interactions between the myosin heads in the closest adjacent crown levels, there were also intra-molecular interactions between the paired heads on the same crown level. Common features of the interactions in both regions were interactions between a portion of the 50-kDa-domain and part of the converter domain of the myosin heads, similar to those found in the phosphorylation-regulated invertebrate myosin. These interactions are primarily electrostatic and the converter domain is responsible for the head-head interactions. Thus multiple head-head interactions of myosin crossbridges also characterize the switched-off state and have an important role in the regulation

Dual role for myosin II in GLUT4-mediated glucose uptake in 3T3-L1 adipocytes

International Nuclear Information System (INIS)

Fulcher, F. Kent; Smith, Bethany T.; Russ, Misty; Patel, Yashomati M.

2008-01-01

Insulin-stimulated glucose uptake requires the activation of several signaling pathways to mediate the translocation and fusion of GLUT4 vesicles to the plasma membrane. Our previous studies demonstrated that GLUT4-mediated glucose uptake is a myosin II-dependent process in adipocytes. The experiments described in this report are the first to show a dual role for the myosin IIA isoform specifically in regulating insulin-stimulated glucose uptake in adipocytes. We demonstrate that inhibition of MLCK but not RhoK results in impaired insulin-stimulated glucose uptake. Furthermore, our studies show that insulin specifically stimulates the phosphorylation of the RLC associated with the myosin IIA isoform via MLCK. In time course experiments, we determined that GLUT4 translocates to the plasma membrane prior to myosin IIA recruitment. We further show that recruitment of myosin IIA to the plasma membrane requires that myosin IIA be activated via phosphorylation of the RLC by MLCK. Our findings also reveal that myosin II is required for proper GLUT4-vesicle fusion at the plasma membrane. We show that once at the plasma membrane, myosin II is involved in regulating the intrinsic activity of GLUT4 after insulin stimulation. Collectively, our results are the first to reveal that myosin IIA plays a critical role in mediating insulin-stimulated glucose uptake in 3T3-LI adipocytes, via both GLUT4 vesicle fusion at the plasma membrane and GLUT4 activity

Myosin X is recruited to nascent focal adhesions at the leading edge and induces multi-cycle filopodial elongation.

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He, Kangmin; Sakai, Tsuyoshi; Tsukasaki, Yoshikazu; Watanabe, Tomonobu M; Ikebe, Mitsuo

2017-10-20

Filopodia protrude from the leading edge of cells and play important roles in cell motility. Here we report the mechanism of myosin X (encoded by Myo10)-induced multi-cycle filopodia extension. We found that actin, Arp2/3, vinculin and integrin-β first accumulated at the cell's leading edge. Myosin X was then gathered at these sites, gradually clustered by lateral movement, and subsequently initiated filopodia formation. During filopodia extension, we found the translocation of Arp2/3 and integrin-β along filopodia. Arp2/3 and integrin-β then became localized at the tip of filopodia, from where myosin X initiated the second extension of filopodia with a change in extension direction, thus producing long filopodia. Elimination of integrin-β, Arp2/3 and vinculin by siRNA significantly attenuated the myosin-X-induced long filopodia formation. We propose the following mechanism. Myosin X accumulates at nascent focal adhesions at the cell's leading edge, where myosin X promotes actin convergence to create the base of filopodia. Then myosin X moves to the filopodia tip and attracts integrin-β and Arp2/3 for further actin nucleation. The tip-located myosin X then initiates the second cycle of filopodia elongation to produce the long filopodia.

Direct photoaffinity labeling by nucleotides of the apparent catalytic site on the heavy chains of smooth muscle and Acanthamoeba myosins

International Nuclear Information System (INIS)

Maruta, H.; Korn, E.D.

1981-01-01

The heavy chains of Acanthamoeba myosins, IA, IB and II, turkey gizzard myosin, and rabbit skeletal muscle myosin subfragment-1 were specifically labeled by radioactive ATP, ADP, and UTP, each of which is a substrate or product of myosin ATPase activity, when irradiated with uv light at 0 0 C. With UTP, as much as 0.45 mol/mol of Acanthamoeba myosin IA heavy chain and 1 mol/mol of turkey gizzard myosin heavy chain was incorporated. Evidence that the ligands were associated with the catalytic site included the observations that reaction occurred only with nucleotides that are substrates or products of the ATPase activity; that the reaction was blocked by pyrophosphate which is an inhibitor of the ATPase activity; that ATP was bound as ADP; and that label was probably restricted to a single peptide following limited subtilisin proteolysis of labeled Acanthamoeba myosin IA heavy chain and extensive cleavage with CNBr and trypsin of labeled turkey gizzard myosin heavy chain

Myosins and DYNLL1/LC8 in the honey bee (Apis mellifera L.) brain.

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Calábria, Luciana Karen; Peixoto, Pablo Marco Veras; Passos Lima, Andreia Barcelos; Peixoto, Leonardo Gomes; de Moraes, Viviane Rodrigues Alves; Teixeira, Renata Roland; Dos Santos, Claudia Tavares; E Silva, Letícia Oliveira; da Silva, Maria de Fátima Rodrigues; dos Santos, Ana Alice Diniz; Garcia-Cairasco, Norberto; Martins, Antônio Roberto; Espreafico, Enilza Maria; Espindola, Foued Salmen

2011-09-01

Honey bees have brain structures with specialized and developed systems of communication that account for memory, learning capacity and behavioral organization with a set of genes homologous to vertebrate genes. Many microtubule- and actin-based molecular motors are involved in axonal/dendritic transport. Myosin-Va is present in the honey bee Apis mellifera nervous system of the larvae and adult castes and subcastes. DYNLL1/LC8 and myosin-IIb, -VI and -IXb have also been detected in the adult brain. SNARE proteins, such as CaMKII, clathrin, syntaxin, SNAP25, munc18, synaptophysin and synaptotagmin, are also expressed in the honey bee brain. Honey bee myosin-Va displayed ATP-dependent solubility and was associated with DYNLL1/LC8 and SNARE proteins in the membrane vesicle-enriched fraction. Myosin-Va expression was also decreased after the intracerebral injection of melittin and NMDA. The immunolocalization of myosin-Va and -IV, DYNLL1/LC8, and synaptophysin in mushroom bodies, and optical and antennal lobes was compared with the brain morphology based on Neo-Timm histochemistry and revealed a distinct and punctate distribution. This result suggested that the pattern of localization is associated with neuron function. Therefore, our data indicated that the roles of myosins, DYNLL1/LC8, and SNARE proteins in the nervous and visual systems of honey bees should be further studied under different developmental, caste and behavioral conditions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Molecular cloning and complete nucleotide sequence of a human ventricular myosin light chain 1

Energy Technology Data Exchange (ETDEWEB)

Hoffmann, E; Shi, Q W; Floroff, M; Mickle, D A.G.; Wu, T W; Olley, P M; Jackowski, G

1988-03-25

Human ventricular plasmid library was constructed. The library was screened with the oligonucleotide probe (17-mer) corresponding to a conserve region of myosin light chain 1 near the carboxy terminal. Full length cDNA recombinant plasmid containing 1100 bp insert was isolated. RNA blot hybridization with this insert detected a message of approximately 1500 bp corresponding to the size of VLCl and mRNA. Complete nucleotide sequence of the coding region was determined in M13 subclones using dideoxy chain termination method. With the isolation of this clone (pCD HLVCl), the publication of the complete nucleotide sequence of HVLCl and the predicted secondary structure of this protein will aid in understanding of the biochemistry of myosin and its function in contraction, the evolution of myosin light genes and the genetic, developmental and physiological regulation of myosin genes.

The fungal myosin I is essential for Fusarium toxisome formation.

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Guangfei Tang

2018-01-01

Full Text Available Myosin-I molecular motors are proposed to function as linkers between membranes and the actin cytoskeleton in several cellular processes, but their role in the biosynthesis of fungal secondary metabolites remain elusive. Here, we found that the myosin I of Fusarium graminearum (FgMyo1, the causal agent of Fusarium head blight, plays critical roles in mycotoxin biosynthesis. Inhibition of myosin I by the small molecule phenamacril leads to marked reduction in deoxynivalenol (DON biosynthesis. FgMyo1 also governs translation of the DON biosynthetic enzyme Tri1 by interacting with the ribosome-associated protein FgAsc1. Disruption of the ATPase activity of FgMyo1 either by the mutation E420K, down-regulation of FgMyo1 expression or deletion of FgAsc1 results in reduced Tri1 translation. The DON biosynthetic enzymes Tri1 and Tri4 are mainly localized to subcellular structures known as toxisomes in response to mycotoxin induction and the FgMyo1-interacting protein, actin, participates in toxisome formation. The actin polymerization disruptor latrunculin A inhibits toxisome assembly. Consistent with this observation, deletion of the actin-associated proteins FgPrk1 and FgEnd3 also results in reduced toxisome formation. Unexpectedly, the FgMyo1-actin cytoskeleton is not involved in biosynthesis of another secondary metabolite tested. Taken together, this study uncovers a novel function of myosin I in regulating mycotoxin biosynthesis in filamentous fungi.

The fungal myosin I is essential for Fusarium toxisome formation.

Science.gov (United States)

Tang, Guangfei; Chen, Yun; Xu, Jin-Rong; Kistler, H Corby; Ma, Zhonghua

2018-01-01

Myosin-I molecular motors are proposed to function as linkers between membranes and the actin cytoskeleton in several cellular processes, but their role in the biosynthesis of fungal secondary metabolites remain elusive. Here, we found that the myosin I of Fusarium graminearum (FgMyo1), the causal agent of Fusarium head blight, plays critical roles in mycotoxin biosynthesis. Inhibition of myosin I by the small molecule phenamacril leads to marked reduction in deoxynivalenol (DON) biosynthesis. FgMyo1 also governs translation of the DON biosynthetic enzyme Tri1 by interacting with the ribosome-associated protein FgAsc1. Disruption of the ATPase activity of FgMyo1 either by the mutation E420K, down-regulation of FgMyo1 expression or deletion of FgAsc1 results in reduced Tri1 translation. The DON biosynthetic enzymes Tri1 and Tri4 are mainly localized to subcellular structures known as toxisomes in response to mycotoxin induction and the FgMyo1-interacting protein, actin, participates in toxisome formation. The actin polymerization disruptor latrunculin A inhibits toxisome assembly. Consistent with this observation, deletion of the actin-associated proteins FgPrk1 and FgEnd3 also results in reduced toxisome formation. Unexpectedly, the FgMyo1-actin cytoskeleton is not involved in biosynthesis of another secondary metabolite tested. Taken together, this study uncovers a novel function of myosin I in regulating mycotoxin biosynthesis in filamentous fungi.

Phosphorylated peptides occur in a non-helical portion of the tail of a catch muscle myosin

International Nuclear Information System (INIS)

Castellani, L.; Elliott, B.W. Jr.; Cohen, C.

1987-01-01

Myosin from a molluscan catch muscle (the Anterior Byssus Retractor (ABRM) of Mytilus edulis) is unusual in being phosphorylated in the rod by an endogenous heavy-chain kinase. This phosphorylation enhances myosin solubility at low ionic strength and induces molecular folding of the myosin tail. Papain and chymotryptic cleavage of this myosin, phosphorylated with [γ- 32 P]ATP, indicates that the phosphorylated residues are associated with the carboxy-terminal end of the light meromyosin. Ion-exchange and reverse-phase HPLC of radiolabeled chymotryptic peptides allow the isolation of two different peptides with high specific activity. One of these peptides is rich in lysine and arginine residues, a finding consistent with the observation that basic residues often determine the substrate specificity of protein kinases. The second peptide contains proline residues. Taken together, these results suggest that, as in the case of Acanthamoeba myosin, phosphorylation occurs in a nonhelical portion of the rod that may also control solubility. Identification of the residues that are phosphorylated and their location in the rod may reveal how the phosphorylation-dependent changes observed in the myosin in vitro are related to changes in intermolecular interactions in the thick filaments in vivo

The Effect of Experimental Hyperthyroidism on Characteristics of Actin-Myosin Interaction in Fast and Slow Skeletal Muscles.

Science.gov (United States)

Kopylova, G V; Shchepkin, D V; Bershitsky, S Y

2018-05-01

The molecular mechanism of the failure of contractile function of skeletal muscles caused by oxidative damage to myosin in hyperthyroidism is not fully understood. Using an in vitro motility assay, we studied the effect of myosin damage caused by oxidative stress in experimental hyperthyroidism on the actin-myosin interaction and its regulation by calcium. We found that hyperthyroidism-induced oxidation of myosin is accompanied by a decrease in the sliding velocity of the regulated thin filaments in the in vitro motility assay, and this effect is increased with the duration of the pathological process.

Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation

NARCIS (Netherlands)

Homburger, J.R. (Julian R.); Green, E.M. (Eric M.); Caleshu, C. (Colleen); Sunitha, M.S. (Margaret S.); Taylor, R.E. (Rebecca E.); Ruppel, K.M. (Kathleen M.); Metpally, R.P.R. (Raghu Prasad Rao); S.D. Colan (Steven); M. Michels (Michelle); Day, S.M. (Sharlene M.); I. Olivotto (Iacopo); Bustamante, C.D. (Carlos D.); Dewey, F.E. (Frederick E.); Ho, C.Y. (Carolyn Y.); Spudich, J.A. (James A.); Ashley, E.A. (Euan A.)

2016-01-01

textabstractMyosin motors are the fundamental force-generating elements of muscle contraction. Variation in the human β-cardiac myosin heavy chain gene (MYH7) can lead to hypertrophic cardiomyopathy (HCM), a heritable disease characterized by cardiac hypertrophy, heart failure, and sudden cardiac

Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus.

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Venit, Tomáš; Dzijak, Rastislav; Kalendová, Alžběta; Kahle, Michal; Rohožková, Jana; Schmidt, Volker; Rülicke, Thomas; Rathkolb, Birgit; Hans, Wolfgang; Bohla, Alexander; Eickelberg, Oliver; Stoeger, Tobias; Wolf, Eckhard; Yildirim, Ali Önder; Gailus-Durner, Valérie; Fuchs, Helmut; de Angelis, Martin Hrabě; Hozák, Pavel

2013-01-01

Nuclear myosin I (NM1) is a nuclear isoform of the well-known "cytoplasmic" Myosin 1c protein (Myo1c). Located on the 11(th) chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous studies revealed its roles in RNA Polymerase I and RNA Polymerase II transcription, chromatin remodeling, and chromosomal movements. Its nuclear localization signal is localized in the middle of the molecule and therefore directs both Myosin 1c isoforms to the nucleus. In order to trace specific functions of the NM1 isoform, we generated mice lacking the NM1 start codon without affecting the cytoplasmic Myo1c protein. Mutant mice were analyzed in a comprehensive phenotypic screen in cooperation with the German Mouse Clinic. Strikingly, no obvious phenotype related to previously described functions has been observed. However, we found minor changes in bone mineral density and the number and size of red blood cells in knock-out mice, which are most probably not related to previously described functions of NM1 in the nucleus. In Myo1c/NM1 depleted U2OS cells, the level of Pol I transcription was restored by overexpression of shRNA-resistant mouse Myo1c. Moreover, we found Myo1c interacting with Pol II. The ratio between Myo1c and NM1 proteins were similar in the nucleus and deletion of NM1 did not cause any compensatory overexpression of Myo1c protein. We observed that Myo1c can replace NM1 in its nuclear functions. Amount of both proteins is nearly equal and NM1 knock-out does not cause any compensatory overexpression of Myo1c. We therefore suggest that both isoforms can substitute each other in nuclear processes.

A novel role for myosin II in insulin-stimulated glucose uptake in 3T3-L1 adipocytes

International Nuclear Information System (INIS)

Steimle, Paul A.; Kent Fulcher, F.; Patel, Yashomati M.

2005-01-01

Insulin-stimulated glucose uptake requires the activation of several signaling pathways to mediate the translocation and fusion of GLUT4 vesicles from an intracellular pool to the plasma membrane. The studies presented here show that inhibition of myosin II activity impairs GLUT4-mediated glucose uptake but not GLUT4 translocation to the plasma membrane. We also show that adipocytes express both myosin IIA and IIB isoforms, and that myosin IIA is recruited to the plasma membrane upon insulin stimulation. Taken together, the data presented here represent the first demonstration that GLUT4-mediated glucose uptake is a myosin II-dependent process in adipocytes. Based on our findings, we hypothesize that myosin II is activated upon insulin stimulation and recruited to the cell cortex to facilitate GLUT4 fusion with the plasma membrane. The identification of myosin II as a key component of GLUT4-mediated glucose uptake represents an important advance in our understanding of the mechanisms regulating glucose homeostasis

Myosin-II sets the optimal response time scale of chemotactic amoeba

Science.gov (United States)

Hsu, Hsin-Fang; Westendorf, Christian; Tarantola, Marco; Bodenschatz, Eberhard; Beta, Carsten

2014-03-01

The response dynamics of the actin cytoskeleton to external chemical stimuli plays a fundamental role in numerous cellular functions. One of the key players that governs the dynamics of the actin network is the motor protein myosin-II. Here we investigate the role of myosin-II in the response of the actin system to external stimuli. We used a microfluidic device in combination with a photoactivatable chemoattractant to apply stimuli to individual cells with high temporal resolution. We directly compare the actin dynamics in Dictyostelium discodelium wild type (WT) cells to a knockout mutant that is deficient in myosin-II (MNL). Similar to the WT a small population of MNL cells showed self-sustained oscillations even in absence of external stimuli. The actin response of MNL cells to a short pulse of chemoattractant resembles WT during the first 15 sec but is significantly delayed afterward. The amplitude of the dominant peak in the power spectrum from the response time series of MNL cells to periodic stimuli with varying period showed a clear resonance peak at a forcing period of 36 sec, which is significantly delayed as compared to the resonance at 20 sec found for the WT. This shift indicates an important role of myosin-II in setting the response time scale of motile amoeba. Institute of Physics und Astronomy, University of Potsdam, Karl-Liebknecht-Str. 24/25, 14476 Potsdam, Germany.

Engineering Circular Gliding of Actin Filaments Along Myosin-Patterned DNA Nanotube Rings To Study Long-Term Actin-Myosin Behaviors.

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Hariadi, Rizal F; Appukutty, Abhinav J; Sivaramakrishnan, Sivaraj

2016-09-27

Nature has evolved molecular motors that are critical in cellular processes occurring over broad time scales, ranging from seconds to years. Despite the importance of the long-term behavior of molecular machines, topics such as enzymatic lifetime are underexplored due to the lack of a suitable approach for monitoring motor activity over long time periods. Here, we developed an "O"-shaped Myosin Empowered Gliding Assay (OMEGA) that utilizes engineered micron-scale DNA nanotube rings with precise arrangements of myosin VI to trap gliding actin filaments. This circular gliding assay platform allows the same individual actin filament to glide over the same myosin ensemble (50-1000 motors per ring) multiple times. First, we systematically characterized the formation of DNA nanotubes rings with 4, 6, 8, and 10 helix circumferences. Individual actin filaments glide along the nanotube rings with high processivity for up to 12.8 revolutions or 11 min in run time. We then show actin gliding speed is robust to variation in motor number and independent of ring curvature within our sample space (ring diameter of 0.5-4 μm). As a model application of OMEGA, we then analyze motor-based mechanical influence on "stop-and-go" gliding behavior of actin filaments, revealing that the stop-to-go transition probability is dependent on motor flexibility. Our circular gliding assay may provide a closed-loop platform for monitoring long-term behavior of broad classes of molecular motors and enable characterization of motor robustness and long time scale nanomechanical processes.

Interaction of c-Cbl with myosin IIA regulates Bleb associated macropinocytosis of Kaposi's sarcoma-associated herpesvirus.

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Mohanan Valiya Veettil

2010-12-01

Full Text Available KSHV is etiologically associated with Kaposi's sarcoma (KS, an angioproliferative endothelial cell malignancy. Macropinocytosis is the predominant mode of in vitro entry of KSHV into its natural target cells, human dermal microvascular endothelial (HMVEC-d cells. Although macropinocytosis is known to be a major route of entry for many viruses, the molecule(s involved in the recruitment and integration of signaling early during macropinosome formation is less well studied. Here we demonstrate that tyrosine phosphorylation of the adaptor protein c-Cbl is required for KSHV induced membrane blebbing and macropinocytosis. KSHV induced the tyrosine phosphorylation of c-Cbl as early as 1 min post-infection and was recruited to the sites of bleb formation. Infection also led to an increase in the interaction of c-Cbl with PI3-K p85 in a time dependent manner. c-Cbl shRNA decreased the formation of KSHV induced membrane blebs and macropinocytosis as well as virus entry. Immunoprecipitation of c-Cbl followed by mass spectrometry identified the interaction of c-Cbl with a novel molecular partner, non-muscle myosin heavy chain IIA (myosin IIA, in bleb associated macropinocytosis. Phosphorylated c-Cbl colocalized with phospho-myosin light chain II in the interior of blebs of infected cells and this interaction was abolished by c-Cbl shRNA. Studies with the myosin II inhibitor blebbistatin demonstrated that myosin IIA is a biologically significant component of the c-Cbl signaling pathway and c-Cbl plays a new role in the recruitment of myosin IIA to the blebs during KSHV infection. Myosin II associates with actin in KSHV induced blebs and the absence of actin and myosin ubiquitination in c-Cbl ShRNA cells suggested that c-Cbl is also responsible for the ubiquitination of these proteins in the infected cells. This is the first study demonstrating the role of c-Cbl in viral entry as well as macropinocytosis, and provides the evidence that a signaling complex

Selective expression of myosin IC Isoform A in mouse and human cell lines and mouse prostate cancer tissues.

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Ivanna Ihnatovych

Full Text Available Myosin IC is a single headed member of the myosin superfamily. We recently identified a novel isoform and showed that the MYOIC gene in mammalian cells encodes three isoforms (isoforms A, B, and C. Furthermore, we demonstrated that myosin IC isoform A but not isoform B exhibits a tissue specific expression pattern. In this study, we extended our analysis of myosin IC isoform expression patterns by analyzing the protein and mRNA expression in various mammalian cell lines and in various prostate specimens and tumor tissues from the transgenic mouse prostate (TRAMP model by immunoblotting, qRT-PCR, and by indirect immunohistochemical staining of paraffin embedded prostate specimen. Analysis of a panel of mammalian cell lines showed an increased mRNA and protein expression of specifically myosin IC isoform A in a panel of human and mouse prostate cancer cell lines but not in non-cancer prostate or other (non-prostate- cancer cell lines. Furthermore, we demonstrate that myosin IC isoform A expression is significantly increased in TRAMP mouse prostate samples with prostatic intraepithelial neoplasia (PIN lesions and in distant site metastases in lung and liver when compared to matched normal tissues. Our observations demonstrate specific changes in the expression of myosin IC isoform A that are concurrent with the occurrence of prostate cancer in the TRAMP mouse prostate cancer model that closely mimics clinical prostate cancer. These data suggest that elevated levels of myosin IC isoform A may be a potential marker for the detection of prostate cancer.

Myosin isoform switching during assembly of the Drosophila flight muscle thick filament lattice.

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Orfanos, Zacharias; Sparrow, John C

2013-01-01

During muscle development myosin molecules form symmetrical thick filaments, which integrate with the thin filaments to produce the regular sarcomeric lattice. In Drosophila indirect flight muscles (IFMs) the details of this process can be studied using genetic approaches. The weeP26 transgenic line has a GFP-encoding exon inserted into the single Drosophila muscle myosin heavy chain gene, Mhc. The weeP26 IFM sarcomeres have a unique MHC-GFP-labelling pattern restricted to the sarcomere core, explained by non-translation of the GFP exon following alternative splicing. Characterisation of wild-type IFM MHC mRNA confirmed the presence of an alternately spliced isoform, expressed earlier than the major IFM-specific isoform. The two wild-type IFM-specific MHC isoforms differ by the presence of a C-terminal 'tailpiece' in the minor isoform. The sequential expression and assembly of these two MHCs into developing thick filaments suggest a role for the tailpiece in initiating A-band formation. The restriction of the MHC-GFP sarcomeric pattern in weeP26 is lifted when the IFM lack the IFM-specific myosin binding protein flightin, suggesting that it limits myosin dissociation from thick filaments. Studies of flightin binding to developing thick filaments reveal a progressive binding at the growing thick filament tips and in a retrograde direction to earlier assembled, proximal filament regions. We propose that this flightin binding restricts myosin molecule incorporation/dissociation during thick filament assembly and explains the location of the early MHC isoform pattern in the IFM A-band.

Formation of contractile networks and fibers in the medial cell cortex through myosin-II turnover, contraction, and stress-stabilization.

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Nie, Wei; Wei, Ming-Tzo; Ou-Yang, H Daniel; Jedlicka, Sabrina S; Vavylonis, Dimitrios

2015-01-01

The morphology of adhered cells depends crucially on the formation of a contractile meshwork of parallel and cross-linked fibers along the contacting surface. The motor activity and minifilament assembly of non-muscle myosin-II is an important component of cortical cytoskeletal remodeling during mechanosensing. We used experiments and computational modeling to study cortical myosin-II dynamics in adhered cells. Confocal microscopy was used to image the medial cell cortex of HeLa cells stably expressing myosin regulatory light chain tagged with GFP (MRLC-GFP). The distribution of MRLC-GFP fibers and focal adhesions was classified into three types of network morphologies. Time-lapse movies show: myosin foci appearance and disappearance; aligning and contraction; stabilization upon alignment. Addition of blebbistatin, which perturbs myosin motor activity, leads to a reorganization of the cortical networks and to a reduction of contractile motions. We quantified the kinetics of contraction, disassembly and reassembly of myosin networks using spatio-temporal image correlation spectroscopy (STICS). Coarse-grained numerical simulations include bipolar minifilaments that contract and align through specified interactions as basic elements. After assuming that minifilament turnover decreases with increasing contractile stress, the simulations reproduce stress-dependent fiber formation in between focal adhesions above a threshold myosin concentration. The STICS correlation function in simulations matches the function measured in experiments. This study provides a framework to help interpret how different cortical myosin remodeling kinetics may contribute to different cell shape and rigidity depending on substrate stiffness. © 2015 Wiley Periodicals, Inc.

Advances in quantum simulations of ATPase catalysis in the myosin motor.

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Kiani, Farooq Ahmad; Fischer, Stefan

2015-04-01

During its contraction cycle, the myosin motor catalyzes the hydrolysis of ATP. Several combined quantum/classical mechanics (QM/MM) studies of this step have been published, which substantially contributed to our thinking about the catalytic mechanism. The methodological difficulties encountered over the years in the simulation of this complex reaction are now understood: (a) Polarization of the protein peptide groups surrounding the highly charged ATP(4-) cannot be neglected. (b) Some unsuspected protein groups need to be treated QM. (c) Interactions with the γ-phosphate versus the β-phosphate favor a concurrent versus a sequential mechanism, respectively. Thus, these practical aspects strongly influence the computed mechanism, and should be considered when studying other catalyzed phosphor-ester hydrolysis reactions, such as in ATPases or GTPases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Direct observation of the myosin Va recovery stroke that contributes to unidirectional stepping along actin.

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Katsuyuki Shiroguchi

2011-04-01

Full Text Available Myosins are ATP-driven linear molecular motors that work as cellular force generators, transporters, and force sensors. These functions are driven by large-scale nucleotide-dependent conformational changes, termed "strokes"; the "power stroke" is the force-generating swinging of the myosin light chain-binding "neck" domain relative to the motor domain "head" while bound to actin; the "recovery stroke" is the necessary initial motion that primes, or "cocks," myosin while detached from actin. Myosin Va is a processive dimer that steps unidirectionally along actin following a "hand over hand" mechanism in which the trailing head detaches and steps forward ∼72 nm. Despite large rotational Brownian motion of the detached head about a free joint adjoining the two necks, unidirectional stepping is achieved, in part by the power stroke of the attached head that moves the joint forward. However, the power stroke alone cannot fully account for preferential forward site binding since the orientation and angle stability of the detached head, which is determined by the properties of the recovery stroke, dictate actin binding site accessibility. Here, we directly observe the recovery stroke dynamics and fluctuations of myosin Va using a novel, transient caged ATP-controlling system that maintains constant ATP levels through stepwise UV-pulse sequences of varying intensity. We immobilized the neck of monomeric myosin Va on a surface and observed real time motions of bead(s attached site-specifically to the head. ATP induces a transient swing of the neck to the post-recovery stroke conformation, where it remains for ∼40 s, until ATP hydrolysis products are released. Angle distributions indicate that the post-recovery stroke conformation is stabilized by ≥ 5 k(BT of energy. The high kinetic and energetic stability of the post-recovery stroke conformation favors preferential binding of the detached head to a forward site 72 nm away. Thus, the recovery

Stress generation by myosin minifilaments in actin bundles

International Nuclear Information System (INIS)

Dasanayake, Nilushi L; Carlsson, Anders E

2013-01-01

Forces and stresses generated by the action of myosin minifilaments are analyzed in idealized computer-generated actin bundles, and compared to results for isotropic actin networks. The bundles are generated as random collections of actin filaments in two dimensions with constrained orientations, crosslinked and attached to two fixed walls. Myosin minifilaments are placed on actin filament pairs and allowed to move and deform the network so that it exerts forces on the walls. The vast majority of simulation runs end with contractile minifilament stress, because minifilaments rotate into energetically stable contractile configurations. This process is aided by the bending and stretching of actin filaments, which accomodate minifilament rotation. Stresses for bundles are greater than those for isotropic networks, and antiparallel filaments generate more tension than parallel filaments. The forces transmitted by the actin network to the walls of the simulation cell often exceed the tension in the minifilament itself. (paper)

Phosphorylation of Tropomyosin Extends Cooperative Binding of Myosin Beyond a Single Regulatory Unit

OpenAIRE

Rao, Vijay S.; Marongelli, Ellisha N.; Guilford, William H.

2009-01-01

Tropomyosin (Tm) is one of the major phosphoproteins comprising the thin filament of muscle. However, the specific role of Tm phosphorylation in modulating the mechanics of actomyosin interaction has not been determined. Here we show that Tm phosphorylation is necessary for long-range cooperative activation of myosin binding. We used a novel optical trapping assay to measure the isometric stall force of an ensemble of myosin molecules moving actin filaments reconstituted with either natively ...

BMP-2 Overexpression Augments Vascular Smooth Muscle Cell Motility by Upregulating Myosin Va via Erk Signaling

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Ming Zhang

2014-01-01

Full Text Available Background. The disruption of physiologic vascular smooth muscle cell (VSMC migration initiates atherosclerosis development. The biochemical mechanisms leading to dysfunctional VSMC motility remain unknown. Recently, cytokine BMP-2 has been implicated in various vascular physiologic and pathologic processes. However, whether BMP-2 has any effect upon VSMC motility, or by what manner, has never been investigated. Methods. VSMCs were adenovirally transfected to genetically overexpress BMP-2. VSMC motility was detected by modified Boyden chamber assay, confocal time-lapse video assay, and a colony wounding assay. Gene chip array and RT-PCR were employed to identify genes potentially regulated by BMP-2. Western blot and real-time PCR detected the expression of myosin Va and the phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2. Immunofluorescence analysis revealed myosin Va expression locale. Intracellular Ca2+ oscillations were recorded. Results. VSMC migration was augmented in VSMCs overexpressing BMP-2 in a dose-dependent manner. siRNA-mediated knockdown of myosin Va inhibited VSMC motility. Both myosin Va mRNA and protein expression significantly increased after BMP-2 administration and were inhibited by Erk1/2 inhibitor U0126. BMP-2 induced Ca2+ oscillations, generated largely by a “cytosolic oscillator”. Conclusion. BMP-2 significantly increased VSMCs migration and myosin Va expression, via the Erk signaling pathway and intracellular Ca2+ oscillations. We provide additional insight into the pathophysiology of atherosclerosis, and inhibition of BMP-2-induced myosin Va expression may represent a potential therapeutic strategy.

Myosin light chain phosphorylation is critical for adaptation to cardiac stress.

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Warren, Sonisha A; Briggs, Laura E; Zeng, Huadong; Chuang, Joyce; Chang, Eileen I; Terada, Ryota; Li, Moyi; Swanson, Maurice S; Lecker, Stewart H; Willis, Monte S; Spinale, Francis G; Maupin-Furlowe, Julie; McMullen, Julie R; Moss, Richard L; Kasahara, Hideko

2012-11-27

Cardiac hypertrophy is a common response to circulatory or neurohumoral stressors as a mechanism to augment contractility. When the heart is under sustained stress, the hypertrophic response can evolve into decompensated heart failure, although the mechanism(s) underlying this transition remain largely unknown. Because phosphorylation of cardiac myosin light chain 2 (MLC2v), bound to myosin at the head-rod junction, facilitates actin-myosin interactions and enhances contractility, we hypothesized that phosphorylation of MLC2v plays a role in the adaptation of the heart to stress. We previously identified an enzyme that predominantly phosphorylates MLC2v in cardiomyocytes, cardiac myosin light-chain kinase (cMLCK), yet the role(s) played by cMLCK in regulating cardiac function in health and disease remain to be determined. We found that pressure overload induced by transaortic constriction in wild-type mice reduced phosphorylated MLC2v levels by ≈40% and cMLCK levels by ≈85%. To examine how a reduction in cMLCK and the corresponding reduction in phosphorylated MLC2v affect function, we generated Mylk3 gene-targeted mice and transgenic mice overexpressing cMLCK specifically in cardiomyocytes. Pressure overload led to severe heart failure in cMLCK knockout mice but not in mice with cMLCK overexpression in which cMLCK protein synthesis exceeded degradation. The reduction in cMLCK protein during pressure overload was attenuated by inhibition of ubiquitin-proteasome protein degradation systems. Our results suggest the novel idea that accelerated cMLCK protein turnover by the ubiquitin-proteasome system underlies the transition from compensated hypertrophy to decompensated heart failure as a result of reduced phosphorylation of MLC2v.

Myosin XI-dependent formation of tubular structures from endoplasmic reticulum isolated from tobacco cultured BY-2 cells.

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Yokota, Etsuo; Ueda, Haruko; Hashimoto, Kohsuke; Orii, Hidefumi; Shimada, Tomoo; Hara-Nishimura, Ikuko; Shimmen, Teruo

2011-05-01

The reticular network of the endoplasmic reticulum (ER) consists of tubular and lamellar elements and is arranged in the cortical region of plant cells. This network constantly shows shape change and remodeling motion. Tubular ER structures were formed when GTP was added to the ER vesicles isolated from tobacco (Nicotiana tabacum) cultured BY-2 cells expressing ER-localized green fluorescent protein. The hydrolysis of GTP during ER tubule formation was higher than that under conditions in which ER tubule formation was not induced. Furthermore, a shearing force, such as the flow of liquid, was needed for the elongation/extension of the ER tubule. The shearing force was assumed to correspond to the force generated by the actomyosin system in vivo. To confirm this hypothesis, the S12 fraction was prepared, which contained both cytosol and microsome fractions, including two classes of myosins, XI (175-kD myosin) and VIII (BY-2 myosin VIII-1), and ER-localized green fluorescent protein vesicles. The ER tubules and their mesh-like structures were arranged in the S12 fraction efficiently by the addition of ATP, GTP, and exogenous filamentous actin. The tubule formation was significantly inhibited by the depletion of 175-kD myosin from the S12 fraction but not BY-2 myosin VIII-1. Furthermore, a recombinant carboxyl-terminal tail region of 175-kD myosin also suppressed ER tubule formation. The tips of tubules moved along filamentous actin during tubule elongation. These results indicated that the motive force generated by the actomyosin system contributes to the formation of ER tubules, suggesting that myosin XI is responsible not only for the transport of ER in cytoplasm but also for the reticular organization of cortical ER.

Myosin IIA participates in docking of Glut4 storage vesicles with the plasma membrane in 3T3-L1 adipocytes

International Nuclear Information System (INIS)

Chung, Le Thi Kim; Hosaka, Toshio; Harada, Nagakatsu; Jambaldorj, Bayasgalan; Fukunaga, Keiko; Nishiwaki, Yuka; Teshigawara, Kiyoshi; Sakai, Tohru; Nakaya, Yutaka; Funaki, Makoto

2010-01-01

In adipocytes and myocytes, insulin stimulation translocates glucose transporter 4 (Glut4) storage vesicles (GSVs) from their intracellular storage sites to the plasma membrane (PM) where they dock with the PM. Then, Glut4 is inserted into the PM and initiates glucose uptake into these cells. Previous studies using chemical inhibitors demonstrated that myosin II participates in fusion of GSVs and the PM and increase in the intrinsic activity of Glut4. In this study, the effect of myosin IIA on GSV trafficking was examined by knocking down myosin IIA expression. Myosin IIA knockdown decreased both glucose uptake and exposures of myc-tagged Glut4 to the cell surface in insulin-stimulated cells, but did not affect insulin signal transduction. Interestingly, myosin IIA knockdown failed to decrease insulin-dependent trafficking of Glut4 to the PM. Moreover, in myosin IIA knockdown cells, insulin-stimulated binding of GSV SNARE protein, vesicle-associated membrane protein 2 (VAMP2) to PM SNARE protein, syntaxin 4 was inhibited. These data suggest that myosin IIA plays a role in insulin-stimulated docking of GSVs to the PM in 3T3-L1 adipocytes through SNARE complex formation.

The local expression of adult chicken heart myosins during development. I. The three days embryonic chicken heart

NARCIS (Netherlands)

Sanders, E.; Moorman, A. F.; Los, J. A.

1984-01-01

Immunofluorescence studies were performed on serial sections of three days embryonic chicken hearts using antibodies specific for adult atrial and ventricular myosin heavy chains respectively. The anti-ventricular myosin serum reacted with the entire myocardium showing a decreasing intensity going

CALIX[4]ARENE C-99 INHIBITS MYOSIN ATPase ACTIVITY AND CHANGES THE ORGANIZATION OF CONTRACTILE FILAMENTS OF MYOMETRIUM.

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Labyntseva, R D; Bevza, A A; Lul'ko, A O; Cherenok, S O; Kalchenko, V I; Kosterin, S O

2015-01-01

Calix[4]arenes are cup-like macrocyclic (polyphenolic) compounds, they are regarded as promising molecular "platforms" for the design of new physiologically active compounds. We have earlier found that calix[4]arene C-99 inhibits the ATPase activity of actomyosin and myosin subfragment-1 of pig uterus in vitro. The aim of this study was to investigate the interaction of calix[4]arene C-99 with myosin from rat uterine myocytes. It was found that the ATPase activity of myosin prepared from pre-incubated with 100 mM of calix[4]arene C-99 myocytes was almost 50% lower than in control. Additionally, we have revealed the effect of calix[4]arene C-99 on the subcellular distribution of actin and myosin in uterus myocytes by the method of confocal microscopy. This effect can be caused by reorganization of the structure of the contractile smooth muscle cell proteins due to their interaction with calix[4]arene. The obtained results demonstrate the ability of calix[4]arene C-99 to penetrate into the uterus muscle cells and affect not only the myosin ATPase activity, but also the structure of the actin and myosin filaments in the myometrial cells. Demonstrated ability of calix[4]arene C-99 can be used for development of new pharmacological agents for efficient normalization of myometrial contractile hyperfunction.

Calix[4]arene C-99 inhibits myosin ATPase activity and changes the organization of contractile filaments of myometrium

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R. D. Labyntseva,

2015-12-01

Full Text Available Calix[4]arenes are cup-like macrocyclic (polyphenolic compounds, they are regarded as promising molecular “platforms” for the design of new physiologically active compounds. We have earlier found that сalix[4]arenе C-99 inhibits the ATPase activity of actomyosin and myosin subfragment-1 of pig uterus іn vitro. The aim of this study was to investigate the interaction of calix[4]arene C-99 with myosin from rat uterine myocytes. It was found that the ATPase activity of myosin prepared from pre-incubated with 100 mM of calix[4]arene C-99 myocytes was almost 50% lower than in control. Additionally, we have revealed the effect of calix[4]arene C-99 on the subcellular distribution of actin and myosin in uterus myocytes by the method of confocal microscopy. This effect can be caused by reorganization of the structure of the contractile smooth muscle cell proteins due to their interaction with calix[4]arene. The obtained results demonstrate the ability of calix[4]arene C-99 to penetrate into the uterus muscle cells and affect not only the myosin ATPase activity, but also the structure of the actin and myosin filaments in the myometrial cells. Demonstrated ability of calix[4]arene C-99 can be used for development of new pharmacological agents for efficient normalization of myometrial contractile hyperfunction.

Lessons from (triggered) tremor

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Gomberg, Joan

2010-01-01

I test a “clock-advance” model that implies triggered tremor is ambient tremor that occurs at a sped-up rate as a result of loading from passing seismic waves. This proposed model predicts that triggering probability is proportional to the product of the ambient tremor rate and a function describing the efficacy of the triggering wave to initiate a tremor event. Using data mostly from Cascadia, I have compared qualitatively a suite of teleseismic waves that did and did not trigger tremor with ambient tremor rates. Many of the observations are consistent with the model if the efficacy of the triggering wave depends on wave amplitude. One triggered tremor observation clearly violates the clock-advance model. The model prediction that larger triggering waves result in larger triggered tremor signals also appears inconsistent with the measurements. I conclude that the tremor source process is a more complex system than that described by the clock-advance model predictions tested. Results of this and previous studies also demonstrate that (1) conditions suitable for tremor generation exist in many tectonic environments, but, within each, only occur at particular spots whose locations change with time; (2) any fluid flow must be restricted to less than a meter; (3) the degree to which delayed failure and secondary triggering occurs is likely insignificant; and 4) both shear and dilatational deformations may trigger tremor. Triggered and ambient tremor rates correlate more strongly with stress than stressing rate, suggesting tremor sources result from time-dependent weakening processes rather than simple Coulomb failure.

Clinical study on the time courses of serum myosin light chain I levels in patients with acute myocardial infarction

International Nuclear Information System (INIS)

Nakanishi, Masako; Saiki, Yasuhiko; Ui, Kazuyo

1992-01-01

Changes of serum myosin light chain I (Myosin LCI) concentrations and creatine kinase (CK) activities were serially measured in 23 patients with acute myocardial infarction. Intracoronary thrombolysis was performed in 14 patients (ICT group) while the remaining 9 patients were treated in the conventional manner (non ICT group). The relationships between the maximum levels of serum Myosin LCI or CK and a myocardial infarct size index or left ventricular function were evaluated in 18 patients. The myocardial infarct size index was determined by 201 Tl myocardial scintigrams performed in the chronic phase. Multiple peaks of Myosin LCI were observed in 64% (9/14) of the ICT group and the first peak in 6 of these patients appeared much earlier in the same time as CK peak than in the non-ICT group, while multiple peaks were seen only in one case in the non-ICT group. The infarct size index by 201 Tl myocardial SPECT correlated with maximum Myosin LCI levels (r=0.88, p<0.001, n=10) and CK activities (r=0.67, p<0.05, n=10). These results indicate that the measurement of serum Myosin LCI is very useful for estimating the extent of myocardial damage and suggest that myocardial degeneration occurs at a very early phase of myocardial infarction. (author)

Drosophila UNC-45 prevents heat-induced aggregation of skeletal muscle myosin and facilitates refolding of citrate synthase

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Melkani, Girish C.; Lee, Chi F.; Cammarato, Anthony [Department of Biology and the Molecular Biology Institute, San Diego State University, San Diego, CA 92182-4614 (United States); Bernstein, Sanford I., E-mail: sbernst@sciences.sdsu.edu [Department of Biology and the Molecular Biology Institute, San Diego State University, San Diego, CA 92182-4614 (United States)

2010-05-28

UNC-45 belongs to the UCS (UNC-45, CRO1, She4p) domain protein family, whose members interact with various classes of myosin. Here we provide structural and biochemical evidence that Escherichia coli-expressed Drosophila UNC-45 (DUNC-45) maintains the integrity of several substrates during heat-induced stress in vitro. DUNC-45 displays chaperone function in suppressing aggregation of the muscle myosin heavy meromyosin fragment, the myosin S-1 motor domain, {alpha}-lactalbumin and citrate synthase. Biochemical evidence is supported by electron microscopy, which reveals the first structural evidence that DUNC-45 prevents inter- or intra-molecular aggregates of skeletal muscle heavy meromyosin caused by elevated temperatures. We also demonstrate for the first time that UNC-45 is able to refold a denatured substrate, urea-unfolded citrate synthase. Overall, this in vitro study provides insight into the fate of muscle myosin under stress conditions and suggests that UNC-45 protects and maintains the contractile machinery during in vivo stress.

Blebbistatin, a myosin II inhibitor, suppresses Ca(2+)-induced and "sensitized"-contraction of skinned tracheal muscles from guinea pig.

Science.gov (United States)

Yumoto, Masatoshi; Watanabe, Masaru

2013-01-01

Blebbistatin, a potent inhibitor of myosin II, has inhibiting effects on Ca(2+)-induced contraction and contractile filament organization without affecting the Ca(2+)-sensitivity to the force and phosphorylation level of myosin regulatory light chain (MLC20) in skinned (cell membrane permeabilized) taenia cecum from the guinea pig (Watanabe et al., Am J Physiol Cell Physiol. 2010; 298: C1118-26). In the present study, we investigated blebbistatin effects on the contractile force of skinned tracheal muscle, in which myosin filaments organization is more labile than that in the taenia cecum. Blebbistatin at 10 μM or higher suppressed Ca(2+)-induced tension development at any given Ca(2+) concentration, but had little effects on the Ca(2+)- induced myosin light chain phosphorylation. Also blebbistatin at 10 μM and higher significantly suppressed GTP-γS-induced "sensitized" force development. Since the force inhibiting effects of blebbistatin on the skinned trachea were much stronger than those in skinned taenia cecum, blebbistatin might directly affect myosin filaments organization.

The Rho kinases I and II regulate different aspects of myosin II activity

DEFF Research Database (Denmark)

Yoneda, Atsuko; Multhaupt, Hinke A B; Couchman, John R

2005-01-01

The homologous mammalian rho kinases (ROCK I and II) are assumed to be functionally redundant, based largely on kinase construct overexpression. As downstream effectors of Rho GTPases, their major substrates are myosin light chain and myosin phosphatase. Both kinases are implicated in microfilament...... bundle assembly and smooth muscle contractility. Here, analysis of fibroblast adhesion to fibronectin revealed that although ROCK II was more abundant, its activity was always lower than ROCK I. Specific reduction of ROCK I by siRNA resulted in loss of stress fibers and focal adhesions, despite...

Influence of fast and slow alkali myosin light chain isoforms on the kinetics of stretch-induced force transients of fast-twitch type IIA fibres of rat.

Science.gov (United States)

Andruchov, Oleg; Galler, Stefan

2008-03-01

This study contributes to understand the physiological role of slow myosin light chain isoforms in fast-twitch type IIA fibres of skeletal muscle. These isoforms are often attached to the myosin necks of rat type IIA fibres, whereby the slow alkali myosin light chain isoform MLC1s is much more frequent and abundant than the slow regulatory myosin light chain isoform MLC2s. In the present study, single-skinned rat type IIA fibres were maximally Ca(2+) activated and subjected to stepwise stretches for causing a perturbation of myosin head pulling cycles. From the time course of the resulting force transients, myosin head kinetics was deduced. Fibres containing MLC1s exhibited slower kinetics independently of the presence or absence of MLC2s. At the maximal MLC1s concentration of about 75%, the slowing was about 40%. The slowing effect of MLC1s is possibly due to differences in the myosin heavy chain binding sites of the fast and slow alkali MLC isoforms, which changes the rigidity of the myosin neck. Compared with the impact of myosin heavy chain isoforms in various fast-twitch fibre types, the influence of MLC1s on myosin head kinetics of type IIA fibres is much smaller. In conclusion, the physiological role of fast and slow MLC isoforms in type IIA fibres is a fine-tuning of the myosin head kinetics.

Effects of BTS (N-benzyl-p-toluene sulphonamide), an inhibitor for myosin-actin interaction, on myofibrillogenesis in skeletal muscle cells in culture.

Science.gov (United States)

Kagawa, Maiko; Sato, Naruki; Obinata, Takashi

2006-11-01

Actin filaments align around myosin filaments in the correct polarity and in a hexagonal arrangement to form cross-striated structures. It has been postulated that this myosin-actin interaction is important in the initial phase of myofibrillogenesis. It was previously demonstrated that an inhibitor of actin-myosin interaction, BDM (2,3-butanedione monoxime), suppresses myofibril formation in muscle cells in culture. However, further study showed that BDM also exerts several additional effects on living cells. In this study, we further examined the role of actin-myosin interaction in myofibril assembly in primary cultures of chick embryonic skeletal muscle by applying a more specific inhibitor, BTS (N-benzyl-p-toluene sulphonamide), of myosin ATPase and actin-myosin interaction. The assembly of sarcomeric structures from myofibrillar proteins was examined by immunocytochemical methods with the application of BTS to myotubes just after fusion. Addition of BTS (10-50 microM) significantly suppressed the organization of actin and myosin into cross-striated structures. BTS also interfered in the organization of alpha-actinin, C-protein (or MyBP-C), and connectin (or titin) into ordered striated structures, though the sensitivity was less. Moreover, when myotubes cultured in the presence of BTS were transferred to a control medium, sarcomeric structures were formed in 2-3 days, indicating that the inhibitory effect of BTS on myotubes is reversible. These results show that actin-myosin interaction plays a critical role in the process of myofibrillogenesis.

Discoidin Domain Receptor 1 Mediates Myosin-Dependent Collagen Contraction

Directory of Open Access Journals (Sweden)

Nuno M. Coelho

2017-02-01

Full Text Available Discoidin domain receptor 1 (DDR1 is a tyrosine kinase collagen adhesion receptor that mediates cell migration through association with non-muscle myosin IIA (NMIIA. Because DDR1 is implicated in cancer fibrosis, we hypothesized that DDR1 interacts with NMIIA to enable collagen compaction by traction forces. Mechanical splinting of rat dermal wounds increased DDR1 expression and collagen alignment. In periodontal ligament of DDR1 knockout mice, collagen mechanical reorganization was reduced >30%. Similarly, cultured cells with DDR1 knockdown or expressing kinase-deficient DDR1d showed 50% reduction of aligned collagen. Tractional remodeling of collagen was dependent on DDR1 clustering, activation, and interaction of the DDR1 C-terminal kinase domain with NMIIA filaments. Collagen remodeling by traction forces, DDR1 tyrosine phosphorylation, and myosin light chain phosphorylation were increased on stiff versus soft substrates. Thus, DDR1 clustering, activation, and interaction with NMIIA filaments enhance the collagen tractional remodeling that is important for collagen compaction in fibrosis.

Probing muscle myosin motor action: x-ray (m3 and m6) interference measurements report motor domain not lever arm movement.

Science.gov (United States)

Knupp, Carlo; Offer, Gerald; Ranatunga, K W; Squire, John M

2009-07-10

The key question in understanding how force and movement are produced in muscle concerns the nature of the cyclic interaction of myosin molecules with actin filaments. The lever arm of the globular head of each myosin molecule is thought in some way to swing axially on the actin-attached motor domain, thus propelling the actin filament past the myosin filament. Recent X-ray diffraction studies of vertebrate muscle, especially those involving the analysis of interference effects between myosin head arrays in the two halves of the thick filaments, have been claimed to prove that the lever arm moves at the same time as the sliding of actin and myosin filaments in response to muscle length or force steps. It was suggested that the sliding of myosin and actin filaments, the level of force produced and the lever arm angle are all directly coupled and that other models of lever arm movement will not fit the X-ray data. Here, we show that, in addition to interference across the A-band, which must be occurring, the observed meridional M3 and M6 X-ray intensity changes can all be explained very well by the changing diffraction effects during filament sliding caused by heads stereospecifically attached to actin moving axially relative to a population of detached or non-stereospecifically attached heads that remain fixed in position relative to the myosin filament backbone. Crucially, and contrary to previous interpretations, the X-ray interference results provide little direct information about the position of the myosin head lever arm; they are, in fact, reporting relative motor domain movements. The implications of the new interpretation are briefly assessed.

Myosin Va Plays a Role in Nitrergic Smooth Muscle Relaxation in Gastric Fundus and Corpora Cavernosa of Penis

Science.gov (United States)

Carew, Josephine A.; Goyal, Raj K.; Sullivan, Maryrose P.

2014-01-01

The intracellular motor protein myosin Va is involved in nitrergic neurotransmission possibly by trafficking of neuronal nitric oxide synthase (nNOS) within the nerve terminals. In this study, we examined the role of myosin Va in the stomach and penis, proto-typical smooth muscle organs in which nitric oxide (NO) mediated relaxation is critical for function. We used confocal microscopy and co-immunoprecipitation of tissue from the gastric fundus (GF) and penile corpus cavernosum (CCP) to localize myosin Va with nNOS and demonstrate their molecular interaction. We utilized in vitro mechanical studies to test whether smooth muscle relaxations during nitrergic neuromuscular neurotransmission is altered in DBA (dilute, brown, non-agouti) mice which lack functional myosin Va. Myosin Va was localized in nNOS-positive nerve terminals and was co-immunoprecipitated with nNOS in both GF and CCP. In comparison to C57BL/6J wild type (WT) mice, electrical field stimulation (EFS) of precontracted smooth muscles of GF and CCP from DBA animals showed significant impairment of nitrergic relaxation. An NO donor, Sodium nitroprusside (SNP), caused comparable levels of relaxation in smooth muscles of WT and DBA mice. These normal postjunctional responses to SNP in DBA tissues suggest that impairment of smooth muscle relaxation resulted from inhibition of NO synthesis in prejunctional nerve terminals. Our results suggest that normal physiological processes of relaxation of gastric and cavernosal smooth muscles that facilitate food accommodation and penile erection, respectively, may be disrupted under conditions of myosin Va deficiency, resulting in complications like gastroparesis and erectile dysfunction. PMID:24516539

Carboxyl-terminal-dependent recruitment of nonmuscle myosin II to megakaryocyte contractile ring during polyploidization.

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Badirou, Idinath; Pan, Jiajia; Legrand, Céline; Wang, Aibing; Lordier, Larissa; Boukour, Siham; Roy, Anita; Vainchenker, William; Chang, Yunhua

2014-10-16

Endomitosis is a unique megakaryocyte (MK) differentiation process that is the consequence of a late cytokinesis failure associated with a contractile ring defect. Evidence from in vitro studies has revealed the distinct roles of 2 nonmuscle myosin IIs (NMIIs) on MK endomitosis: only NMII-B (MYH10), but not NMII-A (MYH9), is localized in the MK contractile ring and implicated in mitosis/endomitosis transition. Here, we studied 2 transgenic mouse models in which nonmuscle myosin heavy chain (NMHC) II-A was genetically replaced either by II-B or by a chimeric NMHCII that combined the head domain of II-A with the rod and tail domains of II-B. This study provides in vivo evidence on the specific role of NMII-B on MK polyploidization. It demonstrates that the carboxyl-terminal domain of the heavy chains determines myosin II localization to the MK contractile ring and is responsible for the specific role of NMII-B in MK polyploidization.

Alterations in rat cardiac myosin isozymes induced by whole-body irradiation are prevented by 3,5,3'-L-triiodothyronine

International Nuclear Information System (INIS)

Litten, R.Z.; Fein, H.G.; Gainey, G.T.; Walden, T.L.; Smallridge, R.C.

1990-01-01

Changes in cardiac myosin isozymes and serum thyroid hormone levels were investigated in rats following 10 Gy whole-body gamma irradiation. The percent beta-myosin heavy chain increased from 21.3 ± 1.8 to 28.1 ± 6.8 (NS) at 3-day postirradiation, 37.7 ± 1.9 (P less than .001) at 6-day postirradiation, and 43.8 ± 3.3 (P less than .001) at 9-day postirradiation. Along with the change in myosin isozymes was a significant 53% decrease (P less than .001) in the serum thyroxine (T4) level by day 3 postirradiation, remaining depressed through day 9 postirradiation. The serum 3,5,3'-triiodothyronine (T3) level, however, was normal until day 9, when significant depression was also observed. In contrast, the thyroid-stimulating hormone (TSH) level was significantly increased by fourfold at day 3, returning to near normal values by day 9 postirradiation. Daily injections of physiological doses of T3 (0.3 microgram/100 g body weight) prevented the change in the myosin isozymes following whole-body irradiation. Daily pharmacological injections of T3 (3.0 micrograms/100 g body weight) to the irradiated rats produced a further decrease in the percent beta-myosin heavy chain (below control values) indicating tissue hyperthyroidism. Thus, this study suggests that the change in myosin isozymes following whole-body irradiation is caused by an alteration in thyroid hormone activity

Coupling between myosin head conformation and the thick filament backbone structure.

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Hu, Zhongjun; Taylor, Dianne W; Edwards, Robert J; Taylor, Kenneth A

2017-12-01

The recent high-resolution structure of the thick filament from Lethocerus asynchronous flight muscle shows aspects of thick filament structure never before revealed that may shed some light on how striated muscles function. The phenomenon of stretch activation underlies the function of asynchronous flight muscle. It is most highly developed in flight muscle, but is also observed in other striated muscles such as cardiac muscle. Although stretch activation is likely to be complex, involving more than a single structural aspect of striated muscle, the thick filament itself, would be a prime site for regulatory function because it must bear all of the tension produced by both its associated myosin motors and any externally applied force. Here we show the first structural evidence that the arrangement of myosin heads within the interacting heads motif is coupled to the structure of the thick filament backbone. We find that a change in helical angle of 0.16° disorders the blocked head preferentially within the Lethocerus interacting heads motif. This observation suggests a mechanism for how tension affects the dynamics of the myosin heads leading to a detailed hypothesis for stretch activation and shortening deactivation, in which the blocked head preferentially binds the thin filament followed by the free head when force production occurs. Copyright © 2017 Elsevier Inc. All rights reserved.

Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle

Science.gov (United States)

Boëda, Batiste; El-Amraoui, Aziz; Bahloul, Amel; Goodyear, Richard; Daviet, Laurent; Blanchard, Stéphane; Perfettini, Isabelle; Fath, Karl R.; Shorte, Spencer; Reiners, Jan; Houdusse, Anne; Legrain, Pierre; Wolfrum, Uwe; Richardson, Guy; Petit, Christine

2002-01-01

Deaf-blindness in three distinct genetic forms of Usher type I syndrome (USH1) is caused by defects in myosin VIIa, harmonin and cadherin 23. Despite being critical for hearing, the functions of these proteins in the inner ear remain elusive. Here we show that harmonin, a PDZ domain-containing protein, and cadherin 23 are both present in the growing stereocilia and that they bind to each other. Moreover, we demonstrate that harmonin b is an F-actin-bundling protein, which is thus likely to anchor cadherin 23 to the stereocilia microfilaments, thereby identifying a novel anchorage mode of the cadherins to the actin cytoskeleton. Moreover, harmonin b interacts directly with myosin VIIa, and is absent from the disorganized hair bundles of myosin VIIa mutant mice, suggesting that myosin VIIa conveys harmonin b along the actin core of the developing stereocilia. We propose that the shaping of the hair bundle relies on a functional unit composed of myosin VIIa, harmonin b and cadherin 23 that is essential to ensure the cohesion of the stereocilia. PMID:12485990

Actin Filaments and Myosin I Alpha Cooperate with Microtubules for the Movement of LysosomesV⃞

OpenAIRE

Cordonnier, Marie-Neige; Dauzonne, Daniel; Louvard, Daniel; Coudrier, Evelyne

2001-01-01

An earlier report suggested that actin and myosin I alpha (MMIα), a myosin associated with endosomes and lysosomes, were involved in the delivery of internalized molecules to lysosomes. To determine whether actin and MMIα were involved in the movement of lysosomes, we analyzed by time-lapse video microscopy the dynamic of lysosomes in living mouse hepatoma cells (BWTG3 cells), producing green fluorescent protein actin or a nonfunctional domain of MMIα. In GFP-actin cells, lysosomes displayed ...

A comparative study of myosin and its subunits in adult and neonatal-rat hearts and in rat heart cells from young and old cultures.

OpenAIRE

Ghanbari, H A; McCarl, R L

1980-01-01

A possible explanation for the decrease in myosin Ca2+-dependent ATPase activity as rat heart cells age in culture is presented. The subunit structure and enzyme kinetics of myosin from adult and neonatal rat hearts and from rat heart cells of young and old cultures are compared. These studies indicate that the loss in Ca-ATPase activity of myosin from older cultures was an intrinsic property of the myosin itself. Myofibrillar fractions from the indicated four sources showed no qualitative or...

Triggering soft bombs at the LHC

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Knapen, Simon; Griso, Simone Pagan; Papucci, Michele; Robinson, Dean J.

2017-08-01

Very high multiplicity, spherically-symmetric distributions of soft particles, with p T ˜ few×100 MeV, may be a signature of strongly-coupled hidden valleys that exhibit long, efficient showering windows. With traditional triggers, such `soft bomb' events closely resemble pile-up and are therefore only recorded with minimum bias triggers at a very low efficiency. We demonstrate a proof-of-concept for a high-level triggering strategy that efficiently separates soft bombs from pile-up by searching for a `belt of fire': a high density band of hits on the innermost layer of the tracker. Seeding our proposed high-level trigger with existing jet, missing transverse energy or lepton hardware-level triggers, we show that net trigger efficiencies of order 10% are possible for bombs of mass several × 100 GeV. We also consider the special case that soft bombs are the result of an exotic decay of the 125 GeV Higgs. The fiducial rate for `Higgs bombs' triggered in this manner is marginally higher than the rate achievable by triggering directly on a hard muon from associated Higgs production.

The fungal myosin I is essential for Fusarium toxisome formation

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The mycotoxin deoxynivalenol (DON) is the most frequently detected secondary metabolite produced by Fusarium graminearum and other Fusarium spp. To date, relatively few studies have addressed how mycotoxin biosynthesis occurs in fungal cells. Here we found that myosin I governs translation of DON bi...

Synthesis of total protein (TP) and myosin heavy chain (HC) isozymes in pressure overloaded rabbit hearts

International Nuclear Information System (INIS)

Nagai, R.; Martin, B.J.; Pritzl, N.; Zak, R.; Low, R.B.; Stirewalt, W.S.; Alpert, N.R.; Litten, R.Z.

1986-01-01

Pulmonary artery banding (PO) leads to a rapid increase in right ventricular (RV) weight as well as a shift toward β myosin isozyme. They determined: (1) the contributions of changes in the capacity (RNA content) and efficiency of total protein synthesis to the increase in RV weight; and (2) the relative contributions of translational and pretranslational mechanisms to the shift in myosin HC isotypes. The rates of synthesis in vivo of TP, α- and β-HC were measured by a constant infusion technique using 3 H-leucine. TP synthesis was 7 +/- 2(SD) mg/day in control (RV:367 +/- 70 mg) and was increased by 2.6 fold at day 2 and 2.9 fold at day 4 following PO (p < 0.01). RV RNA content was increased by 83% at day 2 and 103% at day 4 PO (p < 0.05). The efficiency of synthesis (rate/RNA) was also significantly higher at these time points (1.4- and 1.3-fold). β-HC synthesis was 0.6 +/- 0.2 mg/day in control and increased by 2.6 fold at day 2 and 3.5 fold at day 4 following PO. In contrast, the rate of synthesis of α-HC was unchanged. The relative rates of β-HC to total HC synthesis was correlated linearly with the relative levels of β-myosin mRNA as measured by S1 nuclease mapping. They conclude that increases in the proportion of β-HC myosin following PO is due to increases in the relative amount of β-myosin mRNA and therefore involves modulation of a pretranslational mechanism

Myosin XI-Dependent Formation of Tubular Structures from Endoplasmic Reticulum Isolated from Tobacco Cultured BY-2 Cells1[W][OA

Science.gov (United States)

Yokota, Etsuo; Ueda, Haruko; Hashimoto, Kohsuke; Orii, Hidefumi; Shimada, Tomoo; Hara-Nishimura, Ikuko; Shimmen, Teruo

2011-01-01

The reticular network of the endoplasmic reticulum (ER) consists of tubular and lamellar elements and is arranged in the cortical region of plant cells. This network constantly shows shape change and remodeling motion. Tubular ER structures were formed when GTP was added to the ER vesicles isolated from tobacco (Nicotiana tabacum) cultured BY-2 cells expressing ER-localized green fluorescent protein. The hydrolysis of GTP during ER tubule formation was higher than that under conditions in which ER tubule formation was not induced. Furthermore, a shearing force, such as the flow of liquid, was needed for the elongation/extension of the ER tubule. The shearing force was assumed to correspond to the force generated by the actomyosin system in vivo. To confirm this hypothesis, the S12 fraction was prepared, which contained both cytosol and microsome fractions, including two classes of myosins, XI (175-kD myosin) and VIII (BY-2 myosin VIII-1), and ER-localized green fluorescent protein vesicles. The ER tubules and their mesh-like structures were arranged in the S12 fraction efficiently by the addition of ATP, GTP, and exogenous filamentous actin. The tubule formation was significantly inhibited by the depletion of 175-kD myosin from the S12 fraction but not BY-2 myosin VIII-1. Furthermore, a recombinant carboxyl-terminal tail region of 175-kD myosin also suppressed ER tubule formation. The tips of tubules moved along filamentous actin during tubule elongation. These results indicated that the motive force generated by the actomyosin system contributes to the formation of ER tubules, suggesting that myosin XI is responsible not only for the transport of ER in cytoplasm but also for the reticular organization of cortical ER. PMID:21427277

Alterations in rat cardiac myosin isozymes induced by whole-body irradiation are prevented by 3,5,3'-L-triiodothyronine

Energy Technology Data Exchange (ETDEWEB)

Litten, R.Z.; Fein, H.G.; Gainey, G.T.; Walden, T.L.; Smallridge, R.C. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

1990-01-01

Changes in cardiac myosin isozymes and serum thyroid hormone levels were investigated in rats following 10 Gy whole-body gamma irradiation. The percent beta-myosin heavy chain increased from 21.3 {plus minus} 1.8 to 28.1 {plus minus} 6.8 (NS) at 3-day postirradiation, 37.7 {plus minus} 1.9 (P less than .001) at 6-day postirradiation, and 43.8 {plus minus} 3.3 (P less than .001) at 9-day postirradiation. Along with the change in myosin isozymes was a significant 53% decrease (P less than .001) in the serum thyroxine (T4) level by day 3 postirradiation, remaining depressed through day 9 postirradiation. The serum 3,5,3'-triiodothyronine (T3) level, however, was normal until day 9, when significant depression was also observed. In contrast, the thyroid-stimulating hormone (TSH) level was significantly increased by fourfold at day 3, returning to near normal values by day 9 postirradiation. Daily injections of physiological doses of T3 (0.3 microgram/100 g body weight) prevented the change in the myosin isozymes following whole-body irradiation. Daily pharmacological injections of T3 (3.0 micrograms/100 g body weight) to the irradiated rats produced a further decrease in the percent beta-myosin heavy chain (below control values) indicating tissue hyperthyroidism. Thus, this study suggests that the change in myosin isozymes following whole-body irradiation is caused by an alteration in thyroid hormone activity.

Stable and dynamic microtubules coordinately shape the myosin activation zone during cytokinetic furrow formation

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Foe, Victoria E.; von Dassow, George

2008-01-01

The cytokinetic furrow arises from spatial and temporal regulation of cortical contractility. To test the role microtubules play in furrow specification, we studied myosin II activation in echinoderm zygotes by assessing serine19-phosphorylated regulatory light chain (pRLC) localization after precisely timed drug treatments. Cortical pRLC was globally depressed before cytokinesis, then elevated only at the equator. We implicated cell cycle biochemistry (not microtubules) in pRLC depression, and differential microtubule stability in localizing the subsequent myosin activation. With no microtubules, pRLC accumulation occurred globally instead of equatorially, and loss of just dynamic microtubules increased equatorial pRLC recruitment. Nocodazole treatment revealed a population of stable astral microtubules that formed during anaphase; among these, those aimed toward the equator grew longer, and their tips coincided with cortical pRLC accumulation. Shrinking the mitotic apparatus with colchicine revealed pRLC suppression near dynamic microtubule arrays. We conclude that opposite effects of stable versus dynamic microtubules focuses myosin activation to the cell equator during cytokinesis. PMID:18955555

Pigment granule translocation in red ovarian chromatophores from the palaemonid shrimp Macrobrachium olfersi (Weigmann, 1836): functional roles for the cytoskeleton and its molecular motors.

Science.gov (United States)

Milograna, Sarah Ribeiro; Ribeiro, Márcia Regina; Baqui, Munira Muhammad Abdel; McNamara, John Campbell

2014-12-01

The binding of red pigment concentrating hormone (RPCH) to membrane receptors in crustacean chromatophores triggers Ca²⁺/cGMP signaling cascades that activate cytoskeletal motors, driving pigment granule translocation. We investigate the distributions of microfilaments and microtubules and their associated molecular motors, myosin and dynein, by confocal and transmission electron microscopy, evaluating a functional role for the cytoskeleton in pigment translocation using inhibitors of polymer turnover and motor activity in vitro. Microtubules occupy the chromatophore cell extensions whether the pigment granules are aggregated or dispersed. The inhibition of microtubule turnover by taxol induces pigment aggregation and inhibits re-dispersion. Phalloidin-FITC actin labeling, together with tannic acid fixation and ultrastructural analysis, reveals that microfilaments form networks associated with the pigment granules. Actin polymerization induced by jasplaquinolide strongly inhibits RPCH-induced aggregation, causes spontaneous pigment dispersion, and inhibits pigment re-dispersion. Inhibition of actin polymerization by latrunculin-A completely impedes pigment aggregation and re-dispersion. Confocal immunocytochemistry shows that non-muscle myosin II (NMMII) co-localizes mainly with pigment granules while blebbistatin inhibition of NMMII strongly reduces the RPCH response, also inducing spontaneous pigment dispersion. Myosin II and dynein also co-localize with the pigment granules. Inhibition of dynein ATPase by erythro-9-(2-hydroxy-3-nonyl) adenine induces aggregation, inhibits RPCH-triggered aggregation, and inhibits re-dispersion. Granule aggregation and dispersion depend mainly on microfilament integrity although microtubules may be involved. Both cytoskeletal polymers are functional only when subunit turnover is active. Myosin and dynein may be the molecular motors that drive pigment aggregation. These mechanisms of granule translocation in crustacean

Botulinum Toxin Type A Inhibits α-Smooth Muscle Actin and Myosin II Expression in Fibroblasts Derived From Scar Contracture.

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Chen, Minliang; Yan, Tongtong; Ma, Kui; Lai, Linying; Liu, Chang; Liang, Liming; Fu, Xiaobing

2016-09-01

Scar contracture (SC) is one of the most common complications resulting from major burn injuries. Numerous treatments are currently available but they do not always yield excellent therapeutic results. Recent reports suggest that botulinum toxin type A (BTXA) is effective at reducing SC clinically, but the molecular mechanism for this action is unknown. α-Smooth muscle actin (α-SMA) and myosin II are the main components of stress fibers, which are the contractile structures of fibroblasts. The effects of BTXA on α-SMA and myosin II in SC are still unknown. This study aimed to explore the effect of BTXA on α-SMA and myosin II expression in fibroblasts derived from SC and to elucidate its actual mechanism further. Fibroblasts were isolated from tissue specimens of SC. Fibroblasts were cultured in Dulbecco modified Eagle medium with different concentrations of BTXA and their proliferation was analyzed through the tetrazolium-based colorimetric method at 1, 4, and 7 days. Proteins of α-SMA and myosin II were checked using Western blot in fibroblasts treated with different concentrations of BTXA at 1, 4, and 7 days. Fibroblasts without BTXA treatment had a higher proliferation than that in other groups, which indicated that the proliferation of fibroblasts was significantly inhibited by BTXA (P < 0.05). Proteins of α-SMA and myosin II between fibroblasts with BTXA and fibroblasts without BTXA are statistically significant (P < 0.05). These results suggest that BTXA effectively inhibited the growth of fibroblasts derived from SC and reduced the expression of α-SMA and myosin II, which provided theoretical support for the application of BTXA to control SC.

Myosin helical pitch angle as a quantitative imaging biomarker for characterization of cardiac programming in fetal growth restriction measured by polarization second harmonic microscopy

Science.gov (United States)

Amat-Roldan, I.; Psilodimitrakopoulos, S.,; Eixarch, E.,; Torre, I.; Wotjas, B.; Crispi, F.; Figueras, F.; Artigas, D.,; Loza-Alvarez, P.; Gratacos, E.,

2009-07-01

Fetal growth restriction (FGR) has recently shown a strong association with cardiac programming which predisposes to cardiovascular mortality in adulthood. Polarization Second Harmonic Microscopy can quantify molecular architecture changes with high sensitivity in cardiac myofibrils. In this work, we use myosin helical pitch angle as an example to quantify such alterations related to this high risk population. Importantly, this shows a potential use of the technique as an early diagnostic tool and an alternative method to understand pathophysiological processes.

Metastasis-associated protein Mts1 (S100A4) inhibits CK2-mediated phosphorylation and self-assembly of the heavy chain of nonmuscle myosin

DEFF Research Database (Denmark)

Kriajevska, M; Bronstein, I B; Scott, D J

2000-01-01

a regulatory role in the myosin assembly. In the presence of calcium, Mts1 binds at the C-terminal end of the myosin heavy chain close to the site of phosphorylation by protein kinase CK2 (Ser1944). In the present study, we have shown that interaction of Mts1 with the human platelet myosin or C...

Orientation of spin-labeled light chain 2 of myosin heads in muscle fibers.

Science.gov (United States)

Arata, T

1990-07-20

Electron paramagnetic resonance (e.p.r.) spectroscopy has been used to monitor the orientation of spin labels attached rigidly to a reactive SH residue on the light chain 2 (LC2) of myosin heads in muscle fibers. e.p.r. spectra from spin-labeled myosin subfragment-1 (S1), allowed to diffuse into unlabeled rigor (ATP-free) fibers, were roughly approximated by a narrow angular distribution of spin labels centered at 66 degrees relative to the fiber axis, indicating a uniform orientation of S1 bound to actin. On the other hand, spectra from spin-labeled heavy meromyosin (HMM) were roughly approximated by two narrow angular distributions centered at 42 degrees and 66 degrees, suggesting that the LC2 domains of the two HMM heads have different orientations. In contrast to S1 or HMM, the spectra from rigor fibers, in which LC2 of endogenous myosin heads was labeled, showed a random orientation which may be due to distortion imposed by the structure of the filament lattice and the mismatch of the helical periodicities of the thick and thin filaments. However, spectra from the fibers in the presence of ATP analog 5'-adenylyl imidodiphosphate (AMPPNP) were approximated by two narrow angular distributions similar to those obtained with HMM. Thus, AMPPNP may cause the LC2 domain to be less flexible and/or the S2 portion to be more flexible, so as to release the distortion of the LC2 domain and make it return to its natural position. At high ionic strength, AMPPNP disoriented the spin labels as ATP did under relaxing conditions, suggesting that the myosin head is detached from and/or weakly (flexibly) attached to a thin filament.

Characteristics of myosin profile in human vastus lateralis muscle in relation to training background.

Science.gov (United States)

Zawadowska, B; Majerczak, J; Semik, D; Karasinski, J; Kolodziejski, L; Kilarski, W M; Duda, K; Zoladz, J A

2004-01-01

Twenty-four male volunteers (mean +/- SD: age 25.4+/-5.8 years, height 178.6+/-5.5 cm, body mass 72.1+/-7.7 kg) of different training background were investigated and classified into three groups according to their physical activity and sport discipline: untrained students (group A), national and sub-national level endurance athletes (group B, 7.8+/-2.9 years of specialised training) and sprint-power athletes (group C, 12.8+/-8.7 years of specialised training). Muscle biopsies of vastus lateralis were analysed histochemically for mATPase and SDH activities, immunohistochemically for fast and slow myosin, and electrophoretically followed by Western immunoblotting for myosin heavy chain (MyHC) composition. Significant differences (Pski-jumping, volleyball, soccer and modern dance. Furthermore, the relative amount of the fastest MyHCIIX isoform in vastus lateralis muscle was significantly lower in the athletes from group C than in students (group A). We conclude that the myosin profile in the athletes belonging to group C was unfavourable for their sport disciplines. This could be the reason why those athletes did not reach international level despite of several years of training.

Characterization of the minimum domain required for targeting budding yeast myosin II to the site of cell division

Directory of Open Access Journals (Sweden)

Tolliday Nicola J

2006-06-01

Full Text Available Abstract Background All eukaryotes with the exception of plants use an actomyosin ring to generate a constriction force at the site of cell division (cleavage furrow during mitosis and meiosis. The structure and filament forming abilities located in the C-terminal or tail region of one of the main components, myosin II, are important for localising the molecule to the contractile ring (CR during cytokinesis. However, it remains poorly understood how myosin II is recruited to the site of cell division and how this recruitment relates to myosin filament assembly. Significant conservation between species of the components involved in cytokinesis, including those of the CR, allows the use of easily genetically manipulated organisms, such as budding yeast (Saccharomyces cerevisiae, in the study of cytokinesis. Budding yeast has a single myosin II protein, named Myo1. Unlike most other class II myosins, the tail of Myo1 has an irregular coiled coil. In this report we use molecular genetics, biochemistry and live cell imaging to characterize the minimum localisation domain (MLD of budding yeast Myo1. Results We show that the MLD is a small region in the centre of the tail of Myo1 and that it is both necessary and sufficient for localisation of Myo1 to the yeast bud neck, the pre-determined site of cell division. Hydrodynamic measurements of the MLD, purified from bacteria or yeast, show that it is likely to exist as a trimer. We also examine the importance of a small region of low coiled coil forming probability within the MLD, which we call the hinge region. Removal of the hinge region prevents contraction of the CR. Using fluorescence recovery after photobleaching (FRAP, we show that GFP-tagged MLD is slightly more dynamic than the GFP-tagged full length molecule but less dynamic than the GFP-tagged Myo1 construct lacking the hinge region. Conclusion Our results define the intrinsic determinant for the localization of budding yeast myosin II and show

Identification and biochemical analysis of Slac2-c/MyRIP as a Rab27A-, myosin Va/VIIa-, and actin-binding protein.

Science.gov (United States)

Kuroda, Taruho S; Fukuda, Mitsunori

2005-01-01

Slac2-c/MyRIP is a specific Rab27A-binding protein that contains an N-terminal synaptotagmin-like protein (Slp) homology domain (SHD, a newly identified GTP-Rab27A-binding motif), but in contrast to the Slp family proteins, it lacks C-terminal tandem C2 domains. In vitro Slac2-c simultaneously directly interacts with both Rab27A and an actin-based motor protein, myosin Va, via its N-terminal SHD and middle region, respectively, consistent with the fact that the overall structure of Slac2-c is similar to that of Slac2-a/melanophilin, a linker protein between Rab27A and myosin Va in the melanosome transport in melanocytes. Unlike Slac2-a, however, the middle region of Slac2-c interacts with two types of myosins, myosin Va and myosin VIIa. In addition, the most C-terminal part of both Slac2-a and Slac2-c functions as an actin-binding domain: it directly interacts with globular and fibrous actin in vitro, and the actin-binding domain of Slac2-a and Slac2-c colocalizes with actin filaments when it is expressed in living cells (i.e., PC12 cells and mouse melanocytes). In this chapter we describe the methods that have been used to analyze the protein-protein interactions of Slac2-c, specifically with Rab27A, myosin Va/VIIa, and actin.

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Wesley Smith

Level-1 Trigger Hardware and Software The hardware of the trigger components has been mostly finished. The ECAL Endcap Trigger Concentrator Cards (TCC) are in production while Barrel TCC firmware has been upgraded, and the Trigger Primitives can now be stored by the Data Concentrator Card for readout by the DAQ. The Regional Calorimeter Trigger (RCT) system is complete, and the timing is being finalized. All 502 HCAL trigger links to RCT run without error. The HCAL muon trigger timing has been equalized with DT, RPC, CSC and ECAL. The hardware and firmware for the Global Calorimeter Trigger (GCT) jet triggers are being commissioned and data from these triggers is available for readout. The GCT energy sums from rings of trigger towers around the beam pipe beam have been changed to include two rings from both sides. The firmware for Drift Tube Track Finder, Barrel Sorter and Wedge Sorter has been upgraded, and the synchronization of the DT trigger is satisfactory. The CSC local trigger has operated flawlessly u...

Human Usher 1B/mouse shaker-1: the retinal phenotype discrepancy explained by the presence/absence of myosin VIIA in the photoreceptor cells.

Science.gov (United States)

el-Amraoui, A; Sahly, I; Picaud, S; Sahel, J; Abitbol, M; Petit, C

1996-08-01

Usher syndrome type 1 (USH1) associates severe congenital deafness, vestibular dysfunction and progressive retinitis pigmentosa leading to blindness. The gene encoding myosin VIIA is responsible for USH1B. Mutations in the murine orthologous gene lead to the shaker-1 phenotype, which manifests cochlear and vestibular dysfunction, without any retinal defect. To address this phenotypic discrepancy, the expression of myosin VIIA in retinal cells was analyzed in human and mouse during embryonic development and adult life. In the human embryo, myosin VIIA was present first in the pigment epithelium cells, and later in these cells as well as in the photoreceptor cells. In the adult human retina, myosin VIIA was present in both cell types. In contrast, in mouse, only pigment epithelium cells expressed the protein throughout development and adult life. Myosin VIIA was also found to be absent in the photoreceptor cells of other rodents (rat and guinea-pig), whereas these cells expressed the protein in amphibians, avians and primates. These observations suggest that retinitis pigmentosa of USH1B results from a primary rod and cone defect. The USH1B/shaker-1 paradigm illustrates a species-specific cell pattern of gene expression as a possible cause for the discrepancy between phenotypes involving defective orthologous genes in man and mouse. Interestingly, in the photoreceptor cells, myosin VIIA is mainly localized in the inner and base of outer segments as well as in the synaptic ending region where it is co-localized with the synaptic vesicles. Therefore, we suggest that myosin VIIA might play a role in the trafficking of ribbon-synaptic vesicle complexes and the renewal processes of the outer photoreceptor disks.

Confinement Sensing and Signal Optimization via Piezo1/PKA and Myosin II Pathways

Directory of Open Access Journals (Sweden)

Wei-Chien Hung

2016-05-01

Full Text Available Summary: Cells adopt distinct signaling pathways to optimize cell locomotion in different physical microenvironments. However, the underlying mechanism that enables cells to sense and respond to physical confinement is unknown. Using microfabricated devices and substrate-printing methods along with FRET-based biosensors, we report that, as cells transition from unconfined to confined spaces, intracellular Ca2+ level is increased, leading to phosphodiesterase 1 (PDE1-dependent suppression of PKA activity. This Ca2+ elevation requires Piezo1, a stretch-activated cation channel. Moreover, differential regulation of PKA and cell stiffness in unconfined versus confined cells is abrogated by dual, but not individual, inhibition of Piezo1 and myosin II, indicating that these proteins can independently mediate confinement sensing. Signals activated by Piezo1 and myosin II in response to confinement both feed into a signaling circuit that optimizes cell motility. This study provides a mechanism by which confinement-induced signaling enables cells to sense and adapt to different physical microenvironments. : Hung et al. demonstrate that a Piezo1-dependent intracellular calcium increase negatively regulates protein kinase A (PKA as cells transit from unconfined to confined spaces. The Piezo1/PKA and myosin II signaling modules constitute two confinement-sensing mechanisms. This study provides a paradigm by which signaling enables cells to sense and adapt to different microenvironments.

Regulation of actomyosin ATPase activity by troponin-tropomyosin: effect of the binding of the myosin subfragment 1 (S-1) ATP complex

International Nuclear Information System (INIS)

Greene, L.E.; Williams, D.L. Jr.; Eisenberg, E.

1987-01-01

In the authors' model of regulation, the observed lack of cooperativity in the binding of myosin subfragment 1 (S-1) with bound ATP to the troponin-tropomyosin-actin complex (regulated actin) is explained by S-1 ATP having about the same affinity for the conformation of the regulated actin that activates the myosin ATPase activity (turned-on form) and the conformation that does not activate the myosin ATPase activity (turned-off form). This predicts that, in the absence of Ca 2+ , S-1 ATP should not turn on the regulated actin filament. In the present study, they tested this prediction by using either unmodified S-1 or S-1 chemically modified with N,N'-p-phenylenedimaleimide (pPDM S-1) so that functionally it acts like S-1 ATP, although it does not hydrolyze ATP. [ 14 C]pPDM and [ 32 P]ATP were used as tracers. They found that, in the absence of Ca 2+ , neither S-1 ATP nor pPDM S-1 ATP significantly turns on the ATPase activity of the regulated complex of actin and S-1 (acto S-1). In contrast, in the presence of Ca 2+ , pPDM S-1 ATP binding almost completely turns on the regulated acto S-1 ATPase activity. These results can be explained by their original cooperativity model, with pPDM S-1 ATP binding only ≅ 2 fold more strongly to the turned-on form that to the turned-off form of regulated actin. However, the results are not consistent with our alternative model, which predicts that if pPDM S-1 ATP binds to actin in the absence of Ca 2+ but does not turn on the ATPase activity, then it should also turn on the ATPase activity in the presence of Ca 2+

Lack of replication for the myosin-18B association with mathematical ability in independent cohorts

Science.gov (United States)

Pettigrew, K A; Fajutrao Valles, S F; Moll, K; Northstone, K; Ring, S; Pennell, C; Wang, C; Leavett, R; Hayiou-Thomas, M E; Thompson, P; Simpson, N H; Fisher, S E; Whitehouse, A J O; Snowling, M J; Newbury, D F; Paracchini, S

2015-01-01

Twin studies indicate that dyscalculia (or mathematical disability) is caused partly by a genetic component, which is yet to be understood at the molecular level. Recently, a coding variant (rs133885) in the myosin-18B gene was shown to be associated with mathematical abilities with a specific effect among children with dyslexia. This association represents one of the most significant genetic associations reported to date for mathematical abilities and the only one reaching genome-wide statistical significance. We conducted a replication study in different cohorts to assess the effect of rs133885 maths-related measures. The study was conducted primarily using the Avon Longitudinal Study of Parents and Children (ALSPAC), (N = 3819). We tested additional cohorts including the York Cohort, the Specific Language Impairment Consortium (SLIC) cohort and the Raine Cohort, and stratified them for a definition of dyslexia whenever possible. We did not observe any associations between rs133885 in myosin-18B and mathematical abilities among individuals with dyslexia or in the general population. Our results suggest that the myosin-18B variant is unlikely to be a main factor contributing to mathematical abilities. PMID:25778778

The effect of the substitution of D{sub 2}O for H{sub 2}O on the degradation of myosin {beta} in solution by heat and by {sup 60}Co {gamma} radiation (1962); Effet de la substitution de D{sub 2}O a H{sub 2}O sur l'alteration de la Myosine B en solution par la chaleur et par les rayons {gamma} du {sup 60}CO (1962)

Energy Technology Data Exchange (ETDEWEB)

Pinset-Harstrom, I.; Fritsch, A. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1962-07-01

(1) Alterations of myosin B produced by heat or irradiation are shown to be qualitatively identical as demonstrated by analytical centrifugation. (2) A considerable isotope effect was demonstrated using 75 per cent D{sub 2}O in the solvent. The sensitivity of myosin B to heat and irradiation is discussed in the light of this isotope effect. (3) Polymers appearing upon heat treatment of myosin B seem to be of a very different nature than the polymers occurring alter a similar treatment upon myosin A. Polymers obtained from myosin B can be depolymerized by ATP and they appear in a much narrower temperature range than myosin A polymers. This fact indicates a considerable difference in the activation enthalpies in the two reactions. (authors) [French] (1) Cette etude montre que les alterations de la myosine B provoquees par la chaleur et par l'irradiation aux rayons {gamma} sont - telles qu'elles apparaissent a l'ultracentrifugation analytique - qualitativement semblables. (2) Nous avons observe un effet isotopique considerable de la presence de 75 pour cent de D{sub 2}O dans le solvant sur la sensibilite de la myosine B envers ces deux agents, et nous avons presente une tentative d'explication de ce fait. (3) Les polymeres qui apparaissent apres un traitement par la chaleur de la myosine semblent etre d'une nature tres differente des polymeres que l'on voit apparaitre apres un traitement identique de la myosine A. Ceux obtenus a partir de le myosine B sont depolymerisables par l'intermediaire de l'ATP et apparaissent dans une zone de temperature beaucoup plus etroite que celles de la myosine A. Ce dernier fait indique une difference considerable de l'enthalpie d'activation des deux reactions. (auteurs)

The effect of the substitution of D{sub 2}O for H{sub 2}O on the degradation of myosin {beta} in solution by heat and by {sup 60}Co {gamma} radiation (1962); Effet de la substitution de D{sub 2}O a H{sub 2}O sur l'alteration de la Myosine B en solution par la chaleur et par les rayons {gamma} du {sup 60}CO (1962)

Energy Technology Data Exchange (ETDEWEB)

Pinset-Harstrom, I; Fritsch, A [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1962-07-01

(1) Alterations of myosin B produced by heat or irradiation are shown to be qualitatively identical as demonstrated by analytical centrifugation. (2) A considerable isotope effect was demonstrated using 75 per cent D{sub 2}O in the solvent. The sensitivity of myosin B to heat and irradiation is discussed in the light of this isotope effect. (3) Polymers appearing upon heat treatment of myosin B seem to be of a very different nature than the polymers occurring alter a similar treatment upon myosin A. Polymers obtained from myosin B can be depolymerized by ATP and they appear in a much narrower temperature range than myosin A polymers. This fact indicates a considerable difference in the activation enthalpies in the two reactions. (authors) [French] (1) Cette etude montre que les alterations de la myosine B provoquees par la chaleur et par l'irradiation aux rayons {gamma} sont - telles qu'elles apparaissent a l'ultracentrifugation analytique - qualitativement semblables. (2) Nous avons observe un effet isotopique considerable de la presence de 75 pour cent de D{sub 2}O dans le solvant sur la sensibilite de la myosine B envers ces deux agents, et nous avons presente une tentative d'explication de ce fait. (3) Les polymeres qui apparaissent apres un traitement par la chaleur de la myosine semblent etre d'une nature tres differente des polymeres que l'on voit apparaitre apres un traitement identique de la myosine A. Ceux obtenus a partir de le myosine B sont depolymerisables par l'intermediaire de l'ATP et apparaissent dans une zone de temperature beaucoup plus etroite que celles de la myosine A. Ce dernier fait indique une difference considerable de l'enthalpie d'activation des deux reactions. (auteurs)

The force dependence of isometric and concentric potentiation in mouse muscle with and without skeletal myosin light chain kinase.

Science.gov (United States)

Gittings, William; Aggarwal, Harish; Stull, James T; Vandenboom, Rene

2015-01-01

The isometric potentiation associated with myosin phosphorylation is force dependent. The purpose of this study was to assess the influence of a pre-existing period of isometric force on the concentric force potentiation displayed by mouse muscles with and without the ability to phosphorylate myosin. We tested isometric (ISO) and concentric (CON) potentiation, as well as concentric potentiation after isometric force (ISO-CON), in muscles from wild-type (WT) and skeletal myosin light chain kinase-deficient (skMLCK(-/-)) mice. A conditioning stimulus increased (i.e., potentiated) mean concentric force in the ISO-CON and CON conditions to 1.31 ± 0.02 and 1.35 ± 0.02 (WT) and to 1.19 ± 0.02 and 1.21 ± 0.01 (skMLCK(-/-)) of prestimulus levels, respectively (data n = 6-8, p muscles.

TRIGGER

CERN Multimedia

Wesley Smith

Level-1 Trigger Hardware and Software The trigger synchronization procedures for running with cosmic muons and operating with the LHC were reviewed during the May electronics week. Firmware maintenance issues were also reviewed. Link tests between the new ECAL endcap trigger concentrator cards (TCC48) and the Regional Calorimeter Trigger have been performed. Firmware for the energy sum triggers and an upgraded tau trigger of the Global Calorimeter Triggers has been developed and is under test. The optical fiber receiver boards for the Track-Finder trigger theta links of the DT chambers are now all installed. The RPC trigger is being made more robust by additional chamber and cable shielding and also by firmware upgrades. For the CSC’s the front-end and trigger motherboard firmware have been updated. New RPC patterns and DT/CSC lookup tables taking into account phi asymmetries in the magnetic field configuration are under study. The motherboard for the new pipeline synchronizer of the Global Trigg...

Expression of porcine myosin heavy chain 1 gene in Berkshire loins ...

African Journals Online (AJOL)

Expression of porcine myosin heavy chain 1 gene in Berkshire loins with a high pH24 value. Jin Hun Kang, Woo Young Bang, Eun Jung Kwon, Yong Hwa Lee, Da Hye Park, Eun Seok Cho, Min Ji Kim, Jong-Soon Choi, Hwa Chun Park, Beom Young Park, Chul Wook Kim ...

Regulation of nonmuscle myosin II during 3-methylcholanthrene induced dedifferentiation of C2C12 myotubes

Energy Technology Data Exchange (ETDEWEB)

Dey, Sumit K.; Saha, Shekhar; Das, Provas; Das, Mahua R.; Jana, Siddhartha S., E-mail: bcssj@iacs.res.in

2014-08-01

3-Methylcholanthrene (3MC) induces tumor formation at the site of injection in the hind leg of mice within 110 days. Recent reports reveal that the transformation of normal muscle cells to atypical cells is one of the causes for tumor formation, however the molecular mechanism behind this process is not well understood. Here, we show in an in vitro study that 3MC induces fragmentation of multinucleate myotubes into viable mononucleates. These mononucleates form colonies when they are seeded into soft agar, indicative of cellular transformation. Immunoblot analysis reveals that phosphorylation of myosin regulatory light chain (RLC{sub 20}) is 5.6±0.5 fold reduced in 3MC treated myotubes in comparison to vehicle treated myotubes during the fragmentation of myotubes. In contrast, levels of myogenic factors such as MyoD, Myogenin and cell cycle regulators such as Cyclin D, Cyclin E1 remain unchanged as assessed by real-time PCR array and reverse transcriptase PCR analysis, respectively. Interestingly, addition of the myosin light chain kinase inhibitor, ML-7, enhances the fragmentation, whereas phosphatase inhibitor perturbs the 3MC induced fragmentation of myotubes. These results suggest that decrease in RLC{sub 20} phosphorylation may be associated with the fragmentation step of dedifferentiation. - Highlights: • 3-Methylcholanthrene induces fragmentation of C2C12-myotubes. • Dedifferentiation can be divided into two steps – fragmentation and proliferation. • Fragmentation is associated with rearrangement of nonmuscle myosin II. • Genes associated with differentiation and proliferation are not altered during fragmentation. • Phosphorylation of myosin regulatory light chain is reduced during fragmentation.

Mechanochemical coupling in the myosin motor domain. I. Insights from equilibrium active-site simulations.

Directory of Open Access Journals (Sweden)

Haibo Yu

2007-02-01

Full Text Available Although the major structural transitions in molecular motors are often argued to couple to the binding of Adenosine triphosphate (ATP, the recovery stroke in the conventional myosin has been shown to be dependent on the hydrolysis of ATP. To obtain a clearer mechanistic picture for such "mechanochemical coupling" in myosin, equilibrium active-site simulations with explicit solvent have been carried out to probe the behavior of the motor domain as functions of the nucleotide chemical state and conformation of the converter/relay helix. In conjunction with previous studies of ATP hydrolysis with different active-site conformations and normal mode analysis of structural flexibility, the results help establish an energetics-based framework for understanding the mechanochemical coupling. It is proposed that the activation of hydrolysis does not require the rotation of the lever arm per se, but the two processes are tightly coordinated because both strongly couple to the open/close transition of the active site. The underlying picture involves shifts in the dominant population of different structural motifs as a consequence of changes elsewhere in the motor domain. The contribution of this work and the accompanying paper [] is to propose the actual mechanism behind these "population shifts" and residues that play important roles in the process. It is suggested that structural flexibilities at both the small and large scales inherent to the motor domain make it possible to implement tight couplings between different structural motifs while maintaining small free-energy drops for processes that occur in the detached states, which is likely a feature shared among many molecular motors. The significantly different flexibility of the active site in different X-ray structures with variable level arm orientations supports the notation that external force sensed by the lever arm may transmit into the active site and influence the chemical steps (nucleotide

Parathyroid hormone promotes the disassembly of cytoskeletal actin and myosin in cultured osteoblastic cells: Mediation by cyclic AMP

International Nuclear Information System (INIS)

Egan, J.J.; Gronowicz, G.; Rodan, G.A.

1991-01-01

Parathyroid hormone (PTH) alters the shape of osteoblastic cells both in vivo and in vitro. In this study, we examined the effect of PTH on cytoskeletal actin and myosin, estimated by polyacrylamide gel electrophoresis of Triton X-100 (1%) nonextractable proteins. After 2-5 minutes, PTH caused a rapid and transient decrease of 50-60% in polymerized actin and myosin associated with the Triton X-100 nonextractable cytoskeleton. Polymerized actin returned to control levels by 30 min. The PTH effect was dose-dependent with an IC50 of about 1 nM, and was partially inhibited by the (3-34) PTH antagonist. PTH caused a rapid transient rise in cyclic AMP (cAMP) in these cells that peaked at 4 min, while the nadir in cytoskeletal actin and myosin was recorded around 5 min. The intracellular calcium chelator Quin-2/AM (10 microM) also decreased cytoskeletal actin and myosin, to the same extent as did PTH (100 nM). To distinguish between cAMP elevation and Ca++ reduction as mediators of PTH action, we measured the phosphorylation of the 20 kD (PI 4.9) myosin light chain in cells preincubated with [32P]-orthophosphate. The phosphorylation of this protein decreased within 2-3 min after PTH addition and returned to control levels after 5 min. The calcium ionophore A-23187 did not antagonize this PTH effect. Visualization of microfilaments with rhodamine-conjugated phalloidin showed that PTH altered the cytoskeleton by decreasing the number of stress fibers. These changes in the cytoskeleton paralleled changes in the shape of the cells from a spread configuration to a stellate form with retracting processes. The above findings indicate that the alteration in osteoblast shape produced by PTH involve relatively rapid and transient changes in cytoskeletal organization that appear to be mediated by cAMP

TRIGGER

CERN Multimedia

W. Smith

2012-01-01

  Level-1 Trigger The Level-1 Trigger group is ready to deploy improvements to the L1 Trigger algorithms for 2012. These include new high-PT patterns for the RPC endcap, an improved CSC PT assignment, a new PT-matching algorithm for the Global Muon Trigger, and new calibrations for ECAL, HCAL, and the Regional Calorimeter Trigger. These should improve the efficiency, rate, and stability of the L1 Trigger. The L1 Trigger group also is migrating the online systems to SLC5. To make the data transfer from the Global Calorimeter Trigger to the Global Trigger more reliable and also to allow checking the data integrity online, a new optical link system has been developed by the GCT and GT groups and successfully tested at the CMS electronics integration facility in building 904. This new system is now undergoing further tests at Point 5 before being deployed for data-taking this year. New L1 trigger menus have recently been studied and proposed by Emmanuelle Perez and the L1 Detector Performance Group...

Blebbistain, a myosin II inhibitor, as a novel strategy to regulate detrusor contractility in a rat model of partial bladder outlet obstruction.

Directory of Open Access Journals (Sweden)

Xinhua Zhang

Full Text Available Partial bladder outlet obstruction (PBOO, a common urologic pathology mostly caused by benign prostatic hyperplasia, can coexist in 40-45% of patients with overactive bladder (OAB and is associated with detrusor overactivity (DO. PBOO that induces DO results in alteration in bladder myosin II type and isoform composition. Blebbistatin (BLEB is a myosin II inhibitor we recently demonstrated potently relaxed normal detrusor smooth muscle (SM and reports suggest varied BLEB efficacy for different SM myosin (SMM isoforms and/or SMM vs nonmuscle myosin (NMM. We hypothesize BLEB inhibition of myosin II as a novel contraction protein targeted strategy to regulate DO. Using a surgically-induced male rat PBOO model, organ bath contractility, competitive and Real-Time-RT-PCR were performed. It was found that obstructed-bladder weight significantly increased 2.74-fold while in vitro contractility of detrusor to various stimuli was impaired ∼50% along with decreased shortening velocity. Obstruction also altered detrusor spontaneous activities with significantly increased amplitude but depressed frequency. PBOO switched bladder from a phasic-type to a more tonic-type SM. Expression of 5' myosin heavy chain (MHC alternatively spliced isoform SM-A (associated with tonic-type SM increased 3-fold while 3' MHC SM1 and essential light chain isoform MLC(17b also exhibited increased relative expression. Total SMMHC expression was decreased by 25% while the expression of NMM IIB (SMemb was greatly increased by 4.5-fold. BLEB was found to completely relax detrusor strips from both sham-operated and PBOO rats pre-contracted with KCl, carbachol or electrical field stimulation although sensitivity was slightly decreased (20% only at lower doses for PBOO. Thus we provide the first thorough characterization of the response of rat bladder myosin to PBOO and demonstrate complete BLEB-induced PBOO bladder SM relaxation. Furthermore, the present study provides valuable

Myosin heavy chain-like localizes at cell contact sites during Drosophila myoblast fusion and interacts in vitro with Rolling pebbles 7

Energy Technology Data Exchange (ETDEWEB)

Bonn, Bettina R.; Rudolf, Anja; Hornbruch-Freitag, Christina; Daum, Gabor; Kuckwa, Jessica; Kastl, Lena; Buttgereit, Detlev [Developmental Biology, Department of Biology, Philipps-Universität Marburg, Karl-von-Frisch-Strasse 8, 35037 Marburg (Germany); Renkawitz-Pohl, Renate, E-mail: renkawit@biologie.uni-marburg.de [Developmental Biology, Department of Biology, Philipps-Universität Marburg, Karl-von-Frisch-Strasse 8, 35037 Marburg (Germany)

2013-02-15

Besides representing the sarcomeric thick filaments, myosins are involved in many cellular transport and motility processes. Myosin heavy chains are grouped into 18 classes. Here we show that in Drosophila, the unconventional group XVIII myosin heavy chain-like (Mhcl) is transcribed in the mesoderm of embryos, most prominently in founder cells (FCs). An ectopically expressed GFP-tagged Mhcl localizes in the growing muscle at cell–cell contacts towards the attached fusion competent myoblast (FCM). We further show that Mhcl interacts in vitro with the essential fusion protein Rolling pebbles 7 (Rols7), which is part of a protein complex established at cell contact sites (Fusion-restricted Myogenic-Adhesive Structure or FuRMAS). Here, branched F-actin is likely needed to widen the fusion pore and to integrate the myoblast into the growing muscle. We show that the localization of Mhcl is dependent on the presence of Rols7, and we postulate that Mhcl acts at the FuRMAS as an actin motor protein. We further show that Mhcl deficient embryos develop a wild-type musculature. We thus propose that Mhcl functions redundantly to other myosin heavy chains in myoblasts. Lastly, we found that the protein is detectable adjacent to the sarcomeric Z-discs, suggesting an additional function in mature muscles. - Highlights: ► The class XVIII myosin encoding gene Mhcl is transcribed in the mesoderm. ► Mhcl localization at contact sites of fusing myoblasts depends on Rols7. ► Mhcl interacts in vitro with Rols7 which is essential for myogenesis. ► Functional redundancy with other myosins is likely as mutants show no muscle defects. ► Mhcl localizes adjacent to Z-discs of sarcomeres and might support muscle integrity.

Myosin heavy chain-like localizes at cell contact sites during Drosophila myoblast fusion and interacts in vitro with Rolling pebbles 7

International Nuclear Information System (INIS)

Bonn, Bettina R.; Rudolf, Anja; Hornbruch-Freitag, Christina; Daum, Gabor; Kuckwa, Jessica; Kastl, Lena; Buttgereit, Detlev; Renkawitz-Pohl, Renate

2013-01-01

Besides representing the sarcomeric thick filaments, myosins are involved in many cellular transport and motility processes. Myosin heavy chains are grouped into 18 classes. Here we show that in Drosophila, the unconventional group XVIII myosin heavy chain-like (Mhcl) is transcribed in the mesoderm of embryos, most prominently in founder cells (FCs). An ectopically expressed GFP-tagged Mhcl localizes in the growing muscle at cell–cell contacts towards the attached fusion competent myoblast (FCM). We further show that Mhcl interacts in vitro with the essential fusion protein Rolling pebbles 7 (Rols7), which is part of a protein complex established at cell contact sites (Fusion-restricted Myogenic-Adhesive Structure or FuRMAS). Here, branched F-actin is likely needed to widen the fusion pore and to integrate the myoblast into the growing muscle. We show that the localization of Mhcl is dependent on the presence of Rols7, and we postulate that Mhcl acts at the FuRMAS as an actin motor protein. We further show that Mhcl deficient embryos develop a wild-type musculature. We thus propose that Mhcl functions redundantly to other myosin heavy chains in myoblasts. Lastly, we found that the protein is detectable adjacent to the sarcomeric Z-discs, suggesting an additional function in mature muscles. - Highlights: ► The class XVIII myosin encoding gene Mhcl is transcribed in the mesoderm. ► Mhcl localization at contact sites of fusing myoblasts depends on Rols7. ► Mhcl interacts in vitro with Rols7 which is essential for myogenesis. ► Functional redundancy with other myosins is likely as mutants show no muscle defects. ► Mhcl localizes adjacent to Z-discs of sarcomeres and might support muscle integrity

TRIGGER

CERN Multimedia

Wesley Smith

Level-1 Trigger Hardware and Software The production of the trigger hardware is now basically finished, and in time for the turn-on of the LHC. The last boards produced are the Trigger Concentrator Cards for the ECAL Endcaps (TCC-EE). After the recent installation of the four EE Dees, the TCC-EE prototypes were used for their commissioning. Production boards are arriving and are being tested continuously, with the last ones expected in November. The Regional Calorimeter Trigger hardware is fully integrated after installation of the last EE cables. Pattern tests from the HCAL up to the GCT have been performed successfully. The HCAL triggers are fully operational, including the connection of the HCAL-outer and forward-HCAL (HO/HF) technical triggers to the Global Trigger. The HCAL Trigger and Readout (HTR) board firmware has been updated to permit recording of the tower “feature bit” in the data. The Global Calorimeter Trigger hardware is installed, but some firmware developments are still n...

Lead reduces tension development and the myosin ATPase activity of the rat right ventricular myocardium

Directory of Open Access Journals (Sweden)

D.V. Vassallo

2008-09-01

Full Text Available Lead (Pb2+ poisoning causes hypertension, but little is known regarding its acute effects on cardiac contractility. To evaluate these effects, force was measured in right ventricular strips that were contracting isometrically in 45 male Wistar rats (250-300 g before and after the addition of increasing concentrations of lead acetate (3, 7, 10, 30, 70, 100, and 300 µM to the bath. Changes in rate of stimulation (0.1-1.5 Hz, relative potentiation after pauses of 15, 30, and 60 s, effect of Ca2+ concentration (0.62, 1.25, and 2.5 mM, and the effect of isoproterenol (20 ng/mL were determined before and after the addition of 100 µM Pb2+. Effects on contractile proteins were evaluated after caffeine treatment using tetanic stimulation (10 Hz and measuring the activity of the myosin ATPase. Pb2+ produced concentration-dependent force reduction, significant at concentrations greater than 30 µM. The force developed in response to increasing rates of stimulation became smaller at 0.5 and 0.8 Hz. Relative potentiation increased after 100 µM Pb2+ treatment. Extracellular Ca2+ increment and isoproterenol administration increased force development but after 100 µM Pb2+ treatment the force was significantly reduced suggesting an effect of the metal on the sarcolemmal Ca2+ influx. Concentration of 100 µM Pb2+ also reduced the peak and plateau force of tetanic contractions and reduced the activity of the myosin ATPase. Results showed that acute Pb2+ administration, although not affecting the sarcoplasmic reticulum activity, produces a concentration-dependent negative inotropic effect and reduces myosin ATPase activity. Results suggest that acute lead administration reduced myocardial contractility by reducing sarcolemmal calcium influx and the myosin ATPase activity. These results also suggest that lead exposure is hazardous and has toxicological consequences affecting cardiac muscle.

Myosin II activity is required for functional leading-edge cells and closure of epidermal sheets in fish skin ex vivo.

Science.gov (United States)

Morita, Toshiyuki; Tsuchiya, Akiko; Sugimoto, Masazumi

2011-09-01

Re-epithelialization in skin wound healing is a process in which epidermal sheets grow and close the wound. Although the actin-myosin system is thought to have a pivotal role in re-epithelialization, its role is not clear. In fish skin, re-epithelialization occurs around 500 μm/h and is 50 times faster than in mammalian skin. We had previously reported that leading-edge cells of the epidermal outgrowth have both polarized large lamellipodia and "purse string"-like actin filament cables in the scale-skin culture system of medaka fish, Oryzias latipes (Cell Tissue Res, 2007). The actin purse-string (APS) is a supracellular contractile machinery in which adherens junctions (AJs) link intracellular myosin II-including actin cables between neighboring cells. In this study, we developed a modified "face-to-face" scale-skin culture system as an ex vivo model to study epidermal wound healing, and examined the role of the actin-myosin system in the rapid re-epithelialization using a myosin II ATPase inhibitor, blebbistatin. A low level of blebbistatin suppressed the formation of APS and induced the dissociation of keratocytes from the leading edge without attenuating the growth of the epidermal sheet or the migration rate of solitary keratocytes. AJs in the superficial layer showed no obvious changes elicited by blebbistatin. However, two epidermal sheets without APSs did not make a closure with each other, which was confirmed by inhibiting the connecting AJs between the superficial layers. These results suggest that myosin II activity is required for functional leading-edge cells and for epidermal closure.

TRIGGER

CERN Multimedia

by Wesley Smith

2010-01-01

Level-1 Trigger Hardware and Software The overall status of the L1 trigger has been excellent and the running efficiency has been high during physics fills. The timing is good to about 1%. The fine-tuning of the time synchronization of muon triggers is ongoing and will be completed after more than 10 nb-1 of data have been recorded. The CSC trigger primitive and RPC trigger timing have been refined. A new configuration for the CSC Track Finder featured modified beam halo cuts and improved ghost cancellation logic. More direct control was provided for the DT opto-receivers. New RPC Cosmic Trigger (RBC/TTU) trigger algorithms were enabled for collision runs. There is further work planned during the next technical stop to investigate a few of the links from the ECAL to the Regional Calorimeter Trigger (RCT). New firmware and a new configuration to handle trigger rate spikes in the ECAL barrel are also being tested. A board newly developed by the tracker group (ReTRI) has been installed and activated to block re...

Lack of replication for the myosin-18B association with mathematical ability in independent cohorts.

Science.gov (United States)

Pettigrew, K A; Fajutrao Valles, S F; Moll, K; Northstone, K; Ring, S; Pennell, C; Wang, C; Leavett, R; Hayiou-Thomas, M E; Thompson, P; Simpson, N H; Fisher, S E; Whitehouse, A J O; Snowling, M J; Newbury, D F; Paracchini, S

2015-04-01

Twin studies indicate that dyscalculia (or mathematical disability) is caused partly by a genetic component, which is yet to be understood at the molecular level. Recently, a coding variant (rs133885) in the myosin-18B gene was shown to be associated with mathematical abilities with a specific effect among children with dyslexia. This association represents one of the most significant genetic associations reported to date for mathematical abilities and the only one reaching genome-wide statistical significance. We conducted a replication study in different cohorts to assess the effect of rs133885 maths-related measures. The study was conducted primarily using the Avon Longitudinal Study of Parents and Children (ALSPAC), (N = 3819). We tested additional cohorts including the York Cohort, the Specific Language Impairment Consortium (SLIC) cohort and the Raine Cohort, and stratified them for a definition of dyslexia whenever possible. We did not observe any associations between rs133885 in myosin-18B and mathematical abilities among individuals with dyslexia or in the general population. Our results suggest that the myosin-18B variant is unlikely to be a main factor contributing to mathematical abilities. © 2015 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

Double phosphorylation of the myosin regulatory light chain during rigor mortis of bovine Longissimus muscle.

Science.gov (United States)

Muroya, Susumu; Ohnishi-Kameyama, Mayumi; Oe, Mika; Nakajima, Ikuyo; Shibata, Masahiro; Chikuni, Koichi

2007-05-16

To investigate changes in myosin light chains (MyLCs) during postmortem aging of the bovine longissimus muscle, we performed two-dimensional gel electrophoresis followed by identification with matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The results of fluorescent differential gel electrophoresis showed that two spots of the myosin regulatory light chain (MyLC2) at pI values of 4.6 and 4.7 shifted toward those at pI values of 4.5 and 4.6, respectively, by 24 h postmortem when rigor mortis was completed. Meanwhile, the MyLC1 and MyLC3 spots did not change during the 14 days postmortem. Phosphoprotein-specific staining of the gels demonstrated that the MyLC2 proteins at pI values of 4.5 and 4.6 were phosphorylated. Furthermore, possible N-terminal region peptides containing one and two phosphoserine residues were detected in each mass spectrum of the MyLC2 spots at pI values of 4.5 and 4.6, respectively. These results demonstrated that MyLC2 became doubly phosphorylated during rigor formation of the bovine longissimus, suggesting involvement of the MyLC2 phosphorylation in the progress of beef rigor mortis. Bovine; myosin regulatory light chain (RLC, MyLC2); phosphorylation; rigor mortis; skeletal muscle.

Characteristics of myosin profile in human vastus lateralis muscle in relation to training background.

Directory of Open Access Journals (Sweden)

J A Zoladz

2004-10-01

Full Text Available Twenty-four male volunteers (mean +/- SD: age 25.4+/-5.8 years, height 178.6+/-5.5 cm, body mass 72.1+/-7.7 kg of different training background were investigated and classified into three groups according to their physical activity and sport discipline: untrained students (group A, national and sub-national level endurance athletes (group B, 7.8+/-2.9 years of specialised training and sprint-power athletes (group C, 12.8+/-8.7 years of specialised training. Muscle biopsies of vastus lateralis were analysed histochemically for mATPase and SDH activities, immunohistochemically for fast and slow myosin, and electrophoretically followed by Western immunoblotting for myosin heavy chain (MyHC composition. Significant differences (P<0.05 regarding composition of muscle fibre types and myosin heavy chains were found only between groups A (41.7+/-1.6% of MyHCI, 40.8+/-4.0% of MyHCIIA and 17.5+/-4.0% of MyHCIIX and B (64.3+/-0.8% of MyHCI, 34.0+/-1.4% of MyHCIIA and 1.7+/-1.4% of MyHCIIX and groups A and C (59.6+/-1.6% of MyHCI, 37.2+/-1.3% of MyHCIIA and 3.2+/-1.3% of MyHCIIX. Unexpectedly, endurance athletes (group B such as long-distance runners, cyclists and cross country skiers, did not differ from the athletes representing short term, high power output sports (group C such as ice hockey, karate, ski-jumping, volleyball, soccer and modern dance. Furthermore, the relative amount of the fastest MyHCIIX isoform in vastus lateralis muscle was significantly lower in the athletes from group C than in students (group A. We conclude that the myosin profile in the athletes belonging to group C was unfavourable for their sport disciplines. This could be the reason why those athletes did not reach international level despite of several years of training.

TRIGGER

CERN Multimedia

Roberta Arcidiacono

2013-01-01

Trigger Studies Group (TSG) The Trigger Studies Group has just concluded its third 2013 workshop, where all POGs presented the improvements to the physics object reconstruction, and all PAGs have shown their plans for Trigger development aimed at the 2015 High Level Trigger (HLT) menu. The Strategy for Trigger Evolution And Monitoring (STEAM) group is responsible for Trigger menu development, path timing, Trigger performance studies coordination, HLT offline DQM as well as HLT release, menu and conditions validation – this last task in collaboration with PdmV (Physics Data and Monte Carlo Validation group). In the last months the group has delivered several HLT rate estimates and comparisons, using the available data and Monte Carlo samples. The studies were presented at the Trigger workshops in September and December, and STEAM has contacted POGs and PAGs to understand the origin of the discrepancies observed between 8 TeV data and Monte Carlo simulations. The most recent results show what the...

Myosin phosphorylation improves contractile economy of mouse fast skeletal muscle during staircase potentiation.

Science.gov (United States)

Bunda, Jordan; Gittings, William; Vandenboom, Rene

2018-01-30

Phosphorylation of the myosin regulatory light chain (RLC) by skeletal myosin light chain kinase (skMLCK) potentiates rodent fast twitch muscle but is an ATP-requiring process. Our objective was to investigate the effect of skMLCK-catalyzed RLC phosphorylation on the energetic cost of contraction and the contractile economy (ratio of mechanical output to metabolic input) of mouse fast twitch muscle in vitro (25°C). To this end, extensor digitorum longus (EDL) muscles from wild-type (WT) and from skMLCK-devoid (skMLCK -/- ) mice were subjected to repetitive low-frequency stimulation (10 Hz for 15 s) to produce staircase potentiation of isometric twitch force, after which muscles were quick frozen for determination of high-energy phosphate consumption (HEPC). During stimulation, WT muscles displayed significant potentiation of isometric twitch force while skMLCK -/- muscles did not (i.e. 23% versus 5% change, respectively). Consistent with this, RLC phosphorylation was increased ∼3.5-fold from the unstimulated control value in WT but not in skMLCK -/- muscles. Despite these differences, the HEPC of WT muscles was not greater than that of skMLCK -/- muscles. As a result of the increased contractile output relative to HEPC, the calculated contractile economy of WT muscles was greater than that of skMLCK -/- muscles. Thus, our results suggest that skMLCK-catalyzed phosphorylation of the myosin RLC increases the contractile economy of WT mouse EDL muscle compared with skMLCK -/- muscles without RLC phosphorylation. © 2018. Published by The Company of Biologists Ltd.

Clinical assessment of serum myosin light chain I in patients with dilated cardiomyopathy

Energy Technology Data Exchange (ETDEWEB)

Tsuda, Takashi; Izumi, Tohru; Shibata, Akira (Niigata Univ. (Japan). School of Medicine)

1992-08-01

Serum cardiac myosin light chain I (LCI) levels were quantitated using a radioimmunoassay kit in patients suspected of dilated cardiomyopathy (DCM). In this study, 55 patients were evaluated between 1986 and 1991. They were composed of 40 males and 15 females, and their age was 27-75 years (51[+-]11 years). The patients with renal dysfunction were excluded due to their serum creatinine levels (>2.0 mg/dl). After cardiac catheterization, endomyocardial biopsy and echocardiography, 44 patients were diagnosed as DCM, 2 as ischemic heart disease, 2 as chronic myocarditis, 1 as restrictive cardiomyopathy, 1 as dilated hypertrophic cardiomyopathy, 1 as cardiac amyloidosis, 2 as myopathy, 1 as polymyositis and 1 as hypothyroidism. Only two patients with DCM had elevated LCI. Besides, two patients with myopathy or hypothyroidism had elevated LCI. In the follow-up, one patient died suddenly 6 months later and another showed normal value of LCI four years later. LCI elevation in DCM was not related to either the severity of heart failure or cardiac function and it showed no finding of [sup 201]Tl myocardial defect or elevated CPK. The mechanism for elevated LCI in myopathy is related to a crossreaction with myosin light chain in the skeletal muscle. In hypothyroidism, it may be related to decreased clearance of normal LCI concentration or increased myosin light chain from damaged skeletal muscle. In conclusion, it is evident that the measurement of LCI is not helpful in clinical assessment of patients with DCM, but may be useful in detection of secondary cardiomyopathy. (author).

Clinical assessment of serum myosin light chain I in patients with dilated cardiomyopathy

International Nuclear Information System (INIS)

Tsuda, Takashi; Izumi, Tohru; Shibata, Akira

1992-01-01

Serum cardiac myosin light chain I (LCI) levels were quantitated using a radioimmunoassay kit in patients suspected of dilated cardiomyopathy (DCM). In this study, 55 patients were evaluated between 1986 and 1991. They were composed of 40 males and 15 females, and their age was 27-75 years (51±11 years). The patients with renal dysfunction were excluded due to their serum creatinine levels (>2.0 mg/dl). After cardiac catheterization, endomyocardial biopsy and echocardiography, 44 patients were diagnosed as DCM, 2 as ischemic heart disease, 2 as chronic myocarditis, 1 as restrictive cardiomyopathy, 1 as dilated hypertrophic cardiomyopathy, 1 as cardiac amyloidosis, 2 as myopathy, 1 as polymyositis and 1 as hypothyroidism. Only two patients with DCM had elevated LCI. Besides, two patients with myopathy or hypothyroidism had elevated LCI. In the follow-up, one patient died suddenly 6 months later and another showed normal value of LCI four years later. LCI elevation in DCM was not related to either the severity of heart failure or cardiac function and it showed no finding of 201 Tl myocardial defect or elevated CPK. The mechanism for elevated LCI in myopathy is related to a crossreaction with myosin light chain in the skeletal muscle. In hypothyroidism, it may be related to decreased clearance of normal LCI concentration or increased myosin light chain from damaged skeletal muscle. In conclusion, it is evident that the measurement of LCI is not helpful in clinical assessment of patients with DCM, but may be useful in detection of secondary cardiomyopathy. (author)

TRIGGER

CERN Multimedia

W. Smith

2010-01-01

Level-1 Trigger Hardware and Software The Level-1 Trigger hardware has performed well during both the recent proton-proton and heavy ion running. Efforts were made to improve the visibility and handling of alarms and warnings. The tracker ReTRI boards that prevent fixed frequencies of Level-1 Triggers are now configured through the Trigger Supervisor. The Global Calorimeter Trigger (GCT) team has introduced a buffer cleanup procedure at stops and a reset of the QPLL during configuring to ensure recalibration in case of a switch from the LHC clock to the local clock. A device to test the cables between the Regional Calorimeter Trigger and the GCT has been manufactured. A wrong charge bit was fixed in the CSC Trigger. The ECAL group is improving crystal masking and spike suppression in the trigger primitives. New firmware for the Drift Tube Track Finder (DTTF) sorters was developed to improve fake track tagging and sorting. Zero suppression was implemented in the DT Sector Collector readout. The track finder b...

TRIGGER

CERN Multimedia

Wesley Smith

Trigger Hardware The status of the trigger components was presented during the September CMS Week and Annual Review and at the monthly trigger meetings in October and November. Procedures for cold and warm starts (e.g. refreshing of trigger parameters stored in registers) of the trigger subsystems have been studied. Reviews of parts of the Global Calorimeter Trigger (GCT) and the Global Trigger (GT) have taken place in October and November. The CERN group summarized the status of the Trigger Timing and Control (TTC) system. All TTC crates and boards are installed in the underground counting room, USC55. The central clock system will be upgraded in December (after the Global Run at the end of November GREN) to the new RF2TTC LHC machine interface timing module. Migration of subsystem's TTC PCs to SLC4/ XDAQ 3.12 is being prepared. Work is on going to unify the access to Local Timing Control (LTC) and TTC CMS interface module (TTCci) via SOAP (Simple Object Access Protocol, a lightweight XML-based messaging ...

The importance of subfragment 2 and C-terminus of myosin heavy chain for thick filament assembly in skeletal muscle cells.

Science.gov (United States)

Ojima, Koichi; Oe, Mika; Nakajima, Ikuyo; Shibata, Masahiro; Muroya, Susumu; Chikuni, Koichi; Hattori, Akihito; Nishimura, Takanori

2015-04-01

In skeletal muscle cells, myofibrillar proteins are highly organized into sarcomeres in which thick filaments interdigitate with thin filaments to generate contractile force. The size of thick filaments, which consist mainly of myosin molecules, is strictly controlled. However, little is known about the mechanisms by which myosin molecules assemble into thick filaments. Here, we assessed the ability of each domain of myosin heavy chain (Myh) to form thick filaments. We showed that exogenously expressed subfragment 2 (S2) + light meromyosin (LMM) of Myh was efficiently incorporated into thick filaments in muscle cells, although neither solely expressed S2 nor LMM targeted to thick filaments properly. In nonmuscle COS7 cells, S2+LMM formed more enlarged filaments/speckles than LMM. These results suggest that Myh filament formation is induced by S2 accompanying LMM. We further examined the effects of Myh C-terminus on thick filament assembly. C-terminal deletion mutants were incorporated not into entire thick filaments but rather into restricted regions of thick filaments. Our findings suggest that the elongation of myosin filaments to form thick filaments is regulated by S2 as well as C-terminus of LMM. © 2014 Japanese Society of Animal Science.

Construction and characterization of the alpha form of a cardiac myosin heavy chain cDNA clone and its developmental expression in the Syrian hamster.

OpenAIRE

Liew, C C; Jandreski, M A

1986-01-01

A cDNA clone, pVHC1, was isolated from a Syrian hamster heart cDNA library and was compared to the rat alpha (pCMHC21) and beta (pCMHC5) ventricular myosin heavy chain cDNA clones. The DNA sequence and amino acid sequence deducted from the DNA show more homology with pCMHC21 than pCMHC5. This indicates that pVHC1 is an alpha ventricular myosin heavy chain cDNA clone. However, even though pVHC1 shows a high degree of nucleotide and amino acid conservation with the rat myosin heavy chain sequen...

Gene transfer, expression, and sarcomeric incorporation of a headless myosin molecule in cardiac myocytes: evidence for a reserve in myofilament motor function

Science.gov (United States)

Vandenboom, Rene; Herron, Todd; Favre, Elizabeth; Albayya, Faris P.

2011-01-01

The purpose of this study was to implement a living myocyte in vitro model system to test whether a motor domain-deleted headless myosin construct could be incorporated into the sarcomere and affect contractility. To this end we used gene transfer to express a “headless” myosin heavy chain (headless-MHC) in complement with the native full-length myosin motors in the cardiac sarcomere. An NH2-terminal Flag epitope was used for unique detection of the motor domain-deleted headless-MHC. Total MHC content (i.e., headless-MHC + endogenous MHC) remained constant, while expression of the headless-MHC in transduced myocytes increased from 24 to 72 h after gene transfer until values leveled off at 96 h after gene transfer, at which time the headless-MHC comprised ∼20% of total MHC. Moreover, immunofluorescence labeling and confocal imaging confirmed expression and demonstrated incorporation of the headless-MHC in the A band of the cardiac sarcomere. Functional measurements in intact myocytes showed that headless-MHC modestly reduced amplitude of dynamic twitch contractions compared with controls (P < 0.05). In chemically permeabilized myocytes, maximum steady-state isometric force and the tension-pCa relationship were unaltered by the headless-MHC. These data suggest that headless-MHC can express to 20% of total myosin and incorporate into the sarcomere yet have modest to no effects on dynamic and steady-state contractile function. This would indicate a degree of functional tolerance in the sarcomere for nonfunctional myosin molecules. PMID:21112946

Vascular O-GlcNAcylation augments reactivity to constrictor stimuli by prolonging phosphorylated levels of the myosin light chain

Energy Technology Data Exchange (ETDEWEB)

Lima, V.V. [Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Mato Grosso, Barra do Garças, MT (Brazil); Lobato, N.S.; Filgueira, F.P. [Curso de Medicina, Setor de Fisiologia Humana, Universidade Federal de Goiás, Jataí, GO (Brazil); Webb, R.C. [Department of Physiology, Georgia Regents University, Augusta, GA (United States); Tostes, R.C. [Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Giachini, F.R. [Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Mato Grosso, Barra do Garças, MT (Brazil)

2014-08-15

O-GlcNAcylation is a modification that alters the function of numerous proteins. We hypothesized that augmented O-GlcNAcylation levels enhance myosin light chain kinase (MLCK) and reduce myosin light chain phosphatase (MLCP) activity, leading to increased vascular contractile responsiveness. The vascular responses were measured by isometric force displacement. Thoracic aorta and vascular smooth muscle cells (VSMCs) from rats were incubated with vehicle or with PugNAc, which increases O-GlcNAcylation. In addition, we determined whether proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation. PugNAc enhanced phenylephrine (PE) responses in rat aortas (maximal effect, 14.2±2 vs 7.9±1 mN for vehicle, n=7). Treatment with an MLCP inhibitor (calyculin A) augmented vascular responses to PE (13.4±2 mN) and abolished the differences in PE-response between the groups. The effect of PugNAc was not observed when vessels were preincubated with ML-9, an MLCK inhibitor (7.3±2 vs 7.5±2 mN for vehicle, n=5). Furthermore, our data showed that differences in the PE-induced contractile response between the groups were abolished by the activator of AMP-activated protein kinase (AICAR; 6.1±2 vs 7.4±2 mN for vehicle, n=5). PugNAc increased phosphorylation of myosin phosphatase target subunit 1 (MYPT-1) and protein kinase C-potentiated inhibitor protein of 17 kDa (CPI-17), which are involved in RhoA/Rho-kinase-mediated inhibition of myosin phosphatase activity. PugNAc incubation produced a time-dependent increase in vascular phosphorylation of myosin light chain and decreased phosphorylation levels of AMP-activated protein kinase, which decreased the affinity of MLCK for Ca{sup 2+}/calmodulin. Our data suggest that proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation, favoring vascular contraction.

Nuclear myosin is ubiquitously expressed and evolutionary conserved in vertebrates

Czech Academy of Sciences Publication Activity Database

Kahle, Michal; Přidalová, Jarmila; Špaček, M.; Dzijak, Rastislav; Hozák, Pavel

2007-01-01

Roč. 127, č. 2 (2007), s. 139-184 ISSN 0948-6143 R&D Projects: GA ČR GA204/04/0108; GA AV ČR IAA5039202; GA MŠk LC545; GA ČR GD204/05/H023 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50520514 Keywords : Nuclear myosin I * Transcription * Chromatin Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.893, year: 2007

A novel de novo mutation of β-cardiac myosin heavy chain gene ...

Indian Academy of Sciences (India)

2014-08-18

Aug 18, 2014 ... It is one of the most important diseases causing a sud- den death in ... familial HCM encode contractile proteins such as β-cardiac myosin ... A previously healthy 12-year-old boy was admitted to our hospital for .... Maron B. J. 2002 Hypertrophic cardiomyopathy: A systematic review. JAMA 287, 1308–1320.

Sarcomere lattice geometry influences cooperative myosin binding in muscle.

Directory of Open Access Journals (Sweden)

Bertrand C W Tanner

2007-07-01

Full Text Available In muscle, force emerges from myosin binding with actin (forming a cross-bridge. This actomyosin binding depends upon myofilament geometry, kinetics of thin-filament Ca(2+ activation, and kinetics of cross-bridge cycling. Binding occurs within a compliant network of protein filaments where there is mechanical coupling between myosins along the thick-filament backbone and between actin monomers along the thin filament. Such mechanical coupling precludes using ordinary differential equation models when examining the effects of lattice geometry, kinetics, or compliance on force production. This study uses two stochastically driven, spatially explicit models to predict levels of cross-bridge binding, force, thin-filament Ca(2+ activation, and ATP utilization. One model incorporates the 2-to-1 ratio of thin to thick filaments of vertebrate striated muscle (multi-filament model, while the other comprises only one thick and one thin filament (two-filament model. Simulations comparing these models show that the multi-filament predictions of force, fractional cross-bridge binding, and cross-bridge turnover are more consistent with published experimental values. Furthermore, the values predicted by the multi-filament model are greater than those values predicted by the two-filament model. These increases are larger than the relative increase of potential inter-filament interactions in the multi-filament model versus the two-filament model. This amplification of coordinated cross-bridge binding and cycling indicates a mechanism of cooperativity that depends on sarcomere lattice geometry, specifically the ratio and arrangement of myofilaments.

TRIGGER

CERN Multimedia

Wesley Smith

Level-1 Trigger Hardware and Software The final parts of the Level-1 trigger hardware are now being put in place. For the ECAL endcaps, more than half of the Trigger Concentrator Cards for the ECAL Endcap (TCC-EE) are now available at CERN, such that one complete endcap can be covered. The Global Trigger now correctly handles ECAL calibration sequences, without being influenced by backpressure. The Regional Calorimeter Trigger (RCT) hardware is complete and working in USC55. Intra-crate tests of all 18 RCT crates and the Global Calorimeter Trigger (GCT) are regularly taking place. Pattern tests have successfully captured data from HCAL through RCT to the GCT Source Cards. HB/HE trigger data are being compared with emulator results to track down the very few remaining hardware problems. The treatment of hot and dead cells, including their recording in the database, has been defined. For the GCT, excellent agreement between the emulator and data has been achieved for jets and HF ET sums. There is still som...

TRIGGER

CERN Multimedia

W. Smith

Level-1 Trigger Hardware and Software The trigger system has been constantly in use in cosmic and commissioning data taking periods. During CRAFT running it delivered 300 million muon and calorimeter triggers to CMS. It has performed stably and reliably. During the abort gaps it has also provided laser and other calibration triggers. Timing issues, namely synchronization and latency issues, have been solved. About half of the Trigger Concentrator Cards for the ECAL Endcap (TCC-EE) are installed, and the firmware is being worked on. The production of the other half has started. The HCAL Trigger and Readout (HTR) card firmware has been updated, and new features such as fast parallel zero-suppression have been included. Repairs of drift tube (DT) trigger mini-crates, optical links and receivers of sector collectors are under way and have been completed on YB0. New firmware for the optical receivers of the theta links to the drift tube track finder is being installed. In parallel, tests with new eta track finde...

TRIGGER

CERN Multimedia

R. Carlin with contributions from D. Acosta

2012-01-01

Level-1 Trigger Data-taking continues at cruising speed, with high availability of all components of the Level-1 trigger. We have operated the trigger up to a luminosity of 7.6E33, where we approached 100 kHz using the 7E33 prescale column.  Recently, the pause without triggers in case of an automatic "RESYNC" signal (the "settle" and "recover" time) was reduced in order to minimise the overall dead-time. This may become very important when the LHC comes back with higher energy and luminosity after LS1. We are also preparing for data-taking in the proton-lead run in early 2013. The CASTOR detector will make its comeback into CMS and triggering capabilities are being prepared for this. Steps to be taken include improved cooperation with the TOTEM trigger system and using the LHC clock during the injection and ramp phases of LHC. Studies are being finalised that will have a bearing on the Trigger Technical Design Report (TDR), which is to be rea...

Identification and molecular modelling of a mutation in the motor head domain of myosin VIIA in a family with autosomal dominant hearing impairment (DFNA11)

NARCIS (Netherlands)

Luijendijk, M.W.J.; Wijk, E. van; Bischoff, A.M.L.C.; Krieger, E.; Huygen, P.L.M.; Pennings, R.J.E.; Brunner, H.G.; Cremers, C.W.R.J.; Cremers, F.P.M.; Kremer, J.M.J.

2004-01-01

Myosin VIIA is an unconventional myosin that has been implicated in Usher syndrome type 1B, atypical Usher syndrome, non-syndromic autosomal recessive hearing impairment (DFNB2) and autosomal dominant hearing impairment (DFNA11). Here, we present a family with non-syndromic autosomal dominant

Identification and molecular modelling of a mutation in the motor head domain of myosin VIIA in a family with autosomal dominant hearing impairment (DFNA11).

NARCIS (Netherlands)

Luijendijk, M.W.J.; Wijk, E. van; Bischoff, A.M.L.C.; Krieger, E.; Huygen, P.L.M.; Pennings, R.J.E.; Brunner, H.G.; Cremers, C.W.R.J.; Cremers, F.P.M.; Kremer, J.M.J.

2004-01-01

Myosin VIIA is an unconventional myosin that has been implicated in Usher syndrome type 1B, atypical Usher syndrome, non-syndromic autosomal recessive hearing impairment (DFNB2) and autosomal dominant hearing impairment (DFNA11). Here, we present a family with non-syndromic autosomal dominant

Maintenance of muscle myosin levels in adult C. elegans requires both the double bromodomain protein BET-1 and sumoylation

Directory of Open Access Journals (Sweden)

Kate Fisher

2013-10-01

Attenuation of RAS-mediated signalling is a conserved process essential to control cell proliferation, differentiation, and apoptosis. Cooperative interactions between histone modifications such as acetylation, methylation and sumoylation are crucial for proper attenuation in C. elegans, implying that the proteins recognising these histone modifications could also play an important role in attenuation of RAS-mediated signalling. We sought to systematically identify these proteins and found BET-1. BET-1 is a conserved double bromodomain protein that recognises acetyl-lysines on histone tails and maintains the stable fate of various lineages. Unexpectedly, adults lacking both BET-1 and SUMO-1 are depleted of muscle myosin, an essential component of myofibrils. We also show that this muscle myosin depletion does not occur in all animals at a specific time, but rather that the penetrance of the phenotype increases with age. To gain mechanistic insights into this process, we sought to delay the occurrence of the muscle myosin depletion phenotype and found that it requires caspase activity and MEK-dependent signalling. We also performed transcription profiling on these mutants and found an up-regulation of the FGF receptor, egl-15, a tyrosine kinase receptor acting upstream of MEK. Consistent with a MEK requirement, we could delay the muscle phenotype by systemic or hypodermal knock down of egl-15. Thus, this work uncovered a caspase- and MEK-dependent mechanism that acts specifically on ageing adults to maintain the appropriate net level of muscle myosin.

A high-voltage triggered pseudospark discharge experiment

International Nuclear Information System (INIS)

Ramaswamy, K.; Destler, W.W.; Rodgers, J.

1996-01-01

The design and execution of a pulsed high-voltage (350 endash 400 keV) triggered pseudospark discharge experiment is reported. Experimental studies were carried out to obtain an optimal design for stable and reliable pseudospark operation in a high-voltage regime (approx-gt 350 kV). Experiments were performed to determine the most suitable fill gas for electron-beam formation. The pseudospark discharge is initiated by a trigger mechanism involving a flashover between the trigger electrode and hollow cathode housing. Experimental results characterizing the electron-beam energy using the range-energy method are reported. Source size imaging was carried out using an x-ray pinhole camera and a novel technique using Mylar as a witness plate. It was experimentally determined that strong pinching occurred later in time and was associated with the lower-energy electrons. copyright 1996 American Institute of Physics

Triggering of internal transport barrier in JET

Energy Technology Data Exchange (ETDEWEB)

Joffrin, E. [Association Euratom-CEA pour la Fusion, CEA Cadarache, St. Paul lez Durance (France); Gorini, G. [Istituto di Fisica del Plasma, EURATOM-ENEA-CNR Association, Milan (Italy); Challis, C.D. [Euratom/UKAEA Fusion Association, Culham Science Centre, Abingdon, Oxon (United Kingdom)] [and others

2002-08-01

Internal transport barriers (ITBs) can be produced in JET by the application of strong additional heating during the current rise phase of the plasma discharge. Using up to 3 MW of lower hybrid power to tailor the q-profile prior to the main heating phase, a large variety of q-profiles ranging from low positive to strong negative central shear have been obtained during the current rise (0.4 MA s{sup -1}). With negative central magnetic shear s=(r/q)(r/q), the analysis of ITB triggering reveals a correlation between the formation of the ITB and q{sub andmin;} reaching an integer value (q=2 or q=3). This observation is confirmed by the analysis of the Alfven cascades. The minimum power required to access regimes with ITBs is probably related to the transport and magnetohydrodynamic properties of integer magnetic surfaces. Laser ablation and shallow pellet injection have also been attempted in recent JET ITB triggering experiments. (author)

TRIGGER

CERN Multimedia

W. Smith

At the March meeting, the CMS trigger group reported on progress in production, tests in the Electronics Integration Center (EIC) in Prevessin 904, progress on trigger installation in the underground counting room at point 5, USC55, the program of trigger pattern tests and vertical slice tests and planning for the Global Runs starting this summer. The trigger group is engaged in the final stages of production testing, systems integration, and software and firmware development. Most systems are delivering final tested electronics to CERN. The installation in USC55 is underway and integration testing is in full swing. A program of orderly connection and checkout with subsystems and central systems has been developed. This program includes a series of vertical subsystem slice tests providing validation of a portion of each subsystem from front-end electronics through the trigger and DAQ to data captured and stored. After full checkout, trigger subsystems will be then operated in the CMS Global Runs. Continuous...

TRIGGER

CERN Multimedia

Wesley Smith

2011-01-01

Level-1 Trigger Hardware and Software New Forward Scintillating Counters (FSC) for rapidity gap measurements have been installed and integrated into the Trigger recently. For the Global Muon Trigger, tuning of quality criteria has led to improvements in muon trigger efficiencies. Several subsystems have started campaigns to increase spares by recovering boards or producing new ones. The barrel muon sector collector test system has been reactivated, new η track finder boards are in production, and φ track finder boards are under revision. In the CSC track finder, an η asymmetry problem has been corrected. New pT look-up tables have also improved efficiency. RPC patterns were changed from four out of six coincident layers to three out of six in the barrel, which led to a significant increase in efficiency. A new PAC firmware to trigger on heavy stable charged particles allows looking for chamber hit coincidences in two consecutive bunch-crossings. The redesign of the L1 Trigger Emulator...

TRIGGER

CERN Multimedia

W. Smith from contributions of C. Leonidopoulos, I. Mikulec, J. Varela and C. Wulz.

Level-1 Trigger Hardware and Software Over the past few months, the Level-1 trigger has successfully recorded data with cosmic rays over long continuous stretches as well as LHC splash events, beam halo, and collision events. The L1 trigger hardware, firmware, synchronization, performance and readiness for beam operation were reviewed in October. All L1 trigger hardware is now installed at Point 5, and most of it is completely commissioned. While the barrel ECAL Trigger Concentrator Cards are fully operational, the recently delivered endcap ECAL TCC system is still being commissioned. For most systems there is a sufficient number of spares available, but for a few systems additional reserve modules are needed. It was decided to increase the overall L1 latency by three bunch crossings to increase the safety margin for trigger timing adjustments. In order for CMS to continue data taking during LHC frequency ramps, the clock distribution tree needs to be reset. The procedures for this have been tested. A repl...

Flexible trigger menu implementation on the Global Trigger for the CMS Level-1 trigger upgrade

Science.gov (United States)

MATSUSHITA, Takashi; CMS Collaboration

2017-10-01

The CMS experiment at the Large Hadron Collider (LHC) has continued to explore physics at the high-energy frontier in 2016. The integrated luminosity delivered by the LHC in 2016 was 41 fb-1 with a peak luminosity of 1.5 × 1034 cm-2s-1 and peak mean pile-up of about 50, all exceeding the initial estimations for 2016. The CMS experiment has upgraded its hardware-based Level-1 trigger system to maintain its performance for new physics searches and precision measurements at high luminosities. The Global Trigger is the final step of the CMS Level-1 trigger and implements a trigger menu, a set of selection requirements applied to the final list of objects from calorimeter and muon triggers, for reducing the 40 MHz collision rate to 100 kHz. The Global Trigger has been upgraded with state-of-the-art FPGA processors on Advanced Mezzanine Cards with optical links running at 10 GHz in a MicroTCA crate. The powerful processing resources of the upgraded system enable implementation of more algorithms at a time than previously possible, allowing CMS to be more flexible in how it handles the available trigger bandwidth. Algorithms for a trigger menu, including topological requirements on multi-objects, can be realised in the Global Trigger using the newly developed trigger menu specification grammar. Analysis-like trigger algorithms can be represented in an intuitive manner and the algorithms are translated to corresponding VHDL code blocks to build a firmware. The grammar can be extended in future as the needs arise. The experience of implementing trigger menus on the upgraded Global Trigger system will be presented.

The local expression of adult chicken heart myosins during development. II. Ventricular conducting tissue

NARCIS (Netherlands)

Sanders, E.; de Groot, I. J.; Geerts, W. J.; de Jong, F.; van Horssen, A. A.; Los, J. A.; Moorman, A. F.

1986-01-01

The development of the ventricular conducting tissue of the embryonic chicken heart has been studied using a previous finding that morphologically recognizable atrial conducting tissue coexpresses the atrial and the ventricular myosin isoforms. It is found that, by these criteria, at 9 days part of

The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing

Science.gov (United States)

Fang, Qing; Indzhykulian, Artur A; Mustapha, Mirna; Riordan, Gavin P; Dolan, David F; Friedman, Thomas B; Belyantseva, Inna A; Frolenkov, Gregory I; Camper, Sally A; Bird, Jonathan E

2015-01-01

The precise assembly of inner ear hair cell stereocilia into rows of increasing height is critical for mechanotransduction and the sense of hearing. Yet, how the lengths of actin-based stereocilia are regulated remains poorly understood. Mutations of the molecular motor myosin 15 stunt stereocilia growth and cause deafness. We found that hair cells express two isoforms of myosin 15 that differ by inclusion of an 133-kDa N-terminal domain, and that these isoforms can selectively traffic to different stereocilia rows. Using an isoform-specific knockout mouse, we show that hair cells expressing only the small isoform remarkably develop normal stereocilia bundles. However, a critical subset of stereocilia with active mechanotransducer channels subsequently retracts. The larger isoform with the 133-kDa N-terminal domain traffics to these specialized stereocilia and prevents disassembly of their actin core. Our results show that myosin 15 isoforms can navigate between functionally distinct classes of stereocilia, and are independently required to assemble and then maintain the intricate hair bundle architecture. DOI: http://dx.doi.org/10.7554/eLife.08627.001 PMID:26302205

A programmable DNA origami nanospring that reveals force-induced adjacent binding of myosin VI heads.

Science.gov (United States)

Iwaki, M; Wickham, S F; Ikezaki, K; Yanagida, T; Shih, W M

2016-12-12

Mechanosensitive biological nanomachines such as motor proteins and ion channels regulate diverse cellular behaviour. Combined optical trapping with single-molecule fluorescence imaging provides a powerful methodology to clearly characterize the mechanoresponse, structural dynamics and stability of such nanomachines. However, this system requires complicated experimental geometry, preparation and optics, and is limited by low data-acquisition efficiency. Here we develop a programmable DNA origami nanospring that overcomes these issues. We apply our nanospring to human myosin VI, a mechanosensory motor protein, and demonstrate nanometre-precision single-molecule fluorescence imaging of the individual motor domains (heads) under force. We observe force-induced transitions of myosin VI heads from non-adjacent to adjacent binding, which correspond to adapted roles for low-load and high-load transport, respectively. Our technique extends single-molecule studies under force and clarifies the effect of force on biological processes.

Expression of smooth muscle and non-muscle myosin heavy chain isoforms in cultured vascular smooth muscle cells

International Nuclear Information System (INIS)

Rovner, A.S.; Murphy, R.A.; Owens, G.K.

1986-01-01

Immunocytochemical studies of cultured smooth muscle cells (SMCs) have disagreed on the nature of myosin expression. This investigation was undertaken to test for the presence of heterogeneous myosin heavy chain (MHC) isoforms in cell culture as a possible explanation for these results. Previously, Rovner et al. detected two MHCs in intact smooth muscles which differed in molecular weight by ca. 4000 daltons (SM1 and SM2) using a 3-4% acrylamide gradient SDS gel system. When sub-confluent primary cultures of rat aorta SMCs were assayed by this system, SM1 and SM2 were seen, along with large amounts of a third, unique MHC, NM, which closely resembled the MHC from human platelet in size and antigenicity. Data from 35 S-methionine autoradiograms showed that the log growth phase SMC cultures were producing almost exclusively NM, but the growth arrest, post-confluent cultures synthesized increased relative amounts of the SM MHC forms and contained comparable amounts of SM1, SM2, and NM. The same patterns of MHC synthesis were seen in sub-passaged SMCs. The expression of the SM-specific forms of myosin in quiescent, post-confluent cultures parallels that of smooth muscle actin suggesting that density induced growth arrest promotes cytodifferentiation in cultured vascular SMCs

TRIGGER

CERN Multimedia

R. Arcidiacono

2013-01-01

  In 2013 the Trigger Studies Group (TSG) has been restructured in three sub-groups: STEAM, for the development of new HLT menus and monitoring their performance; STORM, for the development of HLT tools, code and actual configurations; and FOG, responsible for the online operations of the High Level Trigger. The Strategy for Trigger Evolution And Monitoring (STEAM) group is responsible for Trigger Menu development, path timing, trigger performance studies coordination, HLT offline DQM as well as HLT release, menu and conditions validation – in collaboration and with the technical support of the PdmV group. Since the end of proton-proton data taking, the group has started preparing for 2015 data taking, with collisions at 13 TeV and 25 ns bunch spacing. The reliability of the extrapolation to higher energy is being evaluated comparing the trigger rates on 7 and 8 TeV Monte Carlo samples with the data taken in the past two years. The effect of 25 ns bunch spacing is being studied on the d...

TRIGGER

CERN Multimedia

W. Smith

Level-1 Trigger Hardware and Software The road map for the final commissioning of the level-1 trigger system has been set. The software for the trigger subsystems is being upgraded to run under CERN Scientific Linux 4 (SLC4). There is also a new release for the Trigger Supervisor (TS 1.4), which implies upgrade work by the subsystems. As reported by the CERN group, a campaign to tidy the Trigger Timing and Control (TTC) racks has begun. The machine interface was upgraded by installing the new RF2TTC module, which receives RF signals from LHC Point 4. Two Beam Synchronous Timing (BST) signals, one for each beam, can now be received in CMS. The machine group will define the exact format of the information content shortly. The margin on the locking range of the CMS QPLL is planned for study for different subsystems in the next Global Runs, using a function generator. The TTC software has been successfully tested on SLC4. Some TTC subsystems have already been upgraded to SLC4. The TTCci Trigger Supervisor ...

The IQ motif drives the nuclear translocation of nuclear myosin I

Czech Academy of Sciences Publication Activity Database

Dzijak, Rastislav; Yildirim, Sukriye; Kahle, Michal; Hozák, Pavel

2008-01-01

Roč. 275, č. 1 (2008), s. 67-67 E-ISSN 1742-4658. [FEBS Congress /33rd/, IUBMB conference /11th/. 28.06.2008-03.07.2008, Athens] R&D Projects: GA MŠk LC545; GA ČR(CZ) GA204/07/1592 Grant - others:GAČR(CZ) GD204/05/H023 Program:GD Institutional research plan: CEZ:AV0Z50520514 Keywords : nuclear myosin * nuclear transport Subject RIV: EB - Genetics ; Molecular Biology

Technetium-99m labeling of antibodies to cardiac myosin Fab and to human fibrinogen

International Nuclear Information System (INIS)

Khaw, B.A.; Strauss, H.W.; Carvalho, A.; Locke, E.; Gold, H.K.; Haber, E.

1982-01-01

A method of labeling biologically active labile macromolecules, such as human fibrinogen (HF) and anticardiac-myosin Fab (AM-Fab), with Tc-99m at neutral pH was developed. This method uses dithionite reduction of pertechnetate and subsequent labeling to test the method with acid-labile macromolecules. Complexes of diethylene triamine pentaacetic acid with macromolecules such as human fibrinogen (D-HF) and anticardiac-myosin Fab (D-AM-Fab) were labeled and utilized in in vitro and in vivo studies. In biodistribution studies, the Tc-99m D-HF had a two-component blood clearance (half-times 1 hr and 15 hr) and was 80-88% coagulable. The Tc-99m AM-Fab retained its immunoreactivity as tested by affinity chromatography; also during in vivo localization in experimental myocardial infarction. This labeling technique provides an easy and efficient approach to the Tc-99m labeling of other biologically active and acid-labile macromolecules

Clot retraction is mediated by factor XIII-dependent fibrin-αIIbβ3-myosin axis in platelet sphingomyelin-rich membrane rafts.

Science.gov (United States)

Kasahara, Kohji; Kaneda, Mizuho; Miki, Toshiaki; Iida, Kazuko; Sekino-Suzuki, Naoko; Kawashima, Ikuo; Suzuki, Hidenori; Shimonaka, Motoyuki; Arai, Morio; Ohno-Iwashita, Yoshiko; Kojima, Soichi; Abe, Mitsuhiro; Kobayashi, Toshihide; Okazaki, Toshiro; Souri, Masayoshi; Ichinose, Akitada; Yamamoto, Naomasa

2013-11-07

Membrane rafts are spatially and functionally heterogenous in the cell membrane. We observed that lysenin-positive sphingomyelin (SM)-rich rafts are identified histochemically in the central region of adhered platelets where fibrin and myosin are colocalized on activation by thrombin. The clot retraction of SM-depleted platelets from SM synthase knockout mouse was delayed significantly, suggesting that platelet SM-rich rafts are involved in clot retraction. We found that fibrin converted by thrombin translocated immediately in platelet detergent-resistant membrane (DRM) rafts but that from Glanzmann's thrombasthenic platelets failed. The fibrinogen γ-chain C-terminal (residues 144-411) fusion protein translocated to platelet DRM rafts on thrombin activation, but its mutant that was replaced by A398A399 at factor XIII crosslinking sites (Q398Q399) was inhibited. Furthermore, fibrin translocation to DRM rafts was impaired in factor XIII A subunit-deficient mouse platelets, which show impaired clot retraction. In the cytoplasm, myosin translocated concomitantly with fibrin translocation into the DRM raft of thrombin-stimulated platelets. Furthermore, the disruption of SM-rich rafts by methyl-β-cyclodextrin impaired myosin activation and clot retraction. Thus, we propose that clot retraction takes place in SM-rich rafts where a fibrin-αIIbβ3-myosin complex is formed as a primary axis to promote platelet contraction.

Specific nuclear localizing sequence directs two myosin isoforms to the cell nucleus in calmodulin-sensitive manner.

Science.gov (United States)

Dzijak, Rastislav; Yildirim, Sukriye; Kahle, Michal; Novák, Petr; Hnilicová, Jarmila; Venit, Tomáš; Hozák, Pavel

2012-01-01

Nuclear myosin I (NM1) was the first molecular motor identified in the cell nucleus. Together with nuclear actin, they participate in crucial nuclear events such as transcription, chromatin movements, and chromatin remodeling. NM1 is an isoform of myosin 1c (Myo1c) that was identified earlier and is known to act in the cytoplasm. NM1 differs from the "cytoplasmic" myosin 1c only by additional 16 amino acids at the N-terminus of the molecule. This amino acid stretch was therefore suggested to direct NM1 into the nucleus. We investigated the mechanism of nuclear import of NM1 in detail. Using over-expressed GFP chimeras encoding for truncated NM1 mutants, we identified a specific sequence that is necessary for its import to the nucleus. This novel nuclear localization sequence is placed within calmodulin-binding motif of NM1, thus it is present also in the Myo1c. We confirmed the presence of both isoforms in the nucleus by transfection of tagged NM1 and Myo1c constructs into cultured cells, and also by showing the presence of the endogenous Myo1c in purified nuclei of cells derived from knock-out mice lacking NM1. Using pull-down and co-immunoprecipitation assays we identified importin beta, importin 5 and importin 7 as nuclear transport receptors that bind NM1. Since the NLS sequence of NM1 lies within the region that also binds calmodulin we tested the influence of calmodulin on the localization of NM1. The presence of elevated levels of calmodulin interfered with nuclear localization of tagged NM1. We have shown that the novel specific NLS brings to the cell nucleus not only the "nuclear" isoform of myosin I (NM1 protein) but also its "cytoplasmic" isoform (Myo1c protein). This opens a new field for exploring functions of this molecular motor in nuclear processes, and for exploring the signals between cytoplasm and the nucleus.

On the sensitivity of transtensional versus transpressional tectonic regimes to remote dynamic triggering by Coulomb failure

Science.gov (United States)

Hill, David P.

2015-01-01

 Accumulating evidence, although still strongly spatially aliased, indicates that although remote dynamic triggering of small-to-moderate (MwCoulomb failure supports this apparent difference for rapid-onset triggering susceptibility.

Diffraction in ALICE and trigger efficiencies

CERN Document Server

Navin, Sparsh; Lietava, Roman

ALICE is built to measure the properties of strongly interacting matter created in heavy-ion collisions. In addition, taking advantage of the low pT acceptance in the central barrel, ALICE is playing an important role in understanding pp collisions with minimum bias triggers at LHC energies. The work presented in this thesis is based on pp data simulated by the ALICE collaboration and early data collected at a center-of-mass energy of 7 TeV. A procedure to calculate trigger efficiencies and an estimate of the systematic uncertainty due to the limited acceptance of the detector are shown. A kinematic comparison between Monte Carlo event generators, PYTHIA 6, PYTHIA 8 and PHOJET is also presented. To improve the description of diffraction in PYTHIA, a hard diffractive component was added to PYTHIA 8 in 2009, which is described. Finally a trigger with a high efficiency for picking diffractive events is used to select a sample with an enhanced diffractive component from pp data. These data are compared to Monte ...

Nonmuscle Myosin II Is Required for Internalization of the Epidermal Growth Factor Receptor and Modulation of Downstream Signaling*

Science.gov (United States)

Kim, Jong Hyun; Wang, Aibing; Conti, Mary Anne; Adelstein, Robert S.

2012-01-01

Ligand-induced internalization of the epidermal growth factor receptor (EGFR) is an important process for regulating signal transduction, cellular dynamics, and cell-cell communication. Here, we demonstrate that nonmuscle myosin II (NM II) is required for the internalization of the EGFR and to trigger the EGFR-dependent activation of ERK and AKT. The EGFR was identified as a protein that interacts with NM II by co-immunoprecipitation and mass spectrometry analysis. This interaction requires both the regulatory light chain 20 (RLC20) of NM II and the kinase domain of the EGFR. Two paralogs of NM II, NM II-A, and NM II-B can act to internalize the EGFR, depending on the cell type and paralog content of the cell line. Loss (siRNA) or inhibition (25 μm blebbistatin) of NM II attenuates the internalization of the EGFR and impairs EGFR-dependent activation of ERK and AKT. Both internalization of the EGFR and downstream signaling to ERK and AKT can be partially restored in siRNA-treated cells by introduction of wild type (WT) GFP-NM II, but cannot be restored by motor mutant NM II. Taken together, these results suggest that NM II plays a role in the internalization of the EGFR and EGFR-mediated signaling pathways. PMID:22718763

Cosmic ray test of the Belle II z-vertex trigger

Energy Technology Data Exchange (ETDEWEB)

Neuhaus, Sara; Skambraks, Sebastian [Technische Universitaet Muenchen (Germany); Chen, Yang; Kiesling, Christian [Max-Planck-Institut fuer Physik, Muenchen (Germany)

2016-07-01

The z-vertex trigger is part of the first level track trigger in the Belle II experiment. Its task is the rejection of tracks not coming from the interaction region, suppressing a large part of the machine background. Therefore the z-vertex trigger allows to relax other track trigger conditions and thus strongly increases the efficiency for channels with low track multiplicity (e.g. tau pair production). The track trigger works in several steps, first combining hits to track segments, followed by a 2D track finding in the transverse plane and finally the 3D reconstruction. Our method employs neural networks to estimate the z-vertex without explicit track reconstruction. For the first real test with cosmic rays special neural networks have been prepared. Although the track shape in the cosmic test is different than in the Belle II experiment, the neural networks require only a retraining with an appropriate data set to adapt to the new geometry.

Myosin II Motor Activity in the Lateral Amygdala Is Required for Fear Memory Consolidation

Science.gov (United States)

Gavin, Cristin F.; Rubio, Maria D.; Young, Erica; Miller, Courtney; Rumbaugh, Gavin

2012-01-01

Learning induces dynamic changes to the actin cytoskeleton that are required to support memory formation. However, the molecular mechanisms that mediate filamentous actin (F-actin) dynamics during learning and memory are poorly understood. Myosin II motors are highly expressed in actin-rich growth structures including dendritic spines, and we have…

Compositional and expression analyses of the glideosome during the Plasmodium life cycle reveal an additional myosin light chain required for maximum motility.

Science.gov (United States)

Green, Judith L; Wall, Richard J; Vahokoski, Juha; Yusuf, Noor A; Ridzuan, Mohd A Mohd; Stanway, Rebecca R; Stock, Jessica; Knuepfer, Ellen; Brady, Declan; Martin, Stephen R; Howell, Steven A; Pires, Isa P; Moon, Robert W; Molloy, Justin E; Kursula, Inari; Tewari, Rita; Holder, Anthony A

2017-10-27

Myosin A (MyoA) is a Class XIV myosin implicated in gliding motility and host cell and tissue invasion by malaria parasites. MyoA is part of a membrane-associated protein complex called the glideosome, which is essential for parasite motility and includes the MyoA light chain myosin tail domain-interacting protein (MTIP) and several glideosome-associated proteins (GAPs). However, most studies of MyoA have focused on single stages of the parasite life cycle. We examined MyoA expression throughout the Plasmodium berghei life cycle in both mammalian and insect hosts. In extracellular ookinetes, sporozoites, and merozoites, MyoA was located at the parasite periphery. In the sexual stages, zygote formation and initial ookinete differentiation precede MyoA synthesis and deposition, which occurred only in the developing protuberance. In developing intracellular asexual blood stages, MyoA was synthesized in mature schizonts and was located at the periphery of segmenting merozoites, where it remained throughout maturation, merozoite egress, and host cell invasion. Besides the known GAPs in the malaria parasite, the complex included GAP40, an additional myosin light chain designated essential light chain (ELC), and several other candidate components. This ELC bound the MyoA neck region adjacent to the MTIP-binding site, and both myosin light chains co-located to the glideosome. Co-expression of MyoA with its two light chains revealed that the presence of both light chains enhances MyoA-dependent actin motility. In conclusion, we have established a system to study the interplay and function of the three glideosome components, enabling the assessment of inhibitors that target this motor complex to block host cell invasion. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

TRIGGER

CERN Multimedia

by Wesley Smith

2011-01-01

Level-1 Trigger Hardware and Software After the winter shutdown minor hardware problems in several subsystems appeared and were corrected. A reassessment of the overall latency has been made. In the TTC system shorter cables between TTCci and TTCex have been installed, which saved one bunch crossing, but which may have required an adjustment of the RPC timing. In order to tackle Pixel out-of-syncs without influencing other subsystems, a special hardware/firmware re-sync protocol has been introduced in the Global Trigger. The link between the Global Calorimeter Trigger and the Global Trigger with the new optical Global Trigger Interface and optical receiver daughterboards has been successfully tested in the Electronics Integration Centre in building 904. New firmware in the GCT now allows a setting to remove the HF towers from energy sums. The HF sleeves have been replaced, which should lead to reduced rates of anomalous signals, which may allow their inclusion after this is validated. For ECAL, improvements i...

TRIGGER

CERN Multimedia

W. Smith from contributions of C. Leonidopoulos

2010-01-01

Level-1 Trigger Hardware and Software Since nearly all of the Level-1 (L1) Trigger hardware at Point 5 has been commissioned, activities during the past months focused on the fine-tuning of synchronization, particularly for the ECAL and the CSC systems, on firmware upgrades and on improving trigger operation and monitoring. Periodic resynchronizations or hard resets and a shortened luminosity section interval of 23 seconds were implemented. For the DT sector collectors, an automatic power-off was installed in case of high temperatures, and the monitoring capabilities of the opto-receivers and the mini-crates were enhanced. The DTTF and the CSCTF now have improved memory lookup tables. The HCAL trigger primitive logic implemented a new algorithm providing better stability of the energy measurement in the presence of any phase misalignment. For the Global Calorimeter Trigger, additional Source Cards have been manufactured and tested. Testing of the new tau, missing ET and missing HT algorithms is underw...

Comparative genomic analysis of the arthropod muscle myosin heavy chain genes allows ancestral gene reconstruction and reveals a new type of 'partially' processed pseudogene

Directory of Open Access Journals (Sweden)

Kollmar Martin

2008-02-01

Full Text Available Abstract Background Alternative splicing of mutually exclusive exons is an important mechanism for increasing protein diversity in eukaryotes. The insect Mhc (myosin heavy chain gene produces all different muscle myosins as a result of alternative splicing in contrast to most other organisms of the Metazoa lineage, that have a family of muscle genes with each gene coding for a protein specialized for a functional niche. Results The muscle myosin heavy chain genes of 22 species of the Arthropoda ranging from the waterflea to wasp and Drosophila have been annotated. The analysis of the gene structures allowed the reconstruction of an ancient muscle myosin heavy chain gene and showed that during evolution of the arthropods introns have mainly been lost in these genes although intron gain might have happened in a few cases. Surprisingly, the genome of Aedes aegypti contains another and that of Culex pipiens quinquefasciatus two further muscle myosin heavy chain genes, called Mhc3 and Mhc4, that contain only one variant of the corresponding alternative exons of the Mhc1 gene. Mhc3 transcription in Aedes aegypti is documented by EST data. Mhc3 and Mhc4 inserted in the Aedes and Culex genomes either by gene duplication followed by the loss of all but one variant of the alternative exons, or by incorporation of a transcript of which all other variants have been spliced out retaining the exon-intron structure. The second and more likely possibility represents a new type of a 'partially' processed pseudogene. Conclusion Based on the comparative genomic analysis of the alternatively spliced arthropod muscle myosin heavy chain genes we propose that the splicing process operates sequentially on the transcript. The process consists of the splicing of the mutually exclusive exons until one exon out of the cluster remains while retaining surrounding intronic sequence. In a second step splicing of introns takes place. A related mechanism could be responsible for

[Changes in titin and myosin heavy chain isoform composition in skeletal muscles of Mongolian gerbil (Meriones unguiculatus) after 12-day spaceflight].

Science.gov (United States)

Okuneva, A D; Vikhliantsev, I M; Shpagina, M D; Rogachevskiĭ, V V; Khutsian, S S; Poddubnaia, Z A; Grigor'ev, A I

2012-01-01

Changes of titin and myosin heavy chain isoform composition in skeletal muscles (m. soleus, m. gastrocnemius, m. tibialis anterior, m. psoas major) in Mongolian Gerbil (Meriones unguiculatus ) were investigated after 12-day spaceflight on board of Russian space vehicle "Foton-M3". In m. psoas and m. soleus in the gerbils from "Flight" group the expected increase in the content of fast myosin heavy chain isoforms (IIxd and IIa, respectively) were observed. No significant differences were found in the content of IIxd and IIa isoforms of myosin heavy chain in m. tibialis anterior in the gerbils from control group as compared to that in "Flight" group. An unexpected increase in the content of slow myosin heavy chain I isoform and a decrease in the content of fast IIx/d isoform in m. gastrocnemius of the gerbils from "Flight" group were observed. In skeletal muscles of the gerbils from "Flight" group the relative content of titin N2A-isoform was reduced (by 1,2-1,7 times), although the content of its NT-isoform, which was revealed in striated muscles of mammals in our experiments earlier, remained the same. When the content of titin N2A-isoform was decreased, no predictable abnormalities in sarcomeric structure and contractile ability of skeletal muscles in the gerbils from "Flight" group were found. An assumption on the leading role of titin NT-isoform in maintenance of structural and functional properties of striated muscles of mammals was made.

Myosin light chain kinase knockout improves gut barrier function and confers a survival advantage in polymicrobial sepsis.

Science.gov (United States)

Lorentz, C Adam; Liang, Zhe; Meng, Mei; Chen, Ching-Wen; Yoseph, Benyam P; Breed, Elise R; Mittal, Rohit; Klingensmith, Nathan J; Farris, Alton B; Burd, Eileen M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M

2017-06-07

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. Survival was significantly increased in MLCK -/- mice (95% vs. 24%, p<0.0001). Intestinal permeability increased in septic WT mice compared to unmanipulated mice. In contrast, permeability in septic MLCK -/- mice was similar to that seen in unmanipulated animals. Improved gut barrier function in MLCK -/- mice was associated with increases in the tight junction mediators ZO-1 and claudin 15 without alterations in claudin 1, 2, 3, 4, 5, 7, 8, 13, occludin or JAM-A. Other components of intestinal integrity (apoptosis, proliferation and villus length) were unaffected by MLCK deletion as were local peritoneal inflammation and distant lung injury. Systemic IL-10 was decreased greater than 10-fold in MLCK -/- mice; however, survival was similar between septic MLCK -/- mice given exogenous IL-10 or vehicle. These data demonstrate that deletion of MLCK improves survival following sepsis, associated with normalization of intestinal permeability and selected tight junction proteins.

Determining the impact of oxidation on the motility of single muscle-fibres expressing different myosin isoforms

DEFF Research Database (Denmark)

Spanos, Dimitrios; Li, M.; Baron, Caroline P.

2013-01-01

heavy chain (MyHC) isoforms has not been previously investigated. Oxidation of myosin isolated from muscle fibres originating from various porcine muscles with a different metabolic profile was studied using a single muscle fibre in-vitro motility assay, allowing measurements of catalytic properties...... (motility speed) and force-generation capacity of specific MyHC isoforms. In the experimental procedure, single muscle fibres were split in different segments and each segment was exposed to a different concentration of hydrogen peroxide. Speed and force measurements were recorded and compared, to assess...... the effect of myosin oxidation on motility and force. The MyHC isoform expression in the single muscle fibre was subsequently determined on silver-stained gel SDS-PAGE. Preliminary results indicate a decrease of directionality and speed of the in-vitro motility as a result of an oxidative environment...

Method of triggering the vacuum arc in source with a resistor

International Nuclear Information System (INIS)

Zheng Le; Lan Zhaohui; Long Jidong; Peng Yufei; Li Jie; Yang Zhen; Dong Pan; Shi Jinshui

2014-01-01

Background: The metal vapor vacuum arc (MEVVA) ion source is a common source which provides strong metal ion flow. To trigger this ion source, a high-voltage trigger pulse generator and a high-voltage isolation pulse transformer are needed, which makes the power supply system complex. Purpose: To simplify the power supply system, a trigger method with a resistor was introduced, and some characteristics of this method were studied. Methods: The ion flow provided by different main arc current was measured, as well as the trigger current. The main arc current and the ion current were recorded with different trigger resistances. Results: Experimental results showed that, within a certain range of resistances, the larger the resistance value, the more difficult it was to success fully trigger the source. Meanwhile, the main arc rising edge became slower on the increasing in the trigger time. However, the resistance value increment had hardly impact on the intensity of ion flow extracted in the end, The ion flow became stronger with the increasing main arc current. Conclusion: The power supply system of ion source is simplified by using the trigger method with a resistor. Only a suitable resistor was needed to complete the conversion process from trigger to arc initiating. (authors)

Association of Myosin Va and Schwann cells-derived RNA in mammal myelinated axons, analyzed by immunocytochemistry and confocal FRET microscopy.

Science.gov (United States)

Canclini, Lucía; Wallrabe, Horst; Di Paolo, Andrés; Kun, Alejandra; Calliari, Aldo; Sotelo-Silveira, José Roberto; Sotelo, José Roberto

2014-03-15

Evidence from multiple sources supports the hypothesis that Schwann cells in the peripheral nervous system transfer messenger RNA and ribosomes to the axons they ensheath. Several technical and methodological difficulties exist for investigators to unravel this process in myelinated axons - a complex two-cell unit. We present an experimental design to demonstrate that newly synthesized RNA is transferred from Schwann cells to axons in association with Myosin Va. The use of quantitative confocal FRET microscopy to track newly-synthesized RNA and determine the molecular association with Myosin Va, is described in detail. Copyright © 2013 Elsevier Inc. All rights reserved.

/sup 99m/Tc labeling of antibodies to cardiac myosin Fab and to human fibrinogen

International Nuclear Information System (INIS)

Khaw, B.A.; Strauss, H.W.; Carvalho, A.; Locke, E.; Gold, H.K.; Haber, E.

1982-01-01

We have developed a method of labeling biologically active labile macromolecules, such as human fibrinogen (HF) and anticardiac-myosin Fab (AM-Fab), with /sup 99m/Tc at neutral pH. This method uses dithionite reduction of pertechnetate and subsequent labeling, to test the method with acid-labile macromolecules. Complexes of diethylene triamine pentaacetic acid with macromolecules such as human fibrinogen (D-HF) and anticardiac-myosin Fab (D-AM-Fab) were labeled and utilized in in vitro and in vivo studies. In biodistribution studies, the /sup 99m/Tc D-HF had a two-component blood clearance (half-times 1 hr and 15 hr) and was 80--88% coagulable. The /sup 99m/Tc AM-Fab retained its immunoreactivity as tested by affinity chromatography; also during in vivo localization in experimental myocardial infarction. This labeling technique provides an easy and efficient approach to the /sup 99m/Tc labeling of other biologically active and acid-labile macromolecules

TRIGGER

CERN Multimedia

W. Smith

2011-01-01

Level-1 Trigger Hardware and Software Overall the L1 trigger hardware has been running very smoothly during the last months of proton running. Modifications for the heavy-ion run have been made where necessary. The maximal design rate of 100 kHz can be sustained without problems. All L1 latencies have been rechecked. The recently installed Forward Scintillating Counters (FSC) are being used in the heavy ion run. The ZDC scintillators have been dismantled, but the calorimeter itself remains. We now send the L1 accept signal and other control signals to TOTEM. Trigger cables from TOTEM to CMS will be installed during the Christmas shutdown, so that the TOTEM data can be fully integrated within the CMS readout. New beam gas triggers have been developed, since the BSC-based trigger is no longer usable at high luminosities. In particular, a special BPTX signal is used after a quiet period with no collisions. There is an ongoing campaign to provide enough spare modules for the different subsystems. For example...

TRIGGER

CERN Multimedia

J. Alimena

2013-01-01

Trigger Strategy Group The Strategy for Trigger Evolution And Monitoring (STEAM) group is responsible for the development of future High-Level Trigger menus, as well as of its DQM and validation, in collaboration and with the technical support of the PdmV group. Taking into account the beam energy and luminosity expected in 2015, a rough estimate of the trigger rates indicates a factor four increase with respect to 2012 conditions. Assuming that a factor two can be tolerated thanks to the increase in offline storage and processing capabilities, a toy menu has been developed using the new OpenHLT workflow to estimate the transverse energy/momentum thresholds that would halve the current trigger rates. The CPU time needed to run the HLT has been compared between data taken with 25 ns and 50 ns bunch spacing, for equivalent pile-up: no significant difference was observed on the global time per event distribution at the only available data point, corresponding to a pile-up of about 10 interactions. Using th...

Human myosin VIIA responsible for the Usher 1B syndrome: a predicted membrane-associated motor protein expressed in developing sensory epithelia.

Science.gov (United States)

Weil, D; Levy, G; Sahly, I; Levi-Acobas, F; Blanchard, S; El-Amraoui, A; Crozet, F; Philippe, H; Abitbol, M; Petit, C

1996-04-16

The gene encoding human myosin VIIA is responsible for Usher syndrome type III (USH1B), a disease which associates profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. The reconstituted cDNA sequence presented here predicts a 2215 amino acid protein with a typical unconventional myosin structure. This protein is expected to dimerize into a two-headed molecule. The C terminus of its tail shares homology with the membrane-binding domain of the band 4.1 protein superfamily. The gene consists of 48 coding exons. It encodes several alternatively spliced forms. In situ hybridization analysis in human embryos demonstrates that the myosin VIIA gene is expressed in the pigment epithelium and the photoreceptor cells of the retina, thus indicating that both cell types may be involved in the USH1B retinal degenerative process. In addition, the gene is expressed in the human embryonic cochlear and vestibular neuroepithelia. We suggest that deafness and vestibular dysfunction in USH1B patients result from a defect in the morphogenesis of the inner ear sensory cell stereocilia.

Age- and Activity-Related Differences in the Abundance of Myosin Essential and Regulatory Light Chains in Human Muscle

Directory of Open Access Journals (Sweden)

James N. Cobley

2016-04-01

Full Text Available Traditional methods for phenotyping skeletal muscle (e.g., immunohistochemistry are labor-intensive and ill-suited to multixplex analysis, i.e., assays must be performed in a series. Addressing these concerns represents a largely unmet research need but more comprehensive parallel analysis of myofibrillar proteins could advance knowledge regarding age- and activity-dependent changes in human muscle. We report a label-free, semi-automated and time efficient LC-MS proteomic workflow for phenotyping the myofibrillar proteome. Application of this workflow in old and young as well as trained and untrained human skeletal muscle yielded several novel observations that were subsequently verified by multiple reaction monitoring (MRM. We report novel data demonstrating that human ageing is associated with lesser myosin light chain 1 content and greater myosin light chain 3 content, consistent with an age-related reduction in type II muscle fibers. We also disambiguate conflicting data regarding myosin regulatory light chain, revealing that age-related changes in this protein more closely reflect physical activity status than ageing per se. This finding reinforces the need to control for physical activity levels when investigating the natural process of ageing. Taken together, our data confirm and extend knowledge regarding age- and activity-related phenotypes. In addition, the MRM transitions described here provide a methodological platform that can be fine-tuned to suite multiple research needs and thus advance myofibrillar phenotyping.

Flexible trigger menu implementation on the Global Trigger for the CMS Level-1 trigger upgrade

CERN Document Server

Matsushita, Takashi

2017-01-01

The CMS experiment at the Large Hadron Collider (LHC) has continued to explore physics at the high-energy frontier in 2016. The integrated luminosity delivered by the LHC in 2016 was 41~fb$^{-1}$ with a peak luminosity of 1.5 $\\times$ 10$^{34}$ cm$^{-2}$s$^{-1}$ and peak mean pile-up of about 50, all exceeding the initial estimations for 2016. The CMS experiment has upgraded its hardware-based Level-1 trigger system to maintain its performance for new physics searches and precision measurements at high luminosities. The Global Trigger is the final step of the CMS \\mbox{Level-1} trigger and implements a trigger menu, a set of selection requirements applied to the final list of objects from calorimeter and muon triggers, for reducing the 40 MHz collision rate to 100 kHz. The Global Trigger has been upgraded with state-of-the-art FPGA processors on Advanced Mezzanine Cards with optical links running at 10 GHz in a MicroTCA crate. The powerful processing resources of the upgraded system enable implemen...

Cell differentiation through tissue elasticity-coupled, myosin-driven remodeling.

Science.gov (United States)

Zajac, Allison L; Discher, Dennis E

2008-12-01

Cells may lack eyes to see and ears to hear, but cells do seem to have a sense of 'touch' that allows them to feel their microenvironment. This is achieved in part through contractility coupled adhesion to physically flexible 'soft' tissue. Here we summarize some of the known variations in elasticity of solid tissue and review some of the long-term effects of cells 'feeling' this elasticity, focusing on differentiation processes of both committed cell types and stem cells. We then highlight what is known of molecular remodeling in cells under stress on short time scales. Key roles for forces generated by ubiquitous and essential myosin-II motors in feedback remodeling are emphasized throughout.

Earthquake-triggered landslides in southwest China

OpenAIRE

X. L. Chen; Q. Zhou; H. Ran; R. Dong

2012-01-01

Southwest China is located in the southeastern margin of the Tibetan Plateau and it is a region of high seismic activity. Historically, strong earthquakes that occurred here usually generated lots of landslides and brought destructive damages. This paper introduces several earthquake-triggered landslide events in this region and describes their characteristics. Also, the historical data of earthquakes with a magnitude of 7.0 or greater, having occurred in this region, is col...

Diffusion-weighted MR imaging of the abdomen with pulse triggering

International Nuclear Information System (INIS)

Muertz, P.; Pauleit, D.; Traeber, F.; Kreft, B.P.; Schild, H.H.

2000-01-01

Purpose: The aim of this work was to reduce the influence of motion on diffusion-weighted MR images of the abdomen by pulse triggering of single-shot sequences. Methods: Five healthy volunteers were examined both without and with finger pulse-triggering of a diffusion-weighted single-shot echo planar MR imaging sequence at 1.5 T. Series of diffusion-weighted images were acquired at different phases of the cardiac cycle by varying the time delay between finger pulse and sequence acquisition. The measurements were repeated three times. The diffusion weighted images were analysed by measuring the signal intensities and by determining the ADC values within the spleen, kidney and liver. Results: The magnitude of motion artifacts on diffusion weighted images shows a strong dependence on the trigger delay. The optimum trigger delay is found to be between 500 and 600 ms. For these values the abdominal organs appear homogeneous on all diffusion weighted images and the strongest signal intensities are detected. At optimum triggering the accuracy of the apparent diffusion coefficients is up to 10 times better than without triggering. Moreover, the standard deviation of the repeated measurements is smaller than 12% for all volunteers and for all organs. Without triggering the standard deviation is larger by a factor of 4 on average. Conclusion: Pulse triggering of single-shot sequences leads to significant reduction of motion related artifacts on diffusion weighted images of the abdomen and provides more accurate and reproducible ADC values. (orig.) [de

Seismic Intensity Map Triggered by Observed Strong Motion Records Considering Site Amplification and its service based on Geo-spatial International Standard

International Nuclear Information System (INIS)

Matsuoka, Masashi

2014-01-01

Instrumental seismic intensity measurement is carried out at approximately 4,200 points in Japan, but the correct values at points without seismometers cannot always be provided because seismic motion depends on geologic and geomorphologic features. Quick provision of accurate information on seismic intensity distribution over wide areas is required for disaster mitigation. To estimate seismic intensity at specific points, it is important to prepare ground amplification characteristics for local areas beforehand and use an interpolation algorithm. The QuiQuake system (quick estimation system for earthquake maps triggered by using observation records from K-NET and KiK-net that have been released by the National Research Institute for Earth Science and Disaster Prevention), which uses these, was developed; it can be started up automatically using seismograms and can immediately display a seismic intensity distribution map. The calculation results are sent to IAEA and JNES in the form of strong motion evaluation maps with a mesh size of 250 x 250 m. These maps are also sent to the general public via social networking web sites. (author)

Study on the plasma generation characteristics of an induction-triggered coaxial pulsed plasma thruster

Science.gov (United States)

Weisheng, CUI; Wenzheng, LIU; Jia, TIAN; Xiuyang, CHEN

2018-02-01

At present, spark plugs are used to trigger discharge in pulsed plasma thrusters (PPT), which are known to be life-limiting components due to plasma corrosion and carbon deposition. A strong electric field could be formed in a cathode triple junction (CTJ) to achieve a trigger function under vacuum conditions. We propose an induction-triggered electrode structure on the basis of the CTJ trigger principle. The induction-triggered electrode structure could increase the electric field strength of the CTJ without changing the voltage between electrodes, contributing to a reduction in the electrode breakdown voltage. Additionally, it can maintain the plasma generation effect when the breakdown voltage is reduced in the discharge experiments. The induction-triggered electrode structure could ensure an effective trigger when the ablation distance of Teflon increases, and the magnetic field produced by the discharge current could further improve the plasma density and propagation velocity. The induction-triggered coaxial PPT we propose has a simplified trigger structure, and it is an effective attempt to optimize the micro-satellite thruster.

Whistler Triggered Upper Band Chorus Observed in Alaska

Science.gov (United States)

Hosseini, P.; Golkowski, M.

2017-12-01

VLF radiation from lightning discharges is one of several sources of energy injection into the inner magnetosphere from the Earth. Lightning discharges initially produce a broadband impulse or `sferic' but after propagation in the dispersive magnetosphere this waveform soon becomes quasi narrow band with the characteristic spectrographic form of the whistler. Most of the lightning induced VLF wave energy injected into the magnetosphere will be unducted with a k-vector which becomes increasingly oblique. Although unducted radiation is ubiquitous throughout the inner magnetosphere, it is generally of a low amplitude due to Landau damping and is not expected to produce strong nonlinear phenomena such as triggered emissions and chorus waves. However, VLF wave energy ducted or trapped in field-aligned plasma density enhancements can have relatively large amplitudes due to focusing and also linear cyclotron resonance growth. Therefore high amplitude ducted whistler waves can trigger a number of complex nonlinear phenomena. These include the triggering of VLF emissions and triggering of VLF hiss or chorus. Such phenomena are generally considered to result from nonlinear electron cyclotron phase trapping. Observation of such VLF emissions triggered by natural whistlers have been reported since the 1970s in Antarctica. We present observations of whistlers triggered upper band chorus emission from Alaska. Dispersion analyze of whistlers determine the L-shell range to be 4.5 clear frequency band gap between upper and lower band of the observed chorus emissions. The observations point to ducted chorus generation in the vicinity of the plasmapause boundary.

The LHCb trigger

International Nuclear Information System (INIS)

Korolko, I.

1998-01-01

This paper describes progress in the development of the LHCb trigger system since the letter of intent. The trigger philosophy has significantly changed, resulting in an increase of trigger efficiency for signal B events. It is proposed to implement a level-1 vertex topology trigger in specialised hardware. (orig.)

Myosin binding protein-C activates thin filaments and inhibits thick filaments in heart muscle cells.

Science.gov (United States)

Kampourakis, Thomas; Yan, Ziqian; Gautel, Mathias; Sun, Yin-Biao; Irving, Malcolm

2014-12-30

Myosin binding protein-C (MyBP-C) is a key regulatory protein in heart muscle, and mutations in the MYBPC3 gene are frequently associated with cardiomyopathy. However, the mechanism of action of MyBP-C remains poorly understood, and both activating and inhibitory effects of MyBP-C on contractility have been reported. To clarify the function of the regulatory N-terminal domains of MyBP-C, we determined their effects on the structure of thick (myosin-containing) and thin (actin-containing) filaments in intact sarcomeres of heart muscle. We used fluorescent probes on troponin C in the thin filaments and on myosin regulatory light chain in the thick filaments to monitor structural changes associated with activation of demembranated trabeculae from rat ventricle by the C1mC2 region of rat MyBP-C. C1mC2 induced larger structural changes in thin filaments than calcium activation, and these were still present when active force was blocked with blebbistatin, showing that C1mC2 directly activates the thin filaments. In contrast, structural changes in thick filaments induced by C1mC2 were smaller than those associated with calcium activation and were abolished or reversed by blebbistatin. Low concentrations of C1mC2 did not affect resting force but increased calcium sensitivity and reduced cooperativity of force and structural changes in both thin and thick filaments. These results show that the N-terminal region of MyBP-C stabilizes the ON state of thin filaments and the OFF state of thick filaments and lead to a novel hypothesis for the physiological role of MyBP-C in the regulation of cardiac contractility.

TRIGGER

CERN Multimedia

W. Smith

At the December meeting, the CMS trigger group reported on progress in production, tests in the Electronics Integration Center (EIC) in Prevessin 904, progress on trigger installation in the underground counting room at point 5, USC55, and results from the Magnet Test and Cosmic Challenge (MTCC) phase II. The trigger group is engaged in the final stages of production testing, systems integration, and software and firmware development. Most systems are delivering final tested electronics to CERN. The installation in USC55 is underway and moving towards integration testing. A program of orderly connection and checkout with subsystems and central systems has been developed. This program includes a series of vertical subsystem slice tests providing validation of a portion of each subsystem from front-end electronics through the trigger and DAQ to data captured and stored. This is combined with operations and testing without beam that will continue until startup. The plans for start-up, pilot and early running tri...

Septin 7 reduces nonmuscle myosin IIA activity in the SNAP23 complex and hinders GLUT4 storage vesicle docking and fusion

Energy Technology Data Exchange (ETDEWEB)

Wasik, Anita A.; Dumont, Vincent [Department of Pathology, University of Helsinki, 00014 Helsinki (Finland); Tienari, Jukka [Department of Pathology, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, 05850 Hyvinkää (Finland); Nyman, Tuula A. [Institute of Biotechnology, University of Helsinki, 00014 Helsinki (Finland); Fogarty, Christopher L.; Forsblom, Carol; Lehto, Markku [Folkhälsan Institute of Genetics, Folkhälsan Research Center, 00290 Helsinki (Finland); Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, 000290 Helsinki (Finland); Diabetes& Obesity Research Program, Research Program´s Unit, 00014 University of Helsinki (Finland); Lehtonen, Eero [Department of Pathology, University of Helsinki, 00014 Helsinki (Finland); Laboratory Animal Centre, University of Helsinki, 00014 Helsinki (Finland); Groop, Per-Henrik [Folkhälsan Institute of Genetics, Folkhälsan Research Center, 00290 Helsinki (Finland); Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, 000290 Helsinki (Finland); Diabetes& Obesity Research Program, Research Program´s Unit, 00014 University of Helsinki (Finland); Baker IDI Heart & Diabetes Institute, 3004 Melbourne (Australia); Lehtonen, Sanna, E-mail: sanna.h.lehtonen@helsinki.fi [Department of Pathology, University of Helsinki, 00014 Helsinki (Finland)

2017-01-15

Glomerular epithelial cells, podocytes, are insulin responsive and can develop insulin resistance. Here, we demonstrate that the small GTPase septin 7 forms a complex with nonmuscle myosin heavy chain IIA (NMHC-IIA; encoded by MYH9), a component of the nonmuscle myosin IIA (NM-IIA) hexameric complex. We observed that knockdown of NMHC-IIA decreases insulin-stimulated glucose uptake into podocytes. Both septin 7 and NM-IIA associate with SNAP23, a SNARE protein involved in GLUT4 storage vesicle (GSV) docking and fusion with the plasma membrane. We observed that insulin decreases the level of septin 7 and increases the activity of NM-IIA in the SNAP23 complex, as visualized by increased phosphorylation of myosin regulatory light chain. Also knockdown of septin 7 increases the activity of NM-IIA in the complex. The activity of NM-IIA is increased in diabetic rat glomeruli and cultured human podocytes exposed to macroalbuminuric sera from patients with type 1 diabetes. Collectively, the data suggest that the activity of NM-IIA in the SNAP23 complex plays a key role in insulin-stimulated glucose uptake into podocytes. Furthermore, we observed that septin 7 reduces the activity of NM-IIA in the SNAP23 complex and thereby hinders GSV docking and fusion with the plasma membrane. - Highlights: • Septin 7, nonmuscle myosin heavy chain IIA (NMHC-IIA) and SNAP23 form a complex. • Knockdown of septin 7 increases NM-IIA activity in the SNAP23 complex. • Insulin decreases septin 7 level and increases NM-IIA activity in the SNAP23 complex. • Septin 7 hinders GSV docking/fusion by reducing NM-IIA activity in the SNAP23 complex.

Septin 7 reduces nonmuscle myosin IIA activity in the SNAP23 complex and hinders GLUT4 storage vesicle docking and fusion

International Nuclear Information System (INIS)

Wasik, Anita A.; Dumont, Vincent; Tienari, Jukka; Nyman, Tuula A.; Fogarty, Christopher L.; Forsblom, Carol; Lehto, Markku; Lehtonen, Eero; Groop, Per-Henrik; Lehtonen, Sanna

2017-01-01

Glomerular epithelial cells, podocytes, are insulin responsive and can develop insulin resistance. Here, we demonstrate that the small GTPase septin 7 forms a complex with nonmuscle myosin heavy chain IIA (NMHC-IIA; encoded by MYH9), a component of the nonmuscle myosin IIA (NM-IIA) hexameric complex. We observed that knockdown of NMHC-IIA decreases insulin-stimulated glucose uptake into podocytes. Both septin 7 and NM-IIA associate with SNAP23, a SNARE protein involved in GLUT4 storage vesicle (GSV) docking and fusion with the plasma membrane. We observed that insulin decreases the level of septin 7 and increases the activity of NM-IIA in the SNAP23 complex, as visualized by increased phosphorylation of myosin regulatory light chain. Also knockdown of septin 7 increases the activity of NM-IIA in the complex. The activity of NM-IIA is increased in diabetic rat glomeruli and cultured human podocytes exposed to macroalbuminuric sera from patients with type 1 diabetes. Collectively, the data suggest that the activity of NM-IIA in the SNAP23 complex plays a key role in insulin-stimulated glucose uptake into podocytes. Furthermore, we observed that septin 7 reduces the activity of NM-IIA in the SNAP23 complex and thereby hinders GSV docking and fusion with the plasma membrane. - Highlights: • Septin 7, nonmuscle myosin heavy chain IIA (NMHC-IIA) and SNAP23 form a complex. • Knockdown of septin 7 increases NM-IIA activity in the SNAP23 complex. • Insulin decreases septin 7 level and increases NM-IIA activity in the SNAP23 complex. • Septin 7 hinders GSV docking/fusion by reducing NM-IIA activity in the SNAP23 complex.

Harmonic Force Spectroscopy Reveals a Force-Velocity Curve from a Single Human Beta Cardiac Myosin Motor

DEFF Research Database (Denmark)

Sung, Jongmin; Nag, Suman; Vestergaard, Christian L.

2014-01-01

human beta cardiac myosin S1. We also compare load-velocity curves for wild-type motors with load-velocity curves of mutant forms that cause hypertrophic or dilated-cardiomyopathy (HCM or DCM), in order to understand the effects of mutations on the contractile cycle at the single molecule level....

Tinnitus-provoking salicylate treatment triggers social impairments in mice.

Science.gov (United States)

Guitton, Matthieu J

2009-09-01

Tinnitus (perception of sound in silence) strongly affects the quality of life of sufferers. Tinnitus sufferers and their relatives frequently complain about major social impairments. However, it is not known whether this impairment directly results from the occurrence of tinnitus or is the indirect expression of a preexisting psychological vulnerability. Using the well-characterized animal model of salicylate-induced tinnitus, we investigate in mice whether the occurrence of tinnitus can trigger social impairments. Experiments were performed on 32 male Balb/C mice. Tinnitus was induced in mice using salicylate treatment. Social behavior was assessed in experimental and control animals using social interaction paradigm. Interaction time, number of social events, and number of nonsocial events were assessed in all animals. We demonstrate for the first time that treatment known to induce tinnitus triggers complex social impairments in mice. While salicylate-treated animals present a massive decrease in their overall social interactions compared to control untreated animals, they also display a paradoxal increase in the number of conspecific followings. Tinnitus can thus trigger a complex set of modifications of behavior, which will not only find their expression at the individual level, but also at the social level. Our results suggest that tinnitus can directly be a cause of psychosocial impairment in human and have strong implications for the clinical management of tinnitus sufferers.

A Collapsin Response Mediator Protein 2 Isoform Controls Myosin II-Mediated Cell Migration and Matrix Assembly by Trapping ROCK II

Science.gov (United States)

Morgan-Fisher, Marie; Wait, Robin; Couchman, John R.; Wewer, Ulla M.

2012-01-01

Collapsin response mediator protein 2 (CRMP-2) is known as a regulator of neuronal polarity and differentiation through microtubule assembly and trafficking. Here, we show that CRMP-2 is ubiquitously expressed and a splice variant (CRMP-2L), which is expressed mainly in epithelial cells among nonneuronal cells, regulates myosin II-mediated cellular functions, including cell migration. While the CRMP-2 short form (CRMP-2S) is recognized as a substrate of the Rho-GTP downstream kinase ROCK in neuronal cells, a CRMP-2 complex containing 2L not only bound the catalytic domain of ROCK II through two binding domains but also trapped and inhibited the kinase. CRMP-2L protein levels profoundly affected haptotactic migration and the actin-myosin cytoskeleton of carcinoma cells as well as nontransformed epithelial cell migration in a ROCK activity-dependent manner. Moreover, the ectopic expression of CRMP-2L but not -2S inhibited fibronectin matrix assembly in fibroblasts. Underlying these responses, CRMP-2L regulated the kinase activity of ROCK II but not ROCK I, independent of GTP-RhoA levels. This study provides a new insight into CRMP-2 as a controller of myosin II-mediated cellular functions through the inhibition of ROCK II in nonneuronal cells. PMID:22431514

Cardiac myosin binding protein C phosphorylation affects cross-bridge cycle's elementary steps in a site-specific manner.

Directory of Open Access Journals (Sweden)

Li Wang

Full Text Available Based on our recent finding that cardiac myosin binding protein C (cMyBP-C phosphorylation affects muscle contractility in a site-specific manner, we further studied the force per cross-bridge and the kinetic constants of the elementary steps in the six-state cross-bridge model in cMyBP-C mutated transgenic mice for better understanding of the influence of cMyBP-C phosphorylation on contractile functions. Papillary muscle fibres were dissected from cMyBP-C mutated mice of ADA (Ala273-Asp282-Ala302, DAD (Asp273-Ala282-Asp302, SAS (Ser273-Ala282-Ser302, and t/t (cMyBP-C null genotypes, and the results were compared to transgenic mice expressing wide-type (WT cMyBP-C. Sinusoidal analyses were performed with serial concentrations of ATP, phosphate (Pi, and ADP. Both t/t and DAD mutants significantly reduced active tension, force per cross-bridge, apparent rate constant (2πc, and the rate constant of cross-bridge detachment. In contrast to the weakened ATP binding and enhanced Pi and ADP release steps in t/t mice, DAD mice showed a decreased ADP release without affecting the ATP binding and the Pi release. ADA showed decreased ADP release, and slightly increased ATP binding and cross-bridge detachment steps, whereas SAS diminished the ATP binding step and accelerated the ADP release step. t/t has the broadest effects with changes in most elementary steps of the cross-bridge cycle, DAD mimics t/t to a large extent, and ADA and SAS predominantly affect the nucleotide binding steps. We conclude that the reduced tension production in DAD and t/t is the result of reduced force per cross-bridge, instead of the less number of strongly attached cross-bridges. We further conclude that cMyBP-C is an allosteric activator of myosin to increase cross-bridge force, and its phosphorylation status modulates the force, which is regulated by variety of protein kinases.

BAT Triggering Performance

Science.gov (United States)

McLean, Kassandra M.; Fenimore, E. E.; Palmer, D. M.; BAT Team

2006-09-01

The Burst Alert Telescope (BAT) onboard Swift has detected and located about 160 gamma-ray bursts (GRBs) in its first twenty months of operation. BAT employs two triggering systems to find GRBs: image triggering, which looks for a new point source in the field of view, and rate triggering, which looks for a significant increase in the observed counts. The image triggering system looks at 1 minute, 5 minute, and full pointing accumulations of counts in the detector plane in the energy range of 15-50 keV, with about 50 evaluations per pointing (about 40 minutes). The rate triggering system looks through 13 different time scales (from 4ms to 32s), 4 overlapping energy bins (covering 15-350 keV), 9 regions of the detector plane (from the full plane to individual quarters), and two background sampling models to search for GRBs. It evaluates 27000 trigger criteria in a second, for close to 1000 criteria. The image triggering system looks at 1, 5, and 40 minute accumulations of counts in the detector plane in the energy range of 15-50 keV. Both triggering systems are working very well with the settings from before launch and after we turned on BAT. However, we now have more than a year and a half of data to evaluate these triggering systems and tweak them for optimal performance, as well as lessons learned from these triggering systems.

Lessons from a tarantula: new insights into muscle thick filament and myosin interacting-heads motif structure and function.

Science.gov (United States)

Alamo, Lorenzo; Koubassova, Natalia; Pinto, Antonio; Gillilan, Richard; Tsaturyan, Andrey; Padrón, Raúl

2017-10-01

The tarantula skeletal muscle X-ray diffraction pattern suggested that the myosin heads were helically arranged on the thick filaments. Electron microscopy (EM) of negatively stained relaxed tarantula thick filaments revealed four helices of heads allowing a helical 3D reconstruction. Due to its low resolution (5.0 nm), the unambiguous interpretation of densities of both heads was not possible. A resolution increase up to 2.5 nm, achieved by cryo-EM of frozen-hydrated relaxed thick filaments and an iterative helical real space reconstruction, allowed the resolving of both heads. The two heads, "free" and "blocked", formed an asymmetric structure named the "interacting-heads motif" (IHM) which explained relaxation by self-inhibition of both heads ATPases. This finding made tarantula an exemplar system for thick filament structure and function studies. Heads were shown to be released and disordered by Ca 2+ -activation through myosin regulatory light chain phosphorylation, leading to EM, small angle X-ray diffraction and scattering, and spectroscopic and biochemical studies of the IHM structure and function. The results from these studies have consequent implications for understanding and explaining myosin super-relaxed state and thick filament activation and regulation. A cooperative phosphorylation mechanism for activation in tarantula skeletal muscle, involving swaying constitutively Ser35 mono-phosphorylated free heads, explains super-relaxation, force potentiation and post-tetanic potentiation through Ser45 mono-phosphorylated blocked heads. Based on this mechanism, we propose a swaying-swinging, tilting crossbridge-sliding filament for tarantula muscle contraction.

John Strong (1941 - 2006)

CERN Multimedia

Wickens, F

Our friend and colleague John Strong was cruelly taken from us by a brain tumour on Monday 31st July, a few days before his 65th birthday John started his career working with a group from Westfield College, under the leadership of Ted Bellamy. He obtained his PhD and spent the early part of his career on experiments at Rutherford Appleton Laboratory (RAL), but after the early 1970s his research was focussed on experiments in CERN. Over the years he made a number of notable contributions to experiments in CERN: The Omega spectrometer adopted a system John had originally developed for experiments at RAL using vidicon cameras to record the sparks in the spark chambers; He contributed to the success of NA1 and NA7, where he became heavily involved in the electronic trigger systems; He was responsible for the second level trigger system for the ALEPH detector and spent five years leading a team that designed and built the system, which ran for twelve years with only minor interventions. Following ALEPH he tur...

TRIGGER

CERN Multimedia

W. Smith

Level-1 Trigger Hardware The CERN group is working on the TTC system. Seven out of nine sub-detector TTC VME crates with all fibers cabled are installed in USC55. 17 Local Trigger Controller (LTC) boards have been received from production and are in the process of being tested. The RF2TTC module replacing the TTCmi machine interface has been delivered and will replace the TTCci module used to mimic the LHC clock. 11 out of 12 crates housing the barrel ECAL off-detector electronics have been installed in USC55 after commissioning at the Electronics Integration Centre in building 904. The cabling to the Regional Calorimeter Trigger (RCT) is terminated. The Lisbon group has completed the Synchronization and Link mezzanine board (SLB) production. The Palaiseau group has fully tested and installed 33 out of 40 Trigger Concentrator Cards (TCC). The seven remaining boards are being remade. The barrel TCC boards have been tested at the H4 test beam, and good agreement with emulator predictions were found. The cons...

The Quake-Catcher Network: Improving Earthquake Strong Motion Observations Through Community Engagement

Science.gov (United States)

Cochran, E. S.; Lawrence, J. F.; Christensen, C. M.; Chung, A. I.; Neighbors, C.; Saltzman, J.

2010-12-01

The Quake-Catcher Network (QCN) involves the community in strong motion data collection by utilizing volunteer computing techniques and low-cost MEMS accelerometers. Volunteer computing provides a mechanism to expand strong-motion seismology with minimal infrastructure costs, while promoting community participation in science. Micro-Electro-Mechanical Systems (MEMS) triaxial accelerometers can be attached to a desktop computer via USB and are internal to many laptops. Preliminary shake table tests show the MEMS accelerometers can record high-quality seismic data with instrument response similar to research-grade strong-motion sensors. QCN began distributing sensors and software to K-12 schools and the general public in April 2008 and has grown to roughly 1500 stations worldwide. We also recently tested whether sensors could be quickly deployed as part of a Rapid Aftershock Mobilization Program (RAMP) following the 2010 M8.8 Maule, Chile earthquake. Volunteers are recruited through media reports, web-based sensor request forms, as well as social networking sites. Using data collected to date, we examine whether a distributed sensing network can provide valuable seismic data for earthquake detection and characterization while promoting community participation in earthquake science. We utilize client-side triggering algorithms to determine when significant ground shaking occurs and this metadata is sent to the main QCN server. On average, trigger metadata are received within 1-10 seconds from the observation of a trigger; the larger data latencies are correlated with greater server-station distances. When triggers are detected, we determine if the triggers correlate to others in the network using spatial and temporal clustering of incoming trigger information. If a minimum number of triggers are detected then a QCN-event is declared and an initial earthquake location and magnitude is estimated. Initial analysis suggests that the estimated locations and magnitudes are

Spontaneous and trigger-associated substorms compared: Electrodynamic parameters in the polar ionosphere

Science.gov (United States)

Liu, Jun-Ming; Zhang, Bei-Chen; Kamide, Y.; Wu, Zhen-Sen; Hu, Ze-Jun; Yang, Hui-Gen

2011-01-01

An attempt is made to study the difference, if any, between the response of the polar ionosphere to spontaneous substorms and that to trigger-associated substorms in terms of electrodynamic parameters including ionospheric current vectors, the electric potential, and the current function. The results show that, in the first approximation, the ionospheric parameters for the two types of substorms are quite similar. It is therefore conceived that spontaneous substorms are not very different from trigger-associated substorms in the development of substorm processes in the magnetosphere-ionosphere system. We demonstrate, however, that spontaneous substorms seem to have a more clearly identifiable growth phase, whereas trigger-associated substorms have a more powerful unloading process. Changes in the current intensity and the electric potential drop across the polar cap in the recovery phase are also quite different from each other. Both the current intensity and the cross-polar cap potential drop show a larger decrease in the recovery phase of trigger-associated substorms, but the potential drop decreases only slightly and the currents in the late morning sector are still strong for spontaneous substorms. We interpret these findings as an indication of the relative importance of the unloading process and the directly driven process in conjunction with the north-south polarity of the interplanetary magnetic field. There still exists a strong directly driven process in the recovery phase of spontaneous substorms. For trigger-associated substorms, however, both the directly driven process and the unloading process become weak after the peak time.

Cortical mechanics and myosin-II abnormalities associated with post-ovulatory aging: implications for functional defects in aged eggs

Science.gov (United States)

Mackenzie, Amelia C.L.; Kyle, Diane D.; McGinnis, Lauren A.; Lee, Hyo J.; Aldana, Nathalia; Robinson, Douglas N.; Evans, Janice P.

2016-01-01

STUDY HYPOTHESIS Cellular aging of the egg following ovulation, also known as post-ovulatory aging, is associated with aberrant cortical mechanics and actomyosin cytoskeleton functions. STUDY FINDING Post-ovulatory aging is associated with dysfunction of non-muscle myosin-II, and pharmacologically induced myosin-II dysfunction produces some of the same deficiencies observed in aged eggs. WHAT IS KNOWN ALREADY Reproductive success is reduced with delayed fertilization and when copulation or insemination occurs at increased times after ovulation. Post-ovulatory aged eggs have several abnormalities in the plasma membrane and cortex, including reduced egg membrane receptivity to sperm, aberrant sperm-induced cortical remodeling and formation of fertilization cones at the site of sperm entry, and reduced ability to establish a membrane block to prevent polyspermic fertilization. STUDY DESIGN, SAMPLES/MATERIALS, METHODS Ovulated mouse eggs were collected at 21–22 h post-human chorionic gonadotrophin (hCG) (aged eggs) or at 13–14 h post-hCG (young eggs), or young eggs were treated with the myosin light chain kinase (MLCK) inhibitor ML-7, to test the hypothesis that disruption of myosin-II function could mimic some of the effects of post-ovulatory aging. Eggs were subjected to various analyses. Cytoskeletal proteins in eggs and parthenogenesis were assessed using fluorescence microscopy, with further analysis of cytoskeletal proteins in immunoblotting experiments. Cortical tension was measured through micropipette aspiration assays. Egg membrane receptivity to sperm was assessed in in vitro fertilization (IVF) assays. Membrane topography was examined by low-vacuum scanning electron microscopy (SEM). MAIN RESULTS AND THE ROLE OF CHANCE Aged eggs have decreased levels and abnormal localizations of phosphorylated myosin-II regulatory light chain (pMRLC; P = 0.0062). Cortical tension, which is mediated in part by myosin-II, is reduced in aged mouse eggs when compared with

Radioimmunoassay of myosin heavy beta chains in human serum for the evaluation of the size of myocardial infarction: correlation with myocardial Tl-201 SPECT and cardiac angioscintigraphy

International Nuclear Information System (INIS)

Facello, A.; Gries, P.; Demangeat, C.; Brunot, B.; Roul, G.; Demangeat, J.L.; Moulichon, M.; Bareiss, P.; Sacrez, A.; Constantinesco, A.

1990-01-01

To determine the relationship between serum levels of myosin heavy beta chains assessed by an IRMA technique and other radionuclide and enzymatic parameters in the evaluation of the size of myocardial infarction, we studied 22 patients with acute myocardial infarction. Blood samples taken daily between 1st to 13th day of evolution allow the determination of peak and integral of myosine release that showed a good correlation (p [fr

C0 and C1 N-terminal Ig domains of myosin binding protein C exert different effects on thin filament activation.

Science.gov (United States)

Harris, Samantha P; Belknap, Betty; Van Sciver, Robert E; White, Howard D; Galkin, Vitold E

2016-02-09

Mutations in genes encoding myosin, the molecular motor that powers cardiac muscle contraction, and its accessory protein, cardiac myosin binding protein C (cMyBP-C), are the two most common causes of hypertrophic cardiomyopathy (HCM). Recent studies established that the N-terminal domains (NTDs) of cMyBP-C (e.g., C0, C1, M, and C2) can bind to and activate or inhibit the thin filament (TF). However, the molecular mechanism(s) by which NTDs modulate interaction of myosin with the TF remains unknown and the contribution of each individual NTD to TF activation/inhibition is unclear. Here we used an integrated structure-function approach using cryoelectron microscopy, biochemical kinetics, and force measurements to reveal how the first two Ig-like domains of cMyPB-C (C0 and C1) interact with the TF. Results demonstrate that despite being structural homologs, C0 and C1 exhibit different patterns of binding on the surface of F-actin. Importantly, C1 but not C0 binds in a position to activate the TF by shifting tropomyosin (Tm) to the "open" structural state. We further show that C1 directly interacts with Tm and traps Tm in the open position on the surface of F-actin. Both C0 and C1 compete with myosin subfragment 1 for binding to F-actin and effectively inhibit actomyosin interactions when present at high ratios of NTDs to F-actin. Finally, we show that in contracting sarcomeres, the activating effect of C1 is apparent only once low levels of Ca(2+) have been achieved. We suggest that Ca(2+) modulates the interaction of cMyBP-C with the TF in the sarcomere.

Emerging ST121/agr4 community-associated methicillin-resistant Staphylococcus aureus (MRSA with strong adhesin and cytolytic activities: trigger for MRSA pneumonia and fatal aspiration pneumonia in an influenza-infected elderly

Directory of Open Access Journals (Sweden)

T.-W. Wan

2016-09-01

Full Text Available The pathogenesis of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA pneumonia in influenza-infected elderly individuals has not yet been elucidated in detail. In the present study, a 92-year-old man infected with influenza developed CA-MRSA pneumonia. His CA-MRSA was an emerging type, originated in ST121/agr4 S. aureus, with diversities of Panton–Valentine leucocidin (PVL−/spat5110/SCCmecV+ versus PVL+/spat159(etc./SCCmec−, but with common virulence potentials of strong adhesin and cytolytic activities. Resistance to erythromycin/clindamycin (inducible-type and gentamicin was detected. Pneumonia improved with the administration of levofloxacin, but with the subsequent development of fatal aspiration pneumonia. Hence, characteristic CA-MRSA with strong adhesin and cytolytic activities triggered influenza-related sequential complications.

NOMAD Trigger Studies

International Nuclear Information System (INIS)

Varvell, K.

1995-01-01

The author reports on the status of an offline study of the NOMAD triggers, which has several motivations. Of primary importance is to demonstrate, using offline information recorded by the individual subdetectors comprising NOMAD, that the online trigger system is functioning as expected. Such an investigation serves to complement the extensive monitoring which is already carried out online. More specific to the needs of the offline software and analysis, the reconstruction of tracks and vertices in the detector requires some knowledge of the time at which the trigger has occurred, in order to locate relevant hits in the drift chambers and muon chambers in particular. The fact that the different triggers allowed by the MIOTRINO board take varying times to form complicates this task. An offline trigger algorithm may serve as a tool to shed light on situations where the online trigger status bits have not been recorded correctly, as happens in a small number of cases, or as an aid to studies with the aim of further refinement of the online triggers themselves

Therapeutic-Ultrasound-Triggered Shape Memory of a Melamine-Enhanced Poly(vinyl alcohol) Physical Hydrogel.

Science.gov (United States)

Li, Guo; Yan, Qiang; Xia, Hesheng; Zhao, Yue

2015-06-10

Therapeutic-ultrasound-triggered shape memory was demonstrated for the first time with a melamine-enhanced poly(vinyl alcohol) (PVA) physical hydrogel. The addition of a small amount of melamine (up to 1.5 wt %) in PVA results in a strong hydrogel due to the multiple H-bonding between the two constituents. A temporary shape of the hydrogel can be obtained by deformation of the hydrogel (∼65 wt % water) at room temperature, followed by fixation of the deformation by freezing/thawing the hydrogel under strain, which induces crystallization of PVA. We show that the ultrasound delivered by a commercially available device designed for the patient's pain relief could trigger the shape recovery process as a result of ultrasound-induced local heating in the hydrogel that melts the crystallized PVA cross-linking. This hydrogel is thus interesting for potential applications because it combines many desirable properties, being mechanically strong, biocompatible, and self-healable and displaying the shape memory capability triggered by a physiological stimulus.

An adhesome comprising laminin, dystroglycan and myosin IIA is required during notochord development in Xenopus laevis.

Science.gov (United States)

Buisson, Nicolas; Sirour, Cathy; Moreau, Nicole; Denker, Elsa; Le Bouffant, Ronan; Goullancourt, Aline; Darribère, Thierry; Bello, Valérie

2014-12-01

Dystroglycan (Dg) is a transmembrane receptor for laminin that must be expressed at the right time and place in order to be involved in notochord morphogenesis. The function of Dg was examined in Xenopus laevis embryos by knockdown of Dg and overexpression and replacement of the endogenous Dg with a mutated form of the protein. This analysis revealed that Dg is required for correct laminin assembly, for cell polarization during mediolateral intercalation and for proper differentiation of vacuoles. Using mutations in the cytoplasmic domain, we identified two sites that are involved in cell polarization and are required for mediolateral cell intercalation, and a site that is required for vacuolation. Furthermore, using a proteomic analysis, the cytoskeletal non-muscle myosin IIA has been identified for the first time as a molecular link between the Dg-cytoplasmic domain and cortical actin. The data allowed us to identify the adhesome laminin-Dg-myosin IIA as being required to maintain the cortical actin cytoskeleton network during vacuolation, which is crucial to maintain the shape of notochordal cells. © 2014. Published by The Company of Biologists Ltd.

Cloning of skeletal myosin heavy chain gene family from adult pleopod muscle and whole larvae of shrimps.

Science.gov (United States)

Koyama, Hiroki; Piyapattanakorn, Sanit; Watabe, Shugo

2013-06-01

The physiological and biological properties of skeletal muscle in crustacea have not been well understood compared with those of vertebrates. The present study focused on myosin, the major protein in skeletal muscle, from shrimps. In our previous study, two full-length genes encoding myosin heavy chain (MHC), a large subunit of the myosin molecule, were cloned from abdominal fast skeletal muscle of kuruma Marsupenaeus japonicus, black tiger Penaeus monodon and Pacific white Penaeus vannamei shrimps, and named as MHCa and MHCb. In this study, we renamed these as MHC1 and MHC2, respectively, due to the presence of various isoforms newly identified. Partial MHC sequences were identified from pleopod muscle of these shrimps. Two MHCs, named MHC3 and MHC4, were identified from pleopod muscle of kuruma shrimp, whereas two MHCs, named MHC4 and MHC5, were cloned from Pacific white shrimp pleopod. MHC3 was cloned only from black tiger shrimp pleopod. Partial MHC sequences from zoea, mysis, and postlarvae of black tiger and Pacific white shrimps were also determined. The phylogenetic tree demonstrated that most MHCs from pleopod muscle and larval MHCs formed clades with MHC1 and MHC2, respectively. These MHCs were considered to be of fast type, since MHC1 and MHC2 are fast-type MHCs according to our previous study. MHC5 obtained from pleopod muscle of Pacific white shrimp in this study was monophyletic with American lobster Homarus americanus S2 slow tonic MHC previously reported, indicating that MHC5 from Pacific white shrimp is of slow type. Copyright © 2013 Wiley Periodicals, Inc.

Triggering at high luminosity: fake triggers from pile-up

International Nuclear Information System (INIS)

Johnson, R.

1983-01-01

Triggers based on a cut in transverse momentum (p/sub t/) have proved to be useful in high energy physics both because they indicte that a hard constituent scattering has occurred and because they can be made quickly enough to gate electronics. These triggers will continue to be useful at high luminosities if overlapping events do not cause an excessive number of fake triggers. In this paper, I determine if this is indeed a problem at high luminosity machines

Myosin dephosphorylation during rapid relaxation of hog carotid artery smooth muscle.

Science.gov (United States)

Driska, S P; Stein, P G; Porter, R

1989-02-01

Changes in myosin light chain phosphorylation were measured during histamine-induced rhythmic contractions of hog carotid artery smooth muscle strips. Histamine made the muscle strips contract spontaneously every 1-5 min, and this allowed measurement of the time course of phosphorylation in relation to force development under conditions where diffusion of the agonist through tissue would not complicate the interpretation of the data. In the absence of histamine, phosphorylation was low [0.12 +/- 0.04 mol P/mol of the 20,000-Da light chain (LC 20)]. Phosphorylation was slightly (but not significantly) higher in the presence of 10 microM histamine in the relaxed state between contractions (0.20 +/- 0.03 mol P/mol LC 20). In muscle strips frozen during force development, when force had reached half of its peak value, phosphorylation was 0.38 +/- 0.06 mol P/mol LC 20. The highest levels of phosphorylation (0.49 +/- 0.04 mol P/mol LC 20) were found in strips frozen at the peak of the rhythmic contractions. Strips frozen when force had declined to half of the peak force showed low levels of phosphorylation (0.17 +/- 0.07 mol P/mol LC 20), indicating that the myosin light chain phosphatase activity was quite high. Mathematical modeling of the kinase and phosphatase reactions suggested that the apparent first-order phosphatase rate constant was at least 0.08 s-1 under these conditions. To obtain a better estimate of this rate constant, a second series of phosphorylation measurements were made early in the relaxation phase of the rhythmic contractions. The highest phosphatase rate constant obtained from these measurements was 0.23 s-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction between cardiac myosin-binding protein C and formin Fhod3.

Science.gov (United States)

Matsuyama, Sho; Kage, Yohko; Fujimoto, Noriko; Ushijima, Tomoki; Tsuruda, Toshihiro; Kitamura, Kazuo; Shiose, Akira; Asada, Yujiro; Sumimoto, Hideki; Takeya, Ryu

2018-05-08

Mutations in cardiac myosin-binding protein C (cMyBP-C) are a major cause of familial hypertrophic cardiomyopathy. Although cMyBP-C has been considered to regulate the cardiac function via cross-bridge arrangement at the C-zone of the myosin-containing A-band, the mechanism by which cMyBP-C functions remains unclear. We identified formin Fhod3, an actin organizer essential for the formation and maintenance of cardiac sarcomeres, as a cMyBP-C-binding protein. The cardiac-specific N-terminal Ig-like domain of cMyBP-C directly interacts with the cardiac-specific N-terminal region of Fhod3. The interaction seems to direct the localization of Fhod3 to the C-zone, since a noncardiac Fhod3 variant lacking the cMyBP-C-binding region failed to localize to the C-zone. Conversely, the cardiac variant of Fhod3 failed to localize to the C-zone in the cMyBP-C-null mice, which display a phenotype of hypertrophic cardiomyopathy. The cardiomyopathic phenotype of cMyBP-C-null mice was further exacerbated by Fhod3 overexpression with a defect of sarcomere integrity, whereas that was partially ameliorated by a reduction in the Fhod3 protein levels, suggesting that Fhod3 has a deleterious effect on cardiac function under cMyBP-C-null conditions where Fhod3 is aberrantly mislocalized. Together, these findings suggest the possibility that Fhod3 contributes to the pathogenesis of cMyBP-C-related cardiomyopathy and that Fhod3 is critically involved in cMyBP-C-mediated regulation of cardiac function via direct interaction.

Trigger finger

Science.gov (United States)

... digit; Trigger finger release; Locked finger; Digital flexor tenosynovitis ... cut or hand Yellow or green drainage from the cut Hand pain or discomfort Fever If your trigger finger returns, call your surgeon. You may need another surgery.

The influence of temperature on the distribution and intensity of the reaction product in rat muscle fibers obtained with the histochemical method for myosin ATPase

DEFF Research Database (Denmark)

Kirkeby, S; Tuxen, A

1989-01-01

The influence of temperature in the incubation medium on the localization and intensity of myosin ATPase was investigated in striated muscles from the rat using a conventional histochemical technique. It was found that the enzyme reaction was temperature-dependent since the activity in some fibers...... was raised and in others was depressed by alteration of the incubation temperature. There was no obvious correlation between the temperature sensitivity of ATPase in the muscle fibers and their activity for succinic dehydrogenase. It is proposed that the histochemical method for myosin ATPase can be used...

Planar polarization of Vangl2 in the vertebrate neural plate is controlled by Wnt and Myosin II signaling

Directory of Open Access Journals (Sweden)

Olga Ossipova

2015-07-01

Full Text Available The vertebrate neural tube forms as a result of complex morphogenetic movements, which require the functions of several core planar cell polarity (PCP proteins, including Vangl2 and Prickle. Despite the importance of these proteins for neurulation, their subcellular localization and the mode of action have remained largely unknown. Here we describe the anteroposterior planar cell polarity (AP-PCP of the cells in the Xenopus neural plate. At the neural midline, the Vangl2 protein is enriched at anterior cell edges and that this localization is directed by Prickle, a Vangl2-interacting protein. Our further analysis is consistent with the model, in which Vangl2 AP-PCP is established in the neural plate as a consequence of Wnt-dependent phosphorylation. Additionally, we uncover feedback regulation of Vangl2 polarity by Myosin II, reiterating a role for mechanical forces in PCP. These observations indicate that both Wnt signaling and Myosin II activity regulate cell polarity and cell behaviors during vertebrate neurulation.

Topological Trigger Developments

CERN Multimedia

Likhomanenko, Tatiana

2015-01-01

The main b-physics trigger algorithm used by the LHCb experiment is the so-called topological trigger. The topological trigger selects vertices which are a) detached from the primary proton-proton collision and b) compatible with coming from the decay of a b-hadron. In the LHC Run 1, this trigger utilized a custom boosted decision tree algorithm, selected an almost 100% pure sample of b-hadrons with a typical efficiency of 60-70%, and its output was used in about 60% of LHCb papers. This talk presents studies carried out to optimize the topological trigger for LHC Run 2. In particular, we have carried out a detailed comparison of various machine learning classifier algorithms, e.g., AdaBoost, MatrixNet and uBoost. The topological trigger algorithm is designed to select all "interesting" decays of b-hadrons, but cannot be trained on every such decay. Studies have therefore been performed to determine how to optimize the performance of the classification algorithm on decays not used in the training. These inclu...

A Cook, A Cardinal, His Priests, and the Press: Deviance as a Trigger for Intermedia Agenda Setting.

Science.gov (United States)

Breen, Michael J.

1997-01-01

Uses content analysis to examine the changes in trends in the aftermath of deviant acts by individual members of the clergy, given that such acts are "triggering events" for further negative stories. Finds strong media agenda-setting effects of the negative triggering events on subsequent coverage of the clergy in general. (SR)

Development of a digital trigger system to identify recoil protons at COMPASS-II

Energy Technology Data Exchange (ETDEWEB)

Buechele, Maximilian; Fischer, Horst; Gorzellik, Matthias; Grussenmeyer, Tobias; Herrmann, Florian; Joerg, Philipp; Koenigsmann, Kay; Kremser, Paul; Schopferer, Sebastian [Albert-Ludwigs-Universitaet Freiburg (Germany)

2014-07-01

The GANDALF framework has been developed to deliver a high precision, high performance detector readout and trigger system for particle physics experiments such as the COMPASS-II experiment at CERN. Combining the high performance pulse digitization and feature extraction capabilities of twelve GANDALF modules, each comprising a Virtex-5 SX95T, with the strong computation power of a Virtex-6 SX315T FGPA operated on the TIGER module, we present a digital trigger system for a recoil proton detector. The trigger system was setup and commissioned successfully during a data taking period in 2012. It was mainly used for the calibration of the recoil proton detector and in tagging mode to identify proton tracks online.

Human Masseter Muscle Fibers From the Elderly Express Less Neonatal Myosin Than Those of Young Adults

Czech Academy of Sciences Publication Activity Database

Cvetko, E.; Karen, Petr; Janáček, Jiří; Kubínová, Lucie; Plasencia, A.L.; Eržen, I.

2012-01-01

Roč. 295, č. 8 (2012), s. 1364-1372 ISSN 1932-8486 R&D Projects: GA MŠk(CZ) LC06063; GA MŠk(CZ) MEB090910 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : aging * confocal microscopy * myosin heavy chain * immunohistochemistry * muscle fiber types Subject RIV: FH - Neurology Impact factor: 1.343, year: 2012

Cloud-Resolving Model Simulations of Aerosol-Cloud Interactions Triggered by Strong Aerosol Emissions in the Arctic

Science.gov (United States)

Wang, H.; Kravitz, B.; Rasch, P. J.; Morrison, H.; Solomon, A.

2014-12-01

Previous process-oriented modeling studies have highlighted the dependence of effectiveness of cloud brightening by aerosols on cloud regimes in warm marine boundary layer. Cloud microphysical processes in clouds that contain ice, and hence the mechanisms that drive aerosol-cloud interactions, are more complicated than in warm clouds. Interactions between ice particles and liquid drops add additional levels of complexity to aerosol effects. A cloud-resolving model is used to study aerosol-cloud interactions in the Arctic triggered by strong aerosol emissions, through either geoengineering injection or concentrated sources such as shipping and fires. An updated cloud microphysical scheme with prognostic aerosol and cloud particle numbers is employed. Model simulations are performed in pure super-cooled liquid and mixed-phase clouds, separately, with or without an injection of aerosols into either a clean or a more polluted Arctic boundary layer. Vertical mixing and cloud scavenging of particles injected from the surface is still quite efficient in the less turbulent cold environment. Overall, the injection of aerosols into the Arctic boundary layer can delay the collapse of the boundary layer and increase low-cloud albedo. The pure liquid clouds are more susceptible to the increase in aerosol number concentration than the mixed-phase clouds. Rain production processes are more effectively suppressed by aerosol injection, whereas ice precipitation (snow) is affected less; thus the effectiveness of brightening mixed-phase clouds is lower than for liquid-only clouds. Aerosol injection into a clean boundary layer results in a greater cloud albedo increase than injection into a polluted one, consistent with current knowledge about aerosol-cloud interactions. Unlike previous studies investigating warm clouds, the impact of dynamical feedback due to precipitation changes is small. According to these results, which are dependent upon the representation of ice nucleation

Bulkiness or aromatic nature of tyrosine-143 of actin is important for the weak binding between F-actin and myosin-ADP-phosphate

Energy Technology Data Exchange (ETDEWEB)

Gomibuchi, Yuki [Graduate School of Science and Engineering, Teikyo University, Toyosatodai 1-1, Utsunomiya 320-8551 (Japan); Uyeda, Taro Q.P. [Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, AIST Tsukuba Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562 (Japan); Wakabayashi, Takeyuki, E-mail: tw007@nasu.bio.teikyo-u.ac.jp [Graduate School of Science and Engineering, Teikyo University, Toyosatodai 1-1, Utsunomiya 320-8551 (Japan); Department of Judo Therapy, Faculty of Medical Technology, Teikyo University, Toyosatodai 1-1, Utsunomiya 320-8551 (Japan)

2013-11-29

Highlights: •The effect of mutation of Tyr143 that becomes more exposed on assembly was examined. •Mutation of tyrosine-143 of Dictyostelium actin changed actin polymerizability. •The bulkiness or aromatic nature of Tyr143 is important for the weak binding. •The weak interaction between myosin and actin strengthened by Tyr143Trp mutation. -- Abstract: Actin filaments (F-actin) interact with myosin and activate its ATPase to support force generation. By comparing crystal structures of G-actin and the quasi-atomic model of F-actin based on high-resolution cryo-electron microscopy, the tyrosine-143 was found to be exposed more than 60 Å{sup 2} to the solvent in F-actin. Because tyrosine-143 flanks the hydrophobic cleft near the hydrophobic helix that binds to myosin, the mutant actins, of which the tyrosine-143 was replaced with tryptophan, phenylalanine, or isoleucine, were generated using the Dictyostelium expression system. It polymerized significantly poorly when induced by NaCl, but almost normally by KCl. In the presence of phalloidin and KCl, the extents of the polymerization of all the mutant actins were comparable to that of the wild-type actin so that the actin-activated myosin ATPase activity could be reliably compared. The affinity of skeletal heavy meromyosin to F-actin and the maximum ATPase activity (V{sub max}) were estimated by a double reciprocal plot. The Tyr143Trp-actin showed the higher affinity (smaller K{sub app}) than that of the wild-type actin, with the V{sub max} being almost unchanged. The K{sub app} and V{sub max} of the Tyr143Phe-actin were similar to those of the wild-type actin. However, the activation by Tyr143Ile-actin was much smaller than the wild-type actin and the accurate determination of K{sub app} was difficult. Comparison of the myosin ATPase activated by the various mutant actins at the same concentration of F-actin showed that the extent of activation correlates well with the solvent-accessible surface areas (ASA

Remote Triggering of the Mw 6.9 Hokkaido Earthquake as a Result of the Mw 6.6 Indonesian Earthquake on September 11, 2008

Directory of Open Access Journals (Sweden)

Cheng-Horng Lin

2012-01-01

Full Text Available Only just recently, the phenomenon of earthquakes being triggered by a distant earthquake has been well established. Yet, most of the triggered earthquakes have been limited to small earthquakes (M < 3. Also, the exact triggering mechanism for earthquakes is still not clear. Here I show how one strong earthquake (Mw = 6.6 is capable of triggering another (Mw = 6.9 at a remote distance (~4750 km. On September 11, 2008, two strong earthquakes with magnitudes (Mw of 6.6 and 6.9 hit respectively in Indonesia and Japan within a short interval of ~21 minutes time. Careful examination of broadband seismograms recorded in Japan shows that the Hokkaido earthquake occurred just as the surface waves generated by the Indonesia earthquake arrived. Although the peak dynamic stress estimated at the focus of the Hokkaido earthquake was just reaching the lower bound for the capability of triggering earthquakes in general, a more plausible mechanism for triggering an earthquake might be attributed to the change of a fault property by fluid infiltration. These observations suggest that the Hokkaido earthquake was likely triggered from a remote distance by the surface waves generated from the Indonesia earthquake. If some more cases can be observed, a temporal warning of possible interaction between strong earthquakes might be concerned in the future.

The Central Trigger Processor (CTP)

CERN Multimedia

Franchini, Matteo

2016-01-01

The Central Trigger Processor (CTP) receives trigger information from the calorimeter and muon trigger processors, as well as from other sources of trigger. It makes the Level-1 decision (L1A) based on a trigger menu.

Incorporating human-triggered earthquake risks into energy and water policies

Science.gov (United States)

Klose, C. D.; Seeber, L.; Jacob, K. H.

2010-12-01

A comprehensive understanding of earthquake risks in urbanized regions requires an accurate assessment of both urban vulnerabilities and hazards from earthquakes, including ones whose timing might be affected by human activities. Socioeconomic risks associated with human-triggered earthquakes are often misconstrued and receive little scientific, legal, and public attention. Worldwide, more than 200 damaging earthquakes, associated with industrialization and urbanization, were documented since the 20th century. Geomechanical pollution due to large-scale geoengineering activities can advance the clock of earthquakes, trigger new seismic events or even shot down natural background seismicity. Activities include mining, hydrocarbon production, fluid injections, water reservoir impoundments and deep-well geothermal energy production. This type of geohazard has impacts on human security on a regional and national level. Some planned or considered future engineering projects raise particularly strong concerns about triggered earthquakes, such as for instance, sequestration of carbon dioxide by injecting it deep underground and large-scale natural gas production in the Marcellus shale in the Appalacian basin. Worldwide examples of earthquakes are discussed, including their associated losses of human life and monetary losses (e.g., 1989 Newcastle and Volkershausen earthquakes, 2001 Killari earthquake, 2006 Basel earthquake, 2010 Wenchuan earthquake). An overview is given on global statistics of human-triggered earthquakes, including depths and time delay of triggering. Lastly, strategies are described, including risk mitigation measures such as urban planning adaptations and seismic hazard mapping.

The Trigger Processor and Trigger Processor Algorithms for the ATLAS New Small Wheel Upgrade

CERN Document Server

Lazovich, Tomo; The ATLAS collaboration

2015-01-01

The ATLAS New Small Wheel (NSW) is an upgrade to the ATLAS muon endcap detectors that will be installed during the next long shutdown of the LHC. Comprising both MicroMegas (MMs) and small-strip Thin Gap Chambers (sTGCs), this system will drastically improve the performance of the muon system in a high cavern background environment. The NSW trigger, in particular, will significantly reduce the rate of fake triggers coming from track segments in the endcap not originating from the interaction point. We will present an overview of the trigger, the proposed sTGC and MM trigger algorithms, and the hardware implementation of the trigger. In particular, we will discuss both the heart of the trigger, an ATCA system with FPGA-based trigger processors (using the same hardware platform for both MM and sTGC triggers), as well as the full trigger electronics chain, including dedicated cards for transmission of data via GBT optical links. Finally, we will detail the challenges of ensuring that the trigger electronics can ...

β-Arrestin regulation of myosin light chain phosphorylation promotes AT1aR-mediated cell contraction and migration.

Directory of Open Access Journals (Sweden)

Elie Simard

Full Text Available Over the last decade, it has been established that G-protein-coupled receptors (GPCRs signal not only through canonical G-protein-mediated mechanisms, but also through the ubiquitous cellular scaffolds β-arrestin-1 and β-arrestin-2. Previous studies have implicated β-arrestins as regulators of actin reorganization in response to GPCR stimulation while also being required for membrane protrusion events that accompany cellular motility. One of the most critical events in the active movement of cells is the cyclic phosphorylation and activation of myosin light chain (MLC, which is required for cellular contraction and movement. We have identified the myosin light chain phosphatase Targeting Subunit (MYPT-1 as a binding partner of the β-arrestins and found that β-arrestins play a role in regulating the turnover of phosphorylated myosin light chain. In response to stimulation of the angiotensin Type 1a Receptor (AT1aR, MLC phosphorylation is induced quickly and potently. We have found that β-arrestin-2 facilitates dephosphorylation of MLC, while, in a reciprocal fashion, β-arrestin 1 limits dephosphorylation of MLC. Intriguingly, loss of either β-arrestin-1 or 2 blocks phospho-MLC turnover and causes a decrease in the contraction of cells as monitored by atomic force microscopy (AFM. Furthermore, by employing the β-arrestin biased ligand [Sar(1,Ile(4,Ile(8]-Ang, we demonstrate that AT1aR-mediated cellular motility involves a β-arrestin dependent component. This suggests that the reciprocal regulation of MLC phosphorylation status by β-arrestins-1 and 2 causes turnover in the phosphorylation status of MLC that is required for cell contractility and subsequent chemotaxic motility.

Reducing Environmental Allergic Triggers: Policy Issues.

Science.gov (United States)

Abramson, Stuart L

The implementation of policies to reduce environmental allergic triggers can be an important adjunct to optimal patient care for allergic rhinitis and allergic asthma. Policies at the local level in schools and other public as well as private buildings can make an impact on disease morbidity. Occupational exposures for allergens have not yet been met with the same rigorous policy standards applied for exposures to toxicants by Occupational Safety and Health Administration. Further benefit may be obtained through policies by local, county, state, and national governments, and possibly through international cooperative agreements. The reduction of allergenic exposures can and should be affected by policies with strong scientific, evidence-based derivation. However, a judicious application of the precautionary principle may be needed in circumstances where the health effect of inaction could lead to more serious threats to vulnerable populations with allergic disease. This commentary covers the scientific basis, current implementation, knowledge gaps, and pro/con views on policy issues in reducing environmental allergic triggers. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Predictability in the Epidemic-Type Aftershock Sequence model of interacting triggered seismicity

Science.gov (United States)

Helmstetter, AgnèS.; Sornette, Didier

2003-10-01

As part of an effort to develop a systematic methodology for earthquake forecasting, we use a simple model of seismicity on the basis of interacting events which may trigger a cascade of earthquakes, known as the Epidemic-Type Aftershock Sequence model (ETAS). The ETAS model is constructed on a bare (unrenormalized) Omori law, the Gutenberg-Richter law, and the idea that large events trigger more numerous aftershocks. For simplicity, we do not use the information on the spatial location of earthquakes and work only in the time domain. We demonstrate the essential role played by the cascade of triggered seismicity in controlling the rate of aftershock decay as well as the overall level of seismicity in the presence of a constant external seismicity source. We offer an analytical approach to account for the yet unobserved triggered seismicity adapted to the problem of forecasting future seismic rates at varying horizons from the present. Tests presented on synthetic catalogs validate strongly the importance of taking into account all the cascades of still unobserved triggered events in order to predict correctly the future level of seismicity beyond a few minutes. We find a strong predictability if one accepts to predict only a small fraction of the large-magnitude targets. Specifically, we find a prediction gain (defined as the ratio of the fraction of predicted events over the fraction of time in alarms) equal to 21 for a fraction of alarm of 1%, a target magnitude M ≥ 6, an update time of 0.5 days between two predictions, and for realistic parameters of the ETAS model. However, the probability gains degrade fast when one attempts to predict a larger fraction of the targets. This is because a significant fraction of events remain uncorrelated from past seismicity. This delineates the fundamental limits underlying forecasting skills, stemming from an intrinsic stochastic component in these interacting triggered seismicity models. Quantitatively, the fundamental

Two-boundary first exit time of Gauss-Markov processes for stochastic modeling of acto-myosin dynamics.

Science.gov (United States)

D'Onofrio, Giuseppe; Pirozzi, Enrica

2017-05-01

We consider a stochastic differential equation in a strip, with coefficients suitably chosen to describe the acto-myosin interaction subject to time-varying forces. By simulating trajectories of the stochastic dynamics via an Euler discretization-based algorithm, we fit experimental data and determine the values of involved parameters. The steps of the myosin are represented by the exit events from the strip. Motivated by these results, we propose a specific stochastic model based on the corresponding time-inhomogeneous Gauss-Markov and diffusion process evolving between two absorbing boundaries. We specify the mean and covariance functions of the stochastic modeling process taking into account time-dependent forces including the effect of an external load. We accurately determine the probability density function (pdf) of the first exit time (FET) from the strip by solving a system of two non singular second-type Volterra integral equations via a numerical quadrature. We provide numerical estimations of the mean of FET as approximations of the dwell-time of the proteins dynamics. The percentage of backward steps is given in agreement to experimental data. Numerical and simulation results are compared and discussed.

Bifunctional Rhodamine Probes of Myosin Regulatory Light Chain Orientation in Relaxed Skeletal Muscle Fibers

Science.gov (United States)

Brack, Andrew S.; Brandmeier, Birgit D.; Ferguson, Roisean E.; Criddle, Susan; Dale, Robert E.; Irving, Malcolm

2004-01-01

The orientation of the regulatory light chain (RLC) region of the myosin heads in relaxed skinned fibers from rabbit psoas muscle was investigated by polarized fluorescence from bifunctional rhodamine (BR) probes cross-linking pairs of cysteine residues introduced into the RLC. Pure 1:1 BR-RLC complexes were exchanged into single muscle fibers in EDTA rigor solution for 30 min at 30°C; ∼60% of the native RLC was removed and stoichiometrically replaced by BR-RLC, and >85% of the BR-RLC was located in the sarcomeric A-bands. The second- and fourth-rank order parameters of the orientation distributions of BR dipoles linking RLC cysteine pairs 100-108, 100-113, 108-113, and 104-115 were calculated from polarized fluorescence intensities, and used to determine the smoothest RLC orientation distribution—the maximum entropy distribution—consistent with the polarized fluorescence data. Maximum entropy distributions in relaxed muscle were relatively broad. At the peak of the distribution, the “lever” axis, linking Cys707 and Lys843 of the myosin heavy chain, was at 70–80° to the fiber axis, and the “hook” helix (Pro830–Lys843) was almost coplanar with the fiber and lever axes. The temperature and ionic strength of the relaxing solution had small but reproducible effects on the orientation of the RLC region. PMID:15041671

Instructors' Use of Trigger Warnings and Behavior Warnings in Abnormal Psychology

Science.gov (United States)

Boysen, Guy A.; Wells, Anna Mae; Dawson, Kaylee J.

2016-01-01

College students have been increasingly demanding warnings and accommodations in relation to course topics they believe will elicit strong, negative emotions. These "trigger warnings" are highly relevant to Abnormal Psychology because of the sensitive topics covered in the course (e.g., suicide, trauma, sex). A survey of Abnormal…

Conformational distributions and proximity relationships in the rigor complex of actin and myosin subfragment-1.

Science.gov (United States)

Nyitrai, M; Hild, G; Lukács, A; Bódis, E; Somogyi, B

2000-01-28

Cyclic conformational changes in the myosin head are considered essential for muscle contraction. We hereby show that the extension of the fluorescence resonance energy transfer method described originally by Taylor et al. (Taylor, D. L., Reidler, J., Spudich, J. A., and Stryer, L. (1981) J. Cell Biol. 89, 362-367) allows determination of the position of a labeled point outside the actin filament in supramolecular complexes and also characterization of the conformational heterogeneity of an actin-binding protein while considering donor-acceptor distance distributions. Using this method we analyzed proximity relationships between two labeled points of S1 and the actin filament in the acto-S1 rigor complex. The donor (N-[[(iodoacetyl)amino]ethyl]-5-naphthylamine-1-sulfonate) was attached to either the catalytic domain (Cys-707) or the essential light chain (Cys-177) of S1, whereas the acceptor (5-(iodoacetamido)fluorescein) was attached to the actin filament (Cys-374). In contrast to the narrow positional distribution (assumed as being Gaussian) of Cys-707 (5 +/- 3 A), the positional distribution of Cys-177 was found to be broad (102 +/- 4 A). Such a broad positional distribution of the label on the essential light chain of S1 may be important in accommodating the helically arranged acto-myosin binding relative to the filament axis.

Frequency-Dependent Tidal Triggering of Low Frequency Earthquakes Near Parkfield, California

Science.gov (United States)

Xue, L.; Burgmann, R.; Shelly, D. R.

2017-12-01

The effect of small periodic stress perturbations on earthquake generation is not clear, however, the rate of low-frequency earthquakes (LFEs) near Parkfield, California has been found to be strongly correlated with solid earth tides. Laboratory experiments and theoretical analyses show that the period of imposed forcing and source properties affect the sensitivity to triggering and the phase relation of the peak seismicity rate and the periodic stress, but frequency-dependent triggering has not been quantitatively explored in the field. Tidal forcing acts over a wide range of frequencies, therefore the sensitivity to tidal triggering of LFEs provides a good probe to the physical mechanisms affecting earthquake generation. In this study, we consider the tidal triggering of LFEs near Parkfield, California since 2001. We find the LFEs rate is correlated with tidal shear stress, normal stress rate and shear stress rate. The occurrence of LFEs can also be independently modulated by groups of tidal constituents at semi-diurnal, diurnal and fortnightly frequencies. The strength of the response of LFEs to the different tidal constituents varies between LFE families. Each LFE family has an optimal triggering frequency, which does not appear to be depth dependent or systematically related to other known properties. This suggests the period of the applied forcing plays an important role in the triggering process, and the interaction of periods of loading history and source region properties, such as friction, effective normal stress and pore fluid pressure, produces the observed frequency-dependent tidal triggering of LFEs.

Calcium-responsive contractility during fertilization in sea urchin eggs.

Science.gov (United States)

Stack, Christianna; Lucero, Amy J; Shuster, Charles B

2006-04-01

Fertilization triggers a reorganization of oocyte cytoskeleton, and in sea urchins, there is a dramatic increase in cortical F-actin. However, the role that myosin II plays during fertilization remains largely unexplored. Myosin II is localized to the cortical cytoskeleton both before and after fertilization and to examine myosin II contractility in living cells, Lytechinus pictus eggs were observed by time-lapse microscopy. Upon sperm binding, a cell surface deflection traversed the egg that was followed by and dependent on the calcium wave. The calcium-dependence of surface contractility could be reproduced in unfertilized eggs, where mobilization of intracellular calcium in unfertilized eggs under compression resulted in a marked contractile response. Lastly, inhibition of myosin II delayed absorption of the fertilization cone, suggesting that myosin II not only responds to the same signals that activate eggs but also participates in the remodeling of the cortical actomyosin cytoskeleton during the first zygotic cell cycle. (c) 2006 Wiley-Liss, Inc.

Pesquisa de marcadores para os genes da cadeia pesada da beta-miosina cardíaca e da proteína C de ligação à miosina em familiares de pacientes com cardiomiopatia hipertrófica Research of markers for the genes of the heavy chain of cardiac beta-myosin and myosin binding protein C in relatives of patients with hypertrophic cardiomyopathy

Directory of Open Access Journals (Sweden)

Adriana Paula Tirone

2005-06-01

Full Text Available OBJETIVO: Estudar os marcadores moleculares para os genes da cadeia pesada da beta-miosina cardíaca e da proteína-C de ligação à miosina em familiares de portadores de cardiomiopatia hipertrófica. MÉTODOS: Foram estudadas 12 famílias que realizaram anamnese, exame físico, eletrocardiograma, ecocardiograma e coleta de sangue para o estudo genético através da reação em cadeia da polimerasse. RESULTADOS: Dos 227 familiares 25% eram acometidos, sendo 51% do sexo masculino com idade média de 35±19 (2 a 95 anos. A análise genética mostrou ligação com o gene da b-miosina cardíaca em uma família e, em outra, ligação com o gene da proteína C de ligação à miosina. Em cinco famílias foram excluídas ligações com os dois genes; em duas, a ligação com o gene da proteína C de ligação à miosina, porém para o gene da b-miosina os resultados foram inconclusivos; em duas famílias os resultados foram inconclusivos para os dois genes e em uma foi excluída ligação para o gene da b-miosina mas ficou inconclusivo para o gene da proteína C de ligação à miosina. CONCLUSÃO: Em nosso meio, talvez predominem outros genes que não aqueles descritos na literatura, ou que existam outras diferenças genéticas relacionadas com a origem de nossa população e/ou fatores ambientais.OBJECTIVE: To study the molecular markers for the genes of the heavy chain of cardiac beta-myosin and the myosin binding protein C in relatives of carriers of hypertrophic cardiomyopathy. METHODS: Twelve families who had anamnesis, physical exam, electrocardiogram, echocardiogram and blood collection for the genetic study through the chain reaction of polymerase. RESULTS: From the 227 relatives, 25% were ill-taken, with 51% men, with an average age of 35±19 (2 to 95 years old. The genetic analysis showed a connection with the gene of the cardiac b-myosin in a family and, in another, a connection with the gene of the myosin-binding protein C. In five

Reliability model analysis and primary experimental evaluation of laser triggered pulse trigger

International Nuclear Information System (INIS)

Chen Debiao; Yang Xinglin; Li Yuan; Li Jin

2012-01-01

High performance pulse trigger can enhance performance and stability of the PPS. It is necessary to evaluate the reliability of the LTGS pulse trigger, so we establish the reliability analysis model of this pulse trigger based on CARMES software, the reliability evaluation is accord with the statistical results. (authors)

Energetic radiation produced during rocket-triggered lightning.

Science.gov (United States)

Dwyer, Joseph R; Uman, Martin A; Rassoul, Hamid K; Al-Dayeh, Maher; Caraway, Lee; Jerauld, Jason; Rakov, Vladimir A; Jordan, Douglas M; Rambo, Keith J; Corbin, Vincent; Wright, Brian

2003-01-31

Using a NaI(Tl) scintillation detector designed to operate in electrically noisy environments, we observed intense bursts of energetic radiation (> 10 kiloelectron volts) during the dart leader phase of rocket-triggered lightning, just before and possibly at the very start of 31 out of the 37 return strokes measured. The bursts had typical durations of less than 100 microseconds and deposited many tens of megaelectron volts into the detector. These results provide strong evidence that the production of runaway electrons is an important process during lightning.

Stay away from asthma triggers

Science.gov (United States)

Asthma triggers - stay away from; Asthma triggers - avoiding; Reactive airway disease - triggers; Bronchial asthma - triggers ... clothes. They should leave the coat outside or away from your child. Ask people who work at ...

Triggers for Preeclampsia Onset: a Case-Crossover Study.

Science.gov (United States)

Ford, Jane B; Schemann, Kathrin; Patterson, Jillian A; Morris, Jonathan; Herbert, Robert D; Roberts, Christine L

2016-11-01

Risk factors for preeclampsia are well established, whereas, the triggers associated with timing of preeclampsia onset are not. The aim of this study was to establish whether recent infection or other triggers were associated with timing of preeclampsia onset. We used a case-crossover design with preeclampsia cases serving as their own controls. Women with singleton pregnancies of ≥20 weeks gestation presenting at three hospitals were eligible for inclusion. Exposures to potential triggers were identified via guided questionnaire. Infective episodes included symptoms lasting >24 h. Preeclampsia was defined as hypertension (BP ≥140 mmHg and/or ≥90 mmHg) and proteinuria (protein/creatinine ratio ≥30 mg/mmol). Conditional logistic regression was used to compare the odds of exposure to potential triggers in the case windows (1-7 days preceding diagnosis of preeclampsia) and control windows (8-14 days prior to diagnosis); unadjusted odds ratios (ORs) are reported. Among 286 recruited women, 25 (8.7%) reported a new infection in the 7 days prior to preeclampsia onset and 21 (7.3%) in the 8-14 days prior. There was no significant association between onset of infection in the 7 days prior and preeclampsia diagnosis (OR 1.24, 95% CI 0.65, 2.34). Consumption of caffeine (OR 0.51, 95% CI 0.33, 0.77), spicy food (OR 0.49, 95% CI 0.30, 0.81), and alcohol (OR 0.26, 95% CI 0.10, 0.71) were strongly inversely associated with preeclampsia onset. Recent infection does not appear to trigger preeclampsia. Decreased consumption of caffeine, spicy food, and alcohol may be prodromal markers. Such behaviours may be early markers of imminent preeclampsia. © 2016 John Wiley & Sons Ltd.

Contractile properties, fiber types, and myosin isoforms in fast and slow muscles of hyperactive Japanese waltzing mice

Czech Academy of Sciences Publication Activity Database

Asmussen, G.; Schmalbruch, I.; Soukup, Tomáš; Pette, D.

2003-01-01

Roč. 184, č. 2 (2003), s. 758-766 ISSN 0014-4886 R&D Projects: GA ČR GA304/00/1653 Grant - others:Deutsche Forschungsgemeinschaft(DE) -; Sonderforschungsbereich(DE) 156; Schwerpunkt Muskelforschung(DE) As 74/1-2 Institutional research plan: CEZ:AV0Z5011922 Keywords : Japanese waltzing mouse * muscle contraction * myosin isoforms Subject RIV: ED - Physiology Impact factor: 3.676, year: 2003

An inducible mouse model for microvillus inclusion disease reveals a role for myosin Vb in apical and basolateral trafficking

NARCIS (Netherlands)

Schneeberger, Kerstin; Vogel, Georg F; Teunissen, Hans; van Ommen, Domenique D; Begthel, Harry; El Bouazzaoui, Layla; van Vugt, Anke H M; Beekman, Jeffrey M; Klumperman, Judith; Müller, Thomas; Janecke, Andreas; Gerner, Patrick; Huber, Lukas A; Hess, Michael W; Clevers, Hans; van Es, Johan H; Nieuwenhuis, Edward E S; Middendorp, Sabine

2015-01-01

Microvillus inclusion disease (MVID) is a rare intestinal enteropathy with an onset within a few days to months after birth, resulting in persistent watery diarrhea. Mutations in the myosin Vb gene (MYO5B) have been identified in the majority of MVID patients. However, the exact pathophysiology of

Zinc-induced cardiomyocyte relaxation in a rat model of hyperglycemia is independent of myosin isoform

Directory of Open Access Journals (Sweden)

Yi Ting

2012-11-01

Full Text Available Abstract It has been reported previously that diabetic cardiomyopathy can be inhibited or reverted with chronic zinc supplementation. In the current study, we hypothesized that total cardiac calcium and zinc content is altered in early onset diabetes mellitus characterized in part as hyperglycemia (HG and that exposure of zinc ion (Zn2+ to isolated cardiomyocytes would enhance contraction-relaxation function in HG more so than in nonHG controls. To better control for differential cardiac myosin isoform expression as occurs in rodents after β-islet cell necrosis, hypothyroidism was induced in 16 rats resulting in 100% β-myosin heavy chain expression in the heart. β-Islet cell necrosis was induced in half of the rats by streptozocin administration. After 6 wks of HG, both HG and nonHG controls rats demonstrated similar myofilament performance measured as thin filament calcium sensitivity, native thin filament velocity in the myosin motility assay and contractile velocity and power. Extracellular Zn2+ reduced cardiomyocyte contractile function in both groups, but enhanced relaxation function significantly in the HG group compared to controls. Most notably, a reduction in diastolic sarcomere length with increasing pacing frequencies, i.e., incomplete relaxation, was more pronounced in the HG compared to controls, but was normalized with extracellular Zn2+ application. This is a novel finding implicating that the detrimental effect of HG on cardiomyocyte Ca2+ regulation can be amelioration by Zn2+. Among the many post-translational modifications examined, only phosphorylation of ryanodine receptor (RyR at S-2808 was significantly higher in HG compared to nonHG. We did not find in our hypothyroid rats any differentiating effects of HG on myofibrillar protein phosphorylation, lysine acetylation, O-linked N-acetylglucosamine and advanced glycated end-products, which are often implicated as complicating factors in cardiac performance due to HG. Our

Triggered creep as a possible mechanism for delayed dynamic triggering of tremor and earthquakes

Science.gov (United States)

Shelly, David R.; Peng, Zhigang; Hill, David P.; Aiken, Chastity

2011-01-01

The passage of radiating seismic waves generates transient stresses in the Earth's crust that can trigger slip on faults far away from the original earthquake source. The triggered fault slip is detectable in the form of earthquakes and seismic tremor. However, the significance of these triggered events remains controversial, in part because they often occur with some delay, long after the triggering stress has passed. Here we scrutinize the location and timing of tremor on the San Andreas fault between 2001 and 2010 in relation to distant earthquakes. We observe tremor on the San Andreas fault that is initiated by passing seismic waves, yet migrates along the fault at a much slower velocity than the radiating seismic waves. We suggest that the migrating tremor records triggered slow slip of the San Andreas fault as a propagating creep event. We find that the triggered tremor and fault creep can be initiated by distant earthquakes as small as magnitude 5.4 and can persist for several days after the seismic waves have passed. Our observations of prolonged tremor activity provide a clear example of the delayed dynamic triggering of seismic events. Fault creep has been shown to trigger earthquakes, and we therefore suggest that the dynamic triggering of prolonged fault creep could provide a mechanism for the delayed triggering of earthquakes. ?? 2011 Macmillan Publishers Limited. All rights reserved.

LET-99 functions in the astral furrowing pathway, where it is required for myosin enrichment in the contractile ring.

Science.gov (United States)

Price, Kari L; Rose, Lesilee S

2017-09-01

The anaphase spindle determines the position of the cytokinesis furrow, such that the contractile ring assembles in an equatorial zone between the two spindle poles. Contractile ring formation is mediated by RhoA activation at the equator by the centralspindlin complex and midzone microtubules. Astral microtubules also inhibit RhoA accumulation at the poles. In the Caenorhabditis elegans one-cell embryo, the astral microtubule-dependent pathway requires anillin, NOP-1, and LET-99. LET-99 is well characterized for generating the asymmetric cortical localization of the Gα-dependent force-generating complex that positions the spindle during asymmetric division. However, whether the role of LET-99 in cytokinesis is specific to asymmetric division and whether it acts through Gα to promote furrowing are unclear. Here we show that LET-99 contributes to furrowing in both asymmetrically and symmetrically dividing cells, independent of its function in spindle positioning and Gα regulation. LET-99 acts in a pathway parallel to anillin and is required for myosin enrichment into the contractile ring. These and other results suggest a positive feedback model in which LET-99 localizes to the presumptive cleavage furrow in response to the spindle and myosin. Once positioned there, LET-99 enhances myosin accumulation to promote furrowing in both symmetrically and asymmetrically dividing cells. © 2017 Price and Rose. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Dependence of myosin-ATPase on structure bound creatine kinase in cardiac myfibrils from rainbow trout and freshwater turtle

DEFF Research Database (Denmark)

Haagensen, L.; Jensen, D.H.; Gesser, Hans

2008-01-01

The influence of myofibrillar creatine kinase on the myosin-ATPase activity was examined in cardiac ventricular myofibrils isolated from rainbow trout (Oncorhynchus mykiss) and freshwater turtle (Trachemys scripta). The ATPase rate was assessed by recording the rephosphorylation of ADP by the pyr......The influence of myofibrillar creatine kinase on the myosin-ATPase activity was examined in cardiac ventricular myofibrils isolated from rainbow trout (Oncorhynchus mykiss) and freshwater turtle (Trachemys scripta). The ATPase rate was assessed by recording the rephosphorylation of ADP...... by the pyruvate kinase reaction alone or together with the amount of creatine formed, when myofibrillar bound creatine kinase was activated with phosphocreatine. The steady-state concentration of ADP in the solution was varied through the activity of pyruvate kinase added to the solution. For rainbow trout...... myofibrils at a high pyruvate kinase activity, creatine kinase competed for ADP but did not influence the total ATPase activity. When the ADP concentration was elevated within the physiological range by lowering the pyruvate kinase activity, creatine kinase competed efficiently and increased the ATPase...

CMS Trigger Performance

CERN Document Server

Donato, Silvio

2017-01-01

During its second run of operation (Run 2) which started in 2015, the LHC will deliver a peak instantaneous luminosity that may reach $2 \\cdot 10^{34}$ cm$^{-2}$s$^{-1}$ with an average pile-up of about 55, far larger than the design value. Under these conditions, the online event selection is a very challenging task. In CMS, it is realized by a two-level trigger system the Level-1 (L1) Trigger, implemented in custom-designed electronics, and the High Level Trigger (HLT), a streamlined version of the offline reconstruction software running on a computer farm. In order to face this challenge, the L1 trigger has been through a major upgrade compared to Run 1, whereby all electronic boards of the system have been replaced, allowing more sophisticated algorithms to be run online. Its last stage, the global trigger, is now able to perform complex selections and to compute high-level quantities, like invariant masses. Likewise, the algorithms that run in the HLT go through big improvements; in particular, new appr...

Performances of the ATLAS Level-1 Muon barrel trigger during the Run-II data taking

CERN Document Server

Sessa, Marco; The ATLAS collaboration

2017-01-01

The Level-1 Muon Barrel Trigger is one of the main elements of the event selection of the ATLAS experiment at the Large Hadron Collider. It exploits the Resistive Plate Chambers (RPC) detectors to generate the trigger signal. The RPCs are placed in the barrel region of the ATLAS experiment: they are arranged in three concentric double layers and operate in a strong magnetic toroidal field. RPC detectors cover the pseudo-rapidity range $|\\eta|<1.05$ for a total surface of more than $4000\\ m^2$ and about 3600 gas volumes. The Level-1 Muon Trigger in the barrel region allows to select muon candidates with respect to their transverse momentum and associates them with the correct bunch-crossing number. The trigger system is able to take a decision within a latency of about 2 $\\mu s$. The detailed measurement of the RPC detector efficiencies and of the trigger performance during the ATLAS Run-II data taking is here presented.

Performance of the ATLAS Level-1 muon barrel trigger during the Run 2 data taking

CERN Document Server

AUTHOR|(INSPIRE)INSPIRE-00404546; The ATLAS collaboration

2018-01-01

The Level-1 Muon Barrel Trigger is one of the main elements of the event selection of the ATLAS experiment at the Large Hadron Collider. It exploits the Resistive Plate Chambers (RPC) detectors to generate the trigger signal. The RPCs are placed in the barrel region of the ATLAS experiment: they are arranged in three concentric double layers and operate in a strong magnetic toroidal field. RPC detectors cover the pseudo-rapidity range |η| < 1.05 for a total surface of more than 4000 m 2 and about 3600 gas volumes. The Level-1 Muon Trigger in the barrel region allows to select muon candidates according to their transverse momentum and associates them with the correct bunch-crossing. The trigger system is able to take a decision within a latency of about 2 μs. The measurement of the RPC detector efficiencies and the trigger performance during the ATLAS Run-II data taking are here presented.

The NA27 trigger

International Nuclear Information System (INIS)

Bizzarri, R.; Di Capua, E.; Falciano, S.; Iori, M.; Marel, G.; Piredda, G.; Zanello, L.; Haupt, L.; Hellman, S.; Holmgren, S.O.; Johansson, K.E.

1985-05-01

We have designed and implemented a minimum bias trigger together with a fiducial volume trigger for the experiment NA27, performed at the CERN SPS. A total of more than 3 million bubble chamber pictures have been taken with a triggered cross section smaller than 75% of the total inelastic cross section. Events containing charm particles were triggered with an efficiency of 98 +2 sub(-3)%. With the fiducial volume trigger, the probability for a picture to contain an interaction in the visible hydrogen increased from 47.3% to 59.5%, reducing film cost and processing effort with about 20%. The improvement in data taking rate is shown to be negligible. (author)

Changes in myosin S1 orientation and force induced by a temperature increase.

Science.gov (United States)

Griffiths, Peter J; Bagni, Maria A; Colombini, Barbara; Amenitsch, Heinz; Bernstorff, Sigrid; Ashley, Christopher C; Cecchi, Giovanni; Ameritsch, Heinz

2002-04-16

Force generation in myosin-based motile systems is thought to result from an angular displacement of the myosin subfragment 1 (S1) tail domain with respect to the actin filament axis. In muscle, raised temperature increases the force generated by S1, implying a greater change in tail domain angular displacement. We used time-resolved x-ray diffraction to investigate the structural corollary of this force increase by measuring M3 meridional reflection intensity during sinusoidal length oscillations. This technique allows definition of S1 orientation with respect to the myofilament axis. M3 intensity changes were approximately sinusoid at low temperatures but became increasingly distorted as temperature was elevated, with the formation of a double intensity peak at maximum shortening. This increased distortion could be accounted for by assuming a shift in orientation of the tail domain of actin-bound S1 toward the orientation at which M3 intensity is maximal, which is consistent with a tail domain rotation model of force generation in which the tail approaches a more perpendicular projection from the thin filament axis at higher temperatures. In power stroke simulations, the angle between S1 tail mean position during oscillations and the position at maximum intensity decreased by 4.7 degrees, corresponding to a mean tail displacement toward the perpendicular of 0.73 nm for a temperature-induced force increase of 0.28 P(0) from 4 to 22 degrees C. Our findings suggest that at least 62% of crossbridge compliance is associated with the tail domain.

Triggers of oral lichen planus flares and the potential role of trigger avoidance in disease management.

Science.gov (United States)

Chen, Hannah X; Blasiak, Rachel; Kim, Edwin; Padilla, Ricardo; Culton, Donna A

2017-09-01

Many patients with oral lichen planus (OLP) report triggers of flares, some of which overlap with triggers of other oral diseases, including oral allergy syndrome and oral contact dermatitis. The purpose of this study was to evaluate the prevalence of commonly reported triggers of OLP flares, their overlap with triggers of other oral diseases, and the potential role of trigger avoidance as a management strategy. Questionnaire-based survey of 51 patients with biopsy-proven lichen planus with oral involvement seen in an academic dermatology specialty clinic and/or oral pathology clinic between June 2014 and June 2015. Of the participants, 94% identified at least one trigger of their OLP flares. Approximately half of the participants (51%) reported at least one trigger that overlapped with known triggers of oral allergy syndrome, and 63% identified at least one trigger that overlapped with known triggers of oral contact dermatitis. Emotional stress was the most commonly reported trigger (77%). Regarding avoidance, 79% of the study participants reported avoiding their known triggers in daily life. Of those who actively avoided triggers, 89% reported an improvement in symptoms and 70% reported a decrease in the frequency of flares. Trigger identification and avoidance can play a potentially effective role in the management of OLP. Copyright © 2017 Elsevier Inc. All rights reserved.

Angiotensin II induces reorganization of the actin cytoskeleton and myosin light-chain phosphorylation in podocytes through rho/ROCK-signaling pathway

NARCIS (Netherlands)

Wang, Siyuan; Chen, Cheng; Su, Ke; Zha, Dongqing; Liang, Wei; Hillebrands, J L; van Goor, Harry; Ding, Guohua

2016-01-01

Aims In the present study, we have evaluated the effect of angiotensin II (Ang II) on actin cytoskeleton reorganization and myosin light-chain (MLC) phosphorylation in podocytes to demonstrate whether the Rho/Rho-associated coiled kinase (ROCK) pathway is involved podocyte injury. Methods Eighteen

Complex Non-volcanic Tremor in Guerrero Mexico Triggered by the 2010 Mw 8.8 Chilean Earthquake

Science.gov (United States)

Zigone, D.; Campillo, M.; Husker, A. L.; Kostoglodov, V.; Payero, J. S.; Frank, W.; Shapiro, N. M.; Voisin, C.; Cougoulat, G.; Cotte, N.

2010-12-01

In this study we analyze the tremors triggered in Guerrero region (Mexico) by the 2010 magnitude 8.8 Chilean Earthquake using mini-seismic array data from the French-Mexican G-GAP project and broadband data from the Servicio Sismologico Nacional of Mexico. The strong dynamic shaking by the earthquake produced the first observed triggered non-volcanic tremors (NVT) in Mexico so far with at least 3 different types of tremors at different time scales. There was a slow slip event (SSE) occurring at the time of the earthquake, which may have increased the probability of tremor triggering in the region. The first type of observed triggered tremors occurred during the S waves, Love waves and Rayleigh waves as already reported in other subductions zones and continental faults (Miyazawa and Mori, 2005, 2006; Rubinstein et al., 2007; Gomberg et al., 2008; Peng et al, 2009…). The greatest amount of energy and duration accompanies the long-period Rayleigh waves, with smaller bursts during the S and Love waves. For this particular tremor we observed the dispersion of Rayleigh waves in the envelopes of triggered tremors, which indicates a very strong modulation of the source by the passing surface wave. An unexpected short-term tremor occurred approximately one hour later of the arrival of the surface waves on the coastal stations. The NVT has only been previously observed at distances > 100 km inland. It also has a shorter frequency range (3-6 Hz) than other NVT (1-10 Hz) observed in the region. Finally, we observed a significant increase of so-called ambient tremor activity with higher intensity than all triggered NVT during the days after the earthquake. This study adds new types of tremors to the lexicon of triggered NVT observed in the world.

Mechanical Defects of Muscle Fibers with Myosin Light Chain Mutants that Cause Cardiomyopathy

OpenAIRE

Roopnarine, Osha

2003-01-01

Familial hypertrophic cardiomyopathy is a disease caused by single mutations in several sarcomeric proteins, including the human myosin ventricular regulatory light chain (vRLC). The effects of four of these mutations (A13T, F18L, E22K, and P95A) in vRLC on force generation were determined as a function of Ca2+ concentration. The endogenous RLC was removed from skinned rabbit psoas muscle fibers, and replaced with either rat wildtype vRLC or recombinant rat vRLC (G13T, F18L, E22K, and P95A). ...

Minimum Bias Trigger in ATLAS

International Nuclear Information System (INIS)

Kwee, Regina

2010-01-01

Since the restart of the LHC in November 2009, ATLAS has collected inelastic pp collisions to perform first measurements on charged particle densities. These measurements will help to constrain various models describing phenomenologically soft parton interactions. Understanding the trigger efficiencies for different event types are therefore crucial to minimize any possible bias in the event selection. ATLAS uses two main minimum bias triggers, featuring complementary detector components and trigger levels. While a hardware based first trigger level situated in the forward regions with 2.2 < |η| < 3.8 has been proven to select pp-collisions very efficiently, the Inner Detector based minimum bias trigger uses a random seed on filled bunches and central tracking detectors for the event selection. Both triggers were essential for the analysis of kinematic spectra of charged particles. Their performance and trigger efficiency measurements as well as studies on possible bias sources will be presented. We also highlight the advantage of these triggers for particle correlation analyses. (author)

Myosin light chain 2-based selection of human iPSC-derived early ventricular cardiac myocytes.

Science.gov (United States)

Bizy, Alexandra; Guerrero-Serna, Guadalupe; Hu, Bin; Ponce-Balbuena, Daniela; Willis, B Cicero; Zarzoso, Manuel; Ramirez, Rafael J; Sener, Michelle F; Mundada, Lakshmi V; Klos, Matthew; Devaney, Eric J; Vikstrom, Karen L; Herron, Todd J; Jalife, José

2013-11-01

Applications of human induced pluripotent stem cell derived-cardiac myocytes (hiPSC-CMs) would be strengthened by the ability to generate specific cardiac myocyte (CM) lineages. However, purification of lineage-specific hiPSC-CMs is limited by the lack of cell marking techniques. Here, we have developed an iPSC-CM marking system using recombinant adenoviral reporter constructs with atrial- or ventricular-specific myosin light chain-2 (MLC-2) promoters. MLC-2a and MLC-2v selected hiPSC-CMs were purified by fluorescence-activated cell sorting and their biochemical and electrophysiological phenotypes analyzed. We demonstrate that the phenotype of both populations remained stable in culture and they expressed the expected sarcomeric proteins, gap junction proteins and chamber-specific transcription factors. Compared to MLC-2a cells, MLC-2v selected CMs had larger action potential amplitudes and durations. In addition, by immunofluorescence, we showed that MLC-2 isoform expression can be used to enrich hiPSC-CM consistent with early atrial and ventricular myocyte lineages. However, only the ventricular myosin light chain-2 promoter was able to purify a highly homogeneous population of iPSC-CMs. Using this approach, it is now possible to develop ventricular-specific disease models using iPSC-CMs while atrial-specific iPSC-CM cultures may require additional chamber-specific markers. © 2013.

Causality and headache triggers

Science.gov (United States)

Turner, Dana P.; Smitherman, Todd A.; Martin, Vincent T.; Penzien, Donald B.; Houle, Timothy T.

2013-01-01

Objective The objective of this study was to explore the conditions necessary to assign causal status to headache triggers. Background The term “headache trigger” is commonly used to label any stimulus that is assumed to cause headaches. However, the assumptions required for determining if a given stimulus in fact has a causal-type relationship in eliciting headaches have not been explicated. Methods A synthesis and application of Rubin’s Causal Model is applied to the context of headache causes. From this application the conditions necessary to infer that one event (trigger) causes another (headache) are outlined using basic assumptions and examples from relevant literature. Results Although many conditions must be satisfied for a causal attribution, three basic assumptions are identified for determining causality in headache triggers: 1) constancy of the sufferer; 2) constancy of the trigger effect; and 3) constancy of the trigger presentation. A valid evaluation of a potential trigger’s effect can only be undertaken once these three basic assumptions are satisfied during formal or informal studies of headache triggers. Conclusions Evaluating these assumptions is extremely difficult or infeasible in clinical practice, and satisfying them during natural experimentation is unlikely. Researchers, practitioners, and headache sufferers are encouraged to avoid natural experimentation to determine the causal effects of headache triggers. Instead, formal experimental designs or retrospective diary studies using advanced statistical modeling techniques provide the best approaches to satisfy the required assumptions and inform causal statements about headache triggers. PMID:23534872

The D0 calorimeter trigger

International Nuclear Information System (INIS)

Guida, J.

1992-12-01

The D0 calorimeter trigger system consists of many levels to make physics motivated trigger decisions. The Level-1 trigger uses hardware techniques to reduce the trigger rate from ∼ 100kHz to 200Hz. It forms sums of electromagnetic and hadronic energy, globally and in towers, along with finding the missing transverse energy. A minimum energy is set on these energy sums to pass the event. The Level-2 trigger is a set of software filters, operating in a parallel-processing microvax farm which further reduces the trigger rate to a few Hertz. These filters will reject events which lack electron candidates, jet candidates, or missing transverse energy in the event. The performance of these triggers during the early running of the D0 detector will also be discussed

Neuromuscular partitioning, architectural design, and myosin fiber types of the M. vastus lateralis of the llama (Lama glama).

Science.gov (United States)

Graziotti, Guillermo H; Palencia, Pablo; Delhon, Gustavo; Rivero, José-Luis L

2004-11-01

The llama (Lama glama) is one of the few mammals of relatively large body size in which three fast myosin heavy chain isoforms (i.e., IIA, IIX, IIB) are extensively expressed in their locomotory muscles. This study was designed to gain insight into the morphological and functional organization of skeletal musculature in this peculiar animal model. The neuromuscular partitioning, architectural design, and myosin fiber types were systematically studied in the M. vastus lateralis of adult llamas (n = 15). Four nonoverlapping neuromuscular partitions or compartments were identified macroscopically (using a modified Sihler's technique for muscle depigmentation), although they did not conform strictly to the definitions of "neuromuscular compartments." Each neuromuscular partition was innervated by primary branches of the femoral nerve and was arranged within the muscle as paired partitions, two in parallel (deep-superficial compartmentalization) and the other two in-series (proximo-distal compartmentalization). These neuromuscular partitions of the muscle varied in their respective architectural designs (studied after partial digestion with diluted nitric acid) and myosin fiber type characteristics (identified immunohistochemically with specific anti-myosin monoclonal antibodies, then examined by quantitative histochemistry and image analysis). The deep partitions of the muscle had longer fibers, with lower angles of pinnation, and higher percentages of fast-glycolytic fibers than the superficial partitions of the muscle. These differences clearly suggest a division of labor in the whole M. vastus lateralis of llamas, with deep partitions exhibiting features well adapted for dynamic activities in the extension of stifle, whereas superficial portions seem to be related to the antigravitational role of the muscle in preserving the extension of the stifle during standing and stance phase of the stride. This peculiar structural and functional organization of the llama M

A collapsin response mediator protein 2 isoform controls myosin II-mediated cell migration and matrix assembly by trapping ROCK II

DEFF Research Database (Denmark)

Yoneda, Atsuko; Morgan-Fisher, Marie; Wait, Robin

2012-01-01

Collapsin response mediator protein 2 (CRMP-2) is known as a regulator of neuronal polarity and differentiation through microtubule assembly and trafficking. Here, we show that CRMP-2 is ubiquitously expressed and a splice variant (CRMP-2L), which is expressed mainly in epithelial cells among...... nonneuronal cells, regulates myosin II-mediated cellular functions, including cell migration. While the CRMP-2 short form (CRMP-2S) is recognized as a substrate of the Rho-GTP downstream kinase ROCK in neuronal cells, a CRMP-2 complex containing 2L not only bound the catalytic domain of ROCK II through two......-2L but not -2S inhibited fibronectin matrix assembly in fibroblasts. Underlying these responses, CRMP-2L regulated the kinase activity of ROCK II but not ROCK I, independent of GTP-RhoA levels. This study provides a new insight into CRMP-2 as a controller of myosin II-mediated cellular functions...

A general-purpose trigger processor system and its application to fast vertex trigger

International Nuclear Information System (INIS)

Hazumi, M.; Banas, E.; Natkaniec, Z.; Ostrowicz, W.

1997-12-01

A general-purpose hardware trigger system has been developed. The system comprises programmable trigger processors and pattern generator/samplers. The hardware design of the system is described. An application as a prototype of the very fast vertex trigger in an asymmetric B-factory at KEK is also explained. (author)

BTeV Trigger

International Nuclear Information System (INIS)

Gottschalk, Erik E.

2006-01-01

BTeV was designed to conduct precision studies of CP violation in BB-bar events using a forward-geometry detector in a hadron collider. The detector was optimized for high-rate detection of beauty and charm particles produced in collisions between protons and antiprotons. The trigger was designed to take advantage of the main difference between events with beauty and charm particles and more typical hadronic events-the presence of detached beauty and charm decay vertices. The first stage of the BTeV trigger was to receive data from a pixel vertex detector, reconstruct tracks and vertices for every beam crossing, reject at least 98% of beam crossings in which neither beauty nor charm particles were produced, and trigger on beauty events with high efficiency. An overview of the trigger design and its evolution to include commodity networking and computing components is presented

Fluorescent modification and orientation of myosin sulfhydryl 2 in skeletal muscle fibers

International Nuclear Information System (INIS)

Ajtai, K.; Burghardt, T.P.

1989-01-01

The authors describe a protocol for the selective covalent labeling of the sulfhydryl 2 (SH2) on the myosin cross-bridge in glycerinated muscle fibers using the sulfhydryl-selective label 4-[N-[(iodoacetoxy)ethyl]-N-methylamino]-7-nitrobenz-2-oxa-1,3-diazole (IANBD). The protocol promotes the specificity of IANBD by using the ability to protect sulfhydryl 1 (SH1) from modification by binding the cross-bridge to the actin filament and using cross-bridge-bound MgADP to promote the accessibility of SH2. They determined the specificity of the probe using fluorescence gel scanning of fiber-extracted proteins to isolate the probe on myosin subfragment 1 (S1), limited proteolysis of the purified S1 to isolate the probe on the 20-kilodalton fragment of S1, and titration of the free SH1's on purified S1 using the radiolabeled SH1-specific reagent [ 14 C]iodoacetamide or enzymatic activity measurements. They characterized the angular distribution of the IANBD on cross-bridges in fibers when the fibers are in rigor, in relaxation, in the presence of MgADP, and in isometric contraction using wavelength-dependent fluorescence polarization. They find that the SH2 probe distinguishes the different states of the fiber such that rigor and MgADP are ordered and maintain a similar orientation throughout the excitation wavelength domain. The relaxed cross-bridge is ordered and has an orientation that is distinct from the orientation of the cross-bridge in rigor and MgADP over the entire wavelength domain. The active isometric cross-bridge is also oriented differently from the other states, suggesting the presence of a predominant actin-bound cross-bridge state that precedes the power stroke during muscle contraction

Triggering trigeminal neuralgia

DEFF Research Database (Denmark)

Di Stefano, Giulia; Maarbjerg, Stine; Nurmikko, Turo

2018-01-01

Introduction Although it is widely accepted that facial pain paroxysms triggered by innocuous stimuli constitute a hallmark sign of trigeminal neuralgia, very few studies to date have systematically investigated the role of the triggers involved. In the recently published diagnostic classification...

LHCb Topological Trigger Reoptimization

CERN Document Server

INSPIRE-00400931; Ilten, Philip; Khairullin, Egor; Rogozhnikov, Alex; Ustyuzhanin, Andrey; Williams, Michael

2015-12-23

The main b-physics trigger algorithm used by the LHCb experiment is the so-called topological trigger. The topological trigger selects vertices which are a) detached from the primary proton-proton collision and b) compatible with coming from the decay of a b-hadron. In the LHC Run 1, this trigger, which utilized a custom boosted decision tree algorithm, selected a nearly 100% pure sample of b-hadrons with a typical efficiency of 60-70%; its output was used in about 60% of LHCb papers. This talk presents studies carried out to optimize the topological trigger for LHC Run 2. In particular, we have carried out a detailed comparison of various machine learning classifier algorithms, e.g., AdaBoost, MatrixNet and neural networks. The topological trigger algorithm is designed to select all "interesting" decays of b-hadrons, but cannot be trained on every such decay. Studies have therefore been performed to determine how to optimize the performance of the classification algorithm on decays not used in the training. ...

Membrane tubulation in lipid vesicles triggered by the local application of calcium ions

DEFF Research Database (Denmark)

Ali Doosti, Baharan; Pezeshkian, Weria; Bruhn, Dennis Skjøth

2017-01-01

, generates spontaneous curvature and triggers the formation of tubular protrusions that point away from the ion source. This behavior is rationalized by strong binding of the divalent cations to the surface of the charged bilayer which effectively neutralizes the surface charge density of outer leaflet...

Supplementation with 0.1% and 2% vitamin e in diabetic rats: analysis of myenteric neurons immunostained for myosin-V and nNOS in the jejunum

Directory of Open Access Journals (Sweden)

Eleandro Aparecido Tronchini

2012-12-01

Full Text Available CONTEXT: Diabetes mellitus is a disease characterized by hyperglycemia that, when allowed to progress long-term untreated, develops vascular and neurological complications, which are responsible for the development of alterations in the enteric nervous system in diabetic patients. In the gastrointestinal tract, diabetes mellitus promotes motor and sensory changes, and in the reflex function of this system, causing gastroparesis, diarrhea, constipation, megacolon, slow gastrointestinal transit, gastric stasis and dilation with decreased or increased peristaltic contractions. Several studies have shown that oxidative stress is the main responsible for the vascular and neurological complications affecting the enteric nervous system of diabetics. OBJECTIVE: The effects of 0.1% and 2% vitamin E on myosin-V- and nNOS-immunoreactive neurons in the jejunum of diabetic rats were investigated. METHODS: Thirty rats were divided into the groups: normoglycemic, normoglycemic treated with 0.1% vitamin E, normoglycemic treated with 2% vitamin E, diabetic, diabetic treated with 0.1% vitamin E, and diabetic treated with 2% vitamin E. The neuronal density and areas of neuron cell bodies were determined. RESULTS: Diabetes (diabetic group significantly reduced the number of myosin-V-immunoreactive neurons compared with the normoglycemic group. The diabetic treated with 0.1% vitamin E and diabetic treated with 2% vitamin E groups did not exhibit a greater density than the D group (P>0.05. Nitrergic density did not change with diabetes (P>0.05. The areas of myosin-V- and nNOS-immunoreactive neurons significantly increased in the normoglycemic treated with 2% vitamin E and diabetic groups compared with the normoglycemic group. CONCLUSION: Supplementation with 2% vitamin E had a neurotrophic effect only in the area of myosin-V-immunoreactive neurons compared with the diabetic group.

The TOTEM modular trigger system

Energy Technology Data Exchange (ETDEWEB)

Bagliesi, M.G., E-mail: mg.bagliesi@pi.infn.i [University of Siena and INFN Pisa (Italy); Berretti, M.; Cecchi, R.; Greco, V.; Lami, S.; Latino, G.; Oliveri, E.; Pedreschi, E.; Scribano, A.; Spinella, F.; Turini, N. [University of Siena and INFN Pisa (Italy)

2010-05-21

The TOTEM experiment will measure the total cross-section with the luminosity independent method and study elastic and diffractive scattering at the LHC. We are developing a modular trigger system, based on programmable logic, that will select meaningful events within 2.5{mu}s. The trigger algorithm is based on a tree structure in order to obtain information compression. The trigger primitive is generated directly on the readout chip, VFAT, that has a specific fast output that gives low resolution hits information. In two of the TOTEM detectors, Roman Pots and T2, a coincidence chip will perform track recognition directly on the detector readout boards, while for T1 the hits are transferred from the VFATs to the trigger hardware. Starting from more than 2000 bits delivered by the detector electronics, we extract, in a first step, six trigger patterns of 32 LVDS signals each; we build, then, on a dedicated board, a 1-bit (L1) trigger signal for the TOTEM experiment and 16 trigger bits to the CMS experiment global trigger system for future common data taking.

The TOTEM modular trigger system

International Nuclear Information System (INIS)

Bagliesi, M.G.; Berretti, M.; Cecchi, R.; Greco, V.; Lami, S.; Latino, G.; Oliveri, E.; Pedreschi, E.; Scribano, A.; Spinella, F.; Turini, N.

2010-01-01

The TOTEM experiment will measure the total cross-section with the luminosity independent method and study elastic and diffractive scattering at the LHC. We are developing a modular trigger system, based on programmable logic, that will select meaningful events within 2.5μs. The trigger algorithm is based on a tree structure in order to obtain information compression. The trigger primitive is generated directly on the readout chip, VFAT, that has a specific fast output that gives low resolution hits information. In two of the TOTEM detectors, Roman Pots and T2, a coincidence chip will perform track recognition directly on the detector readout boards, while for T1 the hits are transferred from the VFATs to the trigger hardware. Starting from more than 2000 bits delivered by the detector electronics, we extract, in a first step, six trigger patterns of 32 LVDS signals each; we build, then, on a dedicated board, a 1-bit (L1) trigger signal for the TOTEM experiment and 16 trigger bits to the CMS experiment global trigger system for future common data taking.

Trigger Foods: The Influence of “Irrelevant†Alternatives in School Lunchrooms

OpenAIRE

Hanks, Andrew S.; Just, David R.; Wansink, Brian

2012-01-01

Rational choice theory commonly assumes that the presence of unselected choices cannot impact which among the remaining choices is selected–-often referred to as “independence of irrelevant alternatives.†We show that such seemingly irrelevant alternatives influence choice in a school lunch setting. In these lunchrooms, we provide evidence that the presence of specific side dishes-–trigger foods-–can strongly increase the sales of unhealthy à la carte options, even when the trigger foods a...

PULSATION-TRIGGERED MASS LOSS FROM AGB STARS: THE 60 DAY CRITICAL PERIOD

International Nuclear Information System (INIS)

McDonald, I.; Zijlstra, A. A.

2016-01-01

Low- and intermediate-mass stars eject much of their mass during the late, red giant branch (RGB) phase of evolution. The physics of their strong stellar winds is still poorly understood. In the standard model, stellar pulsations extend the atmosphere, allowing a wind to be driven through radiation pressure on condensing dust particles. Here, we investigate the onset of the wind, using nearby RGB stars drawn from the Hipparcos catalog. We find a sharp onset of dust production when the star first reaches a pulsation period of 60 days. This approximately coincides with the point where the star transitions to the first overtone pulsation mode. Models of the spectral energy distributions show stellar mass-loss rate suddenly increasing at this point, by a factor of ∼10 over the existing (chromospherically driven) wind. The dust emission is strongly correlated with both pulsation period and amplitude, indicating stellar pulsation is the main trigger for the strong mass loss, and determines the mass-loss rate. Dust emission does not strongly correlate with stellar luminosity, indicating radiation pressure on dust has little effect on the mass-loss rate. RGB stars do not normally appear to produce dust, whereas dust production by asymptotic giant branch stars appears commonplace, and is probably ubiquitous above the RGB-tip luminosity. We conclude that the strong wind begins with a step change in mass-loss rate and is triggered by stellar pulsations. A second rapid mass-loss-rate enhancement is suggested when the star transitions to the fundamental pulsation mode at a period of ∼300 days.

Remotely Triggered Nano-Theranostics For Cancer Applications

Science.gov (United States)

Sneider, Alexandra; VanDyke, Derek; Paliwal, Shailee; Rai, Prakash

2017-01-01

Nanotechnology has enabled the development of smart theranostic platforms that can concurrently diagnose disease, start primary treatment, monitor response, and, if required, initiate secondary treatments. Recent in vivo experiments demonstrate the promise of using theranostics in the clinic. In this paper, we review the use of remotely triggered theranostic nanoparticles for cancer applications, focusing heavily on advances in the past five years. Remote triggering mechanisms covered include photodynamic, photothermal, phototriggered chemotherapeutic release, ultrasound, electro-thermal, magneto-thermal, X-ray, and radiofrequency therapies. Each section includes a brief overview of the triggering mechanism and summarizes the variety of nanoparticles employed in each method. Emphasis in each category is placed on nano-theranostics with in vivo success. Some of the nanotheranostic platforms highlighted include photoactivatable multi-inhibitor nanoliposomes, plasmonic nanobubbles, reduced graphene oxide-iron oxide nanoparticles, photoswitching nanoparticles, multispectral optoacoustic tomography using indocyanine green, low temperature sensitive liposomes, and receptor-targeted iron oxide nanoparticles loaded with gemcitabine. The studies reviewed here provide strong evidence that the field of nanotheranostics is rapidly evolving. Such nanoplatforms may soon enable unique advances in the clinical management of cancer. However, reproducibility in the synthesis procedures of such “smart” platforms that lend themselves to easy scale-up in their manufacturing, as well as the development of new and improved models of cancer that are more predictive of human responses, need to happen soon for this field to make a rapid clinical impact. PMID:28191450

Myosin-1A Targets to Microvilli Using Multiple Membrane Binding Motifs in the Tail Homology 1 (TH1) Domain*

Science.gov (United States)

Mazerik, Jessica N.; Tyska, Matthew J.

2012-01-01

One of the most abundant components of the enterocyte brush border is the actin-based monomeric motor, myosin-1a (Myo1a). Within brush border microvilli, Myo1a carries out a number of critical functions at the interface between membrane and actin cytoskeleton. Proper physiological function of Myo1a depends on its ability to bind to microvillar membrane, an interaction mediated by a C-terminal tail homology 1 (TH1) domain. However, little is known about the mechanistic details of the Myo1a-TH1/membrane interaction. Structure-function analysis of Myo1a-TH1 targeting in epithelial cells revealed that an N-terminal motif conserved among class I myosins and a C-terminal motif unique to Myo1a-TH1 are both required for steady state microvillar enrichment. Purified Myo1a bound to liposomes composed of phosphatidylserine and phosphoinositol 4,5-bisphosphate, with moderate affinity in a charge-dependent manner. Additionally, peptides of the N- and C-terminal regions required for targeting were able to compete with Myo1a for binding to highly charged liposomes in vitro. Single molecule total internal reflection fluorescence microscopy showed that these motifs are also necessary for slowing the membrane detachment rate in cells. Finally, Myo1a-TH1 co-localized with both lactadherin-C2 (a phosphatidylserine-binding protein) and PLCδ1-PH (a phosphoinositol 4,5-bisphosphate-binding protein) in microvilli, but only lactaderin-C2 expression reduced brush border targeting of Myo1a-TH1. Together, our results suggest that Myo1a targeting to microvilli is driven by membrane binding potential that is distributed throughout TH1 rather than localized to a single motif. These data highlight the diversity of mechanisms that enable different class I myosins to target membranes in distinct biological contexts. PMID:22367206

Comparison of new ELISA method with established SDS-PAGE method for determination of muscle myosin heavy chain isoforms

Czech Academy of Sciences Publication Activity Database

Říčný, Jan; Soukup, Tomáš

2011-01-01

Roč. 60, č. 6 (2011), s. 899-904 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA304/08/0256 Grant - others:EC(XE) LSH-CT-2004-511978 Institutional research plan: CEZ:AV0Z50110509 Keywords : muscle fiber types * myosin heavy chains * SDS - PAGE * immunoreactions * thyroid hormones * ELISA Subject RIV: EA - Cell Biology Impact factor: 1.555, year: 2011

LHCb Topological Trigger Reoptimization

International Nuclear Information System (INIS)

Likhomanenko, Tatiana; Khairullin, Egor; Rogozhnikov, Alex; Ustyuzhanin, Andrey; Ilten, Philip; Williams, Michael

2015-01-01

The main b-physics trigger algorithm used by the LHCb experiment is the so- called topological trigger. The topological trigger selects vertices which are a) detached from the primary proton-proton collision and b) compatible with coming from the decay of a b-hadron. In the LHC Run 1, this trigger, which utilized a custom boosted decision tree algorithm, selected a nearly 100% pure sample of b-hadrons with a typical efficiency of 60-70%; its output was used in about 60% of LHCb papers. This talk presents studies carried out to optimize the topological trigger for LHC Run 2. In particular, we have carried out a detailed comparison of various machine learning classifier algorithms, e.g., AdaBoost, MatrixNet and neural networks. The topological trigger algorithm is designed to select all ’interesting” decays of b-hadrons, but cannot be trained on every such decay. Studies have therefore been performed to determine how to optimize the performance of the classification algorithm on decays not used in the training. Methods studied include cascading, ensembling and blending techniques. Furthermore, novel boosting techniques have been implemented that will help reduce systematic uncertainties in Run 2 measurements. We demonstrate that the reoptimized topological trigger is expected to significantly improve on the Run 1 performance for a wide range of b-hadron decays. (paper)

Limited preemptive scheduling of mixed time-triggered and event-triggered tasks

NARCIS (Netherlands)

Heuvel, van den M.M.H.P.; Bril, R.J.; Zhang, X.; Abdullah, S.M.J.; Isovic, D.

2013-01-01

Many embedded systems have complex timing constraints and, at the same time, have flexibility requirements which prohibit offline planning of the entire system. To support a mixture of time-triggered and event-triggered tasks, some industrial systems deploy a table-driven dispatcher for

Concept of a Stand-Alone Muon Trigger with High Transverse Momentum Resolution for the ATLAS Detector at the High-Luminosity LHC

CERN Document Server

Horii, Yasuyuki; The ATLAS collaboration

2014-01-01

The ATLAS trigger uses a three-level trigger system. The level-1 (L1) trigger for muons with high transverse momentum pT in ATLAS is based on fast chambers with excellent time resolution which are able to identify muons coming from a particular beam crossing. These trigger chambers also provide a fast measurement of the muon transverse momenta, however with limited accuracy caused by the moderate spatial resolution along the deflecting direction of the magnetic field. The higher luminosity foreseen for Phase-II puts stringent limits on the L1 trigger rates. A way to control these rates is the improvement of the spatial resolution of the triggering device which drastically sharpens the turn-on curve of the L1 trigger. To do this, the precision tracking chambers (MDT) can be used in the L1 trigger, if the corresponding trigger latency is increased as planned. The trigger rate reduction is accomplished by strongly decreasing the rate of triggers from muons with pT lower than a predefined threshold (typically 20 ...

Headache triggers in the US military.

Science.gov (United States)

Theeler, Brett J; Kenney, Kimbra; Prokhorenko, Olga A; Fideli, Ulgen S; Campbell, William; Erickson, Jay C

2010-05-01

Headaches can be triggered by a variety of factors. Military service members have a high prevalence of headache but the factors triggering headaches in military troops have not been identified. The objective of this study is to determine headache triggers in soldiers and military beneficiaries seeking specialty care for headaches. A total of 172 consecutive US Army soldiers and military dependents (civilians) evaluated at the headache clinics of 2 US Army Medical Centers completed a standardized questionnaire about their headache triggers. A total of 150 (87%) patients were active-duty military members and 22 (13%) patients were civilians. In total, 77% of subjects had migraine; 89% of patients reported at least one headache trigger with a mean of 8.3 triggers per patient. A wide variety of headache triggers was seen with the most common categories being environmental factors (74%), stress (67%), consumption-related factors (60%), and fatigue-related factors (57%). The types of headache triggers identified in active-duty service members were similar to those seen in civilians. Stress-related triggers were significantly more common in soldiers. There were no significant differences in trigger types between soldiers with and without a history of head trauma. Headaches in military service members are triggered mostly by the same factors as in civilians with stress being the most common trigger. Knowledge of headache triggers may be useful for developing strategies that reduce headache occurrence in the military.

The LHCb trigger

CERN Document Server

Hernando Morata, Jose Angel

2006-01-01

The LHCb experiment relies on an efficient trigger to select a rate up to 2 kHz of events useful for physics analysis from an initial rate of 10 MHz of visible collisions. In this contribution, we describe the different LHCb trigger algorithms and present their expected performance.

The ATLAS High Level Trigger Steering Framework and the Trigger 
Configuration System.

CERN Document Server

Pérez Cavalcanti, Tiago; The ATLAS collaboration

2011-01-01

The ATLAS High Level Trigger Steering Framework and the Trigger 
Configuration System.
 
The ATLAS detector system installed in the Large Hadron Collider (LHC) 
at CERN is designed to study proton-proton and nucleus-nucleus 
collisions with a maximum center of mass energy of 14 TeV at a bunch 
collision rate of 40MHz.  In March 2010 the four LHC experiments saw 
the first proton-proton collisions at 7 TeV. Still within the year a 
collision rate of nearly 10 MHz is expected. At ATLAS, events of 
potential interest for ATLAS physics are selected by a three-level 
trigger system, with a final recording rate of about 200 Hz. The first 
level (L1) is implemented in custom hardware; the two levels of 
the high level trigger (HLT) are software triggers, running on large 
farms of standard computers and network devices. 

Within the ATLAS physics program more than 500 trigger signatures are 
defined. The HLT tests each signature on each L1-accepted event; the 
test outcome is recor...

The ATLAS trigger: high-level trigger commissioning and operation during early data taking

International Nuclear Information System (INIS)

Goncalo, R

2008-01-01

The ATLAS experiment is one of the two general-purpose experiments due to start operation soon at the Large Hadron Collider (LHC). The LHC will collide protons at a centre of mass energy of 14 TeV, with a bunch-crossing rate of 40 MHz. The ATLAS three-level trigger will reduce this input rate to match the foreseen offline storage capability of 100-200 Hz. This paper gives an overview of the ATLAS High Level Trigger focusing on the system design and its innovative features. We then present the ATLAS trigger strategy for the initial phase of LHC exploitation. Finally, we report on the valuable experience acquired through in-situ commissioning of the system where simulated events were used to exercise the trigger chain. In particular we show critical quantities such as event processing times, measured in a large-scale HLT farm using a complex trigger menu

Ionic interaction of myosin loop 2 with residues located beyond the N-terminal part of actin probed by chemical cross-linking.

Science.gov (United States)

Pliszka, Barbara; Martin, Brian M; Karczewska, Emilia

2008-02-01

To probe ionic contacts of skeletal muscle myosin with negatively charged residues located beyond the N-terminal part of actin, myosin subfragment 1 (S1) and actin split by ECP32 protease (ECP-actin) were cross-linked with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). We have found that unmodified S1 can be cross-linked not only to the N-terminal part, but also to the C-terminal 36 kDa fragment of ECP-actin. Subsequent experiments performed on S1 cleaved by elastase or trypsin indicate that the cross-linking site in S1 is located within loop 2. This site is composed of Lys-636 and Lys-637 and can interact with negatively charged residues of the 36 kDa actin fragment, most probably with Glu-99 and Glu-100. Cross-links are formed both in the absence and presence of MgATP.P(i) analog, although the addition of nucleotide decreases the efficiency of the cross-linking reaction.

The trigger supervisor: Managing triggering conditions in a high energy physics experiment

International Nuclear Information System (INIS)

Wadsworth, B.; Lanza, R.; LeVine, M.J.; Scheetz, R.A.; Videbaek, F.

1987-01-01

A trigger supervisor, implemented in VME-bus hardware, is described, which enables the host computer to dynamically control and monitor the trigger configuration for acquiring data from multiple detector partitions in a complex experiment

Increased myosin heavy chain-beta with atrial expression of ventricular light chain-2 in canine cardiomyopathy.

Science.gov (United States)

Fuller, Geraldine A; Bicer, Sabahattin; Hamlin, Robert L; Yamaguchi, Mamoru; Reiser, Peter J

2007-10-01

Dilated cardiomyopathy is a naturally occurring disease in humans and dogs. Human studies have shown increased levels of myosin heavy chain (MHC)-beta in failing ventricles and the left atria (LA) and of ventricular light chain (VLC)-2 in the right atria in dilated cardiomyopathy. This study evaluates the levels of MHC-beta in all heart chambers in prolonged canine right ventricular pacing. In addition, we determined whether levels of VLC2 were altered in these hearts. Failing hearts demonstrated significantly increased levels of MHC-beta in the right atria, right atrial appendage, LA, left atrial appendage (LAA), and right ventricle compared with controls. Significant levels of VLC2 were detected in the right atria of paced hearts. Differences in MHC-beta expression were observed between the LA and the LAA of paced and control dogs. MHC-beta expression was significantly greater in the LA of paced and control dogs compared with their respective LAA. The cardiac myosin isoform shifts in this study were similar to those observed in end-stage human heart failure and more severe than those reported in less prolonged pacing models, supporting the use of this model for further study of end-stage human heart failure. The observation of consistent differences between sampling sites, especially LA versus LAA, indicates the need for rigorous sampling consistency in future studies.

Mutation profile of all 49 exons of the human myosin VIIA gene, and haplotype analysis, in Usher 1B families from diverse origins.

Science.gov (United States)

Adato, A; Weil, D; Kalinski, H; Pel-Or, Y; Ayadi, H; Petit, C; Korostishevsky, M; Bonne-Tamir, B

1997-10-01

Usher syndrome types I (USH1A-USH1E) are a group of autosomal recessive diseases characterized by profound congenital hearing loss, vestibular areflexia, and progressive visual loss due to retinitis pigmentosa. The human myosin VIIA gene, located on 11q14, has been shown to be responsible for Usher syndrome type 1B (USH1B). Haplotypes were constructed in 28 USH1 families by use of the following polymorphic markers spanning the USH1B locus: D11S787, D11S527, D11S1789, D11S906, D11S4186, and OMP. Affected individuals and members of their families from 12 different ethnic origins were screened for the presence of mutations in all 49 exons of the myosin VIIA gene. In 15 families myosin VIIA mutations were detected, verifying their classification as USH1B. All these mutations are novel, including three missense mutations, one premature stop codon, two splicing mutations, one frameshift, and one deletion of >2 kb comprising exons 47 and 48, a part of exon 49, and the introns between them. Three mutations were shared by more than one family, consistent with haplotype similarities. Altogether, 16 USH1B haplotypes were observed in the 15 families; most haplotypes were population specific. Several exonic and intronic polymorphisms were also detected. None of the 20 known USH1B mutations reported so far in other world populations were identified in our families.

Cardiac Myosin Binding Protein-C Autoantibodies Are Potential Early Indicators of Cardiac Dysfunction and Patient Outcome in Acute Coronary Syndrome

Directory of Open Access Journals (Sweden)

Thomas L. Lynch, IVPhD

2017-04-01

Full Text Available Summary: 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 cardiovascular disease patients. Importantly, cMyBP-C-AAbs were significantly detected in acute coronary syndrome patient sera upon arrival to the emergency department, particularly in ST-segment elevation myocardial infarction patients. Patients positive for cMyBP-C-AAbs had reduced left ventricular ejection fraction and elevated levels of clinical biomarkers of myocardial infarction. We conclude that cMyBP-C-AAbs may serve as early predictive indicators of deteriorating cardiac function and patient outcome in acute coronary syndrome patients prior to the infarction. Key Words: acute myocardial infarction, autoantibodies, cardiac myosin binding protein-c, cardiomyopathy

Ambient Tremor, But No Triggered Tremor at the Northern Costa Rica Subduction Zone

Science.gov (United States)

Swiecki, Z.; Schwartz, S. Y.

2010-12-01

Non-volcanic tremor (NVT) has been found to be triggered during the passage of surface waves from various teleseismic events in locations around the world including Cascadia, Southwest Japan, Taiwan, and California. In this study we examine the northern Costa Rica subduction zone for evidence of triggered tremor. The Nicoya Peninsula segment of the northern Costa Rica margin experiences both slow-slip and tremor and is thus a prime candidate for triggered tremor observations. Eleven teleseismic events with magnitudes (Mw) greater than 8 occurring between 2006 and 2010 were examined using data from both broadband and short period sensors deployed on the Nicoya Peninsula, Costa Rica. Waveforms from several large regional events were also considered. The largest teleseismic and regional events (27 February 2010 Chile, Mw 8.8 and 28 May 2009 Honduras, Mw 7.3) induced peak ground velocities (PGV) at the NIcoya stations of ~2 and 6 mm/s, respectively; larger than PGVs in other locations that have triggered tremor. Many of the earthquakes examined occurred during small episodes of background ambient tremor. In spite of this, no triggered tremor was observed during the passage of seismic waves from any event. This is significant because other studies have demonstrated that NVT is not triggered everywhere by all events above some threshold magnitude, indicating that unique conditions are required for its occurrence. The lack of triggered tremor at the Costa Rica margin can help to better quantify the requisite conditions and triggering mechanisms. An inherent difference between the Costa Rica margin and the other subduction zones where triggered tremor exists is its erosional rather than accretionary nature. Its relatively low sediment supply likely results in a drier, lower pore fluid pressure, stronger and less compliant thrust interface that is less receptive to triggering tremor from external stresses generated by teleseismic or strong local earthquakes. Another

Myosin heavy chain composition of single fibres from m. biceps brachii of male body builders

DEFF Research Database (Denmark)

Klitgaard, H; Zhou, M.-Y.; Richter, Erik

1990-01-01

The myosin heavy chain (MHC) composition of single fibres from m. biceps brachii of young sedentary men (28 +/- 0.4 years, mean +/- SE, n = 4) and male body builders (25 +/- 2.0 years, n = 4) was analysed with a sensitive one-dimensional electrophoretic technique. Compared with sedentary men...... expression of MHC isoforms within histochemical type II fibres of human skeletal muscle with body building. Furthermore, in human skeletal muscle differences in expression of MHC isoforms may not always be reflected in the traditional histochemical classification of types I, IIa, IIb and IIc fibres....

Analytical description of missing transverse-momentum trigger rates in ATLAS with 7 and 8 TeV data

CERN Document Server

The ATLAS collaboration

2017-01-01

The missing transverse-momentum (MET) trigger of the ATLAS experiment is based on the measurement of the energy deposited over the full calorimeter acceptance. The MET trigger rate for a fixed threshold therefore strongly depends on the number of collisions per bunch crossing produced by the CERN LHC. For useful trigger thresholds, the MET trigger rate is dominated by mismeasuement giving rise to an apparent transverse-momentum imbalance, rather than particles escaping the detector. This note presents an analytic model for the resulting MET distribution, which arises from two main sources. At low MET values, detector resolution effects dominate. These depend on the scalar sum of the transverse projection of energies measured in the event and on the mean number \\mu of collisions per bunch crossing (a measure of the LHC instantaneous luminosity). In this region, the MET trigger rate decreases exponentially with the trigger’s MET threshold value. However, in the same region the absolute rate of a fixed thresho...

Hypertrophic cardiomyopathy mutation R58Q in the myosin regulatory light chain perturbs thick filament-based regulation in cardiac muscle.

Science.gov (United States)

Kampourakis, Thomas; Ponnam, Saraswathi; Irving, Malcolm

2018-04-01

Hypertrophic cardiomyopathy (HCM) is frequently linked to mutations in the protein components of the myosin-containing thick filaments leading to contractile dysfunction and ultimately heart failure. However, the molecular structure-function relationships that underlie these pathological effects remain largely obscure. Here we chose an example mutation (R58Q) in the myosin regulatory light chain (RLC) that is associated with a severe HCM phenotype and combined the results from a wide range of in vitro and in situ structural and functional studies on isolated protein components, myofibrils and ventricular trabeculae to create an extensive map of structure-function relationships. The results can be understood in terms of a unifying hypothesis that illuminates both the effects of the mutation and physiological signaling pathways. R58Q promotes an OFF state of the thick filaments that reduces the number of myosin head domains that are available for actin interaction and ATP utilization. Moreover this mutation uncouples two aspects of length-dependent activation (LDA), the cellular basis of the Frank-Starling relation that couples cardiac output to venous return; R58Q reduces maximum calcium-activated force with no significant effect on myofilament calcium sensitivity. Finally, phosphorylation of R58Q-RLC to levels that may be relevant both physiologically and pathologically restores the regulatory state of the thick filament and the effect of sarcomere length on maximum calcium-activated force and thick filament structure, as well as increasing calcium sensitivity. We conclude that perturbation of thick filament-based regulation may be a common mechanism in the etiology of missense mutation-associated HCM, and that this signaling pathway offers a promising target for the development of novel therapeutics. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

The ATLAS Muon and Tau Trigger

CERN Document Server

Dell'Asta, L; The ATLAS collaboration

2013-01-01

[Muon] The ATLAS experiment at CERN's Large Hadron Collider (LHC) deploys a three-levels processing scheme for the trigger system. The level-1 muon trigger system gets its input from fast muon trigger detectors. Fast sector logic boards select muon candidates, which are passed via an interface board to the central trigger processor and then to the High Level Trigger (HLT). The muon HLT is purely software based and encompasses a level-2 (L2) trigger followed by an event filter (EF) for a staged trigger approach. It has access to the data of the precision muon detectors and other detector elements to refine the muon hypothesis. Trigger-specific algorithms were developed and are used for the L2 to increase processing speed for instance by making use of look-up tables and simpler algorithms, while the EF muon triggers mostly benefit from offline reconstruction software to obtain most precise determination of the track parameters. There are two algorithms with different approaches, namely inside-out and outside-in...

Performance of the ATLAS Muon Trigger and Phase-1 Upgrade of Level-1 Endcap Muon Trigger

CERN Document Server

Mizukami, Atsushi; The ATLAS collaboration

2017-01-01

The ATLAS experiment utilises a trigger system to efficiently record interesting events. It consists of first-level and high-level triggers. The first-level trigger is implemented with custom-built hardware to reduce the event rate from 40 MHz to100 kHz. Then the software-based high-level triggers refine the trigger decisions reducing the output rate down to 1 kHz. Events with muons in the final state are an important signature for many physics topics at the LHC. An efficient trigger on muons and a detailed understanding of its performance are required. Trigger efficiencies are, for example, obtained from the muon decay of Z boson, with a Tag&Probe method, using proton-proton collision data collected in 2016 at a centre-of-mass energy of 13 TeV. The LHC is expected to increase its instantaneous luminosity to $3\\times10^{34} \\rm{cm^{-2}s^{-1}}$ after the phase-1 upgrade between 2018-2020. The upgrade of the ATLAS trigger system is mandatory to cope with this high-luminosity. In the phase-1 upgrade, new det...

AN INTEGRATIVE WAY OF TEACHING MOLECULAR CELL BIOLOGY AND PROTEIN CHEMISTRY USING ACTIN IMMOBILIZATION ON CHITIN FOR PURIFYING MYOSIN II.

Directory of Open Access Journals (Sweden)

M.G. Souza

2007-05-01

Full Text Available Our intent is to present our experience on teaching Molecular Cell Biology andProtein Chemistry at UNIRIO through an innovative approach that includes myosin IIextraction and purification. We took advantage of the properties of muscle contractionand propose a simple method for purifying myosin II by affinity chromatography. Thisoriginal method is based on the preparation of an affinity column containing actinmolecules covalently bound to chitin particles. We propose a three-week syllabus thatincludes lectures and bench experimental work. The syllabus favors the activelearning of protein extraction and purification, as well as, of scientific concepts suchas muscle contraction, cytoskeleton structure and its importance for the living cell. Italso promotes the learning of the biotechnological applications of chitin and theapplications of protein immobilization in different industrial fields. Furthermore, theactivities also target the development of laboratorial technical abilities, thedevelopment of problem solving skills and the ability to write up a scientific reportfollowing the model of a scientific article. It is very important to mention that thissyllabus can be used even in places where a facility such as ultra-centrifugation islacking.

DUMAND data acquisition with triggering

International Nuclear Information System (INIS)

Brenner, A.E.; Theriot, D.; March, R.H.

1980-01-01

A data acquisition scheme for the standard DUMAND array that includes a simple triggering scheme as a fundamental part of the system is presented. Although there are a number of not yet fully understood parameters, it is assumed that thresholds can be set in such a manner as to give rise to a triggered signal that is not so dominated by randoms that it gives a substantial decrease in the data acquisition rate over that which would be required by a nontriggered system. It is also assumed that the triggering logic is relatively simple and does not need major computational capabilities for a trigger logic decision. With these assumptions, it is possible to generate the trigger at the array and restrict the data transfer to shore. However, with a not unreasonable delay of 200 microseconds, it is even possible to transmit the information for the trigger to shore and perform all that logic on the shore. The critical point is to send the minimum amount of information necessary to construct the trigger such that one need not send all the possible information in all detectors of the array continuously to shore. 1 figure

Self-triggering of radio signals from cosmic ray air showers

International Nuclear Information System (INIS)

Asch, Thomas

2009-02-01

LOPES STAR is a prototype detector for future experiments on the observation of radio emission of ultra high energy cosmic rays. Absolutely calibrated measurements of the electric field strength with the LOPES STAR detector were performed in coincidence with the well-established air shower detector KASCADE-Grande. The experinmental configuration allowed a simultaneous observation of east-west and north-south polarised components of the electric field per antenna used. This thesis discusses in detail the influence of background sources on the detector configuration as well as the resulting self-trigger system. The implemented trigger suppresses strong background signals from the industrial environment on the site of the Forschungszentrum Karlsruhe (rejection >99.9 %) and is the basis for a hardware self-trigger. Therefore, the system is adequate for any other detector site. Two different calibration methods are performed and cross-checked to convert the measured raw data into an electric field strength. Both methods result in the same frequency dependent calibration values within their uncertainties. Furthermore, the probable scale parameter of d 0 =(137±18) m. The comparison of selected events with Monte Carlo simulations on an event-by-event basis points out a good correspondence within the given uncertainties and confirms the geosynchrotron model. The overall angular resolution of the arrival direction results in only a few degrees. The presented methods and algorithms are developed for the trigger system and the analysis and are now standard tools for the data analysis in the LOPES collaboration. (orig.)

The ATLAS hadronic tau trigger

CERN Document Server

Black, C; The ATLAS collaboration

2012-01-01

With the high luminosities of proton-proton collisions achieved at the LHC, the strategies for triggering have become more important than ever for physics analysis. The naive inclusive single tau lepton triggers now suffer from severe rate limitations. To allow for a large program of physics analyses with taus, the development of topological triggers that combine tau signatures with other measured quantities in the event is required. These combined triggers open many opportunities to study new physics beyond the Standard Model and to search for the Standard Model Higgs. We present the status and performance of the hadronic tau trigger in ATLAS. We demonstrate that the ATLAS tau trigger ran remarkably well over 2011, and how the lessons learned from 2011 led to numerous improvements in the preparation of the 2012 run. These improvements include the introduction of tau selection criteria that are robust against varying pileup scenarios, and the implementation of multivariate selection techniques in the tau trig...

The ATLAS hadronic tau trigger

CERN Document Server

Black, C; The ATLAS collaboration

2012-01-01

With the high luminosities of proton-proton collisions achieved at the LHC, the strategies for triggering have become more important than ever for physics analysis. The naïve inclusive single tau lepton triggers now suffer from severe rate limitations. To allow for a large program of physics analyses with taus, the development of topological triggers that combine tau signatures with other measured quantities in the event is required. These combined triggers open many opportunities to study new physics beyond the Standard Model and to search for the Standard Model Higgs. We present the status and performance of the hadronic tau trigger in ATLAS. We demonstrate that the ATLAS tau trigger ran remarkably well over 2011, and how the lessons learned from 2011 led to numerous improvements in the preparation of the 2012 run. These improvements include the introduction of tau selection criteria that are robust against varying pileup scenarios, and the implementation of multivariate selection techniques in the tau tri...

Data analysis at the CMS level-1 trigger: migrating complex selection algorithms from offline analysis and high-level trigger to the trigger electronics

CERN Document Server

Wulz, Claudia

2017-01-01

With ever increasing luminosity at the LHC, optimum online data selection is becoming more and more important. While in the case of some experiments (LHCb and ALICE) this task is being completely transferred to computer farms, the others -- ATLAS and CMS -- will not be able to do this in the medium-term future for technological, detector-related reasons. Therefore, these experiments pursue the complementary approach of migrating more and more of the offline and high-level trigger intelligence into the trigger electronics. The presentation illustrates how the level-1 trigger of the CMS experiment and in particular its concluding stage, the so-called ``Global Trigger", take up this challenge.

A First-Level Muon Trigger Based on the ATLAS Muon Drift Tube Chambers With High Momentum Resolution for LHC Phase II

CERN Document Server

Richter, R; The ATLAS collaboration; Ott, S; Kortner, O; Fras, M; Gabrielyan, V; Danielyan, V; Fink, D; Nowak, S; Schwegler, P; Abovyan, S

2014-01-01

The Level-1 (L1) trigger for muons with high transverse momentum (pT) in ATLAS is based on chambers with excellent time resolution, able to identify muons coming from a particular beam crossing. These trigger chambers also provide a fast pT-measurement of the muons, the accuracy of the measurement being limited by the moderate spatial resolution of the chambers along the deflecting direction of the magnetic field (eta-coordinate). The higher luminosity foreseen for Phase-II puts stringent limits on the L1 trigger rates, and a way to control these rates would be to improve the spatial resolution of the triggering system, drastically sharpening the turn-on curve of the L1 trigger. To do this, the precision tracking chambers (MDT) can be used in the L1 trigger, provided the corresponding trigger latency is increased as foreseen. The trigger rate reduction is accomplished by strongly decreasing the rate of triggers from muons with pT lower than a predefined threshold (typically 20 GeV), which would otherwise trig...

Nonlinear dynamical triggering of slow slip

Energy Technology Data Exchange (ETDEWEB)

Johnson, Paul A [Los Alamos National Laboratory; Knuth, Matthew W [WISCONSIN; Kaproth, Bryan M [PENN STATE; Carpenter, Brett [PENN STATE; Guyer, Robert A [Los Alamos National Laboratory; Le Bas, Pierre - Yves [Los Alamos National Laboratory; Daub, Eric G [Los Alamos National Laboratory; Marone, Chris [PENN STATE

2010-12-10

Among the most fascinating, recent discoveries in seismology have been the phenomena of triggered slip, including triggered earthquakes and triggered-tremor, as well as triggered slow, silent-slip during which no seismic energy is radiated. Because fault nucleation depths cannot be probed directly, the physical regimes in which these phenomena occur are poorly understood. Thus determining physical properties that control diverse types of triggered fault sliding and what frictional constitutive laws govern triggered faulting variability is challenging. We are characterizing the physical controls of triggered faulting with the goal of developing constitutive relations by conducting laboratory and numerical modeling experiments in sheared granular media at varying load conditions. In order to simulate granular fault zone gouge in the laboratory, glass beads are sheared in a double-direct configuration under constant normal stress, while subject to transient perturbation by acoustic waves. We find that triggered, slow, silent-slip occurs at very small confining loads ({approx}1-3 MPa) that are smaller than those where dynamic earthquake triggering takes place (4-7 MPa), and that triggered slow-slip is associated with bursts of LFE-like acoustic emission. Experimental evidence suggests that the nonlinear dynamical response of the gouge material induced by dynamic waves may be responsible for the triggered slip behavior: the slip-duration, stress-drop and along-strike slip displacement are proportional to the triggering wave amplitude. Further, we observe a shear-modulus decrease corresponding to dynamic-wave triggering relative to the shear modulus of stick-slips. Modulus decrease in response to dynamical wave amplitudes of roughly a microstrain and above is a hallmark of elastic nonlinear behavior. We believe that the dynamical waves increase the material non-affine elastic deformation during shearing, simultaneously leading to instability and slow-slip. The inferred

ATLAS: triggers for B-physics

International Nuclear Information System (INIS)

George, Simon

2000-01-01

The LHC will produce bb-bar events at an unprecedented rate. The number of events recorded by ATLAS will be limited by the rate at which they can be stored offline and subsequently analysed. Despite the huge number of events, the small branching ratios mean that analysis of many of the most interesting channels for CP violation and other measurements will be limited by statistics. The challenge for the Trigger and Data Acquisition (DAQ) system is therefore to maximise the fraction of interesting B decays in the B-physics data stream. The ATLAS Trigger/DAQ system is split into three levels. The initial B-physics selection is made in the first-level trigger by an inclusive low-p T muon trigger (∼6 GeV). The second-level trigger strategy is based on identifying classes of final states by their partial reconstruction. The muon trigger is confirmed before proceeding to a track search. Electron/hadron separation is given by the transition radiation tracking detector and the Electromagnetic calorimeter. Muon identification is possible using the muon detectors and the hadronic calorimeter. From silicon strips, pixels and straw tracking, precise track reconstruction is used to make selections based on invariant mass, momentum and impact parameter. The ATLAS trigger group is currently engaged in algorithm development and performance optimisation for the B-physics trigger. This is closely coupled to the R and D programme for the higher-level triggers. Together the two programmes of work will optimise the hardware, architecture and algorithms to meet the challenging requirements. This paper describes the current status and progress of this work

Designing signal-enriched triggers for boosted jets.

CERN Document Server

Toumazou, Marina

2017-01-01

Triggers designed to favour the selection of hadronically decaying massive particles have been studied. Both triggers using solely ET and mass cuts (similar to new 2017 triggers) and triggers exploiting polarization information have been studied. The mass cut triggers show substantial gains in rate reduction, while the benefits of polarization triggers are less obvious. The final conclusion is that it is more useful to identify and trigger on generic boosted decays, irrespective of the polarization of the decaying particle

Towards RTOS support for mixed time-triggered and event-triggered task sets

NARCIS (Netherlands)

Heuvel, van den M.M.H.P.; Bril, R.J.; Lukkien, J.J.; Isovic, D.; Sankar Ramachandran, G.

2012-01-01

Many embedded systems have complex timing constraints and, at the same time, have flexibility requirements which prohibit offline planning of the entire system. To support a mixture of time-triggered and event-triggered tasks, some industrial systems deploy a real-time operating system (RTOS) with a

The Run-2 ATLAS Trigger System

CERN Document Server

AUTHOR|(INSPIRE)INSPIRE-00222798; The ATLAS collaboration

2016-01-01

The ATLAS trigger successfully collected collision data during the first run of the LHC between 2009-2013 at different centre-of-mass energies between 900 GeV and 8 TeV. The trigger system consists of a hardware Level-1 and a software-based high level trigger (HLT) that reduces the event rate from the design bunch-crossing rate of 40 MHz to an average recording rate of a few hundred Hz. In Run-2, the LHC will operate at centre-of-mass energies of 13 and 14 TeV and higher luminosity, resulting in roughly five times higher trigger rates. A brief review of the ATLAS trigger system upgrades that were implemented between Run-1 and Run-2, allowing to cope with the increased trigger rates while maintaining or even improving the efficiency to select physics processes of interest, will be given. This includes changes to the Level-1 calorimeter and muon trigger systems, the introduction of a new Level-1 topological trigger module and the merging of the previously two-level HLT system into a single event filter farm. A ...

The LVL2 trigger goes online

CERN Multimedia

David Berge

On Friday, the 9th of February, the ATLAS TDAQ community reached an important milestone. In a successful integration test, cosmic-ray muons were recorded with parts of the muon spectrometer, the central-trigger system and a second-level trigger algorithm. This was actually the first time that a full trigger slice all the way from the first-level trigger muon chambers up to event building after event selection by the second-level trigger ran online with cosmic rays. The ATLAS trigger and data acquisition system has a three-tier structure that is designed to cope with the enormous demands of proton-proton collisions at a bunch-crossing frequency of 40 MHz, with a typical event size of 1-2 MB. The online event selection has to reduce the incoming rate by a factor of roughly 200,000 to 200 Hz, a rate digestible by the archival-storage and offline-processing facilities. ATLAS has a mixed system: the first-level trigger (LVL1) is in hardware, while the other two consecutive levels, the second-level trigger (LVL2)...

The Database Driven ATLAS Trigger Configuration System

CERN Document Server

Martyniuk, Alex; The ATLAS collaboration

2015-01-01

This contribution describes the trigger selection configuration system of the ATLAS low- and high-level trigger (HLT) and the upgrades it received in preparation for LHC Run 2. The ATLAS trigger configuration system is responsible for applying the physics selection parameters for the online data taking at both trigger levels and the proper connection of the trigger lines across those levels. Here the low-level trigger consists of the already existing central trigger (CT) and the new Level-1 Topological trigger (L1Topo), which has been added for Run 2. In detail the tasks of the configuration system during the online data taking are Application of the selection criteria, e.g. energy cuts, minimum multiplicities, trigger object correlation, at the three trigger components L1Topo, CT, and HLT On-the-fly, e.g. rate-dependent, generation and application of prescale factors to the CT and HLT to adjust the trigger rates to the data taking conditions, such as falling luminosity or rate spikes in the detector readout ...

Drastic increase of myosin light chain MLC-2 in senescent skeletal muscle indicates fast-to-slow fibre transition in sarcopenia of old age.

Science.gov (United States)

Gannon, Joan; Doran, Philip; Kirwan, Anne; Ohlendieck, Kay

2009-11-01

The age-dependent decline in skeletal muscle mass and function is believed to be due to a multi-factorial pathology and represents a major factor that blocks healthy aging by increasing physical disability, frailty and loss of independence in the elderly. This study has focused on the comparative proteomic analysis of contractile elements and revealed that the most striking age-related changes seem to occur in the protein family representing myosin light chains (MLCs). Comparative screening of total muscle extracts suggests a fast-to-slow transition in the aged MLC population. The mass spectrometric analysis of the myofibril-enriched fraction identified the MLC2 isoform of the slow-type MLC as the contractile protein with the most drastically changed expression during aging. Immunoblotting confirmed an increased abundance of slow MLC2, concomitant with a switch in fast versus slow myosin heavy chains. Staining of two-dimensional gels of crude extracts with the phospho-specific fluorescent dye ProQ-Diamond identified the increased MLC2 spot as a muscle protein with a drastically enhanced phosphorylation level in aged fibres. Comparative immunofluorescence microscopy, using antibodies to fast and slow myosin isoforms, confirmed a fast-to-slow transformation process during muscle aging. Interestingly, the dramatic increase in slow MLC2 expression was restricted to individual senescent fibres. These findings agree with the idea that aged skeletal muscles undergo a shift to more aerobic-oxidative metabolism in a slower-twitching fibre population and suggest the slow MLC2 isoform as a potential biomarker for fibre type shifting in sarcopenia of old age.

Association of cardiac myosin binding protein-C with the ryanodine receptor channel: putative retrograde regulation?

Science.gov (United States)

Stanczyk, Paulina J; Seidel, Monika; White, Judith; Viero, Cedric; George, Christopher H; Zissimopoulos, Spyros; Lai, F Anthony

2018-06-21

The cardiac muscle ryanodine receptor-Ca 2+ release channel (RyR2) constitutes the sarcoplasmic reticulum (SR) Ca 2+ efflux mechanism that initiates myocyte contraction, while cardiac myosin binding protein-C (cMyBP-C) mediates regulation of acto-myosin cross-bridge cycling. In this report, we provide the first evidence for the presence of direct interaction between these two proteins, forming a RyR2:cMyBP-C complex. The C-terminus of cMyBP-C binds with the RyR2 N-terminus in mammalian cells and is not mediated by a fibronectin-like domain. Notably, we detected complex formation between both recombinant cMyBP-C and RyR2, as well as with the native proteins in cardiac tissue. Cellular Ca 2+ dynamics in HEK293 cells is altered upon co-expression of cMyBP-C and RyR2, with lowered frequency of RyR2-mediated spontaneous Ca 2+ oscillations, suggesting cMyBP-C exerts a potential inhibitory effect on RyR2-dependent Ca 2+ release. Discovery of a functional RyR2 association with cMyBP-C provides direct evidence for a putative mechanistic link between cytosolic soluble cMyBP-C and SR-mediated Ca 2+ release, via RyR2. Importantly, this interaction may have clinical relevance to the observed cMyBP-C and RyR2 dysfunction in cardiac pathologies, such as hypertrophic cardiomyopathy. © 2018. Published by The Company of Biologists Ltd.

DT Local Trigger performance in 2015

CERN Document Server

CMS Collaboration

2015-01-01

The Local Trigger system of the CMS Drift Tube chambers (DT) was checked applying similar methods as in the LHC Run 1 (2012). The main variables shown in this note are the trigger efficiency, the trigger quality and the fraction of trigger ghosts. The performance was found to be comparable or better than in Run 1.

Intestinal infection with Giardia spp. reduces epithelial barrier function in a myosin light chain kinase-dependent fashion.

Science.gov (United States)

Scott, Kevin G-E; Meddings, Jonathon B; Kirk, David R; Lees-Miller, Susan P; Buret, André G

2002-10-01

Giardiasis causes malabsorptive diarrhea, and symptoms can be present in the absence of any significant morphologic injury to the intestinal mucosa. The effects of giardiasis on epithelial permeability in vivo remain unknown, and the role of T cells and myosin light chain kinase (MLCK) in altered intestinal barrier function is unclear. This study was conducted to determine whether Giardia spp. alters intestinal permeability in vivo, to assess whether these abnormalities are dependent on T cells, and to assess the role of MLCK in altered epithelial barrier function. Immunocompetent and isogenic athymic mice were inoculated with axenic Giardia muris trophozoites or sterile vehicle (control), then assessed for trophozoite colonization and gastrointestinal permeability. Mechanistic studies using nontransformed human duodenal epithelial monolayers (SCBN) determined the effects of Giardia on myosin light chain (MLC) phosphorylation, transepithelial fluorescein isothiocyanate-dextran fluxes, cytoskeletal F-actin, tight junctional zonula occludens-1 (ZO-1), and MLCK. Giardia infection caused a significant increase in small intestinal, but not gastric or colonic, permeability that correlated with trophozoite colonization in both immunocompetent and athymic mice. In vitro, Giardia increased permeability and phosphorylation of MLC and reorganized F-actin and ZO-1. These alterations were abolished with an MLCK inhibitor. Disruption of small intestinal barrier function is T cell independent, disappears on parasite clearance, and correlates with reorganization of cytoskeletal F-actin and tight junctional ZO-1 in an MLCK-dependent fashion.

An Evaluation of Triggering Timing for the TROI Tests

International Nuclear Information System (INIS)

Park, Ik Kyu; Kim, Jong Hwan; Hong, Seong Wan

2009-01-01

In the postulated reactor severe accident, the molten corium can be poured into the remained reactor coolant of the lower pressure vessel or the reactor cavity. This might severely threaten the containment integrity, and thus, the experimental and analytical efforts have been done to reveal this risk. It is generally received by the steam explosion experts that the in-vessel steam explosion steam explosion would not challenge the integrity of the vessel and the containment. The ex-vessel explosion, however, cannot be excluded from the factor to threaten the integrity of the cavity and more the reactor vessel. The worse thing of ex-vessel situation is that water is subcooled under a relative low pressure. The results of steam explosion experiments indicate that the subcooled water under a low pressure might be a good environment to make a strong steam explosion. Furthermore, the calculation results for evaluating ex-vessel steam explosion work are too scattered each other. Thus, the conversion ratio of ex-vessel explosion is still remained as a resolved issue. SERENA phase 2 project which has been conducted since 1st Oct. 2007 is aimed a resolution of the uncertainties on the void fraction, the solidification, and the melt composition effect by performing a limited number of well-designed tests with advanced instrumentations to clarify the nature of a prototypic material with mild steam explosion characteristics and to provide innovative experimental data for a computer code validation. The steam explosion results such as explosion pressure, conversion ratio, and the debris configuration are strongly affected by the initial conditions. Meanwhile, some events like triggering magnitude might not be important for the steam explosion results. The initial conditions of the steam explosion, called premixture, are determined by three factors: first one is melt and water condition, second one is a mixing process, and the other is the triggering timing. The mixing process is

Myosin phosphorylation potentiates steady-state work output without altering contractile economy of mouse fast skeletal muscles.

Science.gov (United States)

Gittings, William; Bunda, Jordan; Vandenboom, Rene

2018-01-30

Skeletal myosin light chain kinase (skMLCK)-catalyzed phosphorylation of the myosin regulatory light chain (RLC) increases (i.e. potentiates) mechanical work output of fast skeletal muscle. The influence of this event on contractile economy (i.e. energy cost/work performed) remains controversial, however. Our purpose was to quantify contractile economy of potentiated extensor digitorum longus (EDL) muscles from mouse skeletal muscles with (wild-type, WT) and without (skMLCK ablated, skMLCK -/- ) the ability to phosphorylate the RLC. Contractile economy was calculated as the ratio of total work performed to high-energy phosphate consumption (HEPC) during a period of repeated isovelocity contractions that followed a potentiating stimulus (PS). Consistent with genotype, the PS increased RLC phosphorylation measured during, before and after isovelocity contractions in WT but not in skMLCK -/- muscles (i.e. 0.65 and 0.05 mol phosphate mol -1 RLC, respectively). In addition, although the PS enhanced work during repeated isovelocity contractions in both genotypes, the increase was significantly greater in WT than in skMLCK -/- muscles (1.51±0.03 versus 1.10±0.05, respectively; all data P economy calculated for WT muscles was similar to that calculated for skMLCK -/- muscles (i.e. 5.74±0.67 and 4.61±0.71 J kg -1  μmol -1 P, respectively ( P economy. © 2018. Published by The Company of Biologists Ltd.

Radioimmunoassay of myosin heavy beta chains in human serum for the evaluation of the size of myocardial infarction: correlation with myocardial Tl-201 SPECT and cardiac angioscintigraphy. Le dosage des chaines lourdes beta de la myosine serique dans l'approche de la taille de l'infarctus du myocarde: correlation avec la tomoscintigraphie myocardique au Tl-201 et l'angioscintigraphie cardiaque

Energy Technology Data Exchange (ETDEWEB)

Facello, A.; Gries, P.; Demangeat, C.; Brunot, B.; Roul, G.; Demangeat, J.L.; Moulichon, M.; Bareiss, P.; Sacrez, A.; Constantinesco, A. (Centre Hospitalier Universitaire Hautepierre, 67 - Strasbourg (FR))

1990-01-01

To determine the relationship between serum levels of myosin heavy beta chains assessed by an IRMA technique and other radionuclide and enzymatic parameters in the evaluation of the size of myocardial infarction, we studied 22 patients with acute myocardial infarction. Blood samples taken daily between 1st to 13th day of evolution allow the determination of peak and integral of myosine release that showed a good correlation (p<0.01) with myocardial underperfusion score in T1-201 SPECT, left ventricular ejection fractions at 1st day and at the pre-discharge study, just as CPK peak. This new assay is an interesting mean to evaluate the size of myocardial infarction.

Monitoring in Language Perception: Mild and Strong Conflicts Elicit Different ERP Patterns

Science.gov (United States)

van de Meerendonk, Nan; Kolk, Herman H. J.; Vissers, Constance Th. W. M.; Chwilla, Dorothee J.

2010-01-01

In the language domain, most studies of error monitoring have been devoted to language production. However, in language perception, errors are made as well and we are able to detect them. According to the monitoring theory of language perception, a strong conflict between what is expected and what is observed triggers reanalysis to check for…

Human-gyrovirus-Apoptin triggers mitochondrial death pathway--Nur77 is required for apoptosis triggering.

Science.gov (United States)

Chaabane, Wiem; Cieślar-Pobuda, Artur; El-Gazzah, Mohamed; Jain, Mayur V; Rzeszowska-Wolny, Joanna; Rafat, Mehrdad; Stetefeld, Joerg; Ghavami, Saeid; Los, Marek J

2014-09-01

The human gyrovirus derived protein Apoptin (HGV-Apoptin) a homologue of the chicken anemia virus Apoptin (CAV-Apoptin), a protein with high cancer cells selective toxicity, triggers apoptosis selectively in cancer cells. In this paper, we show that HGV-Apoptin acts independently from the death receptor pathway as it induces apoptosis in similar rates in Jurkat cells deficient in either FADD (fas-associated death domain) function or caspase-8 (key players of the extrinsic pathway) and their parental clones. HGV-Apoptin induces apoptosis via the activation of the mitochondrial intrinsic pathway. It induces both mitochondrial inner and outer membrane permebilization, characterized by the loss of the mitochondrial potential and the release into cytoplasm of the pro-apoptotic molecules including apoptosis inducing factor and cytochrome c. HGV-Apoptin acts via the apoptosome, as lack of expression of apoptotic protease-activating factor 1 in murine embryonic fibroblast strongly protected the cells from HGV-Apoptin-induced apoptosis. Moreover, QVD-oph a broad-spectrum caspase inhibitor delayed HGV-Apoptin-induced death. On the other hand, overexpression of the anti-apoptotic BCL-XL confers resistance to HGV-Apoptin-induced cell death. In contrast, cells that lack the expression of the pro-apoptotic BAX and BAK are protected from HGV-Apoptin induced apoptosis. Furthermore, HGV-Apoptin acts independently from p53 signal but triggers the cytoplasmic translocation of Nur77. Taking together these data indicate that HGV-Apoptin acts through the mitochondrial pathway, in a caspase-dependent manner but independently from the death receptor pathway. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

The Run-2 ATLAS Trigger System

CERN Document Server

Ruiz-Martinez, Aranzazu; The ATLAS collaboration

2016-01-01

The ATLAS trigger has been successfully collecting collision data during the first run of the LHC between 2009-2013 at a centre-of-mass energy between 900 GeV and 8 TeV. The trigger system consists of a hardware Level-1 (L1) and a software based high-level trigger (HLT) that reduces the event rate from the design bunch-crossing rate of 40 MHz to an average recording rate of a few hundred Hz. In Run-2, the LHC will operate at centre-of-mass energies of 13 and 14 TeV resulting in roughly five times higher trigger rates. We will briefly review the ATLAS trigger system upgrades that were implemented during the shutdown, allowing us to cope with the increased trigger rates while maintaining or even improving our efficiency to select relevant physics processes. This includes changes to the L1 calorimeter and muon trigger systems, the introduction of a new L1 topological trigger module and the merging of the previously two-level HLT system into a single event filter farm. At hand of a few examples, we will show the ...

Calorimetry triggering in ATLAS

CERN Document Server

Igonkina, O; Adragna, P; Aharrouche, M; Alexandre, G; Andrei, V; Anduaga, X; Aracena, I; Backlund, S; Baines, J; Barnett, B M; Bauss, B; Bee, C; Behera, P; Bell, P; Bendel, M; Benslama, K; Berry, T; Bogaerts, A; Bohm, C; Bold, T; Booth, J R A; Bosman, M; Boyd, J; Bracinik, J; Brawn, I, P; Brelier, B; Brooks, W; Brunet, S; Bucci, F; Casadei, D; Casado, P; Cerri, A; Charlton, D G; Childers, J T; Collins, N J; Conde Muino, P; Coura Torres, R; Cranmer, K; Curtis, C J; Czyczula, Z; Dam, M; Damazio, D; Davis, A O; De Santo, A; Degenhardt, J; Delsart, P A; Demers, S; Demirkoz, B; Di Mattia, A; Diaz, M; Djilkibaev, R; Dobson, E; Dova, M, T; Dufour, M A; Eckweiler, S; Ehrenfeld, W; Eifert, T; Eisenhandler, E; Ellis, N; Emeliyanov, D; Enoque Ferreira de Lima, D; Faulkner, P J W; Ferland, J; Flacher, H; Fleckner, J E; Flowerdew, M; Fonseca-Martin, T; Fratina, S; Fhlisch, F; Gadomski, S; Gallacher, M P; Garitaonandia Elejabarrieta, H; Gee, C N P; George, S; Gillman, A R; Goncalo, R; Grabowska-Bold, I; Groll, M; Gringer, C; Hadley, D R; Haller, J; Hamilton, A; Hanke, P; Hauser, R; Hellman, S; Hidvgi, A; Hillier, S J; Hryn'ova, T; Idarraga, J; Johansen, M; Johns, K; Kalinowski, A; Khoriauli, G; Kirk, J; Klous, S; Kluge, E-E; Koeneke, K; Konoplich, R; Konstantinidis, N; Kwee, R; Landon, M; LeCompte, T; Ledroit, F; Lei, X; Lendermann, V; Lilley, J N; Losada, M; Maettig, S; Mahboubi, K; Mahout, G; Maltrana, D; Marino, C; Masik, J; Meier, K; Middleton, R P; Mincer, A; Moa, T; Monticelli, F; Moreno, D; Morris, J D; Mller, F; Navarro, G A; Negri, A; Nemethy, P; Neusiedl, A; Oltmann, B; Olvito, D; Osuna, C; Padilla, C; Panes, B; Parodi, F; Perera, V J O; Perez, E; Perez Reale, V; Petersen, B; Pinzon, G; Potter, C; Prieur, D P F; Prokishin, F; Qian, W; Quinonez, F; Rajagopalan, S; Reinsch, A; Rieke, S; Riu, I; Robertson, S; Rodriguez, D; Rogriquez, Y; Rhr, F; Saavedra, A; Sankey, D P C; Santamarina, C; Santamarina Rios, C; Scannicchio, D; Schiavi, C; Schmitt, K; Schultz-Coulon, H C; Schfer, U; Segura, E; Silverstein, D; Silverstein, S; Sivoklokov, S; Sjlin, J; Staley, R J; Stamen, R; Stelzer, J; Stockton, M C; Straessner, A; Strom, D; Sushkov, S; Sutton, M; Tamsett, M; Tan, C L A; Tapprogge, S; Thomas, J P; Thompson, P D; Torrence, E; Tripiana, M; Urquijo, P; Urrejola, P; Vachon, B; Vercesi, V; Vorwerk, V; Wang, M; Watkins, P M; Watson, A; Weber, P; Weidberg, T; Werner, P; Wessels, M; Wheeler-Ellis, S; Whiteson, D; Wiedenmann, W; Wielers, M; Wildt, M; Winklmeier, F; Wu, X; Xella, S; Zhao, L; Zobernig, H; de Seixas, J M; dos Anjos, A; Asman, B; Özcan, E

2009-01-01

The ATLAS experiment is preparing for data taking at 14 TeV collision energy. A rich discovery physics program is being prepared in addition to the detailed study of Standard Model processes which will be produced in abundance. The ATLAS multi-level trigger system is designed to accept one event in 2 105 to enable the selection of rare and unusual physics events. The ATLAS calorimeter system is a precise instrument, which includes liquid Argon electro-magnetic and hadronic components as well as a scintillator-tile hadronic calorimeter. All these components are used in the various levels of the trigger system. A wide physics coverage is ensured by inclusively selecting events with candidate electrons, photons, taus, jets or those with large missing transverse energy. The commissioning of the trigger system is being performed with cosmic ray events and by replaying simulated Monte Carlo events through the trigger and data acquisition system.

Wired and Wireless Camera Triggering with Arduino

Science.gov (United States)

Kauhanen, H.; Rönnholm, P.

2017-10-01

Synchronous triggering is an important task that allows simultaneous data capture from multiple cameras. Accurate synchronization enables 3D measurements of moving objects or from a moving platform. In this paper, we describe one wired and four wireless variations of Arduino-based low-cost remote trigger systems designed to provide a synchronous trigger signal for industrial cameras. Our wireless systems utilize 315 MHz or 434 MHz frequencies with noise filtering capacitors. In order to validate the synchronization accuracy, we developed a prototype of a rotating trigger detection system (named RoTriDeS). This system is suitable to detect the triggering accuracy of global shutter cameras. As a result, the wired system indicated an 8.91 μs mean triggering time difference between two cameras. Corresponding mean values for the four wireless triggering systems varied between 7.92 and 9.42 μs. Presented values include both camera-based and trigger-based desynchronization. Arduino-based triggering systems appeared to be feasible, and they have the potential to be extended to more complicated triggering systems.

Triggering for charm, beauty, and truth

International Nuclear Information System (INIS)

Appel, J.A.

1982-02-01

As the search for more and more rare processes accelerates, the need for more and more effective event triggers also accelerates. In the earliest experiments, a simple coincidence often sufficed not only as the event trigger, but as the complete record of an event of interest. In today's experiments, not only has the fast trigger become more sophisticated, but one or more additional level of trigger processing precedes writing event data to magnetic tape for later analysis. Further search experiments will certainly require further expansion in the number of trigger levels required to filter those rare events of particular interest

AIDS radio triggers.

Science.gov (United States)

Elias, A M

1991-07-01

In April 1991, the Ethnic Communities' Council of NSW was granted funding under the Community AIDS Prevention and Education Program through the Department of Community Services and Health, to produce a series of 6x50 second AIDS radio triggers with a 10-second tag line for further information. The triggers are designed to disseminate culturally-sensitive information about HIV/AIDS in English, Italian, Greek, Spanish, Khmer, Turkish, Macedonian, Serbo-Croatian, Arabic, Cantonese, and Vietnamese, with the goal of increasing awareness and decreasing the degree of misinformation about HIV/AIDS among people of non-English-speaking backgrounds through radio and sound. The 6 triggers cover the denial that AIDS exists in the community, beliefs that words and feelings do not protect one from catching HIV, encouraging friends to be compassionate, compassion within the family, AIDS information for a young audience, and the provision of accurate and honest information on HIV/AIDS. The triggers are slated to be completed by the end of July 1991 and will be broadcast on all possible community, ethnic, and commercial radio networks across Australia. They will be available upon request in composite form with an information kit for use by health care professionals and community workers.

Application of Vector Triggering Random Decrement

DEFF Research Database (Denmark)

Asmussen, J. C.; Ibrahim, S. R.; Brincker, Rune

result is a Random Decrement function from each measurement. In traditional Random Decrement estimation the triggering condition is a scalar condition, which should only be fulfilled in a single measurement. In vector triggering Random Decrement the triggering condition is a vector condition......This paper deals with applications of the vector triggering Random Decrement technique. This technique is new and developed with the aim of minimizing estimation time and identification errors. The theory behind the technique is discussed in an accompanying paper. The results presented...... in this paper should be regarded as a further documentation of the technique. The key point in Random Decrement estimation is the formulation of a triggering condition. If the triggering condition is fulfilled a time segment from each measurement is picked out and averaged with previous time segments. The final...

Application of Vector Triggering Random Decrement

DEFF Research Database (Denmark)

Asmussen, J. C.; Ibrahim, S. R.; Brincker, Rune

1997-01-01

result is a Random Decrement function from each measurement. In traditional Random Decrement estimation the triggering condition is a scalar condition, which should only be fulfilled in a single measurement. In vector triggering Random Decrement the triggering condition is a vector condition......This paper deals with applications of the vector triggering Random Decrement technique. This technique is new and developed with the aim of minimizing estimation time and identification errors. The theory behind the technique is discussed in an accompanying paper. The results presented...... in this paper should be regarded as a further documentation of the technique. The key point in Random Decrement estimation is the formulation of a triggering condition. If the triggering condition is fulfilled a time segment from each measurement is picked out and averaged with previous time segments. The final...

Geometrical Acceptance Analysis for RPC PAC Trigger

CERN Document Server

Seo, Eunsung

2010-01-01

The CMS(Compact Muon Solenoid) is one of the four experiments that will analyze the collision results of the protons accelerated by the Large Hardron Collider(LHC) at CERN(Conseil Europen pour la Recherche Nuclaire). In case of the CMS experiment, the trigger system is divided into two stages : The Level-1 Trigger and High Level Trigger. The RPC(Resistive Plate Chamber) PAC(PAttern Comparator) Trigger system, which is a subject of this thesis, is a part of the Level-1 Muon Trigger System. Main task of the PAC Trigger is to identify muons, measures transverse momenta and select the best muon candidates for each proton bunch collision occurring every 25 ns. To calculate the value of PAC Trigger efficiency for triggerable muon, two terms of different efficiencies are needed ; acceptance efficiency and chamber efficiency. Main goal of the works described in this thesis is obtaining the acceptance efficiency of the PAC Trigger in each logical cone. Acceptance efficiency is a convolution of the chambers geometry an...

The ATLAS High Level Trigger Steering Framework and the Trigger Configuration System.

CERN Document Server

Perez Cavalcanti, Tiago; The ATLAS collaboration

2011-01-01

The ATLAS detector system installed in the Large Hadron Collider (LHC) at CERN is designed to study proton-proton and nucleus-nucleus collisions with a maximum centre of mass energy of 14 TeV at a bunch collision rate of 40MHz. In March 2010 the four LHC experiments saw the first proton-proton collisions at 7 TeV. Still within the year a collision rate of nearly 10 MHz is expected. At ATLAS, events of potential interest for ATLAS physics are selected by a three-level trigger system, with a final recording rate of about 200 Hz. The first level (L1) is implemented in custom hardware; the two levels of the high level trigger (HLT) are software triggers, running on large farms of standard computers and network devices. Within the ATLAS physics program more than 500 trigger signatures are defined. The HLT tests each signature on each L1-accepted event; the test outcome is recorded for later analysis. The HLT-Steering is responsible for this. It foremost ensures the independent test of each signature, guarantying u...

Triggering the GRANDE array

International Nuclear Information System (INIS)

Wilson, C.L.; Bratton, C.B.; Gurr, J.; Kropp, W.; Nelson, M.; Sobel, H.; Svoboda, R.; Yodh, G.; Burnett, T.; Chaloupka, V.; Wilkes, R.J.; Cherry, M.; Ellison, S.B.; Guzik, T.G.; Wefel, J.; Gaidos, J.; Loeffler, F.; Sembroski, G.; Goodman, J.; Haines, T.J.; Kielczewska, D.; Lane, C.; Steinberg, R.; Lieber, M.; Nagle, D.; Potter, M.; Tripp, R.

1990-01-01

A brief description of the Gamma Ray And Neutrino Detector Experiment (GRANDE) is presented. The detector elements and electronics are described. The trigger logic for the array is then examined. The triggers for the Gamma Ray and the Neutrino portions of the array are treated separately. (orig.)

Calorimetry triggering in ATLAS

International Nuclear Information System (INIS)

Igonkina, O; Achenbach, R; Andrei, V; Adragna, P; Aharrouche, M; Bauss, B; Bendel, M; Alexandre, G; Anduaga, X; Aracena, I; Backlund, S; Bogaerts, A; Baines, J; Barnett, B M; Bee, C; P, Behera; Bell, P; Benslama, K; Berry, T; Bohm, C

2009-01-01

The ATLAS experiment is preparing for data taking at 14 TeV collision energy. A rich discovery physics program is being prepared in addition to the detailed study of Standard Model processes which will be produced in abundance. The ATLAS multi-level trigger system is designed to accept one event in 2 | 10 5 to enable the selection of rare and unusual physics events. The ATLAS calorimeter system is a precise instrument, which includes liquid Argon electro-magnetic and hadronic components as well as a scintillator-tile hadronic calorimeter. All these components are used in the various levels of the trigger system. A wide physics coverage is ensured by inclusively selecting events with candidate electrons, photons, taus, jets or those with large missing transverse energy. The commissioning of the trigger system is being performed with cosmic ray events and by replaying simulated Monte Carlo events through the trigger and data acquisition system.

Calorimetry Triggering in ATLAS

International Nuclear Information System (INIS)

Igonkina, O.; Achenbach, R.; Adragna, P.; Aharrouche, M.; Alexandre, G.; Andrei, V.; Anduaga, X.; Aracena, I.; Backlund, S.; Baines, J.; Barnett, B.M.; Bauss, B.; Bee, C.; Behera, P.; Bell, P.; Bendel, M.; Benslama, K.; Berry, T.; Bogaerts, A.; Bohm, C.; Bold, T.; Booth, J.R.A.; Bosman, M.; Boyd, J.; Bracinik, J.; Brawn, I.P.; Brelier, B.; Brooks, W.; Brunet, S.; Bucci, F.; Casadei, D.; Casado, P.; Cerri, A.; Charlton, D.G.; Childers, J.T.; Collins, N.J.; Conde Muino, P.; Coura Torres, R.; Cranmer, K.; Curtis, C.J.; Czyczula, Z.; Dam, M.; Damazio, D.; Davis, A.O.; De Santo, A.; Degenhardt, J.

2011-01-01

The ATLAS experiment is preparing for data taking at 14 TeV collision energy. A rich discovery physics program is being prepared in addition to the detailed study of Standard Model processes which will be produced in abundance. The ATLAS multi-level trigger system is designed to accept one event in 2/10 5 to enable the selection of rare and unusual physics events. The ATLAS calorimeter system is a precise instrument, which includes liquid Argon electro-magnetic and hadronic components as well as a scintillator-tile hadronic calorimeter. All these components are used in the various levels of the trigger system. A wide physics coverage is ensured by inclusively selecting events with candidate electrons, photons, taus, jets or those with large missing transverse energy. The commissioning of the trigger system is being performed with cosmic ray events and by replaying simulated Monte Carlo events through the trigger and data acquisition system.

Calorimetry triggering in ATLAS

Energy Technology Data Exchange (ETDEWEB)

Igonkina, O [Nikhef National Institute for Subatomic Physics, Amsterdam (Netherlands); Achenbach, R; Andrei, V [Kirchhoff Institut fuer Physik, Universitaet Heidelberg, Heidelberg (Germany); Adragna, P [Physics Department, Queen Mary, University of London, London (United Kingdom); Aharrouche, M; Bauss, B; Bendel, M [Institut fr Physik, Universitt Mainz, Mainz (Germany); Alexandre, G [Section de Physique, Universite de Geneve, Geneva (Switzerland); Anduaga, X [Universidad Nacional de La Plata, La Plata (Argentina); Aracena, I [Stanford Linear Accelerator Center (SLAC), Stanford (United States); Backlund, S; Bogaerts, A [European Laboratory for Particle Physics (CERN), Geneva (Switzerland); Baines, J; Barnett, B M [STFC Rutherford Appleton Laboratory, Harwell Science and Innovation Campus, Didcot, Oxon (United Kingdom); Bee, C [Centre de Physique des Particules de Marseille, IN2P3-CNRS, Marseille (France); P, Behera [Iowa State University, Ames, Iowa (United States); Bell, P [School of Physics and Astronomy, University of Manchester, Manchester (United Kingdom); Benslama, K [University of Regina, Regina (Canada); Berry, T [Department of Physics, Royal Holloway and Bedford New College, Egham (United Kingdom); Bohm, C [Fysikum, Stockholm University, Stockholm (Sweden)

2009-04-01

The ATLAS experiment is preparing for data taking at 14 TeV collision energy. A rich discovery physics program is being prepared in addition to the detailed study of Standard Model processes which will be produced in abundance. The ATLAS multi-level trigger system is designed to accept one event in 2 | 10{sup 5} to enable the selection of rare and unusual physics events. The ATLAS calorimeter system is a precise instrument, which includes liquid Argon electro-magnetic and hadronic components as well as a scintillator-tile hadronic calorimeter. All these components are used in the various levels of the trigger system. A wide physics coverage is ensured by inclusively selecting events with candidate electrons, photons, taus, jets or those with large missing transverse energy. The commissioning of the trigger system is being performed with cosmic ray events and by replaying simulated Monte Carlo events through the trigger and data acquisition system.

The Run-2 ATLAS Trigger System

International Nuclear Information System (INIS)

Martínez, A Ruiz

2016-01-01

The ATLAS trigger successfully collected collision data during the first run of the LHC between 2009-2013 at different centre-of-mass energies between 900 GeV and 8TeV. The trigger system consists of a hardware Level-1 and a software-based high level trigger (HLT) that reduces the event rate from the design bunch-crossing rate of 40 MHz to an average recording rate of a few hundred Hz. In Run-2, the LHC will operate at centre-of-mass energies of 13 and 14 TeV and higher luminosity, resulting in up to five times higher rates of processes of interest. A brief review of the ATLAS trigger system upgrades that were implemented between Run-1 and Run-2, allowing to cope with the increased trigger rates while maintaining or even improving the efficiency to select physics processes of interest, will be given. This includes changes to the Level-1 calorimeter and muon trigger systems, the introduction of a new Level-1 topological trigger module and the merging of the previously two-level HLT system into a single event processing farm. A few examples will be shown, such as the impressive performance improvements in the HLT trigger algorithms used to identify leptons, hadrons and global event quantities like missing transverse energy. Finally, the status of the commissioning of the trigger system and its performance during the 2015 run will be presented. (paper)

The ATLAS Electron and Photon Trigger

CERN Document Server

Jones, Samuel David; The ATLAS collaboration

2017-01-01

Electron and photon triggers covering transverse energies from 5 GeV to several TeV are essential for signal selection in a wide variety of ATLAS physics analyses to study Standard Model processes and to search for new phenomena. Final states including leptons and photons had, for example, an important role in the discovery and measurement of the Higgs boson. Dedicated triggers are also used to collect data for calibration, efficiency and fake rate measurements. The ATLAS trigger system is divided in a hardware-based Level-1 trigger and a software-based high-level trigger, both of which were upgraded during the LHC shutdown in preparation for Run-2 operation. To cope with the increasing luminosity and more challenging pile-up conditions at a center-of-mass energy of 13 TeV, the trigger selections at each level are optimized to control the rates and keep efficiencies high. To achieve this goal multivariate analysis techniques are used. The ATLAS electron and photon triggers and their performance with Run 2 dat...

The ATLAS Electron and Photon Trigger

CERN Document Server

Jones, Samuel David; The ATLAS collaboration

2018-01-01

Electron and photon triggers covering transverse energies from 5 GeV to several TeV are essential for signal selection in a wide variety of ATLAS physics analyses to study Standard Model processes and to search for new phenomena. Final states including leptons and photons had, for example, an important role in the discovery and measurement of the Higgs boson. Dedicated triggers are also used to collect data for calibration, efficiency and fake rate measurements. The ATLAS trigger system is divided in a hardware-based Level-1 trigger and a software-based high-level trigger, both of which were upgraded during the LHC shutdown in preparation for Run-2 operation. To cope with the increasing luminosity and more challenging pile-up conditions at a center-of-mass energy of 13 TeV, the trigger selections at each level are optimized to control the rates and keep efficiencies high. To achieve this goal multivariate analysis techniques are used. The ATLAS electron and photon triggers and their performance with Run 2 dat...

The DOe Silicon Track Trigger

International Nuclear Information System (INIS)

Steinbrueck, Georg

2003-01-01

We describe a trigger preprocessor to be used by the DOe experiment for selecting events with tracks from the decay of long-lived particles. This Level 2 impact parameter trigger utilizes information from the Silicon Microstrip Tracker to reconstruct tracks with improved spatial and momentum resolutions compared to those obtained by the Level 1 tracking trigger. It is constructed of VME boards with much of the logic existing in programmable processors. A common motherboard provides the I/O infrastructure and three different daughter boards perform the tasks of identifying the roads from the tracking trigger data, finding the clusters in the roads in the silicon detector, and fitting tracks to the clusters. This approach provides flexibility for the design, testing and maintenance phases of the project. The track parameters are provided to the trigger framework in 25 μs. The effective impact parameter resolution for high-momentum tracks is 35 μm, dominated by the size of the Tevatron beam

Review Document: Full Software Trigger

CERN Document Server

Albrecht, J; Raven, G

2014-01-01

This document presents a trigger system for the upgraded LHCb detector, scheduled to begin operation in 2020. This document serves as input for the internal review towards the "DAQ, online and trigger TDR". The proposed trigger system is implemented entirely in software. In this document we show that track reconstruction of a similar quality to that available in the offline algorithms can be performed on the full inelastic $pp$-collision rate, without prior event selections implemented in custom hardware and without relying upon a partial event reconstruction. A track nding eciency of 98.8 % relative to oine can be achieved for tracks with $p_T >$ 500 MeV/$c$. The CPU time required for this reconstruction is about 40 % of the available budget. Proof-of-principle selections are presented which demonstrate that excellent performance is achievable using an inclusive beauty trigger, in addition to exclusive beauty and charm triggers. Finally, it is shown that exclusive beauty and charm selections that do not intr...

Effect of ageing on the myosin heavy chain composition of the human sternocleidomastoid muscle.

Science.gov (United States)

Meznaric, M; Eržen, I; Karen, P; Cvetko, E

2018-03-01

The myosin heavy chain (MyHC) composition of ageing limb muscles is transformed into a slower phenotype and expresses fast-twitch fibre type atrophy, presumably due to age-related motor unit remodelling and a change in the patterns of physical activity. It is not known if ageing affects the sternocleidomastoid muscle (SCM) in a similar way. The goal of the study was to analyze the MyHC composition and the size of muscle fibres in the ageing SCM by immunohistochemical methods and quantitative analysis and stereology using our own software for morphometry. We hypothesize that with ageing the MyHC composition of SCM transforms similarly as in ageing limb muscles, but the size of the muscle fibres is less effected as in limb muscles. The study was performed on the autopsy samples of the SCM in 12 older males. The results were compared with those published in our previous study on 15 young adult males. An ageing SCM transforms into a slower MyHC profile: the percentage of slow-twitch fibres is enhanced (numerical proportion 44.6 vs. 31.5%, Pfibres is diminished (numerical proportion 14.1 vs. 26.8%, Pfast-twitch fibres expressing MyHC-2a and 2x is smaller (50.6 vs. 63.5%, Pfibres expressing the fastest myosin isoform MyHC-2x is smaller too (19.0 vs. 34.5%, Pfibres expressing the fastest MyHC-2x provide circumstantial evidence for: (i) more fast-twitch than slow-twitch motor units being lost; and (ii) reinnervation by the surviving motor units. There appears to be no significant influence on muscle fibre size, which is congruent with relatively unchanged SCM activity during life. Copyright © 2017 Elsevier GmbH. All rights reserved.

The ATLAS hadronic tau trigger

International Nuclear Information System (INIS)

Shamim, Mansoora

2012-01-01

The extensive tau physics programs of the ATLAS experiment relies heavily on trigger to select hadronic decays of tau lepton. Such a trigger is implemented in ATLAS to efficiently collect signal events, while keeping the rate of multi-jet background within the allowed bandwidth. This contribution summarizes the performance of the ATLAS hadronic tau trigger system during 2011 data taking period and improvements implemented for the 2012 data collection.

Global search of triggered non-volcanic tremor

Science.gov (United States)

Chao, Tzu-Kai Kevin

Deep non-volcanic tremor is a newly discovered seismic phenomenon with low amplitude, long duration, and no clear P- and S-waves as compared with regular earthquake. Tremor has been observed at many major plate-boundary faults, providing new information about fault slip behaviors below the seismogenic zone. While tremor mostly occurs spontaneously (ambient tremor) or during episodic slow-slip events (SSEs), sometimes tremor can also be triggered during teleseismic waves of distance earthquakes, which is known as "triggered tremor". The primary focus of my Ph.D. work is to understand the physical mechanisms and necessary conditions of triggered tremor by systematic investigations in different tectonic regions. In the first chapter of my dissertation, I conduct a systematic survey of triggered tremor beneath the Central Range (CR) in Taiwan for 45 teleseismic earthquakes from 1998 to 2009 with Mw ≥ 7.5. Triggered tremors are visually identified as bursts of high-frequency (2-8 Hz), non-impulsive, and long-duration seismic energy that are coherent among many seismic stations and modulated by the teleseismic surface waves. A total of 9 teleseismic earthquakes has triggered clear tremor in Taiwan. The peak ground velocity (PGV) of teleseismic surface waves is the most important factor in determining tremor triggering potential, with an apparent threshold of ˜0.1 cm/s, or 7-8 kPa. However, such threshold is partially controlled by the background noise level, preventing triggered tremor with weaker amplitude from being observed. In addition, I find a positive correlation between the PGV and the triggered tremor amplitude, which is consistent with the prediction of the 'clock-advance' model. This suggests that triggered tremor can be considered as a sped-up occurrence of ambient tremor under fast loading from the passing surface waves. Finally, the incident angles of surface waves also play an important rule in controlling the tremor triggering potential. The next

Actin- and myosin-driven movement of viruses along filopodia precedes their entry into cells

Science.gov (United States)

Lehmann, Maik J.; Sherer, Nathan M.; Marks, Carolyn B.; Pypaert, Marc; Mothes, Walther

2005-01-01

Viruses have often been observed in association with the dense microvilli of polarized epithelia as well as the filopodia of nonpolarized cells, yet whether interactions with these structures contribute to infection has remained unknown. Here we show that virus binding to filopodia induces a rapid and highly ordered lateral movement, “surfing” toward the cell body before cell entry. Virus cell surfing along filopodia is mediated by the underlying actin cytoskeleton and depends on functional myosin II. Any disruption of virus cell surfing significantly reduces viral infection. Our results reveal another example of viruses hijacking host machineries for efficient infection by using the inherent ability of filopodia to transport ligands to the cell body. PMID:16027225

Actin- and myosin-driven movement of viruses along filopodia precedes their entry into cells.

Science.gov (United States)

Lehmann, Maik J; Sherer, Nathan M; Marks, Carolyn B; Pypaert, Marc; Mothes, Walther

2005-07-18

Viruses have often been observed in association with the dense microvilli of polarized epithelia as well as the filopodia of nonpolarized cells, yet whether interactions with these structures contribute to infection has remained unknown. Here we show that virus binding to filopodia induces a rapid and highly ordered lateral movement, "surfing" toward the cell body before cell entry. Virus cell surfing along filopodia is mediated by the underlying actin cytoskeleton and depends on functional myosin II. Any disruption of virus cell surfing significantly reduces viral infection. Our results reveal another example of viruses hijacking host machineries for efficient infection by using the inherent ability of filopodia to transport ligands to the cell body.

The Intriguing Dual Lattices of the Myosin Filaments in Vertebrate Striated Muscles: Evolution and Advantage

Directory of Open Access Journals (Sweden)

Pradeep K. Luther

2014-12-01

Full Text Available Myosin filaments in vertebrate striated muscle have a long roughly cylindrical backbone with cross-bridge projections on the surfaces of both halves except for a short central bare zone. In the middle of this central region the filaments are cross-linked by the M-band which holds them in a well-defined hexagonal lattice in the muscle A-band. During muscular contraction the M-band-defined rotation of the myosin filaments around their long axes influences the interactions that the cross-bridges can make with the neighbouring actin filaments. We can visualise this filament rotation by electron microscopy of thin cross-sections in the bare-region immediately adjacent to the M-band where the filament profiles are distinctly triangular. In the muscles of teleost fishes, the thick filament triangular profiles have a single orientation giving what we call the simple lattice. In other vertebrates, for example all the tetrapods, the thick filaments have one of two orientations where the triangles point in opposite directions (they are rotated by 60° or 180° according to set rules. Such a distribution cannot be developed in an ordered fashion across a large 2D lattice, but there are small domains of superlattice such that the next-nearest neighbouring thick filaments often have the same orientation. We believe that this difference in the lattice forms can lead to different contractile behaviours. Here we provide a historical review, and when appropriate cite recent work related to the emergence of the simple and superlattice forms by examining the muscles of several species ranging back to primitive vertebrates and we discuss the functional differences that the two lattice forms may have.

The CLEO-III Trigger: Decision and gating

International Nuclear Information System (INIS)

Bergfeld, T.J.; Gollin, G.D.; Haney, M.J.

1996-01-01

The CLEO-III Trigger provides a trigger decision every 42ns, with a latency of approximately 2.5μs. This paper describes the free-running, pipelined trigger decision logic, the throttling mechanism whereby the data acquisition system can modulate the trigger rate to maximize throughput without buffer overrun, and the subsequent signal distribution mechanism for delivering the trigger decision to the front-end electronics. This paper also describes the multilevel simulation methods employed to allow detailed low-level models of trigger components to be co-simulated with more abstract system models, thus allowing full system modeling without incurring prohibitive computational overheads

Triggers in UA2 and UA1

International Nuclear Information System (INIS)

Dorenbosch, J.

1985-01-01

The UA2 and UA1 trigger systems are described as they will be used after the upgrade of the CERN SPPS. The luminosity of the collider will increase to 3x10 30 . The bunch spacing is 4 microseconds, comparable to the time available for a second level trigger at the SSC. The first level triggers are very powerful and deliver trigger rates of about 100 Hz. The UA1 second level trigger operates on the final digitizings with a combination of special and general purpose processors. At the highest trigger levels a small farm of processors performs the final reduction. (orig.)

Concept of the CMS Trigger Supervisor

CERN Document Server

Magrans de Abril, Ildefons; Varela, Joao

2006-01-01

The Trigger Supervisor is an online software system designed for the CMS experiment at CERN. Its purpose is to provide a framework to set up, test, operate and monitor the trigger components on one hand and to manage their interplay and the information exchange with the run control part of the data acquisition system on the other. The Trigger Supervisor is conceived to provide a simple and homogeneous client interface to the online software infrastructure of the trigger subsystems. This document specifies the functional and non-functional requirements, design and operational details, and the components that will be delivered in order to facilitate a smooth integration of the trigger software in the context of CMS.

Effects of a myosin-II inhibitor (N-benzyl-p-toluene sulphonamide, BTS) on contractile characteristics of intact fast-twitch mammalian muscle fibres.

Science.gov (United States)

Pinniger, G J; Bruton, J D; Westerblad, H; Ranatunga, K W

2005-01-01

We have examined the effects of N-benzyl-p-toluene sulphonamide (BTS), a potent and specific inhibitor of fast muscle myosin-II, using small bundles of intact fibres or single fibres from rat foot muscle. BTS decreased tetanic tension reversibly in a concentration-dependent manner with half-maximal inhibition at approximately approximately 2 microM at 20 degrees C. The inhibition of tension with 10 microM BTS was marked at the three temperatures examined (10, 20 and 30 degrees C), but greatest at 10 degrees C. BTS decreased active muscle stiffness to a lesser extent than tetanic tension indicating that not all of the tension inhibition was due to a reduced number of attached cross-bridges. BTS-induced inhibition of active tension was not accompanied by any change in the free myoplasmic Ca2+ transients. The potency and specificity of BTS make it a very suitable myosin inhibitor for intact mammalian fast muscle and should be a useful tool for the examination of outstanding questions in muscle contraction.

Tools for Trigger Aware Analyses in ATLAS

CERN Document Server

Krasznahorkay, A; The ATLAS collaboration; Stelzer, J

2010-01-01

In order to search for rare processes, all four LHC experiments have to use advanced triggering methods for selecting and recording the events of interest. At the expected nominal LHC operating conditions only about 0.0005% of the collision events can be kept for physics analysis in ATLAS. Therefore the understanding and evaluation of the trigger performance is one of the most crucial parts of any physics analysis. ATLAS’s first level trigger is composed of custom-built hardware, while the second and third levels are implemented using regular PCs running reconstruction and selection algorithms. Because of this split, accessing the results of the trigger execution for the two stages is different. The complexity of the software trigger presents further difficulties in accessing the trigger data. To make the job of the physicists easier when evaluating the trigger performance, multiple general-use tools are provided by the ATLAS Trigger Analysis Tools group. The TrigDecisionTool, a general tool, is provided to...

The ZEUS calorimeter first level trigger

International Nuclear Information System (INIS)

Smith, W.H.; Ali, I.; Behrens, B.; Fordham, C.; Foudas, C.; Goussiou, A.; Jaworski, M.; Kinnel, T.; Lackey, J.; Robl, P.; Silverstein, S.; Dawson, J.W.; Krakauer, D.A.; Talaga, R.L.; Schlereth, J.L.

1994-10-01

The design of the ZEUS Calorimeter First Level Trigger (CFLT) is presented. The CFLT utilizes a pipelined architecture to provide trigger data for a global first leel trigger decision 5 μsec after each beam crossing, occurring every 96 nsec. The charges from 13K phototubes are summed into 1792 trigger tower pulseheights which are digitized by flash ADC's. The digital values are linearized, stored and used for sums and pattern tests. Summary data is forwarded to the Global First Level Trigger for each crossing 2 μsec after the crossing occurred. The CFLT determines the total energy, the total transverse energy, the missing energy, and the energy and number of isolated electrons and muons. It also provides information on the electromagnetic and hadronic energy deposited in various regions of the calorimeter. The CFLT has kept the experimental trigger rate below ∼200 Hz at the highest luminosity experienced at HERA. Performance studies suggest that the CFLT will keep the trigger rate below 1 kHZ against a rate of proton-beam gas interactions on the order of the 100 kHz expected at design luminosity. (orig.)

The Consequences of a Strong Depreciation of the U.S. Dollar on Agricultural Markets

OpenAIRE

Charlebois, Pierre; Hamann, Nathalie

2010-01-01

World prices for basic food commodities increased significantly in 2007-2008, triggering a worldwide food crisis. Among all the factors that contributed to the rise in agricultural prices in 2008, the depreciation of the U.S. dollar relative to other major currencies cannot be overlooked. The currencies of the major players in agricultural markets have shown strong appreciation from 2002 to 2008. The purpose of this study is to determine the effect of a strong depreciation of the U.S. dollar ...

Landslides triggered by the 1946 Ancash earthquake, Peru

Science.gov (United States)

Kampherm, T. S.; Evans, S. G.; Valderrama Murillo, P.

2009-04-01

The 1946 M7.3 Ancash Earthquake triggered a large number of landslides in an epicentral area that straddled the Continental Divide of South America in the Andes of Peru. A small number of landslides were described in reconnaissance reports by E. Silgado and Arnold Heim published shortly after the earthquake, but further details of the landslides triggered by the earthquake have not been reported since. Utilising field traverses, aerial photograph interpretation and GIS, our study mapped 45 landslides inferred to have been triggered by the event. 83% were rock avalanches involving Cretaceous limestones interbedded with shales. The five largest rock/debris avalanches occurred at Rio Llama (est. vol. 37 M m3), Suytucocha (est. vol., 13.5 Mm3), Quiches (est. vol. 10.5 Mm3 ), Pelagatos (est. vol. 8 Mm3), and Shundoy (est. vol. 8 Mm3). The Suytucocha, Quiches, and Pelagatos landslides were reported by Silgado and Heim. Rock slope failure was most common on slopes with a southwest aspect, an orientation corresponding to the regional dip direction of major planar structures in the Andean foreland belt (bedding planes and thrust faults). In valleys oriented transverse to the NW-SE structural grain of the epicentral area, south-westerly dipping bedding planes combined with orthogonal joint sets to form numerous wedge failures. Many initial rock slope failures were transformed into rock/debris avalanches by the entrainment of colluvium in their path. At Acobamba, a rock avalanche that transformed into a debris avalanche (est. vol. 4.3 Mm3) overwhelmed a village resulting in the deaths of 217 people. The cumulative volume-frequency plot shows a strong power law relation below a marked rollover, similar in form to that derived for landslides triggered by the 1994 Northridge Earthquake. The total volume of the 45 landslides is approximately 93 Mm3. The data point for the Ancash Earthquake plots near the regression line calculated by Keefer (1994), and modified by Malamud et al

New approaches to high-throughput structure characterization of SH3 complexes: the example of Myosin-3 and Myosin-5 SH3 domains from S. cerevisiae.

Science.gov (United States)

Musi, Valeria; Birdsall, Berry; Fernandez-Ballester, Gregorio; Guerrini, Remo; Salvatori, Severo; Serrano, Luis; Pastore, Annalisa

2006-04-01

SH3 domains are small protein modules that are involved in protein-protein interactions in several essential metabolic pathways. The availability of the complete genome and the limited number of clearly identifiable SH3 domains make the yeast Saccharomyces cerevisae an ideal proteomic-based model system to investigate the structural rules dictating the SH3-mediated protein interactions and to develop new tools to assist these studies. In the present work, we have determined the solution structure of the SH3 domain from Myo3 and modeled by homology that of the highly homologous Myo5, two myosins implicated in actin polymerization. We have then implemented an integrated approach that makes use of experimental and computational methods to characterize their binding properties. While accommodating their targets in the classical groove, the two domains have selectivity in both orientation and sequence specificity of the target peptides. From our study, we propose a consensus sequence that may provide a useful guideline to identify new natural partners and suggest a strategy of more general applicability that may be of use in other structural proteomic studies.

A trigger simulation framework for the ALICE experiment

International Nuclear Information System (INIS)

Antinori, F; Carminati, F; Gheata, A; Gheata, M

2011-01-01

A realistic simulation of the trigger system in a complex HEP experiment is essential for performing detailed trigger efficiency studies. The ALICE trigger simulation is evolving towards a framework capable of replaying the full trigger chain starting from the input to the individual trigger processors and ending with the decision mechanisms of the ALICE central trigger processor. This paper describes the new ALICE trigger simulation framework that is being tested and deployed. The framework handles details like trigger levels, signal delays and busy signals, implementing the trigger logic via customizable trigger device objects managed by a robust scheduling mechanism. A big advantage is the high flexibility of the framework, which is able to mix together components described with very different levels of detail. The framework is being gradually integrated within the ALICE simulation and reconstruction frameworks.

Trigger Menu in 2017

CERN Document Server

The ATLAS collaboration

2018-01-01

This document summarises the trigger menu deployed by the ATLAS experiment during 2017 data taking at proton-proton collision centre-of-mass energies of $\\sqrt{s}=13$ TeV and $\\sqrt{s}=5$ TeV at the LHC and describes the improvements with respect to the trigger system and menu used in 2016 data taking.

Intelligent trigger processor for the crystal box

International Nuclear Information System (INIS)

Sanders, G.H.; Butler, H.S.; Cooper, M.D.

1981-01-01

A large solid angle modular NaI(Tl) detector with 432 phototubes and 88 trigger scintillators is being used to search simultaneously for three lepton flavor changing decays of muon. A beam of up to 10 6 muons stopping per second with a 6% duty factor would yield up to 1000 triggers per second from random triple coincidences. A reduction of the trigger rate to 10 Hz is required from a hardwired primary trigger processor described in this paper. Further reduction to < 1 Hz is achieved by a microprocessor based secondary trigger processor. The primary trigger hardware imposes voter coincidence logic, stringent timing requirements, and a non-adjacency requirement in the trigger scintillators defined by hardwired circuits. Sophisticated geometric requirements are imposed by a PROM-based matrix logic, and energy and vector-momentum cuts are imposed by a hardwired processor using LSI flash ADC's and digital arithmetic loci. The secondary trigger employs four satellite microprocessors to do a sparse data scan, multiplex the data acquisition channels and apply additional event filtering

The ATLAS Level-1 Topological Trigger Performance

CERN Document Server

AUTHOR|(INSPIRE)INSPIRE-00371751; The ATLAS collaboration

2016-01-01

The LHC will collide protons in the ATLAS detector with increasing luminosity through 2016, placing stringent operational and physical requirements to the ATLAS trigger system in order to reduce the 40 MHz collision rate to a manageable event storage rate of 1 kHz, while not rejecting interesting physics events. The Level-1 trigger is the first rate-reducing step in the ATLAS trigger system with an output rate of 100 kHz and decision latency smaller than 2.5 μs. It consists of a calorimeter trigger, muon trigger and a central trigger processor. During the LHC shutdown after the Run 1 finished in 2013, the Level-1 trigger system was upgraded including hardware, firmware and software updates. In particular, new electronics modules were introduced in the real-time data processing path: the Topological Processor System (L1Topo). It consists of a single AdvancedCTA shelf equipped with two Level-1 topological processor blades. They receive real-time information from the Level-1 calorimeter and muon triggers, which...

The ATLAS trigger high-level trigger commissioning and operation during early data taking

CERN Document Server

Goncalo, R

2008-01-01

The ATLAS experiment is one of the two general-purpose experiments due to start operation soon at the Large Hadron Collider (LHC). The LHC will collide protons at a centre of mass energy of 14~TeV, with a bunch-crossing rate of 40~MHz. The ATLAS three-level trigger will reduce this input rate to match the foreseen offline storage capability of 100-200~Hz. After the Level 1 trigger, which is implemented in custom hardware, the High-Level Trigger (HLT) further reduces the rate from up to 100~kHz to the offline storage rate while retaining the most interesting physics. The HLT is implemented in software running in commercially available computer farms and consists of Level 2 and Event Filter. To reduce the network data traffic and the processing time to manageable levels, the HLT uses seeded, step-wise reconstruction, aiming at the earliest possible rejection. Data produced during LHC commissioning will be vital for calibrating and aligning sub-detectors, as well as for testing the ATLAS trigger and setting up t...

Investigation of index finger triggering force using a cadaver experiment: Effects of trigger grip span, contact location, and internal tendon force.

Science.gov (United States)

Chang, Joonho; Freivalds, Andris; Sharkey, Neil A; Kong, Yong-Ku; Mike Kim, H; Sung, Kiseok; Kim, Dae-Min; Jung, Kihyo

2017-11-01

A cadaver study was conducted to investigate the effects of triggering conditions (trigger grip span, contact location, and internal tendon force) on index finger triggering force and the force efficiency of involved tendons. Eight right human cadaveric hands were employed, and a motion simulator was built to secure and control the specimens. Index finger triggering forces were investigated as a function of different internal tendon forces (flexor digitorum profundus + flexor digitorum superficialis = 40, 70, and 100 N), trigger grip spans (40, 50, and 60 mm), and contact locations between the index finger and a trigger. Triggering forces significantly increased when internal tendon forces increased from 40 to 100 N. Also, trigger grip spans and contact locations had significant effects on triggering forces; maximum triggering forces were found at a 50 mm span and the most proximal contact location. The results revealed that only 10-30% of internal tendon forces were converted to their external triggering forces. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hierarchical trigger of the ALICE calorimeters

CERN Document Server

Muller, Hans; Novitzky, Norbert; Kral, Jiri; Rak, Jan; Schambach, Joachim; Wang, Ya-Ping; Wang, Dong; Zhou, Daicui

2010-01-01

The trigger of the ALICE electromagnetic calorimeters is implemented in 2 hierarchically connected layers of electronics. In the lower layer, level-0 algorithms search shower energy above threshold in locally confined Trigger Region Units (TRU). The top layer is implemented as a single, global trigger unit that receives the trigger data from all TRUs as input to the level-1 algorithm. This architecture was first developed for the PHOS high pT photon trigger before it was adopted by EMCal also for the jet trigger. TRU units digitize up to 112 analogue input signals from the Front End Electronics (FEE) and concentrate their digital stream in a single FPGA. A charge and time summing algorithm is combined with a peakfinder that suppresses spurious noise and is precise to single LHC bunches. With a peak-to-peak noise level of 150 MeV the linear dynamic range above threshold spans from MIP energies at 215 up to 50 GeV. Local level-0 decisions take less than 600 ns after LHC collisions, upon which all TRUs transfer ...

Level-1 Calorimeter Trigger starts firing

CERN Multimedia

Stephen Hillier

2007-01-01

L1Calo is one of the major components of ATLAS First Level trigger, along with the Muon Trigger and Central Trigger Processor. It forms all of the first-level calorimeter-based triggers, including electron, jet, tau and missing ET. The final system consists of over 250 custom designed 9U VME boards, most containing a dense array of FPGAs or ASICs. It is subdivided into a PreProcessor, which digitises the incoming trigger signals from the Liquid Argon and Tile calorimeters, and two separate processor systems, which perform the physics algorithms. All of these are highly flexible, allowing the possibility to adapt to beam conditions and luminosity. All parts of the system are read out through Read-Out Drivers, which provide monitoring data and Region of Interest (RoI) information for the Level-2 trigger. Production of the modules is now essentially complete, and enough modules exist to populate the full scale system in USA15. Installation is proceeding rapidly - approximately 90% of the final modules are insta...

[Track and trigger systems in Denmark - small country, great variations].

Science.gov (United States)

Lønnee, Mads; Bukan, Ramin Brandt; Waldau, Tina; Møller, Ann Merete; Bukan, Katrine Brandt

2018-05-07

A track and trigger (TAT) system and mobile emergency team (MET) can aid observation and care for admitted patients in the hospital ward. We have examined the literature and find evidence, though not strong, that the introduction of TAT and MET systems reduce hospital mortality. However, in Denmark, many different TAT systems are used, and several hospitals do not have MET. We believe, that a standardised national TAT system could encourage interregional research and the investigation of system compliance, cost-benefit and impact on intensive care unit admissions.

The CDF level-3 trigger

International Nuclear Information System (INIS)

Devlin, T.

1993-01-01

The Collider Detector at Fermilab (CDF) has been operating at the Tevatron and collecting data on proton-antiproton interactions with collision rates above 250,000 Hz. Three levels of filtering select events for data logging at a rate of about 4 Hz. The Level 3 trigger provides most of the capabilities of the offline production programs for event reconstruction and physics analysis. The type of physics triggers, application of cuts, and combinations of logical requirements for event selection are controlled at run time by a trigger table using a syntax fully integrated with the Level 1 and Level 2 hardware triggers. The level 3 software operates in 48 RISC/UNIX processors (over 1000 mips) served by four 20-MByte/sec data buses for input, output and control. The system architecture, debugging, code validation, error reporting, analysis capabilities and performance will be described

MR imaging findings of trigger thumb

Energy Technology Data Exchange (ETDEWEB)

Chang, Eric Y.; Chen, Karen C.; Chung, Christine B. [VA San Diego Healthcare System, Radiology Service, San Diego, CA (United States); University of California, San Diego Medical Center, Department of Radiology, San Diego, CA (United States)

2015-08-15

Trigger finger (or trigger thumb), also known as sclerosing tenosynovitis, is a common clinical diagnosis that rarely presents for imaging. Because of this selection bias, many radiologists may not be familiar with the process. Furthermore, patients who do present for imaging frequently have misleading examination indications. To our knowledge, magnetic resonance (MR) imaging findings of trigger thumb have not been previously reported in the literature. In this article, we review the entity of trigger thumb, the anatomy involved, and associated imaging findings, which include flexor pollicis longus tendinosis with a distinct nodule, A1 pulley thickening, and tenosynovitis. In addition, in some cases, an abnormal Av pulley is apparent. In the rare cases of trigger finger that present for MR imaging, accurate diagnosis by the radiologist can allow initiation of treatment and avoid further unnecessary workup. (orig.)

MR imaging findings of trigger thumb

International Nuclear Information System (INIS)

Chang, Eric Y.; Chen, Karen C.; Chung, Christine B.

2015-01-01

Trigger finger (or trigger thumb), also known as sclerosing tenosynovitis, is a common clinical diagnosis that rarely presents for imaging. Because of this selection bias, many radiologists may not be familiar with the process. Furthermore, patients who do present for imaging frequently have misleading examination indications. To our knowledge, magnetic resonance (MR) imaging findings of trigger thumb have not been previously reported in the literature. In this article, we review the entity of trigger thumb, the anatomy involved, and associated imaging findings, which include flexor pollicis longus tendinosis with a distinct nodule, A1 pulley thickening, and tenosynovitis. In addition, in some cases, an abnormal Av pulley is apparent. In the rare cases of trigger finger that present for MR imaging, accurate diagnosis by the radiologist can allow initiation of treatment and avoid further unnecessary workup. (orig.)

Trigger processing using reconfigurable logic in the CMS calorimeter trigger

Energy Technology Data Exchange (ETDEWEB)

Brooke, J J; Cussans, D G; Heath, G P; Maddox, A J; Newbold, D M; Rabbetts, P D

2001-04-01

We present the design of the Global Calorimeter Trigger processor for the CMS detector at LHC. This is a fully pipelined processor system which collects data from all the CMS calorimeters and produces summary information used in forming the Level-1 trigger decision for each event. The design in based on the use of state-of-the-art reconfigurable logic devices (FPGAs) and fast data links. We present the results of device testing using a low-latency pipelined sort algorithm, which demonstrate that an FPGA can be used to perform processing previously foreseen to require custom ASICs. Our design approach results in a powerful, flexible and compact processor system.

Trigger Finger

Science.gov (United States)

... in a bent position. People whose work or hobbies require repetitive gripping actions are at higher risk ... developing trigger finger include: Repeated gripping. Occupations and hobbies that involve repetitive hand use and prolonged gripping ...

Remodeling of repolarization and arrhythmia susceptibility in a myosin-binding protein C knockout mouse model.

Science.gov (United States)

Toib, Amir; Zhang, Chen; Borghetti, Giulia; Zhang, Xiaoxiao; Wallner, Markus; Yang, Yijun; Troupes, Constantine D; Kubo, Hajime; Sharp, Thomas E; Feldsott, Eric; Berretta, Remus M; Zalavadia, Neil; Trappanese, Danielle M; Harper, Shavonn; Gross, Polina; Chen, Xiongwen; Mohsin, Sadia; Houser, Steven R

2017-09-01

Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiac diseases and among the leading causes of sudden cardiac death (SCD) in the young. The cellular mechanisms leading to SCD in HCM are not well known. Prolongation of the action potential (AP) duration (APD) is a common feature predisposing hypertrophied hearts to SCD. Previous studies have explored the roles of inward Na + and Ca 2+ in the development of HCM, but the role of repolarizing K + currents has not been defined. The objective of this study was to characterize the arrhythmogenic phenotype and cellular electrophysiological properties of mice with HCM, induced by myosin-binding protein C (MyBPC) knockout (KO), and to test the hypothesis that remodeling of repolarizing K + currents causes APD prolongation in MyBPC KO myocytes. We demonstrated that MyBPC KO mice developed severe hypertrophy and cardiac dysfunction compared with wild-type (WT) control mice. Telemetric electrocardiographic recordings of awake mice revealed prolongation of the corrected QT interval in the KO compared with WT control mice, with overt ventricular arrhythmias. Whole cell current- and voltage-clamp experiments comparing KO with WT mice demonstrated ventricular myocyte hypertrophy, AP prolongation, and decreased repolarizing K + currents. Quantitative RT-PCR analysis revealed decreased mRNA levels of several key K + channel subunits. In conclusion, decrease in repolarizing K + currents in MyBPC KO ventricular myocytes contributes to AP and corrected QT interval prolongation and could account for the arrhythmia susceptibility. NEW & NOTEWORTHY Ventricular myocytes isolated from the myosin-binding protein C knockout hypertrophic cardiomyopathy mouse model demonstrate decreased repolarizing K + currents and action potential and QT interval prolongation, linking cellular repolarization abnormalities with arrhythmia susceptibility and the risk for sudden cardiac death in hypertrophic cardiomyopathy. Copyright © 2017

Protective Effects of Clenbuterol against Dexamethasone-Induced Masseter Muscle Atrophy and Myosin Heavy Chain Transition.

Directory of Open Access Journals (Sweden)

Daisuke Umeki

Full Text Available Glucocorticoid has a direct catabolic effect on skeletal muscle, leading to muscle atrophy, but no effective pharmacotherapy is available. We reported that clenbuterol (CB induced masseter muscle hypertrophy and slow-to-fast myosin heavy chain (MHC isoform transition through direct muscle β2-adrenergic receptor stimulation. Thus, we hypothesized that CB would antagonize glucocorticoid (dexamethasone; DEX-induced muscle atrophy and fast-to-slow MHC isoform transition.We examined the effect of CB on DEX-induced masseter muscle atrophy by measuring masseter muscle weight, fiber diameter, cross-sectional area, and myosin heavy chain (MHC composition. To elucidate the mechanisms involved, we used immunoblotting to study the effects of CB on muscle hypertrophic signaling (insulin growth factor 1 (IGF1 expression, Akt/mammalian target of rapamycin (mTOR pathway, and calcineurin pathway and atrophic signaling (Akt/Forkhead box-O (FOXO pathway and myostatin expression in masseter muscle of rats treated with DEX and/or CB.Masseter muscle weight in the DEX-treated group was significantly lower than that in the Control group, as expected, but co-treatment with CB suppressed the DEX-induced masseter muscle atrophy, concomitantly with inhibition of fast-to-slow MHC isoforms transition. Activation of the Akt/mTOR pathway in masseter muscle of the DEX-treated group was significantly inhibited compared to that of the Control group, and CB suppressed this inhibition. DEX also suppressed expression of IGF1 (positive regulator of muscle growth, and CB attenuated this inhibition. Myostatin protein expression was unchanged. CB had no effect on activation of the Akt/FOXO pathway. These results indicate that CB antagonizes DEX-induced muscle atrophy and fast-to-slow MHC isoform transition via modulation of Akt/mTOR activity and IGF1 expression. CB might be a useful pharmacological agent for treatment of glucocorticoid-induced muscle atrophy.

Triggers for a high sensitivity charm experiment

International Nuclear Information System (INIS)

Christian, D.C.

1994-07-01

Any future charm experiment clearly should implement an E T trigger and a μ trigger. In order to reach the 10 8 reconstructed charm level for hadronic final states, a high quality vertex trigger will almost certainly also be necessary. The best hope for the development of an offline quality vertex trigger lies in further development of the ideas of data-driven processing pioneered by the Nevis/U. Mass. group

Commissioning the ATLAS Level-1 Central Trigger System

CERN Document Server

Sherman, Daniel

2010-01-01

The ATLAS Level-1 central trigger is a critical part of ATLAS operation. It receives the 40 MHz bunch clock from the LHC and distributes it to all sub-detectors. It initiates their read-out by forming the Level-1 Accept decision, which is based on information from the calorimeter and muon trigger processors and a variety of additional trigger inputs from detectors in the forward region. It also provides trigger summary information to the data acquisition system and the Level-2 trigger system. In this paper, we present the completion of the installed central trigger system, its performance during cosmic-ray data taking and the experience gained with triggering on the first LHC beams.

D0 triggering and data acquisition

International Nuclear Information System (INIS)

Gibbard, B.

1992-10-01

The trigger for D0 is a multi-tier system. Within the 3.5 μsec bunch crossing interval, custom electronics select interesting event candidates based on electromagnetic and hadronic energy deposits in the calorimeter and on indications of tracks in the muon system. Subsequent hardware decisions use refined calculations of electron and muon characteristics. The highest level trigger occurs in one element of a farm of microprocessors, where fully developed algorithms for electrons, muons, jets, or missing E t are executed. This highest level trigger also provides the assembly of the event into its final data structure. Performance of this trigger and data acquisition system in collider operation is described

A review on the study of landslides triggered by rains

International Nuclear Information System (INIS)

Aristizabal E; Martinez H; Velez J I

2010-01-01

This article attempts to give a very detailed perspective to the challenge and advances associated to rainfall-triggered landslides, which are characteristic and very common in tropical environments, such as Colombia. Landslides are one of the most common hazards around the world. Economic losses caused by landslides are huge, and are often exaggerated due to urban sprawl. Recent findings in this topic around the world have been applied for determining critical thresholds by physical or statistical models, combined with rainfall forecasting and near real time monitoring as fundamental component of an early warning system. Landslides are caused by several phenomena, including geological, geomorphologic and anthropogenic dynamics; however, one variable - precipitation - has a uniquely strong capability to cause rapid, intense slope failure. A review of several studies of rainfall-triggered landslides is presented some of who have used statistical tools that define critical thresholds based on intensity and duration rainfall. Other authors have focused upon physical based models combining hydrological and geotechnical aspects of rainfall, water pore pressure and slope stability.

The STAR Level-3 trigger system

International Nuclear Information System (INIS)

Adler, C.; Berger, J.; Demello, M.; Dietel, T.; Flierl, D.; Landgraf, J.; Lange, J.S.; LeVine, M.J.; Ljubicic, A.; Nelson, J.; Roehrich, D.; Stock, R.; Struck, C.; Yepes, P.

2003-01-01

The STAR Level-3 trigger issues a trigger decision upon a complete online reconstruction of Au+Au collisions at relativistic heavy ion collider energies. Central interactions are processed up to a rate of 50 s -1 including a simple analysis of physics observables. The setup of the processor farm and the event reconstruction as well as experiences and the proposed trigger algorithms are described

A Novel in situ Trigger Combination Method

International Nuclear Information System (INIS)

Buzatu, Adrian; Warburton, Andreas; Krumnack, Nils; Yao, Wei-Ming

2012-01-01

Searches for rare physics processes using particle detectors in high-luminosity colliding hadronic beam environments require the use of multi-level trigger systems to reject colossal background rates in real time. In analyses like the search for the Higgs boson, there is a need to maximize the signal acceptance by combining multiple different trigger chains when forming the offline data sample. In such statistically limited searches, datasets are often amassed over periods of several years, during which the trigger characteristics evolve and their performance can vary significantly. Reliable production cross-section measurements and upper limits must take into account a detailed understanding of the effective trigger inefficiency for every selected candidate event. We present as an example the complex situation of three trigger chains, based on missing energy and jet energy, to be combined in the context of the search for the Higgs (H) boson produced in association with a W boson at the Collider Detector at Fermilab (CDF). We briefly review the existing techniques for combining triggers, namely the inclusion, division, and exclusion methods. We introduce and describe a novel fourth in situ method whereby, for each candidate event, only the trigger chain with the highest a priori probability of selecting the event is considered. The in situ combination method has advantages of scalability to large numbers of differing trigger chains and of insensitivity to correlations between triggers. We compare the inclusion and in situ methods for signal event yields in the CDF WH search.

Discrete element modeling of triggered slip in faults with granular gouge: application to dynamic earthquake triggering

International Nuclear Information System (INIS)

Ferdowsi, B.

2014-01-01

Recent seismological observations based on new, more sensitive instrumentation show that seismic waves radiated from large earthquakes can trigger other earthquakes globally. This phenomenon is called dynamic earthquake triggering and is well-documented for over 30 of the largest earthquakes worldwide. Granular materials are at the core of mature earthquake faults and play a key role in fault triggering by exhibiting a rich nonlinear response to external perturbations. The stick-slip dynamics in sheared granular layers is analogous to the seismic cycle for earthquake fault systems. In this research effort, we characterize the macroscopic scale statistics and the grain-scale mechanisms of triggered slip in sheared granular layers. We model the granular fault gouge using three dimensional discrete element method simulations. The modeled granular system is put into stick-slip dynamics by applying a conning pressure and a shear load. The dynamic triggering is simulated by perturbing the spontaneous stick-slip dynamics using an external vibration applied to the boundary of the layer. The influences of the triggering consist in a frictional weakening during the vibration interval, a clock advance of the next expected large slip event and long term effects in the form of suppression and recovery of the energy released from the granular layer. Our study suggests that above a critical amplitude, vibration causes a significant clock advance of large slip events. We link this clock advance to a major decline in the slipping contact ratio as well as a decrease in shear modulus and weakening of the granular gouge layer. We also observe that shear vibration is less effective in perturbing the stick-slip dynamics of the granular layer. Our study suggests that in order to have an effective triggering, the input vibration must also explore the granular layer at length scales about or less than the average grain size. The energy suppression and the subsequent recovery and increased

Upgrade of the CMS Global Muon Trigger

CERN Document Server

Jeitler, Manfred; Rabady, Dinyar; Sakulin, Hannes; Stahl, Achim

2015-01-01

The increase in center-of-mass energy and luminosity for Run-II of the Large Hadron Collider poses new challenges for the trigger systems of the experiments. To keep triggering with a similar performance as in Run-I, the CMS muon trigger is currently being upgraded. The new algorithms will provide higher resolution, especially for the muon transverse momentum and will make use of isolation criteria that combine calorimeter with muon information already in the level-1 trigger. The demands of the new algorithms can only be met by upgrading the level-1 trigger system to new powerful FPGAs with high bandwidth I/O. The processing boards will be based on the new μTCA standard. We report on the planned algorithms for the upgraded Global Muon Trigger (μGMT) which sorts and removes duplicates from boundaries of the muon trigger sub-systems. Furthermore, it determines how isolated the muon candidates are based on calorimetric energy deposits. The μGMT will be implemented using a processing board that features a larg...

Upgrade of the CMS Global Muon Trigger

CERN Document Server

Lingemann, Joschka; Sakulin, Hannes; Jeitler, Manfred; Stahl, Achim

2015-01-01

The increase in center-of-mass energy and luminosity for Run 2 of the Large Hadron Collider pose new challenges for the trigger systems of the experiments. To keep triggering with a similar performance as in Run 1, the CMS muon trigger is currently being upgraded. The new algorithms will provide higher resolution, especially for the muon transverse momentum and will make use of isolation criteria that combine calorimeter with muon information already in the level-1 trigger. The demands of the new algorithms can only be met by upgrading the level-1 trigger system to new powerful FPGAs with high bandwidth I/O. The processing boards will be based on the new microTCA standard. We report on the planned algorithms for the upgraded Global Muon Trigger (GMT) which combines information from the muon trigger sub-systems and assigns the isolation variable. The upgraded GMT will be implemented using a Master Processor 7 card, built by Imperial College, that features a large Xilinx Virtex 7 FPGA. Up to 72 optical links at...

Upgrade trigger: Biannual performance update

CERN Document Server

Aaij, Roel; Couturier, Ben; Esen, Sevda; De Cian, Michel; De Vries, Jacco Andreas; Dziurda, Agnieszka; Fitzpatrick, Conor; Fontana, Marianna; Grillo, Lucia; Hasse, Christoph; Jones, Christopher Rob; Le Gac, Renaud; Matev, Rosen; Neufeld, Niko; Nikodem, Thomas; Polci, Francesco; Del Buono, Luigi; Quagliani, Renato; Schwemmer, Rainer; Seyfert, Paul; Stahl, Sascha; Szumlak, Tomasz; Vesterinen, Mika Anton; Wanczyk, Joanna; Williams, Mark Richard James; Yin, Hang; Zacharjasz, Emilia Anna

2017-01-01

This document presents the performance of the LHCb Upgrade trigger reconstruction sequence, incorporating changes to the underlying reconstruction algorithms and detector description since the Trigger and Online Upgrade TDR. An updated extrapolation is presented using the most recent example of an Event Filter Farm node.

Triggered Release from Polymer Capsules

Energy Technology Data Exchange (ETDEWEB)

Esser-Kahn, Aaron P. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry; Odom, Susan A. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry; Sottos, Nancy R. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Materials Science and Engineering; White, Scott R. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Aerospace Engineering; Moore, Jeffrey S. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry

2011-07-06

Stimuli-responsive capsules are of interest in drug delivery, fragrance release, food preservation, and self-healing materials. Many methods are used to trigger the release of encapsulated contents. Here we highlight mechanisms for the controlled release of encapsulated cargo that utilize chemical reactions occurring in solid polymeric shell walls. Triggering mechanisms responsible for covalent bond cleavage that result in the release of capsule contents include chemical, biological, light, thermal, magnetic, and electrical stimuli. We present methods for encapsulation and release, triggering methods, and mechanisms and conclude with our opinions on interesting obstacles for chemically induced activation with relevance for controlled release.

Congenital heart disease linked to maternal autoimmunity against cardiac myosin.

Science.gov (United States)

Cole, Charles R; Yutzey, Katherine E; Brar, Anoop K; Goessling, Lisa S; Van Vickle-Chavez, Sarah J; Cunningham, Madeleine W; Eghtesady, Pirooz

2014-05-01

Structural congenital heart disease (CHD) has not previously been linked to autoimmunity. In our study, we developed an autoimmune model of structural CHD that resembles hypoplastic left heart syndrome (HLHS), a life-threatening CHD primarily affecting the left ventricle. Because cardiac myosin (CM) is a dominant autoantigen in autoimmune heart disease, we hypothesized that immunization with CM might lead to transplacental passage of maternal autoantibodies and a prenatal HLHS phenotype in exposed fetuses. Elevated anti-CM autoantibodies in maternal and fetal sera, as well as IgG reactivity in fetal myocardium, were correlated with structural CHD that included diminished left ventricular cavity dimensions in the affected progeny. Further, fetuses that developed a marked HLHS phenotype had elevated serum titers of anti-β-adrenergic receptor Abs, as well as increased protein kinase A activity, suggesting a potential mechanism for the observed pathological changes. Our maternal-fetal model presents a new concept linking autoimmunity against CM and cardiomyocyte proliferation with cardinal features of HLHS. To our knowledge, this report shows the first evidence in support of a novel immune-mediated mechanism for pathogenesis of structural CHD that may have implications in its future diagnosis and treatment.

The ATLAS Trigger System: Ready for Run-2

CERN Document Server

Maeda, Junpei; The ATLAS collaboration

2015-01-01

The ATLAS trigger has been successfully collecting collision data during the first run of the LHC between 2009-2013 at a centre-of-mass energy between 900 GeV and 8 TeV. The trigger system consists of a hardware Level-1 and a software based high-level trigger that reduces the event rate from the design bunch-crossing rate of 40 MHz to an average recording rate of a few hundred Hz. During the data-taking period of Run-2 the LHC will operate at a centre-of-mass energy of about 13 TeV resulting in roughly five times higher trigger rates. In these proceedings, we briefly review the ATLAS trigger system upgrades that were implemented during the shutdown, allowing us to cope with the increased trigger rates while maintaining or even improving our efficiency to select relevant physics processes. This includes changes to the Level-1 calorimeter and muon trigger system, the introduction of a new Level-1 topological trigger module and themerging of the previously two-level higher-level trigger system into a single even...

First level trigger of the DIRAC experiment

International Nuclear Information System (INIS)

Afanas'ev, L.G.; Karpukhin, V.V.; Kulikov, A.V.; Gallas, M.

2001-01-01

The logic of the first level trigger of the DIRAC experiment at CERN is described. A parallel running of different trigger modes with tagging of events and optional independent prescaling is realized. A CAMAC-based trigger system is completely computer controlled

Ala397Asp mutation of myosin VIIA gene segregating in a Spanish family with type-Ib Usher syndrome.

Science.gov (United States)

Espinós, C; Millán, J M; Sánchez, F; Beneyto, M; Nájera, C

1998-06-01

In the current study, 12 Spanish families affected by type-I Usher syndrome, that was previously linked to chromosome 11q, were screened for the presence of mutations in the N-terminal coding portion of the motor domain of the myosin VIIA gene by single-strand conformation polymorphism analysis of the first 14 exons. A mutation (Ala397Asp) segregating with the disease was identified, and several polymorphisms were also detected. It is presumed that the other USHIB mutations in these families could be located in the unscreened regions of the gene.

The ATLAS Level-1 Central Trigger Processor (CTP)

CERN Document Server

Spiwoks, Ralf; Ellis, Nick; Farthouat, P; Gällnö, P; Haller, J; Krasznahorkay, A; Maeno, T; Pauly, T; Pessoa-Lima, H; Resurreccion-Arcas, I; Schuler, G; De Seixas, J M; Torga-Teixeira, R; Wengler, T

2005-01-01

The ATLAS Level-1 Central Trigger Processor (CTP) combines information from calorimeter and muon trigger processors and makes the final Level-1 Accept (L1A) decision on the basis of lists of selection criteria (trigger menus). In addition to the event-selection decision, the CTP also provides trigger summary information to the Level-2 trigger and the data acquisition system. It further provides accumulated and bunch-by-bunch scaler data for monitoring of the trigger, detector and beam conditions. The CTP is presented and results are shown from tests with the calorimeter adn muon trigger processors connected to detectors in a particle beam, as well as from stand-alone full-system tests in the laboratory which were used to validate the CTP.

CMS Triggers for the LHC Startup

CERN Document Server

Nhan Nguyen, Chi

2009-01-01

The LHC will collide proton beams at a bunch-crossing rate of 40 MHz. At the design luminosity of $10^{34}$ cm$^{-2}$s$^{-1}$ each crossing results in an average of about 20 inelastic pp events. The CMS trigger system is designed to reduce the input rate to about 100 Hz. This task is carried out in two steps, namely the Level-1 (L1) and the High-Level trigger (HLT). The L1 trigger is built of customized fast electronics and is designed to reduce the rate to 100 kHz. The HLT is implemented in a filter farm running on hundreds of CPUs and is designed to reduce the rate by another factor of ~1000. It combines the traditional L2 and L3 trigger components in a novel way and allows the coherent tuning of the HLT algorithms to accommodate multiple physics channels. We will discuss the strategies for optimizing triggers covering the experiment`s early physics program.

Controllable molecular motors engineered from myosin and RNA

Science.gov (United States)

Omabegho, Tosan; Gurel, Pinar S.; Cheng, Clarence Y.; Kim, Laura Y.; Ruijgrok, Paul V.; Das, Rhiju; Alushin, Gregory M.; Bryant, Zev

2018-01-01

Engineering biomolecular motors can provide direct tests of structure-function relationships and customized components for controlling molecular transport in artificial systems1 or in living cells2. Previously, synthetic nucleic acid motors3-5 and modified natural protein motors6-10 have been developed in separate complementary strategies to achieve tunable and controllable motor function. Integrating protein and nucleic-acid components to form engineered nucleoprotein motors may enable additional sophisticated functionalities. However, this potential has only begun to be explored in pioneering work harnessing DNA scaffolds to dictate the spacing, number and composition of tethered protein motors11-15. Here, we describe myosin motors that incorporate RNA lever arms, forming hybrid assemblies in which conformational changes in the protein motor domain are amplified and redirected by nucleic acid structures. The RNA lever arm geometry determines the speed and direction of motor transport and can be dynamically controlled using programmed transitions in the lever arm structure7,9. We have characterized the hybrid motors using in vitro motility assays, single-molecule tracking, cryo-electron microscopy and structural probing16. Our designs include nucleoprotein motors that reversibly change direction in response to oligonucleotides that drive strand-displacement17 reactions. In multimeric assemblies, the controllable motors walk processively along actin filaments at speeds of 10-20 nm s-1. Finally, to illustrate the potential for multiplexed addressable control, we demonstrate sequence-specific responses of RNA variants to oligonucleotide signals.

Characterization of human cardiac myosin heavy chain genes

International Nuclear Information System (INIS)

Yamauchi-Takihara, K.; Sole, M.J.; Liew, J.; Ing, D.; Liew, C.C.

1989-01-01

The authors have isolated and analyzed the structure of the genes coding for the α and β forms of the human cardiac myosin heavy chain (MYHC). Detailed analysis of four overlapping MYHC genomic clones shows that the α-MYHC and β-MYHC genes constitute a total length of 51 kilobases and are tandemly linked. The β-MYHC-encoding gene, predominantly expressed in the normal human ventricle and also in slow-twitch skeletal muscle, is located 4.5 kilobases upstream of the α-MYHC-encoding gene, which is predominantly expressed in normal human atrium. The authors have determined the nucleotide sequences of the β form of the MYHC gene, which is 100% homologous to the cardiac MYHC cDNA clone (pHMC3). It is unlikely that the divergence of a few nucleotide sequences from the cardiac β-MYHC cDNA clone (pHMC3) reported in a MYHC cDNA clone (PSMHCZ) from skeletal muscle is due to a splicing mechanism. This finding suggests that the same β form of the cardiac MYHC gene is expressed in both ventricular and slow-twitch skeletal muscle. The promoter regions of both α- and β-MYHC genes, as well as the first four coding regions in the respective genes, have also been sequenced. The sequences in the 5'-flanking region of the α- and β-MYHC-encoding genes diverge extensively from one another, suggesting that expression of the α- and β-MYHC genes is independently regulated

The ATLAS Level-1 Calorimeter Trigger

International Nuclear Information System (INIS)

Achenbach, R; Andrei, V; Adragna, P; Apostologlou, P; Barnett, B M; Brawn, I P; Davis, A O; Edwards, J P; Asman, B; Bohm, C; Ay, C; Bauss, B; Bendel, M; Dahlhoff, A; Eckweiler, S; Booth, J R A; Thomas, P Bright; Charlton, D G; Collins, N J; Curtis, C J

2008-01-01

The ATLAS Level-1 Calorimeter Trigger uses reduced-granularity information from all the ATLAS calorimeters to search for high transverse-energy electrons, photons, τ leptons and jets, as well as high missing and total transverse energy. The calorimeter trigger electronics has a fixed latency of about 1 μs, using programmable custom-built digital electronics. This paper describes the Calorimeter Trigger hardware, as installed in the ATLAS electronics cavern

The ATLAS Level-1 Calorimeter Trigger

Energy Technology Data Exchange (ETDEWEB)

Achenbach, R; Andrei, V [Kirchhoff-Institut fuer Physik, University of Heidelberg, D-69120 Heidelberg (Germany); Adragna, P [Physics Department, Queen Mary, University of London, London E1 4NS (United Kingdom); Apostologlou, P; Barnett, B M; Brawn, I P; Davis, A O; Edwards, J P [STFC Rutherford Appleton Laboratory, Harwell Science and Innovation Campus, Didcot, Oxon OX11 0QX (United Kingdom); Asman, B; Bohm, C [Fysikum, Stockholm University, SE-106 91 Stockholm (Sweden); Ay, C; Bauss, B; Bendel, M; Dahlhoff, A; Eckweiler, S [Institut fuer Physik, University of Mainz, D-55099 Mainz (Germany); Booth, J R A; Thomas, P Bright; Charlton, D G; Collins, N J; Curtis, C J [School of Physics and Astronomy, University of Birmingham, Birmingham B15 2TT (United Kingdom)], E-mail: e.eisenhandler@qmul.ac.uk (and others)

2008-03-15

The ATLAS Level-1 Calorimeter Trigger uses reduced-granularity information from all the ATLAS calorimeters to search for high transverse-energy electrons, photons, {tau} leptons and jets, as well as high missing and total transverse energy. The calorimeter trigger electronics has a fixed latency of about 1 {mu}s, using programmable custom-built digital electronics. This paper describes the Calorimeter Trigger hardware, as installed in the ATLAS electronics cavern.

Software trigger for the TOPAZ detector at TRISTAN

International Nuclear Information System (INIS)

Tsukamoto, T.; Yamauchi, M.; Enomoto, R.

1990-01-01

A new software trigger system was developed and installed at the TOPAZ detector to the trigger system for the TRISTAN e + e - collider to take data efficiently in the scheduled high luminosity experiment. This software trigger requires two or more charged tracks originated at the interaction point by examining the timing of signals from the time projection chamber. To execute the vertex finding very quickly, four microprocessors are used in parallel. By this new trigger the rate of the track trigger was reduced down to 30-40% with very small inefficiency. The additional dead time by this trigger is negligible. (orig.)

The Trigger for Early Running

CERN Document Server

The ATLAS Collaboration

2009-01-01

The ATLAS trigger and data acquisition system is based on three levels of event selection designed to capture the physics of interest with high efficiency from an initial bunch crossing rate of 40 MHz. The selections in the three trigger levels must provide sufficient rejection to reduce the rate to 200 Hz, compatible with offline computing power and storage capacity. The LHC is expected to begin its operation with a peak luminosity of 10^31 with a relatively small number of bunches, but quickly ramp up to higher luminosities by increasing the number of bunches, and thus the overall interaction rate. Decisions must be taken every 25 ns during normal LHC operations at the design luminosity of 10^34, where the average bunch crossing will contain more than 20 interactions. Hence, trigger selections must be deployed that can adapt to the changing beam conditions while preserving the interesting physics and satisfying varying detector requirements. In this paper, we provide a menu of trigger selections that can be...

BTeV detached vertex trigger

International Nuclear Information System (INIS)

Gottschalk, E.E.

2001-01-01

BTeV is a collider experiment that has been approved to run in the Tevatron at Fermilab. The experiment will conduct precision studies of CP violation using a forward-geometry detector. The detector will be optimized for high-rate detection of beauty and charm particles produced in collisions between protons and anti-protons. BTeV will trigger on beauty and charm events by taking advantage of the main difference between these heavy quark events and more typical hadronic events - the presence of detached beauty and charm decay vertices. The first stage of the BTeV trigger will receive data from a pixel vertex detector at a rate of 100 gb s -1 , reconstruct tracks and vertices for every beam crossing, reject 99% of beam crossings that do not produce beauty or charm particles, and trigger on beauty events with high efficiency. An overview of the trigger design and its influence on the design of the pixel vertex detector is presented

Rate Predictions and Trigger/DAQ Resource Monitoring in ATLAS

CERN Document Server

Schaefer, D M; The ATLAS collaboration

2012-01-01

Since starting in 2010, the Large Hadron Collider (LHC) has pro- duced collisions at an ever increasing rate. The ATLAS experiment successfully records the collision data with high eciency and excel- lent data quality. Events are selected using a three-level trigger system, where each level makes a more re ned selection. The level-1 trigger (L1) consists of a custom-designed hardware trigger which seeds two higher software based trigger levels. Over 300 triggers compose a trig- ger menu which selects physics signatures such as electrons, muons, particle jets, etc. Each trigger consumes computing resources of the ATLAS trigger system and oine storage. The LHC instantaneous luminosity conditions, desired physics goals of the collaboration, and the limits of the trigger infrastructure determine the composition of the ATLAS trigger menu. We describe a trigger monitoring frame- work for computing the costs of individual trigger algorithms such as data request rates and CPU consumption. This framework has been used...

Nanoparticle-triggered in situ catalytic chemical reactions for tumour-specific therapy.

Science.gov (United States)

Lin, Han; Chen, Yu; Shi, Jianlin

2018-03-21

Tumour chemotherapy employs highly cytotoxic chemodrugs, which kill both cancer and normal cells by cellular apoptosis or necrosis non-selectively. Catalysing/triggering the specific chemical reactions only inside tumour tissues can generate abundant and special chemicals and products locally to initiate a series of unique biological and pathologic effects, which may enable tumour-specific theranostic effects to combat cancer without bringing about significant side effects on normal tissues. Nevertheless, chemical reaction-initiated selective tumour therapy strongly depends on the advances in chemistry, materials science, nanotechnology and biomedicine. This emerging cross-disciplinary research area is substantially different from conventional cancer-theranostic modalities in clinics. In response to the fast developments in cancer theranostics based on intratumoural catalytic chemical reactions, this tutorial review summarizes the very-recent research progress in the design and synthesis of representative nanoplatforms with intriguing nanostructures, compositions, physiochemical properties and biological behaviours for versatile catalytic chemical reaction-enabled cancer treatments, mainly by either endogenous tumour microenvironment (TME) triggering or exogenous physical irradiation. These unique intratumoural chemical reactions can be used in tumour-starving therapy, chemodynamic therapy, gas therapy, alleviation of tumour hypoxia, TME-responsive diagnostic imaging and stimuli-responsive drug release, and even externally triggered versatile therapeutics. In particular, the challenges and future developments of such a novel type of cancer-theranostic modality are discussed in detail to understand the future developments and prospects in this research area as far as possible. It is highly expected that this kind of unique tumour-specific therapeutics by triggering specific in situ catalytic chemical reactions inside tumours would provide a novel but efficient

Convergent and Divergent Signaling in PAMP-Triggered Immunity and Effector-Triggered Immunity.

Science.gov (United States)

Peng, Yujun; van Wersch, Rowan; Zhang, Yuelin

2018-04-01

Plants use diverse immune receptors to sense pathogen attacks. Recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors localized on the plasma membrane leads to PAMP-triggered immunity (PTI). Detection of pathogen effectors by intracellular or plasma membrane-localized immune receptors results in effector-triggered immunity (ETI). Despite the large variations in the magnitude and duration of immune responses triggered by different PAMPs or pathogen effectors during PTI and ETI, plasma membrane-localized immune receptors activate similar downstream molecular events such as mitogen-activated protein kinase activation, oxidative burst, ion influx, and increased biosynthesis of plant defense hormones, indicating that defense signals initiated at the plasma membrane converge at later points. On the other hand, activation of ETI by immune receptors localized to the nucleus appears to be more directly associated with transcriptional regulation of defense gene expression. Here, we review recent progress in signal transductions downstream of different groups of plant immune receptors, highlighting the converging and diverging molecular events.

Development of a level-1 trigger and timing system for the Double Chooz neutrino experiment

International Nuclear Information System (INIS)

Reinhold, Bernd

2009-01-01

The measurement of the mixing angle θ 13 is the goal of several running and planned experiments. The experiments are either accelerator based (super)beam experiments (e.g. MINOS, T2K, Nova) or reactor anti-neutrino disappearance experiments (e.g. Daya Bay, RENO or Double Chooz). In order to measure or constrain θ 13 with the Double Chooz experiment the overall systematic errors have to be controlled at the one-percent or sub-percent level. The limitation of the systematic errors is achieved through various means and techniques. E.g. the experiment consists of two identical detectors at different baselines, which allow to make a differential anti-neutrino flux measurement, where basically only relative normalisation errors remain. The requirements on the systematic errors put also strong constraints on the quality of all components and materials used for both detectors, most prominently on the stability and radiopurity of the scintillator, the photomultiplier tubes, the vessels containing the detector liquids and the shielding against ambient radioactivity. The readout electronics, trigger and data acquisition system have to operate reliably as an integrated and highly efficient whole over several years. The trigger is provided by the Level-1 Trigger and Timing System, which is the subject of this thesis. It has to provide a highly efficient trigger (at the 0.1% level) for neutrino-induced events as well as for several types of background events. Its decision is realized in hardware and based on energy depositions in the muon veto and the target region. The Level-1 Trigger and Timing System furthermore provides a common System Clock and an absolute timestamp for each event. The Level-1 Trigger and Timing System consists of two types of VME modules, several Trigger Boards and a Trigger Master Board, which have been custom-designed and developed in the electronics workshop of our institute for this experiment and purpose, starting in 2005. In this thesis all

Development of a level-1 trigger and timing system for the Double Chooz neutrino experiment

Energy Technology Data Exchange (ETDEWEB)

Reinhold, Bernd

2009-02-25

The measurement of the mixing angle {theta}{sub 13} is the goal of several running and planned experiments. The experiments are either accelerator based (super)beam experiments (e.g. MINOS, T2K, Nova) or reactor anti-neutrino disappearance experiments (e.g. Daya Bay, RENO or Double Chooz). In order to measure or constrain {theta}{sub 13} with the Double Chooz experiment the overall systematic errors have to be controlled at the one-percent or sub-percent level. The limitation of the systematic errors is achieved through various means and techniques. E.g. the experiment consists of two identical detectors at different baselines, which allow to make a differential anti-neutrino flux measurement, where basically only relative normalisation errors remain. The requirements on the systematic errors put also strong constraints on the quality of all components and materials used for both detectors, most prominently on the stability and radiopurity of the scintillator, the photomultiplier tubes, the vessels containing the detector liquids and the shielding against ambient radioactivity. The readout electronics, trigger and data acquisition system have to operate reliably as an integrated and highly efficient whole over several years. The trigger is provided by the Level-1 Trigger and Timing System, which is the subject of this thesis. It has to provide a highly efficient trigger (at the 0.1% level) for neutrino-induced events as well as for several types of background events. Its decision is realized in hardware and based on energy depositions in the muon veto and the target region. The Level-1 Trigger and Timing System furthermore provides a common System Clock and an absolute timestamp for each event. The Level-1 Trigger and Timing System consists of two types of VME modules, several Trigger Boards and a Trigger Master Board, which have been custom-designed and developed in the electronics workshop of our institute for this experiment and purpose, starting in 2005. In

The Trigger System of the CMS Experiment

OpenAIRE

Felcini, Marta

2008-01-01

We give an overview of the main features of the CMS trigger and data acquisition (DAQ) system. Then, we illustrate the strategies and trigger configurations (trigger tables) developed for the detector calibration and physics program of the CMS experiment, at start-up of LHC operations, as well as their possible evolution with increasing luminosity. Finally, we discuss the expected CPU time performance of the trigger algorithms and the CPU requirements for the event filter farm at start-up.

Smart trigger logic for focal plane arrays

Science.gov (United States)

Levy, James E; Campbell, David V; Holmes, Michael L; Lovejoy, Robert; Wojciechowski, Kenneth; Kay, Randolph R; Cavanaugh, William S; Gurrieri, Thomas M

2014-03-25

An electronic device includes a memory configured to receive data representing light intensity values from pixels in a focal plane array and a processor that analyzes the received data to determine which light values correspond to triggered pixels, where the triggered pixels are those pixels that meet a predefined set of criteria, and determines, for each triggered pixel, a set of neighbor pixels for which light intensity values are to be stored. The electronic device also includes a buffer that temporarily stores light intensity values for at least one previously processed row of pixels, so that when a triggered pixel is identified in a current row, light intensity values for the neighbor pixels in the previously processed row and for the triggered pixel are persistently stored, as well as a data transmitter that transmits the persistently stored light intensity values for the triggered and neighbor pixels to a data receiver.

UA1 upgrade first-level calorimeter trigger processor

International Nuclear Information System (INIS)

Bains, N.; Charlton, D.; Ellis, N.; Garvey, J.; Gregory, J.; Jimack, M.P.; Jovanovic, P.; Kenyon, I.R.; Baird, S.A.; Campbell, D.; Cawthraw, M.; Coughlan, J.; Flynn, P.; Galagedera, S.; Grayer, G.; Halsall, R.; Shah, T.P.; Stephens, R.; Eisenhandler, E.; Fensome, I.; Landon, M.

1989-01-01

A new first-level trigger processor has been built for the UA1 experiment on the Cern SppS Collider. The processor exploits the fine granularity of the new UA1 uranium-TMP calorimeter to improve the selectivity of the trigger. The new electron trigger has improved hadron jet rejection, achieved by requiring low energy deposition around the electromagnetic cluster. A missing transverse energy trigger and a total energy trigger have also been implemented. (orig.)

Analysis of positional isotope exchange in ATP by cleavage of the βP-OγP bond. Demonstration of negligible positional isotope exchange by myosin

International Nuclear Information System (INIS)

Dale, M.P.; Hackney, D.D.

1987-01-01

A method for analysis of positional isotope exchange (PIX) during ATP ↔ HOH oxygen exchange is presented that uses a two-step degradation of ATP resulting in cleavage of the βP-OγP bond. This cleavage yields P/sub i/ derived from the γ-phosphoryl of ATP that contains all four of the γ oxygens. Both PIX between the β, γ-bridge and β-nonbridge positions and washout of the γ-nonbridge oxygens can be simultaneously followed by using ATP labeled with 17 O at the β-nonbridge positions and 18 O at the β,γ-bridge and γ-nonbridge positions. Application of this method to ATP ↔ HOH exchange during single turnovers of myosin indicates that the bulk of the ATP undergoes rapid washout of γ-nonbridge oxygens in the virtual absence of PIX. At 25 0 C with subfragment 1 the scrambling rate is at the limit of detectability of approximately 0.001 s -1 , which is 50-fold slower than the steady-state rate. This corresponds to a probability of scrambling for the β-oxygens of bound ADP of 1 in 10,000 for each cycle of reversible hydrolysis of bound ATP. A fraction of the ATP, however, does not undergo rapid washout. With myosin and stoichiometric ATP at 0 0 C, this fraction correspond to 10% of the ATP remaining at 36 s, or 2% of the initial ATP, and an equivalent level of ATP is found that does not bind irreversibly to myosin in a cold chase experiment. A significant level of apparent PIX is observed with subfragment 1 in the fraction that resists washout, and this apparent PIX is shown to be due to contaminant adenylate kinase activity. This apparent PIX due to adenylate kinase provides a possible explanation for the PIX observed by Geeves et al. with subfragment 1

The ATLAS Trigger: Recent Experience and Future Plans

CERN Document Server

The ATLAS collaboration

2009-01-01

This paper will give an overview of the ATLAS trigger design and its innovative features. It will describe the valuable experience gained in running the trigger reconstruction and event selection in the fastchanging environment of the detector commissioning during 2008. It will also include a description of the trigger selection menu and its 2009 deployment plan from first collisions to the nominal luminosity. ATLAS is one of the two general-purpose detectors at the Large Hadron Collider (LHC). The trigger system needs to efficiently reject a large rate of background events and still select potentially interesting ones with high efficiency. After a first level trigger implemented in custom electronics, the trigger event selection is made by the High Level Trigger (HLT) system, implemented in software. To reduce the processing time to manageable levels, the HLT uses seeded, step-wise and fast selection algorithms, aiming at the earliest possible rejection of background events. The ATLAS trigger event selection...

Caractérisation des différents types de fibres musculaires dans plusieurs espèces : production et utilisation d'anticorps monoclonaux dirigés contre les chaînes lourdes de myosine rapide IIa et IIb

OpenAIRE

Société Biocytex; Picard, Brigitte; Lefaucheur, Louis; Fauconneau, Benoit; Rémignon, Hervé; Cherel, Yan; Barrey, Eric; Nédelec, J.

1998-01-01

Des anticorps monoclonaux dirigés contre les chaînes lourdes de myosine (MHC : myosin heavy chain) de différentes espèces d’animaux : bovin, porc, poisson, poulet, dinde, cheval ont été produits. Ils ont été testés par immunohistologie sur des coupes de muscle squelettique chez le bovin, le porc, le poisson, le poulet et la dinde et par ELISA chez le cheval. Les différents anticorps retenus dans ce projet permettent de nouvelles applications pour l’étude du muscle squelettique. En particulier...

Early imaging of experimental myocardial infarction by intracoronary administration of /sup 131/I-labelled anticardiac myosin (Fab')/sub 2/ fragments. [Dogs

Energy Technology Data Exchange (ETDEWEB)

Khaw, B.A.; Gold, H.K.; Leinbach, R.C.; Fallon, J.T.; Strauss, W.; Pohost, G.M.; Haber, E.

1978-12-01

The feasibility of early imaging of myocardial infarcts by intracoronary injection of /sup 131/I-labelled cardiac myosin-specific antibody (Fab')/sub 2/ was examined. The left anterior descending coronary artery was occluded for 5 hs by a balloon catheter introduced through the carotid artery in 12 dogs. The catheter was withdrawn and 1 mCi /sup 201/Tl was injected intravenously and 500 ..mu..Ci of /sup 131/I antibody were injected into the main left coronary artery. Six of these animals demonstrated evidence of myocardial infarction by ECG and subsequent triphenyl-tetrazolium chloride staining, while the others did not. In each of the infarcted animals, in vivo scintograms one-half h after injection of isotope showed uptake of /sup 131/I in the anteroapical region of the heart corresponding to the region of absent /sup 201/Tl uptake. This relationship was confirmed in the excized hearts and in heart slices. In slices, /sup 131/I uptake corresponded to regions that did not stain with triphenyltetrazolium chloride. In the six animals that did not show evidence for infarction after coronary occlusion, uptake of /sup 131/I was not demonstrated, either in vivo or in excized specimens. In four additional dogs subjected to the same procedure, /sup 125/I-labelled (Fab')/sub 2/ from nonimmune IgG was injected simultaneously into the left main coronary artery with /sup 131/I-labelled canine myosin-specific antibody (Fab')/sub 2/. The ratio of uptake between infarct center and normal tissue was 34.3 +- 1.5 (mean +- SEM) for the specific antibody fragment as contrasted to 6.6 +- 0.4 for the nonimmune IgG fragment, indicating that intracoronary injection does not favor nonspecific sequestration of protein in regions of infarction. Thus the intracoronary administration of myosin-specific antibody fragments leads to early and specific one-half h imaging of myocardial infarcts.

Real-time prediction of rain-triggered lahars: incorporating seasonality and catchment recovery

Science.gov (United States)

Jones, Robbie; Manville, Vern; Peakall, Jeff; Froude, Melanie J.; Odbert, Henry M.

2017-12-01

Rain-triggered lahars are a significant secondary hydrological and geomorphic hazard at volcanoes where unconsolidated pyroclastic material produced by explosive eruptions is exposed to intense rainfall, often occurring for years to decades after the initial eruptive activity. Previous studies have shown that secondary lahar initiation is a function of rainfall parameters, source material characteristics and time since eruptive activity. In this study, probabilistic rain-triggered lahar forecasting models are developed using the lahar occurrence and rainfall record of the Belham River valley at the Soufrière Hills volcano (SHV), Montserrat, collected between April 2010 and April 2012. In addition to the use of peak rainfall intensity (PRI) as a base forecasting parameter, considerations for the effects of rainfall seasonality and catchment evolution upon the initiation of rain-triggered lahars and the predictability of lahar generation are also incorporated into these models. Lahar probability increases with peak 1 h rainfall intensity throughout the 2-year dataset and is higher under given rainfall conditions in year 1 than year 2. The probability of lahars is also enhanced during the wet season, when large-scale synoptic weather systems (including tropical cyclones) are more common and antecedent rainfall and thus levels of deposit saturation are typically increased. The incorporation of antecedent conditions and catchment evolution into logistic-regression-based rain-triggered lahar probability estimation models is shown to enhance model performance and displays the potential for successful real-time prediction of lahars, even in areas featuring strongly seasonal climates and temporal catchment recovery.