Dynamic Strength of Titin's Z-Disk End

PubMed Central

Kollár, Veronika; Szatmári, Dávid; Grama, László; Kellermayer, Miklós S. Z.

2010-01-01

Titin is a giant filamentous protein traversing the half sarcomere of striated muscle with putative functions as diverse as providing structural template, generating elastic response, and sensing and relaying mechanical information. The Z-disk region of titin, which corresponds to the N-terminal end of the molecule, has been thought to be a hot spot for mechanosensing while also serving as anchorage for its sarcomeric attachment. Understanding the mechanics of titin's Z-disk region, particularly under the effect of binding proteins, is of great interest. Here we briefly review recent findings on the structure, molecular associations, and mechanics of titin's Z-disk region. In addition, we report experimental results on the dynamic strength of titin's Z1Z2 domains measured by nanomechanical manipulation of the chemical dimer of a recombinant protein fragment. PMID:20414364

Dynamic strength of titin's Z-disk end.

PubMed

Kollár, Veronika; Szatmári, Dávid; Grama, László; Kellermayer, Miklós S Z

2010-01-01

Titin is a giant filamentous protein traversing the half sarcomere of striated muscle with putative functions as diverse as providing structural template, generating elastic response, and sensing and relaying mechanical information. The Z-disk region of titin, which corresponds to the N-terminal end of the molecule, has been thought to be a hot spot for mechanosensing while also serving as anchorage for its sarcomeric attachment. Understanding the mechanics of titin's Z-disk region, particularly under the effect of binding proteins, is of great interest. Here we briefly review recent findings on the structure, molecular associations, and mechanics of titin's Z-disk region. In addition, we report experimental results on the dynamic strength of titin's Z1Z2 domains measured by nanomechanical manipulation of the chemical dimer of a recombinant protein fragment.

Electron-microscopical localization of gelsolin in various crustacean muscles.

PubMed

Unger, Andreas; Hinssen, Horst

2010-08-01

Gelsolin was localized by immunoelectron microscopy in fast and slow cross-striated muscles of the lobster Homarus americanus. When ultrathin sections of the muscles were labelled with anti-gelsolin and a gold-conjugated second antibody, 90% of all gold particles in the myoplasm were detected on myofibrils, preferentially in the I-band and AI-region of the sarcomeres. Both the region of the H-zone (lacking thin filaments) and the Z-disc contained no or little gold label. Under physiological conditions, a close association of gelsolin with the thin filaments was observed for both muscle types. The preferential localization of particles in the I- and AI-region indicated that gelsolin was distributed randomly over the whole length of the thin filaments. Preincubation of muscle strips with Ringer solution containing 0.5 mM EGTA resulted in a significantly different distribution pattern; gold particles were now localized preferentially in the cell periphery close to the sarcolemma, with significantly decreased abundance in the centre of the cell. Compared with the muscle under physiological conditions, the number of gold particles over sarcomeric structures was significantly reduced. Thus, binding of gelsolin to the thin filaments is apparently reversible in vivo and depends on the presence of calcium ions. We assume a functional role for gelsolin in the actin turnover processes in invertebrate muscle systems.

MURC, a muscle-restricted coiled-coil protein, is involved in the regulation of skeletal myogenesis.

PubMed

Tagawa, Masashi; Ueyama, Tomomi; Ogata, Takehiro; Takehara, Naofumi; Nakajima, Norio; Isodono, Koji; Asada, Satoshi; Takahashi, Tomosaburo; Matsubara, Hiroaki; Oh, Hidemasa

2008-08-01

Skeletal myogenesis is a multistep process by which multinucleated mature muscle fibers are formed from undifferentiated, mononucleated myoblasts. However, the molecular mechanisms of skeletal myogenesis have not been fully elucidated. Here, we identified muscle-restricted coiled-coil (MURC) protein as a positive regulator of myogenesis. In skeletal muscle, MURC was localized to the cytoplasm with accumulation in the Z-disc of the sarcomere. In C2C12 myoblasts, MURC expression occurred coincidentally with myogenin expression and preceded sarcomeric myosin expression during differentiation into myotubes. RNA interference (RNAi)-mediated knockdown of MURC impaired differentiation in C2C12 myoblasts, which was accompanied by impaired myogenin expression and ERK activation. Overexpression of MURC in C2C12 myoblasts resulted in the promotion of differentiation with enhanced myogenin expression and ERK activation during differentiation. During injury-induced muscle regeneration, MURC expression increased, and a higher abundance of MURC was observed in immature myofibers compared with mature myofibers. In addition, ERK was activated in regenerating tissue, and ERK activation was detected in MURC-expressing immature myofibers. These findings suggest that MURC is involved in the skeletal myogenesis that results from modulation of myogenin expression and ERK activation. MURC may play pivotal roles in the molecular mechanisms of skeletal myogenic differentiation.

Clock is not a component of Z-bands.

PubMed

Wang, Jushuo; Dube, Dipak K; White, Jennifer; Fan, Yingli; Sanger, Jean M; Sanger, Joseph W

2012-12-01

The process of Z-band assembly begins with the formation of small Z-bodies composed of a complex of proteins rich in alpha-actinin. As additional proteins are added to nascent myofibrils, Z-bodies are transformed into continuous bands that form coherent discs of interacting proteins at the boundaries of sarcomeres. The steps controlling the transition of Z-bodies to Z-bands are not known. The report that a circadian protein, Clock, was localized in the Z-bands of neonatal rat cardiomyocytes raised the question whether this transcription factor could be involved in Z-band assembly. We found that the anti-Clock antibody used in the reported study also stained the Z-bands and Z-bodies of mouse and avian cardiac and skeletal muscle cells. YFP constructs of Clock that were assembled, however, did not localize to the Z-bands of muscle cells. Controls of Clock's activity showed that cotransfection of muscle cells with pYFP-Clock and pCeFP-BMAL1 led to the expected nuclear localization of YFP-Clock with its binding partner CeFP-BMAL1. Neither CeFP-BMAL1 nor antibodies directed against BMAL1 localized to Z-bands. A bimolecular fluorescence complementation assay (VC-BMAL1 and VN-Clock) confirmed the absence of Clock and BMAL1 from Z-bands, and their nuclear colocalization. A second anti-Clock antibody stained nuclei, but not Z-bands, of cells cotransfected with Clock and BMAL1 plasmids. Western blots of reactions of muscle extracts and purified alpha-actinins with the two anti-Clock antibodies showed that the original antibody cross-reacted with alpha-actinin and the second did not. These results cannot confirm Clock as an active component of Z-bands. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.

Ultra-structural time-course study in the C. elegans model for Duchenne muscular dystrophy highlights a crucial role for sarcomere-anchoring structures and sarcolemma integrity in the earliest steps of the muscle degeneration process.

PubMed

Brouilly, Nicolas; Lecroisey, Claire; Martin, Edwige; Pierson, Laura; Mariol, Marie-Christine; Qadota, Hiroshi; Labouesse, Michel; Streichenberger, Nathalie; Mounier, Nicole; Gieseler, Kathrin

2015-11-15

Duchenne muscular dystrophy (DMD) is a genetic disease characterized by progressive muscle degeneration due to mutations in the dystrophin gene. In spite of great advances in the design of curative treatments, most patients currently receive palliative therapies with steroid molecules such as prednisone or deflazacort thought to act through their immunosuppressive properties. These molecules only slightly slow down the progression of the disease and lead to severe side effects. Fundamental research is still needed to reveal the mechanisms involved in the disease that could be exploited as therapeutic targets. By studying a Caenorhabditis elegans model for DMD, we show here that dystrophin-dependent muscle degeneration is likely to be cell autonomous and affects the muscle cells the most involved in locomotion. We demonstrate that muscle degeneration is dependent on exercise and force production. Exhaustive studies by electron microscopy allowed establishing for the first time the chronology of subcellular events occurring during the entire process of muscle degeneration. This chronology highlighted the crucial role for dystrophin in stabilizing sarcomeric anchoring structures and the sarcolemma. Our results suggest that the disruption of sarcomeric anchoring structures and sarcolemma integrity, observed at the onset of the muscle degeneration process, triggers subcellular consequences that lead to muscle cell death. An ultra-structural analysis of muscle biopsies from DMD patients suggested that the chronology of subcellular events established in C. elegans models the pathogenesis in human. Finally, we found that the loss of sarcolemma integrity was greatly reduced after prednisone treatment suggesting a role for this molecule in plasma membrane stabilization. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Evaluation of Electrospun Nanofiber-Anchored Silicone for the Degenerative Intervertebral Disc

PubMed Central

Riahanizad, S.

2017-01-01

The nucleus pulposus (NP) substitution by polymeric gel is one of the promising techniques for the repair of the degenerative intervertebral disc (IVD). Silicone gel is one of the potential candidates for a NP replacement material. Electrospun fiber anchorage to silicone disc, referred as ENAS disc, may not only improve the biomechanical performances of the gel but it can also improve restoration capability of the gel, which is unknown. This study successfully produced a novel process to anchor any size and shape of NP gel with electrospun fiber mesh. Viscoelastic properties of silicone and ENAS disc were measured using standard experimental techniques and compared with the native tissue properties. Ex vivo mechanical tests were conducted on ENAS disc-implanted rabbit tails to the compare the mechanical stability between intact and ENAS implanted spines. This study found that viscoelastic properties of ENAS disc are higher than silicone disc and comparable to the viscoelastic properties of human NP. The ex vivo studies found that the ENAS disc restore the mechanical functionality of rabbit tail spine, after discectomy of native NP and replacing the NP by ENAS disc. Therefore, the PCL ENF mesh anchoring technique to a NP implant can have clinical potential. PMID:29181144

The application of zero-profile anchored spacer in anterior cervical discectomy and fusion.

PubMed

Wang, Zhiwen; Jiang, Weimin; Li, Xuefeng; Wang, Heng; Shi, Jinhui; Chen, Jie; Meng, Bin; Yang, Huilin

2015-01-01

We aimed to analyze the clinical efficacy of the zero-profile anchored spacers in the treatment of one-level or two-level cervical degenerative disc disease. From April 2011 to April 2013, a total of 63 consecutive patients with cervical degenerative disc disease who underwent one- or two-level ACDF using either the zero-profile anchored spacer or the stand-alone cages and a titanium plate fixation were reviewed for the radiological and clinical outcomes and complications. The zero-profile anchored spacers were used in 30 patients (anchored group) and stand-alone cages with an anterior cervical plate were implanted in 33 cases (non-anchored group). Operative time, intraoperative blood loss, clinical and radiological results were compared between the anchored group and the non-anchored group. All patients were followed up for at least 12 months. There were not bolt loosening or rupture of anchoring clips, screws or titanium plates observed in two groups during follow-up period. There were no significant difference in neck disability index scores, Japanese Orthopedic Association scores, fusion rate, and cervical lordosis during follow-up between two groups (P > 0.05), but significant difference in the operation time, blood loss and the presence of dysphagia were found (P < 0.05). There were no adjacent disc degeneration and instability observed in two groups. The zero-profile anchored spacer achieved similar clinical outcomes compared to ACDF with anterior plating for the treatment of the cervical degenerative disc disease. However, zero-profile anchored spacer was associated with a lower risk of postoperative dysphagia, shorter operation time, less blood loss, and relatively greater simplicity than the stand-alone cage with a titanium plate.

Overview of the Muscle Cytoskeleton

PubMed Central

Henderson, Christine A.; Gomez, Christopher G.; Novak, Stefanie M.; Mi-Mi, Lei; Gregorio, Carol C.

2018-01-01

Cardiac and skeletal striated muscles are intricately designed machines responsible for muscle contraction. Coordination of the basic contractile unit, the sarcomere, and the complex cytoskeletal networks are critical for contractile activity. The sarcomere is comprised of precisely organized individual filament systems that include thin (actin), thick (myosin), titin, and nebulin. Connecting the sarcomere to other organelles (e.g., mitochondria and nucleus) and serving as the scaffold to maintain cellular integrity are the intermediate filaments. The costamere, on the other hand, tethers the sarcomere to the cell membrane. Unique structures like the intercalated disc in cardiac muscle and the myotendinous junction in skeletal muscle help synchronize and transmit force. Intense investigation has been done on many of the proteins that make up these cytoskeletal assemblies. Yet the details of their function and how they interconnect have just started to be elucidated. A vast number of human myopathies are contributed to mutations in muscle proteins; thus understanding their basic function provides a mechanistic understanding of muscle disorders. In this review, we highlight the components of striated muscle with respect to their interactions, signaling pathways, functions, and connections to disease. PMID:28640448

Transversal Stiffness and Young's Modulus of Single Fibers from Rat Soleus Muscle Probed by Atomic Force Microscopy

PubMed Central

Ogneva, Irina V.; Lebedev, Dmitry V.; Shenkman, Boris S.

2010-01-01

Abstract The structural integrity of striated muscle is determined by extra-sarcomere cytoskeleton that includes structures that connect the Z-disks and M-bands of a sarcomere to sarcomeres of neighbor myofibrils or to sarcolemma. Mechanical properties of these structures are not well characterized. The surface structure and transversal stiffness of single fibers from soleus muscle of the rat were studied with atomic force microscopy in liquid. We identified surface regions that correspond to projections of the Z-disks, M-bands, and structures between them. Transversal stiffness of the fibers was measured in each of these three regions. The stiffness was higher in the Z-disk regions, minimal between the Z-disks and the M-bands, and intermediate in the M-band regions. The stiffness increased twofold when relaxed fibers were maximally activated with calcium and threefold when they were transferred to rigor (ATP-free) solution. Transversal stiffness of fibers heavily treated with Triton X-100 was about twice higher than that of the permeabilized ones, however, its regional difference and the dependence on physiological state of the fiber remained the same. The data may be useful for understanding mechanics of muscle fibers when it is subjected to both axial and transversal strain and stress. PMID:20141755

Role of the Z band in the mechanical properties of the heart.

PubMed

Goldstein, M A; Schroeter, J P; Michael, L H

1991-05-01

In striated muscle the mechanism of contraction involves the cooperative movement of contractile and elastic components. This review emphasizes a structural approach that describes the cellular and extracellular components with known anatomical, biochemical, and physical properties that make them candidates for these contractile and elastic components. Classical models of contractile and elastic elements and their underlying assumptions are presented. Mechanical properties of cardiac and skeletal muscle are compared and contrasted and then related to ultrastructure. Information from these approaches leads to the conclusion that the Z band is essential for muscle contraction. Our review of Z band structure shows the Z band at the interface where extracellular components meet the cell surface. The Z band is also the interface from cell surface to myofibril, from extra-myofibrillar to myofibril, and finally from sarcomere to sarcomere. Our studies of Z band in defined physiologic states show that this lattice is an integral part of the contractile elements and can function as an elastic component. The Z band is a complex dynamic lattice uniquely suited to play several roles in muscle contraction.

Muscle structure, sarcomere length and influences on meat quality: A review.

PubMed

Ertbjerg, Per; Puolanne, Eero

2017-10-01

The basic contractile unit of muscle, the sarcomere, will contract as the muscle goes into rigor post-mortem. Depending on the conditions, such as the rate of pH decline, the cooling rate and the mechanical restraints on the muscles, this longitudinal shortening will result in various post-mortem sarcomere lengths as well as lateral differences in the distances between the myosin and actin filaments. This shortening is underlying the phenomena described as rigor contraction, thaw rigor, cold shortening and heat shortening. The shortening in combination with the molecular architecture of the sarcomere as defined by the myosin filaments and their S-1 and S-2 units, the interaction with the actin filaments, and the boundaries formed by the Z-disks will subsequently influence basic meat quality traits including tenderness and water-holding capacity. Biochemical reactions from proteolysis and glycogen metabolism interrelate with the sarcomere length in a complex manner. The sarcomere length is also influencing the eating quality of cooked meat and the water-holding in meat products. Copyright © 2017 Elsevier Ltd. All rights reserved.

Large-scale models reveal the two-component mechanics of striated muscle.

PubMed

Jarosch, Robert

2008-12-01

This paper provides a comprehensive explanation of striated muscle mechanics and contraction on the basis of filament rotations. Helical proteins, particularly the coiled-coils of tropomyosin, myosin and alpha-actinin, shorten their H-bonds cooperatively and produce torque and filament rotations when the Coulombic net-charge repulsion of their highly charged side-chains is diminished by interaction with ions. The classical "two-component model" of active muscle differentiated a "contractile component" which stretches the "series elastic component" during force production. The contractile components are the helically shaped thin filaments of muscle that shorten the sarcomeres by clockwise drilling into the myosin cross-bridges with torque decrease (= force-deficit). Muscle stretch means drawing out the thin filament helices off the cross-bridges under passive counterclockwise rotation with torque increase (= stretch activation). Since each thin filament is anchored by four elastic alpha-actinin Z-filaments (provided with force-regulating sites for Ca(2+) binding), the thin filament rotations change the torsional twist of the four Z-filaments as the "series elastic components". Large scale models simulate the changes of structure and force in the Z-band by the different Z-filament twisting stages A, B, C, D, E, F and G. Stage D corresponds to the isometric state. The basic phenomena of muscle physiology, i. e. latency relaxation, Fenn-effect, the force-velocity relation, the length-tension relation, unexplained energy, shortening heat, the Huxley-Simmons phases, etc. are explained and interpreted with the help of the model experiments.

Large-scale Models Reveal the Two-component Mechanics of Striated Muscle

PubMed Central

Jarosch, Robert

2008-01-01

This paper provides a comprehensive explanation of striated muscle mechanics and contraction on the basis of filament rotations. Helical proteins, particularly the coiled-coils of tropomyosin, myosin and α-actinin, shorten their H-bonds cooperatively and produce torque and filament rotations when the Coulombic net-charge repulsion of their highly charged side-chains is diminished by interaction with ions. The classical “two-component model” of active muscle differentiated a “contractile component” which stretches the “series elastic component” during force production. The contractile components are the helically shaped thin filaments of muscle that shorten the sarcomeres by clockwise drilling into the myosin cross-bridges with torque decrease (= force-deficit). Muscle stretch means drawing out the thin filament helices off the cross-bridges under passive counterclockwise rotation with torque increase (= stretch activation). Since each thin filament is anchored by four elastic α-actinin Z-filaments (provided with force-regulating sites for Ca2+ binding), the thin filament rotations change the torsional twist of the four Z-filaments as the “series elastic components”. Large scale models simulate the changes of structure and force in the Z-band by the different Z-filament twisting stages A, B, C, D, E, F and G. Stage D corresponds to the isometric state. The basic phenomena of muscle physiology, i. e. latency relaxation, Fenn-effect, the force-velocity relation, the length-tension relation, unexplained energy, shortening heat, the Huxley-Simmons phases, etc. are explained and interpreted with the help of the model experiments. PMID:19330099

A-kinase anchoring proteins that regulate cardiac remodeling.

PubMed

Carnegie, Graeme K; Burmeister, Brian T

2011-11-01

In response to injury or stress, the adult heart undergoes maladaptive changes, collectively defined as pathological cardiac remodeling. Here, we focus on the role of A-kinase anchoring proteins (AKAPs) in 3 main areas associated with cardiac remodeling and the progression of heart failure: excitation-contraction coupling, sarcomeric regulation, and induction of pathological hypertrophy. AKAPs are a diverse family of scaffold proteins that form multiprotein complexes, integrating cAMP signaling with protein kinases, phosphatases, and other effector proteins. Many AKAPs have been characterized in the heart, where they play a critical role in modulating cardiac function.

A-Kinase Anchoring Proteins That Regulate Cardiac Remodeling

PubMed Central

Carnegie, Graeme K.; Burmeister, Brian T.

2012-01-01

In response to injury or stress, the adult heart undergoes maladaptive changes, collectively defined as pathological cardiac remodeling. Here, we focus on the role of A-kinase anchoring proteins (AKAPs) in 3 main areas associated with cardiac remodeling and the progression of heart failure: excitation–contraction coupling, sarcomeric regulation, and induction of pathological hypertrophy. AKAPs are a diverse family of scaffold proteins that form multi-protein complexes, integrating cAMP signaling with protein kinases, phosphatases, and other effector proteins. Many AKAPs have been characterized in the heart, where they play a critical role in modulating cardiac function. PMID:22075671

The conserved transmembrane proteoglycan Perdido/Kon-tiki is essential for myofibrillogenesis and sarcomeric structure in Drosophila

PubMed Central

Pérez-Moreno, Juan J.; Bischoff, Marcus; Martín-Bermudo, Maria D.; Estrada, Beatriz

2014-01-01

ABSTRACT Muscle differentiation requires the assembly of high-order structures called myofibrils, composed of sarcomeres. Even though the molecular organization of sarcomeres is well known, the mechanisms underlying myofibrillogenesis are poorly understood. It has been proposed that integrin-dependent adhesion nucleates myofibrils at the periphery of the muscle cell to sustain sarcomere assembly. Here, we report a role for the gene perdido (perd, also known as kon-tiki, a transmembrane chondroitin proteoglycan) in myofibrillogenesis. Expression of perd RNAi in muscles, prior to adult myogenesis, can induce misorientation and detachment of Drosophila adult abdominal muscles. In comparison to controls, perd-depleted muscles contain fewer myofibrils, which are localized at the cell periphery. These myofibrils are detached from each other and display a defective sarcomeric structure. Our results demonstrate that the extracellular matrix receptor Perd has a specific role in the assembly of myofibrils and in sarcomeric organization. We suggest that Perd acts downstream or in parallel to integrins to enable the connection of nascent myofibrils to the Z-bands. Our work identifies the Drosophila adult abdominal muscles as a model to investigate in vivo the mechanisms behind myofibrillogenesis. PMID:24794494

Modeling and experimental validation of sawing based lander anchoring and sampling methods for asteroid exploration

NASA Astrophysics Data System (ADS)

Zhang, Jun; Dong, Chengcheng; Zhang, Hui; Li, Song; Song, Aiguo

2018-05-01

This paper presents a novel lander anchoring system based on sawing method for asteroid exploration. The system is composed of three robotic arms, three cutting discs, and a control system. The discs mounted at the end of the arms are able to penetrate into the rock surface of asteroids. After the discs cut into the rock surface, the self-locking function of the arms provides forces to fix the lander on the surface. Modeling, trajectory planning, simulations, mechanism design, and prototype fabrication of the anchoring system are discussed, respectively. The performances of the system are tested on different kinds of rocks, at different sawing angles, locations, and speeds. Results show that the system can cut 15 mm deep into granite rock in 180 s at sawing angle of 60°, with the average power of 58.41 W, and the "weight on bit" (WOB) of 8.637 N. The 7.8 kg anchoring system is capable of providing omni-directional anchoring forces, at least 225 N normal and 157 N tangent to the surface of the rock. The system has the advantages of low-weight, low energy consumption and balance forces, high anchoring efficiency and reliability, and could enable the lander to move and sample or assist astronauts and robots in walking and sampling on asteroids.

A novel membrane anchor for FtsZ is linked to cell wall hydrolysis in Caulobacter crescentus.

PubMed

Meier, Elizabeth L; Razavi, Shiva; Inoue, Takanari; Goley, Erin D

2016-07-01

In most bacteria, the tubulin-like GTPase FtsZ forms an annulus at midcell (the Z-ring) which recruits the division machinery and regulates cell wall remodeling. Although both activities require membrane attachment of FtsZ, few membrane anchors have been characterized. FtsA is considered to be the primary membrane tether for FtsZ in bacteria, however in Caulobacter crescentus, FtsA arrives at midcell after stable Z-ring assembly and early FtsZ-directed cell wall synthesis. We hypothesized that additional proteins tether FtsZ to the membrane and demonstrate that in C. crescentus, FzlC is one such membrane anchor. FzlC associates with membranes directly in vivo and in vitro and recruits FtsZ to membranes in vitro. As for most known membrane anchors, the C-terminal peptide of FtsZ is required for its recruitment to membranes by FzlC in vitro and midcell recruitment of FzlC in cells. In vivo, overproduction of FzlC causes cytokinesis defects whereas deletion of fzlC causes synthetic defects with dipM, ftsE and amiC mutants, implicating FzlC in cell wall hydrolysis. Our characterization of FzlC as a novel membrane anchor for FtsZ expands our understanding of FtsZ regulators and establishes a role for membrane-anchored FtsZ in the regulation of cell wall hydrolysis. © 2016 John Wiley & Sons Ltd.

Tropomyosin 4 defines novel filaments in skeletal muscle associated with muscle remodelling/regeneration in normal and diseased muscle.

PubMed

Vlahovich, Nicole; Schevzov, Galina; Nair-Shaliker, Visalini; Ilkovski, Biljana; Artap, Stanley T; Joya, Josephine E; Kee, Anthony J; North, Kathryn N; Gunning, Peter W; Hardeman, Edna C

2008-01-01

The organisation of structural proteins in muscle into highly ordered sarcomeres occurs during development, regeneration and focal repair of skeletal muscle fibers. The involvement of cytoskeletal proteins in this process has been documented, with nonmuscle gamma-actin found to play a role in sarcomere assembly during muscle differentiation and also shown to be up-regulated in dystrophic muscles which undergo regeneration and repair [Lloyd et al.,2004; Hanft et al.,2006]. Here, we show that a cytoskeletal tropomyosin (Tm), Tm4, defines actin filaments in two novel compartments in muscle fibers: a Z-line associated cytoskeleton (Z-LAC), similar to a structure we have reported previously [Kee et al.,2004], and longitudinal filaments that are orientated parallel to the sarcomeric apparatus, present during myofiber growth and repair/regeneration. Tm4 is upregulated in paradigms of muscle repair including induced regeneration and focal repair and in muscle diseases with repair/regeneration features, muscular dystrophy and nemaline myopathy. Longitudinal Tm4-defined filaments also are present in diseased muscle. Transition of the Tm4-defined filaments from a longitudinal to a Z-LAC orientation is observed during the course of muscle regeneration. This Tm4-defined cytoskeleton is a marker of growth and repair/regeneration in response to injury, disease state and stress in skeletal muscle.

Myozenin: An α-actinin- and γ-filamin-binding protein of skeletal muscle Z lines

PubMed Central

Takada, Fumio; Woude, Douglas L. Vander; Tong, Hui-Qi; Thompson, Terri G.; Watkins, Simon C.; Kunkel, Louis M.; Beggs, Alan H.

2001-01-01

To better understand the structure and function of Z lines, we used sarcomeric isoforms of α-actinin and γ-filamin to screen a human skeletal muscle cDNA library for interacting proteins by using the yeast two-hybrid system. Here we describe myozenin (MYOZ), an α-actinin- and γ-filamin-binding Z line protein expressed predominantly in skeletal muscle. Myozenin is predicted to be a 32-kDa, globular protein with a central glycine-rich domain flanked by α-helical regions with no strong homologies to any known genes. The MYOZ gene has six exons and maps to human chromosome 10q22.1-q22.2. Northern blot analysis demonstrated that this transcript is expressed primarily in skeletal muscle with significantly lower levels of expression in several other tissues. Antimyozenin antisera stain skeletal muscle in a sarcomeric pattern indistinguishable from that seen by using antibodies for α-actinin, and immunogold electron microscopy confirms localization specifically to Z lines. Thus, myozenin is a skeletal muscle Z line protein that may be a good candidate gene for limb-girdle muscular dystrophy or other neuromuscular disorders. PMID:11171996

The vertical structure of gaseous galaxy discs in cold dark matter haloes

NASA Astrophysics Data System (ADS)

Benítez-Llambay, Alejandro; Navarro, Julio F.; Frenk, Carlos S.; Ludlow, Aaron D.

2018-01-01

We study the vertical structure of polytropic centrifugally supported gaseous discs embedded in cold dark matter (CDM) haloes. At fixed radius, R, the shape of the vertical density profile depends weakly on whether the disc is self-gravitating (SG) or non-self-gravitating (NSG). The disc 'characteristic' thickness, zH, set by the midplane sound speed and circular velocity, zNSG = (cs/Vc)R, in the NSG case, and by the sound speed and surface density, z_SG = c_s^2/GΣ, in SG discs, is smaller than zSG and zNSG. SG discs are typically Toomre unstable, NSG discs are stable. Exponential discs in CDM haloes with roughly flat circular velocity curves 'flare' outwards. Flares in mono abundance or coeval populations in galaxies like the Milky Way are thus not necessarily due to radial migration. For the polytropic equation of state of the Evolution and Assembly of GaLaxies and their Environments (EAGLE) simulations, discs that match observational constraints are NSG for Md < 3 × 109 M⊙ and SG at higher masses, if fully gaseous. We test these analytic results using a set of idealized smoothed particle hydrodynamic simulations and find excellent agreement. Our results clarify the role of the gravitational softening on the thickness of simulated discs, and on the onset of radial instabilities. EAGLE low-mass discs are NSG so the softening plays no role in their vertical structure. High-mass discs are expected to be SG and unstable, and may be artificially thickened and stabilized unless gravity is well resolved. Simulations with spatial resolution high enough to not compromise the vertical structure of a disc also resolve the onset of their instabilities, but the converse is not true.

Extensibility of the myofilaments in vertebrate skeletal muscle as revealed by stretching rigor muscle fibers

PubMed Central

1983-01-01

The extensibility of the myofilaments in vertebrate skeletal muscle was studied by stretching glycerinated rabbit psoas muscle fibers in rigor state and examining the resulting extension of sarcomere structures under an electron microscope. Although stretches applied to rigor fibers produced a successive yielding of the weakest sarcomeres, the length of the remaining intact sarcomeres in many myofibrils was fairly uniform, being definitely longer than the sarcomeres in the control, nonstretched part of rigor fibers. The stretch-induced increase in sarcomere length was found to be taken up by the extension of the H zone and the I band, whereas the amount of overlap between the thick and thin filaments did not change appreciably with stretches of 10-20%. The thick filament extension in the H zone was localized in the bare regions, whereas the thin filament extension in the I band appeared to take place uniformly along the filament length. No marked increase in the Z-line width was observed even with stretches of 20-30%. These results clearly demonstrate the extensibility of the thick and thin filaments. The possible contribution of the myofilament compliance to the series elastic component (SEC) in vertebrate skeletal muscle fibers is discussed on the basis of the electron microscopic data and the force-extension curve of the SEC in rigor fibers. PMID:6682885

A node organization in the actomyosin contractile ring generates tension and aids stability

PubMed Central

Thiyagarajan, Sathish; Wang, Shuyuan; O’Shaughnessy, Ben

2017-01-01

During cytokinesis, a contractile actomyosin ring constricts and divides the cell in two. How the ring marshals actomyosin forces to generate tension is not settled. Recently, a superresolution microscopy study of the fission yeast ring revealed that myosins and formins that nucleate actin filaments colocalize in plasma membrane-anchored complexes called nodes in the constricting ring. The nodes move bidirectionally around the ring. Here we construct and analyze a coarse-grained mathematical model of the fission yeast ring to explore essential consequences of the recently discovered ring ultrastructure. The model reproduces experimentally measured values of ring tension, explains why nodes move bidirectionally, and shows that tension is generated by myosin pulling on barbed-end-anchored actin filaments in a stochastic sliding-filament mechanism. This mechanism is not based on an ordered sarcomeric organization. We show that the ring is vulnerable to intrinsic contractile instabilities, and protection from these instabilities and organizational homeostasis require both component turnover and anchoring of components to the plasma membrane. PMID:28954859

Thick-Filament Strain and Interfilament Spacing in Passive Muscle: Effect of Titin-Based Passive Tension

PubMed Central

Irving, Thomas; Wu, Yiming; Bekyarova, Tanya; Farman, Gerrie P.; Fukuda, Norio; Granzier, Henk

2011-01-01

We studied the effect of titin-based passive tension on sarcomere structure by simultaneously measuring passive tension and low-angle x-ray diffraction patterns on passive fiber bundles from rabbit skinned psoas muscle. We used a stretch-hold-release protocol with measurement of x-ray diffraction patterns at various passive tension levels during the hold phase before and after passive stress relaxation. Measurements were performed in relaxing solution without and with dextran T-500 to compress the lattice toward physiological levels. The myofilament lattice spacing was measured in the A-band (d1,0) and Z-disk (dZ) regions of the sarcomere. The axial spacing of the thick-filament backbone was determined from the sixth myosin meridional reflection (M6) and the equilibrium positions of myosin heads from the fourth myosin layer line peak position and the I1,1/I1,0 intensity ratio. Total passive tension was measured during the x-ray experiments, and a differential extraction technique was used to determine the relations between collagen- and titin-based passive tension and sarcomere length. Within the employed range of sarcomere lengths (∼2.2–3.4 μm), titin accounted for >80% of passive tension. X-ray results indicate that titin compresses both the A-band and Z-disk lattice spacing with viscoelastic behavior when fibers are swollen after skinning, and elastic behavior when the lattice is reduced with dextran. Titin also increases the axial thick-filament spacing, M6, in an elastic manner in both the presence and absence of dextran. No changes were detected in either I1,1/I1,0 or the position of peaks on the fourth myosin layer line during passive stress relaxation. Passive tension and M6 measurements were converted to thick-filament compliance, yielding a value of ∼85 m/N, which is several-fold larger than the thick-filament compliance determined by others during the tetanic tension plateau of activated intact muscle. This difference can be explained by the fact that thick filaments are more compliant at low tension (passive muscle) than at high tension (tetanic tension). The implications of our findings are discussed. PMID:21402032

Drosophila small heat shock protein CryAB ensures structural integrity of developing muscles, and proper muscle and heart performance.

PubMed

Wójtowicz, Inga; Jabłońska, Jadwiga; Zmojdzian, Monika; Taghli-Lamallem, Ouarda; Renaud, Yoan; Junion, Guillaume; Daczewska, Malgorzata; Huelsmann, Sven; Jagla, Krzysztof; Jagla, Teresa

2015-03-01

Molecular chaperones, such as the small heat shock proteins (sHsps), maintain normal cellular function by controlling protein homeostasis in stress conditions. However, sHsps are not only activated in response to environmental insults, but also exert developmental and tissue-specific functions that are much less known. Here, we show that during normal development the Drosophila sHsp CryAB [L(2)efl] is specifically expressed in larval body wall muscles and accumulates at the level of Z-bands and around myonuclei. CryAB features a conserved actin-binding domain and, when attenuated, leads to clustering of myonuclei and an altered pattern of sarcomeric actin and the Z-band-associated actin crosslinker Cheerio (filamin). Our data suggest that CryAB and Cheerio form a complex essential for muscle integrity: CryAB colocalizes with Cheerio and, as revealed by mass spectrometry and co-immunoprecipitation experiments, binds to Cheerio, and the muscle-specific attenuation of cheerio leads to CryAB-like sarcomeric phenotypes. Furthermore, muscle-targeted expression of CryAB(R120G), which carries a mutation associated with desmin-related myopathy (DRM), results in an altered sarcomeric actin pattern, in affected myofibrillar integrity and in Z-band breaks, leading to reduced muscle performance and to marked cardiac arrhythmia. Taken together, we demonstrate that CryAB ensures myofibrillar integrity in Drosophila muscles during development and propose that it does so by interacting with the actin crosslinker Cheerio. The evidence that a DRM-causing mutation affects CryAB muscle function and leads to DRM-like phenotypes in the fly reveals a conserved stress-independent role of CryAB in maintaining muscle cell cytoarchitecture. © 2015. Published by The Company of Biologists Ltd.

Age-velocity dispersion relations and heating histories in disc galaxies

NASA Astrophysics Data System (ADS)

Aumer, Michael; Binney, James; Schönrich, Ralph

2016-10-01

We analyse the heating of stellar discs by non-axisymmetric structures and giant molecular clouds (GMCs) in N-body simulations of growing disc galaxies. The analysis resolves long-standing discrepancies between models and data by demonstrating the importance of distinguishing between measured age-velocity dispersion relations (AVRs) and the heating histories of the stars that make up the AVR. We fit both AVRs and heating histories with formulae ∝tβ and determine the exponents βR and βz derived from in-plane and vertical AVRs and tilde{β }_R and tilde{β }_z from heating histories. Values of βz are in almost all simulations larger than values of tilde{β }_z, whereas values of βR are similar to or mildly larger than values of tilde{β }_R. Moreover, values of βz (tilde{β }_z) are generally larger than values of βR (tilde{β }_R). The dominant cause of these relations is the decline over the life of the disc in importance of GMCs as heating agents relative to spiral structure and the bar. We examine how age errors and biases in solar neighbourhood surveys influence the measured AVR: they tend to decrease β values by smearing out ages and thus measured dispersions. We compare AVRs and velocity ellipsoid shapes σz/σR from simulations to solar neighbourhood data. We conclude that for the expected disc mass and dark halo structure, combined GMC and spiral/bar heating can explain the AVR of the Galactic thin disc. Strong departures of the disc mass or the dark halo structure from expectation spoil fits to the data.

Phosphoinositide 3-kinase (PI3K(p110alpha)) directly regulates key components of the Z-disc and cardiac structure.

PubMed

Waardenberg, Ashley J; Bernardo, Bianca C; Ng, Dominic C H; Shepherd, Peter R; Cemerlang, Nelly; Sbroggiò, Mauro; Wells, Christine A; Dalrymple, Brian P; Brancaccio, Mara; Lin, Ruby C Y; McMullen, Julie R

2011-09-02

Maintenance of cardiac structure and Z-disc signaling are key factors responsible for protecting the heart in a setting of stress, but how these processes are regulated is not well defined. We recently demonstrated that PI3K(p110α) protects the heart against myocardial infarction. The aim of this study was to determine whether PI3K(p110α) directly regulates components of the Z-disc and cardiac structure. To address this question, a unique three-dimensional virtual muscle model was applied to gene expression data from transgenic mice with increased or decreased PI3K(p110α) activity under basal conditions (sham) and in a setting of myocardial infarction to display the location of structural proteins. Key findings from this analysis were then validated experimentally. The three-dimensional virtual muscle model visually highlighted reciprocally regulated transcripts associated with PI3K activation that encoded key components of the Z-disc and costamere, including melusin. Studies were performed to assess whether PI3K and melusin interact in the heart. Here, we identify a novel melusin-PI3K interaction that generates lipid kinase activity. The direct impact of PI3K(p110α) on myocyte structure was assessed by treating neonatal rat ventricular myocytes with PI3K(p110α) inhibitors and examining the myofiber morphology of hearts from PI3K transgenic mice. Results demonstrate that PI3K is critical for myofiber maturation and Z-disc alignment. In summary, PI3K regulates the expression of genes essential for cardiac structure and Z-disc signaling, interacts with melusin, and is critical for Z-disc alignment.

Phosphoinositide 3-Kinase (PI3K(p110α)) Directly Regulates Key Components of the Z-disc and Cardiac Structure*

PubMed Central

Waardenberg, Ashley J.; Bernardo, Bianca C.; Ng, Dominic C. H.; Shepherd, Peter R.; Cemerlang, Nelly; Sbroggiò, Mauro; Wells, Christine A.; Dalrymple, Brian P.; Brancaccio, Mara; Lin, Ruby C. Y.; McMullen, Julie R.

2011-01-01

Maintenance of cardiac structure and Z-disc signaling are key factors responsible for protecting the heart in a setting of stress, but how these processes are regulated is not well defined. We recently demonstrated that PI3K(p110α) protects the heart against myocardial infarction. The aim of this study was to determine whether PI3K(p110α) directly regulates components of the Z-disc and cardiac structure. To address this question, a unique three-dimensional virtual muscle model was applied to gene expression data from transgenic mice with increased or decreased PI3K(p110α) activity under basal conditions (sham) and in a setting of myocardial infarction to display the location of structural proteins. Key findings from this analysis were then validated experimentally. The three-dimensional virtual muscle model visually highlighted reciprocally regulated transcripts associated with PI3K activation that encoded key components of the Z-disc and costamere, including melusin. Studies were performed to assess whether PI3K and melusin interact in the heart. Here, we identify a novel melusin-PI3K interaction that generates lipid kinase activity. The direct impact of PI3K(p110α) on myocyte structure was assessed by treating neonatal rat ventricular myocytes with PI3K(p110α) inhibitors and examining the myofiber morphology of hearts from PI3K transgenic mice. Results demonstrate that PI3K is critical for myofiber maturation and Z-disc alignment. In summary, PI3K regulates the expression of genes essential for cardiac structure and Z-disc signaling, interacts with melusin, and is critical for Z-disc alignment. PMID:21757757

Surgical treatment of adolescent internal condylar resorption (AICR) with articular disc repositioning and orthognathic surgery in the growing patient--a pilot study.

PubMed

Bodine, Trevor P; Wolford, Larry M; Araujo, Eustaquio; Oliver, Donald R; Buschang, Peter H

2016-01-01

The aim of this study was to better understand how surgical repositioning and stabilization of anteriorly displaced articular discs using the Mitek mini-anchor technique affects condylar growth in growing patients with adolescent internal condylar resorption (AICR). Twenty-two adolescent patients diagnosed with AICR and anterior temporomandibular disc displacement were compared to untreated control subjects without AICR matched for age, sex, and Angle classification. Pre-surgical (T1 and T2) and post-surgical (T3 and T4) mandibular tracings were superimposed on natural stable structures to evaluate the horizontal, vertical, and total changes in the position of condylion. The treated group showed an overall decrease in condylar height pre-surgically and statistically significant changes in condylar growth direction between the pre- and post-surgical observation periods. Pre-surgically, the treated group showed significantly more posterior condylar growth than the control group; they also showed inferior condylar growth, while the controls showed superior growth. Controls and patients in the treated group showed no significant differences in condylar growth post-surgically. Adolescent patients diagnosed with AICR and anterior disc displacement treated with mandibular ramus and maxillary osteotomies, along with Mitek anchors to reposition internally deranged discs, showed post-surgical normalization of condylar growth.

Increased Titin Compliance Reduced Length-Dependent Contraction and Slowed Cross-Bridge Kinetics in Skinned Myocardial Strips from Rbm (20ΔRRM) Mice.

PubMed

Pulcastro, Hannah C; Awinda, Peter O; Methawasin, Mei; Granzier, Henk; Dong, Wenji; Tanner, Bertrand C W

2016-01-01

Titin is a giant protein spanning from the Z-disk to the M-band of the cardiac sarcomere. In the I-band titin acts as a molecular spring, contributing to passive mechanical characteristics of the myocardium throughout a heartbeat. RNA Binding Motif Protein 20 (RBM20) is required for normal titin splicing, and its absence or altered function leads to greater expression of a very large, more compliant N2BA titin isoform in Rbm20 homozygous mice (Rbm20 (ΔRRM) ) compared to wild-type mice (WT) that almost exclusively express the stiffer N2B titin isoform. Prior studies using Rbm20 (ΔRRM) animals have shown that increased titin compliance compromises muscle ultrastructure and attenuates the Frank-Starling relationship. Although previous computational simulations of muscle contraction suggested that increasing compliance of the sarcomere slows the rate of tension development and prolongs cross-bridge attachment, none of the reported effects of Rbm20 (ΔRRM) on myocardial function have been attributed to changes in cross-bridge cycling kinetics. To test the relationship between increased sarcomere compliance and cross-bridge kinetics, we used stochastic length-perturbation analysis in Ca(2+)-activated, skinned papillary muscle strips from Rbm20 (ΔRRM) and WT mice. We found increasing titin compliance depressed maximal tension, decreased Ca(2+)-sensitivity of the tension-pCa relationship, and slowed myosin detachment rate in myocardium from Rbm20 (ΔRRM) vs. WT mice. As sarcomere length increased from 1.9 to 2.2 μm, length-dependent activation of contraction was eliminated in the Rbm20 (ΔRRM) myocardium, even though myosin MgADP release rate decreased ~20% to prolong strong cross-bridge binding at longer sarcomere length. These data suggest that increasing N2BA expression may alter cardiac performance in a length-dependent manner, showing greater deficits in tension production and slower cross-bridge kinetics at longer sarcomere length. This study also supports the idea that passive mechanical characteristics of the myocardium influence ensemble cross-bridge behavior and maintenance of tension generation throughout the sarcomere.

The Formation Of Bulges, Discs And Two Component Galaxies In The CANDELS Survey At z<3

NASA Astrophysics Data System (ADS)

Margaleff Bentabol, Berta; Conselice, Christopher; CANDELS Team

2016-09-01

The most massive galaxies in the local Universe can be classified as disk-dominated and spheroid-dominated (i.e. Hubble type). However, it is unclear how and when these dominant structures form and the possible connection between them. To address this issue we have investigated massive galaxies (logM>10) in the CANDELS fields at the epoch of 1

FINE STRUCTURAL LOCALIZATION OF ADENOSINETRIPHOSPHATASE ACTIVITY IN HEART MUSCLE MYOFIBRILS

PubMed Central

Tice, Lois W.; Barrnett, Russell J.

1962-01-01

Activity of myofibrillar adenosinetriphosphatase was demonstrated histochemically at a fine structural level in isolated, unfixed or hydroxyadipaldehyde-fixed cardiac myofibrils in the rat, using a lead precipitation technique and either Ca++ or Mg++ as activating ion. Activity in relaxed myofibrils was found in the A band, but not the H, I, or Z bands. Deposits of final product frequently exhibited an axial periodicity of near 365 A, and bore a close relationship to filaments within the A band. Several patterns of distribution occurred in contracted myofibrils. In myofibrils which had shortened to the point of disappearance of the I band, final product was distributed throughout the sarcomere, except for the unreactive Z band. A second type of distribution occurred in strongly contracted fibers in which there was intensification of activity in the center of the sarcomere. These findings are discussed in the light of the recent morphological evidence and it is suggested that the distribution of final product is consistent with localization of enzyme activity to the cross-bridges between the thick and thin filaments. PMID:13981351

In Vivo Function of the Chaperonin TRiC in α-Actin Folding during Sarcomere Assembly.

PubMed

Berger, Joachim; Berger, Silke; Li, Mei; Jacoby, Arie S; Arner, Anders; Bavi, Navid; Stewart, Alastair G; Currie, Peter D

2018-01-09

The TCP-1 ring complex (TRiC) is a multi-subunit group II chaperonin that assists nascent or misfolded proteins to attain their native conformation in an ATP-dependent manner. Functional studies in yeast have suggested that TRiC is an essential and generalized component of the protein-folding machinery of eukaryotic cells. However, TRiC's involvement in specific cellular processes within multicellular organisms is largely unknown because little validation of TRiC function exists in animals. Our in vivo analysis reveals a surprisingly specific role of TRiC in the biogenesis of skeletal muscle α-actin during sarcomere assembly in myofibers. TRiC acts at the sarcomere's Z-disk, where it is required for efficient assembly of actin thin filaments. Binding of ATP specifically by the TRiC subunit Cct5 is required for efficient actin folding in vivo. Furthermore, mutant α-actin isoforms that result in nemaline myopathy in patients obtain their pathogenic conformation via this function of TRiC. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

α-Actinin/titin interaction: A dynamic and mechanically stable cluster of bonds in the muscle Z-disk

PubMed Central

Grison, Marco; Merkel, Ulrich; Kostan, Julius; Djinović-Carugo, Kristina; Rief, Matthias

2017-01-01

Stable anchoring of titin within the muscle Z-disk is essential for preserving muscle integrity during passive stretching. One of the main candidates for anchoring titin in the Z-disk is the actin cross-linker α-actinin. The calmodulin-like domain of α-actinin binds to the Z-repeats of titin. However, the mechanical and kinetic properties of this important interaction are still unknown. Here, we use a dual-beam optical tweezers assay to study the mechanics of this interaction at the single-molecule level. A single interaction of α-actinin and titin turns out to be surprisingly weak if force is applied. Depending on the direction of force application, the unbinding forces can more than triple. Our results suggest a model where multiple α-actinin/Z-repeat interactions cooperate to ensure long-term stable titin anchoring while allowing the individual components to exchange dynamically. PMID:28096424

α-Actinin/titin interaction: A dynamic and mechanically stable cluster of bonds in the muscle Z-disk.

PubMed

Grison, Marco; Merkel, Ulrich; Kostan, Julius; Djinović-Carugo, Kristina; Rief, Matthias

2017-01-31

Stable anchoring of titin within the muscle Z-disk is essential for preserving muscle integrity during passive stretching. One of the main candidates for anchoring titin in the Z-disk is the actin cross-linker α-actinin. The calmodulin-like domain of α-actinin binds to the Z-repeats of titin. However, the mechanical and kinetic properties of this important interaction are still unknown. Here, we use a dual-beam optical tweezers assay to study the mechanics of this interaction at the single-molecule level. A single interaction of α-actinin and titin turns out to be surprisingly weak if force is applied. Depending on the direction of force application, the unbinding forces can more than triple. Our results suggest a model where multiple α-actinin/Z-repeat interactions cooperate to ensure long-term stable titin anchoring while allowing the individual components to exchange dynamically.

Dynamics of myosin-driven skeletal muscle contraction: I. Steady-state force generation.

PubMed

Lan, Ganhui; Sun, Sean X

2005-06-01

Skeletal muscle contraction is a canonical example of motor-driven force generation. Despite the long history of research in this topic, a mechanistic explanation of the collective myosin force generation is lacking. We present a theoretical model of muscle contraction based on the conformational movements of individual myosins and experimentally measured chemical rate constants. Detailed mechanics of the myosin motor and the geometry of the sarcomere are taken into account. Two possible scenarios of force generation are examined. We find only one of the scenarios can give rise to a plausible contraction mechanism. We propose that the synchrony in muscle contraction is due to a force-dependent ADP release step. Computational results of a half sarcomere with 150 myosin heads can explain the experimentally measured force-velocity relationship and efficiency data. We predict that the number of working myosin motors increases as the load force is increased, thus showing synchrony among myosin motors during muscle contraction. We also find that titin molecules anchoring the thick filament are passive force generators in assisting muscle contraction.

Dynamics of Myosin-Driven Skeletal Muscle Contraction: I. Steady-State Force Generation

PubMed Central

Lan, Ganhui; Sun, Sean X.

2005-01-01

Skeletal muscle contraction is a canonical example of motor-driven force generation. Despite the long history of research in this topic, a mechanistic explanation of the collective myosin force generation is lacking. We present a theoretical model of muscle contraction based on the conformational movements of individual myosins and experimentally measured chemical rate constants. Detailed mechanics of the myosin motor and the geometry of the sarcomere are taken into account. Two possible scenarios of force generation are examined. We find only one of the scenarios can give rise to a plausible contraction mechanism. We propose that the synchrony in muscle contraction is due to a force-dependent ADP release step. Computational results of a half sarcomere with 150 myosin heads can explain the experimentally measured force-velocity relationship and efficiency data. We predict that the number of working myosin motors increases as the load force is increased, thus showing synchrony among myosin motors during muscle contraction. We also find that titin molecules anchoring the thick filament are passive force generators in assisting muscle contraction. PMID:15778440

The formation of bulges, discs and two-component galaxies in the CANDELS Survey at z < 3

NASA Astrophysics Data System (ADS)

Margalef-Bentabol, Berta; Conselice, Christopher J.; Mortlock, Alice; Hartley, Will; Duncan, Kenneth; Ferguson, Harry C.; Dekel, Avishai; Primack, Joel R.

2016-09-01

We examine a sample of 1495 galaxies in the CANDELS fields to determine the evolution of two-component galaxies, including bulges and discs, within massive galaxies at the epoch 1 < z < 3 when the Hubble sequence forms. We fit all of our galaxies' light profiles with a single Sérsic fit, as well as with a combination of exponential and Sérsic profiles. The latter is done in order to describe a galaxy with an inner and an outer component, or bulge and disc component. We develop and use three classification methods (visual, F-test and the residual flux fraction) to separate our sample into one-component galaxies (disc/spheroids-like galaxies) and two-component galaxies (galaxies formed by an `inner part' or bulge and an `outer part' or disc). We then compare the results from using these three different ways to classify our galaxies. We find that the fraction of galaxies selected as two-component galaxies increases on average 50 per cent from the lowest mass bin to the most massive galaxies, and decreases with redshift by a factor of 4 from z = 1 to 3. We find that single Sérsic `disc-like' galaxies have the highest relative number densities at all redshifts, and that two-component galaxies have the greatest increase and become at par with Sérsic discs by z = 1. We also find that the systems we classify as two-component galaxies have an increase in the sizes of their outer components, or `discs', by about a factor of 3 from z = 3 to 1.5, while the inner components or `bulges' stay roughly the same size. This suggests that these systems are growing from the inside out, whilst the bulges or protobulges are in place early in the history of these galaxies. This is also seen to a lesser degree in the growth of single `disc-like' galaxies versus `spheroid-like' galaxies over the same epoch.

Localization of sarcomeric proteins during myofibril assembly in cultured mouse primary skeletal myotubes

PubMed Central

White, Jennifer; Barro, Marietta V.; Makarenkova, Helen P.; Sanger, Joseph W.; Sanger, Jean M.

2014-01-01

It is important to understand how muscle forms normally in order to understand muscle diseases that result in abnormal muscle formation. Although the structure of myofibrils is well understood, the process through which the myofibril components form organized contractile units is not clear. Based on the staining of muscle proteins in avian embryonic cardiomyocytes, we previously proposed that myofibrils formation occurred in steps that began with premyofibrils followed by nascent myofibrils and ending with mature myofibrils. The purpose of this study was to determine whether the premyofibril model of myofibrillogenesis developed from studies developed from studies in avian cardiomyocytes was supported by our current studies of myofibril assembly in mouse skeletal muscle. Emphasis was on establishing how the key sarcomeric proteins, F-actin, non-muscle myosin II, muscle myosin II, and α-actinin were organized in the three stages of myofibril assembly. The results also test previous reports that non-muscle myosins II A and B are components of the Z-Bands of mature myofibrils, data that are inconsistent with the premyofibril model. We have also determined that in mouse muscle cells, telethonin is a late assembling protein that is present only in the Z-Bands of mature myofibrils. This result of using specific telethonin antibodies supports the approach of using YFP-tagged proteins to determine where and when these YFP-sarcomeric fusion proteins are localized. The data presented in this study on cultures of primary mouse skeletal myocytes are consistent with the premyofibril model of myofibrillogenesis previously proposed for both avian cardiac and skeletal muscle cells. PMID:25125171

Disc-halo interactions in ΛCDM

NASA Astrophysics Data System (ADS)

Bauer, Jacob S.; Widrow, Lawrence M.; Erkal, Denis

2018-05-01

We present a new method for embedding a stellar disc in a cosmological dark matter halo and provide a worked example from a Λ cold dark matter zoom-in simulation. The disc is inserted into the halo at a redshift z = 3 as a zero-mass rigid body. Its mass and size are then increased adiabatically while its position, velocity, and orientation are determined from rigid-body dynamics. At z = 1, the rigid disc (RD) is replaced by an N-body disc whose particles sample a three-integral distribution function (DF). The simulation then proceeds to z = 0 with live disc (LD) and halo particles. By comparison, other methods assume one or more of the following: the centre of the RD during the growth phase is pinned to the minimum of the halo potential, the orientation of the RD is fixed, or the live N-body disc is constructed from a two rather than three-integral DF. In general, the presence of a disc makes the halo rounder, more centrally concentrated, and smoother, especially in the innermost regions. We find that methods in which the disc is pinned to the minimum of the halo potential tend to overestimate the amount of adiabatic contraction. Additionally, the effect of the disc on the subhalo distribution appears to be rather insensitive to the disc insertion method. The LD in our simulation develops a bar that is consistent with the bars seen in late-type spiral galaxies. In addition, particles from the disc are launched or `kicked up' to high galactic latitudes.

Morera-type theorems in the hyperbolic disc

NASA Astrophysics Data System (ADS)

Volchkov, V. V.; Volchkov, V. V.

2018-02-01

Let G be the group of conformal automorphisms of the unit disc {D}=\\{z\\in{C}\\colon \\vert z\\vert<1\\}. We study the problem of the holomorphicity of functions f on {D} satisfying the equation where γ\\varrho=\\{z\\in{C}\\colon \\vert z\\vert=\\varrho\\} and ρ\\in(0,1) is fixed. We find exact conditions for holomorphicity in terms of the boundary behaviour of such functions. A by-product of our work is a new proof of the Berenstein-Pascuas two-radii theorem.

The infrared-radio correlation of spheroid- and disc-dominated star-forming galaxies to z ˜ 1.5 in the COSMOS field

NASA Astrophysics Data System (ADS)

Molnár, Dániel Cs; Sargent, Mark T.; Delhaize, Jacinta; Delvecchio, Ivan; Smolčić, Vernesa; Novak, Mladen; Schinnerer, Eva; Zamorani, Giovanni; Bondi, Marco; Herrera-Ruiz, Noelia; Murphy, Eric J.; Vardoulaki, Eleni; Karim, Alexander; Leslie, Sarah; Magnelli, Benjamin; Carollo, C. Marcella; Middelberg, Enno

2018-03-01

Using infrared data from the Herschel Space Observatory and Karl G. Jansky Very Large Array 3 GHz observations in the COSMOS field, we investigate the redshift evolution of the infrared-radio correlation (IRRC) for star-forming galaxies (SFGs) we classify as either spheroid- or disc-dominated based on their morphology. The sample predominantly consists of disc galaxies with stellar mass ≳ 1010 M⊙, and residing on the star-forming main sequence (MS). After the removal of AGN using standard approaches, we observe a significant difference between the redshift evolution of the median IR/radio ratio \\overline{q}_{TIR} of (i) a sample of ellipticals, plus discs with a substantial bulge component (`spheroid-dominated' SFGs) and, (ii) virtually pure discs and irregular systems (`disc-dominated' SFGs). The spheroid-dominated population follows a declining \\overline{q}_{TIR} versus z trend similar to that measured in recent evolutionary studies of the IRRC. However, for disc-dominated galaxies, where radio and IR emission should be linked to star formation in the most straightforward way, we measure very little change in \\overline{q}_{TIR}. This suggests that low-redshift calibrations of radio emission as a star formation rate (SFR) tracer may remain valid out to at least z ≃ 1-1.5 for pure star-forming systems. We find that the different redshift evolution of qTIR for the spheroid- and disc-dominated sample is mainly due to an increasing radio excess for spheroid-dominated galaxies at z ≳ 0.8, hinting at some residual AGN activity in these systems. This finding demonstrates that in the absence of AGN, the IRRC is independent of redshift, and that radio observations can therefore be used to estimate SFRs at all redshifts for genuinely star-forming galaxies.

Thin filament diversity and physiological properties of fast and slow fiber types in astronaut leg muscles

NASA Technical Reports Server (NTRS)

Riley, Danny A.; Bain, James L W.; Thompson, Joyce L.; Fitts, Robert H.; Widrick, Jeffrey J.; Trappe, Scott W.; Trappe, Todd A.; Costill, David L.

2002-01-01

Slow type I fibers in soleus and fast white (IIa/IIx, IIx), fast red (IIa), and slow red (I) fibers in gastrocnemius were examined electron microscopically and physiologically from pre- and postflight biopsies of four astronauts from the 17-day, Life and Microgravity Sciences Spacelab Shuttle Transport System-78 mission. At 2.5-microm sarcomere length, thick filament density is approximately 1,012 filaments/microm(2) in all fiber types and unchanged by spaceflight. In preflight aldehyde-fixed biopsies, gastrocnemius fibers possess higher percentages (approximately 23%) of short thin filaments than soleus (9%). In type I fibers, spaceflight increases short, thin filament content from 9 to 24% in soleus and from 26 to 31% in gastrocnemius. Thick and thin filament spacing is wider at short sarcomere lengths. The Z-band lattice is also expanded, except for soleus type I fibers with presumably stiffer Z bands. Thin filament packing density correlates directly with specific tension for gastrocnemius fibers but not soleus. Thin filament density is inversely related to shortening velocity in all fibers. Thin filament structural variation contributes to the functional diversity of normal and spaceflight-unloaded muscles.

Evidence for association between Disrupted-in-schizophrenia 1 (DISC1) gene polymorphisms and autism in Chinese Han population: a family-based association study

PubMed Central

2011-01-01

Background Disrupted-in-Schizophrenia 1 (DISC1) gene is one of the most promising candidate genes for major mental disorders. In a previous study, a Finnish group demonstrated that DISC1 polymorphisms were associated with autism and Asperger syndrome. However, the results were not replicated in Korean population. To determine whether DISC1 is associated with autism in Chinese Han population, we performed a family-based association study between DISC1 polymorphisms and autism. Methods We genotyped seven tag single nucleotide polymorphisms (SNPs) in DISC1, spanning 338 kb, in 367 autism trios (singleton and their biological parents) including 1,101 individuals. Single SNP association and haplotype association analysis were performed using the family-based association test (FBAT) and Haploview software. Results We found three SNPs showed significant associations with autism (rs4366301: G > C, Z = 2.872, p = 0.004; rs11585959: T > C, Z = 2.199, p = 0.028; rs6668845: A > G, Z = 2.326, p = 0.02). After the Bonferroni correction, SNP rs4366301, which located in the first intron of DISC1, remained significant. When haplotype were constructed with two-markers, three haplotypes displayed significant association with autism. These results were still significant after using the permutation method to obtain empirical p values. Conclusions Our study provided evidence that the DISC1 may be the susceptibility gene of autism. It suggested DISC1 might play a role in the pathogenesis of autism. PMID:21569632

[Cleavage time for a hydrogen bond under a load].

PubMed

Bespalov, S V; Tolpygo, K B

1993-01-01

Statistics of the hydrogen bond formation and break in a bundle of actin and myosin filaments realizing the attractive force in the sarcomere of a muscle is studied. Purely mechanical problem of the attractive-force formation and motion of myosin heads and action globules under their action is supplemented by accounting for the irreversible processes: 1. Thermal de-excitation of the latter in the chain of hydrogen bond during the elementary act of the ATP energy use resulting in fixing the extended actin filament. 2. Break of the hydrogen bonds, realizing this fixing, due to thermal fluctuations for the time tau. The average life-time turns out to be the order of time necessary for the movement of z-membrane sarcomere for the value of action filament extension delta 1, which is necessary for the process of muscle contraction to be continued.

The bulge-disc decomposed evolution of massive galaxies at 1 < z < 3 in CANDELS

NASA Astrophysics Data System (ADS)

Bruce, V. A.; Dunlop, J. S.; McLure, R. J.; Cirasuolo, M.; Buitrago, F.; Bowler, R. A. A.; Targett, T. A.; Bell, E. F.; McIntosh, D. H.; Dekel, A.; Faber, S. M.; Ferguson, H. C.; Grogin, N. A.; Hartley, W.; Kocevski, D. D.; Koekemoer, A. M.; Koo, D. C.; McGrath, E. J.

2014-10-01

We present the results of a new and improved study of the morphological and spectral evolution of massive galaxies over the redshift range 1 < z < 3. Our analysis is based on a bulge-disc decomposition of 396 galaxies with M* > 1011 M⊙ uncovered from the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS) Wide Field Camera 3 (WFC3)/IR imaging within the Cosmological Evolution Survey (COSMOS) and UKIRT Infrared Deep Sky Survey (UKIDSS) UDS survey fields. We find that, by modelling the H160 image of each galaxy with a combination of a de Vaucouleurs bulge (Sérsic index n = 4) and an exponential disc (n = 1), we can then lock all derived morphological parameters for the bulge and disc components, and successfully reproduce the shorter-wavelength J125, i814, v606 HST images simply by floating the magnitudes of the two components. This then yields sub-divided four-band HST photometry for the bulge and disc components which, with no additional priors, is well described by spectrophotometric models of galaxy evolution. Armed with this information, we are able to properly determine the masses and star formation rates for the bulge and disc components, and find that: (i) from z = 3 to 1 the galaxies move from disc dominated to increasingly bulge dominated, but very few galaxies are pure bulges/ellipticals by z = 1; (ii) while most passive galaxies are bulge dominated, and most star-forming galaxies disc dominated, 18 ± 5 per cent of passive galaxies are disc dominated, and 11 ± 3 per cent of star-forming galaxies are bulge dominated, a result which needs to be explained by any model purporting to connect star formation quenching with morphological transformations; (iii) there exists a small but significant population of pure passive discs, which are generally flatter than their star-forming counterparts (whose axial ratio distribution peaks at b/a ≃ 0.7); (iv) flatter/larger discs re-emerge at the highest star formation rates, consistent with recent studies of sub-mm galaxies, and with the concept of a maximum surface density for star formation activity.

Aging Enhances Indirect Flight Muscle Fiber Performance yet Decreases Flight Ability in Drosophila

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Mark S.; Lekkas, Panagiotis; Braddock, Joan M.

2008-10-02

We investigated the effects of aging on Drosophila melanogaster indirect flight muscle from the whole organism to the actomyosin cross-bridge. Median-aged (49-day-old) flies were flight impaired, had normal myofilament number and packing, barely longer sarcomeres, and slight mitochondrial deterioration compared with young (3-day-old) flies. Old (56-day-old) flies were unable to beat their wings, had deteriorated ultrastructure with severe mitochondrial damage, and their skinned fibers failed to activate with calcium. Small-amplitude sinusoidal length perturbation analysis showed median-aged indirect flight muscle fibers developed greater than twice the isometric force and power output of young fibers, yet cross-bridge kinetics were similar. Large increasesmore » in elastic and viscous moduli amplitude under active, passive, and rigor conditions suggest that median-aged fibers become stiffer longitudinally. Small-angle x-ray diffraction indicates that myosin heads move increasingly toward the thin filament with age, accounting for the increased transverse stiffness via cross-bridge formation. We propose that the observed protein composition changes in the connecting filaments, which anchor the thick filaments to the Z-disk, produce compensatory increases in longitudinal stiffness, isometric tension, power and actomyosin interaction in aging indirect flight muscle. We also speculate that a lack of MgATP due to damaged mitochondria accounts for the decreased flight performance.« less

FtsZ Placement in Nucleoid-Free Bacteria

PubMed Central

Pazos, Manuel; Casanova, Mercedes; Palacios, Pilar; Margolin, William; Natale, Paolo; Vicente, Miguel

2014-01-01

We describe the placement of the cytoplasmic FtsZ protein, an essential component of the division septum, in nucleoid-free Escherichia coli maxicells. The absence of the nucleoid is accompanied in maxicells by degradation of the SlmA protein. This protein, together with the nucleoid, prevents the placement of the septum in the regions occupied by the chromosome by a mechanism called nucleoid occlusion (NO). A second septum placement mechanism, the MinCDE system (Min) involving a pole-to-pole oscillation of three proteins, nonetheless remains active in maxicells. Both Min and NO act on the polymerization of FtsZ, preventing its assembly into an FtsZ-ring except at midcell. Our results show that even in the total absence of NO, Min oscillations can direct placement of FtsZ in maxicells. Deletion of the FtsZ carboxyl terminal domain (FtsZ*), a central hub that receives signals from a variety of proteins including MinC, FtsA and ZipA, produces a Min-insensitive form of FtsZ unable to interact with the membrane-anchoring FtsA and ZipA proteins. This protein produces a totally disorganized pattern of FtsZ localization inside the maxicell cytoplasm. In contrast, FtsZ*-VM, an artificially cytoplasmic membrane-anchored variant of FtsZ*, forms helical or repetitive ring structures distributed along the entire length of maxicells even in the absence of NO. These results show that membrane anchoring is needed to organize FtsZ into rings and underscore the role of the C-terminal hub of FtsZ for their correct placement. PMID:24638110

FtsZ placement in nucleoid-free bacteria.

PubMed

Pazos, Manuel; Casanova, Mercedes; Palacios, Pilar; Margolin, William; Natale, Paolo; Vicente, Miguel

2014-01-01

We describe the placement of the cytoplasmic FtsZ protein, an essential component of the division septum, in nucleoid-free Escherichia coli maxicells. The absence of the nucleoid is accompanied in maxicells by degradation of the SlmA protein. This protein, together with the nucleoid, prevents the placement of the septum in the regions occupied by the chromosome by a mechanism called nucleoid occlusion (NO). A second septum placement mechanism, the MinCDE system (Min) involving a pole-to-pole oscillation of three proteins, nonetheless remains active in maxicells. Both Min and NO act on the polymerization of FtsZ, preventing its assembly into an FtsZ-ring except at midcell. Our results show that even in the total absence of NO, Min oscillations can direct placement of FtsZ in maxicells. Deletion of the FtsZ carboxyl terminal domain (FtsZ*), a central hub that receives signals from a variety of proteins including MinC, FtsA and ZipA, produces a Min-insensitive form of FtsZ unable to interact with the membrane-anchoring FtsA and ZipA proteins. This protein produces a totally disorganized pattern of FtsZ localization inside the maxicell cytoplasm. In contrast, FtsZ*-VM, an artificially cytoplasmic membrane-anchored variant of FtsZ*, forms helical or repetitive ring structures distributed along the entire length of maxicells even in the absence of NO. These results show that membrane anchoring is needed to organize FtsZ into rings and underscore the role of the C-terminal hub of FtsZ for their correct placement.

Galaxy And Mass Assembly (GAMA): gas fuelling of spiral galaxies in the local Universe II. - direct measurement of the dependencies on redshift and host halo mass of stellar mass growth in central disc galaxies

NASA Astrophysics Data System (ADS)

Grootes, M. W.; Dvornik, A.; Laureijs, R. J.; Tuffs, R. J.; Popescu, C. C.; Robotham, A. S. G.; Liske, J.; Brown, M. J. I.; Holwerda, B. W.; Wang, L.

2018-06-01

We present a detailed analysis of the specific star formation rate-stellar mass (sSFR-M*) of z ≤ 0.13 disc central galaxies using a morphologically selected mass-complete sample (M* ≥ 109.5 M⊙). Considering samples of grouped and ungrouped galaxies, we find the sSFR-M* relations of disc-dominated central galaxies to have no detectable dependence on host dark-matter halo (DMH) mass, even where weak-lensing measurements indicate a difference in halo mass of a factor ≳ 5. We further detect a gradual evolution of the sSFR-M* relation of non-grouped (field) central disc galaxies with redshift, even over a Δz ≈ 0.04 (≈5 × 108 yr) interval, while the scatter remains constant. This evolution is consistent with extrapolation of the `main sequence of star-forming-galaxies' from previous literature that uses larger redshift baselines and coarser sampling. Taken together, our results present new constraints on the paradigm under which the SFR of galaxies is determined by a self-regulated balance between gas inflows and outflows, and consumption of gas by star formation in discs, with the inflow being determined by the product of the cosmological accretion rate and a fuelling efficiency - \\dot{M}_{b,halo}ζ. In particular, maintaining the paradigm requires \\dot{M}_{b,halo}ζ to be independent of the mass Mhalo of the host DMH. Furthermore, it requires the fuelling efficiency ζ to have a strong redshift dependence (∝(1 + z)2.7 for M* = 1010.3 M⊙ over z = 0-0.13), even though no morphological transformation to spheroids can be invoked to explain this in our disc-dominated sample. The physical mechanisms capable of giving rise to such dependencies of ζ on Mhalo and z for discs are unclear.

Wet disc contraction to galactic blue nuggets and quenching to red nuggets

NASA Astrophysics Data System (ADS)

Dekel, A.; Burkert, A.

2014-02-01

We study the origin of high-redshift, compact, quenched spheroids (red nuggets) through the dissipative shrinkage of gaseous discs into compact star-forming systems (blue nuggets). The discs, fed by cold streams, undergo violent disc instability that drives gas into the centre (along with mergers). The inflow is dissipative when its time-scale is shorter than the star formation time-scale. This implies a threshold of ˜0.28 in the cold-to-total mass ratio within the disc radius. For the typical gas fraction ˜0.5 at z ˜ 2, this threshold is traced back to a maximum spin parameter of ˜0.05, implying that ˜half the star-forming galaxies contract to blue nuggets, while the rest form extended stellar discs. Thus, the surface density of blue galaxies is expected to be bimodal about ˜109 M⊙ kpc-2, slightly increasing with mass. The blue nuggets are expected to be rare at low z when the gas fraction is low. The blue nuggets quench to red nuggets by complementary internal and external mechanisms. Internal quenching by a compact bulge, in a fast mode and especially at high z, may involve starbursts, stellar and active galactic nucleus feedback, or Q-quenching. Quenching due to hot-medium haloes above 1012 M⊙ provides maintenance and a slower mode at low redshift. These predictions are confirmed in simulations and are consistent with observations at z = 0-3.

Myofibril growth during cardiac hypertrophy is regulated through dual phosphorylation and acetylation of the actin capping protein CapZ

PubMed Central

Lin, Ying-Hsi; Warren, Chad M.; Li, Jieli; McKinsey, Timothy A.; Russell, Brenda

2016-01-01

The mechanotransduction signaling pathways initiated in heart muscle by increased mechanical loading are known to lead to long-term transcriptional changes and hypertrophy, but the rapid events for adaptation at the sarcomeric level are not fully understood. The goal of this study was to test the hypothesis that actin filament assembly during cardiomyocyte growth is regulated by post-translational modifications (PTMs) of CapZβ1. In rapidly hypertrophying neonatal rat ventricular myocytes (NRVMs) stimulated by phenylephrine (PE), two-dimensional gel electrophoresis (2DGE) of CapZβ1 revealed a shift toward more negative charge. Consistent with this, mass spectrometry identified CapZβ1 phosphorylation on serine-204 and acetylation on lysine-199, two residues which are near the actin binding surface of CapZβ1. Ectopic expression of dominant negative PKCε (dnPKCε) in NRVMs blunted the PE-induced increase in CapZ dynamics, as evidenced by the kinetic constant (Kfrap) of fluorescence recovery after photobleaching (FRAP), and concomitantly reduced phosphorylation and acetylation of CapZβ1. Furthermore, inhibition of class I histone deacetylases (HDACs) increased lysine-199 acetylation on CapZβ1, which increased Kfrap of CapZ and stimulated actin dynamics. Finally, we show that PE treatment of NRVMs results in decreased binding of HDAC3 to myofibrils, suggesting a signal-dependent mechanism for the regulation of sarcomere-associated CapZβ1 acetylation. Taken together, this dual regulation through phosphorylation and acetylation of CapZβ1 provides a novel model for the regulation of myofibril growth during cardiac hypertrophy. PMID:27185186

Does partial titin degradation affect sarcomere length non-uniformities and force in active and passive myofibrils?

PubMed

Joumaa, Venus; Bertrand, Fanny; Liu, Shuyue; Poscente, Sophia; Herzog, Walter

2018-05-16

The aim of this study was to determine the role of titin in preventing the development of sarcomere length non-uniformities following activation and after active and passive stretch, by determining the effect of partial titin degradation on sarcomere length non-uniformities and force in passive and active myofibrils. Selective partial titin degradation was performed using a low dose of trypsin. Myofibrils were set at a sarcomere length of 2.4 µm and then passively stretched to sarcomere lengths of 3.4 µm and 4.4 µm. In the active condition, myofibrils were set at a sarcomere length of 2.8µm, activated and actively stretched by 1 µm/sarcomere. The extent of sarcomere length non-uniformities was calculated for each sarcomere as the absolute difference between sarcomere length and the mean sarcomere length of the myofibril. Our main finding is that partial titin degradation does not increase sarcomere length non-uniformities after passive stretch and activation compared to when titin is intact, but increases the extent of sarcomere length non-uniformities after active stretch. Furthermore, when titin was partially degraded, active and passive stresses were substantially reduced. These results suggest that titin plays a crucial role in actively stretched myofibrils and is likely involved in active and passive force production.

Torus models of the outer disc of the Milky Way using LAMOST survey data

NASA Astrophysics Data System (ADS)

Wang, Qiao; Wang, Yougang; Liu, Chao; Mao, Shude; Long, R. J.

2017-09-01

With a sample of 48 161 K giant stars selected from the LAMOST DR 2 catalogue, we construct torus models in a large volume extending, for the first time, from the solar vicinity to a Galactocentric distance of ∼20 kpc, reaching the outskirts of the Galactic disc. We show that the kinematics of the K giant stars match conventional models, e.g. as created by Binney in 2012, in the Solar vicinity. However such two-disc models fail if they are extended to the outer regions, even if an additional disc component is utilized. If we loosen constraints in Sun's vicinity, we find that an effective thick disc model could explain the anticentre of the MW. The Large Area Multi-Object Spectroscopic Telescope data imply that the sizes of the Galactic discs are much larger, and that the outer disc is much thicker, than previously thought, or alternatively that the outer structure is not a conventional disc at all. However, the velocity dispersion σ0z of the kinematically thick disc in the best-fitting model is about 80 km s-1 and has a scale parameter Rσ for an exponential distribution function of ∼19 kpc. Such a height σ0z is strongly rejected by current measurements in the solar neighbourhood, and thus a model beyond quasi-thermal, two or three thin or thick discs is required.

Titin PEVK segment: charge-driven elasticity of the open and flexible polyampholyte

PubMed Central

FORBES, JEFFREY G.; JIN, ALBERT J.; MA, KAN; GUTIERREZ-CRUZ, GUSTAVO; TSAI, WANXIA L.; WANG, KUAN

2015-01-01

The giant protein titin spans half of the sarcomere length and anchors the myosin thick filament to the Z-line of skeletal and cardiac muscles. The passive elasticity of muscle at a physiological range of stretch arises primarily from the extension of the PEVK segment, which is a polyampholyte with dense and alternating-charged clusters. Force spectroscopy studies of a 51 kDa fragment of the human fetal titin PEVK domain (TP1) revealed that when charge interactions were reduced by raising the ionic strength from 35 to 560 mM, its mean persistence length increased from 0.30±0.04 nm to 0.60±0.07 nm. In contrast, when the secondary structure of TP1 was altered drastically by the presence of 40 and 80% (v/v) of trifluoroethanol, its force-extension behavior showed no significant shift in the mean persistence length of ~0.18±0.03 nm at the ionic strength of 15 mM. Additionally, the mean persistence length also increased from 0.29 to 0.41 nm with increasing calcium concentration from pCa 5–8 to pCa 3–4. We propose that PEVK is not a simple entropic spring as is commonly assumed, but a highly evolved, gel-like enthalpic spring with its elasticity dominated by the sequence-specific charge interactions. A single polyampholyte chain may be fine-tuned to generate a broad range of molecular elasticity by varying charge pairing schemes and chain configurations. PMID:16465472

A node organization in the actomyosin contractile ring generates tension and aids stability.

PubMed

Thiyagarajan, Sathish; Wang, Shuyuan; O'Shaughnessy, Ben

2017-11-07

During cytokinesis, a contractile actomyosin ring constricts and divides the cell in two. How the ring marshals actomyosin forces to generate tension is not settled. Recently, a superresolution microscopy study of the fission yeast ring revealed that myosins and formins that nucleate actin filaments colocalize in plasma membrane-anchored complexes called nodes in the constricting ring. The nodes move bidirectionally around the ring. Here we construct and analyze a coarse-grained mathematical model of the fission yeast ring to explore essential consequences of the recently discovered ring ultrastructure. The model reproduces experimentally measured values of ring tension, explains why nodes move bidirectionally, and shows that tension is generated by myosin pulling on barbed-end-anchored actin filaments in a stochastic sliding-filament mechanism. This mechanism is not based on an ordered sarcomeric organization. We show that the ring is vulnerable to intrinsic contractile instabilities, and protection from these instabilities and organizational homeostasis require both component turnover and anchoring of components to the plasma membrane. © 2017 Thiyagarajan, Wang, and O’Shaughnessy. 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).

Interaction of infectious spleen and kidney necrosis virus ORF119L with PINCH leads to dominant-negative inhibition of integrin-linked kinase and cardiovascular defects in zebrafish.

PubMed

Yuan, Ji-Min; He, Bai-Liang; Yang, Lu-Yun; Guo, Chang-Jun; Weng, Shao-Ping; Li, Shengwen Calvin; He, Jian-Guo

2015-01-01

Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the Megalocytivirus genus, Iridoviridae family, causing a severe systemic disease with high mortality in mandarin fish (Siniperca chuatsi) in China and Southeast Asia. At present, the pathogenesis of ISKNV infection is still not fully understood. Based on a genome-wide bioinformatics analysis of ISKNV-encoded proteins, we found that ISKNV open reading frame 119L (ORF119L) is predicted to encode a three-ankyrin-repeat (3ANK)-domain-containing protein, which shows high similarity to the dominant negative form of integrin-linked kinase (ILK); i.e., viral ORF119L lacks the ILK kinase domain. Thus, we speculated that viral ORF119L might affect the host ILK complex. Here, we demonstrated that viral ORF119L directly interacts with particularly interesting Cys-His-rich protein (PINCH) and affects the host ILK-PINCH interaction in vitro in fathead minnow (FHM) cells. In vivo ORF119L overexpression in zebrafish (Danio rerio) embryos resulted in myocardial dysfunctions with disintegration of the sarcomeric Z disk. Importantly, ORF119L overexpression in zebrafish highly resembles the phenotype of endogenous ILK inhibition, either by overexpressing a dominant negative form of ILK or by injecting an ILK antisense morpholino oligonucleotide. Intriguingly, ISKNV-infected mandarin fish develop disorganized sarcomeric Z disks in cardiomyocytes. Furthermore, phosphorylation of AKT, a downstream effector of ILK, was remarkably decreased in ORF119L-overexpressing zebrafish embryos. With these results, we show that ISKNV ORF119L acts as a domain-negative inhibitor of the host ILK, providing a novel mechanism for the megalocytivirus pathogenesis. Our work is the first to show the role of a dominant negative inhibitor of the host ILK from ISKNV (an iridovirus). Mechanistically, the viral ORF119L directly binds to the host PINCH, attenuates the host PINCH-ILK interaction, and thus impairs ILK signaling. Intriguingly, ORF119L-overexpressing zebrafish embryos and ISKNV-infected mandarin fish develop similar disordered sarcomeric Z disks in cardiomyocytes. These findings provide a novel mechanism for megalocytivirus pathogenesis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Photometric variability in FU Ori and Z CMa as observed by MOST

NASA Astrophysics Data System (ADS)

Siwak, Michal; Rucinski, Slavek M.; Matthews, Jaymie M.; Kuschnig, Rainer; Guenther, David B.; Moffat, Anthony F. J.; Rowe, Jason F.; Sasselov, Dimitar; Weiss, Werner W.

2013-06-01

Photometric observations obtained by the MOST satellite were used to characterize optical small-scale variability of the young stars FU Ori and Z CMa. Wavelet analysis for FU Ori reveals the possible existence of several 2-9 d quasi-periodic features occurring nearly simultaneously; they may be interpreted as plasma parcels or other localized disc heterogeneities revolving at different Keplerian radii in the accretion disc. Their periods may shorten slowly which may be due to spiralling in of individual parcels towards the inner disc radius, estimated at 4.8 ± 0.2 R⊙. Analysis of additional multicolour data confirms the previously obtained relation between variations in the B - V colour index and the V magnitude. In contrast to the FU Ori results, the oscillation spectrum of Z CMa does not reveal any periodicities with the wavelet spectrum possibly dominated by outburst of the Herbig Be component.

Multiscale Characterization of Engineered Cardiac Tissue Architecture.

PubMed

Drew, Nancy K; Johnsen, Nicholas E; Core, Jason Q; Grosberg, Anna

2016-11-01

In a properly contracting cardiac muscle, many different subcellular structures are organized into an intricate architecture. While it has been observed that this organization is altered in pathological conditions, the relationship between length-scales and architecture has not been properly explored. In this work, we utilize a variety of architecture metrics to quantify organization and consistency of single structures over multiple scales, from subcellular to tissue scale as well as correlation of organization of multiple structures. Specifically, as the best way to characterize cardiac tissues, we chose the orientational and co-orientational order parameters (COOPs). Similarly, neonatal rat ventricular myocytes were selected for their consistent architectural behavior. The engineered cells and tissues were stained for four architectural structures: actin, tubulin, sarcomeric z-lines, and nuclei. We applied the orientational metrics to cardiac cells of various shapes, isotropic cardiac tissues, and anisotropic globally aligned tissues. With these novel tools, we discovered: (1) the relationship between cellular shape and consistency of self-assembly; (2) the length-scales at which unguided tissues self-organize; and (3) the correlation or lack thereof between organization of actin fibrils, sarcomeric z-lines, tubulin fibrils, and nuclei. All of these together elucidate some of the current mysteries in the relationship between force production and architecture, while raising more questions about the effect of guidance cues on self-assembly function. These types of metrics are the future of quantitative tissue engineering in cardiovascular biomechanics.

Elastic fibre organization in the intervertebral discs of the bovine tail

PubMed Central

Yu, Jing; Peter, C; Roberts, Sally; Urban, Jill PG

2002-01-01

Elastic fibres have been revealed by both elastin immunostaining and conventional histological orcein-staining in the intervertebral discs of the bovine tail. These fibres are distributed in all regions of the disc but their organization varies from region to region. In the centre of the nucleus, long (>150 μm) elastic fibres are orientated radially. In the transitional region between nucleus and annulus, the orientation of the elastic fibres changes, producing a criss-cross pattern. In the annulus itself, elastic fibres appear densely distributed in the region between the lamellae and also in ‘bridges’ across the lamellae, particularly in the adult. Elastic fibres are apparent within the lamellae, orientated parallel to the collagen fibres of each lamella, particularly in the young (12-day-old) discs. In the region between the disc and the cartilaginous endplate, elastic fibres appear to anchor into the plate and terminate there. The results of this study suggest that elastic fibres contribute to the mechanical functioning of the intervertebral disc. The varying organization of the elastic fibres in the different regions of the disc is likely to relate to the different regional loading patterns PMID:12489758

The neurochemical and neuropharmacological basis of motion sickness

NASA Technical Reports Server (NTRS)

Walker, C. A.

1990-01-01

An apparatus suitable for producing motion sickness in laboratory animals and constructed at the university is herein described. The apparatus is a modified version of that previously described by Fox and Daunton. It consists of a 66-inch steel arm anchored at the center to a wooden platform and attached to a motor that makes the arm move in a see-saw fashion. At each end of the steel arm is mounted an aluminum disc that can be rotated by a motorized device. Detachable cages are mounted on each disc for animal holding. The animal can then be exposed to rotational motion by rotation of the aluminum disc, or to see-saw motion simultaneously (Cross-coupled). The apparatus is presently being used in our laboratory to study the neuropharmacological basis of motion sickness in the rat. The device can be adapted for use with other animal species by modifying the cage mounted on the aluminum discs.

Cell biology of sarcomeric protein engineering: disease modeling and therapeutic potential.

PubMed

Thompson, Brian R; Metzger, Joseph M

2014-09-01

The cardiac sarcomere is the functional unit for myocyte contraction. Ordered arrays of sarcomeric proteins, held in stoichiometric balance with each other, respond to calcium to coordinate contraction and relaxation of the heart. Altered sarcomeric structure-function underlies the primary basis of disease in multiple acquired and inherited heart disease states. Hypertrophic and restrictive cardiomyopathies are caused by inherited mutations in sarcomeric genes and result in altered contractility. Ischemia-mediated acidosis directly alters sarcomere function resulting in decreased contractility. In this review, we highlight the use of acute genetic engineering of adult cardiac myocytes through stoichiometric replacement of sarcomeric proteins in these disease states with particular focus on cardiac troponin I. Stoichiometric replacement of disease causing mutations has been instrumental in defining the molecular mechanisms of hypertrophic and restrictive cardiomyopathy in a cellular context. In addition, taking advantage of stoichiometric replacement through gene therapy is discussed, highlighting the ischemia-resistant histidine-button, A164H cTnI. Stoichiometric replacement of sarcomeric proteins offers a potential gene therapy avenue to replace mutant proteins, alter sarcomeric responses to pathophysiologic insults, or neutralize altered sarcomeric function in disease. © 2014 Wiley Periodicals, Inc.

Stellar and gaseous disc structures in cosmological galaxy equilibrium models

NASA Astrophysics Data System (ADS)

Rathaus, Ben; Sternberg, Amiel

2016-05-01

We present `radially resolved equilibrium models' for the growth of stellar and gaseous discs in cosmologically accreting massive haloes. Our focus is on objects that evolve to redshifts z ˜ 2. We solve the time-dependent equations that govern the radially dependent star formation rates, inflows and outflows from and to the inter- and circumgalactic medium, and inward radial gas flows within the discs. The stellar and gaseous discs reach equilibrium configurations on dynamical time-scales much shorter than variations in the cosmological dark matter halo growth and baryonic accretions rates. We show analytically that mass and global angular momentum conservation naturally give rise to exponential gas and stellar discs over many radial length-scales. As expected, the gaseous discs are more extended as set by the condition Toomre Q < 1 for star formation. The discs rapidly become baryon dominated. For massive, 5 × 1012 M⊙ haloes at redshift z = 2, we reproduced the typical observed star formation rates of ˜100 M⊙ yr-1, stellar masses ˜9 × 1010 M⊙, gas contents ˜1011 M⊙, half-mass sizes of 4.5 and 5.8 kpc for the stars and gas, and characteristic surface densities of 500 and 400 M⊙ pc-2 for the stars and gas.

Destabilization of fructose 1,6-bisphosphatase-Z-line interactions is a mechanism of glyconeogenesis down-regulation in vivo.

PubMed

Gizak, Agnieszka; Mazurek, Jakub; Wozniak, Marta; Maciaszczyk-Dziubinska, Ewa; Rakus, Dariusz

2013-03-01

Although it is well known that insulin controls the synthesis of glycogen from non-carbohydrates by down-regulating expression of several glyconeogenic enzymes, a mechanism of short-term inhibition of glyconeogenesis remains unknown. In recent years, we have shown that in skeletal muscle, fructose 1,6-bisphosphatase (FBPase) is a part of the hypothetical glyconeogenic complex located on sarcomeric Z-line. Here, we show that inhibition of glycogen synthase kinase-3 causes disruption of the FBPase-Z-line interactions and reduction of muscle glycogen content in vivo. The normal, striated pattern of muscle FBPase localization is also disturbed by insulin treatment but preserved when insulin is applied together with Akt inhibitor. We suggest that destabilization of FBPase-Z-line interaction is a universal cellular mechanism of glyconeogenesis down-regulation, allowing for preferential utilization of glucose for insulin-stimulated muscle glycogen synthesis. Copyright © 2012 Elsevier B.V. All rights reserved.

Galaxy And Mass Assembly (GAMA): M_star - R_e relations of z = 0 bulges, discs and spheroids

NASA Astrophysics Data System (ADS)

Lange, Rebecca; Moffett, Amanda J.; Driver, Simon P.; Robotham, Aaron S. G.; Lagos, Claudia del P.; Kelvin, Lee S.; Conselice, Christopher; Margalef-Bentabol, Berta; Alpaslan, Mehmet; Baldry, Ivan; Bland-Hawthorn, Joss; Bremer, Malcolm; Brough, Sarah; Cluver, Michelle; Colless, Matthew; Davies, Luke J. M.; Häußler, Boris; Holwerda, Benne W.; Hopkins, Andrew M.; Kafle, Prajwal R.; Kennedy, Rebecca; Liske, Jochen; Phillipps, Steven; Popescu, Cristina C.; Taylor, Edward N.; Tuffs, Richard; van Kampen, Eelco; Wright, Angus H.

2016-10-01

We perform automated bulge + disc decomposition on a sample of ˜7500 galaxies from the Galaxy And Mass Assembly (GAMA) survey in the redshift range of 0.002 < z < 0.06 using Structural Investigation of Galaxies via Model Analysis, a wrapper around GALFIT3. To achieve robust profile measurements, we use a novel approach of repeatedly fitting the galaxies, varying the input parameters to sample a large fraction of the input parameter space. Using this method, we reduce the catastrophic failure rate significantly and verify the confidence in the fit independently of χ2. Additionally, using the median of the final fitting values and the 16th and 84th percentile produces more realistic error estimates than those provided by GALFIT, which are known to be underestimated. We use the results of our decompositions to analyse the stellar mass - half-light radius relations of bulges, discs and spheroids. We further investigate the association of components with a parent disc or elliptical relation to provide definite z = 0 disc and spheroid M_star - R_e relations. We conclude by comparing our local disc and spheroid M_star - R_e to simulated data from EAGLE and high-redshift data from Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey-Ultra Deep Survey. We show the potential of using the M_star - R_e relation to study galaxy evolution in both cases but caution that for a fair comparison, all data sets need to be processed and analysed in the same manner.

Criteria for the Function Classes UBC and M1No.

NASA Astrophysics Data System (ADS)

Aulaskari, Rauno; Rättyä, Jouni

2011-09-01

For a function f, meromorphic in the unit disc D, and parameter values 0p/2-1|f'(z)|1+|f(z)|p. New characterizations for the classes UBC and M1♯ in terms of fp♯ are obtained.

Animal Models of Congenital Cardiomyopathies Associated With Mutations in Z-Line Proteins.

PubMed

Bang, Marie-Louise

2017-01-01

The cardiac Z-line at the boundary between sarcomeres is a multiprotein complex connecting the contractile apparatus with the cytoskeleton and the extracellular matrix. The Z-line is important for efficient force generation and transmission as well as the maintenance of structural stability and integrity. Furthermore, it is a nodal point for intracellular signaling, in particular mechanosensing and mechanotransduction. Mutations in various genes encoding Z-line proteins have been associated with different cardiomyopathies, including dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, and left ventricular noncompaction, and mutations even within the same gene can cause widely different pathologies. Animal models have contributed to a great advancement in the understanding of the physiological function of Z-line proteins and the pathways leading from mutations in Z-line proteins to cardiomyopathy, although genotype-phenotype prediction remains a great challenge. This review presents an overview of the currently available animal models for Z-line and Z-line associated proteins involved in human cardiomyopathies with special emphasis on knock-in and transgenic mouse models recapitulating the clinical phenotypes of human cardiomyopathy patients carrying mutations in Z-line proteins. Pros and cons of mouse models will be discussed and a future outlook will be given. J. Cell. Physiol. 232: 38-52, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Cervical Stand-Alone Polyetheretherketone Cage versus Zero-Profile Anchored Spacer in Single-Level Anterior Cervical Discectomy and Fusion : Minimum 2-Year Assessment of Radiographic and Clinical Outcome.

PubMed

Cho, Hyun-Jun; Hur, Junseok W; Lee, Jang-Bo; Han, Jin-Sol; Cho, Tai-Hyoung; Park, Jung-Yul

2015-08-01

We compared the clinical and radiographic outcomes of stand-alone polyetheretherketone (PEEK) cage and Zero-Profile anchored spacer (Zero-P) for single level anterior cervical discectomy and fusion (ACDF). We retrospectively reviewed 121 patients who underwent single level ACDF within 2 years (Jan 2011-Jan 2013) in a single institute. Total 50 patients were included for the analysis who were evaluated more than 2-year follow-up. Twenty-nine patients were allocated to the cage group (m : f=19 : 10) and 21 for Zero-P group (m : f=12 : 9). Clinical (neck disability index, visual analogue scale arm and neck) and radiographic (Cobb angle-segmental and global cervical, disc height, vertebral height) assessments were followed at pre-operative, immediate post-operative, post-3, 6, 12, and 24 month periods. Demographic features and the clinical outcome showed no difference between two groups. The change between final follow-up (24 months) and immediate post-op of Cobb-segmental angle (p=0.027), disc height (p=0.002), vertebral body height (p=0.033) showed statistically better outcome for the Zero-P group than the cage group, respectively. The Zero-Profile anchored spacer has some advantage after cage for maintaining segmental lordosis and lowering subsidence rate after single level anterior cervical discectomy and fusion.

Microfluidic perfusion shows intersarcomere dynamics within single skeletal muscle myofibrils

PubMed Central

Minozzo, Fabio C.; Altman, David; Rassier, Dilson E.

2017-01-01

The sarcomere is the smallest functional unit of myofibrils in striated muscles. Sarcomeres are connected in series through a network of elastic and structural proteins. During myofibril activation, sarcomeres develop forces that are regulated through complex dynamics among their structures. The mechanisms that regulate intersarcomere dynamics are unclear, which limits our understanding of fundamental muscle features. Such dynamics are associated with the loss in forces caused by mechanical instability encountered in muscle diseases and cardiomyopathy and may underlie potential target treatments for such conditions. In this study, we developed a microfluidic perfusion system to control one sarcomere within a myofibril, while measuring the individual behavior of all sarcomeres. We found that the force from one sarcomere leads to adjustments of adjacent sarcomeres in a mechanism that is dependent on the sarcomere length and the myofibril stiffness. We concluded that the cooperative work of the contractile and the elastic elements within a myofibril rules the intersarcomere dynamics, with important consequences for muscle contraction. PMID:28765372

A transcriptomics resource reveals a transcriptional transition during ordered sarcomere morphogenesis in flight muscle.

PubMed

Spletter, Maria L; Barz, Christiane; Yeroslaviz, Assa; Zhang, Xu; Lemke, Sandra B; Bonnard, Adrien; Brunner, Erich; Cardone, Giovanni; Basler, Konrad; Habermann, Bianca H; Schnorrer, Frank

2018-05-30

Muscles organise pseudo-crystalline arrays of actin, myosin and titin filaments to build force-producing sarcomeres. To study sarcomerogenesis, we have generated a transcriptomics resource of developing Drosophila flight muscles and identified 40 distinct expression profile clusters. Strikingly, most sarcomeric components group in two clusters, which are strongly induced after all myofibrils have been assembled, indicating a transcriptional transition during myofibrillogenesis. Following myofibril assembly, many short sarcomeres are added to each myofibril. Subsequently, all sarcomeres mature, reaching 1.5 µm diameter and 3.2 µm length and acquiring stretch-sensitivity. The efficient induction of the transcriptional transition during myofibrillogenesis, including the transcriptional boost of sarcomeric components, requires in part the transcriptional regulator Spalt major. As a consequence of Spalt knock-down, sarcomere maturation is defective and fibers fail to gain stretch-sensitivity. Together, this defines an ordered sarcomere morphogenesis process under precise transcriptional control - a concept that may also apply to vertebrate muscle or heart development. © 2018, Spletter et al.

The shape of the cosmic X-ray background: nuclear starburst discs and the redshift evolution of AGN obscuration

NASA Astrophysics Data System (ADS)

Gohil, R.; Ballantyne, D. R.

2018-04-01

A significant number of active galactic nuclei (AGNs) are observed to be hidden behind dust and gas. The distribution of material around AGNs plays an important role in modelling the cosmic X-ray background (CXB), especially the fraction of type 2 AGNs (f2). One of the possible explanations for obscuration in Seyfert galaxies at intermediate redshifts is dusty starburst discs. We compute the two-dimensional (2D) hydrostatic structure of 768 nuclear starburst discs (NSDs) under various physical conditions and also the distribution of column density along the line of sight (NH) associated with these discs. Then the NH distribution is evolved with redshift by using the redshift-dependent distribution function of input parameters. Parameter f2 shows a strong positive evolution up to z = 2, but only a weak level of enhancement at higher z. The Compton-thin and Compton-thick AGN fractions associated with these starburst regions increase ∝ (1 + z)δ, where δ is estimated to be 1.12 and 1.45, respectively. The reflection parameter Rf associated with column density NH ≥ 1023.5 cm-2 extends from 0.13 at z = 0 to 0.58 at z = 4. A CXB model employing this evolving NH distribution indicates that more compact (Rout < 120 pc) NSDs provide a better fit to the CXB. In addition to `Seyfert-like' AGNs obscured by nuclear starbursts, we predict that 40-60 per cent of quasars must be Compton-thick to produce a peak of the CXB spectrum within the observational uncertainty. The predicted total number counts of AGNs in 8-24 keV bands are in fair agreement with observations from the Nuclear Spectroscopic Telescope Array (NuSTAR).

Optimal design of vertebrate and insect sarcomeres.

PubMed

Otten, E

1987-01-01

This paper offers a model for the normalized length-tension relation of a muscle fiber based upon sarcomere design. Comparison with measurements published by Gordon et al. ('66) shows an accurate fit as long as the inhomogeneity of sarcomere length in a single muscle fiber is taken into account. Sequential change of filament length and the length of the cross-bridge-free zone leads the model to suggest that most vertebrate sarcomeres tested match the condition of optimal construction for the output of mechanical energy over a full sarcomere contraction movement. Joint optimization of all three morphometric parameters suggests that a slightly better (0.3%) design is theoretically possible. However, this theoretical sarcomere, optimally designed for the conversion of energy, has a low normalized contraction velocity; it provides a poorer match to the combined functional demands of high energy output and high contraction velocity than the real sarcomeres of vertebrates. The sarcomeres in fish myotomes appear to be built suboptimally for isometric contraction, but built optimally for that shortening velocity generating maximum power. During swimming, these muscles do indeed contract concentrically only. The sarcomeres of insect asynchronous flight muscles contract only slightly. They are not built optimally for maximum output of energy across the full range of contraction encountered in vertebrate sarcomeres, but are built almost optimally for the contraction range that they do in fact employ.

A permian productoid brachiopod: Life history

USGS Publications Warehouse

Grant, R.E.

1966-01-01

Spine arrangements on silicified specimens of Waagenoconcha abichi (Waagen) from the Khisor Range of West Pakistan suggest that the juvenile shell attached itself to a foreign object, and that the adult shell lay on its ventral valve in the substrate, anchored and stabilized by a dense corona of long slender spines around the ventral visceral disc.

Tracing notochord-derived cells using a Noto-cre mouse: implications for intervertebral disc development.

PubMed

McCann, Matthew R; Tamplin, Owen J; Rossant, Janet; Séguin, Cheryle A

2012-01-01

Back pain related to intervertebral disc degeneration is the most common musculoskeletal problem, with a lifetime prevalence of 82%. The lack of effective treatment for this widespread problem is directly related to our limited understanding of disc development, maintenance and degeneration. The aim of this study was to determine the developmental origins of nucleus pulposus cells within the intervertebral disc using a novel notochord-specific Cre mouse. To trace the fate of notochordal cells within the intervertebral disc, we derived a notochord-specific Cre mouse line by targeting the homeobox gene Noto. Expression of this gene is restricted to the node and the posterior notochord during gastrulation [embryonic day 7.5 (E7.5)-E12.5]. The Noto-cre mice were crossed with a conditional lacZ reporter for visualization of notochord fate in whole-mount embryos. We performed lineage-tracing experiments to examine the contribution of the notochord to spinal development from E12.5 through to skeletally mature mice (9 months). Fate mapping studies demonstrated that, following elongation and formation of the primitive axial skeleton, the notochord gives rise to the nucleus pulposus in fully formed intervertebral discs. Cellular localization of β-galactosidase (encoded by lacZ) and cytokeratin-8 demonstrated that both notochordal cells and chondrocyte-like nucleus pulposus cells are derived from the embryonic notochord. These studies establish conclusively that notochordal cells act as embryonic precursors to all cells found within the nucleus pulposus of the mature intervertebral disc. This suggests that notochordal cells might serve as tissue-specific progenitor cells within the disc and establishes the Noto-cre mouse as a unique tool to interrogate the contribution of notochordal cells to both intervertebral disc development and disc degeneration.

Tracing notochord-derived cells using a Noto-cre mouse: implications for intervertebral disc development

PubMed Central

McCann, Matthew R.; Tamplin, Owen J.; Rossant, Janet; Séguin, Cheryle A.

2012-01-01

SUMMARY Back pain related to intervertebral disc degeneration is the most common musculoskeletal problem, with a lifetime prevalence of 82%. The lack of effective treatment for this widespread problem is directly related to our limited understanding of disc development, maintenance and degeneration. The aim of this study was to determine the developmental origins of nucleus pulposus cells within the intervertebral disc using a novel notochord-specific Cre mouse. To trace the fate of notochordal cells within the intervertebral disc, we derived a notochord-specific Cre mouse line by targeting the homeobox gene Noto. Expression of this gene is restricted to the node and the posterior notochord during gastrulation [embryonic day 7.5 (E7.5)-E12.5]. The Noto-cre mice were crossed with a conditional lacZ reporter for visualization of notochord fate in whole-mount embryos. We performed lineage-tracing experiments to examine the contribution of the notochord to spinal development from E12.5 through to skeletally mature mice (9 months). Fate mapping studies demonstrated that, following elongation and formation of the primitive axial skeleton, the notochord gives rise to the nucleus pulposus in fully formed intervertebral discs. Cellular localization of β-galactosidase (encoded by lacZ) and cytokeratin-8 demonstrated that both notochordal cells and chondrocyte-like nucleus pulposus cells are derived from the embryonic notochord. These studies establish conclusively that notochordal cells act as embryonic precursors to all cells found within the nucleus pulposus of the mature intervertebral disc. This suggests that notochordal cells might serve as tissue-specific progenitor cells within the disc and establishes the Noto-cre mouse as a unique tool to interrogate the contribution of notochordal cells to both intervertebral disc development and disc degeneration. PMID:22028328

Towards a more realistic population of bright spiral galaxies in cosmological simulations

NASA Astrophysics Data System (ADS)

Aumer, Michael; White, Simon D. M.; Naab, Thorsten; Scannapieco, Cecilia

2013-10-01

We present an update to the multiphase smoothed particle hydrodynamics galaxy formation code by Scannapieco et al. We include a more elaborate treatment of the production of metals, cooling rates based on individual element abundances and a scheme for the turbulent diffusion of metals. Our supernova feedback model now transfers energy to the interstellar medium (ISM) in kinetic and thermal form, and we include a prescription for the effects of radiation pressure from massive young stars on the ISM. We calibrate our new code on the well-studied Aquarius haloes and then use it to simulate a sample of 16 galaxies with halo masses between 1 × 1011 and 3 × 1012 M⊙. In general, the stellar masses of the sample agree well with the stellar mass to halo mass relation inferred from abundance matching techniques for redshifts z = 0-4. There is however a tendency to overproduce stars at z > 4 and to underproduce them at z < 0.5 in the least massive haloes. Overly high star formation rates (SFRs) at z < 1 for the most massive haloes are likely connected to the lack of active galactic nuclei feedback in our model. The simulated sample also shows reasonable agreement with observed SFRs, sizes, gas fractions and gas-phase metallicities at z = 0-3. Remaining discrepancies can be connected to deviations from predictions for star formation histories from abundance matching. At z = 0, the model galaxies show realistic morphologies, stellar surface density profiles, circular velocity curves and stellar metallicities, but overly flat metallicity gradients. 15 out of 16 of our galaxies contain disc components with kinematic disc fraction ranging between 15 and 65 per cent. The disc fraction depends on the time of the last destructive merger or misaligned infall event. Considering the remaining shortcomings of our simulations we conclude that even higher kinematic disc fractions may be possible for Λ cold dark matter haloes with quiet merger histories, such as the Aquarius haloes.

[Experimental study of restiffening of the rigor mortis].

PubMed

Wang, X; Li, M; Liao, Z G; Yi, X F; Peng, X M

2001-11-01

To observe changes of the length of sarcomere of rat when restiffening. We measured the length of sarcomere of quadriceps in 40 rats in different condition by scanning electron microscope. The length of sarcomere of rigor mortis without destroy is obviously shorter than that of restiffening. The length of sarcomere is negatively correlative to the intensity of rigor mortis. Measuring the length of sarcomere can determine the intensity of rigor mortis and provide evidence for estimation of time since death.

Report: Phytochemical screening and antimicrobial activities of red silk cotton tree (Bombax ceiba L.).

PubMed

Shah, Syed Sadaqat; Shah, Syed Salim; Iqbal, Arshad; Ahmed, Sajjad; Khan, Wisal Muhammad; Hussain, Saddam; Li, Zhijian

2018-05-01

The present study was conducted to investigate the phytochemical screening and antimicrobial activities of stem bark of Bombax ceiba L. The methanol extract was subjected to qualitative phytochemical screening using standard procedures. The results indicated the presence of alkaloids, tannins, glycosides, reducing sugar, saponins, phlobatanins and terpenoids. The antimicrobial activity was measured by disc diffusion method. Data revealed that Pseudomonas aeruginosa was inhibited by both methanol and ethanol extracts at the concentration of 2mg disc -1 {21.8mm (68.12%) and 21.3mm (66.56%)}. Similarly, methanol extract reduced the growth of Bacillus subtilis by 17.1mm (74.34%) at the concentration of 1 mg disc -1 . However, ethanol extract showed a good activity of 18mm (121.6%) and 20.6mm (112.5%) against Xanthomonas maltophilia at concentrations of 1 and 2 mg disc-1, respectively. Aqueous extract showed 16 mm (53.33% Z.I) against Escherichia coli at 2 mg disc -1 . Klebsiella pneumoniae was found resistant to all of the three extracts, while the growth of Candida albicans was inhibited by methanol through 16.5 mm (58.92% Z.I) at 1 mg disc -1 . The above study concluded the medicinal potential of B. ceiba.

High-frequency sarcomeric auto-oscillations induced by heating in living neonatal cardiomyocytes of the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shintani, Seine A.; Oyama, Kotaro; Fukuda, Norio, E-mail: noriof@jikei.ac.jp

2015-02-06

Highlights: • We tested the effects of infra-red laser irradiation on cardiac sarcomere dynamics. • A rise in temperature (>∼38 °C) induced high-frequency sarcomeric auto-oscillations. • These oscillations occurred with and without blockade of intracellular Ca{sup 2+} stores. • Cardiac sarcomeres can play a role as a temperature-dependent rhythm generator. - Abstract: In the present study, we investigated the effects of infra-red laser irradiation on sarcomere dynamics in living neonatal cardiomyocytes of the rat. A rapid increase in temperature to >∼38 °C induced [Ca{sup 2+}]{sub i}-independent high-frequency (∼5–10 Hz) sarcomeric auto-oscillations (Hyperthermal Sarcomeric Oscillations; HSOs). In myocytes with the intactmore » sarcoplasmic reticular functions, HSOs coexisted with [Ca{sup 2+}]{sub i}-dependent spontaneous beating in the same sarcomeres, with markedly varying frequencies (∼10 and ∼1 Hz for the former and latter, respectively). HSOs likewise occurred following blockade of the sarcoplasmic reticular functions, with the amplitude becoming larger and the frequency lower in a time-dependent manner. The present findings suggest that in the mammalian heart, sarcomeres spontaneously oscillate at higher frequencies than the sinus rhythm at temperatures slightly above the physiologically relevant levels.« less

Fully automated muscle quality assessment by Gabor filtering of second harmonic generation images

NASA Astrophysics Data System (ADS)

Paesen, Rik; Smolders, Sophie; Vega, José Manolo de Hoyos; Eijnde, Bert O.; Hansen, Dominique; Ameloot, Marcel

2016-02-01

Although structural changes on the sarcomere level of skeletal muscle are known to occur due to various pathologies, rigorous studies of the reduced sarcomere quality remain scarce. This can possibly be explained by the lack of an objective tool for analyzing and comparing sarcomere images across biological conditions. Recent developments in second harmonic generation (SHG) microscopy and increasing insight into the interpretation of sarcomere SHG intensity profiles have made SHG microscopy a valuable tool to study microstructural properties of sarcomeres. Typically, sarcomere integrity is analyzed by fitting a set of manually selected, one-dimensional SHG intensity profiles with a supramolecular SHG model. To circumvent this tedious manual selection step, we developed a fully automated image analysis procedure to map the sarcomere disorder for the entire image at once. The algorithm relies on a single-frequency wavelet-based Gabor approach and includes a newly developed normalization procedure allowing for unambiguous data interpretation. The method was validated by showing the correlation between the sarcomere disorder, quantified by the M-band size obtained from manually selected profiles, and the normalized Gabor value ranging from 0 to 1 for decreasing disorder. Finally, to elucidate the applicability of our newly developed protocol, Gabor analysis was used to study the effect of experimental autoimmune encephalomyelitis on the sarcomere regularity. We believe that the technique developed in this work holds great promise for high-throughput, unbiased, and automated image analysis to study sarcomere integrity by SHG microscopy.

Convergence of the Rogers-Ramanujan continued fraction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buslaev, V I

2003-06-30

Set q=exp(2{pi}i{tau}), where {tau} is an irrational number, and let R{sub q} be the radius of holomorphy of the Rogers-Ramanujan function G{sub q}(z)=1+{sigma}{sub n=1}{sup {infinity}}z{sup n}(q{sup n{sup 2}})/((1-q)...(1-q{sup n})). As is known, R{sub q}{<=}1 and for each {alpha} element of [0,1] there exists q=q({alpha}) such that R{sub q({alpha})}={alpha}. It is proved here that the function H{sub q}(z)=G{sub q}(z)/G{sub q}(qz) is meromorphic not only in the disc =(|z|

O-GlcNAcylation is a key modulator of skeletal muscle sarcomeric morphometry associated to modulation of protein-protein interactions.

PubMed

Lambert, Matthias; Richard, Elodie; Duban-Deweer, Sophie; Krzewinski, Frederic; Deracinois, Barbara; Dupont, Erwan; Bastide, Bruno; Cieniewski-Bernard, Caroline

2016-09-01

The sarcomere structure of skeletal muscle is determined through multiple protein-protein interactions within an intricate sarcomeric cytoskeleton network. The molecular mechanisms involved in the regulation of this sarcomeric organization, essential to muscle function, remain unclear. O-GlcNAcylation, a post-translational modification modifying several key structural proteins and previously described as a modulator of the contractile activity, was never considered to date in the sarcomeric organization. C2C12 skeletal myotubes were treated with Thiamet-G (OGA inhibitor) in order to increase the global O-GlcNAcylation level. Our data clearly showed a modulation of the O-GlcNAc level more sensitive and dynamic in the myofilament-enriched fraction than total proteome. This fine O-GlcNAc level modulation was closely related to changes of the sarcomeric morphometry. Indeed, the dark-band and M-line widths increased, while the I-band width and the sarcomere length decreased according to the myofilament O-GlcNAc level. Some structural proteins of the sarcomere such as desmin, αB-crystallin, α-actinin, moesin and filamin-C have been identified within modulated protein complexes through O-GlcNAc level variations. Their interactions seemed to be changed, especially for desmin and αB-crystallin. For the first time, our findings clearly demonstrate that O-GlcNAcylation, through dynamic regulations of the structural interactome, could be an important modulator of the sarcomeric structure and may provide new insights in the understanding of molecular mechanisms of neuromuscular diseases characterized by a disorganization of the sarcomeric structure. In the present study, we demonstrated a role of O-GlcNAcylation in the sarcomeric structure modulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Turbulent fluctuations and the excitation of Z Cam outbursts

NASA Astrophysics Data System (ADS)

Ross, Johnathan; Latter, Henrik N.

2017-09-01

Z Cam variables are a subclass of dwarf nova that lie near a global bifurcation between outbursting ('limit cycle') and non-outbursting ('standstill') states. It is believed that variations in the secondary star's mass-injection rate instigate transitions between the two regimes. In this paper, we explore an alternative trigger for these transitions: stochastic fluctuations in the disc's turbulent viscosity. We employ simple one-zone and global viscous models which, though inappropriate for detailed matching to observed light curves, clearly indicate that turbulent disc fluctuations induce outbursts when the system is sufficiently close to the global bifurcation point. While the models easily produce the observed 'outburst/dip' pairs exhibited by Z Cam and Nova-like variables, they struggle to generate long trains of outbursts. We conclude that mass transfer variability is the dominant physical process determining the overall Z Cam standstill/outburst pattern, but that viscous stochasticity provides an additional ingredient explaining some of the secondary features observed.

Reconstructing the velocity dispersion profiles from the line-of-sight kinematic data in disc galaxies

NASA Astrophysics Data System (ADS)

Marchuk, A. A.; Sotnikova, N. Y.

2017-03-01

We present a modification of the method for reconstructing the stellar velocity ellipsoid (SVE) in disc galaxies. Our version does not need any parametrization of the velocity dispersion profiles and uses only one assumption that the ratio σz/σR remains constant along the profile or along several pieces of the profile. The method was tested on two galaxies from the sample of other authors and for the first time applied to three lenticular galaxies NGC 1167, NGC 3245 and NGC 4150, as well as to one Sab galaxy NGC 338. We found that for galaxies with a high inclination (I >55° - 60°) it is difficult or rather impossible to extract the information about SVE, while for galaxies at an intermediate inclination the procedure of extracting is successful. For NGC 1167 we managed to reconstruct SVE, provided that the value of σz/σR is piecewise constant. We found σz/σR = 0.7 for the inner parts of the disc and σz/σR = 0.3 for the outskirts. We also obtained a rigid constraint on the value of the radial velocity dispersion σR for highly inclined galaxies, and tested the result using the asymmetric-drift equation, provided that the gas rotation curve is available.

Sarcomere Length and Tension Changes in Tetanized Frog Muscle Fibers after Quick Stretches and Releases

NASA Astrophysics Data System (ADS)

Sugi, Haruo; Kobayashi, Takakazu

1983-10-01

The sarcomere length changes in tetanized frog muscle fibers in response to quick fiber length changes were examined along the fiber length with a high-sensitivity laser diffraction technique. The experiments were only performed with muscle fibers in which the uniform orientation and sarcomere length of the component myofibrils were well preserved during a tetanus. When the sarcomere length changes were recorded near the fixed fiber end, the delay of the onset of sarcomere length change in response to the applied fiber length change tended to be longer than that of the onset of tension changes recorded at the fixed fiber end. The magnitude of sarcomere length changes was larger near the moving fiber end than near the fixed fiber end. In the case of quick releases, the resulting sarcomere shortening tended to outlast the fiber shortening, so that the quick tension recovery started during the sarcomere shortening. These results indicate (i) that the tension changes in response to quick fiber length changes may not give direct information about the cross-bridge properties and (ii) that the viscoelastic multisegmental nature of muscle fibers should be taken into consideration in interpreting the tension responses to quick length changes.

Percutaneous Transcatheter One-Step Mechanical Aortic Disc Valve Prosthesis Implantation: A Preliminary Feasibility Study in Swine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sochman, Jan; Peregrin, Jan H.; Rocek, Miloslav

Purpose. To evaluate the feasibility of one-step implantation of a new type of stent-based mechanical aortic disc valve prosthesis (MADVP) above and across the native aortic valve and its short-term function in swine with both functional and dysfunctional native valves. Methods. The MADVP consisted of a folding disc valve made of silicone elastomer attached to either a nitinol Z-stent (Z model) or a nitinol cross-braided stent (SX model). Implantation of 10 MADVPs (6 Z and 4 SX models) was attempted in 10 swine: 4 (2 Z and 2 SX models) with a functional native valve and 6 (4 Z andmore » 2 SX models) with aortic regurgitation induced either by intentional valve injury or by MADVP placement across the native valve. MADVP function was observed for up to 3 hr after implantation. Results. MADVP implantation was successful in 9 swine. One animal died of induced massive regurgitation prior to implantation. Four MADVPs implanted above functioning native valves exhibited good function. In 5 swine with regurgitation, MADVP implantation corrected the induced native valve dysfunction and the device's continuous good function was observed in 4 animals. One MADVP (SX model) placed across native valve gradually migrated into the left ventricle. Conclusion. The tested MADVP can be implanted above and across the native valve in a one-step procedure and can replace the function of the regurgitating native valve. Further technical development and testing are warranted, preferably with a manufactured MADVP.« less

Sarcomere mechanics in striated muscles: from molecules to sarcomeres to cells.

PubMed

Rassier, Dilson E

2017-08-01

Muscle contraction is commonly associated with the cross-bridge and sliding filament theories, which have received strong support from experiments conducted over the years in different laboratories. However, there are studies that cannot be readily explained by the theories, showing 1 ) a plateau of the force-length relation extended beyond optimal filament overlap, and forces produced at long sarcomere lengths that are higher than those predicted by the sliding filament theory; 2 ) passive forces at long sarcomere lengths that can be modulated by activation and Ca 2+ , which changes the force-length relation; and 3 ) an unexplained high force produced during and after stretch of activated muscle fibers. Some of these studies even propose "new theories of contraction." While some of these observations deserve evaluation, many of these studies present data that lack a rigorous control and experiments that cannot be repeated in other laboratories. This article reviews these issues, looking into studies that have used intact and permeabilized fibers, myofibrils, isolated sarcomeres, and half-sarcomeres. A common mechanism associated with sarcomere and half-sarcomere length nonuniformities and a Ca 2+ -induced increase in the stiffness of titin is proposed to explain observations that derive from these studies. Copyright © 2017 the American Physiological Society.

DLA Pre-Award Contracting System

DTIC Science & Technology

1993-05-01

Gulley DPSSO Bldg 33 Standards Cheryl Haines DISC-RMO Bldg 36 Lead Time Jeff Hammer DGSC-P Bldg 32 DPACS WorkloadjersonnedALT Judy Harroson DLA-Z...33 DPACS Functionality Lou JuIg DISC-RM Bldg 36 Resource Data Sandra King DLA-ZSM 3A675 Project Oversight Scotie Knott DGSC-P Bldg 33 Post Award Dave

The Effect of the Wooden Breast Myopathy on Sarcomere Structure and Organization.

PubMed

Velleman, Sandra G; Clark, Daniel L; Tonniges, Jeffrey R

2018-03-01

The wooden breast (WB) has been classically identified by the phenotypic presence of a wood-like pectoralis major (p. major) muscle. The WB-affected p. major muscle is characterized by necrotic muscle fibers and the replacement of muscle with connective tissue, water, and fat. The objective of the current study was to determine the effect of the WB myopathy on sarcomere organization by transmission electron microscopy. Sarcomere structure and organization were examined in two broiler lines with a high incidence of WB (Lines A and B) and another broiler line without WB (Line C). Affected muscle had an increase in smaller myofibers with diameters of 20 μm or less. Sarcomere organization decreased with fiber diameter in both Lines A and B. The structure and organization of sarcomeres in Line C were similar to WB-unaffected muscle in Lines A and B. Taken together, these data demonstrate that the WB myopathy detrimentally affects sarcomere organization in a broiler line-specific manner. Disorganization of sarcomere structure will affect the function of the p. major muscle as well as meat quality.

X-ray detection of warm ionized matter in the Galactic halo

NASA Astrophysics Data System (ADS)

Nicastro, F.; Senatore, F.; Gupta, A.; Guainazzi, M.; Mathur, S.; Krongold, Y.; Elvis, M.; Piro, L.

2016-03-01

We report on a systematic investigation of the cold and mildly ionized gaseous baryonic metal components of our Galaxy, through the analysis of high-resolution Chandra and XMM-Newton spectra of two samples of Galactic and extragalactic sources. The comparison between lines of sight towards sources located in the disc of our Galaxy and extragalactic sources allows us for the first time to clearly distinguish between gaseous metal components in the disc and halo of our Galaxy. We find that a warm ionized metal medium (WIMM) permeates a large volume above and below the Galaxy's disc, perhaps up to the circum-galactic space. This halo WIMM imprints virtually the totality of the O I and O II absorption seen in the spectra of our extragalactic targets, has a temperature of T_{WIMM}^{Halo}=2900 ± 900 K, a density < n_H > _{WIMM}^{Halo} = 0.023 ± 0.009 cm-3 and a metallicity Z_{WIMM}^{Halo} = (0.4 ± 0.1) Z⊙. Consistently with previous works, we also confirm that the disc of the Galaxy contains at least two distinct gaseous metal components, one cold and neutral (the CNMM: cold neutral metal medium) and one warm and mildly ionized, with the same temperature of the halo WIMM, but higher density (< n_H > _{WIMM}^{Disc} = 0.09 ± 0.03 cm-3) and metallicity (Z_{WIMM}^{Disc} = 0.8 ± 0.1 Z⊙). By adopting a simple disc+sphere geometry for the Galaxy, we estimate masses of the CNMM and the total (disc + halo) WIMM of MCNMM ≲ 8 × 108 M⊙ and MWIMM ≃ 8.2 × 109 M⊙.

Faint AGN in z ≳ 6 Lyman-break galaxies powered by cold accretion and rapid angular momentum transport

NASA Astrophysics Data System (ADS)

Muñoz, Joseph A.; Furlanetto, Steven

2012-11-01

We develop a radiation pressure-balanced model for the interstellar medium of high-redshift galaxies that describes many facets of galaxy formation at z ≳ 6, including star formation rates and distributions and gas accretion on to central black holes. We first show that the vertical gravitational force in the disc of such a model is dominated by the disc self-gravity supported by the radiation pressure of ionizing starlight on gas. Constraining our model to reproduce the UV luminosity function of Lyman-break galaxies (LBGs), we limit the available parameter space to wind mass-loading factors one to four times the canonical value for momentum-driven winds. We then focus our study by exploring the effects of different angular momentum transport mechanisms in the galactic disc and find that accretion driven by gravitational torques, such as from linear spiral waves or non-linear orbit crossings, can build up black hole masses by z = 6 consistent with the canonical M-σ relation with a duty cycle of unity, while accretion mediated by a local viscosity such as in an α-disc results in negligible black hole (BH) accretion. Both gravitational torque models produce X-ray emission from active galactic nuclei (AGN) in high-redshift LBGs in excess of the estimated contribution from high-mass X-ray binaries. Using a recent analysis of deep Chandra observations by Cowie et al., we can already begin to rule out the most extreme regions of our parameter space: the inflow velocity of gas through the disc must either be less than one per cent of the disc circular velocity or the X-ray luminosity of the AGN must be substantially obscured. Moderately deeper future observations or larger sample sizes will be able to probe the more reasonable range of angular momentum transport models and obscuring geometries.

Stretching of a polymer chain anchored to a surface: the massive field theory approach

NASA Astrophysics Data System (ADS)

Usatenko, Zoryana

2014-09-01

Taking into account the well-known correspondence between the field theoretical φ4 O(n)-vector model in the limit n → 0 and the behaviour of long-flexible polymer chains, the investigation of stretching of an ideal and a real polymer chain with excluded volume interactions in a good solvent anchored to repulsive and inert surfaces is performed. The calculations of the average stretching force which arises when the free end of a polymer chain moves away from a repulsive or inert surface are performed up to one-loop order of the massive field theory approach in fixed space dimensions d = 3. The analysis of the obtained results indicates that the average stretching force for a real polymer chain anchored to a repulsive surface demonstrates different behaviour for the cases \\tilde{z}\\ll1 and \\tilde{z}\\gg1 , where \\tilde{z}=z^\\prime/Rz . Besides, the results obtained in the framework of the massive field theory approach are in good agreement with previous theoretical results for an ideal polymer chain and results of a density functional theory approach for the region of small applied forces when deformation of a polymer chain in the direction of the applied force is not bigger than the linear extension of a polymer chain in this direction. The better agreement between these two methods is observed in the case where the number of monomers increases and the polymer chain becomes longer.

Truncated disc surface brightness profiles produced by flares

NASA Astrophysics Data System (ADS)

Borlaff, Alejandro; Eliche-Moral, M. Carmen; Beckman, John; Font, Joan

2017-03-01

Previous studies have discarded that flares in galactic discs may explain the truncation that are frequently observed in highly-inclined galaxies (Kregel et al. 2002). However, no study has systematically analysed this hypothesis using realistic models for the disc, the flare and the bulge. We derive edge-on and face-on surface brightness profiles for a series of realistic galaxy models with flared discs that sample a wide range of structural and photometric parameters across the Hubble Sequence, accordingly to observations. The surface brightness profile for each galaxy model has been simulated for edge-on and face-on views to find out whether the flared disc produces a significant truncation in the disc in the edge-on view compared to the face-on view or not. In order to simulate realistic images of disc galaxies, we have considered the observational distribution of the photometric parameters as a function of the morphological type for three mass bins (10 < log10(M/M ⊙) < 10.7, 10.7 < log10(M/M ⊙) < 11 and log10(M/M ⊙) > 11), and four morphological type bins (S0-Sa, Sb-Sbc, Sc-Scd and Sd-Sdm). For each mass bin, we have restricted the photometric and structural parameters of each modelled galaxy to their characteristic observational ranges (μ0, disc, μeff, bulge, B/T, M abs, r eff, n bulge, h R, disc) and the flare in the disc (h z, disc/h R, disc, ∂h z, disc/∂R, see de Grijs & Peletier 1997, Graham 2001, López-Corredoira et al. 2002, Yoachim & Dalcanton 2006, Bizyaev et al. 2014, Mosenkov et al. 2015). Contrary to previous claims, the simulations show that realistic flared disks can be responsible for the truncations observed in many edge-on systems, preserving the profile of the non-flared analogous model in face-on view. These breaks reproduce the properties of the weak-to-intermediate breaks observed in many real Type-II galaxies in the diagram relating the radial location of the break (R brkII) in units of the inner disk scale-length with the break strength S (Laine et al. 2014). Radial variation of the scale-height of the disc (flaring) can explain the existence of many breaks in edge-on galaxies, especially of those with low break strengths 10\\frac{ho}{hi} \\sim \\ [-0.3,-0.1]$ .

Intervertebral disc regeneration or repair with biomaterials and stem cell therapy--feasible or fiction?

PubMed

Chan, Samantha C W; Gantenbein-Ritter, Benjamin

2012-05-31

The "gold standard" for treatment of intervertebral disc herniations and degenerated discs is still spinal fusion, corresponding to the saying "no disc - no pain". Mechanical prostheses, which are currently implanted, do only have medium outcome success and have relatively high re-operation rates. Here, we discuss some of the biological intervertebral disc replacement approaches, which can be subdivided into at least two classes in accordance to the two different tissue types, the nucleus pulposus (NP) and the annulus fibrosus (AF). On the side of NP replacement hydrogels have been extensively tested in vitro and in vivo. However, these gels are usually a trade-off between cell biocompatibility and load-bearing capacity, hydrogels which fulfill both are still lacking. On the side of AF repair much less is known and the question of the anchoring of implants is still to be addressed. New hope for cell therapy comes from developmental biology investigations on the existence of intervertebral disc progenitor cells, which would be an ideal cell source for cell therapy. Also notochordal cells (remnants of the embryonic notochord) have been recently pushed back into focus since these cells have regenerative potential and can activate disc cells. Growth factor treatment and molecular therapies could be less problematic. The biological solutions for NP and AF replacement are still more fiction than fact. However, tissue engineering just scratched the tip of the iceberg, more satisfying solutions are yet to be added to the biomedical pipeline.

Sarcomere length influences postmortem proteolysis of excised bovine semitendinosus muscle.

PubMed

Weaver, A D; Bowker, B C; Gerrard, D E

2008-08-01

The interaction between sarcomere length and postmortem proteolysis as related to meat tenderness is not clear. The extent of thick and thin filament overlap alters actomyosin binding and may alter substrate availability during aging-induced tenderization. The objective of this study was to determine the influence of sarcomere length on proteolytic degradation in beef. Strips from bovine semitendinosus were either stretched 40% and restrained or allowed to shorten unrestrained in an ice bath. After rigor completion, 0.6-cm cross sections were fabricated and were randomly assigned to 2, 4, 7, or 10 d of aging treatments. Myofibrils were isolated for sarcomere length determination. Samples were collected and frozen for shear force analysis, and muscle proteins were extracted for SDS-PAGE and Western blotting analyses to determine troponin T (TnT) proteolysis. Sarcomere length was greater (P < 0.01) in stretched muscle samples compared with shortened samples (2.57 vs. 1.43 microm, respectively). Correspondingly, shear force values were greater (P < 0.05) in shortened samples than stretched samples. Western blots revealed the presence of 3 major intact TnT bands that diminished with time postmortem and 4 bands (TnT degradation products) that accumulated during postmortem storage. Quantification of intact TnT showed increased (P < 0.05) proteolysis at 4 and 7 d postmortem in samples with long sarcomeres. By 10 d, only traces of the greatest molecular weight intact TnT band were evident in both shortened and stretched samples, suggesting this TnT band may be more susceptible to proteolysis than other intact TnT bands. Degradation products of TnT appeared earlier postmortem in samples with long sarcomeres. The 30-kDa TnT fragment appeared after 7 d of postmortem storage in samples with long sarcomeres but not until 10 d in muscle containing short sarcomeres. Collectively, these data show that postmortem TnT proteolysis is sarcomere length-dependent and suggest that thick and thin filament overlap may influence the postmortem aging process in beef.

Effects of ionizing radiation on the enzyme activities and ultrastructural changes of poultry

NASA Astrophysics Data System (ADS)

Hwang, H.-I.; Hau, L.-B.

1995-02-01

Enzyme-catalyzed changes are generally recognized as one of the major reasons for fresh meat deterioration after irradiation. In this study, the effects of ionizing radiation and storage on the enzyme activities of poultry as well as the ultrastructural change of muscle were evaluated. When chicken breasts were irradiated at 4°C and -20°C, both Ca 2+-dependent protease and cathepsin D showed some degree of resistance to irradiation. The activities of those two enzymes decreased with the increase of irradiation doses. During storage, Ca 2+-dependent proteases showed a marked decrease in activity. On the other hand, the cathepsin D activity was not significantly changed at either 4°C or -20°C after 20 days. Transmission electron microscope examination showed no structural changes of the myofibrils with a radiation dose of up to 10 kGy at either 4°C or -20°C. Freezing protected the irradiated chicken breasts from autolytic enzymes damage during storage. In contrast, considerable sarcomere degradation occurred in Z-line for irradiated samples when stored at 4°C for 20 days. The action of the proteolytic enzymes may have been responsible for the sarcomere degradation in irradiated chicken breasts.

Morphometric, quantitative, and three-dimensional analysis of the heart muscle fibers of old rats: transmission electron microscopy and high-resolution scanning electron microscopy methods.

PubMed

Cury, Diego Pulzatto; Dias, Fernando José; Sosthenes, Marcia Consentino Kronka; Dos Santos Haemmerle, Carlos Alexandre; Ogawa, Koichi; Da Silva, Marcelo Cavenaghi Pereira; Mardegan Issa, João Paulo; Iyomasa, Mamie Mizusaki; Watanabe, Ii-Sei

2013-02-01

This research investigated the morphological, morphometric, and ultrastructural cardiomyocyte characteristics of male Wistar rats at 18 months of age. The animals were euthanized using an overdose of anesthesia (ketamine and xylazine, 150/10 mg/kg) and perfused transcardially, after which samples were collected for light microscopy, transmission electron microscopy, and high-resolution scanning electron microscopy. The results showed that cardiomyocyte arrangement was disposed parallel between the mitochondria and the A-, I-, and H-bands and their M- and Z-lines from the sarcomere. The sarcomere junction areas had intercalated disks, a specific structure of heart muscle. The ultrastructural analysis revealed several mitochondria of various sizes and shapes intermingled between the blood capillaries and their endothelial cells; some red cells inside vessels are noted. The muscle cell sarcolemma could be observed associated with the described structures. The cardiomyocytes of old rats presented an average sarcomere length of 2.071 ± 0.09 μm, a mitochondrial volume density (Vv) of 0.3383, a mitochondrial average area of 0.537 ± 0.278 μm(2), a mitochondrial average length of 1.024 ± 0.352 μm, an average mitochondrial cristae thickness of 0.038 ± 0.09 μm and a ratio of mitochondrial greater length/lesser length of 1.929 ± 0.965. Of the observed mitochondrial shapes, 23.4% were rounded, 45.3% were elongated, and 31.1% had irregular profiles. In this study, we analyzed the morphology and morphometry of cardiomyocytes in old rats, focusing on mitochondria. These data are important for researchers who focus the changes in cardiac tissue, especially changes owing to pathologies and drug administration that may or may not be correlated with aging. Copyright © 2012 Wiley Periodicals, Inc.

In Vivo Imaging of Human Sarcomere Twitch Dynamics in Individual Motor Units

PubMed Central

Sanchez, Gabriel N.; Sinha, Supriyo; Liske, Holly; Chen, Xuefeng; Nguyen, Viet; Delp, Scott L.; Schnitzer, Mark J.

2017-01-01

SUMMARY Motor units comprise a pre-synaptic motor neuron and multiple post-synaptic muscle fibers. Many movement disorders disrupt motor unit contractile dynamics and the structure of sarcomeres, skeletal muscle’s contractile units. Despite the motor unit’s centrality to neuromuscular physiology, no extant technology can image sarcomere twitch dynamics in live humans. We created a wearable microscope equipped with a microendoscope for minimally invasive observation of sarcomere lengths and contractile dynamics in any major skeletal muscle. By electrically stimulating twitches via the microendoscope and visualizing the sarcomere displacements, we monitored single motor unit contractions in soleus and vastus lateralis muscles of healthy individuals. Control experiments verified that these evoked twitches involved neuromuscular transmission and faithfully reported muscle force generation. In post-stroke patients with spasticity of the biceps brachii, we found involuntary microscopic contractions and sarcomere length abnormalities. The wearable microscope facilitates exploration of many basic and disease-related neuromuscular phenomena never visualized before in live humans. PMID:26687220

In Vivo Imaging of Human Sarcomere Twitch Dynamics in Individual Motor Units.

PubMed

Sanchez, Gabriel N; Sinha, Supriyo; Liske, Holly; Chen, Xuefeng; Nguyen, Viet; Delp, Scott L; Schnitzer, Mark J

2015-12-16

Motor units comprise a pre-synaptic motor neuron and multiple post-synaptic muscle fibers. Many movement disorders disrupt motor unit contractile dynamics and the structure of sarcomeres, skeletal muscle's contractile units. Despite the motor unit's centrality to neuromuscular physiology, no extant technology can image sarcomere twitch dynamics in live humans. We created a wearable microscope equipped with a microendoscope for minimally invasive observation of sarcomere lengths and contractile dynamics in any major skeletal muscle. By electrically stimulating twitches via the microendoscope and visualizing the sarcomere displacements, we monitored single motor unit contractions in soleus and vastus lateralis muscles of healthy individuals. Control experiments verified that these evoked twitches involved neuromuscular transmission and faithfully reported muscle force generation. In post-stroke patients with spasticity of the biceps brachii, we found involuntary microscopic contractions and sarcomere length abnormalities. The wearable microscope facilitates exploration of many basic and disease-related neuromuscular phenomena never visualized before in live humans. Copyright © 2015 Elsevier Inc. All rights reserved.

The age-velocity dispersion relation of the Galactic discs from LAMOST-Gaia data

NASA Astrophysics Data System (ADS)

Yu, Jincheng; Liu, Chao

2018-03-01

We present the age-velocity dispersion relation (AVR) in three dimensions in the solar neighbourhood using 3564 commonly observed sub-giant/red giant branch stars selected from The Large Sky Area Multi-Object Fiber Spectroscopic Telescope, which gives the age and radial velocity, and Gaia, which measures the distance and proper motion. The stars are separated into metal-poor ([Fe/H] < -0.2 dex and metal-rich ([Fe/H] > -0.2 dex) groups, so that the metal-rich stars are mostly α-poor, while the metal-poor group are mostly contributed by α-enhanced stars. Thus, the old and metal-poor stars likely belong to the chemically defined thick disc population, while the metal-rich sample is dominated by the thin disc. The AVR for the metal-poor sample shows an abrupt increase at ≳7 Gyr, which is contributed by the thick disc component. On the other hand, most of the thin disc stars with [Fe/H] > -0.2 dex display a power-law-like AVR with indices of about 0.3-0.4 and 0.5 for the in-plane and vertical dispersions, respectively. This is consistent with the scenario that the disc is gradually heated by the spiral arms and/or the giant molecular clouds. Moreover, the older thin disc stars (>7 Gyr) have a rounder velocity ellipsoid, i.e. σϕ/σz is close to 1.0, probably due to the more efficient heating in vertical direction. Particularly for the old metal-poor sample located with |z| > 270 pc, the vertical dispersion is even larger than its azimuthal counterpart. Finally, the vertex deviations and the tilt angles are plausibly around zero with large uncertainties.

Transgenic Muscle-Specific Nor-1 Expression Regulates Multiple Pathways That Effect Adiposity, Metabolism, and Endurance

PubMed Central

Pearen, Michael A.; Goode, Joel M.; Fitzsimmons, Rebecca L.; Eriksson, Natalie A.; Thomas, Gethin P.; Cowin, Gary J.; Wang, S.-C. Mary; Tuong, Zewen K.

2013-01-01

The mRNA encoding Nor-1/NR4A3 is rapidly and strikingly induced by β2-adrenergic signaling in glycolytic and oxidative skeletal muscle. In skeletal muscle cells, Nor-1 expression is important for the regulation of oxidative metabolism. Transgenic skeletal muscle-specific expression of activated Nor-1 resulted in the acquisition of an endurance phenotype, an increase in type IIA/X oxidative muscle fibers, and increased numbers of mitochondria. In the current study, we used dual-energy x-ray absorptiometry and magnetic resonance imaging analysis to demonstrate decreased adiposity in transgenic (Tg) Nor-1 mice relative to that in wild-type littermates. Furthermore, the Tg-Nor-1 mice were resistant to diet-induced weight gain and maintained fasting glucose at normoglycemic levels. Expression profiling and RT-quantitative PCR analysis revealed significant increases in genes involved in glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, fatty acid oxidation, and glycogen synthesis, in concordance with the lean phenotype. Moreover, expression profiling identified several Z-disc and sarcomeric binding proteins that modulate fiber type phenotype and endurance, eg, α-actinin-3. In addition, we demonstrated that the Tg-Nor-1 mouse line has significantly higher glycogen content in skeletal muscle relative to that in wild-type littermates. Finally, we identified a decreased NAD+/NADH ratio with a concordant increase in peroxisome proliferator-activated receptor γ coactivator-1α1 protein/mRNA expression. Increased NADH was associated with an induction of the genes involved in the malate-aspartate shuttle and a decrease in the glycerol 3-phosphate shuttle, which maximizes aerobic ATP production. In conclusion, skeletal muscle-specific Nor-1 expression regulates genes and pathways that regulate adiposity, muscle fiber type metabolic capacity, and endurance. PMID:24065705

Galactoseismology and the local density of dark matter

DOE PAGES

Banik, Nilanjan; Widrow, Lawrence M.; Dodelson, Scott

2016-10-08

Here, we model vertical breathing mode perturbations in the Milky Way's stellar disc and study their effects on estimates of the local dark matter density, surface density, and vertical force. Evidence for these perturbations, which involve compression and expansion of the Galactic disc perpendicular to its midplane, come from the SEGUE, RAVE, and LAMOST surveys. We show that their existence may lead to systematic errors ofmore » $$10\\%$$ or greater in the vertical force $$K_z(z)$$ at $$|z|=1.1\\,{\\rm kpc}$$. These errors translate to $$\\gtrsim 25\\%$$ errors in estimates of the local dark matter density. Using different mono-abundant subpopulations as tracers offers a way out: if the inferences from all tracers in the Gaia era agree, then the dark matter determination will be robust. Disagreement in the inferences from different tracers will signal the breakdown of the unperturbed model and perhaps provide the means for determining the nature of the perturbation.« less

The sustainable growth of the first black holes

NASA Astrophysics Data System (ADS)

Pezzulli, Edwige; Volonteri, Marta; Schneider, Raffaella; Valiante, Rosa

2017-10-01

Super-Eddington accretion has been suggested as a possible formation pathway of 109 M⊙ supermassive black holes (SMBHs) 800 Myr after the big bang. However, stellar feedback from BH seed progenitors and winds from BH accretion discs may decrease BH accretion rates. In this work, we study the impact of these physical processes on the formation of z ˜ 6 quasar, including new physical prescriptions in the cosmological, data-constrained semi-analytic model GAMETE/QSOdust. We find that the feedback produced by the first stellar progenitors on the surrounding does not play a relevant role in preventing SMBHs formation. In order to grow the z ≳ 6 SMBHs, the accreted gas must efficiently lose angular momentum. Moreover, disc winds, easily originated in super-Eddington accretion regime, can strongly reduce duty cycles. This produces a decrease in the active fraction among the progenitors of z ˜ 6 bright quasars, reducing the probability to observe them.

Nebulette interacts with filamin C.

PubMed

Holmes, William B; Moncman, Carole L

2008-02-01

The actin-binding proteins, nebulette, and nebulin, are comprised of a four-domain layout containing an acidic N-terminal region, a repeat domain, a serine-rich-linker region, and a Src homology-3 domain. Both proteins contain homologous N-terminal regions that are predicted to be in different environments within the sarcomere. The nebulin acidic N-terminal region is found at the distal ends of the thin filaments. Nebulette, however, is predicted to extend 150 nm from the center of the Z-line. To dissect out the functions of the N-terminal domain of nebulette, we have performed a yeast two-hybrid screen using nebulette residues 1-86 as bait. We have identified filamin-C, ZASP-1, and tropomyosin-1 as binding partners. Characterization of the nebulette-filamin interaction indicates that filamin-C predominantly interacts with the modules. These data suggest that filamin-C, a known component of striated muscle Z-lines, interacts with nebulette modules. Copyright 2007 Wiley-Liss, Inc.

Color-size Relations of Disc Galaxies with Similar Stellar Masses

NASA Astrophysics Data System (ADS)

Fu, W.; Chang, R. X.; Shen, S. Y.; Zhang, B.

2011-01-01

To investigate the correlations between colors and sizes of disc galaxies with similar stellar masses, a sample of 7959 local face-on disc galaxies is collected from the main galaxy sample of the Seventh Data Release of Sloan Digital Sky Survey (SDSS DR7). Our results show that, under the condition that the stellar masses of disc galaxies are similar, the relation between u-r and size is weak, while g-r, r-i and r-z colors decrease with disk size. This means that the color-size relations of disc galaxies with similar stellar masses do exist, i.e., the more extended disc galaxies with similar stellar masses tend to have bluer colors. An artificial sample is constructed to confirm that this correlation is not driven by the color-stellar mass relations and size-stellar mass relation of disc galaxies. Our results suggest that the mass distribution of disk galaxies may have an important influence on their stellar formation history, i.e., the galaxies with more extended mass distribution evolve more slowly.

Characterization of muscle contraction with second harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Prent, Nicole

Muscle cells have the ability to change length and generate force due to orchestrated action of myosin nanomotors that cause sliding of actin filaments along myosin filaments in the sarcomeres, the fundamental contractile units, of myocytes. The correlated action of hundreds of sarcomeres is needed to produce the myocyte contractions. This study probes the molecular structure of the myofilaments and investigates the movement correlations between sarcomeres during contraction. In this study, second harmonic generation (SHG) microscopy is employed for imaging striated myocytes. Myosin filaments in striated myocytes inherently have a nonzero second-order susceptibility, [special characters omitted] and therefore generate efficient SHG. Employing polarization-in polarization-out (PIPO) SHG microscopy allows for the accurate determination of the characteristic ratio, [special characters omitted] in birefringent myocytes, which describes the structure of the myosin filament. Analysis shows that the b value at the centre of the myosin filament, where the nonlinear dipoles are better aligned, is slightly lower than the value at the edges of the filament, where there is more disorder in orientation of the nonlinear dipoles from the myosin heads. Forced stretching of myocytes resulted in an SHG intensity increase with the elongation of the sarcomere. SHG microscopy captured individual sarcomeres during contraction, allowing for the measurement of sarcomere length (SL) and SHG intensity (SI) fluctuations. The fluctuations also revealed higher SHG intensity in elongated sarcomeres. The sarcomere synchronization model (SSM) for contracting and quiescent myocytes was developed, and experimentally verified for three cases (isolated cardiomyocyte, embryonic chicken cardiomyocyte, and larva myocyte). During contraction, the action of SLs and SIs between neighbouring sarcomeres partially correlated, whereas in quiescent myocytes the SLs show an anti-correlation and the SIs have no correlations. The characteristic correlation coefficients and amplitudes were obtained for each case, allowing for the characterization of the synchronization of sarcomere movement during muscle contraction. These investigations constitute the basis for studying the structure and physiology of muscle cell contractions with polarization SHG microscopy. Live dynamic imaging of myocytes is applicable for contractility research, drug discovery, and as a diagnostic tool for monitoring muscular diseases.

Do galaxy global relationships emerge from local ones? The SDSS IV MaNGA surface mass density-metallicity relation

NASA Astrophysics Data System (ADS)

Barrera-Ballesteros, Jorge K.; Heckman, Timothy M.; Zhu, Guangtun B.; Zakamska, Nadia L.; Sánchez, Sebastian F.; Law, David; Wake, David; Green, Jenny E.; Bizyaev, Dmitry; Oravetz, Daniel; Simmons, Audrey; Malanushenko, Elena; Pan, Kaike; Roman Lopes, Alexandre; Lane, Richard R.

2016-12-01

We present the stellar surface mass density versus gas metallicity (Σ*-Z) relation for more than 500 000 spatially resolved star-forming resolution elements (spaxels) from a sample of 653 disc galaxies included in the SDSS IV MaNGA survey. We find a tight relation between these local properties, with higher metallicities as the surface density increases. This relation extends over three orders of magnitude in the surface mass density and a factor of 4 in metallicity. We show that this local relationship can simultaneously reproduce two well-known properties of disc galaxies: their global mass-metallicity relationship and their radial metallicity gradients. We also find that the Σ*-Z relation is largely independent of the galaxy's total stellar mass and specific star formation rate (sSFR), except at low stellar mass and high sSFR. These results suggest that in the present-day universe local properties play a key role in determining the gas-phase metallicity in typical disc galaxies.

Alternative pre-rigor foreshank positioning can improve beef shoulder muscle tenderness.

PubMed

Grayson, A L; Lawrence, T E

2013-09-01

Thirty beef carcasses were harvested and the foreshank of each side was independently positioned (cranial, natural, parallel, or caudal) 1h post-mortem to determine the effect of foreshank angle at rigor mortis on the sarcomere length and tenderness of six beef shoulder muscles. The infraspinatus (IS), pectoralis profundus (PP), serratus ventralis (SV), supraspinatus (SS), teres major (TM) and triceps brachii (TB) were excised 48 h post-mortem for Warner-Bratzler shear force (WBSF) and sarcomere length evaluations. All muscles except the SS had altered (P<0.05) sarcomere lengths between positions; the cranial position resulted in the longest sarcomeres for the SV and TB muscles whilst the natural position had longer sarcomeres for the PP and TM muscles. The SV from the cranial position had lower (P<0.05) shear than the caudal position and TB from the natural position had lower (P<0.05) shear than the parallel or caudal positions. Sarcomere length was moderately correlated (r=-0.63; P<0.01) to shear force. Copyright © 2013 Elsevier Ltd. All rights reserved.

Plakins in striated muscle.

PubMed

Boyer, Justin G; Bernstein, Marija A; Boudreau-Larivière, Céline

2010-03-01

Striated muscle cells contain numerous architectural proteins that contribute to the function of muscle as generators of mechanical force. Among these proteins are crosslinkers belonging to the plakin family, namely plectin, microtubule-actin crosslinking factor (ACF7/MACF1), bullous pemphigoid antigen 1 (Bpag1/dystonin), and desmoplakin. These plakin family members, in particular plectin and Bpag1/dystonin, exist as several isoforms. The domain organization of these plakin variants dictates their subcellular location and the proteins with which they interact. Several studies suggest that plakins exert unique functions within various compartments of the muscle cell including the sarcolemma, the sarcomere, both neuromuscular and myotendinous junctions in skeletal muscle, and the intercalated discs in cardiac muscle. Plakins may also regulate the cellular placement and function of specific organelles, notably the nucleus, mitochondria, Golgi apparatus, and sarcoplasmic reticulum. Here we review and summarize our current knowledge of the function of plakins in striated muscle cells.

Electronic Imaging

DTIC Science & Technology

1991-11-01

Tilted Rough Disc," Donald J. Schertler and Nicholas George "Image Deblurring for Multiple-Point Impulse Responses," Bryan J. Stossel and Nicholas George...Rough Disc Donald J. Schertler Nicholas George Image Deblurring for Multiple-Point Impulse Bryan J. Stossel Responses Nicholas George z 0 zw V) w LU 0...number of impulses present in the degradation. IMAGE DEBLURRING FOR MULTIPLE-POINT IMPULSE RESPONSESt Bryan J. Stossel Nicholas George Institute of Optics

The Diversity of Assembly Histories Leading to Disc Galaxy Formation in a ΛCDM Model

NASA Astrophysics Data System (ADS)

Font, Andreea S.; McCarthy, Ian G.; Le Brun, Amandine M. C.; Crain, Robert A.; Kelvin, Lee S.

2017-11-01

Disc galaxies forming in a LambdaCDM cosmology often experience violent mergers. The fact that disc galaxies are ubiquitous suggests that quiescent histories are not necessary. Modern cosmological simulations can now obtain realistic populations of disc galaxies, but it is still unclear how discs manage to survive massive mergers. Here we use a suite of hydrodynamical cosmological simulations to elucidate the fate of discs encountering massive mergers. We follow the changes in the post-merger disc-to-total ratios (D/T) of simulated galaxies and examine the relations between their present-day morphology, assembly history and gas fractions. We find that approximately half of present-day disc galaxies underwent at least one merger with a satellite more massive the host's stellar component and a third had mergers with satellites three times as massive. These mergers lead to a sharp, but often temporary, decrease in the D/T of the hosts, implying that discs are usually disrupted but then quickly re-grow. To do so, high cold gas fractions are required post-merger, as well as a relatively quiescent recent history (over a few Gyrs before z = 0). Our results show that discs can form via diverse merger pathways and that quiescent histories are not the dominant mode of disc formation.

Collective effects of torsion in FtsZ filaments

NASA Astrophysics Data System (ADS)

González de Prado Salas, Pablo; Tarazona, Pedro

2016-04-01

Recent evidence points to the presence of torsion in FtsZ bonds. In addition, experiments with FtsZ mutants on surfaces resulted in new aggregates that cannot be explained by older models for FtsZ dynamics. We use an interaction model for FtsZ derived from molecular dynamics simulations and expand a fine-grained lattice model used to describe FtsZ aggregates on a surface. This new model includes different anchoring angles for the monomers and allows bond twist, two ingredients that oppose each other resulting in a more dynamic and interesting system. We study the role and importance of these conflicting elements and how the aggregates are characterized by the different interaction parameters.

Ultrastructural studies of the mitochondriae in the striated muscles of birds with regard to experimental hypokinesis

NASA Technical Reports Server (NTRS)

Belak, M.; Kocisova, J.; Boda, K.

1980-01-01

Electron microscopic studies were carried out on the mitochrondria of the transversely striated muscles with regard to experimental hypokinesia. As compared to the central group the mitochondria of m. pectoralis thoracicus and the m. iliotibialis posterior in hypokinetic birds reveal marked changes. In filamentous and ovoid mitochondria, vacuoles can be observed which in some cases produced larger light formations with following disappearance of the cristae and destruction of mitochondria. Fat particles located at the poles of the altered mitochondria, sporadically occurring also laterally, presented another finding. The Z-lines of the sarcomere did not form a continuous line, but were somewhat shifted.

The use of roving discs and orthogonal natural frequencies for crack identification and location in rotors

NASA Astrophysics Data System (ADS)

Haji, Zyad N.; Olutunde Oyadiji, S.

2014-11-01

A variety of approaches that have been developed for the identification and localisation of cracks in a rotor system, which exploit natural frequencies, require a finite element model to obtain the natural frequencies of the intact rotor as baseline data. In fact, such approaches can give erroneous results about the location and depth of a crack if an inaccurate finite element model is used to represent an uncracked model. A new approach for the identification and localisation of cracks in rotor systems, which does not require the use of the natural frequencies of an intact rotor as a baseline data, is presented in this paper. The approach, named orthogonal natural frequencies (ONFs), is based only on the natural frequencies of the non-rotating cracked rotor in the two lateral bending vibration x-z and y-z planes. The approach uses the cracked natural frequencies in the horizontal x-z plane as the reference data instead of the intact natural frequencies. Also, a roving disc is traversed along the rotor in order to enhance the dynamics of the rotor at the cracked locations. At each spatial location of the roving disc, the two ONFs of the rotor-disc system are determined from which the corresponding ONF ratio is computed. The ONF ratios are normalised by the maximum ONF ratio to obtain normalised orthogonal natural frequency curves (NONFCs). The non-rotating cracked rotor is simulated by the finite element method using the Bernoulli-Euler beam theory. The unique characteristics of the proposed approach are the sharp, notched peaks at the crack locations but rounded peaks at non-cracked locations. These features facilitate the unambiguous identification and locations of cracks in rotors. The effects of crack depth, crack location, and mass of a roving disc are investigated. The results show that the proposed method has a great potential in the identification and localisation of cracks in a non-rotating cracked rotor.

Load-dependent regulation of neuromuscular system

NASA Technical Reports Server (NTRS)

Ohira, Yoshinobu; Kawano, Fuminori; Stevens, James L.; Wang, Xiao D.; Ishihara, Akihiko

2004-01-01

Roles of gravitational loading, sarcomere length, and/or tension development on the electromyogram (EMG) of soleus and afferent neurogram recorded at the L5 segmental level of spinal cord were investigated during parabolic flight of a jet airplane or hindlimb suspension in conscious rats. Both EMG and neurogram levels were increased when the gravity levels were elevated from 1-G to 2-G during the parabolic flight. They were decreased when the hindlimbs were unloaded by exposure to actual microgravity or by suspension. These phenomena were related to passive shortening of muscle fibers and/or sarcomeres. Unloading-related decrease in sarcomere length was greater at the central rather than the proximal and distal regions of fibers. These activities and tension development were not detected when the mean sarcomere length was less than 2.03 micrometers. It is suggested that load-dependent regulation of neuromuscular system is related to the tension development which is influenced by sarcomere length.

Ultrastructure of the surface structures and haptor of Empleurosoma pyriforme (Ancyrocephalinae; Monopisthocotylea: Monogenea) from the gills of the teleost fish Therapon jarbua.

PubMed

Ramasamy, P; Brennan, G P

2000-02-01

Infections with Empleurosoma pyriforme occur between successive secondary gill lamellae on both sides of the primary lamella of Therapon jarbua. The haptoral disc bears two pairs of anchors and a pair of connecting transverse bars. The attachment of the parasite to the host gill causes inflammation, erosion and degeneration of the gill epithelia. The ventral anchors consist of an inner core of irregularly arranged, electron-dense fibrils and a smooth outer core of electron-lucent fibrils, whereas the surface of the dorsal anchors is ridged. Both the dorsal and the ventral anchors may be extended or withdrawn. The connecting transverse bars consist of longitudinally arranged fibrils in an electron-dense matrix, whereas the tendons consist of fibrils, supported in a less electron-dense matrix, which interconnect the anchor erector-protractor muscles and the haptor muscles. Two types of perikarya are present. The less common type contain large multivesicular bodies and small electron-dense granules and are located only in the haptor region. The second and more common perikarya are present throughout the body surface. The cytoplasmic syncytium contains numerous electron-dense granules and electron-lucent vesicles. Beneath the syncytium, unicellular epidermal gland cells contain electron-dense granules. Neurones containing numerous electron-dense vesicles are present in the haptor region. Uniciliate presumed sensory receptors are distributed over the body surface. Groups of ciliated sensory structures are present in the forebody. Ciliated and non-ciliated presumed sensory receptors are present in the sleeve cavity of the anchors, on the haptor and in the vicinity of the oral apertures.

Hand-Held Model of a Sarcomere to Illustrate the Sliding Filament Mechanism in Muscle Contraction

ERIC Educational Resources Information Center

Jittivadhna, Karnyupha; Ruenwongsa, Pintip; Panijpan, Bhinyo

2009-01-01

From our teaching of the contractile unit of the striated muscle, we have found limitations in using textbook illustrations of sarcomere structure and its related dynamic molecular physiological details. A hand-held model of a striated muscle sarcomere made from common items has thus been made by us to enhance students' understanding of the…

Muscle contraction phenotypic analysis enabled by optogenetics reveals functional relationships of sarcomere components in Caenorhabditis elegans.

PubMed

Hwang, Hyundoo; Barnes, Dawn E; Matsunaga, Yohei; Benian, Guy M; Ono, Shoichiro; Lu, Hang

2016-01-29

The sarcomere, the fundamental unit of muscle contraction, is a highly-ordered complex of hundreds of proteins. Despite decades of genetics work, the functional relationships and the roles of those sarcomeric proteins in animal behaviors remain unclear. In this paper, we demonstrate that optogenetic activation of the motor neurons that induce muscle contraction can facilitate quantitative studies of muscle kinetics in C. elegans. To increase the throughput of the study, we trapped multiple worms in parallel in a microfluidic device and illuminated for photoactivation of channelrhodopsin-2 to induce contractions in body wall muscles. Using image processing, the change in body size was quantified over time. A total of five parameters including rate constants for contraction and relaxation were extracted from the optogenetic assay as descriptors of sarcomere functions. To potentially relate the genes encoding the sarcomeric proteins functionally, a hierarchical clustering analysis was conducted on the basis of those parameters. Because it assesses physiological output different from conventional assays, this method provides a complement to the phenotypic analysis of C. elegans muscle mutants currently performed in many labs; the clusters may provide new insights and drive new hypotheses for functional relationships among the many sarcomere components.

Muscle contraction phenotypic analysis enabled by optogenetics reveals functional relationships of sarcomere components in Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Hwang, Hyundoo; Barnes, Dawn E.; Matsunaga, Yohei; Benian, Guy M.; Ono, Shoichiro; Lu, Hang

2016-01-01

The sarcomere, the fundamental unit of muscle contraction, is a highly-ordered complex of hundreds of proteins. Despite decades of genetics work, the functional relationships and the roles of those sarcomeric proteins in animal behaviors remain unclear. In this paper, we demonstrate that optogenetic activation of the motor neurons that induce muscle contraction can facilitate quantitative studies of muscle kinetics in C. elegans. To increase the throughput of the study, we trapped multiple worms in parallel in a microfluidic device and illuminated for photoactivation of channelrhodopsin-2 to induce contractions in body wall muscles. Using image processing, the change in body size was quantified over time. A total of five parameters including rate constants for contraction and relaxation were extracted from the optogenetic assay as descriptors of sarcomere functions. To potentially relate the genes encoding the sarcomeric proteins functionally, a hierarchical clustering analysis was conducted on the basis of those parameters. Because it assesses physiological output different from conventional assays, this method provides a complement to the phenotypic analysis of C. elegans muscle mutants currently performed in many labs; the clusters may provide new insights and drive new hypotheses for functional relationships among the many sarcomere components.

A catalog of polychromatic bulge-disc decompositions of ˜17.600 galaxies in CANDELS

NASA Astrophysics Data System (ADS)

Dimauro, Paola; Huertas-Company, Marc; Daddi, Emanuele; Pérez-González, Pablo G.; Bernardi, Mariangela; Barro, Guillermo; Buitrago, Fernando; Caro, Fernando; Cattaneo, Andrea; Dominguez-Sánchez, Helena; Faber, Sandra M.; Häußler, Boris; Kocevski, Dale D.; Koekemoer, Anton M.; Koo, David C.; Lee, Christoph T.; Mei, Simona; Margalef-Bentabol, Berta; Primack, Joel; Rodriguez-Puebla, Aldo; Salvato, Mara; Shankar, Francesco; Tuccillo, Diego

2018-05-01

Understanding how bulges grow in galaxies is critical step towards unveiling the link between galaxy morphology and star-formation. To do so, it is necessary to decompose large sample of galaxies at different epochs into their main components (bulges and discs). This is particularly challenging, especially at high redshifts, where galaxies are poorly resolved. This work presents a catalog of bulge-disc decompositions of the surface brightness profiles of ˜17.600 H-band selected galaxies in the CANDELS fields (F160W < 23, 0 < z < 2) in 4 to 7 filters covering a spectral range of 430 - 1600nm. This is the largest available catalog of this kind up to z = 2. By using a novel approach based on deep-learning to select the best model to fit, we manage to control systematics arising from wrong model selection and obtain less contaminated samples than previous works. We show that the derived structural properties are within ˜10 - 20% of random uncertainties. We then fit stellar population models to the decomposed SEDs (Spectral Energy Distribution) of bulges and discs and derive stellar masses (and stellar mass bulge-to-total ratios) as well as rest-frame colors (U,V,J) for bulges and discs separately. All data products are publicly released with this paper and through the web page https://lerma.obspm.fr/huertas/form_CANDELS and will be used for scientific analysis in forthcoming works.

Antimicrobial activities of the rhizome extract of Zingiber zerumbet Linn.

PubMed

Kader, Golam; Nikkon, Farjana; Rashid, Mohammad Abdur; Yeasmin, Tanzima

2011-10-01

To investigate antimicrobial effects of ethanolic extract of Zingiber zerumbet (Z. zerumbet) (L.) Smith and its chloroform and petroleum ether soluble fractions against pathogenic bacteria and fungi. The fresh rhizomes of Zingiber zerumbet were extracted in cold with ethanol (4.0 L) after concentration. The crude ethanol extract was fractionated by petroleum ether and chloroform to form a suspension of ethanol extract (15.0 g), petroleum ether fraction (6.6 g) and chloroform soluble fraction (5.0 g). The crude ethanol extract and its petroleum ether and chloroform fractions were evaluated for antibacterial and antifungal activity against thirteen pathogenic bacteria and three fungi by the disc diffusion method. Commercially available kanamycin (30 µg/disc) was used as standard disc and blank discs impregnated with the respective solvents were used as negative control. At a concentration of 400 µg/disc, all the samples showed mild to moderate antibacterial and antifungal activity and produced the zone of inhibition ranging from 6 mm to 10 mm. Among the tested samples, the crude ethanol extract showed the highest activity against Vibrio parahemolyticus (V. parahemolyticus). The minimum inhibitory concentration (MIC) of the crude ethanol extract and its fractions were within the value of 128-256 µg/mL against two Gram positive and four Gram negative bacteria and all the samples showed the lowest MIC value against V. parahemolyticus (128 µg/mL). It can be concluded that, potent antibacterial and antifungal phytochemicals are present in ethanol extract of Z. zerumbet (L).

Introducing galactic structure finder: the multiple stellar kinematic structures of a simulated Milky Way mass galaxy

NASA Astrophysics Data System (ADS)

Obreja, Aura; Macciò, Andrea V.; Moster, Benjamin; Dutton, Aaron A.; Buck, Tobias; Wang, Gregory S. Stinson Liang

2018-04-01

We present the first results of applying Gaussian Mixture Models in the stellar kinematic space of normalized angular momentum and binding energy on NIHAO high resolution galaxies to separate the stars into multiple components. We exemplify this method using a simulated Milky Way analogue, whose stellar component hosts: thin and thick discs, classical and pseudo bulges, and a stellar halo. The properties of these stellar structures are in good agreement with observational expectations in terms of sizes, shapes and rotational support. Interestingly, the two kinematic discs show surface mass density profiles more centrally concentrated than exponentials, while the bulges and the stellar halo are purely exponential. We trace back in time the Lagrangian mass of each component separately to study their formation history. Between z ˜ 3 and the end of halo virialization, z ˜ 1.3, all components lose a fraction of their angular momentum. The classical bulge loses the most (˜95%) and the thin disc the least (˜60%). Both bulges formed their stars in-situ at high redshift, while the thin disc formed ˜98% in-situ, but with a constant SFR ˜ 1.5M⊙yr-1 over the last ˜ 11 Gyr. Accreted stars (6% of total stellar mass) are mainly incorporated to the thick disc or the stellar halo, which formed ex-situ 8% and 45% of their respective masses. Our analysis pipeline is freely available at https://github.com/aobr/gsf.

Targeted Deletion of the Muscular Dystrophy Gene myotilin Does Not Perturb Muscle Structure or Function in Mice▿

PubMed Central

Moza, Monica; Mologni, Luca; Trokovic, Ras; Faulkner, Georgine; Partanen, Juha; Carpén, Olli

2007-01-01

Myotilin, palladin, and myopalladin form a novel small subfamily of cytoskeletal proteins that contain immunoglobulin-like domains. Myotilin is a thin filament-associated protein localized at the Z-disk of skeletal and cardiac muscle cells. The direct binding to F-actin, efficient cross-linking of actin filaments, and prevention of induced disassembly of filaments are key roles of myotilin that are thought to be involved in structural maintenance and function of the sarcomere. Missense mutations in the myotilin-encoding gene cause dominant limb girdle muscular dystrophy type 1A and spheroid body myopathy and are the molecular defect that can cause myofibrillar myopathy. Here we describe the generation and analysis of mice that lack myotilin, myo−/− mice. Surprisingly, myo−/− mice maintain normal muscle sarcomeric and sarcolemmal integrity. Also, loss of myotilin does not cause alterations in the heart or other organs of newborn or adult myo−/− mice. The mice develop normally and have a normal life span, and their muscle capacity does not significantly differ from wild-type mice even after prolonged physical stress. The results suggest that either myotilin does not participate in muscle development and basal function maintenance or other proteins serve as structural and functional compensatory molecules when myotilin is absent. PMID:17074808

Bending instability in galactic discs: advocacy of the linear theory

NASA Astrophysics Data System (ADS)

Rodionov, S. A.; Sotnikova, N. Ya.

2013-09-01

We demonstrate that in N-body simulations of isolated disc galaxies, there is numerical vertical heating which slowly increases the vertical velocity dispersion and the disc thickness. Even for models with over a million particles in a disc, this heating can be significant. Such an effect is just the same as in numerical experiments by Sellwood. We also show that in a stellar disc, outside a boxy/peanut bulge, if it presents, the saturation level of the bending instability is rather close to the value predicted by the linear theory. We pay attention to the fact that the bending instability develops and decays very fast, so it cannot play any role in secular vertical heating. However, the bending instability defines the minimal value of the ratio between the vertical and radial velocity dispersions σz/σR ≈ 0.3 (so indirectly the minimal thickness), which stellar discs in real galaxies may have. We demonstrate that observations confirm the last statement.

Stellar populations, stellar masses and the formation of galaxy bulges and discs at z < 3 in CANDELS

NASA Astrophysics Data System (ADS)

Margalef-Bentabol, Berta; Conselice, Christopher J.; Mortlock, Alice; Hartley, Will; Duncan, Kenneth; Kennedy, Rebecca; Kocevski, Dale D.; Hasinger, Guenther

2018-02-01

We present a multicomponent structural analysis of the internal structure of 1074 high-redshift massive galaxies at 1 < z < 3 from the CANDELS HST Survey. In particular, we examine galaxies best fitted by two structural components, and thus likely forming discs and bulges. We examine the stellar mass, star formation rates (SFRs) and colours of both the inner 'bulge' and outer 'disc' components for these systems using Spectral Energy Distribution (SED) information from the resolved ACS+WFC3 HST imaging. We find that the majority of both inner and outer components lie in the star-forming region of UVJ space (68 and 90 per cent, respectively). However, the inner portions, or the likely forming bulges, are dominated by dusty star formation. Furthermore, we show that the outer components of these systems have a higher SFR than their inner regions, and the ratio of SFR between 'disc' and 'bulge' increases at lower redshifts. Despite the higher SFR of the outer component, the stellar mass ratio of inner to outer component remains constant through this epoch. This suggests that there is mass transfer from the outer to inner components for typical two-component-forming systems, thus building bulges from discs. Finally, using Chandra data we find that the presence of an active galactic nucleus is more common in both one-component spheroid-like galaxies and two-component systems (13 ± 3 and 11 ± 2 per cent) than in one-component disc-like galaxies (3 ± 1 per cent), demonstrating that the formation of a central inner component likely triggers the formation of central massive black holes in these galaxies.

Response of the Milky Way's disc to the Large Magellanic Cloud in a first infall scenario

NASA Astrophysics Data System (ADS)

Laporte, Chervin F. P.; Gómez, Facundo A.; Besla, Gurtina; Johnston, Kathryn V.; Garavito-Camargo, Nicolas

2018-01-01

We present N-body and hydrodynamical simulations of the response of the Milky Way's baryonic disc to the presence of the Large Magellanic Cloud during a first infall scenario. For a fiducial Galactic model reproducing the gross properties of the Galaxy, we explore a set of six initial conditions for the Large Magellanic Cloud (LMC) of varying mass which all evolve to fit the measured constraints on its current position and velocity with respect to the Galactic Centre. We find that the LMC can produce strong disturbances - warping of the stellar and gaseous discs - in the Galaxy, without violating constraints from the phase-space distribution of stars in the Solar Neighbourhood. All models correctly reproduce the phases of the warp and its antisymmetrical shape about the disc's mid-plane. If the warp is due to the LMC alone, then the largest mass model is favoured (2.5 × 1011 M⊙). Still, some quantitative discrepancies remain, including deficits in height of ΔZ = 0.7 kpc at R = 22 kpc and ΔZ = 0.7 kpc at R = 16 kpc. This suggests that even higher infall masses for the LMC's halo are allowed by the data. A comparison with the vertical perturbations induced by a heavy Sagittarius dSph model (1011 M⊙) suggest that positive interference with the LMC warp is expected at R = 16 kpc. We conclude that the vertical structure of the Galactic disc beyond the Solar Neighbourhood may jointly be shaped by its most massive satellites. As such, the current structure of the Milky Way suggests we are seeing the process of disc heating by satellite interactions in action.

Vertebral body fracture after anterior cervical discectomy and fusion with zero-profile anchored cages in adjacent levels: a cautionary tale.

PubMed

Mattei, Tobias A; Teles, Alisson R; Dinh, Dzung H

2016-01-05

Zero-profile (also called self-locking, anchored or stand-alone cages) have been recently proposed as an interesting alternative for anterior cervical discectomy and fusion (ACDF), as they are supposed to reduce the rates of post-operative cage extrusion without necessarily incurring in the additional surgical time and increased rates of dysphagia associated with plating. Nevertheless, the exact indications of zero-profile anchored cages have not yet been established in the literature. To report the first case of a vertebral body fracture between the blades of zero-profile anchored cages after ACDFs in adjacent levels and to review the available literature on hardware-related complications after multi-level ACDFs with zero-profile anchored cages. Case report and systematic literature review. The authors report the first case of a vertebral body fracture between the blades of zero-profile anchored cages after ACDFs in adjacent levels. The patient presented with refractory mechanical neck pain at the 1-month post-operative follow-up, ultimately requiring a posterior instrumented fusion. A comprehensive systematic literature review on the available data regarding the safety, complications as well as radiological and clinical outcomes of zero-profile anchored cages is also performed. In the reported case, the use of zero-profile anchored cages in adjacent levels on the cervical spine led to a fracture of the vertebral body between the cages at the 1-month follow-up, with anterior avulsion of the part of the vertebral body where the blades from the two cages converged. According to the systematic literature review which included 409 patients from 10 different clinical series (with a total cumulative follow-up of approximately 535 patients-year), there were only two reported hardware-related complications after ACDF with zero-profile anchored cages, none of them involving fracture at the level of convergence of blades or screws. Although hardware-related complications after the use of zero-profile anchored cages seem to be rare events, future biomechanical and clinical studies are warranted in order to evaluate the safety of employing such devices for the treatment of multilevel degenerative disc disease in the cervical spine.

Local stellar kinematics from RAVE data—VIII. Effects of the Galactic disc perturbations on stellar orbits of red clump stars

NASA Astrophysics Data System (ADS)

Önal Taş, Ö.; Bilir, S.; Plevne, O.

2018-02-01

We aim to probe the dynamic structure of the extended Solar neighborhood by calculating the radial metallicity gradients from orbit properties, which are obtained for axisymmetric and non-axisymmetric potential models, of red clump (RC) stars selected from the RAdial Velocity Experiment's Fourth Data Release. Distances are obtained by assuming a single absolute magnitude value in near-infrared, i.e. M_{Ks}=-1.54±0.04 mag, for each RC star. Stellar orbit parameters are calculated by using the potential functions: (i) for the MWPotential2014 potential, (ii) for the same potential with perturbation functions of the Galactic bar and transient spiral arms. The stellar age is calculated with a method based on Bayesian statistics. The radial metallicity gradients are evaluated based on the maximum vertical distance (z_{max}) from the Galactic plane and the planar eccentricity (ep) of RC stars for both of the potential models. The largest radial metallicity gradient in the 0< z_{max} ≤0.5 kpc distance interval is -0.065±0.005 dex kpc^{-1} for a subsample with ep≤0.1, while the lowest value is -0.014±0.006 dex kpc^{-1} for the subsample with ep≤0.5. We find that at z_{max}>1 kpc, the radial metallicity gradients have zero or positive values and they do not depend on ep subsamples. There is a large radial metallicity gradient for thin disc, but no radial gradient found for thick disc. Moreover, the largest radial metallicity gradients are obtained where the outer Lindblad resonance region is effective. We claim that this apparent change in radial metallicity gradients in the thin disc is a result of orbital perturbation originating from the existing resonance regions.

NRIP is newly identified as a Z-disc protein, activating calmodulin signaling for skeletal muscle contraction and regeneration.

PubMed

Chen, Hsin-Hsiung; Chen, Wen-Pin; Yan, Wan-Lun; Huang, Yuan-Chun; Chang, Szu-Wei; Fu, Wen-Mei; Su, Ming-Jai; Yu, I-Shing; Tsai, Tzung-Chieh; Yan, Yu-Ting; Tsao, Yeou-Ping; Chen, Show-Li

2015-11-15

Nuclear receptor interaction protein (NRIP, also known as DCAF6 and IQWD1) is a Ca(2+)-dependent calmodulin-binding protein. In this study, we newly identify NRIP as a Z-disc protein in skeletal muscle. NRIP-knockout mice were generated and found to have reduced muscle strength, susceptibility to fatigue and impaired adaptive exercise performance. The mechanisms of NRIP-regulated muscle contraction depend on NRIP being downstream of Ca(2+) signaling, where it stimulates activation of both 'calcineurin-nuclear factor of activated T-cells, cytoplasmic 1' (CaN-NFATc1; also known as NFATC1) and calmodulin-dependent protein kinase II (CaMKII) through interaction with calmodulin (CaM), resulting in the induction of mitochondrial activity and the expression of genes encoding the slow class of myosin, and in the regulation of Ca(2+) homeostasis through the internal Ca(2+) stores of the sarcoplasmic reticulum. Moreover, NRIP-knockout mice have a delayed regenerative capacity. The amount of NRIP can be enhanced after muscle injury and is responsible for muscle regeneration, which is associated with the increased expression of myogenin, desmin and embryonic myosin heavy chain during myogenesis, as well as for myotube formation. In conclusion, NRIP is a novel Z-disc protein that is important for skeletal muscle strength and regenerative capacity. © 2015. Published by The Company of Biologists Ltd.

The multiple roles of titin in muscle contraction and force production.

PubMed

Herzog, Walter

2018-01-20

Titin is a filamentous protein spanning the half-sarcomere, with spring-like properties in the I-band region. Various structural, signaling, and mechanical functions have been associated with titin, but not all of these are fully elucidated and accepted in the scientific community. Here, I discuss the primary mechanical functions of titin, including its accepted role in passive force production, stabilization of half-sarcomeres and sarcomeres, and its controversial contribution to residual force enhancement, passive force enhancement, energetics, and work production in shortening muscle. Finally, I provide evidence that titin is a molecular spring whose stiffness changes with muscle activation and actin-myosin-based force production, suggesting a novel model of force production that, aside from actin and myosin, includes titin as a "third contractile" filament. Using this three-filament model of sarcomeres, the stability of (half-) sarcomeres, passive force enhancement, residual force enhancement, and the decrease in metabolic energy during and following eccentric contractions can be explained readily.

Sarcomeric Pattern Formation by Actin Cluster Coalescence

PubMed Central

Friedrich, Benjamin M.; Fischer-Friedrich, Elisabeth; Gov, Nir S.; Safran, Samuel A.

2012-01-01

Contractile function of striated muscle cells depends crucially on the almost crystalline order of actin and myosin filaments in myofibrils, but the physical mechanisms that lead to myofibril assembly remains ill-defined. Passive diffusive sorting of actin filaments into sarcomeric order is kinetically impossible, suggesting a pivotal role of active processes in sarcomeric pattern formation. Using a one-dimensional computational model of an initially unstriated actin bundle, we show that actin filament treadmilling in the presence of processive plus-end crosslinking provides a simple and robust mechanism for the polarity sorting of actin filaments as well as for the correct localization of myosin filaments. We propose that the coalescence of crosslinked actin clusters could be key for sarcomeric pattern formation. In our simulations, sarcomere spacing is set by filament length prompting tight length control already at early stages of pattern formation. The proposed mechanism could be generic and apply both to premyofibrils and nascent myofibrils in developing muscle cells as well as possibly to striated stress-fibers in non-muscle cells. PMID:22685394

Divergent regulation of the sarcomere and the cytoskeleton.

PubMed

Schevzov, Galina; Fath, Thomas; Vrhovski, Bernadette; Vlahovich, Nicole; Rajan, Sudarsan; Hook, Jeff; Joya, Josephine E; Lemckert, Frances; Puttur, Franz; Lin, Jim J-C; Hardeman, Edna C; Wieczorek, David F; O'Neill, Geraldine M; Gunning, Peter W

2008-01-04

The existence of a feedback mechanism regulating the precise amounts of muscle structural proteins, such as actin and the actin-associated protein tropomyosin (Tm), in the sarcomeres of striated muscles is well established. However, the regulation of nonmuscle or cytoskeletal actin and Tms in nonmuscle cell structures has not been elucidated. Unlike the thin filaments of striated muscles, the actin cytoskeleton in nonmuscle cells is intrinsically dynamic. Given the differing requirements for the structural integrity of the actin thin filaments of the sarcomere compared with the requirement for dynamicity of the actin cytoskeleton in nonmuscle cells, we postulated that different regulatory mechanisms govern the expression of sarcomeric versus cytoskeletal Tms, as key regulators of the properties of the actin cytoskeleton. Comprehensive analyses of tissues from transgenic and knock-out mouse lines that overexpress the cytoskeletal Tms, Tm3 and Tm5NM1, and a comparison with sarcomeric Tms provide evidence for this. Moreover, we show that overexpression of a cytoskeletal Tm drives the amount of filamentous actin.

Early results of sarcomeric gene screening from the Egyptian National BA-HCM Program.

PubMed

Kassem, Heba Sh; Azer, Remon S; Saber-Ayad, Maha; Ayad, Maha S; Moharem-Elgamal, Sarah; Magdy, Gehan; Elguindy, Ahmed; Cecchi, Franco; Olivotto, Iacopo; Yacoub, Magdi H

2013-02-01

The present study comprised sarcomeric genotyping of the three most commonly involved sarcomeric genes: MYBPC3, MYH7, and TNNT2 in 192 unrelated Egyptian hypertrophic cardiomyopathy (HCM) index patients. Mutations were detected in 40 % of cases. Presence of positive family history was significantly (p=0.002) associated with a higher genetic positive yield (49/78, 62.8 %). The majority of the detected mutations in the three sarcomeric genes were novel (40/62, 65 %) and mostly private (47/62, 77 %). Single nucleotide substitution was the most frequently detected mutation type (51/62, 82 %). Over three quarters of these substitutions (21/27, 78 %) involved CpG dinucleotide sites and resulted from C>T or G>A transition in the three analyzed genes, highlighting the significance of CpG high mutability within the sarcomeric genes examined. This study could aid in global comparative studies in different ethnic populations and constitutes an important step in the evolution of the integrated clinical, translational, and basic science HCM program.

Magnitude of sarcomere extension correlates with initial sarcomere length during lengthening of activated single fibers from soleus muscle of rats.

PubMed

Panchangam, Appaji; Claflin, Dennis R; Palmer, Mark L; Faulkner, John A

2008-08-01

A laser-diffraction technique was developed that rapidly reports the lengths of sarcomeres (L(s)) in serially connected sectors of permeabilized single fibers. The apparatus translates a laser beam along the entire length of a fiber segment within 2 ms, with brief stops at each of 20 contiguous sectors. We tested the hypothesis that during lengthening contractions, when maximally activated fibers are stretched, sectors that contain the longer sarcomeres undergo greater increases in L(s) than those containing shorter sarcomeres. Fibers (n = 16) were obtained from the soleus muscles of adult male rats and the middle portions (length = 1.05 +/- 0.11 mm; mean +/- SD) were investigated. Single stretches of strain 27% and a strain rate of 54% s(-1) were initiated at maximum isometric stress and resulted in a 19 +/- 9% loss in isometric stress. The data on L(s) revealed that 1), the stretch was not distributed uniformly among the sectors, and 2), during the stretch, sectors at long L(s) before the stretch elongated more than those at short lengths. The findings support the hypothesis that during stretches of maximally activated skeletal muscles, sarcomeres at longer lengths are more susceptible to damage by excessive strain.

The titin A-band rod domain is dispensable for initial thick filament assembly in zebrafish.

PubMed

Myhre, J Layne; Hills, Jordan A; Prill, Kendal; Wohlgemuth, Serene L; Pilgrim, David B

2014-03-01

The sarcomeres of skeletal and cardiac muscle are highly structured protein arrays, consisting of thick and thin filaments aligned precisely to one another and to their surrounding matrix. The contractile mechanisms of sarcomeres are generally well understood, but how the patterning of sarcomeres is initiated during early skeletal muscle and cardiac development remains uncertain. Two of the most widely accepted hypotheses for this process include the "molecular ruler" model, in which the massive protein titin defines the length of the sarcomere and provides a scaffold along which the myosin thick filament is assembled, and the "premyofibril" model, which proposes that thick filament formation does not require titin, but that a "premyofibril" consisting of non-muscle myosin, α-actinin and cytoskeletal actin is used as a template. Each model posits a different order of necessity of the various components, but these have been difficult to test in vivo. Zebrafish motility mutants with developmental defects in sarcomere patterning are useful for the elucidation of such mechanisms, and here we report the analysis of the herzschlag mutant, which shows deficits in both cardiac and skeletal muscle. The herzschlag mutant produces a truncated titin protein, lacking the C-terminal rod domain that is proposed to act as a thick filament scaffold, yet muscle patterning is still initiated, with grossly normal thick and thin filament assembly. Only after embryonic muscle contraction begins is breakdown of sarcomeric myosin patterning observed, consistent with the previously noted role of titin in maintaining the contractile integrity of mature sarcomeres. This conflicts with the "molecular ruler" model of early sarcomere patterning and supports a titin-independent model of thick filament organization during sarcomerogenesis. These findings are also consistent with the symptoms of human titin myopathies that exhibit a late onset, such as tibial muscular dystrophy. Copyright © 2013 Elsevier Inc. All rights reserved.

Anchorage Behaviors of Frictional Tieback Anchors in Silty Sand

NASA Astrophysics Data System (ADS)

Hsu, Shih-Tsung; Hsiao, Wen-Ta; Chen, Ke-Ting; Hu, Wen-Chi; Wu, Ssu-Yi

2017-06-01

Soil anchors are extensively used in geotechnical applications, most commonly serve as tieback walls in deep excavations. To investigate the anchorage mechanisms of this tieback anchor, a constitutive model that considers both strain hardening and softening and volume dilatancy entitled SHASOVOD model, and FLAC3D software are used to perform 3-D numerical analyses. The results from field anchor tests are compared with those calculated by numerical analyses to enhance the applicability of the numerical method. After the calibration, this research carried out the parameter studies by numerical analyses. The numerical results reveal that whether the yield of soil around an anchor develops to ground surface and/or touches the diaphragm wall depending on the overburden depth H and the embedded depth Z of an anchor, this study suggests the minimum overburden and embedded depths to avoid the yield of soils develop to ground surface and/or touch the diaphragm wall. When the embedded depth, overburden depth or fixed length of an anchor increases, the anchorage capacity also increases. Increasing fixed length should be the optimum method to increase the anchorage capacity for fixed length less than 20m. However, when the fixed length of an anchor exceeds 30 m, the increasing rate of anchorage capacity per fixed length decreases, and progressive yield occurs obviously between the fixed length and surrounding soil.

Introducing galactic structure finder: the multiple stellar kinematic structures of a simulated Milky Way mass galaxy

NASA Astrophysics Data System (ADS)

Obreja, Aura; Macciò, Andrea V.; Moster, Benjamin; Dutton, Aaron A.; Buck, Tobias; Stinson, Gregory S.; Wang, Liang

2018-07-01

We present the first results of applying Gaussian Mixture Models in the stellar kinematic space of normalized angular momentum and binding energy on NIHAO high-resolution galaxies to separate the stars into multiple components. We exemplify this method, using a simulated Milky Way analogue, whose stellar component hosts thin and thick discs, classical and pseudo bulges, and a stellar halo. The properties of these stellar structures are in good agreement with observational expectations in terms of sizes, shapes, and rotational support. Interestingly, the two kinematic discs show surface mass density profiles more centrally concentrated than exponentials, while the bulges and the stellar halo are purely exponential. We trace back in time the Lagrangian mass of each component separately to study their formation history. Between z ˜ 3 and the end of halo virialization, z ˜ 1.3, all components lose a fraction of their angular momentum. The classical bulge loses the most (˜ 95 per cent) and the thin disc the least (˜ 60 per cent). Both bulges formed their stars in situ at high redshift, while the thin disc formed ˜ 98 per cent in situ, but with a constant SFR ˜ 1.5 M⊙ yr-1 over the last ˜11 Gyr. Accreted stars (6 per cent of total stellar mass) are mainly incorporated to the thick disc or the stellar halo, which formed ex situ 8 per cent and 45 per cent of their respective masses. Our analysis pipeline is freely available at https://github.com/aobr/gsf.

The magnetic field inside a protoplanetary disc gap opened by planets of different masses

NASA Astrophysics Data System (ADS)

Carballido, Augusto; Matthews, Lorin S.; Hyde, Truell W.

2017-12-01

We perform magnetohydrodynamic simulations of protoplanetary disc gaps opened by planets of various masses, with the aim of calculating the strength of the vertical magnetic field threading such gaps. We introduce a gravitational potential at the centre of a shearing box to compute the tidal interaction between the planets and the disc gas, which is turbulent due to the magnetorotational instability. Two types of simulations are executed: 1) In type 'Z', the initial magnetic field has only a uniform, vertical component, and ten planet masses between 0.66 and 6.64 thermal masses are used; 2) In type 'YZ', the initial magnetic field has both toroidal and vertical components, and five planet masses covering the same mass range are used. Our results show that, for low planet masses, higher values of the vertical magnetic field occur inside the gaps than outside, in agreement with the previous work. However, for massive planets, we find that the radial profiles of the field show dips near the gap centre. The interior of the Hill sphere of the most massive planet in the Z runs contains more low-plasma β values (i.e. high magnetic pressure) compared to lower-mass planets. Values of β at a distance of one Hill radius from each planet show a moderate decrease with planet mass. These results are relevant for the magnetic structure of circumplanetary discs and their possible outflows, and may be refined to aid future observational efforts to infer planet masses from high-resolution polarimetric observations of discs with gaps.

Targets for therapy in sarcomeric cardiomyopathies

PubMed Central

Tardiff, Jil C.; Carrier, Lucie; Bers, Donald M.; Poggesi, Corrado; Ferrantini, Cecilia; Coppini, Raffaele; Maier, Lars S.; Ashrafian, Houman; Huke, Sabine; van der Velden, Jolanda

2015-01-01

To date, no compounds or interventions exist that treat or prevent sarcomeric cardiomyopathies. Established therapies currently improve the outcome, but novel therapies may be able to more fundamentally affect the disease process and course. Investigations of the pathomechanisms are generating molecular insights that can be useful for the design of novel specific drugs suitable for clinical use. As perturbations in the heart are stage-specific, proper timing of drug treatment is essential to prevent initiation and progression of cardiac disease in mutation carrier individuals. In this review, we emphasize potential novel therapies which may prevent, delay, or even reverse hypertrophic cardiomyopathy caused by sarcomeric gene mutations. These include corrections of genetic defects, altered sarcomere function, perturbations in intracellular ion homeostasis, and impaired myocardial energetics. PMID:25634554

Star formation quenching in green valley galaxies at 0.5 ≲ z ≲ 1.0 and constraints with galaxy morphologies

NASA Astrophysics Data System (ADS)

Nogueira-Cavalcante, J. P.; Gonçalves, T. S.; Menéndez-Delmestre, K.; Sheth, K.

2018-01-01

We calculate the star formation quenching time-scales in green valley galaxies at intermediate redshifts (z ∼ 0.5-1) using stacked zCOSMOS spectra of different galaxy morphological types: spheroidal, disc-like, irregular and merger, dividing disc-like galaxies further into unbarred, weakly barred and strongly barred, assuming a simple exponentially decaying star formation history model and based on the H δ absorption feature and the 4000 Å break. We find that different morphological types present different star formation quenching time-scales, reinforcing the idea that the galaxy morphology is strongly correlated with the physical processes responsible for quenching star formation. Our quantification of the star formation quenching time-scale indicates that discs have typical time-scales 60 per cent to five times longer than that of galaxies presenting spheroidal, irregular or merger morphologies. Barred galaxies, in particular, present the slowest transition time-scales through the green valley. This suggests that although secular evolution may ultimately lead to gas exhaustion in the host galaxy via bar-induced gas inflows that trigger star formation activity, secular agents are not major contributors in the rapid quenching of galaxies at these redshifts. Galaxy interaction, associated with the elliptical, irregular and merger morphologies, contributes, to a more significant degree, to the fast transition through the green valley at these redshifts. In light of previous works suggesting that both secular and merger processes are responsible for the star formation quenching at low redshifts, our results provide an explanation to the recent findings that star formation quenching happened at a faster pace at z ∼ 0.8.

Velocity of sarcomere shortening in rat cardiac muscle: relationship to force, sarcomere length, calcium and time.

PubMed

Daniels, M; Noble, M I; ter Keurs, H E; Wohlfart, B

1984-10-01

The relation between force and velocity was determined in sixteen trabeculae of rat right ventricle as a function of time during a twitch, of sarcomere length and of external Ca2+ concentration, [Ca2+]o. The trabeculae were studied in modified Krebs-Henseleit solution at 25 degrees C. Force was measured with a semiconductor strain gauge. Sarcomere length was measured with a laser diffraction system. A servomotor system was used in which control could be switched between sarcomere length, muscle length and force. Force-velocity relations were derived from load clamps and from contractions in which sarcomere length was initially held constant followed by a quick release and slower release of the sarcomeres at controlled velocity. Force-velocity relations were fitted by Hill's equation (Hill, 1938), (Po-P) b = (P+a) V, where P = force, V = velocity, Po = isometric force in mN/mm2 and a and b are constants. For [Ca2+]o = 2.5 mM, with both interventions the values (mean +/- S.D.) were: b = 1.00 +/- 0.45 micron/s; a = 9.52 +/- 5.60 mN/mm2; Vo measured = 13.6 +/- 3.0 micron/s; Vo calculated = 13.4 +/- 3.4 micron/s; Po measured = 96.5 +/- 25.0 mN/mm2; Po calculated = 119.3 +/- 34.5 mN/mm2. Vo rose with [Ca2+]o to a maximum at [Ca2+]o = 1.2 mM when Po was about 50% of maximum, while Po rose with [Ca2+]o to a maximum at above 2.5 mM. Vo rose with time during the twitch to a maximum at 25 ms following onset of contraction; Po was then about 50% of the maximum that was obtained at 120 ms. Vo increased with sarcomere length from zero at a sarcomere length of 1.6 micron to a maximum at 1.85 micron. Between 1.85 micron and 2.3 micron, Vo was constant. At 1.85 micron, Po was about 60% of maximum Po. These results are compatible with the hypothesis that Vo is more sensitive than Po to the amount of Ca2+ bound to the contractile proteins, and that Vo reaches a maximal value with an amount of Ca2+ bound to the contractile proteins at which Po has obtained only about 50% of its maximal value.

T1 Measurements Identify Extracellular Volume Expansion in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers With and Without Left Ventricular Hypertrophy

PubMed Central

Ho, Carolyn Y.; Abbasi, Siddique A.; Neilan, Tomas G.; Shah, Ravi V.; Chen, Yucheng; Heydari, Bobak; Cirino, Allison L.; Lakdawala, Neal K.; Orav, E. John; González, Arantxa; López, Begoña; Díez, Javier; Jerosch-Herold, Michael; Kwong, Raymond Y.

2013-01-01

Background Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy (HCM) and a potential substrate for arrhythmias and heart failure. Sarcomere mutations appear to induce profibrotic changes before left ventricular hypertrophy (LVH) develops. To further evaluate these processes, we used cardiac magnetic resonance (CMR) with T1 measurements on a genotyped HCM population to quantify myocardial extracellular volume (ECV). Methods and Results Sarcomere mutation carriers with LVH (G+/LVH+, n = 37) and without LVH (G+/LVH−, n = 29); HCM patients without mutations (sarcomere-negative HCM, n = 11); and healthy controls (n = 11) underwent contrast CMR, measuring T1 times pre- and post-gadolinium infusion. Concurrent echocardiography and serum biomarkers of collagen synthesis, hemodynamic stress, and myocardial injury were also available in a subset. Compared to controls, ECV was increased in patients with overt HCM, as well as G+/LVH− mutation carriers (ECV= 0.36±0.01, 0.33±0.01, 0.27±0.01 in G+/LVH+, G+/LVH−, controls, respectively, P≤0.001 for all comparisons). ECV correlated with NT-proBNP levels (r = 0.58, P<0.001) and global E’ velocity (r = −0.48, P<0.001). Late gadolinium enhancement (LGE) was present in >60% of overt HCM patients but absent from G+/LVH− subjects. Both ECV and LGE were more extensive in sarcomeric HCM than sarcomere-negative HCM. Conclusions Myocardial ECV is increased in HCM sarcomere mutation carriers even in the absence of LVH. These data provide additional support that fibrotic remodeling is triggered early in disease pathogenesis. Quantifying ECV may help characterize the development myocardial fibrosis in HCM and ultimately assist in developing novel disease-modifying therapy, targeting interstitial fibrosis. PMID:23549607

The Seismic Design of Waterfront Retaining Structures

DTIC Science & Technology

1992-11-01

a higher posi- tion along the back of the wall than the static active earth pressure force due to the concentration of soil mass comprising the...inertia force k.’W acting downward). = tan-1 [. ] (by eq 35) - 5.35- KAB = CO2 (30-5. 35)cos (5.35)cosZ(0)cos(5.35+3)f1 + /sin(30+3)sin(30-5. 35-6...distance between the anchor and the sheet pile. Two anchored bulkheads were in place in the harbor of San Antonio, Chile , during the very large earthquake

Random myosin loss along thick-filaments increases myosin attachment time and the proportion of bound myosin heads to mitigate force decline in skeletal muscle

PubMed Central

Tanner, Bertrand C.W.; McNabb, Mark; Palmer, Bradley M.; Toth, Michael J.; Miller, Mark S.

2014-01-01

Diminished skeletal muscle performance with aging, disuse, and disease may be partially attributed to the loss of myofilament proteins. Several laboratories have found a disproportionate loss of myosin protein content relative to other myofilament proteins, but due to methodological limitations, the structural manifestation of this protein loss is unknown. To investigate how variations in myosin content affect ensemble cross-bridge behavior and force production we simulated muscle contraction in the half-sarcomere as myosin was removed either i) uniformly, from the Z-line end of thick-filaments, or ii) randomly, along the length of thick-filaments. Uniform myosin removal decreased force production, showing a slightly steeper force-to-myosin content relationship than the 1:1 relationship that would be expected from the loss of cross-bridges. Random myosin removal also decreased force production, but this decrease was less than observed with uniform myosin loss, largely due to increased myosin attachment time (ton) and fractional cross-bridge binding with random myosin loss. These findings support our prior observations that prolonged ton may augment force production in single fibers with randomly reduced myosin content from chronic heart failure patients. These simulation also illustrate that the pattern of myosin loss along thick-filaments influences ensemble cross-bridge behavior and maintenance of force throughout the sarcomere. PMID:24486373

Analysis of the ACTN3 heterozygous genotype suggests that α-actinin-3 controls sarcomeric composition and muscle function in a dose-dependent fashion

PubMed Central

Hogarth, Marshall W.; Garton, Fleur C.; Houweling, Peter J.; Tukiainen, Taru; Lek, Monkol; Macarthur, Daniel G.; Seto, Jane T.; Quinlan, Kate G.R.; Yang, Nan; Head, Stewart I.; North, Kathryn N.

2016-01-01

A common null polymorphism (R577X) in ACTN3 causes α-actinin-3 deficiency in ∼18% of the global population. There is no associated disease phenotype, but α-actinin-3 deficiency is detrimental to sprint and power performance in both elite athletes and the general population. However, despite considerable investigation to date, the functional consequences of heterozygosity for ACTN3 are unclear. A subset of studies have shown an intermediate phenotype in 577RX individuals, suggesting dose-dependency of α-actinin-3, while others have shown no difference between 577RR and RX genotypes. Here, we investigate the effects of α-actinin-3 expression level by comparing the muscle phenotypes of Actn3+/− (HET) mice to Actn3+/+ [wild-type (WT)] and Actn3−/− [knockout (KO)] littermates. We show reduction in α-actinin-3 mRNA and protein in HET muscle compared with WT, which is associated with dose-dependent up-regulation of α-actinin-2, z-band alternatively spliced PDZ-motif and myotilin at the Z-line, and an incremental shift towards oxidative metabolism. While there is no difference in force generation, HET mice have an intermediate endurance capacity compared with WT and KO. The R577X polymorphism is associated with changes in ACTN3 expression consistent with an additive model in the human genotype-tissue expression cohort, but does not influence any other muscle transcripts, including ACTN2. Overall, ACTN3 influences sarcomeric composition in a dose-dependent fashion in mouse skeletal muscle, which translates directly to function. Variance in fibre type between biopsies likely masks this phenomenon in human skeletal muscle, but we suggest that an additive model is the most appropriate for use in testing ACTN3 genotype associations. PMID:26681802

Sarcomeric protein modification during adrenergic stress enhances cross-bridge kinetics and cardiac output

PubMed Central

Gresham, Kenneth S.; Mamidi, Ranganath; Li, Jiayang; Kwak, Hyerin

2017-01-01

Molecular adaptations to chronic neurohormonal stress, including sarcomeric protein cleavage and phosphorylation, provide a mechanism to increase ventricular contractility and enhance cardiac output, yet the link between sarcomeric protein modifications and changes in myocardial function remains unclear. To examine the effects of neurohormonal stress on posttranslational modifications of sarcomeric proteins, mice were administered combined α- and β-adrenergic receptor agonists (isoproterenol and phenylephrine, IPE) for 14 days using implantable osmotic pumps. In addition to significant cardiac hypertrophy and increased maximal ventricular pressure, IPE treatment accelerated pressure development and relaxation (74% increase in dP/dtmax and 14% decrease in τ), resulting in a 52% increase in cardiac output compared with saline (SAL)-treated mice. Accelerated pressure development was maintained when accounting for changes in heart rate and preload, suggesting that myocardial adaptations contribute to enhanced ventricular contractility. Ventricular myocardium isolated from IPE-treated mice displayed a significant reduction in troponin I (TnI) and myosin-binding protein C (MyBP-C) expression and a concomitant increase in the phosphorylation levels of the remaining TnI and MyBP-C protein compared with myocardium isolated from saline-treated control mice. Skinned myocardium isolated from IPE-treated mice displayed a significant acceleration in the rate of cross-bridge (XB) detachment (46% increase) and an enhanced magnitude of XB recruitment (43% increase) at submaximal Ca2+ activation compared with SAL-treated mice but unaltered myofilament Ca2+ sensitivity of force generation. These findings demonstrate that sarcomeric protein modifications during neurohormonal stress are molecular adaptations that enhance in vivo ventricular contractility through accelerated XB kinetics to increase cardiac output. NEW & NOTEWORTHY Posttranslational modifications to sarcomeric regulatory proteins provide a mechanism to modulate cardiac function in response to stress. In this study, we demonstrate that neurohormonal stress produces modifications to myosin-binding protein C and troponin I, including a reduction in protein expression within the sarcomere and increased phosphorylation of the remaining protein, which serve to enhance cross-bridge kinetics and increase cardiac output. These findings highlight the importance of sarcomeric regulatory protein modifications in modulating ventricular function during cardiac stress. PMID:27909224

Sarcomeric protein modification during adrenergic stress enhances cross-bridge kinetics and cardiac output.

PubMed

Gresham, Kenneth S; Mamidi, Ranganath; Li, Jiayang; Kwak, Hyerin; Stelzer, Julian E

2017-03-01

Molecular adaptations to chronic neurohormonal stress, including sarcomeric protein cleavage and phosphorylation, provide a mechanism to increase ventricular contractility and enhance cardiac output, yet the link between sarcomeric protein modifications and changes in myocardial function remains unclear. To examine the effects of neurohormonal stress on posttranslational modifications of sarcomeric proteins, mice were administered combined α- and β-adrenergic receptor agonists (isoproterenol and phenylephrine, IPE) for 14 days using implantable osmotic pumps. In addition to significant cardiac hypertrophy and increased maximal ventricular pressure, IPE treatment accelerated pressure development and relaxation (74% increase in dP/d t max and 14% decrease in τ), resulting in a 52% increase in cardiac output compared with saline (SAL)-treated mice. Accelerated pressure development was maintained when accounting for changes in heart rate and preload, suggesting that myocardial adaptations contribute to enhanced ventricular contractility. Ventricular myocardium isolated from IPE-treated mice displayed a significant reduction in troponin I (TnI) and myosin-binding protein C (MyBP-C) expression and a concomitant increase in the phosphorylation levels of the remaining TnI and MyBP-C protein compared with myocardium isolated from saline-treated control mice. Skinned myocardium isolated from IPE-treated mice displayed a significant acceleration in the rate of cross-bridge (XB) detachment (46% increase) and an enhanced magnitude of XB recruitment (43% increase) at submaximal Ca 2+ activation compared with SAL-treated mice but unaltered myofilament Ca 2+ sensitivity of force generation. These findings demonstrate that sarcomeric protein modifications during neurohormonal stress are molecular adaptations that enhance in vivo ventricular contractility through accelerated XB kinetics to increase cardiac output. NEW & NOTEWORTHY Posttranslational modifications to sarcomeric regulatory proteins provide a mechanism to modulate cardiac function in response to stress. In this study, we demonstrate that neurohormonal stress produces modifications to myosin-binding protein C and troponin I, including a reduction in protein expression within the sarcomere and increased phosphorylation of the remaining protein, which serve to enhance cross-bridge kinetics and increase cardiac output. These findings highlight the importance of sarcomeric regulatory protein modifications in modulating ventricular function during cardiac stress. Copyright © 2017 the American Physiological Society.

Patterns of sarcomere activation, temperature dependence, and effect of ryanodine in chemically skinned cardiac fibers

PubMed Central

1986-01-01

Functionally skinned and electrochemically shunted myocytes were prepared by perfusing rat hearts with collagenase in order to obtain a technically improved measurement of sarcomere dynamics and to evaluate the role of sarcoplasmic reticulum in situ with respect to contractile activation. In the presence of micromolar calcium, the myocytes exhibited phasic and propagated contraction waves beginning at one end and proceeding along the myocyte. Beating rates, the propagation velocity of the activation wave, and single sarcomere shortening and relaxation velocities were obtained by manual or automated analysis of 16-mm film recorded at 170 frames/s from a camera attached to a microscope that was equipped with a temperature-controlled stage. In parallel experiments, calcium accumulation by the sarcoplasmic reticulum of the myocytes in situ was measured by direct isotopic tracer methods. The frequency (10-38 min-1) of spontaneous contractions, the velocity (1.9-7.4 microns . s-1) of sarcomere shortening, and the velocity (1.7-6.8 microns . s-1) of sarcomere relaxation displayed identical temperature dependences (Q10 = 2.2), which are similar to that of the calcium pump of sarcoplasmic reticulum and are consistent with a rate limit imposed by enzyme-catalyzed mechanisms on all these parameters. On the other hand, the velocity (77- 159 microns . s-1) of sequential sarcomere activation displayed a lower temperature dependence (Q10 = 1.5), which is consistent with a diffusion-limited and self-propagating release of calcium from one sarcomere to the other. The phasic contractile activity of the dissociated myocytes was inhibited by 10(-8)-10(6) M ryanodine (and not by myolemmal calcium blockers) under conditions in which calcium accumulation by sarcoplasmic reticulum in situ was demonstrated to proceed optimally. The effect of ryanodine is attributed to an interaction of this drug with sarcotubular structures, producing inhibition of calcium release from the sarcoplasmic reticulum. The consequent lack of sarcomere activation underlines the role of sarcoplasmic reticulum uptake and release in the phasic contractile activation of the electrochemically shunted myocytes. PMID:3522803

MIRADCOM/AFATL Hybrid Simulation Facility Compatibility Study. Volume 1

DTIC Science & Technology

1977-02-08

34» " GO TO HnNIltlR": (50 TO AtmiUF.R VIR MEM FILE": DUMP ALL PARTS TO MAG TAPE": DUMP All PARTS TO SOURCE FILE DN DISC 1": MAKE LISTING ÜF ALL...8600,9500^ DHHCF3 = 0 0MNCF6=ti "ÜMPi^ZTT^T?, OHP <,P2=1.0613 ,3,5 ŕ Z7T Fl(DUHN) 62577 = 1.00 ,i5,ZC,Zl,Zg,23,Z’>,^b,Z6,Zy.Z«,ü’J,^y.b,3l

An Obstacle-Tolerant Path Planning Algorithm for Mobile-Anchor-Node-Assisted Localization

PubMed Central

Tsai, Rong-Guei

2018-01-01

The location information obtained using a sensor is a critical requirement in wireless sensor networks. Numerous localization schemes have been proposed, among which mobile-anchor-node-assisted localization (MANAL) can reduce costs and overcome environmental constraints. A mobile anchor node (MAN) provides its own location information to assist the localization of sensor nodes. Numerous path planning schemes have been proposed for MANAL, but most scenarios assume the absence of obstacles in the environment. However, in a realistic environment, sensor nodes cannot be located because the obstacles block the path traversed by the MAN, thereby rendering the sensor incapable of receiving sufficient three location information from the MAN. This study proposes the obstacle-tolerant path planning (OTPP) approach to solve the sensor location problem owing to obstacle blockage. OTPP can approximate the optimum beacon point number and path planning, thereby ensuring that all the unknown nodes can receive the three location information from the MAN and reduce the number of MAN broadcast packet times. Experimental results demonstrate that OTPP performs better than Z-curves because it reduces the total number of beacon points utilized and is thus more suitable in an obstacle-present environment. Compared to the Z-curve, OTPP can reduce localization error and improve localization coverage. PMID:29547582

Monitoring muscle optical scattering properties during rigor mortis

NASA Astrophysics Data System (ADS)

Xia, J.; Ranasinghesagara, J.; Ku, C. W.; Yao, G.

2007-09-01

Sarcomere is the fundamental functional unit in skeletal muscle for force generation. In addition, sarcomere structure is also an important factor that affects the eating quality of muscle food, the meat. The sarcomere structure is altered significantly during rigor mortis, which is the critical stage involved in transforming muscle to meat. In this paper, we investigated optical scattering changes during the rigor process in Sternomandibularis muscles. The measured optical scattering parameters were analyzed along with the simultaneously measured passive tension, pH value, and histology analysis. We found that the temporal changes of optical scattering, passive tension, pH value and fiber microstructures were closely correlated during the rigor process. These results suggested that sarcomere structure changes during rigor mortis can be monitored and characterized by optical scattering, which may find practical applications in predicting meat quality.

Differential Sarcomere and Electrophysiological Maturation of Human iPSC-Derived Cardiac Myocytes in Monolayer vs. Aggregation-Based Differentiation Protocols

PubMed Central

Jeziorowska, Dorota; Fontaine, Vincent; Jouve, Charlène; Villard, Eric; Dussaud, Sébastien; Akbar, David; Letang, Valérie; Cervello, Pauline; Itier, Jean-Michiel; Pruniaux, Marie-Pierre; Hulot, Jean-Sébastien

2017-01-01

Human induced pluripotent stem cells (iPSCs) represent a powerful human model to study cardiac disease in vitro, notably channelopathies and sarcomeric cardiomyopathies. Different protocols for cardiac differentiation of iPSCs have been proposed either based on embroid body formation (3D) or, more recently, on monolayer culture (2D). We performed a direct comparison of the characteristics of the derived cardiomyocytes (iPSC-CMs) on day 27 ± 2 of differentiation between 3D and 2D differentiation protocols with two different Wnt-inhibitors were compared: IWR1 (inhibitor of Wnt response) or IWP2 (inhibitor of Wnt production). We firstly found that the level of Troponin T (TNNT2) expression measured by FACS was significantly higher for both 2D protocols as compared to the 3D protocol. In the three methods, iPSC-CM show sarcomeric structures. However, iPSC-CM generated in 2D protocols constantly displayed larger sarcomere lengths as compared to the 3D protocol. In addition, mRNA and protein analyses reveal higher cTNi to ssTNi ratios in the 2D protocol using IWP2 as compared to both other protocols, indicating a higher sarcomeric maturation. Differentiation of cardiac myocytes with 2D monolayer-based protocols and the use of IWP2 allows the production of higher yield of cardiac myocytes that have more suitable characteristics to study sarcomeric cardiomyopathies. PMID:28587156

Disorder profile of nebulin encodes a vernierlike position sensor for the sliding thin and thick filaments of the skeletal muscle sarcomere

NASA Astrophysics Data System (ADS)

Wu, Ming-Chya; Forbes, Jeffrey G.; Wang, Kuan

2016-06-01

Nebulin is an about 1 μ m long intrinsically disordered scaffold for the thin filaments of skeletal muscle sarcomere. It is a multifunctional elastic protein that wraps around actin filament, stabilizes thin filaments, and regulates Ca-dependent actomyosin interactions. This study investigates whether the disorder profile of nebulin might encode guidelines for thin and thick filament interactions in the sarcomere of the skeletal muscle. The question was addressed computationally by analyzing the predicted disorder profile of human nebulin (6669 residues, ˜200 actin-binding repeats) by pondr and the periodicity of the A-band stripes (reflecting the locations of myosin-associated proteins) in the electron micrographs of the sarcomere. Using the detrended fluctuation analysis, a scale factor for the A-band stripe image data with respect to the nebulin disorder profile was determined to make the thin and thick filaments aligned to have maximum correlation. The empirical mode decomposition method was then applied to identify hidden periodicities in both the nebulin disorder profile and the rescaled A-band data. The decomposition reveals three characteristic length scales (45 nm, 100 nm, and 200 nm) that are relevant for correlational analysis. The dynamical cross-correlation analyses with moving windows at various sarcomere lengths depict a vernierlike design for both periodicities, thus enabling nebulin to sense position and fine tune sarcomere overlap. This shows that the disorder profile of scaffolding proteins may encode a guideline for cellular architecture.

Effects of Mg2+ on Ca2+ release from sarcoplasmic reticulum of skeletal muscle fibres from yabby (crustacean) and rat.

PubMed

Launikonis, B S; Stephenson, D G

2000-07-15

1. The role of myoplasmic [Mg2+] on Ca2+ release from the sarcoplasmic reticulum (SR) was examined in the two major types of crustacean muscle fibres, the tonic, long sarcomere fibres and the phasic, short sarcomere fibres of the fresh water decapod crustacean Cherax destructor (yabby) and in the fast-twitch rat muscle fibres using the mechanically skinned muscle fibre preparation. 2. A robust Ca2+-induced Ca2+-release (CICR) mechanism was present in both long and short sarcomere fibres and 1 mM Mg2+ exerted a strong inhibitory action on the SR Ca2+ release in both fibre types. 3. The SR displayed different properties with respect to Ca2+ loading in the long and the short sarcomere fibres and marked functional differences were identified with respect to Mg2+ inhibition between the two crustacean fibre types. Thus, in long sarcomere fibres, the submaximally loaded SR was able to release Ca2+ when [Mg2+] was lowered from 1 to 0.01 mM in the presence of 8 mM ATPtotal and in the virtual absence of Ca2+ (< 5 nM) even when the CICR was suppressed. In contrast, negligible Ca2+ was released from the submaximally loaded SR of short sarcomere yabby fibres when [Mg2+] was lowered from 1 to 0.01 mM under the same conditions as for the long sarcomere fibres. Nevertheless, the rate of SR Ca2+ release in short sarcomere fibres increased markedly when [Mg2+] was lowered in the presence of [Ca2+] approaching the normal resting levels (50-100 nM). 4. Rat fibres were able to release SR Ca2+ at a faster rate than the long sarcomere yabby fibres when [Mg2+] was lowered from 1 to 0. 01 mM in the virtual absence of Ca2+ but, unlike with yabby fibres, the net rate of Ca2+ release was actually increased for conditions that were considerably less favourable to CICR. 5. In summary, it is concluded that crustacean skeletal muscles have more that one functional type of Ca2+-release channels, that these channels display properties that are intermediate between those of mammalian skeletal and cardiac isoforms, that the inhibition exerted by Mg2+ at rest on the crustacean SR Ca2+-release channels must be removed during excitation-contraction coupling and that, unlike in crustacean fibres, CICR cannot play the major role in the activation of SR Ca2+-release channels in the rat skeletal muscle.

Electro thermal analysis of rotary type micro thermal actuator

NASA Astrophysics Data System (ADS)

Anwar, M. Arefin; Packirisamy, Muthukumaran; Ahmed, A. K. Waiz

2005-09-01

In micro domain, thermal actuators are favored because it provides higher force and deflection than others. This paper presents a new type of micro thermal actuator that provides rotary motion of the circular disc shaped cold arm, which can be used in various optical applications, such as, switching, attenuation, diffraction, etc. The device has been fabricated in MUMPS technology. In this new design, the hot arms are arranged with the cold disc in such a way that thermal expansion of the hot arms due to Joule heating, will make the cold disc to rotate and the rotation is unidirectional on loading. The dominant heat transfer modes in the operating temperature zone are through the anchor and the air between the structure and the substrate because of the very low gap provided by MUMPS. A mathematical model was used for predicting steady state temperature profile along the actuator length and rotational behavior of the cold disc under different applied voltages. A 3-D coupled field finite element analysis (FEM) for the device is also presented. A FEM analysis was done by defining an air volume around the structure and substrate below the structure. Results obtained from the mathematical model, was compared with that of the finite element analysis. The presented results confirm the applicability of this novel rotary type thermal actuator for many optical MEMS applications.

The Galactic thick disc density profile traced with RR Lyrae stars

NASA Astrophysics Data System (ADS)

Mateu, Cecilia; Vivas, A. Katherina

2018-05-01

We used a combination of public RR Lyrae star catalogs and a Bayesian methodology to derive robust structural parameters of the inner halo (<25 kpc) and thick disc of the Milky Way. RR Lyrae stars are an unequivocal tracer of old metal-poor populations, for which accurate distances and extinctions can be individually estimated and so, are a reliable independent means of tracing the population of the old high-[α/Fe] disc usually associated to the thick disc. In particular, the chosen RR Lyrae sample spans regions at low galactic latitude toward the anti-center direction, allowing to probe the outermost parts of the disc. Our results favour a thick disc with short scale height and short scale length, h_z=0.65_{-0.05}^{+0.09} kpc, h_R=2.1_{-0.25}^{+0.82} kpc, for a model in which the inner halo has a constant flattening of q=0.90_{-0.03}^{+0.05} and a power law index of n=-2.78_{-0.05}^{+0.05}. Similar short scales for the thick disc are also found when considering an inner halo with flattening dependent on radius. We also explored a model in which the thick disc has a flare and, although this is only mildly constrained with our data, a flare onset in the inner ˜11 kpc is highly disfavoured.

VizieR Online Data Catalog: Tully-Fisher relation for SDSS galaxies (Reyes+, 2011)

NASA Astrophysics Data System (ADS)

Reyes, R.; Mandelbaum, R.; Gunn, J. E.; Pizagno, J.; Lackner, C. N.

2012-05-01

In this paper, we derive scaling relations between photometric observable quantities and disc galaxy rotation velocity Vrot or Tully-Fisher relations (TFRs). Our methodology is dictated by our purpose of obtaining purely photometric, minimal-scatter estimators of Vrot applicable to large galaxy samples from imaging surveys. To achieve this goal, we have constructed a sample of 189 disc galaxies at redshifts z<0.1 with long-slit Hα spectroscopy from Pizagno et al. (2007, Cat. J/AJ/134/945) and new observations. By construction, this sample is a fair subsample of a large, well-defined parent disc sample of ~170000 galaxies selected from the Sloan Digital Sky Survey Data Release 7 (SDSS DR7). (4 data files).

Bulge Growth Through Disc Instabilities in High-Redshift Galaxies

NASA Astrophysics Data System (ADS)

Bournaud, Frédéric

The role of disc instabilities, such as bars and spiral arms, and the associated resonances, in growing bulges in the inner regions of disc galaxies have long been studied in the low-redshift nearby Universe. There it has long been probed observationally, in particular through peanut-shaped bulges (Chap. 14 10.1007/978-3-319-19378-6_14"). This secular growth of bulges in modern disc galaxies is driven by weak, non-axisymmetric instabilities: it mostly produces pseudobulges at slow rates and with long star-formation timescales. Disc instabilities at high redshift (z > 1) in moderate-mass to massive galaxies (1010 to a few 1011 M⊙ of stars) are very different from those found in modern spiral galaxies. High-redshift discs are globally unstable and fragment into giant clumps containing 108-9 M⊙ of gas and stars each, which results in highly irregular galaxy morphologies. The clumps and other features associated to the violent instability drive disc evolution and bulge growth through various mechanisms on short timescales. The giant clumps can migrate inward and coalesce into the bulge in a few 108 years. The instability in the very turbulent media drives intense gas inflows toward the bulge and nuclear region. Thick discs and supermassive black holes can grow concurrently as a result of the violent instability. This chapter reviews the properties of high-redshift disc instabilities, the evolution of giant clumps and other features associated to the instability, and the resulting growth of bulges and associated sub-galactic components.

Shining in the dark: the spectral evolution of the first black holes

NASA Astrophysics Data System (ADS)

Pacucci, Fabio; Ferrara, Andrea; Volonteri, Marta; Dubus, Guillaume

2015-12-01

Massive black hole (MBH) seeds at redshift z ≳ 10 are now thought to be key ingredients to explain the presence of the supermassive (109-10 M⊙) black holes in place <1 Gyr after the big bang. Once formed, massive seeds grow and emit copious amounts of radiation by accreting the left-over halo gas; their spectrum can then provide crucial information on their evolution. By combining radiation-hydrodynamic and spectral synthesis codes, we simulate the time-evolving spectrum emerging from the host halo of a MBH seed with initial mass 105 M⊙, assuming both standard Eddington-limited accretion, or slim accretion discs, appropriate for super-Eddington flows. The emission occurs predominantly in the observed infrared-submm (1-1000 μm) and X-ray (0.1-100 keV) bands. Such signal should be easily detectable by JWSTaround ˜ 1 μm up to z ˜ 25, and by ATHENA (between 0.1 and 10 keV, up to z ˜ 15). Ultra-deep X-ray surveys like the Chandra Deep Field South could have already detected these systems up to z ˜ 15. Based on this, we provide an upper limit for the z ≳ 6 MBH mass density of ρ• ≲ 2.5 × 102 M⊙ Mpc-3 assuming standard Eddington-limited accretion. If accretion occurs in the slim disc mode the limits are much weaker, ρ• ≲ 7.6 × 103 M⊙ Mpc-3 in the most constraining case.

The magnitude of muscle strain does not influence serial sarcomere number adaptations following eccentric exercise.

PubMed

Butterfield, Timothy A; Herzog, Walter

2006-02-01

It is generally accepted that eccentric exercise, when performed by a muscle that is unaccustomed to that type of contraction, results in a delayed onset of muscle soreness (DOMS). A prolonged exposure to eccentric exercise leads to the disappearance of the signs and symptoms associated with DOMS, which has been referred to as the repeated bout effect (RBE). Although the mechanisms underlying the RBE remain unclear, several mechanisms have been proposed, including the serial sarcomere number addition following exercise induced muscle damage. In the traditional DOMS and RBE protocols, muscle injury has been treated as a global parameter, with muscle force and strain assumed to be uniform throughout the muscle. To assess the effects of muscle-tendon unit strain, fiber strain, torque and injury on serial sarcomere number adaptations, three groups of New Zealand White (NZW) rabbits were subjected to chronic repetitive eccentric exercise bouts of the ankle dorsiflexors for 6 weeks. These eccentric exercise protocols consisted of identical muscle tendon unit (MTU) strain, but other mechanical factors were systematically altered. Following chronic eccentric exercise, serial sarcomere number adaptations were not identical between the three eccentric exercise protocols, and serial sarcomere number adaptations were not uniform across all regions of the muscle. Peak torque and relaxation fiber strain were the best predictors of serial sarcomere number across all three protocols. Therefore, MTU strain does not appear to be the primary cause for sarcomerogenesis, and differential adaptations within the muscle may be explained by the nonuniform architecture of the muscle, resulting in differential local fiber strains.

Real-time determination of sarcomere length of a single cardiomyocyte during contraction

PubMed Central

Kalda, Mari; Vendelin, Marko

2013-01-01

Sarcomere length of a cardiomyocyte is an important control parameter for physiology studies on a single cell level; for instance, its accurate determination in real time is essential for performing single cardiomyocyte contraction experiments. The aim of this work is to develop an efficient and accurate method for estimating a mean sarcomere length of a contracting cardiomyocyte using microscopy images as an input. The novelty in developed method lies in 1) using unbiased measure of similarities to eliminate systematic errors from conventional autocorrelation function (ACF)-based methods when applied to region of interest of an image, 2) using a semianalytical, seminumerical approach for evaluating the similarity measure to take into account spatial dependence of neighboring image pixels, and 3) using a detrend algorithm to extract the sarcomere striation pattern content from the microscopy images. The developed sarcomere length estimation procedure has superior computational efficiency and estimation accuracy compared with the conventional ACF and spectral analysis-based methods using fast Fourier transform. As shown by analyzing synthetic images with the known periodicity, the estimates obtained by the developed method are more accurate at the subpixel level than ones obtained using ACF analysis. When applied in practice on rat cardiomyocytes, our method was found to be robust to the choice of the region of interest that may 1) include projections of carbon fibers and nucleus, 2) have uneven background, and 3) be slightly disoriented with respect to average direction of sarcomere striation pattern. The developed method is implemented in open-source software. PMID:23255581

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

PubMed Central

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

Probing the structure of the gas in the Milky Way through X-ray high-resolution spectroscopy

NASA Astrophysics Data System (ADS)

Gatuzz, Efraín; Churazov, Eugene

2018-02-01

We have developed a new X-ray absorption model, called IONeq, which computes the optical depth τ(E) simultaneously for ions of all abundant elements, assuming ionization equilibrium and taking into account turbulent broadening. We use this model to analyse the interstellar medium (ISM) absorption features in the Milky Way for a sample of 18 Galactic (LMXBs) and 42 extragalactic sources (mainly Blazars). The absorbing ISM was modelled as a combination of three components/phases - neutral (T ≲ 1 × 104 K), warm (T ˜ 5 × 104 K) and hot (T ˜ 2 × 106 K). We found that the spatial distribution of both, neutral and warm components, are difficult to describe using smooth profiles due to non-uniform distribution of the column densities over the sky. For the hot phase we used a combination of a flattened disc and a halo, finding comparable column densities for both spatial components, of the order of ˜6-7 × 1018 cm-2, although this conclusion depends on the adopted parametrization. If the halo component has sub-solar abundance Z, then the column density has to be scaled up by a factor of Z_{⊙}/Z. The vertically integrated column densities of the disc components suggest the following mass fractions for these three ISM phases in the Galactic disc: neutral ˜ 89 per cent, warm ˜ 8 per cent and hot ˜ 3 per cent components, respectively. The constraints on the radial distribution of the halo component of the hot component are weak.

Electronic Imaging: Rochester Imaging Consortium, Abstracts of Research Topics Reported at the Annual Meeting of the Optical Society of America Held in San Jose, California on 3-8 November 1991

DTIC Science & Technology

1991-11-01

Nicholas George "Image Deblurring for Multiple-Point Impulse Responses," Bryan J. Stossel and Nicholas George 14. SUBJECT TERMS 15. NUMBER OF PAGES...Keith B. Farr Nicholas George Backscatter from a Tilted Rough Disc Donald J. Schertler Nicholas George Image Deblurring for Multiple-Point Impulse ...correlation components. Uf) c)z 0 CL C/) Ix I- z 0 0 LL C,z -J a 0l IMAGE DEBLURRING FOR MULTIPLE-POINT IMPULSE RESPONSES Bryan J. Stossel and Nicholas George

Andromeda and its Satellites: A Kinematic Perspective

NASA Astrophysics Data System (ADS)

Collins, M. L. M.; Rich, R. M.; Chapman, S. C.

2012-08-01

Using spectroscopic data taken with Keck II DEIMOS by the Z-PAndAS team in the Andromeda-Triangulum region, I present a comparison of the disc and satellite systems of Andromeda with those of our own Galaxy. I discuss the observed discrepancies between the masses and scale radii of Andromeda dwarf spheroidal galaxies of a given luminosity with those of the Milky Way. I also present an analysis of the newly discovered M31 thick disc, which is measured to be hotter, more extended and thicker than that seen in the Milky Way.

Disc structure and variability in dwarf novae

NASA Astrophysics Data System (ADS)

Harlaftis, Emilios Theofanus

An introduction is given to dwarf novae reviewing the current research status in the field. We present IUE observations of Z Cha which support the mass transfer instability as the cause of the superoutbursts observed in SU UMa type dwarf novae. Comparison between the superoutburst and a normal outburst of Z Cha shows that the disc is flatter and has significantly less azimuthal structure than during superoutburst. Z Cha exhibits a soft x-ray deficit during superoutburst compared to OY Car. We find that the secondary star of Z Cha contributes approximately 30 percent of the infrared flux at peak of outburst. The second part of the thesis presents results from the 1988 International Time Project at the Observatorio del Roque de los Muchachos. Investigation of the behavior of SU UMa and YZ Cnc is carried out through the outburst cycle. The secular changes of the equivalent widths of both systems shows an increasing trend even during quiescence and are caused by the continuum decrease. Both systems show a low-velocity emission component which contaminates the wings of the H(alpha) profile. In addition to doppler broadening, the Stark effect is found to cause significant broadening to the line profile. The radial dependence of the emission lines is discussed in relation to other cataclysmic variables. H(alpha) emission from the secondary star of YZ Cnc is found during superoutburst, during outburst and during quiescence after outburst. Photometry during late decline of outburst shows a sinusoidal, weak variation peaking at 0.5 orbital phase and which is related to heating of the red star or to a transient disc event. During quiescence, the flickering is found to be caused by the bright spot. This modulation increases with time and is maximum before the outburst. Doppler tomography of IP Peg during quiescence reveals an emission line distribution not consistent to the standard model. We find Balmer emission from the secondary star, at a level of only 2.5 percent of the total flux during quiescence. Simultaneously to this, line emission from the outer disc decreases by approximately 70 percent 5 days before an outburst.

Muscle assembly: a titanic achievement?

PubMed

Gregorio, C C; Granzier, H; Sorimachi, H; Labeit, S

1999-02-01

The formation of perfectly aligned myofibrils in striated muscle represents a dramatic example of supramolecular assembly in eukaryotic cells. Recently, considerable progress has been made in deciphering the roles that titin, the third most abundant protein in muscle, has in this process. An increasing number of sarcomeric proteins (ligands) are being identified that bind to specific titin domains. Titin may serve as a molecular blueprint for sarcomere assembly and turnover by specifying the precise position of its ligands within each half-sarcomere in addition to functioning as a molecular spring that maintains the structural integrity of the contracting myofibrils.

Myosin filament activation in the heart is tuned to the mechanical task

PubMed Central

Reconditi, Massimo; Caremani, Marco; Pinzauti, Francesca; Powers, Joseph D.; Narayanan, Theyencheri; Stienen, Ger J. M.; Linari, Marco; Lombardi, Vincenzo

2017-01-01

The mammalian heart pumps blood through the vessels, maintaining the dynamic equilibrium in a circulatory system driven by two pumps in series. This vital function is based on the fine-tuning of cardiac performance by the Frank–Starling mechanism that relates the pressure exerted by the contracting ventricle (end systolic pressure) to its volume (end systolic volume). At the level of the sarcomere, the structural unit of the cardiac myocytes, the Frank–Starling mechanism consists of the increase in active force with the increase of sarcomere length (length-dependent activation). We combine sarcomere mechanics and micrometer–nanometer-scale X-ray diffraction from synchrotron light in intact ventricular trabeculae from the rat to measure the axial movement of the myosin motors during the diastole–systole cycle under sarcomere length control. We find that the number of myosin motors leaving the off, ATP hydrolysis-unavailable state characteristic of the diastole is adjusted to the sarcomere length-dependent systolic force. This mechanosensing-based regulation of the thick filament makes the energetic cost of the systole rapidly tuned to the mechanical task, revealing a prime aspect of the Frank–Starling mechanism. The regulation is putatively impaired by cardiomyopathy-causing mutations that affect the intramolecular and intermolecular interactions controlling the off state of the motors. PMID:28265101

Morphology Is a Link to the Past: Examining Formative and Secular Galactic Evolution through Morphology

NASA Astrophysics Data System (ADS)

Galloway, Melanie A.

Galaxy morphology is one of the primary keys to understanding a galaxy's evolutionary history. External mechanisms (environment/clustering, mergers) have a strong impact on the formative evolution of the major galactic components (disk, bulge, Hubble type), while internal instabilities created by bars, spiral arms, or other substructures drive secular evolution via the rearrangement of material within the disk. This thesis will explore several ways in which morphology impacts the dynamics and evolution of a galaxy using visual classifications from several Galaxy Zoo projects. The first half of this work will detail the motivations of using morphology to study galaxy evolution, and describe how morphology is measured, debiased, and interpreted using crowdsourced classification data via Galaxy Zoo. The second half will present scientific studies which make use of these classifications; first by focusing on the morphology of galaxies in the local Universe (z < 0.2) using data from Galaxy Zoo 2 and Galaxy Zoo UKIDSS. Last, the high-redshift Universe will be explored by examining populations of morphologies at various lookback times, from z = 0 out to z = 1 using data from Galaxy Zoo Hubble. The investigation of the physical implications of morphology in the local Universe will first be presented in Chapter 4, in a study of the impact of bars on the fueling of an active galactic nucleus (AGN). Using a sample of 19,756 disk galaxies at 0.01 < z < 0.05 imaged by the Sloan Digital Sky Survey and morphologically classified by Galaxy Zoo 2 (GZ2), the difference in AGN fraction in barred and unbarred disks was measured. A weak, but statistically significant, effect was found in that the population of AGN hosts exhibited a 16.0% increase in bar fraction as compared to their unbarred counterparts at fixed mass and color. These results are consistent with a cosmological model in which bar-driven fueling contributes to the growth of black holes, but other dynamical mechanisms must also play a significant role. Next, the morphological dependence on wavelength is studied in Chapter 5 by comparing the optical morphological classifications from GZ2 to classifications done on infrared images in GZ:UKIDSS. Consistent morphologies were found in both sets and similar bar fractions, which confirms that for most galaxies, both old and young stellar populations follow similar spatial distributions. Last, the morphological changes in galaxy populations are computed as a function of their age using classifications from Galaxy Zoo: Hubble (Chapter 6). The evolution of the passive disc population from z = 1 to z = 0.3 was studied in a sample of 20,000 galaxies from the COSMOS field and morphologically classified by the Galaxy Zoo: Hubble project. It was found that the fraction of disc galaxies that are red, as well as the fraction of red sequence galaxies that are discs, decreases for the most massive galaxies (log(M/M solar masses) > 11) but increases for lower masses. The observations are consistent with a physical scenario in which more massive galaxies are more likely to enter a red disc phase, and more massive red discs are more likely to morphologically transform into ellipticals than their less massive counterparts. Additionally, the challenges of visual classification that are particular to galaxies at high redshift were investigated. To address these biases, a new correction technique is presented using simulated images of nearby SDSS galaxies which were artificially redshifted using the FERENGI code and classified in GZH.

X-ray and multiwavelength insights into the inner structure of high-luminosity disc-like emitters

NASA Astrophysics Data System (ADS)

Luo, B.; Brandt, W. N.; Eracleous, M.; Wu, Jian; Hall, P. B.; Rafiee, A.; Schneider, D. P.; Wu, Jianfeng

2013-02-01

We present X-ray and multiwavelength studies of a sample of eight high-luminosity active galactic nuclei (AGN) with disc-like Hβ emission-line profiles selected from the Sloan Digital Sky Survey Data Release 7. These sources have higher redshift (z ≈ 0.6) than the majority of the known disc-like emitters, and they occupy a largely unexplored space in the luminosity-redshift plane. Seven sources have typical AGN X-ray spectra with power-law photon indices of Γ ≈ 1.4-2.0; two of them show some X-ray absorption (column density NH ≈ 1021-1022 cm-2 for neutral gas). The other source, J0850+4451, has only three hard X-ray photons detected and is probably heavily obscured (NH ≳ 3 × 1023 cm-2). This object is also identified as a low-ionization broad absorption line (BAL) quasar based on Mg II λ2799 absorption; it is the first disc-like emitter reported that is also a BAL quasar. The infrared-to-ultraviolet (UV) spectral energy distributions (SEDs) of these eight sources are similar to the mean SEDs of typical quasars with a UV `bump', suggestive of standard accretion discs radiating with high efficiency, which differs from low-luminosity disc-like emitters. Studies of the X-ray-to-optical power-law slope parameters (αOX) indicate that there is no significant excess X-ray emission in these high-luminosity disc-like emitters. Energy budget analysis suggests that for disc-like emitters in general, the inner disc must illuminate and ionize the outer disc efficiently (≈15 per cent of the nuclear ionizing radiation is required on average) via direct illumination and/or scattering. Warped accretion discs are probably needed for direct illumination to work in high-luminosity objects, as their geometrically thin inner discs decrease the amount of direct illumination possible for a flat disc.

Pelvic muscles' mechanical response to strains in the absence and presence of pregnancy-induced adaptations in a rat model.

PubMed

Catanzarite, Tatiana; Bremner, Shannon; Barlow, Caitlin L; Bou-Malham, Laura; O'Connor, Shawn; Alperin, Marianna

2018-05-01

Maternal birth trauma to the pelvic floor muscles is thought to be consequent to mechanical demands placed on these muscles during fetal delivery that exceed muscle physiological limits. The above is consistent with studies of striated limb muscles that identify hyperelongation of sarcomeres, the functional muscle units, as the primary cause of mechanical muscle injury and resultant muscle dysfunction. However, pelvic floor muscles' mechanical response to strains have not been examined at a tissue level. Furthermore, we have previously demonstrated that during pregnancy, rat pelvic floor muscles acquire structural and functional adaptations in preparation for delivery, which likely protect against mechanical muscle injury by attenuating the strain effect. We sought to determine the mechanical impact of parturition-related strains on pelvic floor muscles' microstructure, and test the hypothesis that pregnancy-induced adaptations modulate muscle response to strains associated with vaginal delivery. Three-month-old Sprague-Dawley late-pregnant (N = 20) and nonpregnant (N = 22) rats underwent vaginal distention, replicating fetal crowning, with variable distention volumes. Age-matched uninjured pregnant and nonpregnant rats served as respective controls. After sacrifice, pelvic floor muscles, which include coccygeus, iliocaudalis, and pubocaudalis, were fixed in situ and harvested for fiber and sarcomere length measurements. To ascertain the extent of physiological strains during spontaneous vaginal delivery, analogous measurements were obtained in intrapartum rats (N = 4) sacrificed during fetal delivery. Data were compared with repeated measures and 2-way analysis of variance, followed by pairwise comparisons, with significance set at P < .05. Gross anatomic changes were observed in the pelvic floor muscles following vaginal distention, particularly in the entheseal region of pubocaudalis, which appeared translucent. The above appearance resulted from dramatic stretch of the myofibers, as indicated by significantly longer fiber length compared to controls. Stretch ratios, calculated as fiber length after vaginal distention divided by baseline fiber length, increased gradually with increasing distention volume. Paralleling these macroscopic changes, vaginal distention resulted in acute and progressive increase in sarcomere length with rising distention volume. The magnitude of strain effect varied by muscle, with the greatest sarcomere elongation observed in coccygeus, followed by pubocaudalis, and a smaller increase in iliocaudalis, observed only at higher distention volumes. The average fetal rat volume approximated 3 mL. Pelvic floor muscle sarcomere lengths in pregnant animals undergoing vaginal distention with 3 mL were similar to intrapartum sarcomere lengths in all muscles (P > .4), supporting the validity of our experimental approach. Vaginal distention resulted in dramatically longer sarcomere lengths in nonpregnant compared to pregnant animals, especially in coccygeus and pubocaudalis (P < .0001), indicating significant attenuation of sarcomere elongation in the presence of pregnancy-induced adaptations in pelvic floor muscles. Delivery-related strains lead to acute sarcomere elongation, a well-established cause of mechanical injury in skeletal muscles. Sarcomere hyperelongation resultant from mechanical strains is attenuated by pregnancy-induced adaptations acquired by the pelvic floor muscles prior to parturition. Copyright © 2018 Elsevier Inc. All rights reserved.

Chaotic Expansions of Elements of the Universal Enveloping Superalgebra Associated with a Z2-graded Quantum Stochastic Calculus

NASA Astrophysics Data System (ADS)

Eyre, T. M. W.

Given a polynomial function f of classical stochastic integrator processes whose differentials satisfy a closed Ito multiplication table, we can express the stochastic derivative of f as We establish an analogue of this formula in the form of a chaotic decomposition for Z2-graded theories of quantum stochastic calculus based on the natural coalgebra structure of the universal enveloping superalgebra.

Galaxy Zoo: morphological classifications for 120 000 galaxies in HST legacy imaging

NASA Astrophysics Data System (ADS)

Willett, Kyle W.; Galloway, Melanie A.; Bamford, Steven P.; Lintott, Chris J.; Masters, Karen L.; Scarlata, Claudia; Simmons, B. D.; Beck, Melanie; Cardamone, Carolin N.; Cheung, Edmond; Edmondson, Edward M.; Fortson, Lucy F.; Griffith, Roger L.; Häußler, Boris; Han, Anna; Hart, Ross; Melvin, Thomas; Parrish, Michael; Schawinski, Kevin; Smethurst, R. J.; Smith, Arfon M.

2017-02-01

We present the data release paper for the Galaxy Zoo: Hubble (GZH) project. This is the third phase in a large effort to measure reliable, detailed morphologies of galaxies by using crowdsourced visual classifications of colour-composite images. Images in GZH were selected from various publicly released Hubble Space Telescope legacy programmes conducted with the Advanced Camera for Surveys, with filters that probe the rest-frame optical emission from galaxies out to z ˜ 1. The bulk of the sample is selected to have mI814W < 23.5, but goes as faint as mI814W < 26.8 for deep images combined over five epochs. The median redshift of the combined samples is = 0.9 ± 0.6, with a tail extending out to z ≃ 4. The GZH morphological data include measurements of both bulge- and disc-dominated galaxies, details on spiral disc structure that relate to the Hubble type, bar identification, and numerous measurements of clump identification and geometry. This paper also describes a new method for calibrating morphologies for galaxies of different luminosities and at different redshifts by using artificially redshifted galaxy images as a baseline. The GZH catalogue contains both raw and calibrated morphological vote fractions for 119 849 galaxies, providing the largest data set to date suitable for large-scale studies of galaxy evolution out to z ˜ 1.

On the UV compactness and morphologies of typical Lyman α emitters from z ˜ 2 to z ˜ 6

NASA Astrophysics Data System (ADS)

Paulino-Afonso, Ana; Sobral, David; Ribeiro, Bruno; Matthee, Jorryt; Santos, Sérgio; Calhau, João; Forshaw, Alex; Johnson, Andrea; Merrick, Joanna; Pérez, Sara; Sheldon, Oliver

2018-06-01

We investigate the rest-frame UV morphologies of a large sample of Lyman α emitters (LAEs) from z ˜ 2 to z ˜ 6, selected in a uniform way with 16 different narrow and medium bands over the full COSMOS field. We use 3045 LAEs with Hubble Space Telescope coverage in a stacking analysis and find that they have MUV ˜ -20, below M_UV^\\ast at these redshifts. We also focus our analysis on a subsample of 780 individual galaxies with iAB < 25 for which GALFIT converges for 429 of them. The individual median size (re ˜ 1 kpc), ellipticities [slightly elongated with (b/a) ˜ 0.45], Sérsic index (disc-like with n ≲ 2), and light concentration (comparable to that of disc or irregular galaxies, with C ˜ 2.7) of LAEs show mild evolution from z ˜ 2 to z ˜ 6. LAEs with the highest rest-frame equivalent widths (EWs) are the smallest/most compact (re ˜ 0.8 kpc, compared to re ˜ 1.5 kpc for the lower EW LAEs). When stacking our samples in bins of fixed Lyα luminosity and Lyα EW, we find evidence for redshift evolution in n and C, but not in galaxy sizes. The evolution seems to be stronger for LAEs with 25 < EW < 100 Å. When compared to other star-forming galaxies (SFGs), LAEs are found to be smaller at all redshifts. The difference between the two populations changes with redshift, from a factor of ˜1 at z ≳ 5 to SFGs being a factor of ˜2-4 larger than LAEs for z ≲ 2. This means that at the highest redshifts, where typical sizes approach those of LAEs, the fraction of galaxies showing Lyα in emission (and with a high Lyα escape fraction) should be much higher, consistent with observations.

Isolation and expression of scabrous, a gene regulating neurogenesis in Drosophila.

PubMed

Mlodzik, M; Baker, N E; Rubin, G M

1990-11-01

Mutations in the Drosophila scabrous (sca) gene affect eye and bristle development, leading to irregular spacing of ommatidia and bristle duplications in the adult fly. We have cloned the sca gene by P-element tagging. The sca transcription unit is 12 kb and consists of four exons that are joined in a 3.2-kb mRNA. In an enhancer trap screen we have isolated several P[lacZ] insertions close to the sca transcription start site. We have examined the expression pattern of sca by in situ hybridization to sca transcripts, by beta-galactosidase localization in the P[lacZ] lines, and by immunocytochemistry with an anti-sca antiserum. During embryogenesis, sca is expressed in a dynamic pattern associated with neural development. During imaginal development, sca is mainly expressed in the R8 photoreceptor precursor cells in the eye imaginal disc and in sensory organ precursor cells in other discs. In the wing disc, sca expression is coextensive with the anlagen for bristles and is controlled by genes of the achaete-scute complex. Based on its loss-of-function phenotype, expression pattern, and the predicted structure of its product, a secreted peptide with homology to the fibrinogen gene family, we propose that sca encodes a signal involved in lateral inhibition within individual domains of the developing nervous system.

Numerical simulations of Z-Pinch experiments to create supersonic differentially-rotating plasma flows

NASA Astrophysics Data System (ADS)

Bochi, Matteo; Ummels, Sebastiaan; Chittenden, Jeremy; Lebedev, Sergey

2011-10-01

Recently, it was proposed that a small number of plasma jets produced by lasers could be used to generate a plasma configuration relevant to some features of astrophysical accretion disc physics. We propose complementary experimental configurations which employ converging flows generated in a cylindrical wire array Z-pinch modified to produce a rotating plasma. In this paper we present 3D MHD simulations using the code GORGON which show how this approach can be implemented at the MAGPIE facility at Imperial College, London. We will present the general scenario and the results of a parametric study relating the parameters of the array with the features of the resulting plasma. In particular, we will show how a rotating plasma cylinder or ring, with typical rotation velocity 30 Km/s and Mach number 8 is formed, and how, after about 1-2 revolutions, the material of the plasma ring is ejected in a pair of thermally driven, conical outflows propagating along the rotation axis. We will discuss to what aspects of the physics of accretion discs, the results of such experiments could be relevant. We will also consider the effects of different magnetic configurations, which further expand the possibility to relate the experiments with the astrophysical discs. Experimental implementation of some of these setups is currently in progress on MAGPIE.

Galaxy Zoo: the dependence of the star formation-stellar mass relation on spiral disc morphology

NASA Astrophysics Data System (ADS)

Willett, Kyle W.; Schawinski, Kevin; Simmons, Brooke D.; Masters, Karen L.; Skibba, Ramin A.; Kaviraj, Sugata; Melvin, Thomas; Wong, O. Ivy; Nichol, Robert C.; Cheung, Edmond; Lintott, Chris J.; Fortson, Lucy

2015-05-01

We measure the stellar mass-star formation rate (SFR) relation in star-forming disc galaxies at z ≤ 0.085, using Galaxy Zoo morphologies to examine different populations of spirals as classified by their kiloparsec-scale structure. We examine the number of spiral arms, their relative pitch angle, and the presence of a galactic bar in the disc, and show that both the slope and dispersion of the M⋆-SFR relation is constant when varying all the above parameters. We also show that mergers (both major and minor), which represent the strongest conditions for increases in star formation at a constant mass, only boost the SFR above the main relation by ˜0.3 dex; this is significantly smaller than the increase seen in merging systems at z > 1. Of the galaxies lying significantly above the M⋆-SFR relation in the local Universe, more than 50 per cent are mergers. We interpret this as evidence that the spiral arms, which are imperfect reflections of the galaxy's current gravitational potential, are either fully independent of the various quenching mechanisms or are completely overwhelmed by the combination of outflows and feedback. The arrangement of the star formation can be changed, but the system as a whole regulates itself even in the presence of strong dynamical forcing.

Origin of chemically distinct discs in the Auriga cosmological simulations

NASA Astrophysics Data System (ADS)

Grand, Robert J. J.; Bustamante, Sebastián; Gómez, Facundo A.; Kawata, Daisuke; Marinacci, Federico; Pakmor, Rüdiger; Rix, Hans-Walter; Simpson, Christine M.; Sparre, Martin; Springel, Volker

2018-03-01

The stellar disc of the Milky Way shows complex spatial and abundance structure that is central to understanding the key physical mechanisms responsible for shaping our Galaxy. In this study, we use six very high resolution cosmological zoom-in simulations of Milky Way-sized haloes to study the prevalence and formation of chemically distinct disc components. We find that our simulations develop a clearly bimodal distribution in the [α/Fe]-[Fe/H] plane. We find two main pathways to creating this dichotomy, which operate in different regions of the galaxies: (a) an early (z > 1) and intense high-[α/Fe] star formation phase in the inner region (R ≲ 5 kpc) induced by gas-rich mergers, followed by more quiescent low-[α/Fe] star formation; and (b) an early phase of high-[α/Fe] star formation in the outer disc followed by a shrinking of the gas disc owing to a temporarily lowered gas accretion rate, after which disc growth resumes. In process (b), a double-peaked star formation history around the time and radius of disc shrinking accentuates the dichotomy. If the early star formation phase is prolonged (rather than short and intense), chemical evolution proceeds as per process (a) in the inner region, but the dichotomy is less clear. In the outer region, the dichotomy is only evident if the first intense phase of star formation covers a large enough radial range before disc shrinking occurs; otherwise, the outer disc consists of only low-[α/Fe] sequence stars. We discuss the implication that both processes occurred in the Milky Way.

Retraction: Myostatin Induces Degradation of Sarcomeric Proteins through a Smad3 Signaling Mechanism During Skeletal Muscle Wasting

PubMed Central

Lokireddy, Sudarsanareddy; McFarlane, Craig; Ge, Xiaojia; Zhang, Huoming; Sze, Siu Kwan; Sharma, Mridula

2011-01-01

Ubiquitination-mediated proteolysis is a hallmark of skeletal muscle wasting manifested in response to negative growth factors, including myostatin. Thus, the characterization of signaling mechanisms that induce the ubiquitination of intracellular and sarcomeric proteins during skeletal muscle wasting is of great importance. We have recently characterized myostatin as a potent negative regulator of myogenesis and further demonstrated that elevated levels of myostatin in circulation results in the up-regulation of the muscle-specific E3 ligases, Atrogin-1 and muscle ring finger protein 1 (MuRF1). However, the exact signaling mechanisms by which myostatin regulates the expression of Atrogin-1 and MuRF1, as well as the proteins targeted for degradation in response to excess myostatin, remain to be elucidated. In this report, we have demonstrated that myostatin signals through Smad3 (mothers against decapentaplegic homolog 3) to activate forkhead box O1 and Atrogin-1 expression, which further promotes the ubiquitination and subsequent proteasome-mediated degradation of critical sarcomeric proteins. Smad3 signaling was dispensable for myostatin-dependent overexpression of MuRF1. Although down-regulation of Atrogin-1 expression rescued approximately 80% of sarcomeric protein loss induced by myostatin, only about 20% rescue was seen when MuRF1 was silenced, implicating that Atrogin-1 is the predominant E3 ligase through which myostatin manifests skeletal muscle wasting. Furthermore, we have highlighted that Atrogin-1 not only associates with myosin heavy and light chain, but it also ubiquitinates these sarcomeric proteins. Based on presented data we propose a model whereby myostatin induces skeletal muscle wasting through targeting sarcomeric proteins via Smad3-mediated up-regulation of Atrogin-1 and forkhead box O1. PMID:21964591

Mechanical principles of effects of botulinum toxin on muscle length-force characteristics: an assessment by finite element modeling.

PubMed

Turkoglu, Ahu N; Huijing, Peter A; Yucesoy, Can A

2014-05-07

Recent experiments involving muscle force measurements over a range of muscle lengths show that effects of botulinum toxin (BTX) are complex e.g., force reduction varies as a function of muscle length. We hypothesized that altered conditions of sarcomeres within active parts of partially paralyzed muscle is responsible for this effect. Using finite element modeling, the aim was to test this hypothesis and to study principles of how partial activation as a consequence of BTX affects muscle mechanics. In order to model the paralyzing effect of BTX, only 50% of the fascicles (most proximal, or middle, or most distal) of the modeled muscle were activated. For all muscle lengths, a vast majority of sarcomeres of these BTX-cases were at higher lengths than identical sarcomeres of the BTX-free muscle. Due to such "longer sarcomere effect", activated muscle parts show an enhanced potential of active force exertion (up to 14.5%). Therefore, a muscle force reduction originating exclusively from the paralyzed muscle fiber populations, is compromised by the changes of active sarcomeres leading to a smaller net force reduction. Moreover, such "compromise to force reduction" varies as a function of muscle length and is a key determinant of muscle length dependence of force reduction caused by BTX. Due to longer sarcomere effect, muscle optimum length tends to shift to a lower muscle length. Muscle fiber-extracellular matrix interactions occurring via their mutual connections along full peripheral fiber lengths (i.e., myofascial force transmission) are central to these effects. Our results may help improving our understanding of mechanisms of how the toxin secondarily affects the muscle mechanically. Copyright © 2014 Elsevier Ltd. All rights reserved.

Familial hypertrophic cardiomyopathy: functional variance among individual cardiomyocytes as a trigger of FHC-phenotype development

PubMed Central

Brenner, Bernhard; Seebohm, Benjamin; Tripathi, Snigdha; Montag, Judith; Kraft, Theresia

2014-01-01

Familial hypertrophic cardiomyopathy (FHC) is the most frequent inherited cardiac disease. It has been related to numerous mutations in many sarcomeric and even some non-sarcomeric proteins. So far, however, no common mechanism has been identified by which the many different mutations in different sarcomeric and non-sarcomeric proteins trigger development of the FHC phenotype. Here we show for different MYH7 mutations variance in force pCa-relations from normal to highly abnormal as a feature common to all mutations we studied, while direct functional effects of the different FHC-mutations, e.g., on force generation, ATPase or calcium sensitivity of the contractile system, can be quite different. The functional variation among individual M. soleus fibers of FHC-patients is accompanied by large variation in mutant vs. wildtype β-MyHC-mRNA. Preliminary results show a similar variation in mutant vs. wildtype β-MyHC-mRNA among individual cardiomyocytes. We discuss our previously proposed concept as to how different mutations in the β-MyHC and possibly other sarcomeric and non-sarcomeric proteins may initiate an FHC-phenotype by functional variation among individual cardiomyocytes that results in structural distortions within the myocardium, leading to cellular and myofibrillar disarray. In addition, distortions can activate stretch-sensitive signaling in cardiomyocytes and non-myocyte cells which is known to induce cardiac remodeling with interstitial fibrosis and hypertrophy. Such a mechanism will have major implications for therapeutic strategies to prevent FHC-development, e.g., by reducing functional imbalances among individual cardiomyocytes or by inhibition of their triggering of signaling paths initiating remodeling. Targeting increased or decreased contractile function would require selective targeting of mutant or wildtype protein to reduce functional imbalances. PMID:25346696

Cardiac alpha-myosin (MYH6) is the predominant sarcomeric disease gene for familial atrial septal defects.

PubMed

Posch, Maximilian G; Waldmuller, Stephan; Müller, Melanie; Scheffold, Thomas; Fournier, David; Andrade-Navarro, Miguel A; De Geeter, Bernard; Guillaumont, Sophie; Dauphin, Claire; Yousseff, Dany; Schmitt, Katharina R; Perrot, Andreas; Berger, Felix; Hetzer, Roland; Bouvagnet, Patrice; Özcelik, Cemil

2011-01-01

Secundum-type atrial septal defects (ASDII) account for approximately 10% of all congenital heart defects (CHD) and are associated with a familial risk. Mutations in transcription factors represent a genetic source for ASDII. Yet, little is known about the role of mutations in sarcomeric genes in ASDII etiology. To assess the role of sarcomeric genes in patients with inherited ASDII, we analyzed 13 sarcomeric genes (MYH7, MYBPC3, TNNT2, TCAP, TNNI3, MYH6, TPM1, MYL2, CSRP3, ACTC1, MYL3, TNNC1, and TTN kinase region) in 31 patients with familial ASDII using array-based resequencing. Genotyping of family relatives and control subjects as well as structural and homology analyses were used to evaluate the pathogenic impact of novel non-synonymous gene variants. Three novel missense mutations were found in the MYH6 gene encoding alpha-myosin heavy chain (R17H, C539R, and K543R). These mutations co-segregated with CHD in the families and were absent in 370 control alleles. Interestingly, all three MYH6 mutations are located in a highly conserved region of the alpha-myosin motor domain, which is involved in myosin-actin interaction. In addition, the cardiomyopathy related MYH6-A1004S and the MYBPC3-A833T mutations were also found in one and two unrelated subjects with ASDII, respectively. No mutations were found in the 11 other sarcomeric genes analyzed. The study indicates that sarcomeric gene mutations may represent a so far underestimated genetic source for familial recurrence of ASDII. In particular, perturbations in the MYH6 head domain seem to play a major role in the genetic origin of familial ASDII.

The nature of the island and banana states in atoll sources and a unified model for low-mass X-ray binaries

NASA Astrophysics Data System (ADS)

Church, M. J.; Gibiec, A.; Bałucińska-Church, M.

2014-03-01

We propose an explanation of the island and banana states and the relation between atoll and Z-track sources, constituting a unified model for low-mass X-ray binaries (LMXB). We find a dramatic transition at a luminosity of 1-2 × 1037 erg s-1 above which the high-energy cut-off ECO of the Comptonized emission in all sources is low at a few keV. There is thermal equilibrium between the neutron star at ˜2 keV and the Comptonizing accretion disc corona (ADC) causing the low ECO in the banana state of atolls and all states of the Z-track sources. Below this luminosity, ECO increases towards 100 keV causing the hardness of the island state. Thermal equilibrium is lost, the ADC becoming much hotter than the neutron star via an additional coronal heating mechanism. This suggests a unified model of LMXB: the banana state is a basic state with the mass accretion rate dot{M} increasing, corresponding to the normal branch of Z-track sources. The island state has high ADC temperature, this state not existing in the Z-sources with luminosities much greater than the critical value. The Z-track sources have an additional flaring branch consistent with unstable nuclear burning on the neutron star at high dot{M}. This burning regime does not exist at low dot{M} so this branch is not seen in atolls (except GX atolls). The horizontal branch in Z-track sources has a strong increase in radiation pressure disrupting the inner disc and launching relativistic jets.

Tubulin homolog TubZ in a phage-encoded partition system

PubMed Central

Oliva, María A.; Martin-Galiano, Antonio J.; Sakaguchi, Yoshihiko; Andreu, José M.

2012-01-01

Partition systems are responsible for the process whereby large and essential plasmids are accurately positioned to daughter cells during bacterial division. They are typically made of three components: a centromere-like DNA zone, an adaptor protein, and an assembling protein that is either a Walker-box ATPase (type I) or an actin-like ATPase (type II). A recently described type III segregation system has a tubulin/FtsZ-like protein, called TubZ, for plasmid movement. Here, we present the 2.3 Å structure and dynamic assembly of a TubZ tubulin homolog from a bacteriophage and unravel the Clostridium botulinum phage c-st type III partition system. Using biochemical and biophysical approaches, we prove that a gene upstream from tubZ encodes the partner TubR and localize the centromeric region (tubS), both of which are essential for anchoring phage DNA to the motile TubZ filaments. Finally, we describe a conserved fourth component, TubY, which modulates the TubZ-R-S complex interaction. PMID:22538818

Growth promoting in vitro effect of synthetic cyclic RGD-peptides on human osteoblast-like cells attached to cancellous bone.

PubMed

Magdolen, Ursula; Auernheimer, Jörg; Dahmen, Claudia; Schauwecker, Johannes; Gollwitzer, Hans; Tübel, Jutta; Gradinger, Reiner; Kessler, Horst; Schmitt, Manfred; Diehl, Peter

2006-06-01

In tissue engineering, the application of biofunctional compounds on biomaterials such as integrin binding RGD-peptides has gained growing interest. Anchorage-dependent cells like osteoblasts bind to these peptides thus ameliorating the integration of a synthetic implant. In case sterilized bone grafts are used as substitutes for reconstruction of bone defects, the ingrowth of the implanted bone is often disturbed because of severe pretreatment such as irradiation or autoclaving, impairing the biological and mechanical properties of the bone. We report for the first time on the in vitro coating of the surface of freshly resected, cleaned bone discs with synthetic, cyclic RGD-peptides. For this approach, two different RGD-peptides were used, one containing two phosphonate anchors, the other peptide four of these binding moieties to allow efficient association of these reactive RGD-peptides to the inorganic bone matrix. Human osteoblast-like cells were cultured on RGD-coated bone discs and the adherence and growth of the cells were analyzed. Coating of bone discs with RGD-peptides did not improve the adhesion rate of osteoblast-like cells to the discs but significantly (up to 40%) accelerated growth of these cells within 8 days after attachment. This effect points to pretreatment of bone implants, especially at the critical interface area between the implanted bone and the non-resected residual bone structure, before re-implantation in order to stimulate and enhance osteointegration of a bone implant.

Pulse splitter-based nonlinear microscopy for live-cardiomyocyte imaging

PubMed Central

Wang, Zhonghai; Qin, Wan; Shao, Yonghong; Ma, Siyu; Borg, Thomas K.; Gao, Bruce Z.

2015-01-01

Second harmonic generation (SHG) microscopy is a new imaging technique used in sarcomeric-addition studies. However, during the early stage of cell culture in which sarcomeric additions occur, the neonatal cardiomyocytes that we have been working with are very sensitive to photodamage, the resulting high rate of cell death prevents systematic study of sarcomeric addition using a conventional SHG system. To address this challenge, we introduced use of the pulse-splitter system developed by Na Ji et al. in our two photon excitation fluorescence (TPEF) and SHG hybrid microscope. The system dramatically reduced photodamage to neonatal cardiomyocytes in early stages of culture, greatly increasing cell viability. Thus continuous imaging of live cardiomyocytes was achieved with a stronger laser and for a longer period than has been reported in the literature. The pulse splitter-based TPEF-SHG microscope constructed in this study was demonstrated to be an ideal imaging system for sarcomeric addition-related investigations of neonatal cardiomyocytes in early stages of culture. PMID:25767692

Mechanical Properties of Respiratory Muscles

PubMed Central

Sieck, Gary C.; Ferreira, Leonardo F.; Reid, Michael B.; Mantilla, Carlos B.

2014-01-01

Striated respiratory muscles are necessary for lung ventilation and to maintain the patency of the upper airway. The basic structural and functional properties of respiratory muscles are similar to those of other striated muscles (both skeletal and cardiac). The sarcomere is the fundamental organizational unit of striated muscles and sarcomeric proteins underlie the passive and active mechanical properties of muscle fibers. In this respect, the functional categorization of different fiber types provides a conceptual framework to understand the physiological properties of respiratory muscles. Within the sarcomere, the interaction between the thick and thin filaments at the level of cross-bridges provides the elementary unit of force generation and contraction. Key to an understanding of the unique functional differences across muscle fiber types are differences in cross-bridge recruitment and cycling that relate to the expression of different myosin heavy chain isoforms in the thick filament. The active mechanical properties of muscle fibers are characterized by the relationship between myoplasmic Ca2+ and cross-bridge recruitment, force generation and sarcomere length (also cross-bridge recruitment), external load and shortening velocity (cross-bridge cycling rate), and cross-bridge cycling rate and ATP consumption. Passive mechanical properties are also important reflecting viscoelastic elements within sarcomeres as well as the extracellular matrix. Conditions that affect respiratory muscle performance may have a range of underlying pathophysiological causes, but their manifestations will depend on their impact on these basic elemental structures. PMID:24265238

The local stellar velocity distribution of the Galaxy. Galactic structure and potential

NASA Astrophysics Data System (ADS)

Bienaymé, O.

1999-01-01

The velocity distribution of neighbouring stars is deduced from the Hipparcos proper motions. We have used a classical Schwarzschild decomposition and also developed a dynamical model for quasi-exponential stellar discs. This model is a 3-D derivation of Shu's model in the framework of Stäckel potentials with three integrals of motion. We determine the solar motion relative to the local standard of rest (LSR) (U_sun=9.7+/-0.3kms , V_sun=5.2+/-1.0kms and W_sun=6.7+/-0.2kms ), the density and kinematic radial gradients, as well as the local slope of the velocity curve. We find out that the scale density length of the Galaxy is 1.8+/-0.2kpc . We measure a large kinematic scale length for blue (young) stars, R_{sigma_r }=17+/-4kpc , while for red stars (predominantly old) we find R_{sigma_r }=9.7+/-0.8kpc (or R_{sigma_r (2}=4.8+/-0.4kpc ) ). From the stellar disc dynamical model, we determine explicitly the link between the tangential-vertical velocity (v_theta , v_z) coupling and the local shape of the potential. Using a restricted sample of 3-D velocity data, we measure z_o, the focus of the spheroidal coordinate system defining the best fitted Stäckel potential. The parameter z_o is related to the tilt of the velocity ellipsoid and more fundamentally to the mass gradient in the galactic disc. This parameter is found to be 5.7+/-1.4kpc . This implies that the galactic potential is not extremely flat and that the dark matter component is not confined in the galactic plane. Based on data from the Hipparcos astrometry satellite.

Hypertrophic Stimulation Increases β-actin Dynamics in Adult Feline Cardiomyocytes

PubMed Central

Balasubramanian, Sundaravadivel; Mani, Santhosh K.; Kasiganesan, Harinath; Baicu, Catalin C.; Kuppuswamy, Dhandapani

2010-01-01

The myocardium responds to hemodynamic stress through cellular growth and organ hypertrophy. The impact of cytoskeletal elements on this process, however, is not fully understood. While α-actin in cardiomyocytes governs muscle contraction in combination with the myosin motor, the exact role of β-actin has not been established. We hypothesized that in adult cardiomyocytes, as in non-myocytes, β-actin can facilitate cytoskeletal rearrangement within cytoskeletal structures such as Z-discs. Using a feline right ventricular pressure overload (RVPO) model, we measured the level and distribution of β-actin in normal and pressure overloaded myocardium. Resulting data demonstrated enriched levels of β-actin and enhanced translocation to the Triton-insoluble cytoskeletal and membrane skeletal complexes. In addition, RVPO in vivo and in vitro hypertrophic stimulation with endothelin (ET) or insulin in isolated adult cardiomyocytes enhanced the content of polymerized fraction (F-actin) of β-actin. To determine the localization and dynamics of β-actin, we adenovirally expressed GFP-tagged β-actin in isolated adult cardiomyocytes. The ectopically expressed β-actin-GFP localized to the Z-discs, costameres, and cell termini. Fluorescence recovery after photobleaching (FRAP) measurements of β-actin dynamics revealed that β-actin at the Z-discs is constantly being exchanged with β-actin from cytoplasmic pools and that this exchange is faster upon hypertrophic stimulation with ET or insulin. In addition, in electrically stimulated isolated adult cardiomyocytes, while β-actin overexpression improved cardiomyocyte contractility, immunoneutralization of β-actin resulted in a reduced contractility suggesting that β-actin could be important for the contractile function of adult cardiomyocytes. These studies demonstrate the presence and dynamics of β-actin in the adult cardiomyocyte and reinforce its usefulness in measuring cardiac cytoskeletal rearrangement during hypertrophic stimulation. PMID:20635003

Hypertrophic stimulation increases beta-actin dynamics in adult feline cardiomyocytes.

PubMed

Balasubramanian, Sundaravadivel; Mani, Santhosh K; Kasiganesan, Harinath; Baicu, Catalin C; Kuppuswamy, Dhandapani

2010-07-12

The myocardium responds to hemodynamic stress through cellular growth and organ hypertrophy. The impact of cytoskeletal elements on this process, however, is not fully understood. While alpha-actin in cardiomyocytes governs muscle contraction in combination with the myosin motor, the exact role of beta-actin has not been established. We hypothesized that in adult cardiomyocytes, as in non-myocytes, beta-actin can facilitate cytoskeletal rearrangement within cytoskeletal structures such as Z-discs. Using a feline right ventricular pressure overload (RVPO) model, we measured the level and distribution of beta-actin in normal and pressure overloaded myocardium. Resulting data demonstrated enriched levels of beta-actin and enhanced translocation to the Triton-insoluble cytoskeletal and membrane skeletal complexes. In addition, RVPO in vivo and in vitro hypertrophic stimulation with endothelin (ET) or insulin in isolated adult cardiomyocytes enhanced the content of polymerized fraction (F-actin) of beta-actin. To determine the localization and dynamics of beta-actin, we adenovirally expressed GFP-tagged beta-actin in isolated adult cardiomyocytes. The ectopically expressed beta-actin-GFP localized to the Z-discs, costameres, and cell termini. Fluorescence recovery after photobleaching (FRAP) measurements of beta-actin dynamics revealed that beta-actin at the Z-discs is constantly being exchanged with beta-actin from cytoplasmic pools and that this exchange is faster upon hypertrophic stimulation with ET or insulin. In addition, in electrically stimulated isolated adult cardiomyocytes, while beta-actin overexpression improved cardiomyocyte contractility, immunoneutralization of beta-actin resulted in a reduced contractility suggesting that beta-actin could be important for the contractile function of adult cardiomyocytes. These studies demonstrate the presence and dynamics of beta-actin in the adult cardiomyocyte and reinforce its usefulness in measuring cardiac cytoskeletal rearrangement during hypertrophic stimulation.

Differences in the intensity of light-induced fluorescence emitted by resin composites.

PubMed

Kim, Bo-Ra; Kang, Si-Mook; Kim, Gyung-Min; Kim, Baek-Il

2016-03-01

The aims of this study were to compare the intensities of fluorescence emitted by different resin composites as detected using quantitative light-induced fluorescence (QLF) technology, and to compare the fluorescence intensity contrast with the color contrast between a restored composite and the adjacent region of the tooth. Six brands of light-cured resin composites (shade A2) were investigated. The composites were used to prepare composite discs, and fill holes that had been prepared in extracted human teeth. White-light and fluorescence images of all specimens were obtained using a fluorescence camera based on QLF technology (QLF-D) and converted into 8-bit grayscale images. The fluorescence intensity of the discs as well as the fluorescence intensity contrast and the color contrast between the composite restoration and adjacent tooth region were calculated as grayscale levels. The grayscale levels for the composite discs differed significantly with the brand (p<0.001): DenFil (10.84±0.35, mean±SD), Filtek Z350 (58.28±1.37), Premisa (156.94±1.58), Grandio (177.20±0.81), Charisma (207.05±0.77), and Gradia direct posterior (211.52±1.66). The difference in grayscale levels between a resin restoration and the adjacent tooth was significantly greater in fluorescence images for each brand than in white-light images, except for the Filtek Z350 (p<0.05). However, the Filtek Z350 restoration was distinguishable from the adjacent tooth in a fluorescence image. The intensities of fluorescence detected from the resin composites varied. The differences between the composite and adjacent tooth were greater for the fluorescence intensity contrast than for the colors observed in the white-light images. Copyright © 2016 Elsevier B.V. All rights reserved.

Formation of S0s via disc accretion around high-redshift compact ellipticals

NASA Astrophysics Data System (ADS)

Diaz, Jonathan; Bekki, Kenji; Forbes, Duncan A.; Couch, Warrick J.; Drinkwater, Michael J.; Deeley, Simon

2018-06-01

We present hydrodynamical N-body models which demonstrate that elliptical galaxies can transform into S0s by acquiring a disc. In particular, we show that the merger with a massive gas-rich satellite can lead to the formation of a baryonic disc around an elliptical. We model the elliptical as a massive, compact galaxy which could be observed as a `red nugget' in the high-z universe. This scenario contrasts with existing S0 formation scenarios in the literature in two important ways. First, the progenitor is an elliptical galaxy whereas scenarios in the literature typically assume a spiral progenitor. Secondly, the physical conditions underlying our proposed scenario can exist in low-density environments such as the field, in contrast to scenarios in the literature which typically address dense environments like clusters and groups. As a consequence, S0s in the field may be the most likely candidates to have evolved from elliptical progenitors. Our scenario also naturally explains recent observations which indicate that field S0s may have older bulges than discs, contrary to cluster S0s which seem to have older discs than bulges.

Long term multiwavelength studies of the corona/disc connection in AGN

NASA Astrophysics Data System (ADS)

Buisson, D.; Lohfink, A.; Alston, W.; Fabian, A.; Gallo, L.; Kara, E.; Zoghbi, A.; Wilkins, D.; Miller, J.; Cackett, E.

2017-10-01

One way of increasing our understanding of AGN is determining the nature of the connection between the optical/UV emitting accretion disc and the X-ray emitting corona. Studies of variability in these two bands are a key tool for gaining insight into the processes involved. We will present results from a sample of long-term AGN monitoring campaigns in the optical, UV and X-ray with Swift. In particular, we will explore UV/optical-X-ray correlations and associated time lags. We will compare these measurements and the UV/optical RMS spectra with theoretical reprocessing models and confront recent claims of the observed lags being longer than those which are expected for a standard thin disc. Additionally, a new Swift monitoring campaign of the z=2 quasar PG 1247+267 allows us to probe the shorter wavelengths at the peak of the accretion disc spectrum, providing information on the region of the disc closest to the black hole. However, not all AGN show such correlations, including IRAS 13224-3809, the subject of a recent 1.5 Ms XMM observation. Using this and other examples, we will explore the possible reasons for the lack of observed correlation.

Bright Compact Bulges (BCBs) at intermediate redshifts

NASA Astrophysics Data System (ADS)

Sachdeva, Sonali; Saha, Kanak

2018-04-01

Studying bright (MB < -20), intermediate-redshift (0.4 < z < 1.0), disc dominated (nB < 2.5) galaxies from HST/ACS and WFC3 in Chandra Deep Field South, in rest-frame B and I-band, we found a new class of bulges which is brighter and more compact than ellipticals. We refer to them as "Bright, Compact Bulges" (BCBs) - they resemble neither classical nor pseudo-bulges and constitute ˜12% of the total bulge population at these redshifts. Examining free-bulge + disc decomposition sample and elliptical galaxy sample from Simard et al. (2011), we find that only ˜0.2% of the bulges can be classified as BCBs in the local Universe. Bulge to total ratio (B/T) of disc galaxies with BCBs is (at ˜0.4) a factor of ˜2 and ˜4 larger than for those with classical and pseudo bulges. BCBs are ˜2.5 and ˜6 times more massive than classical and pseudo bulges. Although disc galaxies with BCBs host the most massive and dominant bulge type, their specific star formation rate is 1.5-2 times higher than other disc galaxies. This is contrary to the expectations that a massive compact bulge would lead to lower star formation rates. We speculate that our BCB host disc galaxies are descendant of massive, compact and passive elliptical galaxies observed at higher redshifts. Those high redshift ellipticals lack local counterparts and possibly evolved by acquiring a compact disc around them. The overall properties of BCBs supports a picture of galaxy assembly in which younger discs are being accreted around massive pre-existing spheroids.

Anchoring genome sequence to chromosomes of the central bearded dragon (Pogona vitticeps) enables reconstruction of ancestral squamate macrochromosomes and identifies sequence content of the Z chromosome.

PubMed

Deakin, Janine E; Edwards, Melanie J; Patel, Hardip; O'Meally, Denis; Lian, Jinmin; Stenhouse, Rachael; Ryan, Sam; Livernois, Alexandra M; Azad, Bhumika; Holleley, Clare E; Li, Qiye; Georges, Arthur

2016-06-10

Squamates (lizards and snakes) are a speciose lineage of reptiles displaying considerable karyotypic diversity, particularly among lizards. Understanding the evolution of this diversity requires comparison of genome organisation between species. Although the genomes of several squamate species have now been sequenced, only the green anole lizard has any sequence anchored to chromosomes. There is only limited gene mapping data available for five other squamates. This makes it difficult to reconstruct the events that have led to extant squamate karyotypic diversity. The purpose of this study was to anchor the recently sequenced central bearded dragon (Pogona vitticeps) genome to chromosomes to trace the evolution of squamate chromosomes. Assigning sequence to sex chromosomes was of particular interest for identifying candidate sex determining genes. By using two different approaches to map conserved blocks of genes, we were able to anchor approximately 42 % of the dragon genome sequence to chromosomes. We constructed detailed comparative maps between dragon, anole and chicken genomes, and where possible, made broader comparisons across Squamata using cytogenetic mapping information for five other species. We show that squamate macrochromosomes are relatively well conserved between species, supporting findings from previous molecular cytogenetic studies. Macrochromosome diversity between members of the Toxicofera clade has been generated by intrachromosomal, and a small number of interchromosomal, rearrangements. We reconstructed the ancestral squamate macrochromosomes by drawing upon comparative cytogenetic mapping data from seven squamate species and propose the events leading to the arrangements observed in representative species. In addition, we assigned over 8 Mbp of sequence containing 219 genes to the Z chromosome, providing a list of genes to begin testing as candidate sex determining genes. Anchoring of the dragon genome has provided substantial insight into the evolution of squamate genomes, enabling us to reconstruct ancestral macrochromosome arrangements at key positions in the squamate phylogeny, demonstrating that fusions between macrochromosomes or fusions of macrochromosomes and microchromosomes, have played an important role during the evolution of squamate genomes. Assigning sequence to the sex chromosomes has identified NR5A1 as a promising candidate sex determining gene in the dragon.

The KMOS Redshift One Spectroscopic Survey (KROSS): the origin of disc turbulence in z ≈ 1 star-forming galaxies

NASA Astrophysics Data System (ADS)

Johnson, H. L.; Harrison, C. M.; Swinbank, A. M.; Tiley, A. L.; Stott, J. P.; Bower, R. G.; Smail, Ian; Bunker, A. J.; Sobral, D.; Turner, O. J.; Best, P.; Bureau, M.; Cirasuolo, M.; Jarvis, M. J.; Magdis, G.; Sharples, R. M.; Bland-Hawthorn, J.; Catinella, B.; Cortese, L.; Croom, S. M.; Federrath, C.; Glazebrook, K.; Sweet, S. M.; Bryant, J. J.; Goodwin, M.; Konstantopoulos, I. S.; Lawrence, J. S.; Medling, A. M.; Owers, M. S.; Richards, S.

2018-03-01

We analyse the velocity dispersion properties of 472 z ˜ 0.9 star-forming galaxies observed as part of the KMOS Redshift One Spectroscopic Survey (KROSS). The majority of this sample is rotationally dominated (83 ± 5 per cent with vC/σ0 > 1) but also dynamically hot and highly turbulent. After correcting for beam smearing effects, the median intrinsic velocity dispersion for the final sample is σ0 = 43.2 ± 0.8 km s-1 with a rotational velocity to dispersion ratio of vC/σ0 = 2.6 ± 0.1. To explore the relationship between velocity dispersion, stellar mass, star formation rate, and redshift, we combine KROSS with data from the SAMI survey (z ˜ 0.05) and an intermediate redshift MUSE sample (z ˜ 0.5). Whilst there is, at most, a weak trend between velocity dispersion and stellar mass, at fixed mass there is a strong increase with redshift. At all redshifts, galaxies appear to follow the same weak trend of increasing velocity dispersion with star formation rate. Our results are consistent with an evolution of galaxy dynamics driven by discs that are more gas rich, and increasingly gravitationally unstable, as a function of increasing redshift. Finally, we test two analytic models that predict turbulence is driven by either gravitational instabilities or stellar feedback. Both provide an adequate description of the data, and further observations are required to rule out either model.

Protein degradation and post-deboning tenderization in broiler breast meat with different degrees of muscle shortening

USDA-ARS?s Scientific Manuscript database

Deboning broiler breast fillets prior to rigor mortis negatively influences tenderness due to sarcomere shortening. The effects of sarcomere shortening on muscle protein degradation and breast meat tenderization during post-deboning aging are not well understood. The objective of this study was to m...

An abnormal Ca2+ response in mutant sarcomere protein–mediated familial hypertrophic cardiomyopathy

PubMed Central

Fatkin, Diane; McConnell, Bradley K.; Mudd, James O.; Semsarian, Christopher; Moskowitz, Ivan G.P.; Schoen, Frederick J.; Giewat, Michael; Seidman, Christine E.; Seidman, J.G.

2000-01-01

Dominant-negative sarcomere protein gene mutations cause familial hypertrophic cardiomyopathy (FHC), a disease characterized by left-ventricular hypertrophy, angina, and dyspnea that can result in sudden death. We report here that a murine model of FHC bearing a cardiac myosin heavy-chain gene missense mutation (αMHC403/+), when treated with calcineurin inhibitors or a K+-channel agonist, developed accentuated hypertrophy, worsened histopathology, and was at risk for early death. Despite distinct pharmacologic targets, each agent augmented diastolic Ca2+ concentrations in wild-type cardiac myocytes; αMHC403/+ myocytes failed to respond. Pretreatment with a Ca2+-channel antagonist abrogated diastolic Ca2+ changes in wild-type myocytes and prevented the exaggerated hypertrophic response of treated αMHC403/+ mice. We conclude that FHC-causing sarcomere protein gene mutations cause abnormal Ca2+ responses that initiate a hypertrophic response. These data define an important Ca2+-dependent step in the pathway by which mutant sarcomere proteins trigger myocyte growth and remodel the heart, provide definitive evidence that environment influences progression of FHC, and suggest a rational therapeutic approach to this prevalent human disease. PMID:11104788

Molecular cloning and expression profile analysis of porcine TCAP gene.

PubMed

Cheng, Hunjun; Xu, Xuewen; Zhao, Shuhong; Liu, Bang; Yu, Mei; Fan, Bin

2010-03-01

The gradually discovered sarcomeric proteins play important roles for structural integrity and signal transduction of sarcomere during myofibril genesis. TCAP (also described as telethonin, T-cap), one of the sarcomeric protein genes, is regulated developmentally. In this study, we reported the molecular characteristics of porcine TCAP gene. A 979 bp TCAP cDNA nucleotide sequence was obtained in pig and the deduced amino acid sequence had 92 and 91% identity to those of human and mouse homologous genes, respectively. One SNP was discovered and the allele frequency analysis showed that G allele frequency was low among 221 unrelated pigs from seven breeds. The tissue distribution patterns revealed that TCAP mRNA was expressed abundantly in skeletal and heart muscle tissue. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) results displayed TCAP mRNA was up-regulated in both Tongcheng and Landrace pigs during prenatal skeletal muscle development stages. This study suggested that TCAP gene might be a prospective candidate gene affecting muscle mass and meat quality traits in the pig, and also implicated the possible significance of TCAP on sarcomere assembly.

Development and regeneration of the electric organ.

PubMed

Zakon, H H; Unguez, G A

1999-05-01

The electric organ has evolved independently from muscle in at least six lineages of fish. How does a differentiated muscle cell change its fate to become an electrocyte? Is the process by which this occurs similar in different lineages? We have begun to answer these questions by studying the formation and maintenance of electrocytes in the genus Sternopygus, a weakly electric teleost. Electrocytes arise from the fusion of fully differentiated muscle fibers, mainly those expressing fast isoforms of myosin. Electrocytes briefly co-express sarcomeric proteins, such as myosin and tropomyosin, and keratin, a protein not found in mature muscle. The sarcomeric proteins are subsequently down-regulated, but keratin expression persists. We investigated whether the maintenance of the electrocyte phenotype depends on innervation. We found that, after spinal cord transection, which silences the electromotor neurons that innervate the electrocytes, or destruction of the spinal cord, which denervates the electrocytes, mature electrocytes re-express sarcomeric myosin and tropomyosin, although keratin expression persists. Ultrastructural examination of denervated electrocytes revealed nascent sarcomeres. Thus, the maintenance of the electrocyte phenotype depends on neural activity.

Muscle contraction and the elasticity-mediated crosstalk effect

NASA Astrophysics Data System (ADS)

Dharan, Nadiv; Farago, Oded

2013-05-01

Cooperative action of molecular motors is essential for many cellular processes. One possible regulator of motor coordination is the elasticity-mediated crosstalk (EMC) coupling between myosin II motors whose origin is the tensile stress that they collectively generate in actin filaments. Here, we use a statistical mechanical analysis to investigate the influence of the EMC effect on the sarcomere — the basic contractile unit of skeletal muscles. We demonstrate that the EMC effect leads to an increase in the attachment probability of motors located near the end of the sarcomere while simultaneously decreasing the attachment probability of the motors in the central part. Such a polarized attachment probability would impair the motors' ability to cooperate efficiently. Interestingly, this undesired phenomenon becomes significant only when the system size exceeds that of the sarcomere in skeletal muscles, which provides an explanation for the remarkable lack of sarcomere variability in vertebrates. Another phenomenon that we investigate is the recently observed increase in the duty ratio of the motors with the tension in muscle. We reveal that the celebrated Hill's equation for muscle contraction is very closely related to this observation.

3D Asymmetrical motions of the Galactic outer disc with LAMOST K giant stars

NASA Astrophysics Data System (ADS)

Wang, Haifeng; López-Corredoira, Martín; Carlin, Jeffrey L.; Deng, Licai

2018-07-01

We present a three dimensional velocity analysis of Milky Way disc kinematics using LAMOST K giant stars and the GPS1 proper motion catalogue. We find that Galactic disc stars near the anticentre direction (in the range of Galactocentric distance between R = 8 and 13 kpc and vertical position between Z = -2 and 2 kpc) exhibit asymmetrical motions in the Galactocentric radial, azimuthal, and vertical components. Radial motions are not zero, thus departing from circularity in the orbits; they increase outwards within R ≲ 12 kpc, show some oscillation in the northern (0 < Z < 2 kpc) stars, and have north-south asymmetry in the region corresponding to a well-known nearby northern structure in the velocity field. There is a clear vertical gradient in azimuthal velocity, and also an asymmetry that shifts from a larger azimuthal velocity above the plane near the solar radius to faster rotation below the plane at radii of 11-12 kpc. Stars both above and below the plane at R ≳ 9 kpc exhibit net upward vertical motions. We discuss some possible mechanisms that might create the asymmetrical motions, such as external perturbations due to dwarf galaxy minor mergers or dark matter sub-haloes, warp dynamics, internal processes due to spiral arms or the Galactic bar, and (most likely) a combination of some or all of these components.

A study of the gas-star formation relation over cosmic time

NASA Astrophysics Data System (ADS)

Genzel, R.; Tacconi, L. J.; Gracia-Carpio, J.; Sternberg, A.; Cooper, M. C.; Shapiro, K.; Bolatto, A.; Bouché, N.; Bournaud, F.; Burkert, A.; Combes, F.; Comerford, J.; Cox, P.; Davis, M.; Schreiber, N. M. Förster; Garcia-Burillo, S.; Lutz, D.; Naab, T.; Neri, R.; Omont, A.; Shapley, A.; Weiner, B.

2010-10-01

We use the first systematic data sets of CO molecular line emission in z ~ 1-3 normal star-forming galaxies (SFGs) for a comparison of the dependence of galaxy-averaged star formation rates on molecular gas masses at low and high redshifts, and in different galactic environments. Although the current high-z samples are still small and biased towards the luminous and massive tail of the actively star-forming `main-sequence', a fairly clear picture is emerging. Independent of whether galaxy-integrated quantities or surface densities are considered, low- and high-z SFG populations appear to follow similar molecular gas-star formation relations with slopes 1.1 to 1.2, over three orders of magnitude in gas mass or surface density. The gas-depletion time-scale in these SFGs grows from 0.5 Gyr at z ~ 2 to 1.5 Gyr at z ~ 0. The average corresponds to a fairly low star formation efficiency of 2 per cent per dynamical time. Because star formation depletion times are significantly smaller than the Hubble time at all redshifts sampled, star formation rates and gas fractions are set by the balance between gas accretion from the halo and stellar feedback. In contrast, very luminous and ultraluminous, gas-rich major mergers at both low and high z produce on average four to 10 times more far-infrared luminosity per unit gas mass. We show that only some fraction of this difference can be explained by uncertainties in gas mass or luminosity estimators; much of it must be intrinsic. A possible explanation is a top-heavy stellar mass function in the merging systems but the most likely interpretation is that the star formation relation is driven by global dynamical effects. For a given mass, the more compact merger systems produce stars more rapidly because their gas clouds are more compressed with shorter dynamical times, so that they churn more quickly through the available gas reservoir than the typical normal disc galaxies. When the dependence on galactic dynamical time-scale is explicitly included, disc galaxies and mergers appear to follow similar gas-to-star formation relations. The mergers may be forming stars at slightly higher efficiencies than the discs. Based on observations with the Plateau de Bure millimetre interferometre, operated by the Institute for Radio Astronomy in the Millimetre Range (IRAM), which is funded by a partnership of INSU/CNRS (France), MPG (Germany) and IGN (Spain). E-mail: genzel@mpe.mpg.de; linda@mpe.mpg.de ‡ Spitzer Fellow. § MPG-Fellow at MPE.

Effect of Elastase-induced Emphysema on the Force-generating Ability of the Diaphragm

PubMed Central

Supinski, Gerald S.; Kelsen, Steven G.

1982-01-01

The effect of emphysema on the ability of the diaphragm to generate force was examined in costal diaphragm muscle strips from 10 Golden hamsters killed 18 mo after intratracheal injection of pancreatic elastase in a dose producing hyperinflation (mean total lung capacity [TLC] = 163% of control) and generalized panacinar emphysema. 13 saline-injected normal animals served as controls. The time course of isometric tension and the effect of alterations in muscle fiber and sarcomere length on the isometric tension (T) generated in response to tetanizing electrical stimuli (length-tension [L-T] relationship) were examined. Elastase administration caused an increase in diaphragm muscle thickness and reduction in the length of costal diaphragm muscle fibers measured in situ. Emphysema significantly increased the maximum tetanic tension as a result of hypertrophy. Maximal tension corrected for increases in muscle cross-sectional area (T/cm2), however, was the same in emphysematous (E) and control (C) animals. Emphysema also shifted the muscle fiber L-T curve of the diaphragm but not of a control muscle, the soleus, toward shorter lengths. In contrast to the effects of E on the diaphragm muscle fiber L-T curve, the sarcomere L-T curve was the same in E and C. Since the length at which tension was maximal correlated closely with sarcomere number (r = 0.94; P < 0.001) reduction in the number of sarcomeres in series in muscles from emphysematous animals appeared to explain the shift in the muscle fiber L-T curve. We conclude that in elastase-induced emphysema adaptive changes both in diaphragm cross-sectional area and sarcomere number augment the force-generating ability of the diaphragm. We speculate that changes in sarcomere number compensate for alterations in muscle fiber length resulting from chronic hyperinflation of the thorax, while diaphragmatic muscle hypertrophy represents a response to changes in respiratory load and/or diaphragm configuration (LaPlace relationship). Images PMID:6922866

Architecture of the ring formed by the tubulin homologue FtsZ in bacterial cell division

PubMed Central

Szwedziak, Piotr; Wang, Qing; Bharat, Tanmay A M; Tsim, Matthew; Löwe, Jan

2014-01-01

Membrane constriction is a prerequisite for cell division. The most common membrane constriction system in prokaryotes is based on the tubulin homologue FtsZ, whose filaments in E. coli are anchored to the membrane by FtsA and enable the formation of the Z-ring and divisome. The precise architecture of the FtsZ ring has remained enigmatic. In this study, we report three-dimensional arrangements of FtsZ and FtsA filaments in C. crescentus and E. coli cells and inside constricting liposomes by means of electron cryomicroscopy and cryotomography. In vivo and in vitro, the Z-ring is composed of a small, single-layered band of filaments parallel to the membrane, creating a continuous ring through lateral filament contacts. Visualisation of the in vitro reconstituted constrictions as well as a complete tracing of the helical paths of the filaments with a molecular model favour a mechanism of FtsZ-based membrane constriction that is likely to be accompanied by filament sliding. DOI: http://dx.doi.org/10.7554/eLife.04601.001 PMID:25490152

Hubble Space Telescope Hx Imaging of Star-forming Galaxies at z approximately equal to 1-1.5: Evolution in the Size and Luminosity of Giant H II Regions

NASA Technical Reports Server (NTRS)

Livermore, R. C.; Jones, T.; Richard, J.; Bower, R. G.; Ellis, R. S.; Swinbank, A. M.; Rigby, J. R.; Smail, Ian; Arribas, S.; Rodriguez-Zaurin, J.;

The kinematics of the white dwarf population from the SDSS DR12

NASA Astrophysics Data System (ADS)

Anguiano, B.; Rebassa-Mansergas, A.; García-Berro, E.; Torres, S.; Freeman, K.; Zwitter, T.

2018-04-01

We use the Sloan Digital Sky Survey Data Release 12, which is the largest available white dwarf catalog to date, to study the evolution of the kinematical properties of the population of white dwarfs in the Galactic disc. We derive masses, ages, photometric distances and radial velocities for all white dwarfs with hydrogen-rich atmospheres. For those stars for which proper motions from the USNO-B1 catalog are available the true three-dimensional components of the stellar space velocity are obtained. This subset of the original sample comprises 20,247 objects, making it the largest sample of white dwarfs with measured three-dimensional velocities. Furthermore, the volume probed by our sample is large, allowing us to obtain relevant kinematical information. In particular, our sample extends from a Galactocentric radial distance R G = 7.8 kpc to 9.3 kpc, and vertical distances from the Galactic plane ranging from Z = -0.5 kpc to 0.5 kpc. We examine the mean components of the stellar three-dimensional velocities, as well as their dispersions with respect to the Galactocentric and vertical distances. We confirm the existence of a mean Galactocentric radial velocity gradient, ∂/∂R G = -3 +/- 5 km s-1 kpc-1. We also confirm North-South differences in . Specifically, we find that white dwarfs with Z > 0 (in the North Galactic hemisphere) have < 0, while the reverse is true for white dwarfs with Z < 0. The age-velocity dispersion relation derived from the present sample indicates that the Galactic population of white dwarfs may have experienced an additional source of heating, which adds to the secular evolution of the Galactic disc.

Giant rectification in graphene nanoflake molecular devices with asymmetric graphene nanoribbon electrodes

NASA Astrophysics Data System (ADS)

Ji, Xiao-Li; Xie, Zhen; Zuo, Xi; Zhang, Guang-Ping; Li, Zong-Liang; Wang, Chuan-Kui

2016-09-01

By applying density functional theory based nonequilibrium Green's function method, we theoretically investigate the electron transport properties of a zigzag-edged trigonal graphene nanoflake (ZTGNF) sandwiched between two asymmetric zigzag graphene nanoribbon (zGNR) and armchair graphene nanoribbon (aGNR) electrodes with carbon atomic chains (CACs) as the anchoring groups. Significant rectifying effects have been observed for these molecular devices in low bias voltage regions. Interestingly, the rectifying performance of molecular devices can be optimized by changing the width of the aGNR electrode and the number of anchoring CACs. Especially, the molecular device displays giant rectification ratios up to the order of 104 when two CACs are used as the anchoring group between the ZTGNF and the right aGNR electrode. Further analysis indicates that the asymmetric shift of the perturbed molecular energy levels and the spatial parity of the electron wavefunctions in the electrodes around the Fermi level play key roles in determining the rectification performance. And the spatial distributions of tunneling electron wavefunctions under negative bias voltages can be modified to be very localized by changing the number of anchoring CACs, which is found to be the origin of the giant rectification ratios.

Distinct Effects of Rac1 on Differentiation of Primary Avian Myoblasts

PubMed Central

Gallo, Rita; Serafini, Marco; Castellani, Loriana; Falcone, Germana; Alemà, Stefano

1999-01-01

Rho family GTPases have been implicated in the regulation of the actin cytoskeleton in response to extracellular cues and in the transduction of signals from the membrane to the nucleus. Their role in development and cell differentiation, however, is little understood. Here we show that the transient expression of constitutively active Rac1 and Cdc42 in unestablished avian myoblasts is sufficient to cause inhibition of myogenin expression and block of the transition to the myocyte compartment, whereas activated RhoA affects myogenic differentiation only marginally. Activation of c-Jun N-terminal kinase (JNK) appears not to be essential for block of differentiation because, although Rac1 and Cdc42 GTPases modestly activate JNK in quail myoblasts, a Rac1 mutant defective for JNK activation can still inhibit myogenic differentiation. Stable expression of active Rac1, attained by infection with a recombinant retrovirus, is permissive for terminal differentiation, but the resulting myotubes accumulate severely reduced levels of muscle-specific proteins. This inhibition is the consequence of posttranscriptional events and suggests the presence of a novel level of regulation of myogenesis. We also show that myotubes expressing constitutively active Rac1 fail to assemble ordered sarcomeres. Conversely, a dominant-negative Rac1 variant accelerates sarcomere maturation and inhibits v-Src–induced selective disassembly of I-Z-I complexes. Collectively, our findings provide a role for Rac1 during skeletal muscle differentiation and strongly suggest that Rac1 is required downstream of v-Src in the signaling pathways responsible for the dismantling of tissue-specific supramolecular structures. PMID:10512856

T-tubule disease: Relationship between t-tubule organization and regional contractile performance in human dilated cardiomyopathy.

PubMed

Crossman, David J; Young, Alistair A; Ruygrok, Peter N; Nason, Guy P; Baddelely, David; Soeller, Christian; Cannell, Mark B

2015-07-01

Evidence from animal models suggest that t-tubule changes may play an important role in the contractile deficit associated with heart failure. However samples are usually taken at random with no regard as to regional variability present in failing hearts which leads to uncertainty in the relationship between contractile performance and possible t-tubule derangement. Regional contraction in human hearts was measured by tagged cine MRI and model fitting. At transplant, failing hearts were biopsy sampled in identified regions and immunocytochemistry was used to label t-tubules and sarcomeric z-lines. Computer image analysis was used to assess 5 different unbiased measures of t-tubule structure/organization. In regions of failing hearts that showed good contractile performance, t-tubule organization was similar to that seen in normal hearts, with worsening structure correlating with the loss of regional contractile performance. Statistical analysis showed that t-tubule direction was most highly correlated with local contractile performance, followed by the amplitude of the sarcomeric peak in the Fourier transform of the t-tubule image. Other area based measures were less well correlated. We conclude that regional contractile performance in failing human hearts is strongly correlated with the local t-tubule organization. Cluster tree analysis with a functional definition of failing contraction strength allowed a pathological definition of 't-tubule disease'. The regional variability in contractile performance and cellular structure is a confounding issue for analysis of samples taken from failing human hearts, although this may be overcome with regional analysis by using tagged cMRI and biopsy mapping. Copyright © 2015 Elsevier Ltd. All rights reserved.

Exact solution of finite parabolic potential disc-like quantum dot with and without electric field R. Djelti, S. Bentata and Z. Aziz: Trimer barrier hight effect oh the nature of the electronic state of the superlatice GaAs/AlxGa1-xAs Bibhas K. Dutta and Prasanta K. Mahapatra: Study of velocity-dependent collision effects on Lamb dip and crossover resonances in three-level system

NASA Astrophysics Data System (ADS)

Hassanien, H. H.; Abdelmoly, S. S.; Elmeshad, N.

The exact series solutions of finite parabolic potential disc-like quantum dot are given in the absence and presence of uniform applied electric field. We define some normalized parameters. From the complex eigenenergy E=E0 - i G/2, due to the electric field, we calculate the resonance width G of a bounded state. The ground and the first excited state of the electron and the hole are obtained with and without the electric field. The corresponding envelope functions are presented as a function of the disc dimensionality, radius R and half-width L.

Bright compact bulges at intermediate redshifts

NASA Astrophysics Data System (ADS)

Sachdeva, Sonali; Saha, Kanak

2018-07-01

Studying bright (MB < -20), intermediate-redshift (0.4 < z< 1.0), disc-dominated (nB < 2.5) galaxies from Hubble Space Telescope/Advanced Camera for Surveys and Wide Field Camera 3 in Chandra Deep Field-South, in rest-frame B and I band, we found a new class of bulges that is brighter and more compact than ellipticals. We refer to them as `bright, compact bulges' (BCBs) - they resemble neither classical nor pseudo-bulges and constitute ˜12 per cent of the total bulge population at these redshifts. Examining free-bulge + disc decomposition sample and elliptical galaxy sample from Simard et al., we find that only ˜0.2 per cent of the bulges can be classified as BCBs in the local Universe. Bulge to total light ratio of disc galaxies with BCBs is (at ˜0.4) a factor of ˜2 and ˜4 larger than for those with classical and pseudo-bulges. BCBs are ˜2.5 and ˜6 times more massive than classical and pseudo-bulges. Although disc galaxies with BCBs host the most massive and dominant bulge type, their specific star formation rate is 1.5-2 times higher than other disc galaxies. This is contrary to the expectations that a massive compact bulge would lead to lower star formation rates. We speculate that our BCB host disc galaxies are descendant of massive, compact, and passive elliptical galaxies observed at higher redshifts. Those high-redshift ellipticals lack local counterparts and possibly evolved by acquiring a compact disc around them. The overall properties of BCBs support a picture of galaxy assembly in which younger discs are being accreted around massive pre-existing spheroids.

Bacterial actin MreB assembles in complex with cell shape protein RodZ.

PubMed

van den Ent, Fusinita; Johnson, Christopher M; Persons, Logan; de Boer, Piet; Löwe, Jan

2010-03-17

Bacterial actin homologue MreB is required for cell shape maintenance in most non-spherical bacteria, where it assembles into helical structures just underneath the cytoplasmic membrane. Proper assembly of the actin cytoskeleton requires RodZ, a conserved, bitopic membrane protein that colocalises to MreB and is essential for cell shape determination. Here, we present the first crystal structure of bacterial actin engaged with a natural partner and provide a clear functional significance of the interaction. We show that the cytoplasmic helix-turn-helix motif of Thermotoga maritima RodZ directly interacts with monomeric as well as filamentous MreB and present the crystal structure of the complex. In vitro and in vivo analyses of mutant T. maritima and Escherichia coli RodZ validate the structure and reveal the importance of the MreB-RodZ interaction in the ability of cells to propagate as rods. Furthermore, the results elucidate how the bacterial actin cytoskeleton might be anchored to the membrane to help constrain peptidoglycan synthesis in the periplasm.

A Role for the p38 Mitogen-activated Protein Kinase Pathway in Myocardial Cell Growth, Sarcomeric Organization, and Cardiac-specific Gene Expression

PubMed Central

Zechner, Dietmar; Thuerauf, Donna J.; Hanford, Deanna S.; McDonough, Patrick M.; Glembotski, Christopher C.

1997-01-01

Three hallmark features of the cardiac hypertrophic growth program are increases in cell size, sarcomeric organization, and the induction of certain cardiac-specific genes. All three features of hypertrophy are induced in cultured myocardial cells by α1- adrenergic receptor agonists, such as phenylephrine (PE) and other growth factors that activate mitogen- activated protein kinases (MAPKs). In this study the MAPK family members extracellular signal–regulated kinase (ERK), c-jun NH2-terminal kinase (JNK), and p38 were activated by transfecting cultured cardiac myocytes with constructs encoding the appropriate kinases possessing gain-of-function mutations. Transfected cells were then analyzed for changes in cell size, sarcomeric organization, and induction of the genes for the A- and B-type natriuretic peptides (NPs), as well as the α-skeletal actin (α-SkA) gene. While activation of JNK and/or ERK with MEKK1COOH or Raf-1 BXB, respectively, augmented cell size and effected relatively modest increases in NP and α-SkA promoter activities, neither upstream kinase conferred sarcomeric organization. However, transfection with MKK6 (Glu), which specifically activated p38, augmented cell size, induced NP and α-Ska promoter activities by up to 130-fold, and elicited sarcomeric organization in a manner similar to PE. Moreover, all three growth features induced by MKK6 (Glu) or PE were blocked with the p38-specific inhibitor, SB 203580. These results demonstrate novel and potentially central roles for MKK6 and p38 in the regulation of myocardial cell hypertrophy. PMID:9314533

An Inexpensive 2-D and 3-D Model of the Sarcomere as a Teaching Aid

ERIC Educational Resources Information Center

Rios, Vitor Passos; Bonfim, Vanessa Maria Gomes

2013-01-01

To address a common problem of teaching the sliding filament theory (that is, students have difficulty in visualizing how the component proteins of the sarcomere differ, how they organize themselves into a single working unit, and how they function in relation to each other), we have devised a simple model, with inexpensive materials, to be built…

In vivo cardiac nano-imaging: A new technology for high-precision analyses of sarcomere dynamics in the heart.

PubMed

Shimozawa, Togo; Hirokawa, Erisa; Kobirumaki-Shimozawa, Fuyu; Oyama, Kotaro; Shintani, Seine A; Terui, Takako; Kushida, Yasuharu; Tsukamoto, Seiichi; Fujii, Teruyuki; Ishiwata, Shin'ichi; Fukuda, Norio

2017-03-01

The cardiac pump function is a result of a rise in intracellular Ca 2+ and the ensuing sarcomeric contractions [i.e., excitation-contraction (EC) coupling] in myocytes in various locations of the heart. In order to elucidate the heart's mechanical properties under various settings, cardiac imaging is widely performed in today's clinical as well as experimental cardiology by using echocardiogram, magnetic resonance imaging and computed tomography. However, because these common techniques detect local myocardial movements at a spatial resolution of ∼100 μm, our knowledge on the sub-cellular mechanisms of the physiology and pathophysiology of the heart in vivo is limited. This is because (1) EC coupling occurs in the μm partition in a myocyte and (2) cardiac sarcomeres generate active force upon a length change of ∼100 nm on a beat-to-beat basis. Recent advances in optical technologies have enabled measurements of intracellular Ca 2+ dynamics and sarcomere length displacements at high spatial and temporal resolution in the beating heart of living rodents. Future studies with these technologies are warranted to open a new era in cardiac research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Explaining the variation in the shear force of lamb meat using sarcomere length, the rate of rigor onset and pH.

PubMed

Hopkins, D L; Toohey, E S; Lamb, T A; Kerr, M J; van de Ven, R; Refshauge, G

2011-08-01

The temperature when the pH=6.0 (temp@pH6) impacts on the tenderness and eating quality of sheep meat. Due to the expense, sarcomere length is not routinely measured as a variable to explain variation in shear force, but whether measures such as temp@pH6 are as useful a parameter needs to be established. Measures of rigor onset in 261 carcases, including the temp@pH6, were evaluated in this study for their ability to explain some of the variation in shear force. The results show that for 1 day aged product combinations of the temp@pH6, the pH at 18 °C and the pH at 24 h provided a larger reduction (almost double) in total shear force variation than sarcomere length alone, with pH at 24 h being the single best measure. For 5 day aged product, pH at 18 °C was the single best measure. Inclusion of sarcomere length did represent some improvement, but the marginal increase would not be cost effective. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Fabrication of High Thermal Conductivity NARloy-Z-Diamond Composite Combustion Chamber Liner for Advanced Rocket Engines

NASA Technical Reports Server (NTRS)

Bhat, Biliyar N.; Greene, Sandra E.; Singh, Jogender

2016-01-01

This paper describes the process development for fabricating a high thermal conductivity NARloy-Z-Diamond composite (NARloy-Z-D) combustion chamber liner for application in advanced rocket engines. The fabrication process is challenging and this paper presents some details of these challenges and approaches used to address them. Prior research conducted at NASA-MSFC and Penn State had shown that NARloy-Z-40%D composite material has significantly higher thermal conductivity than the state of the art NARloy-Z alloy. Furthermore, NARloy-Z-40 %D is much lighter than NARloy-Z. These attributes help to improve the performance of the advanced rocket engines. Increased thermal conductivity will directly translate into increased turbopump power, increased chamber pressure for improved thrust and specific impulse. Early work on NARloy-Z-D composites used the Field Assisted Sintering Technology (FAST, Ref. 1, 2) for fabricating discs. NARloy-Z-D composites containing 10, 20 and 40vol% of high thermal conductivity diamond powder were investigated. Thermal conductivity (TC) data. TC increased with increasing diamond content and showed 50% improvement over pure copper at 40vol% diamond. This composition was selected for fabricating the combustion chamber liner using the FAST technique.

Antioxidant capacity of synovial fluid in the temporomandibular joint correlated with radiological morphology of temporomandibular disorders.

PubMed

Ishimaru, Kyoko; Ohba, Seigo; Yoshimura, Hitoshi; Matsuda, Shinpei; Ishimaru, Jun-Ichi; Sano, Kazuo

2015-02-01

We investigated the correlation between the antioxidant capacity of synovial fluid and radiological findings of intra-articular structures in patients with disorders of the temporomandibular joint (TMJ). We recruited 21 patients (9 men and 12 women, aged 18-84 years of age) with such disorders, excluding myofascial pain and dysfunction syndrome, or other muscular disorders. The clinical variables recorded included age, sex, interincisal distance, and visual analogue pain scores (VAS). Radiological findings were obtained from diagnostic arthrogram and cone-beam computed tomography (CT). The antioxidant capacity of the synovial fluid was measured by chemiluminescence. Eleven patients were radiologically diagnosed with closed lock, and the remaining 10 with no closed lock. An anchored intra-articular disc was most often seen on cone-beam CT (n=19) followed by perforated disc (n=7), osteoarthrosis (n=7), and anterior disc displacement without reduction (n=5). Although there were no significant differences between antioxidant capacity and age, sex, VAS, or any findings on cone-beam CT, antioxidant capacity was significantly decreased in the patients with closed lock compared with those who did not have closed lock (p=0.02). The results suggest an association between the oxidative stress of the synovial fluid and closed-lock in disorders of the TMJ. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Pre-mRNA mis-splicing of sarcomeric genes in heart failure.

PubMed

Zhu, Chaoqun; Chen, Zhilong; Guo, Wei

2017-08-01

Pre-mRNA splicing is an important biological process that allows production of multiple proteins from a single gene in the genome, and mainly contributes to protein diversity in eukaryotic organisms. Alternative splicing is commonly governed by RNA binding proteins to meet the ever-changing demands of the cell. However, the mis-splicing may lead to human diseases. In the heart of human, mis-regulation of alternative splicing has been associated with heart failure. In this short review, we focus on alternative splicing of sarcomeric genes and review mis-splicing related heart failure with relatively well studied Sarcomeric genes and splicing mechanisms with identified regulatory factors. The perspective of alternative splicing based therapeutic strategies in heart failure has also been discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

The 1.5 Ms observing campaign on IRAS 13224-3809 - I. X-ray spectral analysis

NASA Astrophysics Data System (ADS)

Jiang, J.; Parker, M. L.; Fabian, A. C.; Alston, W. N.; Buisson, D. J. K.; Cackett, E. M.; Chiang, C.-Y.; Dauser, T.; Gallo, L. C.; García, J. A.; Harrison, F. A.; Lohfink, A. M.; De Marco, B.; Kara, E.; Miller, J. M.; Miniutti, G.; Pinto, C.; Walton, D. J.; Wilkins, D. R.

2018-07-01

We present a detailed spectral analysis of the recent 1.5 Ms XMM-Newton observing campaign on the narrow-line Seyfert 1 galaxy IRAS 13224-3809, taken simultaneously with 500 ks of NuSTAR data. The X-ray light curve shows three flux peaks, registering at about 100 times the minimum flux seen during the campaign, and rapid variability with a time-scale of kiloseconds. The spectra are well fit with a primary power-law continuum, two relativistic-blurred reflection components from the inner accretion disc with very high iron abundance, and a simple blackbody-shaped model for the remaining soft excess. The spectral variability is dominated by the power-law continuum from a corona region within a few gravitational radii from the black hole. Additionally, blueshifted Ne X, Mg XII, Si XIV, and S XVI absorption lines are identified in the stacked low-flux spectrum, confirming the presence of a highly ionized outflow with velocity up to v = 0.267 and 0.225 c. We fit the absorption features with xstar models and find a relatively constant velocity outflow through the whole observation. Finally, we replace the bbody and supersolar abundance reflection models by fitting the soft excess successfully with the extended reflection model relxillD, which allows for higher densities than the standard relxill model. This returns a disc electron density ne > 1018.7 cm-3 and lowers the iron abundance from Z_Fe = 24^{+3}_{-4} Z_{⊙} with ne ≡ 1015 cm-3 to Z_Fe = 6.6^{+0.8}_{-2.1} Z_{⊙}.

Three-dimensional contractile muscle tissue consisting of human skeletal myocyte cell line.

PubMed

Shima, Ai; Morimoto, Yuya; Sweeney, H Lee; Takeuchi, Shoji

2018-06-18

This paper describes a method to construct three-dimensional (3D) contractile human skeletal muscle tissues from a cell line. The 3D tissue was fabricated as a fiber-based structure and cultured for two weeks under tension by anchoring its both ends. While myotubes from the immortalized human skeletal myocytes used in this study never contracted in the conventional two-dimensional (2D) monolayer culture, myotubes in the 3D tissue showed spontaneous contraction at a high frequency and also reacted to the electrical stimulation. Immunofluorescence revealed that the myotubes in the 3D tissues had sarcomeres and expressed ryanodine receptor (RyR) and sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA). In addition, intracellular calcium oscillations in the myotubes in the 3D tissue were observed. These results indicated that the 3D culture enabled the myocyte cell line to reach a more highly matured state compared to 2D culture. Since contraction is the most significant feature of skeletal muscle, we believe that our 3D human muscle tissue with the contractile ability would be a useful tool for both basic biology research and drug discovery as one of the muscle-on-chips. Copyright © 2018. Published by Elsevier Inc.

Enhancement of soft X-ray lasing action with thin blade radiators

DOEpatents

Suckewer, Szymon; Skinner, Charles H.; Voorhees, David R.

1988-01-01

An enhancement of approximately 100 of stimulated emission over spontaneous emission of the CVI 182 Angstrom line was obtained in a recombining magnetically confined plasma column. The plasma was formed by focusing a CO.sub.2 laser beam on a carbon disc. A magnetic solenoid produced a strong magnetic field which confined the plasma to the shape of a column. A single thin carbon blade extended parallel to the plasma column and served to make the column axially more uniform and also acted as a heat sink. Axial and transverse measurements of the soft X-ray lasing action were made from locations off-set from the central axis of the plasma column. Multiple carbon blades located at equal intervals around the plasma column were also found to produce acceptable results. According to another embodiment 10 a thin coating of aluminum or magnesium was placed on the carbon disc and blade. The Z of the coating should preferably be at least 5 greater than the Z of the target. Measurements of the soft X-rays generated at 182 Angstroms showed a significant increase in intensity enhancement.

MaGICC baryon cycle: the enrichment history of simulated disc galaxies

NASA Astrophysics Data System (ADS)

Brook, C. B.; Stinson, G.; Gibson, B. K.; Shen, S.; Macciò, A. V.; Obreja, A.; Wadsley, J.; Quinn, T.

2014-10-01

Using cosmological galaxy formation simulations from the MaGICC (Making Galaxies in a Cosmological Context) project, spanning stellar mass from ˜107 to 3 × 1010 M⊙, we trace the baryonic cycle of infalling gas from the virial radius through to its eventual participation in the star formation process. An emphasis is placed upon the temporal history of chemical enrichment during its passage through the corona and circumgalactic medium. We derive the distributions of time between gas crossing the virial radius and being accreted to the star-forming region (which allows for mixing within the corona), as well as the time between gas being accreted to the star-forming region and then ultimately forming stars (which allows for mixing within the disc). Significant numbers of stars are formed from gas that cycles back through the hot halo after first accreting to the star-forming region. Gas entering high-mass galaxies is pre-enriched in low-mass proto-galaxies prior to entering the virial radius of the central progenitor, with only small amounts of primordial gas accreted, even at high redshift (z ˜ 5). After entering the virial radius, significant further enrichment occurs prior to the accretion of the gas to the star-forming region, with gas that is feeding the star-forming region surpassing 0.1 Z⊙ by z = 0. Mixing with halo gas, itself enriched via galactic fountains, is thus crucial in determining the metallicity at which gas is accreted to the disc. The lowest mass simulated galaxy (Mvir ˜ 2 × 1010 M⊙, with M⋆ ˜ 107 M⊙), by contrast, accretes primordial gas through the virial radius and on to the disc, throughout its history. Much like the case for classical analytical solutions to the so-called `G-dwarf problem', overproduction of low-metallicity stars is ameliorated by the interplay between the time of accretion on to the disc and the subsequent involvement in star formation - i.e. due to the inefficiency of star formation. Finally, gas outflow/metal removal rates from star-forming regions as a function of galactic mass are presented.

An independent determination of the local Hubble constant

NASA Astrophysics Data System (ADS)

Fernández Arenas, David; Terlevich, Elena; Terlevich, Roberto; Melnick, Jorge; Chávez, Ricardo; Bresolin, Fabio; Telles, Eduardo; Plionis, Manolis; Basilakos, Spyros

2018-02-01

The relationship between the integrated H β line luminosity and the velocity dispersion of the ionized gas of H II galaxies and giant H II regions represents an exciting standard candle that presently can be used up to redshifts z ˜ 4. Locally it is used to obtain precise measurements of the Hubble constant by combining the slope of the relation obtained from nearby (z ≤ 0.2) H II galaxies with the zero-point determined from giant H II regions belonging to an `anchor sample' of galaxies for which accurate redshift-independent distance moduli are available. We present new data for 36 giant H II regions in 13 galaxies of the anchor sample that includes the megamaser galaxy NGC 4258. Our data are the result of the first 4 yr of observation of our primary sample of 130 giant H II regions in 73 galaxies with Cepheid determined distances. Our best estimate of the Hubble parameter is 71.0 ± 2.8(random) ± 2.1(systematic) km s- 1Mpc- 1. This result is the product of an independent approach and, although at present less precise than the latest SNIa results, it is amenable to substantial improvement.

Primary limited lumbar discectomy with an annulus closure device: one-year clinical and radiographic results from a prospective, multi-center study.

PubMed

Lequin, Michiel B; Barth, Martin; Thomė, Claudius; Bouma, Gerrit J

2012-12-01

Discectomy as a treatment for herniated lumbar discs results in outcomes after surgery that are not uniformly positive. Surgeons face the dilemma between limited nucleus removal which is associated with a higher risk of recurrence, or more aggressive nucleus removal which may lead to disc height loss and persistent back-pain. annulus closure devices may allow for the benefits of limited nucleus removal without the increased risk of recurrence. This is an interim report of an ongoing 24-month post-marketing study of the Barricaid® annulus closure device, consisting of a flexible polymer mesh that blocks the defect, held in place by a titanium bone anchor. We prospectively enrolled 45 patients at four hospitals, and implanted the Barricaid® after a limited discectomy. annulus defect size and volume of removed nucleus were recorded. Reherniations were reported, pain and function were monitored and imaging was performed at regular intervals during 24 months of follow-up. At 12 months postsurgery, pain and function were significantly improved, comparing favorably to reported results from limited discectomy. Disc height has been well maintained. One reherniation has occurred (2.4%), which was associated with a misplaced device. No device fracture, subsidence or migration has been observed. The use of an annulus closure device may provide a reduction in reherniation rate for lumbar discectomy patients with large annulus defects who are at the greatest risk of recurrence. Using such a device should provide the surgeon increased confidence in minimizing nucleus removal, which, in turn, may preserve disc height and biomechanics, reducing degeneration and associated poor clinical outcomes in the long-term. A randomized multicenter study evaluating limited discectomy with and without the Barricaid® is currently underway, and will provide a higher level of evidence.

Size and speed of the working stroke of cardiac myosin in situ

PubMed Central

Caremani, Marco; Pinzauti, Francesca; Reconditi, Massimo; Piazzesi, Gabriella; Stienen, Ger J. M.; Lombardi, Vincenzo; Linari, Marco

2016-01-01

The power in the myocardium sarcomere is generated by two bipolar arrays of the motor protein cardiac myosin II extending from the thick filament and pulling the thin, actin-containing filaments from the opposite sides of the sarcomere. Despite the interest in the definition of myosin-based cardiomyopathies, no study has yet been able to determine the mechanokinetic properties of this motor protein in situ. Sarcomere-level mechanics recorded by a striation follower is used in electrically stimulated intact ventricular trabeculae from the rat heart to determine the isotonic velocity transient following a stepwise reduction in force from the isometric peak force TP to a value T (0.8–0.2 TP). The size and the speed of the early rapid shortening (the isotonic working stroke) increase by reducing T from ∼3 nm per half-sarcomere (hs) and 1,000 s−1 at high load to ∼8 nm⋅hs−1 and 6,000 s−1 at low load. Increases in sarcomere length (1.9–2.2 μm) and external [Ca2+]o (1–2.5 mM), which produce an increase of TP, do not affect the dependence on T, normalized for TP, of the size and speed of the working stroke. Thus, length- and Ca2+-dependent increase of TP and power in the heart can solely be explained by modulation of the number of myosin motors, an emergent property of their array arrangement. The motor working stroke is similar to that of skeletal muscle myosin, whereas its speed is about three times slower. A new powerful tool for investigations and therapies of myosin-based cardiomyopathies is now within our reach. PMID:26984499

Loss of zebrafish Smyd1a interferes with myofibrillar integrity without triggering the misfolded myosin response.

PubMed

Paone, Christoph; Rudeck, Steven; Etard, Christelle; Strähle, Uwe; Rottbauer, Wolfgang; Just, Steffen

2018-02-05

Sarcomeric protein turnover needs to be tightly balanced to assure proper assembly and renewal of sarcomeric units within muscle tissues. The mechanisms regulating these fundamental processes are only poorly understood, but of great clinical importance since many cardiac and skeletal muscle diseases are associated with defective sarcomeric organization. The SET- and MYND domain containing protein 1b (Smyd1b) is known to play a crucial role in myofibrillogenesis by functionally interacting with the myosin chaperones Unc45b and Hsp90α1. In zebrafish, Smyd1b, Unc45b and Hsp90α1 are part of the misfolded myosin response (MMR), a regulatory transcriptional response that is activated by disturbed myosin homeostasis. Genome duplication in zebrafish led to a second smyd1 gene, termed smyd1a. Morpholino- and CRISPR/Cas9-mediated knockdown of smyd1a led to significant perturbations in sarcomere structure resulting in decreased cardiac as well as skeletal muscle function. Similar to Smyd1b, we found Smyd1a to localize to the sarcomeric M-band in skeletal and cardiac muscles. Overexpression of smyd1a efficiently compensated for the loss of Smyd1b in flatline (fla) mutant zebrafish embryos, rescued the myopathic phenotype and suppressed the MMR in Smyd1b-deficient embryos, suggesting overlapping functions of both Smyd1 paralogs. Interestingly, Smyd1a is not transcriptionally activated in Smyd1b-deficient fla mutants, demonstrating lack of genetic compensation despite the functional redundancy of both zebrafish Smyd1 paralogs. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

On high heels and short muscles: A multiscale model for sarcomere loss in the gastrocnemius muscle

PubMed Central

Zöllner, Alexander M.; Pok, Jacquelynn M.; McWalter, Emily J.; Gold, Garry E.; Kuhl, Ellen

2014-01-01

High heels are a major source of chronic lower limb pain. Yet, more than one third of all women compromise health for looks and wear high heels on a daily basis. Changing from flat footwear to high heels induces chronic muscle shortening associated with discomfort, fatigue, reduced shock absorption, and increased injury risk. However, the long-term effects of high-heeled footwear on the musculoskeletal kinematics of the lower extremities remain poorly understood. Here we create a multiscale computational model for chronic muscle adaptation to characterize the acute and chronic effects of global muscle shortening on local sarcomere lengths. We perform a case study of a healthy female subject and show that raising the heel by 13 cm shortens the gastrocnemius muscle by 5% while the Achilles tendon remains virtually unaffected. Our computational simulation indicates that muscle shortening displays significant regional variations with extreme values of 22% in the central gastrocnemius. Our model suggests that the muscle gradually adjusts to its new functional length by a chronic loss of sarcomeres in series. Sarcomere loss varies significantly across the muscle with an average loss of 9%, virtually no loss at the proximal and distal ends, and a maximum loss of 39% in the central region. These changes reposition the remaining sarcomeres back into their optimal operating regime. Computational modeling of chronic muscle shortening provides a valuable tool to shape our understanding of the underlying mechanisms of muscle adaptation. Our study could open new avenues in orthopedic surgery and enhance treatment for patients with muscle contracture caused by other conditions than high heel wear such as paralysis, muscular atrophy, and muscular dystrophy. PMID:25451524

S-Nitrosylation of Sarcomeric Proteins Depresses Myofilament Ca2+ Sensitivity in Intact Cardiomyocytes

PubMed Central

Figueiredo-Freitas, Cícero; Dulce, Raul A.; Foster, Matthew W.; Liang, Jingsheng; Yamashita, Aline M.S.; Lima-Rosa, Frederico L.; Thompson, J. Will; Moseley, M. Arthur; Hare, Joshua M.; Nogueira, Leonardo; Sorenson, Martha M.

2015-01-01

Abstract Aims: The heart responds to physiological and pathophysiological stress factors by increasing its production of nitric oxide (NO), which reacts with intracellular glutathione to form S-nitrosoglutathione (GSNO), a protein S-nitrosylating agent. Although S-nitrosylation protects some cardiac proteins against oxidative stress, direct effects on myofilament performance are unknown. We hypothesize that S-nitrosylation of sarcomeric proteins will modulate the performance of cardiac myofilaments. Results: Incubation of intact mouse cardiomyocytes with S-nitrosocysteine (CysNO, a cell-permeable low-molecular-weight nitrosothiol) significantly decreased myofilament Ca2+ sensitivity. In demembranated (skinned) fibers, S-nitrosylation with 1 μM GSNO also decreased Ca2+ sensitivity of contraction and 10 μM reduced maximal isometric force, while inhibition of relaxation and myofibrillar ATPase required higher concentrations (≥100 μM). Reducing S-nitrosylation with ascorbate partially reversed the effects on Ca2+ sensitivity and ATPase activity. In live cardiomyocytes treated with CysNO, resin-assisted capture of S-nitrosylated protein thiols was combined with label-free liquid chromatography–tandem mass spectrometry to quantify S-nitrosylation and determine the susceptible cysteine sites on myosin, actin, myosin-binding protein C, troponin C and I, tropomyosin, and titin. The ability of sarcomere proteins to form S-NO from 10–500 μM CysNO in intact cardiomyocytes was further determined by immunoblot, with actin, myosin, myosin-binding protein C, and troponin C being the more susceptible sarcomeric proteins. Innovation and Conclusions: Thus, specific physiological effects are associated with S-nitrosylation of a limited number of cysteine residues in sarcomeric proteins, which also offer potential targets for interventions in pathophysiological situations. Antioxid. Redox Signal. 23, 1017–1034. PMID:26421519

Perturbed length-dependent activation in human hypertrophic cardiomyopathy with missense sarcomeric gene mutations.

PubMed

Sequeira, Vasco; Wijnker, Paul J M; Nijenkamp, Louise L A M; Kuster, Diederik W D; Najafi, Aref; Witjas-Paalberends, E Rosalie; Regan, Jessica A; Boontje, Nicky; Ten Cate, Folkert J; Germans, Tjeerd; Carrier, Lucie; Sadayappan, Sakthivel; van Slegtenhorst, Marjon A; Zaremba, Ruud; Foster, D Brian; Murphy, Anne M; Poggesi, Corrado; Dos Remedios, Cris; Stienen, Ger J M; Ho, Carolyn Y; Michels, Michelle; van der Velden, Jolanda

2013-05-24

High-myofilament Ca(2+) sensitivity has been proposed as a trigger of disease pathogenesis in familial hypertrophic cardiomyopathy (HCM) on the basis of in vitro and transgenic mice studies. However, myofilament Ca(2+) sensitivity depends on protein phosphorylation and muscle length, and at present, data in humans are scarce. To investigate whether high myofilament Ca(2+) sensitivity and perturbed length-dependent activation are characteristics for human HCM with mutations in thick and thin filament proteins. Cardiac samples from patients with HCM harboring mutations in genes encoding thick (MYH7, MYBPC3) and thin (TNNT2, TNNI3, TPM1) filament proteins were compared with sarcomere mutation-negative HCM and nonfailing donors. Cardiomyocyte force measurements showed higher myofilament Ca(2+) sensitivity in all HCM samples and low phosphorylation of protein kinase A (PKA) targets compared with donors. After exogenous PKA treatment, myofilament Ca(2+) sensitivity was similar (MYBPC3mut, TPM1mut, sarcomere mutation-negative HCM), higher (MYH7mut, TNNT2mut), or even significantly lower (TNNI3mut) compared with donors. Length-dependent activation was significantly smaller in all HCM than in donor samples. PKA treatment increased phosphorylation of PKA-targets in HCM myocardium and normalized length-dependent activation to donor values in sarcomere mutation-negative HCM and HCM with truncating MYBPC3 mutations but not in HCM with missense mutations. Replacement of mutant by wild-type troponin in TNNT2mut and TNNI3mut corrected length-dependent activation to donor values. High-myofilament Ca(2+) sensitivity is a common characteristic of human HCM and partly reflects hypophosphorylation of PKA targets compared with donors. Length-dependent sarcomere activation is perturbed by missense mutations, possibly via posttranslational modifications other than PKA hypophosphorylation or altered protein-protein interactions, and represents a common pathomechanism in HCM.

Graph C ∗-algebras and Z2-quotients of quantum spheres

NASA Astrophysics Data System (ADS)

Hajac, Piotr M.; Matthes, Rainer; Szymański, Wojciech

2003-06-01

We consider two Z2-actions on the Podleś generic quantum spheres. They yield, as noncommutative quotient spaces, the Klimek-Lesmewski q-disc and the quantum real projective space, respectively. The C ∗-algebas of all these quantum spaces are described as graph C ∗-algebras. The K-groups of the thus presented C ∗-algebras are then easily determined from the general theory of graph C ∗-algebas. For the quantum real projective space, we also recall the classification of the classes of irreducible ∗-representations of its algebra and give a linear basis for this algebra.

Echinobothrium chisholmae n. sp. (Cestoda, Diphyllidea) from the giant shovel-nose ray Rhinobatos typus from Australia, with observations on the ultrastructure of its scolex musculature and peduncular spines.

PubMed

Jones, M K; Beveridge, I

2001-09-01

Echinobothrium chisholmae n. sp. is described from Rhinobatos typus Bennett (Rhinobatidae), collected from Heron Island, Great Barrier Reef, Australia. E. chisholmae differs from all congeners in possessing 11 hooks in each dorsal and ventral group on the rostellum and groups of 3-6 hooklets on either side of the hooks. A single metacestode of E. chisholmae was collected from the decapod crustacean Penaeus longistylus Kubo. Yellow pigmentation of the cephalic peduncle in immature adults is caused by the accumulation of large vesicles in the distal cytoplasm of the tegument. The vesicles probably provide materials for spine formation. Ultrastructural examination of the rostellar musculature revealed that the muscles are stratified (striated-like), consisting of a periodic repetition of sarcomeres separated by perforated Z-like lines that are oblique to the long axes of the myofilaments.

Galaxy Zoo: secular evolution of barred galaxies from structural decomposition of multiband images

NASA Astrophysics Data System (ADS)

Kruk, Sandor J.; Lintott, Chris J.; Bamford, Steven P.; Masters, Karen L.; Simmons, Brooke D.; Häußler, Boris; Cardamone, Carolin N.; Hart, Ross E.; Kelvin, Lee; Schawinski, Kevin; Smethurst, Rebecca J.; Vika, Marina

2018-02-01

We present the results of two-component (disc+bar) and three-component (disc+bar+bulge) multiwavelength 2D photometric decompositions of barred galaxies in five Sloan Digital Sky Survey (SDSS) bands (ugriz). This sample of ∼3500 nearby (z < 0.06) galaxies with strong bars selected from the Galaxy Zoo citizen science project is the largest sample of barred galaxies to be studied using photometric decompositions that include a bar component. With detailed structural analysis, we obtain physical quantities such as the bar- and bulge-to-total luminosity ratios, effective radii, Sérsic indices and colours of the individual components. We observe a clear difference in the colours of the components, the discs being bluer than the bars and bulges. An overwhelming fraction of bulge components have Sérsic indices consistent with being pseudo-bulges. By comparing the barred galaxies with a mass-matched and volume-limited sample of unbarred galaxies, we examine the connection between the presence of a large-scale galactic bar and the properties of discs and bulges. We find that the discs of unbarred galaxies are significantly bluer compared to the discs of barred galaxies, while there is no significant difference in the colours of the bulges. We find possible evidence of secular evolution via bars that leads to the build-up of pseudo-bulges and to the quenching of star formation in the discs. We identify a subsample of unbarred galaxies with an inner lens/oval and find that their properties are similar to barred galaxies, consistent with an evolutionary scenario in which bars dissolve into lenses. This scenario deserves further investigation through both theoretical and observational work.

Genetic advances in sarcomeric cardiomyopathies: state of the art

PubMed Central

Ho, Carolyn Y.; Charron, Philippe; Richard, Pascale; Girolami, Francesca; Van Spaendonck-Zwarts, Karin Y.; Pinto, Yigal

2015-01-01

Genetic studies in the 1980s and 1990s led to landmark discoveries that sarcomere mutations cause both hypertrophic and dilated cardiomyopathies. Sarcomere mutations also likely play a role in more complex phenotypes and overlap cardiomyopathies with features of hypertrophy, dilation, diastolic abnormalities, and non-compaction. Identification of the genetic cause of these important conditions provides unique opportunities to interrogate and characterize disease pathogenesis and pathophysiology, starting from the molecular level and expanding from there. With such insights, there is potential for clinical translation that may transform management of patients and families with inherited cardiomyopathies. If key pathways for disease development can be identified, they could potentially serve as targets for novel disease-modifying or disease-preventing therapies. By utilizing gene-based diagnostic testing, we can identify at-risk individuals prior to the onset of clinical disease, allowing for disease-modifying therapy to be initiated early in life, at a time that such treatment may be most successful. In this section, we review the current application of genetics in clinical management, focusing on hypertrophic cardiomyopathy as a paradigm; discuss state-of-the-art genetic testing technology; review emerging knowledge of gene expression in sarcomeric cardiomyopathies; and discuss both the prospects, as well as the challenges, of bringing genetics to medicine. PMID:25634555

Tropomyosin 1: Multiple roles in the developing heart and in the formation of congenital heart defects.

PubMed

England, Jennifer; Granados-Riveron, Javier; Polo-Parada, Luis; Kuriakose, Diji; Moore, Christopher; Brook, J David; Rutland, Catrin S; Setchfield, Kerry; Gell, Christopher; Ghosh, Tushar K; Bu'Lock, Frances; Thornborough, Christopher; Ehler, Elisabeth; Loughna, Siobhan

2017-05-01

Tropomyosin 1 (TPM1) is an essential sarcomeric component, stabilising the thin filament and facilitating actin's interaction with myosin. A number of sarcomeric proteins, such as alpha myosin heavy chain, play crucial roles in cardiac development. Mutations in these genes have been linked to congenital heart defects (CHDs), occurring in approximately 1 in 145 live births. To date, TPM1 has not been associated with isolated CHDs. Analysis of 380 CHD cases revealed three novel mutations in the TPM1 gene; IVS1+2T>C, I130V, S229F and a polyadenylation signal site variant GATAAA/AATAAA. Analysis of IVS1+2T>C revealed aberrant pre-mRNA splicing. In addition, abnormal structural properties were found in hearts transfected with TPM1 carrying I130V and S229F mutations. Phenotypic analysis of TPM1 morpholino-treated embryos revealed roles for TPM1 in cardiac looping, atrial septation and ventricular trabeculae formation and increased apoptosis was seen within the heart. In addition, sarcomere assembly was affected and altered action potentials were exhibited. This study demonstrated that sarcomeric TPM1 plays vital roles in cardiogenesis and is a suitable candidate gene for screening individuals with isolated CHDs. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The interdependence of Ca2+ activation, sarcomere length, and power output in the heart.

PubMed

McDonald, Kerry S

2011-07-01

Myocardium generates power to perform external work on the circulation; yet, many questions regarding intermolecular mechanisms regulating power output remain unresolved. Power output equals force × shortening velocity, and some interesting new observations regarding control of these two factors have arisen. While it is well established that sarcomere length tightly controls myocyte force, sarcomere length-tension relationships also appear to be markedly modulated by PKA-mediated phosphorylation of myofibrillar proteins. Concerning loaded shortening, historical models predict independent cross-bridge mechanics; however, it seems that the mechanical state of one population of cross-bridges affects the activity of other cross-bridges by, for example, recruitment of cross-bridges from the non-cycling pool to the cycling force-generating pool during submaximal Ca(2+) activation. This is supported by the findings that Ca(2+) activation levels, myofilament phosphorylation, and sarcomere length are all modulators of loaded shortening and power output independent of their effects on force. This fine tuning of power output probably helps optimize myocardial energetics and to match ventricular supply with peripheral demand; yet, the discernment of the chemo-mechanical signals that modulate loaded shortening needs further clarification since power output may be a key convergent point and feedback regulator of cytoskeleton and cellular signals that control myocyte growth and survival.

Animal and in silico models for the study of sarcomeric cardiomyopathies

PubMed Central

Duncker, Dirk J.; Bakkers, Jeroen; Brundel, Bianca J.; Robbins, Jeff; Tardiff, Jil C.; Carrier, Lucie

2015-01-01

Over the past decade, our understanding of cardiomyopathies has improved dramatically, due to improvements in screening and detection of gene defects in the human genome as well as a variety of novel animal models (mouse, zebrafish, and drosophila) and in silico computational models. These novel experimental tools have created a platform that is highly complementary to the naturally occurring cardiomyopathies in cats and dogs that had been available for some time. A fully integrative approach, which incorporates all these modalities, is likely required for significant steps forward in understanding the molecular underpinnings and pathogenesis of cardiomyopathies. Finally, novel technologies, including CRISPR/Cas9, which have already been proved to work in zebrafish, are currently being employed to engineer sarcomeric cardiomyopathy in larger animals, including pigs and non-human primates. In the mouse, the increased speed with which these techniques can be employed to engineer precise ‘knock-in’ models that previously took years to make via multiple rounds of homologous recombination-based gene targeting promises multiple and precise models of human cardiac disease for future study. Such novel genetically engineered animal models recapitulating human sarcomeric protein defects will help bridging the gap to translate therapeutic targets from small animal and in silico models to the human patient with sarcomeric cardiomyopathy. PMID:25600962

Spontaneous oscillation of tension and sarcomere length in skeletal myofibrils. Microscopic measurement and analysis.

PubMed

Anazawa, T; Yasuda, K; Ishiwata, S

1992-05-01

We have devised a simple method for measuring tension development of single myofibrils by micromanipulation with a pair of glass micro-needles. The tension was estimated from the deflection of a flexible needle under an inverted phase-contrast microscope equipped with an image processor, so that the tension development is always accompanied by the shortening of the myofibril (auxotonic condition) in the present setup. The advantage of this method is that the measurement of tension (1/30 s for time resolution and about 0.05 micrograms for accuracy of tension measurement; 0.05 microns as a spatial resolution for displacement of the micro-needle) and the observation of sarcomere structure are possible at the same time, and the technique to hold myofibrils, even single myofibrils, is very simple. This method has been applied to study the tension development of glycerinated skeletal myofibrils under the condition where spontaneous oscillation of sarcomeres is induced, i.e., the coexistence of MgATP, MgADP and inorganic phosphate without free Ca2+. Under this condition, we found that the tension of myofibrils spontaneously oscillates accompanied by the oscillation of sarcomere length with a main period of a few seconds; the period was lengthened and shortened with stretch and release of myofibrils. A possible mechanism of the oscillation is discussed.

Vortices and the saturation of the vertical shear instability in protoplanetary discs

NASA Astrophysics Data System (ADS)

Latter, Henrik N.; Papaloizou, John

2018-03-01

If sufficiently irradiated by its central star, a protoplanetary disc falls into an equilibrium state exhibiting vertical shear. This state may be subject to a hydrodynamical instability, the `vertical shear instability' (VSI), whose breakdown into turbulence transports a moderate amount of angular momentum while also facilitating planet formation, possibly via the production of small-scale vortices. In this paper, we show that VSI modes (a) exhibit arbitrary spatial profiles and (b) remain non-linear solutions to the incompressible local equations, no matter their amplitude. The modes are themselves subject to parasitic Kelvin-Helmholtz instability, though the disc rotation significantly impedes the parasites and permits the VSI to attain large amplitudes (fluid velocities ≲ 10 per cent the sound speed). This `delay' in saturation probably explains the prominence of the VSI linear modes in global simulations. More generally, the parasites may set the amplitude of VSI turbulence in strongly irradiated discs. They are also important in breaking the axisymmetry of the flow, via the unavoidable formation of vortices. The vortices, however, are not aligned with the orbital plane and thus express a pronounced z-dependence. We also briefly demonstrate that the vertical shear has little effect on the magnetorotational instability, whereas magnetic fields easily quench the VSI, a potential issue in the ionized surface regions of the disc and also at larger radii.

Diltiazem Treatment for Preclinical Hypertrophic Cardiomyopathy Mutation Carriers: A Pilot Randomized Trial to Modify Disease Expression

PubMed Central

Ho, Carolyn Y.; Lakdawala, Neal K.; Cirino, Allison L.; Lipshultz, Steven E.; Sparks, Elizabeth; Abbasi, Siddique A.; Kwong, Raymond Y.; Antman, Elliott M.; Semsarian, Christopher; González, Arantxa; López, Begoña; Diez, Javier; Orav, E. John; Colan, Steven D.; Seidman, Christine E.

2014-01-01

Background Hypertrophic cardiomyopathy (HCM) is caused by sarcomere mutations and characterized by left ventricular hypertrophy (LVH) with increased risk of heart failure and sudden death. HCM typically cannot be diagnosed early in life, although subtle phenotypes are present. Animal studies indicate alterations in intracellular calcium handling before LVH develops. Furthermore, early treatment with diltiazem appeared to attenuate disease emergence. Objectives To assess the safety, feasibility, and effect of diltiazem as disease-modifying therapy for at-risk HCM mutation carriers. Methods In a pilot, double-blind trial, we randomly assigned 38 sarcomere mutation carriers without LVH (mean age 15.8 years) to therapy with diltiazem 360 mg/day (or 5 mg/kg/day) or placebo. Treatment duration ranged from 12 to 42 months (median 25 months). Study procedures included electrocardiography, echocardiography, cardiac magnetic resonance imaging, and serum biomarker measurement. Results Diltiazem was not associated with serious adverse events. Heart rate and blood pressure did not differ significantly between groups. However, mean left ventricular end diastolic diameter improved towards normal in the diltiazem group but decreased further in controls (change in z-scores, +0.6 vs. −0.5; P<0.001). Mean LV thickness-to-dimension ratio was stable in the diltiazem group, but increased in controls (−0.02 vs. +0.15; P=0.04). Among MYBPC3 mutation carriers, LV wall thickness and mass, diastolic filling, and cardiac troponin I levels improved in those taking diltiazem compared with controls. Four participants developed overt HCM, two in each treatment group. Conclusions Preclinical administration of diltiazem is safe and may improve early LV remodeling in HCM. This novel strategy merits further exploration. PMID:25543971

The Holy Grail of Orthopedic Surgery: Mesenchymal Stem Cells—Their Current Uses and Potential Applications

PubMed Central

Berebichez-Fridman, Roberto; Gómez-García, Ricardo; Berebichez-Fastlicht, Enrique; Olivos-Meza, Anell; Granados, Julio; Velasquillo, Cristina

2017-01-01

Only select tissues and organs are able to spontaneously regenerate after disease or trauma, and this regenerative capacity diminishes over time. Human stem cell research explores therapeutic regenerative approaches to treat various conditions. Mesenchymal stem cells (MSCs) are derived from adult stem cells; they are multipotent and exert anti-inflammatory and immunomodulatory effects. They can differentiate into multiple cell types of the mesenchyme, for example, endothelial cells, osteoblasts, chondrocytes, fibroblasts, tenocytes, vascular smooth muscle cells, and sarcomere muscular cells. MSCs are easily obtained and can be cultivated and expanded in vitro; thus, they represent a promising and encouraging treatment approach in orthopedic surgery. Here, we review the application of MSCs to various orthopedic conditions, namely, orthopedic trauma; muscle injury; articular cartilage defects and osteoarthritis; meniscal injuries; bone disease; nerve, tendon, and ligament injuries; spinal cord injuries; intervertebral disc problems; pediatrics; and rotator cuff repair. The use of MSCs in orthopedics may transition the practice in the field from predominately surgical replacement and reconstruction to bioregeneration and prevention. However, additional research is necessary to explore the safety and effectiveness of MSC treatment in orthopedics, as well as applications in other medical specialties. PMID:28698718

Induction of rat alkaline phosphatase isozymes bearing a glycan-phosphatidylinositol anchor modified by in vivo treatment with a benzimidazole derivative linked to ethylbenzene.

PubMed

Harada, T; Koyama, I; Sato, K; Komoda, T

2000-10-01

Serum alkaline phosphatase (ALP) is detected in soluble-form as a result of translocation from the membrane site by cleavage at the glycosyl-phosphatidylinositol moiety (GPI anchor). It is known that membrane-bound ALP (mALP) can be detected in serum in certain pathological and physiological conditions, and that it can be solubilized in vitro to soluble-ALP (sALP) by phosphatidylinositol-specific phospholipase C (PIPLC), phospholipase D, bile salt, detergent, etc. We observed a marked increase in ALP activity in the serum of rats given a benzimidazole derivative by gavage, and detected it as slow-migrating ALPs (SM-ALPs), which were mALP-like but resistant to PIPLC and n-butanol treatment on disc PAGE. On the other hand, ficin treatment made SM-ALPs shift to the sALP position. The molecular size of the SM-ALPs was smaller than that of sALP on sodium dodecyl sulphide-polyacrylamide slab-gel electrophoresis (SDS-PAGE), and immunoreactivity revealed the intestinal type. SM-ALPs were also detected in the duodenum and jejunum. The main sugar chain structure of SM-ALPs was the biantennary complex-type, which was coincided with intestinal sALP sugar chain. These results suggest that intestinal ALPs induced by the benzimidazole derivative were modified in their C-terminus or GPI anchor region and modification of this region may also participate in translocation into the bloodstream.

What is the changing frequency of diamond burs?

PubMed

Emir, Faruk; Ayyildiz, Simel; Sahin, Cem

2018-04-01

The purpose of this study was to determine the changing frequency of a diamond bur after multiple usages on 3 different surfaces. Human premolar teeth (N = 26), disc shaped direct metal laser sintered CoCr (N = 3) and zirconia specimens (N = 3) were used in this study. Groups named basically as Group T for teeth, Group M for CoCr, and Group Z for zirconia. Round tapered black-band diamond bur was used. The specimens were randomly divided into three groups and placed with a special assembly onto the surveyor. 1, 5, and 10 preparation protocols were performed to the first, second, and third sub-groups, respectively. The subgroups were named according to preparation numbers (1, 5, 10). The mentioned bur of each group was then used at another horizontal preparation on a new tooth sample. The same procedure was used for CoCr and zirconia disc specimens. All of the bur surfaces were evaluated using roughness analysis. Then, horizontal tooth preparation surfaces were examined under both stereomicroscope and SEM. The depth maps of tooth surfaces were also obtained from digital stereomicroscopic images. The results were statistically analyzed using One-Way ANOVA, and the Tukey HSD post-hoc tests (α=.05). All of the groups were significantly different from the control group ( P <.001). There was no significant difference between groups Z5 and Z10 ( P =.928). Significant differences were found among groups T5, M5, and Z5 ( P <.001). Diamond burs wear after multiple use and they should be changed after 5 teeth preparations at most. A diamond bur should not be used for teeth preparation after try-in procedures of metal or zirconia substructures.

The influence of Sagittarius and the Large Magellanic Cloud on the stellar disc of the Milky Way Galaxy

NASA Astrophysics Data System (ADS)

Laporte, Chervin F. P.; Johnston, Kathryn V.; Gómez, Facundo A.; Garavito-Camargo, Nicolas; Besla, Gurtina

2018-06-01

We present N-body simulations of a Sagittarius-like dwarf spheroidal galaxy (Sgr) that follow its orbit about the Milky Way (MW) since its first crossing of the Galaxy's virial radius to the present day. As Sgr orbits around the MW, it excites vertical oscillations, corrugating and flaring the Galactic stellar disc. These responses can be understood by a two-phase picture in which the interaction is first dominated by torques from the wake excited by Sgr in the MW dark halo before transitioning to tides from Sgr's direct impact on the disc at late times. We show for the first time that a massive Sgr model simultaneously reproduces the locations and motions of arc-like over densities, such as the Monoceros Ring and the Triangulum Andromeda stellar clouds, that have been observed at the extremities of the disc, while also satisfying the solar neighbourhood constraints on the vertical structure and streaming motions of the disc. In additional simulations, we include the Large Magellanic Cloud (LMC) self consistently with Sgr. The LMC introduces coupling through constructive and destructive interference, but no new corrugations. In our models, the excitation of the current structure of the outer disk can be traced to interactions as far back as 6-7 Gyr ago (corresponding to z ≤ 1). Given the apparently quiescent accretion history of the MW over this timescale, this places Sgr as the main culprit behind the vertical oscillations of the disc and the last major accretion event for the Galaxy with the capacity to modulate its chemodynamical structure.

Titin Mutations in iPS cells Define Sarcomere Insufficiency as a Cause of Dilated Cardiomyopathy

PubMed Central

Hinson, John T.; Chopra, Anant; Nafissi, Navid; Polacheck, William J.; Benson, Craig C.; Swist, Sandra; Gorham, Joshua; Yang, Luhan; Schafer, Sebastian; Sheng, Calvin C.; Haghighi, Alireza; Homsy, Jason; Hubner, Norbert; Church, George; Cook, Stuart A.; Linke, Wolfgang A.; Chen, Christopher S.; Seidman, J. G.; Seidman, Christine E.

2015-01-01

Human mutations that truncate the massive sarcomere protein titin (TTNtv) are the most common genetic cause for dilated cardiomyopathy (DCM), a major cause of heart failure and premature death. Here we show that cardiac microtissues engineered from human induced pluripotent stem (iPS) cells are a powerful system for evaluating the pathogenicity of titin gene variants. We found that certain missense mutations, like TTNtv, diminish contractile performance and are pathogenic. By combining functional analyses with RNAseq, we explain why truncations in the A-band domain of TTN cause DCM while truncations in the I-band are better tolerated. Finally, we demonstrate that mutant titin protein in iPS-cardiomyocytes results in sarcomere insufficiency, impaired responses to mechanical and β-adrenergic stress, and attenuated growth factor and cell signaling activation. Our findings indicate that titin mutations cause DCM by disrupting critical linkages between sarcomerogenesis and adaptive remodelling. PMID:26315439

Effect of two fluoride varnishes on the color stability of three resin-based restorative materials: an in vitro study.

PubMed

Tafaroji, Raha; Biria, Mina; Ameri, Farhad; Torabzadeh, Hassan; Qahari, Pasha; Akbarzadeh Baghban, Alireza

2016-11-01

The aim of the present study was to evaluate the effect of two fluoride varnishes on color stability of three resin-based restorative materials. Fifty-four discs (14.5 × 1.7 mm) were fabricated from A2 and A3 shades of a compomer (F2000), a flowable composite (Z350), and a hybrid composite (Z250), and incubated at 37°C for 48 h. Dura Shield (colored) and Fluor Protector (colorless) fluoride varnishes were applied onto the discs. The coating was cleaned using a low-speed handpiece and nylon bristle brush after 24 h of storage in distilled water. A second coating was then applied. A control group with no coating was immersed in distilled water and used. The CIE L*a*b* color scale was measured before the treatments and following each cleaning utilizing a spectrophotometer. The colored fluoride varnish exhibited the highest overall color change (∆E) after the first and the second cleaning procedures in all the materials. Among these, the greatest color change was observed in the A3 shade of F2000, followed by the A3 shade of Z-250. The ∆E was less than 3.3 in all groups, and was therefore clinically acceptable. Color changes following the application of fluoride varnishes were found to be clinically acceptable in all groups. © 2015 Wiley Publishing Asia Pty Ltd.

The Tully-Fisher relation for 25 000 Sloan Digital Sky Survey galaxies as a function of environment

NASA Astrophysics Data System (ADS)

Mocz, P.; Green, A.; Malacari, M.; Glazebrook, K.

2012-09-01

We construct Tully-Fisher relationships (TFRs) in the u, g, r, i and z bands and stellar mass TFRs for a sample of 25 698 late spiral-type galaxies (with 0.045 < z < 0.085) from the Sloan Digital Sky Survey (SDSS) and study the effects of environment on the relation. We use SDSS-measured Balmer emission line widths, vFWHM, as a proxy for disc circular velocity, vcirc. A priori, it is not clear whether we can construct accurate TFRs given the small 3 arcsec diameter of the fibres used for SDSS spectroscopic measurements. However, we show by modelling the Hα emission profile as observed through a 3 arcsec aperture that for galaxies at appropriate redshifts (z > 0.045) the fibres sample enough of the disc to obtain a linear relationship between vFWHM and vcirc, allowing us to obtain a TFR and to investigate dependence on other variables. We also develop a methodology for distinguishing between astrophysical and sample bias in the fibre TFR trends. We observe the well-known steepening of the TFR in redder bands in our sample. We divide the sample of galaxies into four equal groups using projected neighbour density (Σ) quartiles and find no significant dependence on environment, extending previous work to a wider range of environments and a much larger sample. Having demonstrated that we can construct SDSS-based TFRs is very useful for future TFR studies because of the large sample size available in the SDSS.

Differentiation and sarcomere formation in skeletal myocytes directly prepared from human induced pluripotent stem cells using a sphere-based culture.

PubMed

Jiwlawat, Saowanee; Lynch, Eileen; Glaser, Jennifer; Smit-Oistad, Ivy; Jeffrey, Jeremy; Van Dyke, Jonathan M; Suzuki, Masatoshi

Human induced-pluripotent stem cells (iPSCs) are a promising resource for propagation of myogenic progenitors. Our group recently reported a unique protocol for the derivation of myogenic progenitors directly (without genetic modification) from human pluripotent cells using free-floating spherical culture. Here we expand our previous efforts and attempt to determine how differentiation duration, culture surface coatings, and nutrient supplements in the medium influence progenitor differentiation and formation of skeletal myotubes containing sarcomeric structures. A long differentiation period (over 6 weeks) promoted the differentiation of iPSC-derived myogenic progenitors and subsequent myotube formation. These iPSC-derived myotubes contained representative sarcomeric structures, consisting of organized myosin and actin filaments, and could spontaneously contract. We also found that a bioengineering approach using three-dimensional (3D) artificial muscle constructs could facilitate the formation of elongated myotubes. Lastly, we determined how culture surface coating matrices and different supplements would influence terminal differentiation. While both Matrigel and laminin coatings showed comparable effects on muscle differentiation, B27 serum-free supplement in the differentiation medium significantly enhanced myogenesis compared to horse serum. Our findings support the possibility to create an in vitro model of contractile sarcomeric myofibrils for disease modeling and drug screening to study neuromuscular diseases. Copyright © 2017 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Genetic advances in sarcomeric cardiomyopathies: state of the art.

PubMed

Ho, Carolyn Y; Charron, Philippe; Richard, Pascale; Girolami, Francesca; Van Spaendonck-Zwarts, Karin Y; Pinto, Yigal

2015-04-01

Genetic studies in the 1980s and 1990s led to landmark discoveries that sarcomere mutations cause both hypertrophic and dilated cardiomyopathies. Sarcomere mutations also likely play a role in more complex phenotypes and overlap cardiomyopathies with features of hypertrophy, dilation, diastolic abnormalities, and non-compaction. Identification of the genetic cause of these important conditions provides unique opportunities to interrogate and characterize disease pathogenesis and pathophysiology, starting from the molecular level and expanding from there. With such insights, there is potential for clinical translation that may transform management of patients and families with inherited cardiomyopathies. If key pathways for disease development can be identified, they could potentially serve as targets for novel disease-modifying or disease-preventing therapies. By utilizing gene-based diagnostic testing, we can identify at-risk individuals prior to the onset of clinical disease, allowing for disease-modifying therapy to be initiated early in life, at a time that such treatment may be most successful. In this section, we review the current application of genetics in clinical management, focusing on hypertrophic cardiomyopathy as a paradigm; discuss state-of-the-art genetic testing technology; review emerging knowledge of gene expression in sarcomeric cardiomyopathies; and discuss both the prospects, as well as the challenges, of bringing genetics to medicine. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

The role of titin in eccentric muscle contraction.

PubMed

Herzog, Walter

2014-08-15

Muscle contraction and force regulation in skeletal muscle have been thought to occur exclusively through the relative sliding of and the interaction between the contractile filaments actin and myosin. While this two-filament sarcomere model has worked well in explaining the properties of isometrically and concentrically contracting muscle, it has failed miserably in explaining experimental observations in eccentric contractions. Here, I suggest, and provide evidence, that a third filament, titin, is involved in force regulation of sarcomeres by adjusting its stiffness in an activation-dependent (calcium) and active force-dependent manner. Upon muscle activation, titin binds calcium at specific sites, thereby increasing its stiffness, and cross-bridge attachment to actin is thought to free up binding sites for titin on actin, thereby reducing titin's free-spring length, thus increasing its stiffness and force upon stretch of active muscle. This role of titin as a third force regulating myofilament in sarcomeres, although not fully proven, would account for many of the unexplained properties of eccentric muscle contraction, while simultaneously not affecting the properties predicted by the two-filament cross-bridge model in isometric and concentric muscle function. Here, I identify the problems of the two-filament sarcomere model and demonstrate the advantages of the three-filament model by providing evidence of titin's contribution to active force in eccentric muscle function. © 2014. Published by The Company of Biologists Ltd.

The role of sarcomere gene mutations in patients with idiopathic dilated cardiomyopathy

PubMed Central

Møller, Daniel Vega; Andersen, Paal Skytt; Hedley, Paula; Ersbøll, Mads Kristian; Bundgaard, Henning; Moolman-Smook, Johanna; Christiansen, Michael; Køber, Lars

2009-01-01

We investigated a Danish cohort of 31 unrelated patients with idiopathic dilated cardiomyopathy (IDC), to assess the role that mutations in sarcomere protein genes play in IDC. Patients were genetically screened by capillary electrophoresis single strand conformation polymorphism and subsequently by bidirectional DNA sequencing of conformers in the coding regions of MYH7, MYBPC3, TPM1, ACTC, MYL2, MYL3, TNNT2, CSRP3 and TNNI3. Eight probands carried disease-associated genetic variants (26%). In MYH7, three novel mutations were found; in MYBPC3, one novel variant and two known mutations were found; and in TNNT2, a known mutation was found. One proband was double heterozygous. We find evidence of phenotypic plasticity: three mutations described earlier as HCM causing were found in four cases of IDC, with no history of a hypertrophic phase. Furthermore, one pedigree presented with several cases of classic DCM as well as one case with left ventricular non-compaction. Disease-causing sarcomere gene mutations were found in about one-quarter of IDC patients, and seem to play an important role in the causation of the disease. The genetics is as complex as seen in HCM. Thus, our data suggest that a genetic work-up should include screening of the most prominent sarcomere genes even in the absence of a family history of the disease. PMID:19293840

SarcOptiM for ImageJ: high-frequency online sarcomere length computing on stimulated cardiomyocytes.

PubMed

Pasqualin, Côme; Gannier, François; Yu, Angèle; Malécot, Claire O; Bredeloux, Pierre; Maupoil, Véronique

2016-08-01

Accurate measurement of cardiomyocyte contraction is a critical issue for scientists working on cardiac physiology and physiopathology of diseases implying contraction impairment. Cardiomyocytes contraction can be quantified by measuring sarcomere length, but few tools are available for this, and none is freely distributed. We developed a plug-in (SarcOptiM) for the ImageJ/Fiji image analysis platform developed by the National Institutes of Health. SarcOptiM computes sarcomere length via fast Fourier transform analysis of video frames captured or displayed in ImageJ and thus is not tied to a dedicated video camera. It can work in real time or offline, the latter overcoming rotating motion or displacement-related artifacts. SarcOptiM includes a simulator and video generator of cardiomyocyte contraction. Acquisition parameters, such as pixel size and camera frame rate, were tested with both experimental recordings of rat ventricular cardiomyocytes and synthetic videos. It is freely distributed, and its source code is available. It works under Windows, Mac, or Linux operating systems. The camera speed is the limiting factor, since the algorithm can compute online sarcomere shortening at frame rates >10 kHz. In conclusion, SarcOptiM is a free and validated user-friendly tool for studying cardiomyocyte contraction in all species, including human. Copyright © 2016 the American Physiological Society.

The Chloroplast Division Protein ARC6 Acts to Inhibit Disassembly of GDP-bound FtsZ2.

PubMed

Sung, Min Woo; Shaik, Rahamthulla; TerBush, Allan D; Osteryoung, Katherine W; Vitha, Stanislav; Holzenburg, Andreas

2018-05-16

Chloroplasts host photosynthesis and fulfill other metabolic functions that are essential to plant life. They have to divide by binary fission to maintain their numbers throughout cycles of cell division. Chloroplast division is achieved by a complex ring-shaped division machinery located on both the inner (stromal) and the outer (cytosolic) side of the chloroplast envelope. The inner division ring (termed the Z ring) is formed by the assembly of tubulin-like FtsZ1 and FtsZ2 proteins. ARC6 is a key chloroplast division protein that interacts with the Z ring. ARC6 spans the inner envelope membrane, is known to stabilize or maintain the Z ring, and anchors the Z ring to the inner membrane through interaction with FtsZ2. The underlying mechanism of Z-ring stabilization is not well understood. Here, biochemical and structural characterization of ARC6 was conducted using light scattering, sedimentation, and light and transmission electron microscopy. The recombinant protein was purified as a dimer. The results indicated that a truncated form of ARC6 (tARC6), representing the stromal portion of ARC6, affects FtsZ2 assembly without forming higher-order structures, and exerts its effect via FtsZ2 dynamics. tARC6 prevented GDP-induced FtsZ2 disassembly and caused a significant net increase in FtsZ2 assembly when GDP was present. Single particle analysis and 3D reconstruction were performed to elucidate the structural basis of ARC6 activity. Together, the data reveal that a dimeric form of tARC6 binds to FtsZ2 filaments and does not increase FtsZ polymerization rates but rather inhibits GDP-associated FtsZ2 disassembly. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Structure of the Z Ring-associated Protein, ZapD, Bound to the C-terminal Domain of the Tubulin-like Protein, FtsZ, Suggests Mechanism of Z Ring Stabilization through FtsZ Cross-linking.

PubMed

Schumacher, Maria A; Huang, Kuo-Hsiang; Zeng, Wenjie; Janakiraman, Anuradha

2017-03-03

Cell division in most bacteria is mediated by the tubulin-like FtsZ protein, which polymerizes in a GTP-dependent manner to form the cytokinetic Z ring. A diverse repertoire of FtsZ-binding proteins affects FtsZ localization and polymerization to ensure correct Z ring formation. Many of these proteins bind the C-terminal domain (CTD) of FtsZ, which serves as a hub for FtsZ regulation. FtsZ ring-associated proteins, ZapA-D (Zaps), are important FtsZ regulatory proteins that stabilize FtsZ assembly and enhance Z ring formation by increasing lateral assembly of FtsZ protofilaments, which then form the Z ring. There are no structures of a Zap protein bound to FtsZ; therefore, how these proteins affect FtsZ polymerization has been unclear. Recent data showed ZapD binds specifically to the FtsZ CTD. Thus, to obtain insight into the ZapD-CTD interaction and how it may mediate FtsZ protofilament assembly, we determined the Escherichia coli ZapD-FtsZ CTD structure to 2.67 Å resolution. The structure shows that the CTD docks within a hydrophobic cleft in the ZapD helical domain and adopts an unusual structure composed of two turns of helix separated by a proline kink. FtsZ CTD residue Phe-377 inserts into the ZapD pocket, anchoring the CTD in place and permitting hydrophobic contacts between FtsZ residues Ile-374, Pro-375, and Leu-378 with ZapD residues Leu-74, Trp-77, Leu-91, and Leu-174. The structural findings were supported by mutagenesis coupled with biochemical and in vivo studies. The combined data suggest that ZapD acts as a molecular cross-linking reagent between FtsZ protofilaments to enhance FtsZ assembly. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Length dependence of force generation exhibit similarities between rat cardiac myocytes and skeletal muscle fibres.

PubMed

Hanft, Laurin M; McDonald, Kerry S

2010-08-01

According to the Frank-Starling relationship, increased ventricular volume increases cardiac output, which helps match cardiac output to peripheral circulatory demand. The cellular basis for this relationship is in large part the myofilament length-tension relationship. Length-tension relationships in maximally calcium activated preparations are relatively shallow and similar between cardiac myocytes and skeletal muscle fibres. During twitch activations length-tension relationships become steeper in both cardiac and skeletal muscle; however, it remains unclear whether length dependence of tension differs between striated muscle cell types during submaximal activations. The purpose of this study was to compare sarcomere length-tension relationships and the sarcomere length dependence of force development between rat skinned left ventricular cardiac myocytes and fast-twitch and slow-twitch skeletal muscle fibres. Muscle cell preparations were calcium activated to yield 50% maximal force, after which isometric force and rate constants (k(tr)) of force development were measured over a range of sarcomere lengths. Myofilament length-tension relationships were considerably steeper in fast-twitch fibres compared to slow-twitch fibres. Interestingly, cardiac myocyte preparations exhibited two populations of length-tension relationships, one steeper than fast-twitch fibres and the other similar to slow-twitch fibres. Moreover, myocytes with shallow length-tension relationships were converted to steeper length-tension relationships by protein kinase A (PKA)-induced myofilament phosphorylation. Sarcomere length-k(tr) relationships were distinct between all three cell types and exhibited patterns markedly different from Ca(2+) activation-dependent k(tr) relationships. Overall, these findings indicate cardiac myocytes exhibit varied length-tension relationships and sarcomere length appears a dominant modulator of force development rates. Importantly, cardiac myocyte length-tension relationships appear able to switch between slow-twitch-like and fast-twitch-like by PKA-mediated myofibrillar phosphorylation, which implicates a novel means for controlling Frank-Starling relationships.

A Novel, In-solution Separation of Endogenous Cardiac Sarcomeric Proteins and Identification of Distinct Charged Variants of Regulatory Light Chain*

PubMed Central

Scruggs, Sarah B.; Reisdorph, Rick; Armstrong, Mike L.; Warren, Chad M.; Reisdorph, Nichole; Solaro, R. John; Buttrick, Peter M.

2010-01-01

The molecular conformation of the cardiac myosin motor is modulated by intermolecular interactions among the heavy chain, the light chains, myosin binding protein-C, and titin and is governed by post-translational modifications (PTMs). In-gel digestion followed by LC/MS/MS has classically been applied to identify cardiac sarcomeric PTMs; however, this approach is limited by protein size, pI, and difficulties in peptide extraction. We report a solution-based work flow for global separation of endogenous cardiac sarcomeric proteins with a focus on the regulatory light chain (RLC) in which specific sites of phosphorylation have been unclear. Subcellular fractionation followed by OFFGEL electrophoresis resulted in isolation of endogenous charge variants of sarcomeric proteins, including regulatory and essential light chains, myosin heavy chain, and myosin-binding protein-C of the thick filament. Further purification of RLC using reverse-phase HPLC separation and UV detection enriched for RLC PTMs at the intact protein level and provided a stoichiometric and quantitative assessment of endogenous RLC charge variants. Digestion and subsequent LC/MS/MS unequivocally identified that the endogenous charge variants of cardiac RLC focused in unique OFFGEL electrophoresis fractions were unphosphorylated (78.8%), singly phosphorylated (18.1%), and doubly phosphorylated (3.1%) RLC. The novel aspects of this study are that 1) milligram amounts of endogenous cardiac sarcomeric subproteome were focused with resolution comparable with two-dimensional electrophoresis, 2) separation and quantification of post-translationally modified variants were achieved at the intact protein level, 3) separation of intact high molecular weight thick filament proteins was achieved in solution, and 4) endogenous charge variants of RLC were separated; a novel doubly phosphorylated form was identified in mouse, and singly phosphorylated, singly deamidated, and deamidated/phosphorylated forms were identified and quantified in human non-failing and failing heart samples, thus demonstrating the clinical utility of the method. PMID:20445002

Sarcomere length-dependence of activity-dependent twitch potentiation in mouse skeletal muscle

PubMed Central

Rassier, Dilson E; MacIntosh, Brian R

2002-01-01

Background It has been reported that potentiation of a skeletal muscle twitch response is proportional to muscle length with a negative slope during staircase, and a positive slope during posttetanic potentiation. This study was done to directly compare staircase and posttetanic responses with measurement of sarcomere length to compare their length-dependence. Methods Mouse extensor digitorum longus (EDL) muscles were dissected to small bundles of fibers, which permit measurement of sarcomere length (SL), by laser diffraction. In vitro fixed-end contractions of EDL fiber bundles were elicited at 22°C and 35°C at sarcomere lengths ranging from 2.35 μm to 3.85 μm. Twitch contractions were assessed before and after 1.5 s of 75 Hz stimulation at 22°C or during 10 s of 10 Hz stimulation at 22°C or 35°C. Results Staircase potentiation was greater at 35°C than 22°C, and the relative magnitude of the twitch contraction (Pt*/Pt) was proportional to sarcomere length with a negative slope, over the range 2.3 μm – 3.7 μm. Linear regression yielded the following: Pt*/Pt = -0.59·SL+3.27 (r2 = 0.74); Pt*/Pt = -0.39·SL+2.34 (r2 = 0.48); and Pt*/Pt = -0.50·SL+2.45 (r2 = 0.80) for staircase at 35°C, and 22°C and posttetanic response respectively. Posttetanic depression rather than potentiation was present at long SL. This indicates that there may be two processes operating in these muscles to modulate the force: one that enhances and a second that depresses the force. Either or both of these processes may have a length-dependence of its mechanism. Conclusion There is no evidence that posttetanic potentiation is fundamentally different from staircase in these muscles. PMID:12475395

Powering low-power implants using PZT transducer discs operated in the radial mode

NASA Astrophysics Data System (ADS)

Sanni, Ayodele; Vilches, Antonio

2013-11-01

This paper reports experimental results that are used to compare operation characteristics of lead zirconate titanate (PZT) piezoelectric ceramic discs operated in the radial mode. The devices are driven to radially vibrate at their lowest fundamental resonant frequency and thus transmit and receive power when immersed in a liquid phantom. A number of 1 mm × 10 mm (thickness × diameter) PZT discs are characterized experimentally within a propagation tank and results discussed. On the basis of these measured characteristics, a novel application is developed and reported for the first time. This consists of a tuned LC resonator circuit which is used at the receiving disc to maximize sensitivity as well as a Seiko start-up IC S-882Z which is employed to charge a capacitor that drives a PIC microcontroller (μC) once the voltage exceeds 2 V DC. We show that a mean input power of 486 mW RMS results in 976 μW RMS received over a range of 80 mm and that this is sufficient to periodically (every 60 s) power the μC to directly drive a red LED for 5 ms with a current of 4.8 mA/flash. This approach is suitable for low-power, periodically activated analogue bio-implant applications.

Percutaneous left atrial appendage occlusion: Effect of device positioning on outcome.

PubMed

Wolfrum, Mathias; Attinger-Toller, Adrian; Shakir, Samera; Gloekler, Steffen; Seifert, Burkhardt; Moschovitis, Aris; Khattab, Ahmed; Maisano, Francesco; Meier, Bernhard; Nietlispach, Fabian

2016-10-01

The study in patients with percutaneous left atrial appendage (LAA) occlusion investigates clinical outcomes according to the position of the Amplatzer Cardiac Plug (ACP) disc. The ACP consists of a disc and an anchoring lobe. The disc is meant to cover the ostium of the LAA, but frequently retracts partially or completely into the neck of the LAA. It is not known whether a retracted disc affects outcome. Outcomes of 169 consecutive patients (age 73.1 ± 10.4 years; 76% male) with successful LAA closure were analyzed according to the position of the ACP disc: group A had complete coverage of the LAA ostium; in group B the disc prolapsed partially or completely into the LAA-neck. Transesophageal echocardiography was performed 1-6 months after ACP implantation. The safety endpoint was the composite of clinically significant pericardial effusion, device embolization, procedure-related stroke/transient ischemic attack (TIA), major bleeding, or device thrombus. The efficacy endpoint was the composite of death, neurological events (ischemic and hemorrhagic stroke, TIA), or systemic embolism during follow-up. Group A comprised 76 patients (age 73.0 ± 9.9 years; 74% male) and group B 93 patients (age 73.3 ± 10.9 years; 79% male). Mean CHA 2 DS 2 -Vasc score and HASBLED score were 4.2 ± 1.7 (group A 4.3 ± 1.6; group B 4.2 ± 1.8) and 2.9 ± 1.1 (group A 2.9 ± 1.0; group B 3.0 ± 1.2), respectively. Mean follow-up of the study population was 13.0 ± 10.4 months. Overall, the composite safety and efficacy endpoints occurred in 20 (12%) and 6 patients (4%), respectively. There was no significant difference between groups A and B in the occurrence of the safety endpoint (13% vs. 11%, P = 0.64), or the efficacy endpoint (4% vs. 3%, P = 1.0). No evidence for a difference in the occurrence of the safety and efficacy endpoint was found between patients with complete vs. incomplete ACP disc coverage of the LAA ostium. The risk of repositioning attempts in case of incomplete coverage does not seem to be warranted. Current findings need further confirmation in a larger scale clinical trial. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Gas dynamics in tidal dwarf galaxies: Disc formation at z = 0

NASA Astrophysics Data System (ADS)

Lelli, Federico; Duc, Pierre-Alain; Brinks, Elias; Bournaud, Frédéric; McGaugh, Stacy S.; Lisenfeld, Ute; Weilbacher, Peter M.; Boquien, Médéric; Revaz, Yves; Braine, Jonathan; Koribalski, Bärbel S.; Belles, Pierre-Emmanuel

2015-12-01

Tidal dwarf galaxies (TDGs) are recycled objects that form within the collisional debris of interacting and merging galaxies. They are expected to be devoid of non-baryonic dark matter, since they can only form from dissipative material ejected from the discs of the progenitor galaxies. We investigate the gas dynamics in a sample of six bona fide TDGs around three interacting and post-interacting systems: NGC 4694, NGC 5291, and NGC 7252 ("Atoms for Peace"). For NGC 4694 and NGC 5291, we analyse existing H I data from the Very Large Array (VLA), while for NGC 7252 we present new H I observations from the Jansky VLA, together with long-slit and integral-field optical spectroscopy. For all six TDGs, the H I emission can be described by rotating disc models. These H I discs, however, have undergone less than a full rotation since the time of the interaction/merger event, raising the question of whether they are in dynamical equilibrium. Assuming that these discs are in equilibrium, the inferred dynamical masses are consistent with the observed baryonic masses, implying that TDGs are devoid of dark matter. This puts constraints on putative "dark discs" (either baryonic or non-baryonic) in the progenitor galaxies. Moreover, TDGs seem to systematically deviate from the baryonic Tully-Fisher relation. These results provide a challenging test for alternative theories like MOND. Based on observations made with ESO telescopes at Paranal Observatory under programmes 65.O-0563, 67.B-0049, and 083.B-0647.Appendices are available in electronic form at http://www.aanda.orgThe reduced data cubes are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/584/A113

Galaxy and Mass Assembly (GAMA): Morphological transformation of galaxies across the green valley

NASA Astrophysics Data System (ADS)

Bremer, M. N.; Phillipps, S.; Kelvin, L. S.; De Propris, R.; Kennedy, Rebecca; Moffett, Amanda J.; Bamford, S.; Davies, L. J. M.; Driver, S. P.; Häußler, B.; Holwerda, B.; Hopkins, A.; James, P. A.; Liske, J.; Percival, S.; Taylor, E. N.

2018-05-01

We explore constraints on the joint photometric and morphological evolution of typical low redshift galaxies as they move from the blue cloud through the green valley and on to the red sequence. We select Galaxy And Mass Assembly (GAMA) survey galaxies with 10.25 < log(M*/M⊙) < 10.75 and z < 0.2 classified according to their intrinsic u* - r* colour. From single component Sérsic fits, we find that the stellar mass-sensitive K-band profiles of red and green galaxy populations are very similar while g-band profiles indicate more disc-like morphologies for the green galaxies: apparent (optical) morphological differences arise primarily from radial mass-to-light ratio variations. Two-component fits show that most green galaxies have significant bulge and disc components and that the blue to red evolution is driven by colour change in the disc. Together, these strongly suggest that galaxies evolve from blue to red through secular disc fading and that a strong bulge is present prior to any decline in star formation. The relative abundance of the green population implies a typical time-scale for traversing the green valley ˜1-2 Gyr and is independent of environment, unlike that of the red and blue populations. While environment likely plays a rôle in triggering the passage across the green valley, it appears to have little effect on time taken. These results are consistent with a green valley population dominated by (early type) disc galaxies that are insufficiently supplied with gas to maintain previous levels of disc star formation, eventually attaining passive colours. No single event is needed to quench their star formation.

New mass anchor points for neutron-deficient heavy nuclei from direct mass measurements of radium and actinium isotopes

NASA Astrophysics Data System (ADS)

Rosenbusch, M.; Ito, Y.; Schury, P.; Wada, M.; Kaji, D.; Morimoto, K.; Haba, H.; Kimura, S.; Koura, H.; MacCormick, M.; Miyatake, H.; Moon, J. Y.; Morita, K.; Murray, I.; Niwase, T.; Ozawa, A.; Reponen, M.; Takamine, A.; Tanaka, T.; Wollnik, H.

2018-06-01

The masses of the exotic isotopes Ac-214210 and Ra-214210 have been measured with a multireflection time-of-flight mass spectrograph. These isotopes were obtained in flight as fusion-evaporation products behind the gas-filled recoil ion separator GARIS-II at RIKEN. The new direct mass measurements serve as an independent and direct benchmark for existing α -γ spectroscopy data in this mass region. Further, new mass anchor points are set for U and Np nuclei close to the N =126 shell closure for a future benchmark of the Z =92 subshell for neutron-deficient heavy isotopes. Our mass results are in general in good agreement with the previously indirectly determined mass values. Together with the measurement data, reasons for possible mass ambiguities from decay-data links between ground states are discussed.

Knockdown of desmin in zebrafish larvae affects interfilament spacing and mechanical properties of skeletal muscle.

PubMed

Li, Mei; Andersson-Lendahl, Monika; Sejersen, Thomas; Arner, Anders

2013-03-01

Skeletal muscle was examined in zebrafish larvae in order to address questions related to the function of the intermediate filament protein desmin and its role in the pathogenesis of human desminopathy. A novel approach including mechanical and structural studies of 4-6-d-old larvae was applied. Morpholino antisense oligonucleotides were used to knock down desmin. Expression was assessed using messenger RNA and protein analyses. Histology and synchrotron light-based small angle x-ray diffraction were applied. Functional properties were analyzed with in vivo studies of swimming behavior and with in vitro mechanical examinations of muscle. The two desmin genes normally expressed in zebrafish could be knocked down by ~50%. This resulted in a phenotype with disorganized muscles with altered attachments to the myosepta. The knockdown larvae were smaller and had diminished swimming activity. Active tension was lowered and muscles were less vulnerable to acute stretch-induced injury. X-ray diffraction revealed wider interfilament spacing. In conclusion, desmin intermediate filaments are required for normal active force generation and affect vulnerability during eccentric work. This is related to the role of desmin in anchoring sarcomeres for optimal force transmission. The results also show that a partial lack of desmin, without protein aggregates, is sufficient to cause muscle pathology resembling that in human desminopathy.

Harmonic force spectroscopy reveals a force-velocity curve from a single human beta cardiac myosin motor

NASA Astrophysics Data System (ADS)

Sung, Jongmin; Nag, Suman; Vestergaard, Christian; Mortensen, Kim; Flyvbjerg, Henrik; Spudich, James

2014-03-01

A muscle contracts rapidly under low load, but slowly under high load. Its molecular mechanisms remain to be elucidated, however. During contraction, myosins in thick filaments interact with actin in thin filaments in the sarcomere, cycling between a strongly bound (force producing) state and a weakly bound (relaxed) state. Huxley et al. have previously proposed that the transition from the strong to the weak interaction can be modulated by a load. We use a new method we call ``harmonic force spectroscopy'' to extract a load-velocity curve from a single human beta cardiac myosin II motor. With a dual-beam optical trap, we hold an actin dumbbell over a myosin molecule anchored to the microscope stage that oscillates sinusoidally. Upon binding, the motor experiences an oscillatory load with a mean that is directed forward or backward, depending on binding location We find that the bound time at saturating [ATP] is exponentially correlated with the mean load, which is explained by Arrhenius transition theory. With a stroke size measurement, we obtained a load-velocity curve from a single myosin. We compare the curves for wild-type motors with mutants that cause hypertrophic cardiomyopathies, to understand the effects on the contractile cycle

A Collection of Reprints,

DTIC Science & Technology

1986-01-01

developed an empirical model for calculating the wind shear velocity U,. The wird shear velocity is an indication of aerodynamic roughness at the...Fleming (1976) disc-isses the cause of scale variations. In 1978 a new digital side-scan system (SMS 960) was developed by EG & G which uses...Naval Postgraduate School Monterey, CA 93940 G. Z. Forristall Shell Development Company Houston, Texas 77001 ABSTRACT This paper catalogs and

The SCUBA-2 Cosmology Legacy Survey: The EGS deep field - II. Morphological transformation and multiwavelength properties of faint submillimetre galaxies

NASA Astrophysics Data System (ADS)

Zavala, J. A.; Aretxaga, I.; Dunlop, J. S.; Michałowski, M. J.; Hughes, D. H.; Bourne, N.; Chapin, E.; Cowley, W.; Farrah, D.; Lacey, C.; Targett, T.; van der Werf, P.

2018-04-01

We present a multiwavelength analysis of galaxies selected at 450 and 850 μm from the deepest SCUBA-2 observations in the Extended Groth Strip (EGS) field, which have an average depth of σ450 = 1.9 and σ850 = 0.46 mJy beam- 1 over ˜70 arcmin2. The final sample comprises 95 sources: 56 (59 per cent) are detected at both wavelengths, 31 (33 per cent) are detected only at 850 μm, and 8 (8 per cent) are detected only at 450 μm. We identify counterparts for 75 per cent of the whole sample. The redshift distributions of the 450 and 850 μm samples peak at different redshifts with median values of \\bar{z}=1.66± 0.18 and \\bar{z}=2.30± 0.20, respectively. However, the two populations have similar IR luminosities, SFRs, and stellar masses, with mean values of 1.5 ± 0.2 × 1012 L⊙, 150 ± 20 M⊙ yr-1, and 9.0 ± 0.6 × 1010 M⊙, respectively. This places most of our sources (≳85 per cent) on the high-mass end of the main sequence of star-forming galaxies. Exploring the IR excess versus UV-slope (IRX-β) relation we find that the most luminous galaxies are consistent with the Meurer law, while the less luminous galaxies lie below this relation. Using the results of a two-dimensional modelling of the HSTH160-band imaging, we derive a median Sérsic index of n=1.4^{+0.3}_{-0.1} and a median half-light radius of r1/2 = 4.8 ± 0.4 kpc. Based on a visual-like classification in the same band, we find that the dominant component for most of the galaxies at all redshifts is a disc-like structure, although there is a transition from irregular discs to discs with a spheroidal component at z ˜ 1.4, which morphologically supports the scenario of SMGs as progenitors of massive elliptical galaxies.

Cofilin-2 controls actin filament length in muscle sarcomeres

PubMed Central

Kremneva, Elena; Makkonen, Maarit H.; Skwarek-Maruszewska, Aneta; Gateva, Gergana; Michelot, Alphee; Dominguez, Roberto; Lappalainen, Pekka

2014-01-01

SUMMARY ADF/cofilins drive cytoskeletal dynamics by promoting the disassembly of ‘aged’ ADP-actin filaments. Mammals express several ADF/cofilin isoforms, but their specific biochemical activities and cellular functions have not been studied in detail. Here we demonstrate that the muscle-specific isoform cofilin-2 promotes actin filament disassembly in sarcomeres to control the precise length of thin filaments in the contractile apparatus. In contrast to other isoforms, cofilin-2 efficiently binds and disassembles both ADP- and ATP/ADP-Pi-actin filaments. We mapped surface-exposed cofilin-2-specific residues required for ATP-actin binding and propose that these residues function as an ‘actin nucleotide-state sensor’ among ADF/cofilins. The results suggest that cofilin-2 evolved specific biochemical and cellular properties allowing it to control actin dynamics in sarcomeres, where filament pointed ends may contain a mixture of ADP- and ATP/ADP-Pi-actin subunits. Our findings also offer a rationale for why cofilin-2 mutations in humans lead to myopathies. PMID:25373779

α-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy

PubMed Central

Mogensen, Jens; Klausen, Ib C.; Pedersen, Anders K.; Egeblad, Henrik; Bross, Peter; Kruse, Torben A.; Gregersen, Niels; Hansen, Peter S.; Baandrup, Ulrik; Børglum, Anders D.

1999-01-01

We identified the α-cardiac actin gene (ACTC) as a novel disease gene in a pedigree suffering from familial hypertrophic cardiomyopathy (FHC). Linkage analyses excluded all the previously reported FHC loci as possible disease loci in the family studied, with lod scores varying between –2.5 and –6.0. Further linkage analyses of plausible candidate genes highly expressed in the adult human heart identified ACTC as the most likely disease gene, showing a maximal lod score of 3.6. Mutation analysis of ACTC revealed an Ala295Ser mutation in exon 5 close to 2 missense mutations recently described to cause the inherited form of idiopathic dilated cardiomyopathy (IDC). ACTC is the first sarcomeric gene described in which mutations are responsible for 2 different cardiomyopathies. We hypothesize that ACTC mutations affecting sarcomere contraction lead to FHC and that mutations affecting force transmission from the sarcomere to the surrounding syncytium lead to IDC. PMID:10330430

Drebrin-like protein DBN-1 is a sarcomere component that stabilizes actin filaments during muscle contraction.

PubMed

Butkevich, Eugenia; Bodensiek, Kai; Fakhri, Nikta; von Roden, Kerstin; Schaap, Iwan A T; Majoul, Irina; Schmidt, Christoph F; Klopfenstein, Dieter R

2015-07-06

Actin filament organization and stability in the sarcomeres of muscle cells are critical for force generation. Here we identify and functionally characterize a Caenorhabditis elegans drebrin-like protein DBN-1 as a novel constituent of the muscle contraction machinery. In vitro, DBN-1 exhibits actin filament binding and bundling activity. In vivo, DBN-1 is expressed in body wall muscles of C. elegans. During the muscle contraction cycle, DBN-1 alternates location between myosin- and actin-rich regions of the sarcomere. In contracted muscle, DBN-1 is accumulated at I-bands where it likely regulates proper spacing of α-actinin and tropomyosin and protects actin filaments from the interaction with ADF/cofilin. DBN-1 loss of function results in the partial depolymerization of F-actin during muscle contraction. Taken together, our data show that DBN-1 organizes the muscle contractile apparatus maintaining the spatial relationship between actin-binding proteins such as α-actinin, tropomyosin and ADF/cofilin and possibly strengthening actin filaments by bundling.

Non-weight bearing-induced muscle weakness: the role of myosin quantity and quality in MHC type II fibers.

PubMed

Kim, Jong-Hee; Thompson, LaDora V

2014-07-15

We tested the hypothesis that non-weight bearing-induced muscle weakness (i.e., specific force) results from decreases in myosin protein quantity (i.e., myosin content per half-sarcomere and the ratio of myosin to actin) and quality (i.e., force per half-sarcomere and population of myosin heads in the strong-binding state during muscle contraction) in single myosin heavy chain (MHC) type II fibers. Fisher-344 rats were assigned to weight-bearing control (Con) or non-weight bearing (NWB). The NWB rats were hindlimb unloaded for 2 wk. Diameter, force, and MHC content were determined in permeabilized single fibers from the semimembranosus muscle. MHC isoform and the ratio of MHC to actin in each fiber were determined by gel electrophoresis and silver staining techniques. The structural distribution of myosin from spin-labeled fiber bundles during maximal isometric contraction was evaluated using electron paramagnetic resonance spectroscopy. Specific force (peak force per cross-sectional area) in MHC type IIB and IIXB fibers from NWB was significantly reduced by 38% and 18%, respectively. MHC content per half-sarcomere was significantly reduced by 21%. Two weeks of hindlimb unloading resulted in a reduced force per half-sarcomere of 52% and fraction of myosin strong-binding during contraction of 34%. The results suggest that reduced myosin and actin content (quantity) and myosin quality concomitantly contribute to non-weight bearing-related muscle weakness. Copyright © 2014 the American Physiological Society.

Spectrum of Mutations in Hypertrophic Cardiomyopathy Genes Among Tunisian Patients.

PubMed

Jaafar, Nawel; Gómez, Juan; Kammoun, Ikram; Zairi, Ihsen; Amara, Wael Ben; Kachboura, Salem; Kraiem, Sondes; Hammami, Mohamed; Iglesias, Sara; Alonso, Belén; Coto, Eliecer

2016-11-01

Hypertrophic cardiomyopathy (HCM) is a common cardiac genetic disorder associated with heart failure and sudden death. Mutations in the cardiac sarcomere genes are found in approximately half of HCM patients and are more common among cases with a family history of the disease. Data about the mutational spectrum of the sarcomeric genes in HCM patients from Northern Africa are limited. The population of Tunisia is particularly interesting due to its Berber genetic background. As founder mutations have been reported in other disorders. We performed semiconductor chip (Ion Torrent PGM) next generation sequencing of the nine main sarcomeric genes (MYH7, MYBPC3, TNNT2, TNNI3, ACTC1, TNNC1, MYL2, MYL3, TPM1) as well as the recently identified as an HCM gene, FLNC, in 45 Tunisian HCM patients. We found sarcomere gene polymorphisms in 12 patients (27%), with MYBPC3 and MYH7 representing 83% (10/12) of the mutations. One patient was homozygous for a new MYL3 mutation and two were double MYBPC3 + MYH7 mutation carriers. Screening of the FLNC gene identified three new mutations, which points to FLNC mutations as an important cause of HCM among Tunisians. The mutational background of HCM in Tunisia is heterogeneous. Unlike other Mendelian disorders, there were no highly prevalent mutations that could explain most of the cases. Our study also suggested that FLNC mutations may play a role on the risk for HCM among Tunisians.

Engineered Microenvironments for the Maturation and Observation of Human Embryonic Stem Cell Derived Cardiomyocytes

NASA Astrophysics Data System (ADS)

Salick, Max R.

The human heart is a dynamic system that undergoes substantial changes as it develops and adapts to the body's growing needs. To better understand the physiology of the heart, researchers have begun to produce immature heart muscle cells, or cardiomyocytes, from pluripotent stem cell sources with remarkable efficiency. These stem cell-derived cardiomyocytes hold great potential in the understanding and treatment of heart disease; however, even after prolonged culture, these cells continue to exhibit an immature phenotype, as indicated by poor sarcomere organization and calcium handling, among other features. The lack of maturation that is observed in these cardiomyocytes greatly limits their applicability towards drug screening, disease modeling, and cell therapy applications. The mechanical environment surrounding a cell has been repeatedly shown to have a large impact on that cell's behavior. For this reason, we have implemented micropatterning methods to mimic the level of alignment that occurs in the heart in vivo in order to study how this alignment may help the cells to produce a more mature sarcomere phenotype. It was discovered that the level of sarcomere organization of a cardiomyocyte can be strongly influenced by the micropattern lane geometry on which it adheres. Steps were taken to optimize this micropattern platform, and studies of protein organization, gene expression, and myofibrillogenesis were conducted. Additionally, a set of programs was developed to provide quantitative analysis of the level of sarcomere organization, as well as to assist with several other tissue engineering applications.

Mutation-Specific Effects on Thin Filament Length in Thin Filament Myopathy

PubMed Central

de Winter, Josine M.; Joureau, Barbara; Lee, Eun-Jeong; Kiss, Balázs; Yuen, Michaela; Gupta, Vandana A.; Pappas, Christopher T.; Gregorio, Carol C.; Stienen, Ger J. M.; Edvardson, Simon; Wallgren-Pettersson, Carina; Lehtokari, Vilma-Lotta; Pelin, Katarina; Malfatti, Edoardo; Romero, Norma B.; van Engelen, Baziel G.; Voermans, Nicol C.; Donkervoort, Sandra; Bönnemann, C. G.; Clarke, Nigel F.; Beggs, Alan H.; Granzier, Henk; Ottenheijm, Coen A. C.

2016-01-01

Objective Thin filament myopathies are among the most common nondystrophic congenital muscular disorders, and are caused by mutations in genes encoding proteins that are associated with the skeletal muscle thin filament. Mechanisms underlying muscle weakness are poorly understood, but might involve the length of the thin filament, an important determinant of force generation. Methods We investigated the sarcomere length-dependence of force, a functional assay that provides insights into the contractile strength of muscle fibers as well as the length of the thin filaments, in muscle fibers from 51 patients with thin filament myopathy caused by mutations in NEB, ACTA1, TPM2, TPM3, TNNT1, KBTBD13, KLHL40, and KLHL41. Results Lower force generation was observed in muscle fibers from patients of all genotypes. In a subset of patients who harbor mutations in NEB and ACTA1, the lower force was associated with downward shifted force–sarcomere length relations, indicative of shorter thin filaments. Confocal microscopy confirmed shorter thin filaments in muscle fibers of these patients. A conditional Neb knockout mouse model, which recapitulates thin filament myopathy, revealed a compensatory mechanism; the lower force generation that was associated with shorter thin filaments was compensated for by increasing the number of sarcomeres in series. This allowed muscle fibers to operate at a shorter sarcomere length and maintain optimal thin–thick filament overlap. Interpretation These findings might provide a novel direction for the development of therapeutic strategies for thin filament myopathy patients with shortened thin filament lengths. PMID:27074222

Association of the ACTN3 R577X Polymorphism in Polish Power-Orientated Athletes

PubMed Central

Cięszczyk, Paweł; Eider, Jerzy; Ostanek, Magdalena; Arczewska, Aleksandra; Leońska-Duniec, Agata; Sawczyn, Stanisław; Ficek, Krzysztof; Krupecki, Krzysztof

2011-01-01

Alpha-actinins are an ancient family of actin-binding proteins that play structural and regulatory roles in cytoskeletal organization. In skeletal muscle, α-actinin-3 protein is an important structural component of the Z disc, where it anchors actin thin filaments, helping to maintain the myofibrillar array. A common nonsense polymorphism in codon 577 of the ACTN3 gene (R577X) results in α-actinin-3 deficiency in XX homozygotes. Based on knowledge about the role of ACTN3 R557X polymorphism in skeletal muscle function, we postulated that the genetic polymorphism of ACTN3 could also improve sprint and power ability. We compared genotypic and allelic frequencies of the ACTN3 R557X polymorphism in two groups of men of the same Caucasian descent: 158 power-orientated athletes and 254 volunteers not involved in competitive sport. The genotype distribution in the group of power-oriented athletes showed significant differences (P=0.008) compared to controls. However, among the investigated subgroups of athletes, only the difference of ACTN3 R577X genotype between sprinters and controls reached statistical significance (P=0.041). The frequencies of the ACTN3 577X allele (30.69% vs. 40.35%; P=0.005) were significantly different in all athletes compared to controls. Our results support the hypothesis that the ACTN3 577XX allele may have some beneficial effect on sprint-power performance, because the ACTN3 XX genotype is significantly reduced in Polish power-oriented athletes compared to controls. This finding seems to be in agreement with previously reported case-control studies. However, ACTN3 polymorphism as a genetic marker for sport talent identification should be interpreted with great caution. PMID:23486986

Magnetic field formation in the Milky Way like disc galaxies of the Auriga project

NASA Astrophysics Data System (ADS)

Pakmor, Rüdiger; Gómez, Facundo A.; Grand, Robert J. J.; Marinacci, Federico; Simpson, Christine M.; Springel, Volker; Campbell, David J. R.; Frenk, Carlos S.; Guillet, Thomas; Pfrommer, Christoph; White, Simon D. M.

2017-08-01

The magnetic fields observed in the Milky Way and nearby galaxies appear to be in equipartition with the turbulent, thermal and cosmic ray energy densities, and hence are expected to be dynamically important. However, the origin of these strong magnetic fields is still unclear, and most previous attempts to simulate galaxy formation from cosmological initial conditions have ignored them altogether. Here, we analyse the magnetic fields predicted by the simulations of the Auriga Project, a set of 30 high-resolution cosmological zoom simulations of Milky Way like galaxies, carried out with a moving-mesh magnetohydrodynamics code and a detailed galaxy formation physics model. We find that the magnetic fields grow exponentially at early times owing to a small-scale dynamo with an e-folding time of roughly 100 Myr in the centre of haloes until saturation occurs around z = 2-3, when the magnetic energy density reaches about 10 per cent of the turbulent energy density with a typical strength of 10-50 {μ G}. In the galactic centres, the ratio between magnetic and turbulent energies remains nearly constant until z = 0. At larger radii, differential rotation in the discs leads to linear amplification that typically saturates around z = 0.5-0. The final radial and vertical variations of the magnetic field strength can be well described by two joint exponential profiles, and are in good agreement with observational constraints. Overall, the magnetic fields have only little effect on the global evolution of the galaxies as it takes too long to reach equipartition. We also demonstrate that our results are well converged with numerical resolution.

MinC/MinD copolymers are not required for Min function

PubMed Central

Park, Kyung-Tae; Du, Shishen; Lutkenhaus, Joe

2015-01-01

Summary In Escherichia coli, precise placement of the cytokinetic Z ring at midcell requires the concerted action of the three Min proteins. MinD activates MinC, an inhibitor of FtsZ, at least in part, by recruiting it to the membrane and targeting it to the Z ring, while MinE stimulates the MinD ATPase inducing an oscillation that directs MinC/MinD activity away from midcell. Recently, MinC and MinD were shown to form copolymers of alternating dimers of MinC and MinD and it was suggested that these copolymers are the active form of MinC/MinD. Here, we use MinD mutants defective in binding MinC to generate heterodimers with wild type MinD that are unable to form MinC/MinD copolymers. Similarly, MinC mutants defective in binding to MinD were used to generate heterodimers with wild type MinC that are unable to form copolymers. Such heterodimers are active and in the case of MinC were shown to mediate spatial regulation of the Z ring demonstrating that MinC/MinD copolymer formation is not required. Our results are consistent with a model in which a membrane anchored MinC/MinD complex is targeted to the Z ring through the conserved carboxy tail of FtsZ leading to breakage of FtsZ filaments. PMID:26268537

Biomechanical properties of patellar and hamstring graft tibial fixation techniques in anterior cruciate ligament reconstruction: experimental study with roentgen stereometric analysis.

PubMed

Adam, Frank; Pape, Dietrich; Schiel, Karin; Steimer, Oliver; Kohn, Dieter; Rupp, Stefan

2004-01-01

Reliable fixation of the soft hamstring grafts in ACL reconstruction has been reported as problematic. The biomechanical properties of patellar tendon (PT) grafts fixed with biodegradable screws (PTBS) are superior compared to quadrupled hamstring grafts fixed with BioScrew (HBS) or Suture-Disc fixation (HSD). Controlled laboratory study with roentgen stereometric analysis (RSA). Ten porcine specimens were prepared for each group. In the PT group, the bone plugs were fixed with a 7 x 25 mm BioScrew. In the hamstring group, four-stranded tendon grafts were anchored within a tibial tunnel of 8 mm diameter either with a 7 x 25 mm BioScrew or eight polyester sutures knotted over a Suture-Disc. The grafts were loaded stepwise, and micromotion of the graft inside the tibial tunnel was measured with RSA. Hamstring grafts failed at lower loads (HBS: 536 N, HSD 445 N) than the PTBS grafts (658 N). Stiffness in the PTBS group was much greater compared to the hamstring groups (3500 N/mm versus HBS = 517 N/mm and HSD = 111 N/mm). Irreversible graft motion after graft loading with 200 N was measured at 0.03 mm (PTBS), 0.38mm (HBS), and 1.85mm (HSD). Elasticity for the HSD fixation was measured at 0.67 mm at 100 N and 1.32 mm at 200 N load. Hamstring graft fixation with BioScrew and Suture-Disc displayed less stiffness and early graft motion compared to PTBS fixation. Screw fixation of tendon grafts is superior to Suture-Disc fixation with linkage material since it offers greater stiffness and less graft motion inside the tibial tunnel. Our results revealed graft motion for hamstring fixation with screw or linkage material at loads that occur during rehabilitation. This, in turn, may lead to graft laxity.

Survival Of Pure Disc Galaxies Over The Last 8 Billion Years

NASA Astrophysics Data System (ADS)

Sachdeva, Sonali

2016-09-01

The presence of pure disk galaxies without any bulge component, i.e., neither classical nor pseudo, poses a severe challenge not just to the hierarchical galaxy formation models but also to the theories of internal secular evolution. We discover that a significant fraction of disk galaxies ( 15-18 %) in the Hubble Deep Field (0.4 < z < 1.0) as well as in the local Universe (0.02 < z < 0.05) are such pure disk systems (PDS). We trace the evolution of this population to find how they survived the merger violence and other disk instabilities to remain dynamically undisturbed. We find that smooth accretion of cold gas via cosmic filaments is the most probable mode of their growth in mass and size since z 1. We speculate that PDSs are dynamically hotter and cushioned in massive dark matter haloes which may prevent them from undergoing strong secular evolution.

The cardiac ultrastructure of Chimaera monstrosa L. (Elasmobranchii: Holocephali).

PubMed

Berge, P I

1979-09-03

The ultrastructure of the heart in Chimaera monstrosa L. is described. The endocardial and the epicardial cells are similar in the three cardiac regions. Myocardial cells show small variations. The myofibred, 4--6 microns thick, contains one or a few myofibrils. Each myosin filament is surrounded by six actin filaments. The sarcomere banding pattern includes the Z-, A-, I-, M-, N-, and H-band. End-to-end attachments between myofibres are composed of alternating desmosomes and fasciae adhaerentes. Desmosomes and nexuses occur between longitudinally oriented cell surfaces. The sarcoplasmic reticulum is poorly developed but well defined. Peripheral coupling-like structures are common, T-tubules are absent. Membrane bound dense bodies occur in all regions. Areas with ribosomes and single myosin filaments are often seen. The epicardial cells have a regular hexagonal surface and are much thicker than the endocardial cells. Numerous short and few longer cytoplasmic extensions face the pericardial cavity. The flat endocardial cells contain a large nucleus and small amounts of cytoplasm.

Work Done by Titin Protein Folding Assists Muscle Contraction.

PubMed

Rivas-Pardo, Jaime Andrés; Eckels, Edward C; Popa, Ionel; Kosuri, Pallav; Linke, Wolfgang A; Fernández, Julio M

2016-02-16

Current theories of muscle contraction propose that the power stroke of a myosin motor is the sole source of mechanical energy driving the sliding filaments of a contracting muscle. These models exclude titin, the largest protein in the human body, which determines the passive elasticity of muscles. Here, we show that stepwise unfolding/folding of titin immunoglobulin (Ig) domains occurs in the elastic I band region of intact myofibrils at physiological sarcomere lengths and forces of 6-8 pN. We use single-molecule techniques to demonstrate that unfolded titin Ig domains undergo a spontaneous stepwise folding contraction at forces below 10 pN, delivering up to 105 zJ of additional contractile energy, which is larger than the mechanical energy delivered by the power stroke of a myosin motor. Thus, it appears inescapable that folding of titin Ig domains is an important, but as yet unrecognized, contributor to the force generated by a contracting muscle. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

On a class of unsteady three-dimensional Navier Stokes solutions relevant to rotating disc flows: Threshold amplitudes and finite time singularities

NASA Technical Reports Server (NTRS)

Hall, Philip; Balakumar, P.

1990-01-01

A class of exact steady and unsteady solutions of the Navier Stokes equations in cylindrical polar coordinates is given. The flows correspond to the motion induced by an infinite disc rotating with constant angular velocity about the z-axis in a fluid occupying a semi-infinite region which, at large distances from the disc, has velocity field proportional to (x,-y,O) with respect to a Cartesian coordinate system. It is shown that when the rate of rotation is large, Karman's exact solution for a disc rotating in an otherwise motionless fluid is recovered. In the limit of zero rotation rate a particular form of Howarth's exact solution for three-dimensional stagnation point flow is obtained. The unsteady form of the partial differential system describing this class of flow may be generalized to time-periodic equilibrium flows. In addition the unsteady equations are shown to describe a strongly nonlinear instability of Karman's rotating disc flow. It is shown that sufficiently large perturbations lead to a finite time breakdown of that flow whilst smaller disturbances decay to zero. If the stagnation point flow at infinity is sufficiently strong, the steady basic states become linearly unstable. In fact there is then a continuous spectrum of unstable eigenvalues of the stability equations but, if the initial value problem is considered, it is found that, at large values of time, the continuous spectrum leads to a velocity field growing exponentially in time with an amplitude decaying algebraically in time.

Revisiting the stellar velocity ellipsoid-Hubble-type relation: observations versus simulations

NASA Astrophysics Data System (ADS)

Pinna, F.; Falcón-Barroso, J.; Martig, M.; Martínez-Valpuesta, I.; Méndez-Abreu, J.; van de Ven, G.; Leaman, R.; Lyubenova, M.

2018-04-01

The stellar velocity ellipsoid (SVE) in galaxies can provide important information on the processes that participate in the dynamical heating of their disc components (e.g. giant molecular clouds, mergers, spiral density waves, and bars). Earlier findings suggested a strong relation between the shape of the disc SVE and Hubble type, with later-type galaxies displaying more anisotropic ellipsoids and early types being more isotropic. In this paper, we revisit the strength of this relation using an exhaustive compilation of observational results from the literature on this issue. We find no clear correlation between the shape of the disc SVE and morphological type, and show that galaxies with the same Hubble type display a wide range of vertical-to-radial velocity dispersion ratios. The points are distributed around a mean value and scatter of σz/σR = 0.7 ± 0.2. With the aid of numerical simulations, we argue that different mechanisms might influence the shape of the SVE in the same manner and that the same process (e.g. mergers) does not have the same impact in all the galaxies. The complexity of the observational picture is confirmed by these simulations, which suggest that the vertical-to-radial axis ratio of the SVE is not a good indicator of the main source of disc heating. Our analysis of those simulations also indicates that the observed shape of the disc SVE may be affected by several processes simultaneously and that the signatures of some of them (e.g. mergers) fade over time.

Gradual surface degradation of restorative materials by acidic agents.

PubMed

Hengtrakool, Chanothai; Kukiattrakoon, Boonlert; Kedjarune-Leggat, Ureporn

2011-01-01

The aim of this study was to investigate the effect of acidic agents on surface roughness and characteristics of four restorative materials. Fifty-two discs were created from each restorative material: metal-reinforced glass ionomer cement (Ketac-S), resin-modified glass ionomer cement (Fuji II LC), resin composite (Filtek Z250), and amalgam (Valiant-PhD); each disc was 12 mm in diameter and 2.5 mm thick. The specimens were divided into four subgroups (n=13) and immersed for 168 hours in four storage media: deionized water (control); citrate buffer solution; green mango juice; and pineapple juice. Surface roughness measurements were performed with a profilometer, both before and after storage media immersion. Surface characteristics were examined using scanning electron microscopy (SEM). Statistical significance among each group was analyzed using two-way repeated ANOVA and Tukey's tests. Ketac-S demonstrated the highest roughness changes after immersion in acidic agents (p<0.05), followed by Fuji II LC. Valiant-PhD and Filtek Z250 illustrated some minor changes over 168 hours. The mango juice produced the greatest degradation effect of all materials tested (p<0.05). SEM photographs demonstrated gradual surface changes of all materials tested after immersions. Of the materials evaluated, amalgam and resin composite may be the most suitable for restorations for patients with tooth surface loss.

Effect of Naturally Acidic Agents on Microhardness and Surface Micromorphology of Restorative Materials

PubMed Central

Hengtrakool, Chanothai; Kukiattrakoon, Boonlert; Kedjarune-Leggat, Ureporn

2011-01-01

Objectives: This study investigated the titratable acidity and erosive potential of acidic agents on the microhardness and surface micromorphology of four restorative materials. Methods: Forty-seven discs of each restorative material; metal-reinforced glass ionomer cement (Ketac-S), resin-modified glass ionomer cement (Fuji II LC), resin composite (Filtek Z250) and amalgam (Valiant-Ph.D.), 12 mm in diameter and 2.5 mm in thickness, were divided into four groups (5 discs/group). Specimens were then immersed for 7 days into four storage media; deionized water (control), citrate buffer solution, green mango juice and pineapple juice. Microhardness testing before and after immersions was performed. Micromorphological changes were evaluated under a scanning electron microscope (SEM). Statistical significance among each group was analyzed using two-way repeated ANOVA and Tukey’s tests. Results: The Fuji II LC and the Ketac-S showed the highest reduction in microhardness (P<.05). The Valiant-Ph.D. and the Filtek Z250 showed some minor changes over the period of 7 days. The mango juice produced the greatest degradation effect (P<.05). Conclusions: This study suggested that for restorations in patients who have tooth surface loss, materials selected should be considered. In terms of materials evaluated, amalgam and resin composite are the most suitable for restorations. PMID:21311608

Diversity of the Lyman continuum escape fractions of high-z galaxies and its origins

NASA Astrophysics Data System (ADS)

Sumida, Takumi; Kashino, Daichi; Hasegawa, Kenji

2018-04-01

The Lyman continuum (LyC) escape fraction is a key quantity to determine the contribution of galaxies to cosmic reionization. It has been known that the escape fractions estimated by observations and numerical simulations show a large diversity. However, the origins of the diversity are still uncertain. In this work, to understand what quantities of galaxies are responsible for controlling the escape fraction, we numerically evaluate the escape fraction by performing ray-tracing calculation with simplified disc galaxy models. With a smooth disc model, we explore the dependence of the escape fraction on the disposition of ionizing sources and find that the escape fraction varies up to ˜3 orders of magnitude. It is also found that the halo mass dependence of disc scale height determines whether the escape fraction increases or decreases with halo mass. With a clumpy disc model, it turns out that the escape fraction increases as the clump mass fraction increases because the density in the inter-clump region decreases. In addition, we find that clumpiness regulates the escape fraction via two ways when the total clump mass dominates the total gas mass; the escape fraction is controlled by the covering factor of clumps if the clumps are dense sufficient to block LyC photons, otherwise the clumpiness works to reduce the escape fraction by increasing the total number of recombination events in a galaxy.

Retinal fundus images for glaucoma analysis: the RIGA dataset

NASA Astrophysics Data System (ADS)

Almazroa, Ahmed; Alodhayb, Sami; Osman, Essameldin; Ramadan, Eslam; Hummadi, Mohammed; Dlaim, Mohammed; Alkatee, Muhannad; Raahemifar, Kaamran; Lakshminarayanan, Vasudevan

2018-03-01

Glaucoma neuropathy is a major cause of irreversible blindness worldwide. Current models of chronic care will not be able to close the gap of growing prevalence of glaucoma and challenges for access to healthcare services. Teleophthalmology is being developed to close this gap. In order to develop automated techniques for glaucoma detection which can be used in tele-ophthalmology we have developed a large retinal fundus dataset. A de-identified dataset of retinal fundus images for glaucoma analysis (RIGA) was derived from three sources for a total of 750 images. The optic cup and disc boundaries for each image was marked and annotated manually by six experienced ophthalmologists and included the cup to disc (CDR) estimates. Six parameters were extracted and assessed (the disc area and centroid, cup area and centroid, horizontal and vertical cup to disc ratios) among the ophthalmologists. The inter-observer annotations were compared by calculating the standard deviation (SD) for every image between the six ophthalmologists in order to determine if the outliers amongst the six and was used to filter the corresponding images. The data set will be made available to the research community in order to crowd source other analysis from other research groups in order to develop, validate and implement analysis algorithms appropriate for tele-glaucoma assessment. The RIGA dataset can be freely accessed online through University of Michigan, Deep Blue website (doi:10.7302/Z23R0R29).

A specific role for the ZipA protein in cell division: stabilization of the FtsZ protein.

PubMed

Pazos, Manuel; Natale, Paolo; Vicente, Miguel

2013-02-01

In Escherichia coli, the cell division protein FtsZ is anchored to the cytoplasmic membrane by the action of the bitopic membrane protein ZipA and the cytoplasmic protein FtsA. Although the presence of both ZipA and FtsA is strictly indispensable for cell division, an FtsA gain-of-function mutant FtsA* (R286W) can bypass the ZipA requirement for cell division. This observation casts doubts on the role of ZipA and its need for cell division. Maxicells are nucleoid-free bacterial cells used as a whole cell in vitro system to probe protein-protein interactions without the need of protein purification. We show that ZipA protects FtsZ from the ClpXP-directed degradation observed in E. coli maxicells and that ZipA-stabilized FtsZ forms membrane-attached spiral-like structures in the bacterial cytoplasm. The overproduction of the FtsZ-binding ZipA domain is sufficient to protect FtsZ from degradation, whereas other C-terminal ZipA partial deletions lacking it are not. Individual overproduction of the proto-ring component FtsA or its gain-of-function mutant FtsA* does not result in FtsZ protection. Overproduction of FtsA or FtsA* together with ZipA does not interfere with the FtsZ protection. Moreover, neither FtsA nor FtsA* protects FtsZ when overproduced together with ZipA mutants lacking the FZB domain. We propose that ZipA protects FtsZ from degradation by ClpP by making the FtsZ site of interaction unavailable to the ClpX moiety of the ClpXP protease. This role cannot be replaced by either FtsA or FtsA*, suggesting a unique function for ZipA in proto-ring stability.

Hypertrophic Cardiomyopathy: A Vicious Cycle Triggered by Sarcomere Mutations and Secondary Disease Hits.

PubMed

Wijnker, Paul J M; Sequeira, Vasco; Kuster, Diederik W D; Velden, Jolanda van der

2018-04-11

Hypertrophic cardiomyopathy (HCM) is a cardiac genetic disease characterized by left ventricular hypertrophy, diastolic dysfunction, and myocardial disarray. Disease onset occurs between 20 and 50 years of age, thus affecting patients in the prime of their life. HCM is caused by mutations in sarcomere proteins, the contractile building blocks of the heart. Despite increased knowledge of causal mutations, the exact path from genetic defect leading to cardiomyopathy is complex and involves additional disease hits. Recent Advances: Laboratory-based studies indicate that HCM development not only depends on the primary sarcomere impairment caused by the mutation but also on secondary disease-related alterations in the heart. Here we propose a vicious mutation-induced disease cycle, in which a mutation-induced energy depletion alters cellular metabolism with increased mitochondrial work, which triggers secondary disease modifiers that will worsen disease and ultimately lead to end-stage HCM. Evidence shows excessive cellular reactive oxygen species (ROS) in HCM patients and HCM animal models. Oxidative stress markers are increased in the heart (oxidized proteins, DNA, and lipids) and serum of HCM patients. In addition, increased mitochondrial ROS production and changes in endogenous antioxidants are reported in HCM. Mutant sarcomeric protein may drive excessive levels of cardiac ROS via changes in cardiac efficiency and metabolism, mitochondrial activation and/or dysfunction, impaired protein quality control, and microvascular dysfunction. Interventions restoring metabolism, mitochondrial function, and improved ROS balance may be promising therapeutic approaches. We discuss the effects of current HCM pharmacological therapies and potential future therapies to prevent and reverse HCM. Antioxid. Redox Signal. 00, 000-000.

The Effect of Myofilament Compliance on Kinetics of Force Generation by Myosin Motors in Muscle

PubMed Central

Linari, M.; Piazzesi, G.; Lombardi, V.

2009-01-01

Abstract We use the inhibitor of isometric force of skeletal muscle N-benzyl-p-toluene sulfonamide (BTS) to decrease, in a dose dependent way, the number of myosin motors attached to actin during the steady isometric contraction of single fibers from frog skeletal muscle (4°C, 2.1 μm sarcomere length). In this way we can reduce the strain in the myofilament compliance during the isometric tetanus (T0) from 3.54 nm in the control solution (T0,NR) to ∼0.5 nm in 1 μM BTS, where T0 is reduced to ∼0.15 T0,NR. The quick force recovery after a step release (1–3 nm per half-sarcomere) becomes faster with the increase of BTS concentration and the decrease of T0. The simulation of quick force recovery with a multistate model of force generation, that adapts Huxley and Simmons model to account for both the high stiffness of the myosin motor (∼3 pN/nm) and the myofilament compliance, shows that the increase in the rate of quick force recovery by BTS is explained by the reduced strain in the myofilaments, consequent to the decrease in half-sarcomere force. The model estimates that i), for the same half-sarcomere release the state transition kinetics in the myosin motor are five times faster in the absence of filament compliance than in the control; and ii), the rate of force recovery from zero to T0 is ∼6000/s in the absence of filament compliance. PMID:19167306

The effect of myofilament compliance on kinetics of force generation by myosin motors in muscle.

PubMed

Linari, M; Piazzesi, G; Lombardi, V

2009-01-01

We use the inhibitor of isometric force of skeletal muscle N-benzyl-p-toluene sulfonamide (BTS) to decrease, in a dose dependent way, the number of myosin motors attached to actin during the steady isometric contraction of single fibers from frog skeletal muscle (4 degrees C, 2.1 microm sarcomere length). In this way we can reduce the strain in the myofilament compliance during the isometric tetanus (T(0)) from 3.54 nm in the control solution (T(0,NR)) to approximately 0.5 nm in 1 microM BTS, where T(0) is reduced to approximately 0.15 T(0,NR). The quick force recovery after a step release (1-3 nm per half-sarcomere) becomes faster with the increase of BTS concentration and the decrease of T(0). The simulation of quick force recovery with a multistate model of force generation, that adapts Huxley and Simmons model to account for both the high stiffness of the myosin motor (approximately 3 pN/nm) and the myofilament compliance, shows that the increase in the rate of quick force recovery by BTS is explained by the reduced strain in the myofilaments, consequent to the decrease in half-sarcomere force. The model estimates that i), for the same half-sarcomere release the state transition kinetics in the myosin motor are five times faster in the absence of filament compliance than in the control; and ii), the rate of force recovery from zero to T(0) is approximately 6000/s in the absence of filament compliance.

Force deficits and breakage rates after single lengthening contractions of single fast fibers from unconditioned and conditioned muscles of young and old rats.

PubMed

Lynch, Gordon S; Faulkner, John A; Brooks, Susan V

2008-07-01

The deficit in force generation is a measure of the magnitude of damage to sarcomeres caused by lengthening contractions of either single fibers or whole muscles. In addition, permeabilized single fibers may suffer breakages. Our goal was to understand the interaction between breakages and force deficits in "young" and "old" permeabilized single fibers from control muscles of young and old rats and "conditioned" fibers from muscles that completed a 6-wk program of in vivo lengthening contractions. Following single lengthening contractions of old-control fibers compared with young-control fibers, the twofold greater force deficits at a 10% strain support the concept of an age-related increase in the susceptibility of fibers to mechanical damage. In addition, the much higher breakage rates for old fibers at all strains tested indicate an increase with aging in the number of fibers at risk of being severely injured during any given stretch. Following the 6-wk program of lengthening contractions, young-conditioned fibers and old-conditioned fibers were not different with respect to force deficit or the frequency of breakages. A potential mechanism for the increased resistance to stretch-induced damage of old-conditioned fibers is that, through intracellular damage and subsequent degeneration and regeneration, weaker sarcomeres were replaced by stronger sarcomeres. These data indicate that, despite the association of high fiber breakage rates and large force deficits with aging, the detrimental characteristics of old fibers were improved by a conditioning program that altered both sarcomeric characteristics as well as the overall structural integrity of the fibers.

Mutation-specific effects on thin filament length in thin filament myopathy.

PubMed

Winter, Josine M de; Joureau, Barbara; Lee, Eun-Jeong; Kiss, Balázs; Yuen, Michaela; Gupta, Vandana A; Pappas, Christopher T; Gregorio, Carol C; Stienen, Ger J M; Edvardson, Simon; Wallgren-Pettersson, Carina; Lehtokari, Vilma-Lotta; Pelin, Katarina; Malfatti, Edoardo; Romero, Norma B; Engelen, Baziel G van; Voermans, Nicol C; Donkervoort, Sandra; Bönnemann, C G; Clarke, Nigel F; Beggs, Alan H; Granzier, Henk; Ottenheijm, Coen A C

2016-06-01

Thin filament myopathies are among the most common nondystrophic congenital muscular disorders, and are caused by mutations in genes encoding proteins that are associated with the skeletal muscle thin filament. Mechanisms underlying muscle weakness are poorly understood, but might involve the length of the thin filament, an important determinant of force generation. We investigated the sarcomere length-dependence of force, a functional assay that provides insights into the contractile strength of muscle fibers as well as the length of the thin filaments, in muscle fibers from 51 patients with thin filament myopathy caused by mutations in NEB, ACTA1, TPM2, TPM3, TNNT1, KBTBD13, KLHL40, and KLHL41. Lower force generation was observed in muscle fibers from patients of all genotypes. In a subset of patients who harbor mutations in NEB and ACTA1, the lower force was associated with downward shifted force-sarcomere length relations, indicative of shorter thin filaments. Confocal microscopy confirmed shorter thin filaments in muscle fibers of these patients. A conditional Neb knockout mouse model, which recapitulates thin filament myopathy, revealed a compensatory mechanism; the lower force generation that was associated with shorter thin filaments was compensated for by increasing the number of sarcomeres in series. This allowed muscle fibers to operate at a shorter sarcomere length and maintain optimal thin-thick filament overlap. These findings might provide a novel direction for the development of therapeutic strategies for thin filament myopathy patients with shortened thin filament lengths. Ann Neurol 2016;79:959-969. © 2016 American Neurological Association.

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

PubMed

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.

Silk fibroin scaffolds enhance cell commitment of adult rat cardiac progenitor cells.

PubMed

Di Felice, Valentina; Serradifalco, Claudia; Rizzuto, Luigi; De Luca, Angela; Rappa, Francesca; Barone, Rosario; Di Marco, Patrizia; Cassata, Giovanni; Puleio, Roberto; Verin, Lucia; Motta, Antonella; Migliaresi, Claudio; Guercio, Annalisa; Zummo, Giovanni

2015-11-01

The use of three-dimensional (3D) cultures may induce cardiac progenitor cells to synthesize their own extracellular matrix (ECM) and sarcomeric proteins to initiate cardiac differentiation. 3D cultures grown on synthetic scaffolds may favour the implantation and survival of stem cells for cell therapy when pharmacological therapies are not efficient in curing cardiovascular diseases and when organ transplantation remains the only treatment able to rescue the patient's life. Silk fibroin-based scaffolds may be used to increase cell affinity to biomaterials and may be chemically modified to improve cell adhesion. In the present study, porous, partially orientated and electrospun nanometric nets were used. Cardiac progenitor cells isolated from adult rats were seeded by capillarity in the 3D structures and cultured inside inserts for 21 days. Under this condition, the cells expressed a high level of sarcomeric and cardiac proteins and synthesized a great quantity of ECM. In particular, partially orientated scaffolds induced the synthesis of titin, which is a fundamental protein in sarcomere assembly. Copyright © 2013 John Wiley & Sons, Ltd.

Three-dimensional force measurements with mandibular overdentures connected to implants by ball-shaped retentive anchors. A clinical study.

PubMed

Mericske-Stern, R

1998-01-01

The purpose of this in vivo study was to determine maximum and functional forces simultaneously in three dimensions on mandibular implants supporting overdentures. The anchorage system for overdenture connection was the ball-shaped retentive anchor. Five edentulous patients, each with two mandibular ITI implants, were selected as test subjects. A novel miniaturized piezo-electric force transducer was developed for specific use with ITI implants. Force magnitudes and directions were registered under various test conditions by means of electrostatic plotter records. The test modalities were maximum biting in centric occlusion, maximum biting on a bite plate, grinding, and chewing bread. Maximum forces measured in centric occlusion and on the ipsilateral implant when using a bite plate were slightly increased in vertical and backward-forward dimension (z-, y-axis) compared to the lateral-medial direction (x-axis). On the contralateral implant, equally low values were found in all three dimensions. This may be the effect of a nonsplinted anchorage device. With the use of a bite plate, force magnitudes on the ipsilateral implant were significantly higher on the z- and y-axis than mean maximum forces in centric occlusion (P < .001). Chewing and grinding resulted in lower forces compared to maximum biting, particularly in the vertical direction. The transverse force component in backward-forward direction, however, reached magnitudes that exceeded the vertical component by 100% to 300% during chewing function. This chewing pattern had not been observed in previous investigations with bars and telescopes, and therefore appears to be specific for retentive ball anchors. The prevalent or exclusive force direction registered on both implants in the vertical direction was downward under all test conditions. In the transverse direction during maximum biting the forward direction was more frequently registered, while no obvious prevalence of transverse force direction was observed during chewing and grinding.

Effects of rhodomyrtone on Gram-positive bacterial tubulin homologue FtsZ

PubMed Central

Saeloh, Dennapa; Wenzel, Michaela; Rungrotmongkol, Thanyada; Hamoen, Leendert Willem

2017-01-01

Rhodomyrtone, a natural antimicrobial compound, displays potent activity against many Gram-positive pathogenic bacteria, comparable to last-defence antibiotics including vancomycin and daptomycin. Our previous studies pointed towards effects of rhodomyrtone on the bacterial membrane and cell wall. In addition, a recent molecular docking study suggested that the compound could competitively bind to the main bacterial cell division protein FtsZ. In this study, we applied a computational approach (in silico), in vitro, and in vivo experiments to investigate molecular interactions of rhodomyrtone with FtsZ. Using molecular simulation, FtsZ conformational changes were observed in both (S)- and (R)-rhodomyrtone binding states, compared with the three natural states of FtsZ (ligand-free, GDP-, and GTP-binding states). Calculations of free binding energy showed a higher affinity of FtsZ to (S)-rhodomyrtone (−35.92 ± 0.36 kcal mol−1) than the GDP substrate (−23.47 ± 0.25 kcal mol−1) while less affinity was observed in the case of (R)-rhodomyrtone (−18.11 ± 0.11 kcal mol−1). In vitro experiments further revealed that rhodomyrtone reduced FtsZ polymerization by 36% and inhibited GTPase activity by up to 45%. However, the compound had no effect on FtsZ localization in Bacillus subtilis at inhibitory concentrations and cells also did not elongate after treatment. Higher concentrations of rhodomyrtone did affect localization of FtsZ and also affected localization of its membrane anchor proteins FtsA and SepF, showing that the compound did not specifically inhibit FtsZ but rather impaired multiple divisome proteins. Furthermore, a number of cells adopted a bean-like shape suggesting that rhodomyrtone possibly possesses further targets involved in cell envelope synthesis and/or maintenance. PMID:28168121

Effects of rhodomyrtone on Gram-positive bacterial tubulin homologue FtsZ.

PubMed

Saeloh, Dennapa; Wenzel, Michaela; Rungrotmongkol, Thanyada; Hamoen, Leendert Willem; Tipmanee, Varomyalin; Voravuthikunchai, Supayang Piyawan

2017-01-01

Rhodomyrtone, a natural antimicrobial compound, displays potent activity against many Gram-positive pathogenic bacteria, comparable to last-defence antibiotics including vancomycin and daptomycin. Our previous studies pointed towards effects of rhodomyrtone on the bacterial membrane and cell wall. In addition, a recent molecular docking study suggested that the compound could competitively bind to the main bacterial cell division protein FtsZ. In this study, we applied a computational approach ( in silico ), in vitro , and in vivo experiments to investigate molecular interactions of rhodomyrtone with FtsZ. Using molecular simulation, FtsZ conformational changes were observed in both (S)- and (R)-rhodomyrtone binding states, compared with the three natural states of FtsZ (ligand-free, GDP-, and GTP-binding states). Calculations of free binding energy showed a higher affinity of FtsZ to (S)-rhodomyrtone (-35.92 ± 0.36 kcal mol -1 ) than the GDP substrate (-23.47 ± 0.25 kcal mol -1 ) while less affinity was observed in the case of (R)-rhodomyrtone (-18.11 ± 0.11 kcal mol -1 ). In vitro experiments further revealed that rhodomyrtone reduced FtsZ polymerization by 36% and inhibited GTPase activity by up to 45%. However, the compound had no effect on FtsZ localization in Bacillus subtilis at inhibitory concentrations and cells also did not elongate after treatment. Higher concentrations of rhodomyrtone did affect localization of FtsZ and also affected localization of its membrane anchor proteins FtsA and SepF, showing that the compound did not specifically inhibit FtsZ but rather impaired multiple divisome proteins. Furthermore, a number of cells adopted a bean-like shape suggesting that rhodomyrtone possibly possesses further targets involved in cell envelope synthesis and/or maintenance.

The gene for creatine kinase, mitochondrial 2 (sarcomeric; CKMT2), maps to chromosome 5q13. 3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richard, I.; Devaud, C.; Cherif, D.

1993-10-01

YAC clones for the creatine kinase, mitochrondial 2 (sarcomeric; CKMT2), gene were isolated. One of these YACs was localized on chromosome 5q13.3 by fluorescence in situ hybridization. A polymorphic dinucleotide repeat (heterozygosity 0.77) was identified within the seventh intron of the CKMT2 gene. Genotyping of CEPH families allowed positioning of CKMT2 on the multipoint map of chromosome 5 between D5S424 and D5S428, distal to spinal muscular atrophy (SMA) (5q12-q14). 8 refs., 1 fig., 2 tabs.

Imaging 2D optical diffuse reflectance in skeletal muscle

NASA Astrophysics Data System (ADS)

Ranasinghesagara, Janaka; Yao, Gang

2007-04-01

We discovered a unique pattern of optical reflectance from fresh prerigor skeletal muscles, which can not be described using existing theories. A numerical fitting function was developed to quantify the equiintensity contours of acquired reflectance images. Using this model, we studied the changes of reflectance profile during stretching and rigor process. We found that the prominent anisotropic features diminished after rigor completion. These results suggested that muscle sarcomere structures played important roles in modulating light propagation in whole muscle. When incorporating the sarcomere diffraction in a Monte Carlo model, we showed that the resulting reflectance profiles quantitatively resembled the experimental observation.

Effects of adenosine triphosphate concentration on motor force regulation during skeletal muscle contraction

NASA Astrophysics Data System (ADS)

Wei, J.; Dong, C.; Chen, B.

2017-04-01

We employ a mechanical model of sarcomere to quantitatively investigate how adenosine triphosphate (ATP) concentration affects motor force regulation during skeletal muscle contraction. Our simulation indicates that there can be negative cross-bridges resisting contraction within the sarcomere and higher ATP concentration would decrease the resistance force from negative cross-bridges by promoting their timely detachment. It is revealed that the motor force is well regulated only when ATP concentration is above a certain level. These predictions may provide insights into the role of ATP in regulating coordination among multiple motors.

Calibrated Tully-Fisher relations for improved estimates of disc rotation velocities

NASA Astrophysics Data System (ADS)

Reyes, R.; Mandelbaum, R.; Gunn, J. E.; Pizagno, J.; Lackner, C. N.

2011-11-01

In this paper, we derive scaling relations between photometric observable quantities and disc galaxy rotation velocity Vrot or Tully-Fisher relations (TFRs). Our methodology is dictated by our purpose of obtaining purely photometric, minimal-scatter estimators of Vrot applicable to large galaxy samples from imaging surveys. To achieve this goal, we have constructed a sample of 189 disc galaxies at redshifts z < 0.1 with long-slit Hα spectroscopy from Pizagno et al. and new observations. By construction, this sample is a fair subsample of a large, well-defined parent disc sample of ˜170 000 galaxies selected from the Sloan Digital Sky Survey Data Release 7 (SDSS DR7). The optimal photometric estimator of Vrot we find is stellar mass M★ from Bell et al., based on the linear combination of a luminosity and a colour. Assuming a Kroupa initial mass function (IMF), we find: log [V80/(km s-1)] = (2.142 ± 0.004) + (0.278 ± 0.010)[log (M★/M⊙) - 10.10], where V80 is the rotation velocity measured at the radius R80 containing 80 per cent of the i-band galaxy light. This relation has an intrinsic Gaussian scatter ? dex and a measured scatter σmeas= 0.056 dex in log V80. For a fixed IMF, we find that the dynamical-to-stellar mass ratios within R80, (Mdyn/M★)(R80), decrease from approximately 10 to 3, as stellar mass increases from M★≈ 109 to 1011 M⊙. At a fixed stellar mass, (Mdyn/M★)(R80) increases with disc size, so that it correlates more tightly with stellar surface density than with stellar mass or disc size alone. We interpret the observed variation in (Mdyn/M★)(R80) with disc size as a reflection of the fact that disc size dictates the radius at which Mdyn/M★ is measured, and consequently, the fraction of the dark matter 'seen' by the gas at that radius. For the lowest M★ galaxies, we find a positive correlation between TFR residuals and disc sizes, indicating that the total density profile is dominated by dark matter on these scales. For the highest M★ galaxies, we find instead a weak negative correlation, indicating a larger contribution of stars to the total density profile. This change in the sense of the correlation (from positive to negative) is consistent with the decreasing trend in (Mdyn/M★)(R80) with stellar mass. In future work, we will use these results to study disc galaxy formation and evolution and perform a fair, statistical analysis of the dynamics and masses of a photometrically selected sample of disc galaxies.

The kinematics of the white dwarf population from the SDSS DR12

NASA Astrophysics Data System (ADS)

Anguiano, B.; Rebassa-Mansergas, A.; García-Berro, E.; Torres, S.; Freeman, K. C.; Zwitter, T.

2017-08-01

We use the Sloan Digital Sky Survey Data Release 12, which is the largest available white dwarf catalogue to date, to study the evolution of the kinematical properties of the population of white dwarfs in the Galactic disc. We derive masses, ages, photometric distances and radial velocities for all white dwarfs with hydrogen-rich atmospheres. For those stars for which proper motions from the USNO-B1 catalogue are available, the true three-dimensional components of the stellar space velocity are obtained. This subset of the original sample comprises 20 247 objects, making it the largest sample of white dwarfs with measured three-dimensional velocities. Furthermore, the volume probed by our sample is large, allowing us to obtain relevant kinematical information. In particular, our sample extends from a Galactocentric radial distance RG = 7.8 to 9.3 kpc, and vertical distances from the Galactic plane ranging from Z = -0.5 to 0.5 kpc. We examine the mean components of the stellar three-dimensional velocities, as well as their dispersions with respect to the Galactocentric and vertical distances. We confirm the existence of a mean Galactocentric radial velocity gradient, ∂/∂RG = -3 ± 5 km s-1 kpc-1. We also confirm north-south differences in . Specifically, we find that white dwarfs with Z > 0 (in the North Galactic hemisphere) have < 0, while the reverse is true for white dwarfs with Z < 0. The age-velocity dispersion relation derived from the present sample indicates that the Galactic population of white dwarfs may have experienced an additional source of heating, which adds to the secular evolution of the Galactic disc.

Effect of finishing/polishing techniques and time on surface roughness of esthetic restorative materials.

PubMed

Madhyastha, Prashanthi Sampath; Hegde, Shreya; Srikant, N; Kotian, Ravindra; Iyer, Srividhya Sriraman

2017-01-01

Surface roughness associated with improper finishing/polishing of restorations can result in plaque accumulation, gingival irritation, surface staining, and poor esthetic of restored teeth. The study aimed to evaluate the efficiency of various finishing and polishing systems and time using various procedures on surface roughness of some esthetic restorative materials. In this in vitro study, samples of two composite materials, compomer and glass ionomer cement (GIC) materials, were fabricated. Finishing and polishing were done immediately ( n = 40) and after 1 week ( n = 40) using four systems (diamond bur + soflex discs; diamond bur + Astropol polishing brush; tungsten carbide bur + soflex discs; tungsten carbide bur + Astropol polishing brush). Surface roughness was measured using surface profilometer. Data were statistically analyzed by t -test (for each material and time period) and one-way analysis of variance followed by Tukey's post hoc (for finishing and polishing systems) at a significant level of P < 0.05. Analysis of time period, irrespective of finishing and polishing system showed that Ra values were greater ( P < 0.05) in delayed polishing in GIC > Z100 > Filtek P90 > Dyract AP, suggesting immediate polishing is better. Among the materials, Filtek P90 had the least Ra values indicating the smoothest surface among all materials, followed by Z100, Dyract AP, and GIC. Comparison of polishing and finishing systems irrespective of materials showed that Ra values were lower ( P > 0.05) in diamond + Astropol combination whereas diamond + soflex had the greatest Ra values. It might be concluded that: (i) Filtek P90 showed least Ra values followed by < Z100 < Dyract < GIC; (ii) immediate (24 h) finishing/polishing of materials is better than delayed; and (iii) among all these polishing systems, diamond bur-Astropol and Astrobrush showed good surface finish.

Confidence set inference with a prior quadratic bound

NASA Technical Reports Server (NTRS)

Backus, George E.

1988-01-01

In the uniqueness part of a geophysical inverse problem, the observer wants to predict all likely values of P unknown numerical properties z = (z sub 1,...,z sub p) of the earth from measurement of D other numerical properties y(0)=(y sub 1(0),...,y sub D(0)) knowledge of the statistical distribution of the random errors in y(0). The data space Y containing y(0) is D-dimensional, so when the model space X is infinite-dimensional the linear uniqueness problem usually is insoluble without prior information about the correct earth model x. If that information is a quadratic bound on x (e.g., energy or dissipation rate), Bayesian inference (BI) and stochastic inversion (SI) inject spurious structure into x, implied by neither the data nor the quadratic bound. Confidence set inference (CSI) provides an alternative inversion technique free of this objection. CSI is illustrated in the problem of estimating the geomagnetic field B at the core-mantle boundary (CMB) from components of B measured on or above the earth's surface. Neither the heat flow nor the energy bound is strong enough to permit estimation of B(r) at single points on the CMB, but the heat flow bound permits estimation of uniform averages of B(r) over discs on the CMB, and both bounds permit weighted disc-averages with continous weighting kernels. Both bounds also permit estimation of low-degree Gauss coefficients at the CMB. The heat flow bound resolves them up to degree 8 if the crustal field at satellite altitudes must be treated as a systematic error, but can resolve to degree 11 under the most favorable statistical treatment of the crust. These two limits produce circles of confusion on the CMB with diameters of 25 deg and 19 deg respectively.

Optical-to-virial velocity ratios of local disc galaxies from combined kinematics and galaxy-galaxy lensing

NASA Astrophysics Data System (ADS)

Reyes, R.; Mandelbaum, R.; Gunn, J. E.; Nakajima, R.; Seljak, U.; Hirata, C. M.

2012-10-01

In this paper, we measure the optical-to-virial velocity ratios Vopt/V200c of disc galaxies in the Sloan Digital Sky Survey (SDSS) at a mean redshift of = 0.07 and with stellar masses 109 < M* < 1011 M⊙. Vopt/V200c, the ratio of the circular velocity measured at the optical radius of the disc (˜10 kpc) to that at the virial radius of the dark matter halo (˜150 kpc), is a powerful observational constraint on disc galaxy formation. It links galaxies to their dark matter haloes dynamically and constrains the total mass profile of disc galaxies over an order of magnitude in length scale. For this measurement, we combine Vopt derived from the Tully-Fisher relation (TFR) from Reyes et al. with V200c derived from halo masses measured with galaxy-galaxy lensing. In anticipation of this combination, we use similarly selected galaxy samples for both the TFR and lensing analysis. For three M* bins with lensing-weighted mean stellar masses of 0.6, 2.7 and 6.5 × 1010 M⊙, we find halo-to-stellar mass ratios M200c/M* = 41, 23 and 26, with 1σ statistical uncertainties of around 0.1 dex, and Vopt/V200c = 1.27 ± 0.08, 1.39 ± 0.06 and 1.27 ± 0.08 (1σ), respectively. Our results suggest that the dark matter and baryonic contributions to the mass within the optical radius are comparable, if the dark matter halo profile has not been significantly modified by baryons. The results obtained in this work will serve as inputs to and constraints on disc galaxy formation models, which will be explored in future work. Finally, we note that this paper presents a new and improved galaxy shape catalogue for weak lensing that covers the full SDSS Data Release 7 footprint.

Comparison of two-step versus four-step composite finishing/polishing disc systems: evaluation of a new two-step composite polishing disc system.

PubMed

da Costa, Juliana B; Goncalves, Flavia; Ferracane, Jack L

2011-01-01

The purpose of this study was to evaluate surface finish and gloss of a two-step composite finishing/polishing (F/P) disc system compared with two multistep systems on five composites. Seventy-five disc-shaped composite specimens (D=10.0 mm, 2 mm thick, n=15 per composite) were made of microfill (Durafill-D), nanofill (Filtek Supreme-FS), nanohybrid (Premise-PR), and microhybrids (Filtek Z250-FZ, Esthet-EX). One side of each specimen was initially finished with a carbide bur. Five specimens of each resin composite were randomly assigned to receive full F/P by each of the disc systems: two-step (Enhance Flex NST-EF) and four-step (Sof-Lex-SL, Super-Snap-SS). Surface gloss was measured with a glossmeter and surface roughness was measured with a profilometer. Results were analyzed by two-way analysis of variance (ANOVA)/Tukey's (α<0.05). No difference in gloss was noted among the three F/P systems when used with D and EX; no difference between SL and EF when used with any composite, except for FS; and no difference between SL and SS when used with any composite. SL and EF showed similar surface roughness when used on all composites, except for EX. EF and SS showed similar surface roughness on PR. SL and SS showed similar surface roughness values on every composite, except for FZ. EF was capable of providing similar gloss and surface roughness to SL on four composites evaluated but was not able to produce as glossy or as smooth a surface as SS for three of the five composites.

SDSS-IV MaNGA: bulge-disc decomposition of IFU data cubes (BUDDI)

NASA Astrophysics Data System (ADS)

Johnston, Evelyn J.; Häußler, Boris; Aragón-Salamanca, Alfonso; Merrifield, Michael R.; Bamford, Steven; Bershady, Matthew A.; Bundy, Kevin; Drory, Niv; Fu, Hai; Law, David; Nitschelm, Christian; Thomas, Daniel; Roman Lopes, Alexandre; Wake, David; Yan, Renbin

2017-02-01

With the availability of large integral field unit (IFU) spectral surveys of nearby galaxies, there is now the potential to extract spectral information from across the bulges and discs of galaxies in a systematic way. This information can address questions such as how these components built up with time, how galaxies evolve and whether their evolution depends on other properties of the galaxy such as its mass or environment. We present bulge-disc decomposition of IFU data cubes (BUDDI), a new approach to fit the two-dimensional light profiles of galaxies as a function of wavelength to extract the spectral properties of these galaxies' discs and bulges. The fitting is carried out using GALFITM, a modified form of GALFIT which can fit multiwaveband images simultaneously. The benefit of this technique over traditional multiwaveband fits is that the stellar populations of each component can be constrained using knowledge over the whole image and spectrum available. The decomposition has been developed using commissioning data from the Sloan Digital Sky Survey-IV Mapping Nearby Galaxies at APO (MaNGA) survey with redshifts z < 0.14 and coverage of at least 1.5 effective radii for a spatial resolution of 2.5 arcsec full width at half-maximum and field of view of > 22 arcsec, but can be applied to any IFU data of a nearby galaxy with similar or better spatial resolution and coverage. We present an overview of the fitting process, the results from our tests, and we finish with example stellar population analyses of early-type galaxies from the MaNGA survey to give an indication of the scientific potential of applying bulge-disc decomposition to IFU data.

Transcriptomic Modification in the Cerebral Cortex following Noninvasive Brain Stimulation: RNA-Sequencing Approach

DTIC Science & Technology

2017-04-20

was attached to the skull in order to anchor the acrylic and maintain the integrity of the head cap. 2.3. Whole Transcriptome RNA-Sequencing...no. 12, article 550, 2014. [24] D. W. Huang, B. T. Sherman, and R. A. Lempicki, “Systematic and integrative analysis of large gene lists using DAVID...BMC Bioinformatics, vol. 9, article 559, 2008. [29] Z. Hu, E. S. Snitkin, and C. DeLisi, “VisANT: an integrative framework for networks in systems

Advantages of Direct Insertion of a Straight Probe Without a Guide Tube During Anterior Odontoid Screw Fixation of Odontoid Fractures.

PubMed

Park, Jin Hoon; Kang, Dong-Ho; Lee, Moon Kyu; Yoo, Byoungwoo; Jung, Sang Ku; Hwang, Soo-Hyun; Kim, Jeoung Hee; Oh, Sunkyu; Lee, Eun Jung; Jeon, Sang Ryong; Roh, Sung Woo; Rhim, Seung Chul

2016-05-01

A retrospective cohort study. The aim of this study was to compare the anterior odontoid screw fixation (AOSF) with a guide tube or with a straight probe. AOSF associates with several complications, including malpositioning, fixation loss, and screw breakage. Screw pull-out from the C2 body is the most common complication. All consecutive patients with type II or rostral shallow type III odontoid fractures who underwent AOSFs during the study period were enrolled retrospectively. The guide-tube AOSF method followed the standard published method except C3 body and C2-3 disc annulus rimming was omitted to prevent disc injury; instead, the guide tube was anchored at the anterior inferior C2 vertebra corner. After 2 screw pull-outs, the guide-tube cohort was analyzed to identify the cause of instrument failure. Thereafter, the straight-probe method was developed. A guide tube was not used. A small pilot hole was made on the most anterior side of the inferior endplate, followed by insertion of a 2.5 mm straight probe through the C2 body. Non-union and instrument failure rates and screw-direction angles of the guide-tube and straight-probe groups were recorded. The guide-tube group (n = 13) had 2 screw pull-outs and 1 non-union. The straight-probe group (n = 8) had no complications and significantly larger screw-direction angles than the guide-tube group (60.5 ± 4.63 vs. 54.8 ± 3.82 degrees; P = 0.047). Straight-probe AOSF yielded larger direction angles without injuring bone and disc. Complications were absent. The procedure was easier than guide-tube AOSF and assured sufficient engagement, even in horizontal fracture orientation cases. 3.

Effect of Accelerated Artificial Aging on Translucency of Methacrylate and Silorane-Based Composite Resins.

PubMed

Shirinzad, Mehdi; Rezaei-Soufi, Loghman; Mirtorabi, Maryam Sadat; Vahdatinia, Farshid

2016-03-01

Composite restorations must have tooth-like optical properties namely color and translucency and maintain them for a long time. This study aimed to compare the effect of accelerated artificial aging (AAA) on the translucency of three methacrylate-based composites (Filtek Z250, Filtek Z250XT and Filtek Z350XT) and one silorane-based composite resin (Filtek P90). For this in vitro study, 56 composite discs were fabricated (n=14 for each group). Using scanning spectrophotometer, CIE L*a*b* parameters and translucency of each specimen were measured at 24 hours and after AAA for 384 hours. Data were analyzed using one-way ANOVA, Tukey's test and paired t-test at P=0.05 level of significance. The mean (±standard deviation) translucency parameter for Filtek Z250, Filtek Z250XT, Filtek Z350XT and Filtek P90 was 5.67±0.64, 4.59±0.77, 7.87±0.82 and 4.21±0.71 before AAA and 4.25±0.615, 3.53±0.73, 5.94±0.57 and 4.12±0.54 after AAA, respectively. After aging, the translucency of methacrylate-based composites decreased significantly (P<0.05). However, the translucency of Filtek P90 did not change significantly (P>0.05). The AAA significantly decreased the translucency of methacrylate-based composites (Filtek Z250, Filtek Z250XT and Filtek Z350XT) but no change occurred in the translucency of Filtek P90 silorane-based composite.

Effect of Accelerated Artificial Aging on Translucency of Methacrylate and Silorane-Based Composite Resins

PubMed Central

Shirinzad, Mehdi; Rezaei-Soufi, Loghman; Mirtorabi, Maryam Sadat; Vahdatinia, Farshid

2016-01-01

Objectives: Composite restorations must have tooth-like optical properties namely color and translucency and maintain them for a long time. This study aimed to compare the effect of accelerated artificial aging (AAA) on the translucency of three methacrylate-based composites (Filtek Z250, Filtek Z250XT and Filtek Z350XT) and one silorane-based composite resin (Filtek P90). Materials and Methods: For this in vitro study, 56 composite discs were fabricated (n=14 for each group). Using scanning spectrophotometer, CIE L*a*b* parameters and translucency of each specimen were measured at 24 hours and after AAA for 384 hours. Data were analyzed using one-way ANOVA, Tukey's test and paired t-test at P=0.05 level of significance. Results: The mean (±standard deviation) translucency parameter for Filtek Z250, Filtek Z250XT, Filtek Z350XT and Filtek P90 was 5.67±0.64, 4.59±0.77, 7.87±0.82 and 4.21±0.71 before AAA and 4.25±0.615, 3.53±0.73, 5.94±0.57 and 4.12±0.54 after AAA, respectively. After aging, the translucency of methacrylate-based composites decreased significantly (P<0.05). However, the translucency of Filtek P90 did not change significantly (P>0.05). Conclusions: The AAA significantly decreased the translucency of methacrylate-based composites (Filtek Z250, Filtek Z250XT and Filtek Z350XT) but no change occurred in the translucency of Filtek P90 silorane-based composite. PMID:27928237

Sarcomeric hypertrophic cardiomyopathy: genetic profile in a Portuguese population.

PubMed

Brito, Dulce; Miltenberger-Miltenyi, Gabriel; Vale Pereira, Sónia; Silva, Doroteia; Diogo, António Nunes; Madeira, Hugo

2012-09-01

Sarcomeric hypertrophic cardiomyopathy has heterogeneous phenotypic expressions, of which sudden cardiac death is the most feared. A genetic diagnosis is essential to identify subjects at risk in each family. The spectrum of disease-causing mutations in the Portuguese population is unknown. Seventy-seven unrelated probands with hypertrophic cardiomyopathy were systematically screened for mutations by PCR and sequencing of five sarcomeric genes: MYBPC3, MYH7, TNNT2, TNNI3 and MYL2. Familial cosegregation analysis was performed in most patients. Thirty-four different mutations were identified in 41 (53%) index patients, 71% with familial hypertrophic cardiomyopathy. The most frequently involved gene was MYBPC3 (66%) with 22 different mutations (8 novel) in 27 patients, followed by MYH7 (22%), TNNT2 (12%) and TNNI3 (2.6%). In three patients (7%), two mutations were found in MYBPC3 and/or MYH7. Additionally, 276 relatives were screened, leading to the identification of a mean of three other affected relatives for each pedigree with the familial form of the disease. Disease-associated mutations were identified mostly in familial hypertrophic cardiomyopathy, corroborating the idea that rarely studied genes may be implicated in sporadic forms. Private mutations are the rule, MYBPC3 being the most commonly involved gene. Mutations in MYBPC3 and MYH7 accounted for most cases of sarcomere-related disease. Multiple mutations in these genes may occur, which highlights the importance of screening both. The detection of novel mutations strongly suggests that all coding regions should be systematically screened. Genotyping in hypertrophic cardiomyopathy enables a more precise diagnosis of the disease, with implications for risk stratification and genetic counseling. Copyright © 2011 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Recent advances in the understanding of the repeated bout effect: the protective effect against muscle damage from a single bout of eccentric exercise.

PubMed

McHugh, Malachy P

2003-04-01

The repeated bout effect refers to the adaptation whereby a single bout of eccentric exercise protects against muscle damage from subsequent eccentric bouts. While the mechanism for this adaptation is poorly understood there have been significant recent advances in the understanding of this phenomenon. The purpose of this review is to provide an update on previously proposed theories and address new theories that have been advanced. The potential adaptations have been categorized as neural, mechanical and cellular. There is some evidence to suggest that the repeated bout effect is associated with a shift toward greater recruitment of slow twitch motor units. However, the repeated bout effect has been demonstrated with electrically stimulated contractions, indicating that a peripheral, non-neural adaptation predominates. With respect to mechanical adaptations there is evidence that both dynamic and passive muscle stiffness increase with eccentric training but there are no studies on passive or dynamic stiffness adaptations to a single eccentric bout. The role of the cytoskeleton in regulating dynamic stiffness is a possible area for future research. With respect to cellular adaptations there is evidence of longitudinal addition of sarcomeres and adaptations in the inflammatory response following an initial bout of eccentric exercise. Addition of sarcomeres is thought to reduce sarcomere strain during eccentric contractions thereby avoiding sarcomere disruption. Inflammatory adaptations are thought to limit the proliferation of damage that typically occurs in the days following eccentric exercise. In conclusion, there have been significant advances in the understanding of the repeated bout effect, however, a unified theory explaining the mechanism or mechanisms for this protective adaptation remains elusive.

A novel optical imaging system for investigating sarcomere dynamics in single skeletal muscle fibers

NASA Astrophysics Data System (ADS)

Panchangam, Appaji; Witte, Russell S.; Claflin, Dennis R.; O'Donnell, Matthew; Faulkner, John A.

2006-02-01

The protein substructure of skeletal muscle fibers forms a diffraction grating with repeating units, termed 'sarcomeres'. A laser scanning system is described that maps the lengths of sarcomeres (SL) and the widths of the first-order diffraction lines (DLW) of permeabilized single fibers in real-time. The apparatus translates a laser beam (λ = 670 nm and w 0 = ~75 μm) along the length of a fiber segment through 20 contiguous regions per sweep at 500 sweeps/s. The fiber segments (~1 mm long) were obtained from vastus lateralis muscles of humans by needle biopsy. During both passive stretches and maximum fixed-end activations, the mappings of SL and DLW of the fibers were extracted from the diffraction spectra. Heterogeneity of SLs was evaluated by computing the standard deviation ( σ SL) of the 20 SLs measured during a single sweep. Compared with the σ SL before a passive stretch, the increase of 5+/-0.5% in σ SL after the passive stretch, indicated differences in passive length-tension relationships along the fiber. In contrast, no change, ~0.5+/-0.1%, was observed in DLW. Within 10s after the fiber was returned to its initial length, the shape of the SL profile returned close to pre-stretch conditions ( σ SL = 1+/- 0.2%). Following maximum Ca 2+ - activation of the fiber, the heterogeneity of the steady state SLs increased greatly (DLW up by ~300% and σ SL up by ~100%). The scanning system provided high resolution tracking of sarcomere behavior single muscle fibers. Potential applications are for studies of the mechanisms of muscle fiber injury and injury propagation.

Effects of anisosmotic stress on cardiac muscle cell length, diameter, area, and sarcomere length

NASA Technical Reports Server (NTRS)

Tanaka, R.; Barnes, M. A.; Cooper, G. 4th; Zile, M. R.

1996-01-01

The purpose of this study was to examine the effects of anisosmotic stress on adult mammalian cardiac muscle cell (cardiocyte) size. Cardiocyte size and sarcomere length were measured in cardiocytes isolated from 10 normal rats and 10 normal cats. Superfusate osmolarity was decreased from 300 +/- 6 to 130 +/- 5 mosM and increased to 630 +/- 8 mosM. Cardiocyte size and sarcomere length increased progressively when osmolarity was decreased, and there were no significant differences between cat and rat cardiocytes with respect to percent change in cardiocyte area or diameter; however, there were significant differences in cardiocyte length (2.8 +/- 0.3% in cat vs. 6.1 +/- 0.3% in rat, P < 0.05) and sarcomere length (3.3 +/- 0.3% in cat vs. 6.1 +/- 0.3% in rat, P < 0.05). To determine whether these species-dependent differences in length were related to diastolic interaction of the contractile elements or differences in relative passive stiffness, cardiocytes were subjected to the osmolarity gradient 1) during treatment with 7 mM 2,3-butanedione monoxime (BDM), which inhibits cross-bridge interaction, or 2) after pretreatment with 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N, N,N',N'-tetraacetic acid (EGTA), a bivalent Ca2+ chelator. Treatment with EGTA or BDM abolished the differences between cat and rat cardiocytes. Species-dependent differences therefore appeared to be related to the degree of diastolic cross-bridge association and not differences in relative passive stiffness. In conclusion, the osmolarity vs. cell size relation is useful in assessing the cardiocyte response to anisosmotic stress and may in future studies be useful in assessing changes in relative passive cardiocyte stiffness produced by pathological processes.

Cardiomyopathy mutations in the tail of β-cardiac myosin modify the coiled-coil structure and affect integration into thick filaments in muscle sarcomeres in adult cardiomyocytes.

PubMed

Wolny, Marcin; Colegrave, Melanie; Colman, Lucy; White, Ed; Knight, Peter J; Peckham, Michelle

2013-11-01

It is unclear why mutations in the filament-forming tail of myosin heavy chain (MHC) cause hypertrophic or dilated cardiomyopathy as these mutations should not directly affect contraction. To investigate this, we first investigated the impact of five hypertrophic cardiomyopathy-causing (N1327K, E1356K, R1382W, E1555K, and R1768K) and one dilated cardiomyopathy-causing (R1500W) tail mutations on their ability to incorporate into muscle sarcomeres in vivo. We used adenoviral delivery to express full-length wild type or mutant enhanced GFP-MHC in isolated adult cardiomyocytes. Three mutations (N1327K, E1356K, and E1555K) reduced enhanced GFP-MHC incorporation into muscle sarcomeres, whereas the remainder had no effect. No mutations significantly affected contraction. Fluorescence recovery after photobleaching showed that fluorescence recovery for the mutation that incorporated least well (N1327K) was significantly faster than that of WT with half-times of 25.1 ± 1.8 and 32.2 ± 2.5 min (mean ± S.E.), respectively. Next, we determined the effects of each mutation on the helical properties of wild type and seven mutant peptides (7, 11, or 15 heptads long) from the myosin tail by circular dichroism. R1382W and E1768K slightly increased the α-helical nature of peptides. The remaining mutations reduced α-helical content, with N1327K showing the greatest reduction. Only peptides containing residues 1301-1329 were highly α-helical suggesting that this region helps in initiation of coiled coil. These results suggest that small effects of mutations on helicity translate into a reduced ability to incorporate into sarcomeres, which may elicit compensatory hypertrophy.

The distribution of interstellar dust in CALIFA edge-on galaxies via oligochromatic radiative transfer fitting

NASA Astrophysics Data System (ADS)

De Geyter, Gert; Baes, Maarten; Camps, Peter; Fritz, Jacopo; De Looze, Ilse; Hughes, Thomas M.; Viaene, Sébastien; Gentile, Gianfranco

2014-06-01

We investigate the amount and spatial distribution of interstellar dust in edge-on spiral galaxies, using detailed radiative transfer modelling of a homogeneous sample of 12 galaxies selected from the Calar Alto Legacy Integral Field Area survey. Our automated fitting routine, FITSKIRT, was first validated against artificial data. This is done by simultaneously reproducing the Sloan Digital Sky Survey g-, r-, i- and z-band observations of a toy model in order to combine the information present in the different bands. We show that this combined, oligochromatic fitting has clear advantages over standard monochromatic fitting especially regarding constraints on the dust properties. We model all galaxies in our sample using a three-component model, consisting of a double-exponential disc to describe the stellar and dust discs and using a Sérsic profile to describe the central bulge. The full model contains 19 free parameters, and we are able to constrain all these parameters to a satisfactory level of accuracy without human intervention or strong boundary conditions. Apart from two galaxies, the entire sample can be accurately reproduced by our model. We find that the dust disc is about 75 per cent more extended but only half as high as the stellar disc. The average face-on optical depth in the V band is 0.76 and the spread of 0.60 within our sample is quite substantial, which indicates that some spiral galaxies are relatively opaque even when seen face-on.

Magnetorotational instability in protoplanetary discs: the effect of dust grains

NASA Astrophysics Data System (ADS)

Salmeron, Raquel; Wardle, Mark

2008-08-01

We investigate the linear growth and vertical structure of the magnetorotational instability (MRI) in weakly ionized, stratified protoplanetary discs. The magnetic field is initially vertical and dust grains are assumed to be well mixed with the gas over the entire vertical dimension of the disc. For simplicity, all the grains are assumed to have the same radius (a = 0.1,1 or 3μm) and constitute a constant fraction (1 per cent) of the total mass of the gas. Solutions are obtained at representative radial locations (R = 5 and 10 au) from the central protostar for a minimum-mass solar nebula model and different choices of the initial magnetic field strength, configuration of the diffusivity tensor and grain sizes. We find that when no grain are present, or they are >~1μm in radius, the mid-plane of the disc remains magnetically coupled for field strengths up to a few gauss at both radii. In contrast, when a population of small grains (a = 0.1μm) is mixed with the gas, the section of the disc within two tidal scaleheights from the mid-plane is magnetically inactive and only magnetic fields weaker than ~50 mG can effectively couple to the fluid. At 5 au, Ohmic diffusion dominates for z/H <~ 1 when the field is relatively weak (B <~ a few milligauss), irrespective of the properties of the grain population. Conversely, at 10 au this diffusion term is unimportant in all the scenarios studied here. High above the mid-plane (z/H >~ 5), ambipolar diffusion is severe and prevents the field from coupling to the gas for all B. Hall diffusion is dominant for a wide range of field strengths at both radii when dust grains are present. The growth rate, wavenumber and range of magnetic field strengths for which MRI-unstable modes exist are all drastically diminished when dust grains are present, particularly when they are small (a ~ 0.1μm). In fact, MRI perturbations grow at 5 au (10 au) for B <~ 160 mG (130 mG) when 3μm grains are mixed with the gas. This upper limit on the field strength is reduced to only ~16 mG (10 mG) when the grain size is reduced to 0.1μm. In contrast, when the grains are assumed to have settled, MRI-unstable modes are found for B <~ 800 mG at 5 au and 250 mG at 10 au. Similarly, as the typical size of the dust grains diminishes, the vertical extent of the dead zone increases, as expected. For 0.1μm grains, the disc is magnetically inactive within two scaleheights of the mid-plane at both radii, but perturbations grow over the entire section of the disc for grain sizes of 1μm or larger. When dust grains are mixed with the gas, perturbations that incorporate Hall diffusion grow faster, and are active over a more extended cross-section of the disc, than those obtained under the ambipolar diffusion approximation. Note that the stabilizing effect of small dust grains (e.g. a = 0.1μm) is not strong enough to completely suppress the perturbations. We find, in fact, that even in this scenario, the magnetic field is able to couple to the gas and shear over a range of fluid conditions. Despite the low-magnetic coupling, MRI modes grow for a range of magnetic field strengths and Hall diffusion largely determines the properties of the perturbations in the inner regions of the disc.

Histone Code Modulation by Oncogenic PWWP-domain Protein in Breast Cancers

DTIC Science & Technology

2012-06-01

imaginal discs, the Drosophila melanogaster homologue of human retinoblastoma binding protein 2. Genetics 2000; 156: 645-663. [10] Zeng J, Ge Z, Wang...in breast cancer patients. Earlier, we used genomic analysis of copy number and gene expression to perform a detailed analysis of the 8p11-12...1 Figure 1. Representative view of ChIP-seq peak of a histone modifying factor at the UBR2V2 genomic locus in the

Fomblin Z25: A New Method for its Degradation Assessment & Proposal for Safe Operation in Space

NASA Astrophysics Data System (ADS)

Buttery, M.; Gaillard, L.; Rajala, S.; Roberts, E.; Rohr, T.; Merstallinger, A.

2013-09-01

We present an overview of the studies of the past two years performed by the Mechanisms Section of the European Space Research and Technology Centre (ESA-ESTEC), the European Space Tribology Laboratory (ESTL) and Aerospace & Advanced Composites GmbH (AAC) on the tribological and chemical degradation mechanisms of PFPE oil Fomblin Z25.Tests have been performed using a spiral orbit tribometer (SOT), demonstrating the susceptibility of the lifetime of this lubricant to a range of variables (including load and temperature). A residual gas analyser was implemented, demonstrating a technique for detecting the failure of a PFPE lubricant independent of the friction coefficient through in-situ monitoring of selected volatile gases throughout the tests. To the authors knowledge this work is the first demonstration of the failure of Fomblin Z25 oil independent from friction, torque, or motor current increase.In addition, SOT and pin-on-disc (POD) research efforts have been aimed at identifying the so called auto- catalytic effect during lubricant degradation.

Determination of the source of SHG verniers in zebrafish skeletal muscle

NASA Astrophysics Data System (ADS)

Dempsey, William P.; Hodas, Nathan O.; Ponti, Aaron; Pantazis, Periklis

2015-12-01

SHG microscopy is an emerging microscopic technique for medically relevant imaging because certain endogenous proteins, such as muscle myosin lattices within muscle cells, are sufficiently spatially ordered to generate detectable SHG without the use of any fluorescent dye. Given that SHG signal is sensitive to the structural state of muscle sarcomeres, SHG functional imaging can give insight into the integrity of muscle cells in vivo. Here, we report a thorough theoretical and experimental characterization of myosin-derived SHG intensity profiles within intact zebrafish skeletal muscle. We determined that “SHG vernier” patterns, regions of bifurcated SHG intensity, are illusory when sarcomeres are staggered with respect to one another. These optical artifacts arise due to the phase coherence of SHG signal generation and the Guoy phase shift of the laser at the focus. In contrast, two-photon excited fluorescence images obtained from fluorescently labeled sarcomeric components do not contain such illusory structures, regardless of the orientation of adjacent myofibers. Based on our results, we assert that complex optical artifacts such as SHG verniers should be taken into account when applying functional SHG imaging as a diagnostic readout for pathological muscle conditions.

A high rigor temperature, not sarcomere length, determines light scattering properties and muscle colour in beef M. sternomandibularis meat and muscle fibres.

PubMed

Hughes, J; Clarke, F; Purslow, P; Warner, R

2018-05-18

Beef meat colour is impacted by both myoglobin status and the light scattering properties of the muscle, and the specific causative scattering elements of the latter are still unknown. We hypothesize that stretching muscles during rigor will generate a structure which favours light scattering, by increasing the length of the I-band (longer sarcomeres) and that a high rigor temperature will cause protein reconfiguration, changing the muscle structure and promoting light scattering. Muscle fibre fragments were isolated from four beef M. sternomandibularis and subjected to stretching (plus, minus) and three incubation temperatures (5, 15, 35 °C). Reflectance confocal laser scanning microscopy (rCLSM) revealed sarcomere stretching alone was not solely responsible for light scattering development. A high rigor temperature (35 °C) was more favourable for light scattering. Stretching and taking muscle into rigor at 35 °C promoted transverse shrinkage of muscle fibres and increased light scattering and could be applied post-mortem (PM) to reduce the occurrence of problematic dark meat. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Genetic engineering and therapy for inherited and acquired cardiomyopathies.

PubMed

Day, Sharlene; Davis, Jennifer; Westfall, Margaret; Metzger, Joseph

2006-10-01

The cardiac myofilaments consist of a highly ordered assembly of proteins that collectively generate force in a calcium-dependent manner. Defects in myofilament function and its regulation have been implicated in various forms of acquired and inherited human heart disease. For example, during cardiac ischemia, cardiac myocyte contractile performance is dramatically downregulated due in part to a reduced sensitivity of the myofilaments to calcium under acidic pH conditions. Over the last several years, the thin filament regulatory protein, troponin I, has been identified as an important mediator of this response. Mutations in troponin I and other sarcomere genes are also linked to several distinct inherited cardiomyopathic phenotypes, including hypertrophic, dilated, and restrictive cardiomyopathies. With the cardiac sarcomere emerging as a central player for such a diverse array of human heart diseases, genetic-based strategies that target the myofilament will likely have broad therapeutic potential. The development of safe vector systems for efficient gene delivery will be a critical hurdle to overcome before these types of therapies can be successfully applied. Nonetheless, studies focusing on the principles of acute genetic engineering of the sarcomere hold value as they lay the essential foundation on which to build potential gene-based therapies for heart disease.

Molecular cytogenetic map of the central bearded dragon, Pogona vitticeps (Squamata: Agamidae).

PubMed

Young, M J; O'Meally, D; Sarre, S D; Georges, A; Ezaz, T

2013-07-01

Reptiles, as the sister group to birds and mammals, are particularly valuable for comparative genomic studies among amniotes. The Australian central bearded dragon (Pogona vitticeps) is being developed as a reptilian model for such comparisons, with whole-genome sequencing near completion. The karyotype consists of 6 pairs of macrochromosomes and 10 pairs microchromosomes (2n = 32), including a female heterogametic ZW sex microchromosome pair. Here, we present a molecular cytogenetic map for P. vitticeps comprising 87 anchor bacterial artificial chromosome clones that together span each macro- and microchromosome. It is the first comprehensive cytogenetic map for any non-avian reptile. We identified an active nucleolus organizer region (NOR) on the sub-telomeric region of 2q by mapping 18S rDNA and Ag-NOR staining. We identified interstitial telomeric sequences in two microchromosome pairs and the W chromosome, indicating that microchromosome fusion has been a mechanism of karyotypic evolution in Australian agamids within the last 21 to 19 million years. Orthology searches against the chicken genome revealed an intrachromosomal rearrangement of P. vitticeps 1q, identified regions orthologous to chicken Z on P. vitticeps 2q, snake Z on P. vitticeps 6q and the autosomal microchromosome pair in P. vitticeps orthologous to turtle Pelodiscus sinensis ZW and lizard Anolis carolinensis XY. This cytogenetic map will be a valuable reference tool for future gene mapping studies and will provide the framework for the work currently underway to physically anchor genome sequences to chromosomes for this model Australian squamate.

The star formation history of the Hubble sequence: spatially resolved colour distributions of intermediate-redshift galaxies in the Hubble Deep Field

NASA Astrophysics Data System (ADS)

Abraham, R. G.; Ellis, R. S.; Fabian, A. C.; Tanvir, N. R.; Glazebrook, K.

1999-03-01

We analyse the spatially resolved colours of distant galaxies of known redshift in the Hubble Deep Field, using a new technique based on matching resolved four-band colour data to the predictions of evolutionary synthesis models. Given some simplifying assumptions, we demonstrate how our technique is capable of probing the evolutionary history of high-redshift systems, noting the specific advantage of observing galaxies at an epoch closer to the time of their formation. We quantify the relative age, dispersion in age, on-going star formation rate and star formation history of distinct components. We explicitly test for the presence of dust and quantify its effect on our conclusions. To demonstrate the potential of the method, we study the spirals and ellipticals in the near-complete sample of 32 I_814<21.9 mag galaxies with z~0.5 studied by Bouwens, Broadhurst & Silk. The dispersion of the internal colours of a sample of 0.4

Evolution of the anti-truncated stellar profiles of S0 galaxies since z = 0.6 in the SHARDS survey. I. Sample and methods

NASA Astrophysics Data System (ADS)

Borlaff, Alejandro; Eliche-Moral, M. Carmen; Beckman, John E.; Ciambur, Bogdan C.; Pérez-González, Pablo G.; Barro, Guillermo; Cava, Antonio; Cardiel, Nicolas

2017-08-01

Context. The controversy about the origin of the structure of early-type S0-E/S0 galaxies may be due to the difficulty of comparing surface brightness profiles with different depths, photometric corrections and point spread function (PSF) effects (which are almost always ignored). Aims: We aim to quantify the properties of Type-III (anti-truncated) discs in a sample of S0 galaxies at 0.2

Through thick and thin: Structure of the Galactic thick disc from extragalactic surveys

NASA Astrophysics Data System (ADS)

Kordopatis, G.; Hill, V.; Irwin, M.; Gilmore, G.; Wyse, R. F. G.; Tolstoy, E.; de Laverny, P.; Recio-Blanco, A.; Battaglia, G.; Starkenburg, E.

2013-07-01

Context. We aim to understand the accretion history of the Milky Way by exploring the vertical and radial properties of the Galactic thick disc. Aims: We study the chemical and kinematic properties of roughly a thousand spectra of faint magnitude foreground Galactic stars observed serendipitously during extra-galactic surveys in four lines-of-sight: three in the southern Galactic hemisphere (surveys of the Carina, Fornax and Sculptor dwarf spheroidal galaxies) and one in the northern Galactic hemisphere (a survey of the Sextans dwarf spheroidal galaxy). The foreground stars span distances up to ~3 kpc from the Galactic plane and Galactocentric radii up to 11 kpc. Methods: The stellar atmospheric parameters (effective temperature, surface gravity, metallicity) are obtained by an automated parameterisation pipeline and the distances of the stars are then derived by a projection of the atmospheric parameters on a set of theoretical isochrones using a Bayesian approach. The metallicity gradients are estimated for each line-of-sight and compared with predictions from the Besançon model of the Galaxy, in order to test the chemical structure of the thick disc. Finally, we use the radial velocities in each line-of-sight to derive a proxy for either the azimuthal or the vertical component of the orbital velocity of the stars. Results: Only three lines-of-sight have a sufficient number of foreground stars for a robust analysis. Towards Sextans in the Northern Galactic hemisphere and Sculptor in the South, we measure a consistent decrease in mean metallicity with height from the Galactic plane, suggesting a chemically symmetric thick disc. This decrease can either be due to an intrinsic thick disc metallicity gradient, or simply due to a change in the thin disc/thick disc population ratio and no intrinsic metallicity gradients for the thick disc. We favour the latter explanation. In contrast, we find evidence of an unpredicted metal-poor population in the direction of Carina. This population was earlier detected, but our more detailed analysis provides robust estimates of its location (|Z| < 1 kpc), metallicity (-2 < [M/H] < -1 dex) and azimuthal orbital velocity (Vφ ~ 120 km s-1). Conclusions: Given the chemo-dynamical properties of the over-density towards the Carina line-of-sight, we suggest that it represents the metal-poor tail of the canonical thick disc. In spite of the small number of stars available, we suggest that this metal-weak thick disc follows the often suggested canonical thick disc velocity-metallicity correlation of ∂Vφ/∂ [M/H] ~ 40-50 km s-1 dex-1. Based on observations collected at the European Southern Observatory at Paranal, Chile, ESO Large Programme 171.B-0588 (DART) and 171.B-0520(A).Full Tables 2 and 4 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/555/A12

Actin capping protein CAPZB regulates cell morphology, differentiation, and neural crest migration in craniofacial morphogenesis†

PubMed Central

Mukherjee, Kusumika; Ishii, Kana; Pillalamarri, Vamsee; Kammin, Tammy; Atkin, Joan F.; Hickey, Scott E.; Xi, Qiongchao J.; Zepeda, Cinthya J.; Gusella, James F.; Talkowski, Michael E.; Morton, Cynthia C.; Maas, Richard L.; Liao, Eric C.

2016-01-01

CAPZB is an actin-capping protein that caps the growing end of F-actin and modulates the cytoskeleton and tethers actin filaments to the Z-line of the sarcomere in muscles. Whole-genome sequencing was performed on a subject with micrognathia, cleft palate and hypotonia that harbored a de novo, balanced chromosomal translocation that disrupts the CAPZB gene. The function of capzb was analyzed in the zebrafish model. capzb−/− mutants exhibit both craniofacial and muscle defects that recapitulate the phenotypes observed in the human subject. Loss of capzb affects cell morphology, differentiation and neural crest migration. Differentiation of both myogenic stem cells and neural crest cells requires capzb. During palate morphogenesis, defective cranial neural crest cell migration in capzb−/− mutants results in loss of the median cell population, creating a cleft phenotype. capzb is also required for trunk neural crest migration, as evident from melanophores disorganization in capzb−/− mutants. In addition, capzb over-expression results in embryonic lethality. Therefore, proper capzb dosage is important during embryogenesis, and regulates both cell behavior and tissue morphogenesis. PMID:26758871

Moisture migration, microstructure damage and protein structure changes in porcine longissimus muscle as influenced by multiple freeze-thaw cycles.

PubMed

Zhang, Mingcheng; Li, Fangfei; Diao, Xinping; Kong, Baohua; Xia, Xiufang

2017-11-01

This study investigated the effects of multiple freeze-thaw (F-T) cycles on water mobility, microstructure damage and protein structure changes in porcine longissimus muscle. The transverse relaxation time T 2 increased significantly when muscles were subjected to multiple F-T cycles (P<0.05), which means that immobile water shifted to free water and the free water mobility increased. Multiple F-T cycles caused sarcomere shortening, Z line fractures, and I band weakening and also led to microstructural destruction of muscle tissue. The decreased free amino group content and increased dityrosine in myofibrillar protein (MP) revealed that multiple F-T cycles caused protein cross-linking and oxidation. In addition, the results of size exclusion chromatography, circular dichroism spectra, UV absorption spectra, and intrinsic fluorescence spectroscopy indirectly proved that multiple F-T cycles could cause protein aggregation and degradation, α-helix structure disruption, hydrophobic domain exposure, and conformational changes of MP. Overall, repeated F-T cycles changed the protein structure and water distribution within meat. Copyright © 2017 Elsevier Ltd. All rights reserved.

Histone Code Modulation by Oncogenic PWWP-Domain Protein in Breast Cancers

DTIC Science & Technology

2014-08-01

discs, the Drosophila melanogaster homo- logue of human retinoblastoma binding protein 2. Genetics 2000; 156: 645-663. [10] Zeng J, Ge Z, Wang L...in breast cancer patients (7-11). Earlier, we used genomic analysis of copy number and gene expression to perform a detailed analysis of the 8p11-12...from the 8p11-12 region (14). Very recently, we searched the Cancer Genome Atlas database that contains 744 breast invasive carcinomas. We found DNA or

The cytoskeleton is disrupted by the bacterial effector HrpZ, but not by the bacterial PAMP flg22, in tobacco BY-2 cells.

PubMed

Guan, Xin; Buchholz, Günther; Nick, Peter

2013-04-01

Plant innate immunity is composed of two layers. Basal immunity is triggered by pathogen-associated molecular patterns (PAMPs) such as the flagellin-peptide flg22 and is termed PAMP-triggered immunity (PTI). In addition, effector-triggered immunity (ETI) linked with programmed cell death and cytoskeletal reorganization can be induced by pathogen-derived factors, such as the Harpin proteins originating from phytopathogenic bacteria. To get insight into the link between cytoskeleton and PTI or ETI, this study followed the responses of actin filaments and microtubules to flg22 and HrpZ in vivo by spinning-disc confocal microscopy in GFP-tagged marker lines of tobacco BY-2. At a concentration that clearly impairs mitosis, flg22 can induce only subtle cytoskeletal responses. In contrast, HrpZ causes a rapid and massive bundling of actin microfilaments (completed in ~20 min, i.e. almost simultaneously with extracellular alkalinization), which is followed by progressive disintegration of actin cables and cytoplasmic microtubules, a loss of cytoplasmic structure, and vacuolar disintegration. Cytoskeletal disruption is proposed as an early event that discriminates HrpZ-triggered ETI-like defence from flg22-triggered PTI.

The cytoskeleton is disrupted by the bacterial effector HrpZ, but not by the bacterial PAMP flg22, in tobacco BY-2 cells

PubMed Central

Guan, Xin; Buchholz, Günther; Nick, Peter

2013-01-01

Plant innate immunity is composed of two layers. Basal immunity is triggered by pathogen-associated molecular patterns (PAMPs) such as the flagellin-peptide flg22 and is termed PAMP-triggered immunity (PTI). In addition, effector-triggered immunity (ETI) linked with programmed cell death and cytoskeletal reorganization can be induced by pathogen-derived factors, such as the Harpin proteins originating from phytopathogenic bacteria. To get insight into the link between cytoskeleton and PTI or ETI, this study followed the responses of actin filaments and microtubules to flg22 and HrpZ in vivo by spinning-disc confocal microscopy in GFP-tagged marker lines of tobacco BY-2. At a concentration that clearly impairs mitosis, flg22 can induce only subtle cytoskeletal responses. In contrast, HrpZ causes a rapid and massive bundling of actin microfilaments (completed in ~20min, i.e. almost simultaneously with extracellular alkalinization), which is followed by progressive disintegration of actin cables and cytoplasmic microtubules, a loss of cytoplasmic structure, and vacuolar disintegration. Cytoskeletal disruption is proposed as an early event that discriminates HrpZ-triggered ETI-like defence from flg22-triggered PTI. PMID:23408828

Testing the hierarchical assembly of massive galaxies using accurate merger rates out to z ˜ 1.5

NASA Astrophysics Data System (ADS)

Rodrigues, Myriam; Puech, M.; Flores, H.; Hammer, F.; Pirzkal, N.

2018-04-01

We established an accurate comparison between observationally and theoretically estimated major merger rates over a large range of mass (log Mbar/M⊙ =9.9-11.4) and redshift (z = 0.7-1.6). For this, we combined a new estimate of the merger rate from an exhaustive count of pairs within the virial radius of massive galaxies at z ˜ 1.265 and cross-validated with their morphology, with estimates from the morpho-kinematic analysis of two other samples. Theoretical predictions were estimated using semi-empirical models with inputs matching the properties of the observed samples, while specific visibility time-scales scaled to the observed samples were used. Both theory and observations are found to agree within 30 per cent of the observed value, which provides strong support to the hierarchical assembly of galaxies over the probed ranges of mass and redshift. Here, we find that ˜60 per cent of population of local massive (Mstellar =1010.3-11.6 M⊙) galaxies would have undergone a wet major merger since z = 1.5, consistently with previous studies. Such recent mergers are expected to result in the (re-)formation of a significant fraction of local disc galaxies.

Extraction of convective cloud parameters from Doppler Weather Radar MAX(Z) product using Image Processing Technique

NASA Astrophysics Data System (ADS)

Arunachalam, M. S.; Puli, Anil; Anuradha, B.

2016-07-01

In the present work continuous extraction of convective cloud optical information and reflectivity (MAX(Z) in dBZ) using online retrieval technique for time series data production from Doppler Weather Radar (DWR) located at Indian Meteorological Department, Chennai has been developed in MATLAB. Reflectivity measurements for different locations within the DWR range of 250 Km radii of circular disc area can be retrieved using this technique. It gives both time series reflectivity of point location and also Range Time Intensity (RTI) maps of reflectivity for the corresponding location. The Graphical User Interface (GUI) developed for the cloud reflectivity is user friendly; it also provides the convective cloud optical information such as cloud base height (CBH), cloud top height (CTH) and cloud optical depth (COD). This technique is also applicable for retrieving other DWR products such as Plan Position Indicator (Z, in dBZ), Plan Position Indicator (Z, in dBZ)-Close Range, Volume Velocity Processing (V, in knots), Plan Position Indicator (V, in m/s), Surface Rainfall Intensity (SRI, mm/hr), Precipitation Accumulation (PAC) 24 hrs at 0300UTC. Keywords: Reflectivity, cloud top height, cloud base, cloud optical depth

The CD59 family member Leaky/Coiled is required for the establishment of the blood-brain barrier in Drosophila.

PubMed

Syed, Mubarak Hussain; Krudewig, Alice; Engelen, Daniel; Stork, Tobias; Klämbt, Christian

2011-05-25

The blood-brain barrier of Drosophila is established by the subperineurial glial cells that encase the CNS and PNS. The subperineurial glial cells are thin, highly interdigitated cells with epithelial character. The establishment of extensive septate junctions between these cells is crucial for the prevention of uncontrolled paracellular leakage of ions and solutes from the hemolymph into the nervous system. In the absence of septate junctions, macromolecules such as fluorescently labeled dextran can easily cross the blood-brain barrier. To identify additional components of the blood-brain barrier, we followed a genetic approach and injected Texas-Red-conjugated dextran into the hemolymph of embryos homozygous for chromosomal deficiencies. In this way, we identified the 153-aa-large protein Coiled, a new member of the Ly6 (leukocyte antigen 6) family, as being crucially required for septate junction formation and blood-brain barrier integrity. In coiled mutants, the normal distribution of septate junction markers such as NeurexinIV, Coracle, or Discs large is disturbed. EM analyses demonstrated that Coiled is required for the formation of septate junctions. We further show that Coiled is expressed by the subsperineurial glial cells in which it is anchored to the cell membrane via a glycosylphosphatidylinositol anchor and mediates adhesive properties. Clonal rescue studies indicate that the presence of Coiled is required symmetrically on both cells engaged in septate junction formation.

Galaxy Zoo: evidence for diverse star formation histories through the green valley

NASA Astrophysics Data System (ADS)

Smethurst, R. J.; Lintott, C. J.; Simmons, B. D.; Schawinski, K.; Marshall, P. J.; Bamford, S.; Fortson, L.; Kaviraj, S.; Masters, K. L.; Melvin, T.; Nichol, R. C.; Skibba, R. A.; Willett, K. W.

2015-06-01

Does galaxy evolution proceed through the green valley via multiple pathways or as a single population? Motivated by recent results highlighting radically different evolutionary pathways between early- and late-type galaxies, we present results from a simple Bayesian approach to this problem wherein we model the star formation history (SFH) of a galaxy with two parameters, [t, τ] and compare the predicted and observed optical and near-ultraviolet colours. We use a novel method to investigate the morphological differences between the most probable SFHs for both disc-like and smooth-like populations of galaxies, by using a sample of 126 316 galaxies (0.01 < z < 0.25) with probabilistic estimates of morphology from Galaxy Zoo. We find a clear difference between the quenching time-scales preferred by smooth- and disc-like galaxies, with three possible routes through the green valley dominated by smooth- (rapid time-scales, attributed to major mergers), intermediate- (intermediate time-scales, attributed to minor mergers and galaxy interactions) and disc-like (slow time-scales, attributed to secular evolution) galaxies. We hypothesize that morphological changes occur in systems which have undergone quenching with an exponential time-scale τ < 1.5 Gyr, in order for the evolution of galaxies in the green valley to match the ratio of smooth to disc galaxies observed in the red sequence. These rapid time-scales are instrumental in the formation of the red sequence at earlier times; however, we find that galaxies currently passing through the green valley typically do so at intermediate time-scales.†

On the effect of galactic outflows in cosmological simulations of disc galaxies

NASA Astrophysics Data System (ADS)

Valentini, Milena; Murante, Giuseppe; Borgani, Stefano; Monaco, Pierluigi; Bressan, Alessandro; Beck, Alexander M.

2017-09-01

We investigate the impact of galactic outflow modelling on the formation and evolution of a disc galaxy, by performing a suite of cosmological simulations with zoomed-in initial conditions (ICs) of a Milky Way-sized halo. We verify how sensitive the general properties of the simulated galaxy are to the way in which stellar feedback triggered outflows are implemented, keeping ICs, simulation code and star formation (SF) model all fixed. We present simulations that are based on a version of the gadget3 code where our sub-resolution model is coupled with an advanced implementation of smoothed particle hydrodynamics that ensures a more accurate fluid sampling and an improved description of gas mixing and hydrodynamical instabilities. We quantify the strong interplay between the adopted hydrodynamic scheme and the sub-resolution model describing SF and feedback. We consider four different galactic outflow models, including the one introduced by Dalla Vecchia & Schaye (2012) and a scheme that is inspired by the Springel & Hernquist (2003) model. We find that the sub-resolution prescriptions adopted to generate galactic outflows are the main shaping factor of the stellar disc component at low redshift. The key requirement that a feedback model must have to be successful in producing a disc-dominated galaxy is the ability to regulate the high-redshift SF (responsible for the formation of the bulge component), the cosmological infall of gas from the large-scale environment, and gas fall-back within the galactic radius at low redshift, in order to avoid a too high SF rate at z = 0.

Coherent Raman Imaging of Live Muscle Sarcomeres Assisted by SFG Microscopy.

PubMed

Kim, Hyunmin; Kim, Do-Young; Joo, Kyung-Il; Kim, Jung-Hye; Jeong, Soon Moon; Lee, Eun Seong; Hahm, Jeong-Hoon; Kim, Kyuhyung; Moon, Dae Woon

2017-08-23

In this study, we used spectrally focused coherent anti-Stokes Raman scattering (spCARS) microscopy assisted by sum-frequency generation (SFG) to monitor the variations in the structural morphology and molecular vibrations of a live muscle of Caenorhabditis elegans. The subunits of the muscle sarcomeres, such as the M-line, myosin, dense body, and α-actinin, were alternatively observed using spCARS microscopy for different sample orientations, with the guidance of a myosin positional marker captured by SFG microscopy. Interestingly enough, the beam polarization dependence of the spCARS contrasts for two parallel subunits (dense body and myosin) showed a ~90° phase difference. The chemically sensitive spCARS spectra induced by the time-varying overlap of two pulses allowed (after a robust subtraction of the non-resonant background using a modified Kramers-Krönig transformation method) high-fidelity detection of various genetically modified muscle sarcomeres tuned to the C-H vibration (2800-3100 cm -1 ). Conversely, SFG image mapping assisted by phase-retrieved spCARS spectra also facilitated label-free monitoring of the changes in the muscle content of C. elegans that are associated with aging, based on the hypothesis that the C-H vibrational modes could serve as qualitative chemical markers sensitive to the amount and/or structural modulation of the muscle.

Myosin head orientation: a structural determinant for the Frank-Starling relationship

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farman, Gerrie P.; Gore, David; Allen, Edward

The cellular mechanism underlying the Frank-Starling law of the heart is myofilament length-dependent activation. The mechanism(s) whereby sarcomeres detect changes in length and translate this into increased sensitivity to activating calcium has been elusive. Small-angle X-ray diffraction studies have revealed that the intact myofilament lattice undergoes numerous structural changes upon an increase in sarcomere length (SL): lattice spacing and the I{sub 1,1}/I{sub 1,0} intensity ratio decreases, whereas the M3 meridional reflection intensity (I{sub M3}) increases, concomitant with increases in diastolic and systolic force. Using a short ({approx}10 ms) X-ray exposure just before electrical stimulation, we were able to obtain detailedmore » structural information regarding the effects of external osmotic compression (with mannitol) and obtain SL on thin intact electrically stimulated isolated rat right ventricular trabeculae. We show that over the same incremental increases in SL, the relative changes in systolic force track more closely to the relative changes in myosin head orientation (as reported by IM3) than to the relative changes in lattice spacing. We conclude that myosin head orientation before activation determines myocardial sarcomere activation levels and that this may be the dominant mechanism for length-dependent activation.« less

Role of dystroglycan in limiting contraction-induced injury to the sarcomeric cytoskeleton of mature skeletal muscle.

PubMed

Rader, Erik P; Turk, Rolf; Willer, Tobias; Beltrán, Daniel; Inamori, Kei-Ichiro; Peterson, Taylor A; Engle, Jeffrey; Prouty, Sally; Matsumura, Kiichiro; Saito, Fumiaki; Anderson, Mary E; Campbell, Kevin P

2016-09-27

Dystroglycan (DG) is a highly expressed extracellular matrix receptor that is linked to the cytoskeleton in skeletal muscle. DG is critical for the function of skeletal muscle, and muscle with primary defects in the expression and/or function of DG throughout development has many pathological features and a severe muscular dystrophy phenotype. In addition, reduction in DG at the sarcolemma is a common feature in muscle biopsies from patients with various types of muscular dystrophy. However, the consequence of disrupting DG in mature muscle is not known. Here, we investigated muscles of transgenic mice several months after genetic knockdown of DG at maturity. In our study, an increase in susceptibility to contraction-induced injury was the first pathological feature observed after the levels of DG at the sarcolemma were reduced. The contraction-induced injury was not accompanied by increased necrosis, excitation-contraction uncoupling, or fragility of the sarcolemma. Rather, disruption of the sarcomeric cytoskeleton was evident as reduced passive tension and decreased titin immunostaining. These results reveal a role for DG in maintaining the stability of the sarcomeric cytoskeleton during contraction and provide mechanistic insight into the cause of the reduction in strength that occurs in muscular dystrophy after lengthening contractions.

Cross-bridge mechanism of residual force enhancement after stretching in a skeletal muscle.

PubMed

Tamura, Youjiro

2018-01-01

A muscle model that uses a modified Langevin equation with actomyosin potentials was used to describe the residual force enhancement after active stretching. Considering that the new model uses cross-bridge theory to describe the residual force enhancement, it is different from other models that use passive stretching elements. Residual force enhancement was simulated using a half sarcomere comprising 100 myosin molecules. In this paper, impulse is defined as the integral of an excess force from the steady isometric force over the time interval for which a stretch is applied. The impulse was calculated from the force response due to fast and slow muscle stretches to demonstrate the viscoelastic property of the cross-bridges. A cross-bridge mechanism was proposed as a way to describe the residual force enhancement on the basis of the impulse results with reference to the compliance of the actin filament. It was assumed that the period of the actin potential increased by 0.5% and the amplitude of the potential decreased by 0.5% when the half sarcomere was stretched by 10%. The residual force enhancement after 21.0% sarcomere stretching was 6.9% of the maximum isometric force of the muscle; this value was due to the increase in the number of cross-bridges.

Differentiation of human skeletal muscle cells in culture: maturation as indicated by titin and desmin striation.

PubMed

van der Ven, P F; Schaart, G; Jap, P H; Sengers, R C; Stadhouders, A M; Ramaekers, F C

1992-10-01

This report describes a phenotyping study of differentiating human skeletal muscle cells in tissue culture. Satellite cells (adult myoblasts), isolated from biopsy material, showed a proliferative behaviour in high-nutrition medium, but fused to form myotubes when grown in low-nutrition medium. The expression and structural organization of the intermediate filament proteins desmin and vimentin as well as the sarcomeric constituents alpha-actin, alpha-actinin, nebulin, myosin and especially titin during myofibrillogenesis in vitro, were studied by means of indirect immunofluorescence assays. The proliferating myoblasts contained both desmin and vimentin, alpha-actinin and the filamentous form of actin. Shortly after the change of medium, expression of titin, sarcomeric myosin and skeletal muscle alpha-actin was found in mononuclear cells in a diffuse, filamentous (titin, myosin, alpha-actin) or punctate (titin, myosin) pattern. Four to 10 days after the medium change, mature myotubes showed desmin, titin, alpha-actinin, nebulin, sarcomeric myosin and actin cross-striations, while vimentin was no longer detected. We conclude that human skeletal muscle cell cultures are an appropriate model system to study the molecular basis of myofibrillogenesis. Especially the presence of desmin in a striated fashion points to a high degree of maturation of the muscle cell cultures.

Muscle enzyme and fiber type-specific sarcomere protein increases in serum after inertial concentric-eccentric exercise.

PubMed

Carmona, G; Guerrero, M; Cussó, R; Padullés, J M; Moras, G; Lloret, M; Bedini, J L; Cadefau, J A

2015-12-01

Muscle damage induced by inertial exercise performed on a flywheel device was assessed through the serum evolution of muscle enzymes, interleukin 6, and fiber type-specific sarcomere proteins such as fast myosin (FM) and slow myosin (SM). We hypothesized that a model of muscle damage could be constructed by measuring the evolution of serum concentration of muscle proteins following inertial exercise, according to their molecular weight and the fiber compartment in which they are located. Moreover, by measuring FM and SM, the type of fibers that are affected could be assessed. Serum profiles were registered before and 24, 48, and 144 h after exercise in 10 healthy and recreationally active young men. Creatine kinase (CK) and CK-myocardial band isoenzyme increased in serum early (24 h) and returned to baseline values after 48 h. FM increased in serum late (48 h) and remained elevated 144 h post-exercise. The increase in serum muscle enzymes suggests increased membrane permeability of both fast and slow fibers, and the increase in FM reveals sarcomere disruption as well as increased membrane permeability of fast fibers. Consequently, FM could be adopted as a fiber type-specific biomarker of muscle damage. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Patient-Specific Induced Pluripotent Stem Cell as a Model for Familial Dilated Cardiomyopathy

PubMed Central

Sun, Ning; Yazawa, Masayuki; Liu, Jianwei; Han, Leng; Sanchez-Freire, Veronica; Abilez, Oscar J.; Navarrete, Enrique G.; Hu, Shijun; Wang, Li; Lee, Andrew; Pavlovic, Aleksandra; Lin, Shin; Chen, Rui; Hajjar, Roger J.; Snyder, Michael P.; Dolmetsch, Ricardo E.; Butte, Manish J.; Ashley, Euan A.; Longaker, Michael T.; Robbins, Robert C.; Wu, Joseph C.

2013-01-01

Dilated cardiomyopathy (DCM) is the most common cardiomyopathy, characterized by ventricular dilatation, systolic dysfunction, and progressive heart failure. DCM is the most common diagnosis leading to heart transplantation and places a significant burden on healthcare worldwide. The advent of induced pluripotent stem cells (iPSCs) offers an exceptional opportunity for creating disease-specific models, investigating underlying mechanisms, and optimizing therapy. Here we generated cardiomyocytes (CMs) from iPSCs derived from patients of a DCM family carrying a point mutation (R173W) in the gene encoding sarcomeric protein cardiac troponin T. Compared to the control healthy individuals in the same family cohort, DCM iPSC-CMs exhibited altered Ca2+ handling, decreased contractility, and abnormal sarcomeric α-actinin distribution. When stimulated with β-adrenergic agonist, DCM iPSC-CMs showed characteristics of failure such as reduced beating rates, compromised contraction, and significantly more cells with abnormal sarcomeric α-actinin distribution. β-adrenergic blocker treatment and over-expression of sarcoplasmic reticulum Ca2+ ATPase (Serca2a) improved DCM iPSC-CMs function. Our study demonstrated that human DCM iPSC-CMs recapitulated to some extent the disease phenotypes morphologically and functionally, and thus can serve as a useful platform for exploring molecular and cellular mechanisms and optimizing treatment of this particular disease. PMID:22517884

Alternative S2 Hinge Regions of the Myosin Rod Affect Myofibrillar Structure and Myosin Kinetics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Mark S.; Dambacher, Corey M.; Knowles, Aileen F.

2009-07-01

The subfragment 2/light meromyosin 'hinge' region has been proposed to significantly contribute to muscle contraction force and/or speed. Transgenic replacement of the endogenous fast muscle isovariant hinge A (exon 15a) in Drosophila melanogaster indirect flight muscle with the slow muscle hinge B (exon 15b) allows examination of the structural and functional changes when only this region of the myosin molecule is different. Hinge B was previously shown to increase myosin rod length, increase A-band and sarcomere length, and decrease flight performance compared to hinge A. We applied additional measures to these transgenic lines to further evaluate the consequences of modifyingmore » this hinge region. Structurally, the longer A-band and sarcomere lengths found in the hinge B myofibrils appear to be due to the longitudinal addition of myosin heads. Functionally, hinge B, although a significant distance from the myosin catalytic domain, alters myosin kinetics in a manner consistent with this region increasing myosin rod length. These structural and functional changes combine to decrease whole fly wing-beat frequency and flight performance. Our results indicate that this hinge region plays an important role in determining myosin kinetics and in regulating thick and thin filament lengths as well as sarcomere length.« less

Molecular analysis of the ependymin gene and functional test of its promoter region by transient expression in Brachydanio rerio.

PubMed

Rinder, H; Bayer, T A; Gertzen, E M; Hoffmann, W

1992-01-01

Ependymins are secretory products of meningeal cells and represent the predominant glycoproteins in the cerebrospinal fluid from various orders of teleost fish. In the zebrafish, their expression starts between 48 and 72 h post-fertilization. Generally, they share characteristics with proteins involved in cell-contact phenomena. Here, we characterize the ependymin gene from Brachydanio rerio and its flanking regions. The sequence was obtained from clones generated using the polymerase chain reaction (PCR), including a variation of an "anchored" PCR. Also, clones from a conventional phage library were analyzed. We found that the transcribed portion is arranged in six exons. Transient expression of an ependymin-promoter-lacZ gene fusion in zebrafish embryos revealed that the 2.0-kb upstream regulatory region used is sufficient to direct the ependymin-specific correct temporal and spatial expression pattern of the lacZ reporter gene.

a New Generation Mining Head with Disc Tool of Complex Trajectory / GŁOWICA URABIAJĄCA Nowej Generacji Z NARZĘDZIAMI Dyskowymi O ZŁOŻONEJ Trajektorii

NASA Astrophysics Data System (ADS)

Gospodarczyk, Piotr; Kotwica, Krzysztof; Stopka, Grzegorz

2013-12-01

In Polish underground mining plenty of dog headings are drilled with mechanical methods with the use of arm roadheaders equipped with milling units. Cutting tools applied on the units - rotary tangent bits in unfavourable mining and geological conditions or improper work conditions are affected by an accelerated wear process. It influences the speed and costs of drilling such excavations. The article presents a new and innovative solution of a mining head with asymmetric disc tools of complex trajectory elaborated at the Department of Mining, Dressing and Transport Machines, AGH University of Science and Technology, Krakow as an alternative for standard milling units. Advantages of the applied mining method using so called back incision were described as well as principles of construction and work of the suggested solution of the head. In order to work out a construction of the head prototype it was necessary to determine principles and guidelines based on laboratory tests. A construction of a specially prepared laboratory stand for examination of disc tools of complex trajectory, planned research methodology, course of tests and obtained results were presented. An analysis of the results allowed determining the above listed principles and guidelines for a construction of a prototype head. They were the base to work out, with cooperation of the REMAG Ltd Company in Katowice, a technical project of a new head solution, adapted for mounting on the arm of a medium arm roadheader KR 150. A constructed head underwent tests on a research stand on the REMAG testing area and received positive preliminary tests results. W polskim górnictwie podziemnym bardzo duża liczba wyrobisk korytarzowych drążona jest metodami mechanicznymi z wykorzystaniem ramionowych kombajnów chodnikowych, wyposażonych w organy frezujące. Stosowane na tych organach narzędzia skrawające - noże styczno-obrotowe, w niekorzystnych warunkach górniczo-geologicznych lub przy nieprawidłowych warunkach pracy, ulegają przyspieszonemu zużyciu. Wpływa to na prędkość i koszty drążenia tych wyrobisk. W artykule przedstawiono opracowane w Katedrze MGPiT AGH Kraków nowe i innowacyjne rozwiązanie głowicy urabiającej, z narzędziami dyskowymi niesymetrycznymi o złożonej trajektorii, jako alternatywę dla standardowych organów frezujących. Opisano zalety zastosowanej metody urabiania z wykorzystaniem tzw. tylnego podcinaniaoraz zasadę budowy i pracy zaproponowanego rozwiązania przedmiotowej głowicy. Dla opracowania konstrukcji prototypowego egzemplarza tej głowicy koniecznym było określenie, na podstawie badań laboratoryjnych, założeń i wytycznych. Przedstawiono konstrukcję opracowanego specjalnego stanowiska laboratoryjnego do badania narzędzi dyskowych o złożonej trajektorii, założoną metodykę badawczą, przebieg badań oraz uzyskane wyniki. Analiza tych wyników umożliwiła określenie wyżej wymienionych założeń i wytycznych dla konstrukcji głowicy prototypowej. Na ich podstawie opracowano, we współpracy z Zakładami REMAG S.A. w Katowicach, projekt techniczny nowego rozwiązania głowicy, dostosowanej do zabudowy na ramieniu średniego kombajnu chodnikowego KR 150. Wykonany egzemplarz głowicy został poddany próbom na stanowisku badawczym na poligonie Zakładów REMAG i uzyskał pozytywne wyniki badań wstępnych.

Galaxy Zoo: quantitative visual morphological classifications for 48 000 galaxies from CANDELS

NASA Astrophysics Data System (ADS)

Simmons, B. D.; Lintott, Chris; Willett, Kyle W.; Masters, Karen L.; Kartaltepe, Jeyhan S.; Häußler, Boris; Kaviraj, Sugata; Krawczyk, Coleman; Kruk, S. J.; McIntosh, Daniel H.; Smethurst, R. J.; Nichol, Robert C.; Scarlata, Claudia; Schawinski, Kevin; Conselice, Christopher J.; Almaini, Omar; Ferguson, Henry C.; Fortson, Lucy; Hartley, William; Kocevski, Dale; Koekemoer, Anton M.; Mortlock, Alice; Newman, Jeffrey A.; Bamford, Steven P.; Grogin, N. A.; Lucas, Ray A.; Hathi, Nimish P.; McGrath, Elizabeth; Peth, Michael; Pforr, Janine; Rizer, Zachary; Wuyts, Stijn; Barro, Guillermo; Bell, Eric F.; Castellano, Marco; Dahlen, Tomas; Dekel, Avishai; Ownsworth, Jamie; Faber, Sandra M.; Finkelstein, Steven L.; Fontana, Adriano; Galametz, Audrey; Grützbauch, Ruth; Koo, David; Lotz, Jennifer; Mobasher, Bahram; Mozena, Mark; Salvato, Mara; Wiklind, Tommy

2017-02-01

We present quantified visual morphologies of approximately 48 000 galaxies observed in three Hubble Space Telescope legacy fields by the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS) and classified by participants in the Galaxy Zoo project. 90 per cent of galaxies have z ≤ 3 and are observed in rest-frame optical wavelengths by CANDELS. Each galaxy received an average of 40 independent classifications, which we combine into detailed morphological information on galaxy features such as clumpiness, bar instabilities, spiral structure, and merger and tidal signatures. We apply a consensus-based classifier weighting method that preserves classifier independence while effectively down-weighting significantly outlying classifications. After analysing the effect of varying image depth on reported classifications, we also provide depth-corrected classifications which both preserve the information in the deepest observations and also enable the use of classifications at comparable depths across the full survey. Comparing the Galaxy Zoo classifications to previous classifications of the same galaxies shows very good agreement; for some applications, the high number of independent classifications provided by Galaxy Zoo provides an advantage in selecting galaxies with a particular morphological profile, while in others the combination of Galaxy Zoo with other classifications is a more promising approach than using any one method alone. We combine the Galaxy Zoo classifications of `smooth' galaxies with parametric morphologies to select a sample of featureless discs at 1 ≤ z ≤ 3, which may represent a dynamically warmer progenitor population to the settled disc galaxies seen at later epochs.

Differences in Contractile Function of Myofibrils within Human Embryonic Stem Cell-Derived Cardiomyocytes vs. Adult Ventricular Myofibrils Are Related to Distinct Sarcomeric Protein Isoforms

PubMed Central

Iorga, Bogdan; Schwanke, Kristin; Weber, Natalie; Wendland, Meike; Greten, Stephan; Piep, Birgit; dos Remedios, Cristobal G.; Martin, Ulrich; Zweigerdt, Robert; Kraft, Theresia; Brenner, Bernhard

2018-01-01

Characterizing the contractile function of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is key for advancing their utility for cellular disease models, promoting cell based heart repair, or developing novel pharmacological interventions targeting cardiac diseases. The aim of the present study was to understand whether steady-state and kinetic force parameters of β-myosin heavy chain (βMyHC) isoform-expressing myofibrils within human embryonic stem cell-derived cardiomyocytes (hESC-CMs) differentiated in vitro resemble those of human ventricular myofibrils (hvMFs) isolated from adult donor hearts. Contractile parameters were determined using the same micromechanical method and experimental conditions for both types of myofibrils. We identified isoforms and phosphorylation of main sarcomeric proteins involved in the modulation of force generation of both, chemically demembranated hESC-CMs (d-hESC-CMs) and hvMFs. Our results indicate that at saturating Ca2+ concentration, both human-derived contractile systems developed forces with similar rate constants (0.66 and 0.68 s−1), reaching maximum isometric force that was significantly smaller for d-hESC-CMs (42 kPa) than for hvMFs (94 kPa). At submaximal Ca2+-activation, where intact cardiomyocytes normally operate, contractile parameters of d-hESC-CMs and hvMFs exhibited differences. Ca2+ sensitivity of force was higher for d-hESC-CMs (pCa50 = 6.04) than for hvMFs (pCa50 = 5.80). At half-maximum activation, the rate constant for force redevelopment was significantly faster for d-hESC-CMs (0.51 s−1) than for hvMFs (0.28 s−1). During myofibril relaxation, kinetics of the slow force decay phase were significantly faster for d-hESC-CMs (0.26 s−1) than for hvMFs (0.21 s−1), while kinetics of the fast force decay were similar and ~20x faster. Protein analysis revealed that hESC-CMs had essentially no cardiac troponin-I, and partially non-ventricular isoforms of some other sarcomeric proteins, explaining the functional discrepancies. The sarcomeric protein isoform pattern of hESC-CMs had features of human cardiomyocytes at an early developmental stage. The study indicates that morphological and ultrastructural maturation of βMyHC isoform-expressing hESC-CMs is not necessarily accompanied by ventricular-like expression of all sarcomeric proteins. Our data suggest that hPSC-CMs could provide useful tools for investigating inherited cardiac diseases affecting contractile function during early developmental stages. PMID:29403388

Comparison of palatability characteristics of beef gluteus medius and triceps brachii muscles.

PubMed

King, D A; Wheeler, T L; Shackelford, S D; Koohmaraie, M

2009-01-01

The objective of this experiment was to evaluate triceps brachii steaks as a substitute for gluteus medius steaks in foodservice and retail applications, including the effect of aging time and USDA quality grade on the palatability of both muscles. Top sirloin butts (n = 600) and shoulder clod arm roasts (n = 600) representing US Choice and US Select quality grades were selected at 48 h postmortem and aged for 7, 14, 21, 28, 35, or 42 d. Steaks were evaluated using a trained sensory panel, slice shear force, sarcomere length, and Western blotting of desmin measurements. Sarcomere length was measured only on steaks at 14 and 42 d. Triceps brachii and gluteus medius steaks were similar in tenderness rating at 7 and 14 d, but triceps brachii steaks aged longer were more tender (P < 0.05) than were gluteus medius steaks. Triceps brachii steaks reached ultimate tenderness values by 21 d. Gluteus medius steak tenderness ratings improved through 35 d, and at 42 d were similar to those given to triceps brachii steaks at 21 d. Sarcomere lengths were longer (P < 0.05) in triceps brachii than in gluteus medius (2.09 and 1.58 mum, respectively). Significant increases in desmin degradation were detected through 42 d in both muscles (30.9, 46.3, 50.6, 51.0, 57.6, and 64.1% at d 7, 14, 21, 28, 35, and 42 for gluteus medius and 28.9, 40.8, 49.3, 59.2, 61.8, and 71.9% at d 7, 14, 21, 28, 35, and 42 for triceps brachii). At 14 d, gluteus medius had more (P < 0.05) desmin degraded than triceps brachii, but by 28 d, desmin degradation was greater (P < 0.05) in triceps brachii. Quality grade had minimal effects on palatability traits. Desmin degradation contributed to gluteus medius tenderness variation (r = 0.36) across all aging times, but not at individual aging times. Sarcomere length contributed to variation in slice shear force values of gluteus medius at 14 and 42 d (r = -0.59 and -0.48, respectively). Sarcomere length contributed to triceps brachii tenderness variation at 14 d, but not 42 d (r = 0.44 and -0.12, respectively). Desmin degradation was strongly correlated (r = 0.55) to triceps brachii tenderness ratings pooled across aging times but not at individual aging times. These data indicate that triceps brachii steaks could provide the same or improved palatability as gluteus medius steaks at the same or slightly shorter aging times.

Performance of the STAR Event Plane Detector

NASA Astrophysics Data System (ADS)

Ewigleben, Justin; Justin Ewigleben Collaboration

2017-09-01

The Beam Energy Scan (BES) program at the Relativistic Heavy-Ion Collider has shown hints of a critical point and first order phase transition at the BES energies. Key measurements for locating the critical point and determining the first order phase transition are limited by poor event plane resolution, limited statistics and a TPC-only centrality determination. A new event plane and collision centrality detector (EPD) is planned to replace the existing detector, the Beam-Beam Counter (BBC), with higher granularity and acceptance. The design of the EPD consists of two scintillator discs at z = +/- 3.75m from the center of STAR, covering 2.2 < η < 5.1. One quarter of a single disc was installed in STAR for the 2017 run for commissioning. In this talk we will discuss the detector performance during this commissioning run in both proton-proton collisions at √{ s = 510 } GeV and Au-Au collisions at √{sNN = 54.4 } GeV. NSF Grant 1614474.

Novel Methods of Automated Quantification of Gap Junction Distribution and Interstitial Collagen Quantity from Animal and Human Atrial Tissue Sections

PubMed Central

Yan, Jiajie; Thomson, Justin K.; Wu, Xiaomin; Zhao, Weiwei; Pollard, Andrew E.; Ai, Xun

2014-01-01

Background Gap junctions (GJs) are the principal membrane structures that conduct electrical impulses between cardiac myocytes while interstitial collagen (IC) can physically separate adjacent myocytes and limit cell-cell communication. Emerging evidence suggests that both GJ and interstitial structural remodeling are linked to cardiac arrhythmia development. However, automated quantitative identification of GJ distribution and IC deposition from microscopic histological images has proven to be challenging. Such quantification is required to improve the understanding of functional consequences of GJ and structural remodeling in cardiac electrophysiology studies. Methods and Results Separate approaches were employed for GJ and IC identification in images from histologically stained tissue sections obtained from rabbit and human atria. For GJ identification, we recognized N-Cadherin (N-Cad) as part of the gap junction connexin 43 (Cx43) molecular complex. Because N-Cad anchors Cx43 on intercalated discs (ID) to form functional GJ channels on cell membranes, we computationally dilated N-Cad pixels to create N-Cad units that covered all ID-associated Cx43 pixels on Cx43/N-Cad double immunostained confocal images. This approach allowed segmentation between ID-associated and non-ID-associated Cx43. Additionally, use of N-Cad as a unique internal reference with Z-stack layer-by-layer confocal images potentially limits sample processing related artifacts in Cx43 quantification. For IC quantification, color map thresholding of Masson's Trichrome blue stained sections allowed straightforward and automated segmentation of collagen from non-collagen pixels. Our results strongly demonstrate that the two novel image-processing approaches can minimize potential overestimation or underestimation of gap junction and structural remodeling in healthy and pathological hearts. The results of using the two novel methods will significantly improve our understanding of the molecular and structural remodeling associated functional changes in cardiac arrhythmia development in aged and diseased hearts. PMID:25105669

Skeletal muscle design to meet functional demands

PubMed Central

Lieber, Richard L.; Ward, Samuel R.

2011-01-01

Skeletal muscles are length- and velocity-sensitive force producers, constructed of a vast array of sarcomeres. Muscles come in a variety of sizes and shapes to accomplish a wide variety of tasks. How does muscle design match task performance? In this review, we outline muscle's basic properties and strategies that are used to produce movement. Several examples are provided, primarily for human muscles, in which skeletal muscle architecture and moment arms are tailored to a particular performance requirement. In addition, the concept that muscles may have a preferred sarcomere length operating range is also introduced. Taken together, the case is made that muscles can be fine-tuned to perform specific tasks that require actuators with a wide range of properties. PMID:21502118

Comparison of the Effects of Two Different Drinks on Microhardness of a Silorane-based Composite Resin.

PubMed

Sadat HashemiKamangar, Sedighe; Ghavam, Maryam; Mirkhezri, Zhina; Karazifard, Mohammad Javad

2015-09-01

Acidic foods and drinks can erode composite resins. Silorane-based composite is a new low shrinkage composite with higher hydrophobicity which might resist the erosive effect of beverages. The aim of this study was to determine the effects of 100% orange juice and non-alcoholic carbonated beer on microhardness of a silorane-based composite in comparison with two methacrylate-based composite resins. Ninety disc-shaped composite specimens were fabricated of Filtek P90, Filtek Z350 XT Enamel and Filtek Z250 (3M-ESPE) (n=30) and randomly divided into 3 subgroups of 10.Group 1 was immersed in distilled water, group 2 in 100% orange juice, and group 3 in non-alcoholic beer for 3 h/day. Primary, secondary and final Vickers microhardness tests were performed at the beginning of the study and 7 and 28 days later. Surface of 2 specimens in each group was evaluated under scanning electron microscope on day 28. Data were analyzed using repeated measures of ANOVA model (α=0.05). The primary and secondary microhardness of P90 was significantly lower than that of Z350, and Z250 (p< 0.001). Microhardness of Z350 was also lower than that of Z250 (p= 0.002). On day 28, microhardness of P90 was lower than Z250 and Z350 (p< 0.001); however, microhardness values of Z250 and Z350 were not significantly different (p= 0.054). Microhardness of specimens subjected to non-alcoholic beer was significantly lower than that of controls (p= 0.003). Meanwhile, the microhardness value of resins in orange juice was somewhere between the two mentioned values with no significant difference with any of them (p> 0.05). Although 28 days of immersion in 100% orange juice and non-alcoholic beer decreased the microhardness of all specimens, P90 experienced the greatest reduction of microhardness and non-alcoholic beer had the highest effect on reducing microhardness.

Numerical simulations of Z-Pinch experiments to create supersonic differentially-rotating plasma flows

NASA Astrophysics Data System (ADS)

Bocchi, M.; Ummels, B.; Chittenden, J. P.; Lebedev, S. V.

2012-02-01

In the context of high energy density laboratory astrophysics, we aim to produce and study a rotating plasma relevant to accretion discs physics. We devised an experimental setup based on a modified cylindrical wire array and we studied it numerically with the three-dimensional, resistive magneto-hydrodynamic code GORGON. The simulations show that a rotating plasma cylinder is formed, with typical rotation velocity ~35 km/s and Mach number ~5. In addition, the plasma ring is differentially rotating and strongly radiatively cooled. The introduction of external magnetic fields is discussed.

An Experimental Study of Dropwise Condensation on Vertical Discs.

DTIC Science & Technology

1979-12-01

Tested--------------------- 45 Table II. Summary of Heat Transfer Results ---------------- 46 Table III. Thermophysical Properties of Pertinent Materials...flow for selected speci- ments. The values obtained for heat flux agreed within 22 per- cent. Using the values for heat flux, surface temperature and...4 n.* V- 4 n- C\\) *.- --t ~C m, z, C E-1 E-4 E-0 E4 46 N 4) ) Cd 4~ ~ C)4 S ) 0) 4- C) 4 0 4)0 .4E-4 UU I~ U 47 Thermophysical Properties 1. Thermal

Biomechanical behavior of cavity configuration on micropush-out test: a finite-element-study.

PubMed

Cekic-Nagas, Isil; Shinya, Akikazu; Ergun, Gulfem; Vallittu, Pekka K; Lassila, Lippo V J

2011-01-01

The objective of this study was to simulate the micropush-out bond strength test from a biomechanical point of view. For this purpose, stress analysis using finite element (FE) method was performed. Three different occlusal cavity shapes were simulated in disc specimens (model A: 1.5 mm cervical, 2 mm occlusal diameter; model B: 1.5 mm cervical, 1.75 mm occlusal diameter; model C: 1.5 mm cervical, 1.5 mm occlusal diameter). Quarter sizes of 3D FE specimen models of 4.0 x 4.0 x 1.25 mm3 were constructed. In order to avoid quantitative differences in the stress value in the models, models were derived from a single mapping mesh pattern that generated 47.182 elements and 66.853 nodes. The materials that were used were resin composite (Filtek Z250, 3M ESPE), bonding agent (Adper Scotchbond Multi-Purpose, 3M ESPE) and dentin as an isotropic material. Loading conditions consisted of subjecting a press of 4 MPa to the top of the resin composite discs. The postprocessing files allowed the calculation of the maximum principal stress, minimum principal stress and displacement within the disc specimens and stresses at the bonding layer. FE model construction and analysis were performed on PC workstation (Precision Work Station 670, Dell Inc.) using FE analysis program (ANSYS 10 Sp, ANSYS Inc.). Compressive stress concentrations were observed equally in the bottom interface edge of dentin. Tensile stresses were observed on the top area of dentin and at the half of lower side of composite under the loading point in all of the FE models. The FE model revealed differences in displacement and stress between different cavity shaped disc specimens. As the slope of the cavity was increased, the maximum displacement, compressive and tensile stresses also increased.

Effects of local thermodynamics and of stellar mass ratio on accretion disc stability in close binaries

NASA Astrophysics Data System (ADS)

Lanzafame, G.

2009-08-01

Inflow kinematics at the inner Lagrangian point L1, gas compressibility, and physical turbulent viscosity play a fundamental role on accretion disc dynamics and structure in a close binary (CB). Physical viscosity supports the accretion disc development inside the primary gravitational potential well, developing the gas radial transport, converting mechanical energy into heat. The Stellar-Mass-Ratio (SMR) between the compact primary and the secondary star (M1/M2) is also effective, not only in the location of the inner Lagrangian point, but also in the angular kinematics of the mass transfer and in the geometry of the gravitational potential wells. In this work we pay attention in particular to the role of the SMR, evaluating boundaries, separating theoretical domains in compressibility-viscosity graphs where physical conditions allow a well-bound disc development, as a function of mass transfer kinematic conditions. In such domains, the lower is the gas compressibility (the higher the polytropic index γ), the higher is the physical viscosity (α) requested. In this work, we show how the boundaries of such domains vary as a function of M1/M2. Conclusions as far as dwarf novae outbursts are concerned, induced by mass transfer rate variations, are also reported. The smaller M1/M2, the shorter the duration of the active-to-quiet and vice-versa transitional phases. Time-scales are of the order of outburst duration of SU Uma, OY Car, Z Cha and SS Cyg-like objects. Moreover, conclusions as far as active-quiet-active phenomena in a CB, according to viscous-thermal instabilities, in accordance to such domains, are also reported.

Jumping the gap: the formation conditions and mass function of `pebble-pile' planetesimals

NASA Astrophysics Data System (ADS)

Hopkins, Philip F.

2016-03-01

In a turbulent proto-planetary disc, dust grains undergo large-density fluctuations and under the right circumstances, grain overdensities can collapse under self-gravity (forming a `pebble-pile' planetesimal). Using a simple model for fluctuations predicted in simulations, we estimate the rate of formation and mass function of self-gravitating planetesimal-mass bodies formed by this mechanism. This depends sensitively on the grain size, disc surface density, and turbulent Mach numbers. However, when it occurs, the resulting planetesimal mass function is broad and quasi-universal, with a slope dN/dM ∝ M-(1-2), spanning size/mass range ˜10-104 km (˜10-9-5 M⊕). Collapse to planetesimal through super-Earth masses is possible. The key condition is that grain density fluctuations reach large amplitudes on large scales, where gravitational instability proceeds most easily (collapse of small grains is suppressed by turbulence). This leads to a new criterion for `pebble-pile' formation: τs ≳ 0.05 ln (Q1/2/Zd)/ln (1 + 10 α1/4) ˜ 0.3 ψ(Q, Z, α) where τs = ts Ω is the dimensionless particle stopping time. In a minimum-mass solar nebula, this requires grains larger than a = (50, 1, 0.1) cm at r=(1, 30, 100) au}. This may easily occur beyond the ice line, but at small radii would depend on the existence of large boulders. Because density fluctuations depend strongly on τs (inversely proportional to disc surface density), lower density discs are more unstable. Conditions for pebble-pile formation also become more favourable around lower mass, cooler stars.

The three phases of galaxy formation

NASA Astrophysics Data System (ADS)

Clauwens, Bart; Schaye, Joop; Franx, Marijn; Bower, Richard G.

2018-05-01

We investigate the origin of the Hubble sequence by analysing the evolution of the kinematic morphologies of central galaxies in the EAGLE cosmological simulation. By separating each galaxy into disc and spheroidal stellar components and tracing their evolution along the merger tree, we find that the morphology of galaxies follows a common evolutionary trend. We distinguish three phases of galaxy formation. These phases are determined primarily by mass, rather than redshift. For M* ≲ 109.5M⊙ galaxies grow in a disorganised way, resulting in a morphology that is dominated by random stellar motions. This phase is dominated by in-situ star formation, partly triggered by mergers. In the mass range 109.5M⊙ ≲ M* ≲ 1010.5M⊙ galaxies evolve towards a disc-dominated morphology, driven by in-situ star formation. The central spheroid (i.e. the bulge) at z = 0 consists mostly of stars that formed in-situ, yet the formation of the bulge is to a large degree associated with mergers. Finally, at M* ≳ 1010.5M⊙ growth through in-situ star formation slows down considerably and galaxies transform towards a more spheroidal morphology. This transformation is driven more by the buildup of spheroids than by the destruction of discs. Spheroid formation in these galaxies happens mostly by accretion at large radii of stars formed ex-situ (i.e. the halo rather than the bulge).

Negative Inotropic Effects of High Mobility Box Group 1 Protein in Isolated Contracting Cardiac Myocytes

PubMed Central

Tzeng, Huei-Ping; Fan, Jinping; Vallejo, Jesus G.; Dong, Jian Wen; Chen, Xiongwen; Houser, Steven R.; Mann, Douglas L.

2013-01-01

HMGB1 released from necrotic cells or macrophages functions as a late inflammatory mediator, and has been shown to induce cardiovascular collapse during sepsis. Thus far, however, the effect(s) of HMGB1 in the heart are not known. We determined the effects of HMGB1 on isolated feline cardiac myocytes by measuring sarcomere shortening in contracting cardiac myocytes, intracellular Ca2+ transients using fluo-3, and L-type calcium currents using whole cell perforate configuration of the patch clamp technique. Treatment of isolated myocytes with HMGB1 (100 ng/ml) resulted in a 70% decrease in sarcomere shortening and a 50% decrease in the height of the peak Ca++ transient within 5 min (p <0.01). The immediate negative inotropic effects HMGB1 on cell contractility and calcium homeostasis were partially reversible upon washout of HMGB1. A significant inhibition of the inward L-type calcium currents also was documented by the patch clamp technique. HMGB1 induced the PKCε translocation and a PKC inhibitor significantly attenuated the negative inotropic effects of HMGB1. These studies show for the first time that HMGB1 impairs sarcomere shortening by decreasing calcium availability in cardiac myocytes through modulating membrane calcium influx, and suggest that HMGB1 maybe act as a novel myocardial depressant factor during cardiac injury. PMID:18223193

Passive mechanical properties of rat abdominal wall muscles suggest an important role of the extracellular connective tissue matrix.

PubMed

Brown, Stephen H M; Carr, John Austin; Ward, Samuel R; Lieber, Richard L

2012-08-01

Abdominal wall muscles have a unique morphology suggesting a complex role in generating and transferring force to the spinal column. Studying passive mechanical properties of these muscles may provide insights into their ability to transfer force among structures. Biopsies from rectus abdominis (RA), external oblique (EO), internal oblique (IO), and transverse abdominis (TrA) were harvested from male Sprague-Dawley rats, and single muscle fibers and fiber bundles (4-8 fibers ensheathed in their connective tissue matrix) were isolated and mechanically stretched in a passive state. Slack sarcomere lengths were measured and elastic moduli were calculated from stress-strain data. Titin molecular mass was also measured from single muscle fibers. No significant differences were found among the four abdominal wall muscles in terms of slack sarcomere length or elastic modulus. Interestingly, across all four muscles, slack sarcomere lengths were quite long in individual muscle fibers (>2.4 µm), and demonstrated a significantly longer slack length in comparison to fiber bundles (p < 0.0001). Also, the extracellular connective tissue matrix provided a stiffening effect and enhanced the resistance to lengthening at long muscle lengths. Titin molecular mass was significantly less in TrA compared to each of the other three muscles (p < 0.0009), but this difference did not correspond to hypothesized differences in stiffness. Copyright © 2012 Orthopaedic Research Society.

Severe myopathy in mice lacking the MEF2/SRF-dependent gene leiomodin-3

PubMed Central

Cenik, Bercin K.; Garg, Ankit; McAnally, John R.; Shelton, John M.; Richardson, James A.; Bassel-Duby, Rhonda; Olson, Eric N.; Liu, Ning

2015-01-01

Maintenance of skeletal muscle structure and function requires a precise stoichiometry of sarcomeric proteins for proper assembly of the contractile apparatus. Absence of components of the sarcomeric thin filaments causes nemaline myopathy, a lethal congenital muscle disorder associated with aberrant myofiber structure and contractility. Previously, we reported that deficiency of the kelch-like family member 40 (KLHL40) in mice results in nemaline myopathy and destabilization of leiomodin-3 (LMOD3). LMOD3 belongs to a family of tropomodulin-related proteins that promote actin nucleation. Here, we show that deficiency of LMOD3 in mice causes nemaline myopathy. In skeletal muscle, transcription of Lmod3 was controlled by the transcription factors SRF and MEF2. Myocardin-related transcription factors (MRTFs), which function as SRF coactivators, serve as sensors of actin polymerization and are sequestered in the cytoplasm by actin monomers. Conversely, conditions that favor actin polymerization de-repress MRTFs and activate SRF-dependent genes. We demonstrated that the actin nucleator LMOD3, together with its stabilizing partner KLHL40, enhances MRTF-SRF activity. In turn, SRF cooperated with MEF2 to sustain the expression of LMOD3 and other components of the contractile apparatus, thereby establishing a regulatory circuit to maintain skeletal muscle function. These findings provide insight into the molecular basis of the sarcomere assembly and muscle dysfunction associated with nemaline myopathy. PMID:25774500

Post-transcriptional regulation of myotube elongation and myogenesis by Hoi Polloi

PubMed Central

Johnson, Aaron N.; Mokalled, Mayssa H.; Valera, Juliana M.; Poss, Kenneth D.; Olson, Eric N.

2013-01-01

Striated muscle development requires the coordinated expression of genes involved in sarcomere formation and contractility, as well as genes that determine muscle morphology. However, relatively little is known about the molecular mechanisms that control the early stages of muscle morphogenesis. To explore this facet of myogenesis, we performed a genetic screen for regulators of somatic muscle morphology in Drosophila, and identified the putative RNA-binding protein (RBP) Hoi Polloi (Hoip). Hoip is expressed in striated muscle precursors within the muscle lineage and controls two genetically separable events: myotube elongation and sarcomeric protein expression. Myotubes fail to elongate in hoip mutant embryos, even though the known regulators of somatic muscle elongation, target recognition and muscle attachment are expressed normally. In addition, a majority of sarcomeric proteins, including Myosin Heavy Chain (MHC) and Tropomyosin, require Hoip for their expression. A transgenic MHC construct that contains the endogenous MHC promoter and a spliced open reading frame rescues MHC protein expression in hoip embryos, demonstrating the involvement of Hoip in pre-mRNA splicing, but not in transcription, of muscle structural genes. In addition, the human Hoip ortholog NHP2L1 rescues muscle defects in hoip embryos, and knockdown of endogenous nhp2l1 in zebrafish disrupts skeletal muscle development. We conclude that Hoip is a conserved, post-transcriptional regulator of muscle morphogenesis and structural gene expression. PMID:23942517

Myosin-driven rescue of contractile reserve and energetics in mouse hearts bearing familial hypertrophic cardiomyopathy-associated mutant troponin T is mutation-specific.

PubMed

He, Huamei; Hoyer, Kirsten; Tao, Hai; Rice, Ronald; Jimenez, Jesus; Tardiff, Jil C; Ingwall, Joanne S

2012-11-01

The thin filament protein troponin T (TnT) is a regulator of sarcomere function. Whole heart energetics and contractile reserve are compromised in transgenic mice bearing missense mutations at R92 within the tropomyosin-binding domain of cTnT, despite being distal to the ATP hydrolysis domain of myosin. These mutations are associated with familial hypertrophic cardiomyopathy (FHC). Here we test the hypothesis that genetically replacing murine αα-MyHC with murine ββ-MyHC in hearts bearing the R92Q cTnT mutation, a particularly lethal FHC-associated mutation, leads to sufficiently large perturbations in sarcomere function to rescue whole heart energetics and decrease the cost of contraction. By comparing R92Q cTnT and R92L cTnT mutant hearts, we also test whether any rescue is mutation-specific. We defined the energetic state of the isolated perfused heart using (31)P-NMR spectroscopy while simultaneously measuring contractile performance at four work states. We found that the cost of increasing contraction in intact mouse hearts with R92Q cTnT depends on the type of myosin present in the thick filament. We also found that the salutary effect of this manoeuvre is mutation-specific, demonstrating the major regulatory role of cTnT on sarcomere function at the whole heart level.

Unexpectedly low mutation rates in beta-myosin heavy chain and cardiac myosin binding protein genes in Italian patients with hypertrophic cardiomyopathy.

PubMed

Roncarati, Roberta; Latronico, Michael V G; Musumeci, Beatrice; Aurino, Stefania; Torella, Annalaura; Bang, Marie-Louise; Jotti, Gloria Saccani; Puca, Annibale A; Volpe, Massimo; Nigro, Vincenzo; Autore, Camillo; Condorelli, Gianluigi

2011-11-01

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease. Fourteen sarcomeric and sarcomere-related genes have been implicated in HCM etiology, those encoding β-myosin heavy chain (MYH7) and cardiac myosin binding protein C (MYBPC3) reported as the most frequently mutated: in fact, these account for around 50% of all cases related to sarcomeric gene mutations, which are collectively responsible for approximately 70% of all HCM cases. Here, we used denaturing high-performance liquid chromatography followed by bidirectional sequencing to screen the coding regions of MYH7 and MYBPC3 in a cohort (n = 125) of Italian patients presenting with HCM. We found 6 MHY7 mutations in 9/125 patients and 18 MYBPC3 mutations in 19/125 patients. Of the three novel MYH7 mutations found, two were missense, and one was a silent mutation; of the eight novel MYBPC3 mutations, one was a substitution, three were stop codons, and four were missense mutations. Thus, our cohort of Italian HCM patients did not harbor the high frequency of mutations usually found in MYH7 and MYBPC3. This finding, coupled to the clinical diversity of our cohort, emphasizes the complexity of HCM and the need for more inclusive investigative approaches in order to fully understand the pathogenesis of this disease. Copyright © 2011 Wiley-Liss, Inc.

Sarcomere protein gene mutations and inherited heart disease: a beta-cardiac myosin heavy chain mutation causing endocardial fibroelastosis and heart failure.

PubMed

Kamisago, Mitsuhiro; Schmitt, Joachim P; McNamara, Dennis; Seidman, Christine; Seidman, J G

2006-01-01

Inherited human cardiomyopathies often lead to heart failure. A common feature of these conditions is that affected individuals can express the disease causing mutations for many years without showing clinical signs of the disease. Previous studies have demonstrated that sarcomere protein gene mutations can cause either dilated cardiomyopathy or hypertrophic cardiomyopathy. Here we demonstrate that the Arg442His missense mutation in beta-cardiac myosin heavy chain (betaMHC) causes dilated cardiomyopathy, endocardial fibroelastosis and heart failure at a very early age. Using standard genetic engineering tools we and others have made murine models by introducing human disease causing mutations into mice. The central hypothesis of these studies has been that by identifying the pathophysiological pathways activated by these mutations we can define enzymatic activities that are modified during the disease process and which may be involved in pathways that involve more common forms of cardiac disease. Murine models bearing different mutant myosins are being used to address whether each disease causing mutant betaMHC activates the same or different cellular pathways. Dissecting the molecular pathways modulated by mutations in sarcomere protein genes as well as other genes has already demonstrated that there are multiple pathways leading to cardiac remodelling and heart failure. Defining the mechanisms by which mutations in the same genes activate different cellular pathways remains an important question.

Constriction model of actomyosin ring for cytokinesis by fission yeast using a two-state sliding filament mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jung, Yong-Woon; Mascagni, Michael, E-mail: Mascagni@fsu.edu

2014-09-28

We developed a model describing the structure and contractile mechanism of the actomyosin ring in fission yeast, Schizosaccharomyces pombe. The proposed ring includes actin, myosin, and α-actinin, and is organized into a structure similar to that of muscle sarcomeres. This structure justifies the use of the sliding-filament mechanism developed by Huxley and Hill, but it is probably less organized relative to that of muscle sarcomeres. Ring contraction tension was generated via the same fundamental mechanism used to generate muscle tension, but some physicochemical parameters were adjusted to be consistent with the proposed ring structure. Simulations allowed an estimate of ringmore » constriction tension that reproduced the observed ring constriction velocity using a physiologically possible, self-consistent set of parameters. Proposed molecular-level properties responsible for the thousand-fold slower constriction velocity of the ring relative to that of muscle sarcomeres include fewer myosin molecules involved, a less organized contractile configuration, a low α-actinin concentration, and a high resistance membrane tension. Ring constriction velocity is demonstrated as an exponential function of time despite a near linear appearance. We proposed a hypothesis to explain why excess myosin heads inhibit constriction velocity rather than enhance it. The model revealed how myosin concentration and elastic resistance tension are balanced during cytokinesis in S. pombe.« less

Cardiac-specific inactivation of LPP3 in mice leads to myocardial dysfunction and heart failure.

PubMed

Chandra, Mini; Escalante-Alcalde, Diana; Bhuiyan, Md Shenuarin; Orr, Anthony Wayne; Kevil, Christopher; Morris, Andrew J; Nam, Hyung; Dominic, Paari; McCarthy, Kevin J; Miriyala, Sumitra; Panchatcharam, Manikandan

2018-04-01

Lipid Phosphate phosphatase 3 (LPP3), encoded by the Plpp3 gene, is an enzyme that dephosphorylates the bioactive lipid mediator lysophosphatidic acid (LPA). To study the role of LPP3 in the myocardium, we generated a cardiac specific Plpp3 deficient mouse strain. Although these mice were viable at birth in contrast to global Plpp3 knockout mice, they showed increased mortality ~ 8 months. LPP3 deficient mice had enlarged hearts with reduced left ventricular performance as seen by echocardiography. Cardiac specific Plpp3 deficient mice had longer ventricular effective refractory periods compared to their Plpp3 littermates. We observed that lack of Lpp3 enhanced cardiomyocyte hypertrophy based on analysis of cell surface area. We found that lack of Lpp3 signaling was mediated through the activation of Rho and phospho-ERK pathways. There are increased levels of fetal genes Natriuretic Peptide A and B (Nppa and Nppb) expression indicating myocardial dysfunction. These mice also demonstrate mitochondrial dysfunction as evidenced by a significant decrease (P < 0.001) in the basal oxygen consumption rate, mitochondrial ATP production, and spare respiratory capacity as measured through mitochondrial bioenergetics. Histology and transmission electron microscopy of these hearts showed disrupted sarcomere organization and intercalated disc, with a prominent disruption of the cristae and vacuole formation in the mitochondria. Our findings suggest that LPA/LPP3-signaling nexus plays an important role in normal function of cardiomyocytes. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

PKS 2123-463: A Confirmed Gamma-ray Blazar at High Redshift

NASA Technical Reports Server (NTRS)

D'Ammando, F.; Rau, A.; Schady, P.; Finke, J.; Orienti, M.; Greiner, J.; Kann, D. A.; Ojha, R.; Foley, A. R.; Stevens, J.;

An unusual very low-mass high-amplitude pre-main sequence periodic variable

NASA Astrophysics Data System (ADS)

Rodríguez-Ledesma, M. V.; Mundt, R.; Ibrahimov, M.; Messina, S.; Parihar, P.; Hessman, F. V.; Alves de Oliveira, C.; Herbst, W.

2012-08-01

Aims: We have investigated the nature of the variability of CHS 7797, an unusual periodic variable in the Orion Nebula Cluster. Methods: An extensive I-band photometric data set of CHS 7797 was compiled between 2004-2010 using various telescopes. Further optical data have been collected in R and z' bands. In addition, simultaneous observations of the ONC region including CHS 7797 were performed in the I,J,Ks & IRAC 3.6 and 4.5 μm bands over a time interval of ≈40 d. Results: CHS 7797 shows an unusual large-amplitude variation of ≈1.7 mag in the R,I, and z' bands with a period 17.786 ± 0.03 d (FAP = 1 × 10-15%). The amplitude of the brightness modulation decreases only slightly at longer wavelengths. The star is faint during ≈2/3 of the period and the shape of the phased light-curves for the seven different observing seasons shows minor changes and small-amplitude variations. Interestingly, there are no significant colour-flux correlations for λ ≲ 2 μm, while the object becomes redder when fainter at longer wavelengths. CHS 7797 has a spectral type of M 6 and an estimated mass between 0.04-0.1 M⊙. Conclusions: The analysis of the data suggests that the periodic variability of CHS 7797 is most probably caused by an orbital motion. Variability as a result of rotational brightness modulation by a hot spot is excluded by the lack of any colour-brightness correlation in the optical. The latter indicates that CHS 7797 is most probably occulted by circumstellar matter in which grains have grown from typical 0.1 μm to ≈1-2 μm sizes. We discuss two possible scenarios in which CHS 7797 is periodically eclipsed by structures in a disc, namely that CHS 7797 is a single object with a circumstellar disc, or that CHS 7797 is a binary system, similar to KH 15D, in which an inclined circumbinary disc is responsible of the variability. Possible reasons for the typical 0.3 mag variations in I-band at a given phase are discussed.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perry, Theodore Sonne; Dodd, Evan S.; DeVolder, Barbara Gloria

X-ray opacity is a crucial factor in all radiation-hydrodynamics calculations, yet it is one of the least validated of the material properties in simulation codes for high-energy-density plasmas. Recent opacity experiments at the Sandia Z-machine have shown up to factors of two discrepancies between theory and experiment for various mid-Z elements (Fe, Cr, Ni). These discrepancies raise doubts regarding the accuracy of the opacity models which are used in ICF and stewardship as well as in astrophysics. Therefore, a new experimental opacity platform has been developed on the National Ignition Facility (NIF), not only to verify the Z-machine experimental results,more » but also to extend the experiments to other temperatures and densities. Within the context of the national opacity strategy, the first NIF experiments were directed towards measuring the opacity of iron at a temperature of ~160 eV and an electron density of ~7xl021 cm-3(Anchor 1). The Z data agree with theory at these conditions, providing a reference point for validation of the NIF platform. Development shots on NIF have demonstrated the ability to create a sufficiently bright point backlighter using an imploding plastic capsule, and also a combined hohlraum, sample and laser drive able to produce iron plasmas at the desired conditions. Spectrometer qualification has been completed, albeit with additional improvements planned, and the first iron absorption spectra have now been obtained.« less

Mechanotransduction and Metabolism in Cardiomyocyte Microdomains.

PubMed

Pasqualini, Francesco S; Nesmith, Alexander P; Horton, Renita E; Sheehy, Sean P; Parker, Kevin Kit

2016-01-01

Efficient contractions of the left ventricle are ensured by the continuous transfer of adenosine triphosphate (ATP) from energy production sites, the mitochondria, to energy utilization sites, such as ionic pumps and the force-generating sarcomeres. To minimize the impact of intracellular ATP trafficking, sarcomeres and mitochondria are closely packed together and in proximity with other ultrastructures involved in excitation-contraction coupling, such as t-tubules and sarcoplasmic reticulum junctions. This complex microdomain has been referred to as the intracellular energetic unit. Here, we review the literature in support of the notion that cardiac homeostasis and disease are emergent properties of the hierarchical organization of these units. Specifically, we will focus on pathological alterations of this microdomain that result in cardiac diseases through energy imbalance and posttranslational modifications of the cytoskeletal proteins involved in mechanosensing and transduction.

Why do high-redshift galaxies show diverse gas-phase metallicity gradients?

NASA Astrophysics Data System (ADS)

Ma, Xiangcheng; Hopkins, Philip F.; Feldmann, Robert; Torrey, Paul; Faucher-Giguère, Claude-André; Kereš, Dušan

2017-04-01

Recent spatially resolved observations of galaxies at z ˜ 0.6-3 reveal that high-redshift galaxies show complex kinematics and a broad distribution of gas-phase metallicity gradients. To understand these results, we use a suite of high-resolution cosmological zoom-in simulations from the Feedback in Realistic Environments project, which include physically motivated models of the multiphase interstellar medium, star formation and stellar feedback. Our simulations reproduce the observed diversity of kinematic properties and metallicity gradients, broadly consistent with observations at z ˜ 0-3. Strong negative metallicity gradients only appear in galaxies with a rotating disc, but not all rotationally supported galaxies have significant gradients. Strongly perturbed galaxies with little rotation always have flat gradients. The kinematic properties and metallicity gradient of a high-redshift galaxy can vary significantly on short time-scales, associated with starburst episodes. Feedback from a starburst can destroy the gas disc, drive strong outflows and flatten a pre-existing negative metallicity gradient. The time variability of a single galaxy is statistically similar to the entire simulated sample, indicating that the observed metallicity gradients in high-redshift galaxies reflect the instantaneous state of the galaxy rather than the accretion and growth history on cosmological time-scales. We find weak dependence of metallicity gradient on stellar mass and specific star formation rate (sSFR). Low-mass galaxies and galaxies with high sSFR tend to have flat gradients, likely due to the fact that feedback is more efficient in these galaxies. We argue that it is important to resolve feedback on small scales in order to produce the diverse metallicity gradients observed.

Early-type galaxies have been the predominant morphological class for massive galaxies since only z ˜ 1

NASA Astrophysics Data System (ADS)

Buitrago, Fernando; Trujillo, Ignacio; Conselice, Christopher J.; Häußler, Boris

2013-01-01

Present-day massive galaxies are composed mostly of early-type objects. It is unknown whether this was also the case at higher redshifts. In a hierarchical assembling scenario the morphological content of the massive population is expected to change with time from disc-like objects in the early Universe to spheroid-like galaxies at present. In this paper we have probed this theoretical expectation by compiling a large sample of massive (Mstellar ≥ 1011 h- 270 M⊙) galaxies in the redshift interval 0 < z < 3. Our sample of 1082 objects comprises 207 local galaxies selected from Sloan Digital Sky Survey plus 875 objects observed with the Hubble Space Telescope belonging to the Palomar Observatory Wide-field InfraRed/DEEP2 and GOODS NICMOS Survey surveys. 639 of our objects have spectroscopic redshifts. Our morphological classification is performed as close as possible to the optical rest frame according to the photometric bands available in our observations both quantitatively (using the Sérsic index as a morphological proxy) and qualitatively (by visual inspection). Using both techniques we find an enormous change on the dominant morphological class with cosmic time. The fraction of early-type galaxies among the massive galaxy population has changed from ˜20-30 per cent at z ˜ 3 to ˜70 per cent at z = 0. Early-type galaxies have been the predominant morphological class for massive galaxies since only z ˜ 1.

Effect of incorporation of silane in the bonding agent on the repair potential of machinable esthetic blocks

PubMed Central

Zaghloul, Hanaa; Elkassas, Dina Wafik; Haridy, Mohamed Fouad

2014-01-01

Objective: To investigate the repair potential of CAD/CAM (computer-aided design/computer-aided manufacturing) ceramic and composite blocks using a silane-containing bonding agent with different repair protocols. Materials and Methods: Twenty-four discs were constructed from CAD/CAM ceramic and composite blocks. The discs were divided into six groups according to surface pre-treatment employed; GI: Diamond stone roughening (SR), GII: SR+ silanization (SR+S), GIII: Hydrofluoric acid etching (HF), GIV: HF+ silanization (HF+S), GV: Silica coating (SC), GVI: SC+ silanization (SC+S). Silane-containing bonding agent (Single Bond Universal adhesive, 3M ESPE) was applied to the pre-treated discs. Prior to light curing, irises were cut from tygon tubes (internal diameter = 0.8 mm and height = 0.5 mm) and mounted on each treated surface. Nanofilled resin composite (Filtek Z350XT, 3M ESPE) was packed into the cylinder lumen and light-cured (n = 10). The specimens were subjected to microshear bond strength testing (μ-SBS) using universal testing machine. Failure modes of the fractured specimens were analyzed using field emission scanning electron microscope (FESEM). Eight representative discs were prepared to analyze the effect of surface treatments on surface topography using FESEM. μ-SBS results were analyzed using ANOVA and Tukeys post-hoc test. Results: Three-way ANOVA results showed that the materials, surface pre-treatment protocols, and silanization step had a statistically significant effect on the mean μ-SBS values at P ≤ 0.001. For ceramic discs, the groups were ranked; GIV (24.45 ± 7.35)> GVI ((20.18 ± 2.84)> GV (7.14 ± 14)= GII (6.72 ± 1.91)=GI (6.34 ± 2.21)=GIII (5.72 ± 2.18). For composite discs, groups were ranked; GI (24.98 ± 7.69)=GVI (24.84 ± 7.00) >GII (15.85 ± 5.29) =GV (14.65 ± 4.5)= GIV (14.24 ± 2.95)≥ GIII ((9.37 ± 2.78). Conclusion: The additional silanization step cannot be omitted if the repair protocol comprises of either hydrofluoric acid etching or silica coating for both CAD/CAM esthetic restorative materials. However, this step can be suppressed by using silane-containing adhesive with diamond stone roughened repair protocol. PMID:24966745

Myofibril Changes in the Copepod Pseudodiaptomus marinus Exposed to Haline and Thermal Stresses.

PubMed

Ibrahim, Ali; Souissi, Anissa; Leray, Aymeric; Héliot, Laurent; Vandenbunder, Bernard; Souissi, Sami

2016-01-01

Copepods are small crustaceans capable to survive in various aquatic environments. Their responses to changes in different external factors such as salinity and temperature can be observed at different integration levels from copepod genes to copepod communities. Until now, no thorough observation of the temperature or salinity effect stresses on copepods has been done by optical microscopy. In this study, we used autofluorescence to visualize these effects on the morphology of the calanoid copepod Pseudodiaptomus marinus maintained during several generations in the laboratory at favorable and stable conditions of salinity (30 psu) and temperature (18°C). Four different stress experiments were conducted: at a sharp decrease in temperature (18 to 4°C), a moderate decrease in salinity (from 30 to 15 psu), a major decrease in salinity (from 30 to 0 psu), and finally a combined stress with a decrease in both temperature and salinity (from 18°C and 30 psu to 4°C and 0 psu). After these stresses, images acquired by confocal laser scanning microscopy (CLSM) revealed changes in copepod cuticle and muscle structure. Low salinity and/or temperature stresses affected both the detection of fluorescence emitted by muscle sarcomeres and the distance between them. In the remaining paper we will use the term sarcomeres to describe the elements located within sarcomeres and emitted autofluorescence signals. Quantitative study showed an increase in the average distance between two consecutive sarcomeres from 2.06 +/- 0.11 μm to 2.44 +/- 0.42 μm and 2.88 +/- 0.45μm after the exposure to major haline stress (18°C, 0 psu) and the combined stress (4°C, 0 psu), respectively. These stresses also caused cuticle cracks which often occurred at the same location, suggesting the cuticle as a sensitive area for osmoregulation. Our results suggest the use of cuticular and muscle autofluorescence as new biomarkers of stress detectable in formalin-preserved P. marinus individuals. Our label-free method can be easily applied to a large number of other copepod species or invertebrates with striated musculature.

Thin filament length in the cardiac sarcomere varies with sarcomere length but is independent of titin and nebulin.

PubMed

Kolb, Justin; Li, Frank; Methawasin, Mei; Adler, Maya; Escobar, Yael-Natalie; Nedrud, Joshua; Pappas, Christopher T; Harris, Samantha P; Granzier, Henk

2016-08-01

Thin filament length (TFL) is an important determinant of the force-sarcomere length (SL) relation of cardiac muscle. However, the various mechanisms that control TFL are not well understood. Here we tested the previously proposed hypothesis that the actin-binding protein nebulin contributes to TFL regulation in the heart by using a cardiac-specific nebulin cKO mouse model (αMHC Cre Neb cKO). Atrial myocytes were studied because nebulin expression has been reported to be most prominent in this cell type. TFL was measured in right and left atrial myocytes using deconvolution optical microscopy and staining for filamentous actin with phalloidin and for the thin filament pointed-end with an antibody to the capping protein Tropomodulin-1 (Tmod1). Results showed that TFLs in Neb cKO and littermate control mice were not different. Thus, deletion of nebulin in the heart does not alter TFL. However, TFL was found to be ~0.05μm longer in the right than in the left atrium and Tmod1 expression was increased in the right atrium. We also tested the hypothesis that the length of titin's spring region is a factor controlling TFL by studying the Rbm20(ΔRRM) mouse which expresses titins that are ~500kDa (heterozygous mice) and ~1000kDa (homozygous mice) longer than in control mice. Results revealed that TFL was not different in Rbm20(ΔRRM) mice. An unexpected finding in all genotypes studied was that TFL increased as sarcomeres were stretched (~0.1μm per 0.35μm of SL increase). This apparent increase in TFL reached a maximum at a SL of ~3.0μm where TFL was ~1.05μm. The SL dependence of TFL was independent of chemical fixation or the presence of cardiac myosin-binding protein C (cMyBP-C). In summary, we found that in cardiac myocytes TFL varies with SL in a manner that is independent of the size of titin or the presence of nebulin. Copyright © 2016. Published by Elsevier Ltd.

Sarcomere length dependence of rat skinned cardiac myocyte mechanical properties: dependence on myosin heavy chain

PubMed Central

Korte, F Steven; McDonald, Kerry S

2007-01-01

The effects of sarcomere length (SL) on sarcomeric loaded shortening velocity, power output and rates of force development were examined in rat skinned cardiac myocytes that contained either α-myosin heavy chain (α-MyHC) or β-MyHC at 12 ± 1°C. When SL was decreased from 2.3 μm to 2.0 μm submaximal isometric force decreased ∼40% in both α-MyHC and β-MyHC myocytes while peak absolute power output decreased 55% in α-MyHC myocytes and 70% in β-MyHC myocytes. After normalization for the fall in force, peak power output decreased about twice as much in β-MyHC as in α-MyHC myocytes (41%versus 20%). To determine whether the fall in normalized power was due to the lower force levels, [Ca2+] was increased at short SL to match force at long SL. Surprisingly, this led to a 32% greater peak normalized power output at short SL compared to long SL in α-MyHC myocytes, whereas in β-MyHC myocytes peak normalized power output remained depressed at short SL. The role that interfilament spacing plays in determining SL dependence of power was tested by myocyte compression at short SL. Addition of 2% dextran at short SL decreased myocyte width and increased force to levels obtained at long SL, and increased peak normalized power output to values greater than at long SL in both α-MyHC and β-MyHC myocytes. The rate constant of force development (ktr) was also measured and was not different between long and short SL at the same [Ca2+] in α-MyHC myocytes but was greater at short SL in β-MyHC myocytes. At short SL with matched force by either dextran or [Ca2+], ktr was greater than at long SL in both α-MyHC and β-MyHC myocytes. Overall, these results are consistent with the idea that an intrinsic length component increases loaded crossbridge cycling rates at short SL and β-MyHC myocytes exhibit a greater sarcomere length dependence of power output. PMID:17347271

A Hypertrophic Cardiomyopathy-associated MYBPC3 Mutation Common in Populations of South Asian Descent Causes Contractile Dysfunction*

PubMed Central

Kuster, Diederik W. D.; Govindan, Suresh; Springer, Tzvia I.; Martin, Jody L.; Finley, Natosha L.; Sadayappan, Sakthivel

2015-01-01

Hypertrophic cardiomyopathy (HCM) results from mutations in genes encoding sarcomeric proteins, most often MYBPC3, which encodes cardiac myosin binding protein-C (cMyBP-C). A recently discovered HCM-associated 25-base pair deletion in MYBPC3 is inherited in millions worldwide. Although this mutation causes changes in the C10 domain of cMyBP-C (cMyBP-CC10mut), which binds to the light meromyosin (LMM) region of the myosin heavy chain, the underlying molecular mechanism causing HCM is unknown. In this study, adenoviral expression of cMyBP-CC10mut in cultured adult rat cardiomyocytes was used to investigate protein localization and evaluate contractile function and Ca2+ transients, compared with wild-type cMyBP-C expression (cMyBP-CWT) and controls. Forty-eight hours after infection, 44% of cMyBP-CWT and 36% of cMyBP-CC10mut protein levels were determined in total lysates, confirming equal expression. Immunofluorescence experiments showed little or no localization of cMyBP-CC10mut to the C-zone, whereas cMyBP-CWT mostly showed C-zone staining, suggesting that cMyBP-CC10mut could not properly integrate in the C-zone of the sarcomere. Subcellular fractionation confirmed that most cMyBP-CC10mut resided in the soluble fraction, with reduced presence in the myofilament fraction. Also, cMyBP-CC10mut displayed significantly reduced fractional shortening, sarcomere shortening, and relaxation velocities, apparently caused by defects in sarcomere function, because Ca2+ transients were unaffected. Co-sedimentation and protein cross-linking assays confirmed that C10mut causes the loss of C10 domain interaction with myosin LMM. Protein homology modeling studies showed significant structural perturbation in cMyBP-CC10mut, providing a potential structural basis for the alteration in its mode of interaction with myosin LMM. Therefore, expression of cMyBP-CC10mut protein is sufficient to cause contractile dysfunction in vitro. PMID:25583989

A Bridging Water Anchors the Tethered 5-(3-Aminopropyl)-2′-deoxyuridine Amine in the DNA Major Groove Proximate to the N+2 C·G Base Pair: Implications for Formation of Interstrand 5′-GNC-3′ Cross-Links by Nitrogen Mustards‡

PubMed Central

Wang, Feng; Li, Feng; Ganguly, Manjori; Marky, Luis A.; Gold, Barry; Egli, Martin; Stone, Michael P.

2009-01-01

Site-specific insertion of 5-(3-aminopropyl)-2′-deoxyuridine (Z3dU) and 7-deaza-dG into the Dickerson-Drew dodecamers 5′-d(C1G2C3G4A5A6T7T8C9Z10C11G12)-3′ · 5′-d(C13G14C15G16A17A18T19T20-C21Z22C23G24)-3′ (named DDDZ10) and 5′-d(C1G2C3G4A5A6T7X8C9Z10C11G12)-3′ · 5′-d(C13G14C15G16A17A18-T19X20C21Z22C23G24)-3′ (named DDD2+Z10)(X = Z3dU; Z = 7-deaza-dG) suggests a mechanism underlying the formation of interstrand N+2 DNA cross-links by nitrogen mustards, e.g., melphalan and mechlorethamine. Analysis of the DDD2+Z10 duplex reveals that the tethered cations at base pairs A5 · X20 and X8 · A17 extend within the major groove in the 3′-direction, toward conserved Mg2+ binding sites located adjacent to N+2 base pairs C3 · Z22 and Z10 · C15. Bridging waters located between the tethered amines and either Z10 or Z22 O6 stabilize the tethered cations and allow interactions with the N + 2 base pairs without DNA bending. Incorporation of 7-deaza-dG into the DDD2+Z10 duplex weakens but does not eliminate electrostatic interactions between tethered amines and Z10 O6 and Z22 O6. The results suggest a mechanism by which tethered N7-dG aziridinium ions, the active species involved in formation of interstrand 5′-GNC-3′ cross-links by nitrogen mustards, modify the electrostatics of the major groove and position the aziridinium ions proximate to the major groove edge of the N+2 C · G base pair, facilitating interstrand cross-linking. PMID:18549246

Effect of bleaching on color change and surface topography of composite restorations.

PubMed

Pruthi, Gunjan; Jain, Veena; Kandpal, H C; Mathur, Vijay Prakash; Shah, Naseem

2010-01-01

This study was conducted to determine the effect of 15% carbamide peroxide bleaching agent on color change and surface topography of different composite veneering materials (Filtek Z350 (3M ESPE), Esthet X (Dentsply India), and Admira (Voco, Germany). Methods. 30 samples were fabricated for evaluation of color change using CIELAB color system and Gonioreflectometer (GK 311/M, ZEISS). 45 disc-shaped specimens were made for evaluation of surface topography after bleaching (Nupro White Gold; Dentsply) using SEM. Statistical analysis. One way ANOVA and Multiple comparison tests were used to analyze the data. Statistical significance was declared if the P value was .05 or less. Results and conclusion. All the specimens showed significant discoloration (ΔE > 3.3) after their immersion in solutions representing food and beverages. The total color change after bleaching as compared to baseline color was significant in Filtek Z350 (P = .000) and Esthet X (P = .002), while it was insignificant for Admira (P = .18). Esthet X showed maximum surface roughness followed by Admira and Filtek Z350. Bleaching was effective in reducing the discoloration to a clinically acceptable value in all the three groups (ΔE < 3.3).

In vitro synergistic antibacterial activity of the essential oil from Zingiber cassumunar Roxb against extensively drug-resistant Acinetobacter baumannii strains.

PubMed

Boonyanugomol, Wongwarut; Kraisriwattana, Kairin; Rukseree, Kamolchanok; Boonsam, Kraisorn; Narachai, Panchaporn

In this study, we determined the antibacterial and synergistic activities of the essential oil from Zingiber cassumunar against the extensively drug-resistant (XDR) Acinetobacter baumannii strains. The antibacterial and synergistic properties of the essential oil from Z. cassumunar were examined by agar disc diffusion tests. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated by broth microdilution using the resazurin assay. The in vitro time-kill antibacterial kinetics was analyzed using the plate count technique. We found that the essential oil from Z. cassumunar had antibacterial activity against A. baumannii, with MIC and MBC ranging from 7.00 to 9.24mg/ml. The essential oil could completely inhibit A. baumannii at 1h, and coccoid-shaped bacteria were found after treatment. In addition, the essential oil had a synergistic effect when combined with antibiotics, e.g., aminoglycosides, fluoroquinolones, tetracyclines, and folate pathway inhibitors. Thus, the essential oil from Z. cassumunar has strong antibacterial and synergistic activities against XDR A. baumannii, which may provide the basis for the development of a new therapy against drug-resistant bacteria. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

LOGMARS (Logistics Applications of Automated Marking and Reading Symbols) Clearinghouse. Applications Directory.

DTIC Science & Technology

1985-09-01

iD- A1t62 3 ? LOOM S (LOGISTICS APPLIC TIONS OF UTO NTED M ARING 1/2 WARND READING SYMBOLS) C EARINGHOUSE APPLICATIONS DIRECTORY(U) DEFENSE GENERAL...Rubin Patterson, SC, USN, DLA DMECSO, (AV) 695-4787. 1 Encl T. R. WILD Captain, SC, U. S . Navy Chief, DLA Depot Mechanization Support Office cc; . DLA-OW...DIc.-TRIBUTrION: DLA-L DLA-Z DLA-ZS DLA- S DLA-WS DGSC-T * DPSC-C DCSC-T DFSC-W DESC-L - DESC-Q * DISC-LO * DDOU-T DDt4P--T - - DDTC-T DDMT-T DRMS DSAC

Genetics Home Reference: nemaline myopathy

MedlinePlus

... nemaline myopathy interact within the sarcomere to facilitate muscle contraction. When the skeletal muscle cells of people with ... The disorganized proteins cannot interact normally, which disrupts muscle contraction. Inefficient muscle contraction leads to muscle weakness and ...

Capillary muscle

PubMed Central

Cohen, Caroline; Mouterde, Timothée; Quéré, David; Clanet, Christophe

2015-01-01

The contraction of a muscle generates a force that decreases when increasing the contraction velocity. This “hyperbolic” force–velocity relationship has been known since the seminal work of A. V. Hill in 1938 [Hill AV (1938) Proc R Soc Lond B Biol Sci 126(843):136–195]. Hill’s heuristic equation is still used, and the sliding-filament theory for the sarcomere [Huxley H, Hanson J (1954) Nature 173(4412):973–976; Huxley AF, Niedergerke R (1954) Nature 173(4412):971–973] suggested how its different parameters can be related to the molecular origin of the force generator [Huxley AF (1957) Prog Biophys Biophys Chem 7:255–318; Deshcherevskiĭ VI (1968) Biofizika 13(5):928–935]. Here, we develop a capillary analog of the sarcomere obeying Hill’s equation and discuss its analogy with muscles. PMID:25944938

Mechanotransduction and Metabolism in Cardiomyocyte Microdomains

PubMed Central

Nesmith, Alexander P.; Horton, Renita E.; Sheehy, Sean P.; Parker, Kevin Kit

2016-01-01

Efficient contractions of the left ventricle are ensured by the continuous transfer of adenosine triphosphate (ATP) from energy production sites, the mitochondria, to energy utilization sites, such as ionic pumps and the force-generating sarcomeres. To minimize the impact of intracellular ATP trafficking, sarcomeres and mitochondria are closely packed together and in proximity with other ultrastructures involved in excitation-contraction coupling, such as t-tubules and sarcoplasmic reticulum junctions. This complex microdomain has been referred to as the intracellular energetic unit. Here, we review the literature in support of the notion that cardiac homeostasis and disease are emergent properties of the hierarchical organization of these units. Specifically, we will focus on pathological alterations of this microdomain that result in cardiac diseases through energy imbalance and posttranslational modifications of the cytoskeletal proteins involved in mechanosensing and transduction. PMID:28044126

Some distinctive features of zebrafish myogenesis based on unexpected distributions of the muscle cytoskeletal proteins actin, myosin, desmin, alpha-actinin, troponin and titin.

PubMed

Costa, Manoel L; Escaleira, Roberta C; Rodrigues, Viviane B; Manasfi, Muhamed; Mermelstein, Claudia S

2002-08-01

The current myofibrillogenesis model is based mostly on in vitro cell cultures and on avian and mammalian embryos in situ. We followed the expression of actin, myosin, desmin, alpha-actinin, titin, and troponin using immunofluorescence microscopy of zebrafish (Danio rerio) embryos. We could see young mononucleated myoblasts with sharp striations. The striations were positive for all the sarcomeric proteins. Desmin distribution during muscle maturation changes from dispersed aggregates to a perinuclear concentration to striated afterwards. We could not observe desmin-positive, myofibrillar-proteins-negative cells, and we could not find any non-striated distribution of sarcomeric proteins, such as stress fiber-like structures. Some steps, like fusion before striation, seem to be different in the zebrafish when compared with the previously described myogenesis sequences.

VizieR Online Data Catalog: Massive early-type galaxies (Buitrago+, 2013)

NASA Astrophysics Data System (ADS)

Buitrago, F.; Trujillo, I.; Conselice, C. J.; Haussler, B.

2013-08-01

Present-day massive galaxies are composed mostly of early-type objects. It is unknown whether this was also the case at higher redshifts. In a hierarchical assembling scenario the morphological content of the massive population is expected to change with time from disc-like objects in the early Universe to spheroid-like galaxies at present. In this paper we have probed this theoretical expectation by compiling a large sample of massive (Mstellar>=1011h-270M⊙) galaxies in the redshift interval 0

Rigor mortis development at elevated temperatures induces pale exudative turkey meat characteristics.

PubMed

McKee, S R; Sams, A R

1998-01-01

Development of rigor mortis at elevated post-mortem temperatures may contribute to turkey meat characteristics that are similar to those found in pale, soft, exudative pork. To evaluate this effect, 36 Nicholas tom turkeys were processed at 19 wk of age and placed in water at 40, 20, and 0 C immediately after evisceration. Pectoralis muscle samples were taken at 15 min, 30 min, 1 h, 2 h, and 4 h post-mortem and analyzed for R-value (an indirect measure of adenosine triphosphate), glycogen, pH, color, and sarcomere length. At 4 h, the remaining intact Pectoralis muscle was harvested, and aged on ice 23 h, and analyzed for drip loss, cook loss, shear values, and sarcomere length. By 15 min post-mortem, the 40 C treatment had higher R-values, which persisted through 4 h. By 1 h, the 40 C treatment pH and glycogen levels were lower than the 0 C treatment; however, they did not differ from those of the 20 C treatment. Increased L* values indicated that color became more pale by 2 h post-mortem in the 40 C treatment when compared to the 20 and 0 C treatments. Drip loss, cook loss, and shear value were increased whereas sarcomere lengths were decreased as a result of the 40 C treatment. These findings suggested that elevated post-mortem temperatures during processing resulted in acceleration of rigor mortis and biochemical changes in the muscle that produced pale, exudative meat characteristics in turkey.

Persistent fibrosis, hypertrophy and sarcomere disorganisation after endoscopy-guided heart resection in adult Xenopus

PubMed Central

Girardot, Fabrice; Péricard, Louise; Demeneix, Barbara A.; Coen, Laurent; Chai, Norin

2017-01-01

Models of cardiac repair are needed to understand mechanisms underlying failure to regenerate in human cardiac tissue. Such studies are currently dominated by the use of zebrafish and mice. Remarkably, it is between these two evolutionary separated species that the adult cardiac regenerative capacity is thought to be lost, but causes of this difference remain largely unknown. Amphibians, evolutionary positioned between these two models, are of particular interest to help fill this lack of knowledge. We thus developed an endoscopy-based resection method to explore the consequences of cardiac injury in adult Xenopus laevis. This method allowed in situ live heart observation, standardised tissue amputation size and reproducibility. During the first week following amputation, gene expression of cell proliferation markers remained unchanged, whereas those relating to sarcomere organisation decreased and markers of inflammation, fibrosis and hypertrophy increased. One-month post-amputation, fibrosis and hypertrophy were evident at the injury site, persisting through 11 months. Moreover, cardiomyocyte sarcomere organisation deteriorated early following amputation, and was not completely recovered as far as 11 months later. We conclude that the adult Xenopus heart is unable to regenerate, displaying cellular and molecular marks of scarring. Our work suggests that, contrary to urodeles and teleosts, with the exception of medaka, adult anurans share a cardiac injury outcome similar to adult mammals. This observation is at odds with current hypotheses that link loss of cardiac regenerative capacity with acquisition of homeothermy. PMID:28278282

Myosin-driven rescue of contractile reserve and energetics in mouse hearts bearing familial hypertrophic cardiomyopathy-associated mutant troponin T is mutation-specific

PubMed Central

He, Huamei; Hoyer, Kirsten; Tao, Hai; Rice, Ronald; Jimenez, Jesus; Tardiff, Jil C; Ingwall, Joanne S

2012-01-01

The thin filament protein troponin T (TnT) is a regulator of sarcomere function. Whole heart energetics and contractile reserve are compromised in transgenic mice bearing missense mutations at R92 within the tropomyosin-binding domain of cTnT, despite being distal to the ATP hydrolysis domain of myosin. These mutations are associated with familial hypertrophic cardiomyopathy (FHC). Here we test the hypothesis that genetically replacing murine αα-MyHC with murine ββ-MyHC in hearts bearing the R92Q cTnT mutation, a particularly lethal FHC-associated mutation, leads to sufficiently large perturbations in sarcomere function to rescue whole heart energetics and decrease the cost of contraction. By comparing R92Q cTnT and R92L cTnT mutant hearts, we also test whether any rescue is mutation-specific. We defined the energetic state of the isolated perfused heart using 31P-NMR spectroscopy while simultaneously measuring contractile performance at four work states. We found that the cost of increasing contraction in intact mouse hearts with R92Q cTnT depends on the type of myosin present in the thick filament. We also found that the salutary effect of this manoeuvre is mutation-specific, demonstrating the major regulatory role of cTnT on sarcomere function at the whole heart level. PMID:22907055

Allosteric modulation of cardiac myosin dynamics by omecamtiv mecarbil

PubMed Central

Tiberti, Matteo

2017-01-01

New promising avenues for the pharmacological treatment of skeletal and heart muscle diseases rely on direct sarcomeric modulators, which are molecules that can directly bind to sarcomeric proteins and either inhibit or enhance their activity. A recent breakthrough has been the discovery of the myosin activator omecamtiv mecarbil (OM), which has been shown to increase the power output of the cardiac muscle and is currently in clinical trials for the treatment of heart failure. While the overall effect of OM on the mechano-chemical cycle of myosin is to increase the fraction of myosin molecules in the sarcomere that are strongly bound to actin, the molecular basis of its action is still not completely clear. We present here a Molecular Dynamics study of the motor domain of human cardiac myosin bound to OM, where the effects of the drug on the dynamical properties of the protein are investigated for the first time with atomistic resolution. We found that OM has a double effect on myosin dynamics, inducing a) an increased coupling of the motions of the converter and lever arm subdomains to the rest of the protein and b) a rewiring of the network of dynamic correlations, which produces preferential communication pathways between the OM binding site and distant functional regions. The location of the residues responsible for these effects suggests possible strategies for the future development of improved drugs and the targeting of specific cardiomyopathy-related mutations. PMID:29108014

The Large Area Radio Galaxy Evolution Spectroscopic Survey (LARGESS): survey design, data catalogue and GAMA/WiggleZ spectroscopy

NASA Astrophysics Data System (ADS)

Ching, John H. Y.; Sadler, Elaine M.; Croom, Scott M.; Johnston, Helen M.; Pracy, Michael B.; Couch, Warrick J.; Hopkins, A. M.; Jurek, Russell J.; Pimbblet, K. A.

2017-01-01

We present the Large Area Radio Galaxy Evolution Spectroscopic Survey (LARGESS), a spectroscopic catalogue of radio sources designed to include the full range of radio AGN populations out to redshift z ˜ 0.8. The catalogue covers ˜800 deg2 of sky, and provides optical identifications for 19 179 radio sources from the 1.4 GHz Faint Images of the Radio Sky at Twenty-cm (FIRST) survey down to an optical magnitude limit of Imod < 20.5 in Sloan Digital Sky Survey (SDSS) images. Both galaxies and point-like objects are included, and no colour cuts are applied. In collaboration with the WiggleZ and Galaxy And Mass Assembly (GAMA) spectroscopic survey teams, we have obtained new spectra for over 5000 objects in the LARGESS sample. Combining these new spectra with data from earlier surveys provides spectroscopic data for 12 329 radio sources in the survey area, of which 10 856 have reliable redshifts. 85 per cent of the LARGESS spectroscopic sample are radio AGN (median redshift z = 0.44), and 15 per cent are nearby star-forming galaxies (median z = 0.08). Low-excitation radio galaxies (LERGs) comprise the majority (83 per cent) of LARGESS radio AGN at z < 0.8, with 12 per cent being high-excitation radio galaxies (HERGs) and 5 per cent radio-loud QSOs. Unlike the more homogeneous LERG and QSO sub-populations, HERGs are a heterogeneous class of objects with relatively blue optical colours and a wide dispersion in mid-infrared colours. This is consistent with a picture in which most HERGs are hosted by galaxies with recent or ongoing star formation as well as a classical accretion disc.

Computer Simulation of an Aircraft Seat and Occupant in a Crash Environment. Volume 1. Technical Report

DTIC Science & Technology

1983-03-01

q18 q2 8 q 2 q1 9 = 06q 2 9 812 7 (11)1q0 3 q 2 0 : ś The above coordinates include the Cartesian coordinates of the mass ce-nter of segment 1 ( Xl ...l P0 zC SC Lap Lap belt anchor point ( XL ’ YL’ ZL) 0 Inertial coordinate system Figure 30. Forces acting on occupant torso (nose-down attitude). 87...position calculated by equation (104) for the level flight assumption. The angle is defined according to 0 = sin-- ZL)/ X - XL )2 + (Zp - ZL)2 (106

Enzyme-linked immunosorbent assays for Z-DNA.

PubMed

Thomas, M J; Strobl, J S

1988-10-01

Dot blot and transblot enzyme-linked immunosorbent assays (e.l.i.s.a.) are described which provide sensitive non-radioactive methods for screening Z-DNA-specific antisera and for detecting Z-DNA in polydeoxyribonucleotides and supercoiled plasmids. In the alkaline phosphatase dot blot e.l.i.s.a., Z-DNA, Br-poly(dG-dC).poly(dG-dC), or B-DNA, poly(dG-dC).poly(dG-dC), poly(dA-dT).poly(dA-dT), Br-poly(dI-dC).poly(dI-dC), or salmon sperm DNA were spotted onto nitrocellulose discs and baked. The e.l.i.s.a. was conducted in 48-well culture dishes at 37 degrees C using a rabbit polyclonal antiserum developed against Br-poly(dG-dC).poly(dG-dC), an alkaline phosphatase-conjugated second antibody, and p-nitrophenol as the substrate. Under conditions where antibody concentrations were not limiting, alkaline phosphatase activity was linear for 2 h. Dot blot e.l.i.s.a. conditions are described which allow quantification of Z-DNA [Br-poly(dG-dC).poly(dG-dC)] within the range 5-250 ng. Dot blot and transblot horseradish peroxidase e.l.i.s.a. are described that detect Z-DNA within supercoiled plasmid DNAs immobilized on diazophenylthioether (DPT) paper. In the transblot e.l.i.s.a., plasmid pUC8 derivatives containing 16, 24, or 32 residues of Z-DNA were electrophoresed in agarose gels and electrophoretically transferred to DPT paper. Z-DNA-antibody complexes were detected by the horseradish peroxidase-catalysed conversion of 4-chloro-1-naphthol to a coloured product that was covalently bound to the DPT paper. Z-DNA antibody reactivity was specific for supercoiled Z-DNA containing plasmids after removal of the antibodies cross-reactive with B-DNA by absorption onto native DNA-cellulose. The transblot e.l.i.s.a. was sensitive enough to detect 16 base pairs of alternating G-C residues in 100 ng of pUC8 DNA.

Light microscopy and image analysis of thin filament lengths utilizing dual probes on beef, chicken, and rabbit myofibrils.

PubMed

Ringkob, T P; Swartz, D R; Greaser, M L

2004-05-01

Image analysis procedures for immunofluorescence microscopy were developed to measure muscle thin filament lengths of beef, rabbit, and chicken myofibrils. Strips of beef cutaneous trunci, rectus abdominis, psoas, and masseter; chicken pectoralis; and rabbit psoas muscles were excised 5 to 30 min postmortem. Fluorescein phalloidin and rhodamine myosin subfragment-1 (S1) were used to probe the myofibril structure. Digital images were recorded with a cooled charge-coupled device controlled with IPLab Spectrum software (Signal Analytics Corp.) on a Macintosh operating system. The camera was attached to an inverted microscope, using both the phase-contrast and fluorescence illumination modes. Unfixed myofibrils incubated with fluorescein phalloidin showed fluorescence primarily at the Z-line and the tips of the thin filaments in the overlap region. Images were processed using IPLab and the National Institutes of Health's Image software. A region of interest was selected and scaled by a factor of 18.18, which enlarged the image from 11 pixels/microm to approximately 200 pixels/microm. An X-Y plot was exported to Spectrum 1.1 (Academic Software Development Group), where the signal was processed with a second derivative routine, so a cursor function could be used to measure length. Fixation before phalloidin incubation resulted in greatest intensity at the Z lines but a more-uniform staining over the remainder of the thin filament zone. High-resolution image capture and processing showed that thin filament lengths were significantly different (P < 0.01) among beef, rabbit, and chicken, with lengths of 1.28 to 1.32 microm, 1.16 microm, and 1.05 microm, respectively. Measurements using the S1 signal confirmed the phalloidin results. Fluorescent probes may be useful to study sarcomere structure and help explain species and muscle differences in meat texture.

Dominant negative Ras attenuates pathological ventricular remodeling in pressure overload cardiac hypertrophy

PubMed Central

Ramos-Kuri, Manuel; Rapti, Kleopatra; Mehel, Hind; Zhang, Shihong; Dhandapany, Perundurai S.; Liang, Lifan; García-Carrancá, Alejandro; Bobe, Regis; Fischmeister, Rodolphe; Adnot, Serge; Lebeche, Djamel; Hajjar, Roger J.; Lipskaia, Larissa; Chemaly, Elie R.

2015-01-01

The importance of the oncogene Ras in cardiac hypertrophy is well appreciated. The hypertrophic effects of the constitutively active mutant Ras-Val12 are revealed by clinical syndromes due to the Ras mutations and experimental studies. We examined the possible anti-hypertrophic effect of Ras inhibition in vitro using rat neonatal cardiomyocytes (NRCM) and in vivo in the setting of pressure-overload left ventricular (LV) hypertrophy (POH) in rats. Ras functions were modulated via adenovirus directed gene transfer of active mutant Ras-Val12 or dominant negative mutant N17-DN-Ras (DN-Ras). Ras-Val12 expression in vitro activates NFAT resulting in pro-hypertrophic and cardio-toxic effects on NRCM beating and Z-line organization. In contrast, the DN-Ras was antihypertrophic on NRCM, inhibited NFAT and exerted cardio-protective effects attested by preserved NRCM beating and Z line structure. Additional experiments with silencing H-Ras gene strategy corroborated the antihypertrophic effects of siRNA-H-Ras on NRCM. In vivo, with the POH model, both Ras mutants were associated with similar hypertrophy two weeks after simultaneous induction of POH and Ras-mutant gene transfer. However, LV diameters were higher and LV fractional shortening lower in the Ras-Val12 group compared to control and DN-Ras. Moreover, DN-Ras reduced the cross-sectional area of cardiomyocytes in vivo, and decreased the expression of markers of pathologic cardiac hypertrophy. In isolated adult cardiomyocytes after 2 weeks of POH and Ras-mutant gene transfer, DN-Ras improved sarcomere shortening and calcium transients compared to Ras-Val12. Overall, DN-Ras promotes a more physiological form of hypertrophy, suggesting an interesting therapeutic target for pathological cardiac hypertrophy. PMID:26260012

[COMPARISON OF EFFECTIVENESS BETWEEN TWO OPERATIVE TECHNIQUES OF CORACOCLAVICULAR LIGAMENT RECONSTRUCTION FOR TREATMENT OF Tossy TYPE III ACROMIOCLAVICULAR JOINT DISLOCATION].

PubMed

Tang, Hongwei; Gao, Sheng; Yin, Yong; Li, Yunfei; Han, Qingtian; Li, Huizhang

2015-11-01

To evaluate and compare the effectiveness of double Endobutton technique and suture anchor combined Endobutton plate in the treatment of Tossy type III acromioclavicular joint dislocation. Between May 2010 and March 2014, a retrospective study was preformed on 56 patients with Tossy type III acromioclavicular joint dislocation. The coracoclavicular ligament was reconstructed with double Endobutton technique in 31 cases (Endobutton group), and with suture anchor combined Endobutton plate in 25 cases (Anchor group). There was no significant difference in age, gender, injury causes, injury side, associated injury, medical comorbidities, and disease duration between 2 groups (P>0.05). The operation time, medical device expenses, postoperative complications, preoperative and postoperative Constant-Murley scores, and postoperative Karlsson grading of the injured shoulder were compared between 2 groups. The average operation time in Endobutton group was significantly greater than that in Anchor group (t = 4.285, P = 0.000); there was no significant difference in the medical device expenses between 2 groups (t = 1.555, P = 0.126). Primary healing of incision was obtained in all patients of 2 groups; no early complications of infection and skin necrosis occurred. All patients were followed up 15.6 months on average (range, 11-35 months). During follow-up, some loss of reduction and ectopic ossification in the coracoclavicular gap were observed in 1 case and 6 cases of Endobutton group, respectively. No recurrence of acromioclavicular joint dislocation, implant fixation loosening and broken, and secondary fractures occurred in the other patients. There was significant difference in the incidence of postoperative complications between 2 groups (P = 0.013). Constant-Murley scores of the injured shoulder significantly increased at 9 months after operation when compared with preoperative values in 2 groups (P < 0.05), but no significant difference was observed between 2 groups (P > 0.05). At last follow-up, there was no significant difference in Karlsson grading between 2 groups (Z = -0.628, P = 0.530). Both double Endobutton technique and suture anchor combined Endobutton plate have good effectiveness in the treatment of Tossy type III acromioclavicular joint dislocation. But the latter is associated with easier operation, less operation time, and less complications.

Genetics Home Reference: familial atrial fibrillation

MedlinePlus

... genes provide instructions for making parts of structural elements of cardiac muscle, such as sarcomeres. These structures ... Citation on PubMed or Free article on PubMed Central Hucker WJ, Saini H, Lubitz SA, Ellinor PT. ...

Image decomposition of barred galaxies and AGN hosts

NASA Astrophysics Data System (ADS)

Gadotti, Dimitri Alexei

2008-02-01

I present the results of multicomponent decomposition of V and R broad-band images of a sample of 17 nearby galaxies, most of them hosting bars and active galactic nuclei (AGN). I use BUDDA v2.1 to produce the fits, allowing the inclusion of bars and AGN in the models. A comparison with previous results from the literature shows a fairly good agreement. It is found that the axial ratio of bars, as measured from ellipse fits, can be severely underestimated if the galaxy axisymmetric component is relatively luminous. Thus, reliable bar axial ratios can only be determined by taking into account the contributions of bulge and disc to the light distribution in the galaxy image. Through a number of tests, I show that neglecting bars when modelling barred galaxies can result in an overestimation of the bulge-to-total luminosity ratio of a factor of 2. Similar effects result when bright, type 1 AGN are not considered in the models. By artificially redshifting the images, I show that the structural parameters of more distant galaxies can in general be reliably retrieved through image fitting, at least up to the point where the physical spatial resolution is ~1.5kpc. This corresponds, for instance, to images of galaxies at z = 0.05 with a seeing full width at half-maximum (FWHM) of 1.5arcsec, typical of the Sloan Digital Sky Survey (SDSS). In addition, such a resolution is also similar to what can be achieved with the Hubble Space Telescope (HST), and ground-based telescopes with adaptive optics, at z ~ 1-2. Thus, these results also concern deeper studies such as COSMOS and SINS. This exercise shows that disc parameters are particularly robust, but bulge parameters are prone to errors if its effective radius is small compared to the seeing radius, and might suffer from systematic effects. For instance, the bulge-to-total luminosity ratio is systematically overestimated, on average, by 0.05 (i.e. 5 per cent of the galaxy total luminosity). In this low-resolution regime, the effects of ignoring bars are still present, but AGN light is smeared out. I briefly discuss the consequences of these results to studies of the structural properties of galaxies, in particular on the stellar mass budget in the local Universe. With reasonable assumptions, it is possible to show that the stellar content in bars can be similar to that in classical bulges and elliptical galaxies. Finally, I revisit the cases of NGC4608 and 5701 and show that the lack of stars in the disc region inside the bar radius is significant. Accordingly, the best-fitting model for the former uses a Freeman type II disc.

A novel bioreactor for the generation of highly aligned 3D skeletal muscle-like constructs through orientation of fibrin via application of static strain.

PubMed

Heher, Philipp; Maleiner, Babette; Prüller, Johanna; Teuschl, Andreas Herbert; Kollmitzer, Josef; Monforte, Xavier; Wolbank, Susanne; Redl, Heinz; Rünzler, Dominik; Fuchs, Christiane

2015-09-01

The generation of functional biomimetic skeletal muscle constructs is still one of the fundamental challenges in skeletal muscle tissue engineering. With the notion that structure strongly dictates functional capabilities, a myriad of cell types, scaffold materials and stimulation strategies have been combined. To further optimize muscle engineered constructs, we have developed a novel bioreactor system (MagneTissue) for rapid engineering of skeletal muscle-like constructs with the aim to resemble native muscle in terms of structure, gene expression profile and maturity. Myoblasts embedded in fibrin, a natural hydrogel that serves as extracellular matrix, are subjected to mechanical stimulation via magnetic force transmission. We identify static mechanical strain as a trigger for cellular alignment concomitant with the orientation of the scaffold into highly organized fibrin fibrils. This ultimately yields myotubes with a more mature phenotype in terms of sarcomeric patterning, diameter and length. On the molecular level, a faster progression of the myogenic gene expression program is evident as myogenic determination markers MyoD and Myogenin as well as the Ca(2+) dependent contractile structural marker TnnT1 are significantly upregulated when strain is applied. The major advantage of the MagneTissue bioreactor system is that the generated tension is not exclusively relying on the strain generated by the cells themselves in response to scaffold anchoring but its ability to subject the constructs to individually adjustable strain protocols. In future work, this will allow applying mechanical stimulation with different strain regimes in the maturation process of tissue engineered constructs and elucidating the role of mechanotransduction in myogenesis. Mechanical stimulation of tissue engineered skeletal muscle constructs is a promising approach to increase tissue functionality. We have developed a novel bioreactor-based 3D culture system, giving the user the possibility to apply different strain regimes like static, cyclic or ramp strain to myogenic precursor cells embedded in a fibrin scaffold. Application of static mechanical strain leads to alignment of fibrin fibrils along the axis of strain and concomitantly to highly aligned myotube formation. Additionally, the pattern of myogenic gene expression follows the temporal progression observed in vivo with a more thorough induction of the myogenic program when static strain is applied. Ultimately, the strain protocol used in this study results in a higher degree of muscle maturity demonstrated by enhanced sarcomeric patterning and increased myotube diameter and length. The introduced bioreactor system enables new possibilities in muscle tissue engineering as longer cultivation periods and different strain applications will yield tissue engineered muscle-like constructs with improved characteristics in regard to functionality and biomimicry. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The KMOS Deep Survey (KDS) - I. Dynamical measurements of typical star-forming galaxies at z ≃ 3.5

NASA Astrophysics Data System (ADS)

Turner, O. J.; Cirasuolo, M.; Harrison, C. M.; McLure, R. J.; Dunlop, J. S.; Swinbank, A. M.; Johnson, H. L.; Sobral, D.; Matthee, J.; Sharples, R. M.

2017-10-01

We present dynamical measurements from the KMOS (K-band multi-object spectrograph) Deep Survey (KDS), which comprises 77 typical star-forming galaxies at z ≃ 3.5 in the mass range 9.0 < log (M⋆/M⊙) < 10.5. These measurements constrain the internal dynamics, the intrinsic velocity dispersions (σint) and rotation velocities (VC) of galaxies in the high-redshift Universe. The mean velocity dispersion of the galaxies in our sample is σ _int = 70.8^{+3.3}_{-3.1} km s^{-1}, revealing that the increasing average σint with increasing redshift, reported for z ≲ 2, continues out to z ≃ 3.5. Only 36 ± 8 per cent of our galaxies are rotation-dominated (VC/σint > 1), with the sample average VC/σint value much smaller than at lower redshift. After carefully selecting comparable star-forming samples at multiple epochs, we find that the rotation-dominated fraction evolves with redshift with a z-0.2 dependence. The rotation-dominated KDS galaxies show no clear offset from the local rotation velocity-stellar mass (I.e. VC-M⋆) relation, although a smaller fraction of the galaxies are on the relation due to the increase in the dispersion-dominated fraction. These observations are consistent with a simple equilibrium model picture, in which random motions are boosted in high-redshift galaxies by a combination of the increasing gas fractions, accretion efficiency, specific star formation rate and stellar feedback and which may provide significant pressure support against gravity on the galactic disc scale.

A new methodology for fluorescence analysis of composite resins used in anterior direct restorations.

PubMed

de Lima, Liliane Motta; Abreu, Jessica Dantas; Cohen-Carneiro, Flavia; Regalado, Diego Ferreira; Pontes, Danielson Guedes

2015-01-01

The aim of this study was to use a new methodology to evaluate the fluorescence of composite resins for direct restorations. Microhybrid (group 1, Amelogen; group 2, Opallis; group 3, Filtek Z250) and nanohybrid (group 4, Filtek Z350 XT; group 5, Brilliant NG; group 6, Evolu-X) composite resins were analyzed in this study. A prefabricated matrix was used to prepare 60 specimens of 7.0 × 3.0 mm (n = 10 per group); the composite resin discs were prepared in 2 increments (1.5 mm each) and photocured for 20 seconds. To establish a control group of natural teeth, 10 maxillary central incisor crowns were horizontally sectioned to create 10 discs of dentin and enamel tissues with the same dimensions as the composite resin specimens. The specimens were placed in a box with ultraviolet light, and photographs were taken. Aperture 3.0 software was used to quantify the central portion of the image of each specimen in shades of red (R), green (G), and blue (B) of the RGB color space. The brighter the B shade in the evaluated area of the image, the greater the fluorescence shown by the specimen. One-way analysis of variance revealed significant differences between the groups. The fluorescence achieved in group 1 was statistically similar to that of the control group and significantly different from those of the other groups (Bonferroni test). Groups 3 and 4 had the lowest fluorescence values, which were significantly different from those of the other groups. According to the results of this study, neither the size nor the amount of inorganic particles in the evaluated composite resin materials predicts if the material will exhibit good fluorescence.

SDSS-IV MaNGA: Spatially resolved star formation histories in galaxies as a function of galaxy mass and type

NASA Astrophysics Data System (ADS)

Goddard, D.; Thomas, D.; Maraston, C.; Westfall, K.; Etherington, J.; Riffel, R.; Mallmann, N. D.; Zheng, Z.; Argudo-Fernández, M.; Lian, J.; Bershady, M.; Bundy, K.; Drory, N.; Law, D.; Yan, R.; Wake, D.; Weijmans, A.; Bizyaev, D.; Brownstein, J.; Lane, R. R.; Maiolino, R.; Masters, K.; Merrifield, M.; Nitschelm, C.; Pan, K.; Roman-Lopes, A.; Storchi-Bergmann, T.; Schneider, D. P.

2017-04-01

We study the internal gradients of stellar population properties within 1.5 Re for a representative sample of 721 galaxies, with stellar masses ranging between 109 M⊙ and 1011.5 M⊙ from the SDSS-IV MaNGA Integral-Field-Unit survey. Through the use of our full spectral fitting code firefly, we derive light- and mass-weighted stellar population properties and their radial gradients, as well as full star formation and metal enrichment histories. We also quantify the impact that different stellar population models and full spectral fitting routines have on the derived stellar population properties and the radial gradient measurements. In our analysis, we find that age gradients tend to be shallow for both early-type and late-type galaxies. Mass-weighted age gradients of early-types arepositive (˜0.09 dex/Re) pointing to 'outside-in' progression of star formation, while late-type galaxies have negative light-weighted age gradients (˜-0.11 dex/Re), suggesting an 'inside-out' formation of discs. We detect negative metallicity gradients in both early- and late-type galaxies, but these are significantly steeper in late-types, suggesting that the radial dependence of chemical enrichment processes and the effect of gas inflow and metal transport are far more pronounced in discs. Metallicity gradients of both morphological classes correlate with galaxy mass, with negative metallicity gradients becoming steeper with increasing galaxy mass. The correlation with mass is stronger for late-type galaxies, with a slope of d(∇[Z/H])/d(log M) ˜ -0.2 ± 0.05 , compared to d(∇[Z/H])/d(log M) ˜ -0.05 ± 0.05 for early-types. This result suggests that the merger history plays a relatively small role in shaping metallicity gradients of galaxies.

Sarcomere mechanics in uniform and non-uniform cardiac muscle: a link between pump function and arrhythmias.

PubMed

ter Keurs, Henk E D J; Shinozaki, Tsuyoshi; Zhang, Ying Ming; Zhang, Mei Luo; Wakayama, Yuji; Sugai, Yoshinao; Kagaya, Yutaka; Miura, Masahito; Boyden, Penelope A; Stuyvers, Bruno D M; Landesberg, Amir

2008-01-01

Starling's Law and the well-known end-systolic pressure-volume relationship (ESPVR) of the left ventricle reflect the effect of sarcomere length (SL) on stress (sigma) development and shortening by myocytes in the uniform ventricle. We show here that tetanic contractions of rat cardiac trabeculae exhibit a sigma-SL relationship at saturating [Ca2+] that depends on sarcomere geometry in a manner similar to skeletal sarcomeres and the existence of opposing forces in cardiac muscle shortened below slack length. The sigma-SL-[Ca2+]free relationships (sigma-SL-CaR) at submaximal [Ca2+] in intact and skinned trabeculae were similar, albeit that the sensitivity for Ca2+ of intact muscle was higher. We analyzed the mechanisms underlying the sigma-SL-CaR using a kinetic model where we assumed that the rates of Ca2+ binding by Troponin-C (Tn-C) and/or cross-bridge (XB) cycling are determined by SL, [Ca2+] or stress. We analyzed the correlation between the model results and steady state stress measurements at varied SL and [Ca2+] from skinned rat cardiac trabeculae to test the hypotheses that: (i) the dominant feedback mechanism is SL, stress or [Ca2+]-dependent; and (ii) the feedback mechanism regulates: Tn-C-Ca2+ affinity, XB kinetics or, unitary XB-force. The analysis strongly suggests that feedback of the number of strong XBs to cardiac Tn-C-Ca2+ affinity is the dominant mechanism that regulates XB recruitment. Application of this concept in a mathematical model of twitch-stress accurately reproduced the sigma-SL-CaR and the time course of twitch-stress as well as the time course of intracellular [Ca2+]i. Modeling of the response of the cardiac twitch to rapid stress changes using the above feedback model uniquely predicted the occurrence of [Ca2+]i transients as a result of accelerated Ca2+ dissociation from Tn-C. The above concept has important repercussions for the non-uniformly contracting heart in which arrhythmogenic Ca2+ waves arise from weakened areas in cardiac muscle. These Ca2+ waves can reversibly be induced in muscle with non-uniform excitation contraction coupling (ECC) by the cycle of stretch and release in the border zone between the damaged and intact regions. Stimulus trains induced propagating Ca2+ waves and reversibly induced arrhythmias. We hypothesize that rapid force loss by sarcomeres in the border zone during relaxation causes Ca2+ release from Tn-C and initiates Ca2+ waves propagated by the sarcoplasmic reticulum (SR). These observations suggest the unifying hypothesis that force feedback to Ca2+ binding by Tn-C is responsible for Starling's Law and the ESPVR in uniform myocardium and leads in non-uniform myocardium to a surge of Ca2+ released by the myofilaments during relaxation, which initiates arrhythmogenic propagating Ca2+ release by the SR.

On the possibility of the determining the average mass composition near 10 to the 14th power eV through the solar magnetic field

NASA Technical Reports Server (NTRS)

Lloyd-Evans, J.

1985-01-01

The discovery of primary ultrahigh energy (UHE) gamma-rays has spawned plans for a new generation of air shower experiments with unprecedented directional resolution. Such accuracy permits observation of a cosmic ray shadow due to the solar disc. Particle trajectory simulations through models of the large scale solar magnetic field were performed. The shadow is apparent above 10 to the 15th power eV for all cosmic ray charges /Z/ 26; at lower energies, trajectories close to the Sun are bent sufficiently for this shadow to be lost. The onset of the shadow is rigidity dependent, and occurs at an energy per nucleus of approx. Z x 10 to the 13th power eV. The possibility of determining the average mass composition near 10 to the 14th power eV from 1 year's observation at a mountain altitude array is investigated.

Cardiac myofilaments: mechanics and regulation

NASA Technical Reports Server (NTRS)

de Tombe, Pieter P.; Bers, D. M. (Principal Investigator)

2003-01-01

The mechanical properties of the cardiac myofilament are an important determinant of pump function of the heart. This report is focused on the regulation of myofilament function in cardiac muscle. Calcium ions form the trigger that induces activation of the thin filament which, in turn, allows for cross-bridge formation, ATP hydrolysis, and force development. The structure and protein-protein interactions of the cardiac sarcomere that are responsible for these processes will be reviewed. The molecular mechanism that underlies myofilament activation is incompletely understood. Recent experimental approaches have been employed to unravel the mechanism and regulation of myofilament mechanics and energetics by activator calcium and sarcomere length, as well as contractile protein phosphorylation mediated by protein kinase A. Central to these studies is the question whether such factors impact on muscle function simply by altering thin filament activation state, or whether modulation of cross-bridge cycling also plays a part in the responses of muscle to these stimuli.

Muscle Contraction.

PubMed

Sweeney, H Lee; Hammers, David W

2018-02-01

SUMMARYMuscle cells are designed to generate force and movement. There are three types of mammalian muscles-skeletal, cardiac, and smooth. Skeletal muscles are attached to bones and move them relative to each other. Cardiac muscle comprises the heart, which pumps blood through the vasculature. Skeletal and cardiac muscles are known as striated muscles, because the filaments of actin and myosin that power their contraction are organized into repeating arrays, called sarcomeres, that have a striated microscopic appearance. Smooth muscle does not contain sarcomeres but uses the contraction of filaments of actin and myosin to constrict blood vessels and move the contents of hollow organs in the body. Here, we review the principal molecular organization of the three types of muscle and their contractile regulation through signaling mechanisms and discuss their major structural and functional similarities that hint at the possible evolutionary relationships between the cell types. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Direct adenovirus-mediated gene delivery to the temporomandibular joint in guinea-pigs.

PubMed

Kuboki, T; Nakanishi, T; Kanyama, M; Sonoyama, W; Fujisawa, T; Kobayashi, K; Ikeda, T; Kubo, T; Yamashita, A; Takigawa, M

1999-09-01

Adenovirus vector system is expected to be useful for direct gene therapy for joint disease. This study first sought to confirm that foreign genes can be transferred to articular chondrocytes in primary culture. Next, recombinant adenovirus vectors harbouring beta-galactosidase gene (LacZ) was injected directly into the temporomandibular joints of Hartley guinea-pigs to clarify the in vivo transfer availability of the adenovirus vectors. Specifically, recombinant adenovirus harbouring LacZ gene (AxlCALacZ) was injected into the upper joint cavities of both mandibular joints of four male 6-week-old Hartley guinea-pigs. Either the same amount of recombinant adenovirus without LacZ gene (Axlw) suspension (placebo) or the same amount of phosphate-buffered saline solution (control) were injected into the upper joint cavities of both joints of another four male guinea-pigs. At 1, 2, 3 and 4 weeks after injection, the joints were dissected and the expression of delivered LacZ was examined by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) staining and reverse transcriptase-polymerase chain reaction (RT-PCR). To investigate the expression of transferred gene in other organs, total RNA was extracted from liver, kidney, heart and brain and the expression of LacZ mRNA and 18 S ribosomal RNA were analysed by RT-PCR. Clear expression of LacZ was observed in the articular surfaces of the temporal tubercle, articular disc and synovium of the temporomandibular joints even 4 weeks after injection in the AxlCALacZ-injected group, while no expression was detected in placebo and control groups. Histological examination confirmed that LacZ activity was clearly detected in a few cell layers of the articular surface tissues, which is much more efficient than in a previously study of the knee joint. In the other organs, expression of the delivered transgene was not observed. Based on these findings, direct gene delivery into the articular surface of the temporomandibular joint using the adenovirus vector is feasible as an effective in vivo method.

Imaging the cold molecular gas in SDSS J1148 + 5251 at z = 6.4

NASA Astrophysics Data System (ADS)

Stefan, Irina I.; Carilli, Chris L.; Wagg, Jeff; Walter, Fabian; Riechers, Dominik A.; Bertoldi, Frank; Green, David A.; Fan, Xiaohui; Menten, Karl; Wang, Ran

2015-08-01

We present Karl G. Jansky Very Large Array (VLA) observations of the CO (J = 2 → 1) line emission towards the z = 6.419 quasar SDSS J114816.64 + 525150.3 (J1148 + 5251). The molecular gas is found to be marginally resolved with a major axis of 0.9 arcsec (consistent with previous size measurements of the CO (J = 7 → 6) emission). We observe tentative evidence for extended line emission towards the south-west on a scale of ˜1.4 arcsec, but this is only detected at 3.3σ significance and should be confirmed. The position of the molecular emission region is in excellent agreement with previous detections of low-frequency radio continuum emission as well as [C II] line and thermal dust continuum emission. These CO (J = 2 → 1) observations provide an anchor for the low-excitation part of the molecular line spectral energy distribution. We find no evidence for extended low-excitation component, neither in the spectral line energy distribution nor the image. We fit a single kinetic gas temperature model of 50 K. We revisit the gas and dynamical masses in light of this new detection of a low-order transition of CO, and confirm previous findings that there is no extended reservoir of cold molecular gas in J1148 + 5251, and that the source departs substantially from the low-z relationship between black hole mass and bulge mass. Hence, the characteristics of J1148 + 5251 at z = 6.419 are very similar to z ˜ 2 quasars, in the lack of a diffuse cold gas reservoir and kpc-size compactness of the star-forming region.

The influence of large-scale magnetic field in the structure of supercritical accretion flow with outflow

NASA Astrophysics Data System (ADS)

Ghasemnezhad, Maryam; Abbassi, Shahram

2017-08-01

We present the effects of ordered large-scale magnetic field on the structure of supercritical accretion flow in the presence of an outflow. In the cylindrical coordinates (r, φ, z), we write the 1.5-dimensional, steady-state (partial /partial t= 0) and axisymmetric (partial /partial \\varphi = 0) inflow-outflow equations by using self-similar solutions. Also, a model for radiation pressure supported accretion flow threaded by both toroidal and vertical components of magnetic field has been formulated. For studying the outflows, we adopt a radius-dependent mass accretion rate as \\dot{M}=\\dot{M}_{out}{(r/r_{out})^{s+1/2}} with s = 1/2. Also, by following the previous works, we have considered the interchange of mass, radial and angular momentum and the energy between inflow and outflow. We have found numerically that two components of magnetic field have the opposite effects on the thickness of the disc and similar effects on the radial and angular velocities of the flow. We have found that the existence of the toroidal component of magnetic field will lead to an increase in the radial and azimuthal velocities as well as the relative thickness of the disc. Moreover, in a magnetized flow, the thickness of the disc decreases with increase in the vertical component of magnetic field. The solutions indicated that the mass inflow rate and the specific energy of outflow strongly affect the advection parameter. We have shown that by increasing the two components of magnetic field, the temperature of the accretion flow decreases significantly. On the other hand, we have shown that the bolometric luminosity of the slim discs for high values of \\dot{m} (\\dot{m}>>1)\\dot{m} (\\dot{m}≫ 1) is not sensitive to mass accretion rate and is kept constant (L ≈ 10LE).

Gas kinematics, morphology and angular momentum in the FIRE simulations

NASA Astrophysics Data System (ADS)

El-Badry, Kareem; Quataert, Eliot; Wetzel, Andrew; Hopkins, Philip F.; Weisz, Daniel R.; Chan, T. K.; Fitts, Alex; Boylan-Kolchin, Michael; Kereš, Dušan; Faucher-Giguère, Claude-André; Garrison-Kimmel, Shea

2018-01-01

We study the z = 0 gas kinematics, morphology and angular momentum content of isolated galaxies in a suite of cosmological zoom-in simulations from the FIRE project spanning Mstar = 106-11 M⊙. Gas becomes increasingly rotationally supported with increasing galaxy mass. In the lowest mass galaxies (Mstar < 108 M⊙), gas fails to form a morphological disc and is primarily dispersion and pressure supported. At intermediate masses (Mstar = 108-10 M⊙), galaxies display a wide range of gas kinematics and morphologies, from thin, rotating discs to irregular spheroids with negligible net rotation. All the high-mass (Mstar = 1010-11 M⊙) galaxies form rotationally supported gas discs. Many of the haloes whose galaxies fail to form discs harbour high angular momentum gas in their circumgalactic medium. The ratio of the specific angular momentum of gas in the central galaxy to that of the dark matter halo increases significantly with galaxy mass, from 〈jgas〉/〈jDM〉 ∼ 0.1 at M_star=10^{6-7} M_{⊙} to 〈jgas〉/〈jDM〉 ∼ 2 at Mstar = 1010-11 M⊙. The reduced rotational support in the lowest mass galaxies owes to (a) stellar feedback and the UV background suppressing the accretion of high angular momentum gas at late times, and (b) stellar feedback driving large non-circular gas motions. We broadly reproduce the observed scaling relations between galaxy mass, gas rotation velocity, size and angular momentum, but may somewhat underpredict the incidence of disky, high angular momentum galaxies at the lowest observed masses (Mstar = (106-2 × 107) M⊙). Stars form preferentially from low angular momentum gas near the galactic centre and are less rotationally supported than gas. The common assumption that stars follow the same rotation curve as gas thus substantially overestimates the simulated galaxies' stellar angular momentum, particularly at low masses.

The rise and fall of stellar across the peak of cosmic star formation history: effects of mergers versus diffuse stellar mass acquisition

NASA Astrophysics Data System (ADS)

Welker, C.; Dubois, Y.; Devriendt, J.; Pichon, C.; Kaviraj, S.; Peirani, S.

2017-02-01

Building galaxy merger trees from a state-of-the-art cosmological hydrodynamical simulation, Horizon-AGN, we perform a statistical study of how mergers and diffuse stellar mass acquisition processes drive galaxy morphologic properties above z > 1. By diffuse mass acquisition here, we mean both accretion of stars by unresolved mergers (relative stellar mass growth smaller than 4.5 per cent) as well as in situ star formation when no resolved mergers are detected along the main progenitor branch of a galaxy. We investigate how stellar densities, galaxy sizes and galaxy morphologies (defined via shape parameters derived from the inertia tensor of the stellar density) depend on mergers of different mass ratios. We investigate how stellar densities, effective radii and shape parameters derived from the inertia tensor depend on mergers of different mass ratios. We find strong evidence that diffuse stellar accretion and in situ formation tend to flatten small galaxies over cosmic time, leading to the formation of discs. On the other hand, mergers, and not only the major ones, exhibit a propensity to puff up and destroy stellar discs, confirming the origin of elliptical galaxies. We confirm that mergers grow galaxy sizes more efficiently than diffuse processes (r_{0.5}∝ M_s^{0.85} and r_{0.5}∝ M_s^{0.1} on average, respectively) and we also find that elliptical galaxies are more susceptible to grow in size through mergers than disc galaxies with a size-mass evolution r_{0.5}∝ M_s^{1.2} instead of r_{0.5}∝ M_s^{-0.5}-M^{0.5} for discs depending on the merger mass ratio. The gas content drives the size-mass evolution due to merger with a faster size growth for gas-poor galaxies r_{0.5}∝ M_s2 than for gas-rich galaxies r0.5 ∝ Ms.

Mechanical properties of frog skeletal muscles in iodoacetic acid rigor.

PubMed Central

Mulvany, M J

1975-01-01

1. Methods have been developed for describing the length: tension characteristics of frog skeletal muscles which go into rigor at 4 degrees C following iodoacetic acid poisoning either in the presence of Ca2+ (Ca-rigor) or its absence (Ca-free-rigor). 2. Such rigor muscles showed less resistance to slow stretch (slow rigor resistance) that to fast stretch (fast rigor resistance). The slow and fast rigor resistances of Ca-free-rigor muscles were much lower than those of Ca-rigor muscles. 3. The slow rigor resistance of Ca-rigor muscles was proportional to the amount of overlap between the contractile filaments present when the muscles were put into rigor. 4. Withdrawing Ca2+ from Ca-rigor muscles (induced-Ca-free rigor) reduced their slow and fast rigor resistances. Readdition of Ca2+ (but not Mg2+, Mn2+ or Sr2+) reversed the effect. 5. The slow and fast rigor resistances of Ca-rigor muscles (but not of Ca-free-rigor muscles) decreased with time. 6.The sarcomere structure of Ca-rigor and induced-Ca-free rigor muscles stretched by 0.2lo was destroyed in proportion to the amount of stretch, but the lengths of the remaining intact sarcomeres were essentially unchanged. This suggests that there had been a successive yielding of the weakeast sarcomeres. 7. The difference between the slow and fast rigor resistance and the effect of calcium on these resistances are discussed in relation to possible variations in the strength of crossbridges between the thick and thin filaments. Images Plate 1 Plate 2 PMID:1082023

Sarcomeric gene mutations in sudden infant death syndrome (SIDS).

PubMed

Brion, Maria; Allegue, Catarina; Santori, Montserrat; Gil, Rocio; Blanco-Verea, Alejandro; Haas, Cordula; Bartsch, Christine; Poster, Simone; Madea, Burkhard; Campuzano, Oscar; Brugada, Ramon; Carracedo, Angel

2012-06-10

In developed countries, sudden infant death syndrome (SIDS) represents the most prevalent cause of death in children between 1 month and 1 year of age. SIDS is a diagnosis of exclusion, a negative autopsy which requires the absence of structural organ disease. Although investigators have confirmed that a significant percentage of SIDS cases are actually channelopathies, no data have been made available as to whether other sudden cardiac death-associated diseases, such as hypertrophic cardiomyopathy (HCM), could be responsible for some cases of SIDS. The presence of a genetic mutation in the sarcomeric protein usually affects the force of contraction of the myocyte, whose weakness is compensated with progressive hypertrophy and disarray. However, it is unclear whether in the most incipient forms, that is, first years of life, the lack of these phenotypes still confers a risk of arrhythmogenesis. The main goal of the present study is to wonder whether genetic defects in the sarcomeric proteins, previously associated with HCM, could be responsible for SIDS. We have analysed 286 SIDS cases for the most common genes implicated in HCM in adults. A total of 680 mutations localised in 16 genes were analysed by semi-automated matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDITOF-MS) using the Sequenom MassARRAY(®) System. Ten subjects with completely normal hearts showed mutated alleles at nine of the genetic variants analysed, and one additional novel mutation was detected by conventional sequencing. Therefore, a genetic mutation associated with HCM may cause sudden cardiac death in the absence of an identifiable phenotype. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Radial stiffness characteristics of the overlap regions of sarcomeres in isolated skeletal myofibrils in pre-force generating state.

PubMed

Miyashiro, Daisuke; Ohtsuki, Misato; Shimamoto, Yuta; Wakayama, Jun'ichi; Kunioka, Yuki; Kobayashi, Takakazu; Ishiwata, Shin'ichi; Yamada, Takenori

2017-01-01

We have studied the stiffness of myofilament lattice in sarcomeres in the pre-force generating state, which was realized by a relaxing reagent, BDM (butane dione monoxime). First, the radial stiffness for the overlap regions of sarcomeres of isolated single myofibrils was estimated from the resulting decreases in diameter by osmotic pressure applied with the addition of Dextran. Then, the radial stiffness was also estimated from force-distance curve measurements with AFM technology. The radial stiffness for the overlap regions thus obtained was composed of a soft and a rigid component. The soft component visco-elastically changed in a characteristic fashion depending on the physiological conditions of myofibrils, suggesting that it comes from cross-bridge structures. BDM treatments significantly affected the soft radial component of contracting myofibrils depending on the approach velocity of cantilever: It was nearly equal to that in the contracting state at high approach velocity, whereas as low as that in the relaxing state at low approach velocity. However, comparable BDM treatments greatly suppressed the force production and the axial stiffness in contracting glycerinated muscle fibers and also the sliding velocity of actin filaments in the in vitro motility assay. Considering that BDM shifts the cross-bridge population from force generating to pre-force generating states in contracting muscle, the obtained results strongly suggest that cross-bridges in the pre-force generating state are visco-elastically attached to the thin filaments in such a binding manner that the axial stiffness is low but the radial stiffness significantly high similar to that in force generating state.

Targeted Gene Silencing of Tumor Necrosis Factor Attenuates the Negative Inotropic Effects of Lipopolysaccharide in Isolated Contracting Cardiac Myocytes

PubMed Central

Ramabadran, R. S.; Chancey, Amanda; Vallejo, Jesus G.; Barger, Philip M.; Sivasubramanian, Natarajan; Mann, Douglas L.

2008-01-01

Bacterial endotoxin (lipopolysaccharide) depresses cardiovascular function; however, the mediators and signaling pathways that are responsible for the negative inotropic effects of lipopolysaccharide are not fully known. We used RNA interference to determine the relative role of tumor necrosis factor with respect to mediating the negative inotropic effects of lipopolysaccharide in isolated cardiac myocytes. Cardiac myocyte cultures were treated with lipopolysaccharide in the presence or absence of small interfering RNAs (siRNA) for tumor necrosis factor. We examined the effects of tumor necrosis factor siRNA on lipopolysaccharide-induced tumor necrosis factor messenger RNA (mRNA) and protein biosynthesis, as well as the negative inotropic effects of lipopolysaccharide in isolated contracting cardiac myocytes. Treatment of adult cardiac myocyte cultures with tumor necrosis factor siRNA significantly attenuated lipopolysaccharide-induced tumor necrosis factor mRNA and protein biosynthesis, whereas transfection with a double-stranded RNA that does not target mammalian mRNA had no effect. Pretreatment with tumor necrosis factor siRNA significantly attenuated, but did not abrogate, the lipopolysaccharide-induced decrease in sarcomere shortening in isolated contracting cardiac myocytes. In contrast, tumor necrosis factor siRNA had a comparatively smaller effect on improving sarcomere shortening once the negative inotropic effects of lipopolysaccharide were fully established. These results suggest that tumor necrosis factor plays an important upstream role in lipopolysaccharide-induced negative inotropic effects in isolated contracting cardiac myocytes and that other molecular mechanisms are responsible for the decrease in sarcomere shortening after sustained lipopolysaccharide signaling. PMID:18427645

Histone Deacetylase 3 (HDAC3)-dependent Reversible Lysine Acetylation of Cardiac Myosin Heavy Chain Isoforms Modulates Their Enzymatic and Motor Activity*

PubMed Central

Samant, Sadhana A.; Pillai, Vinodkumar B.; Sundaresan, Nagalingam R.; Shroff, Sanjeev G.; Gupta, Mahesh P.

2015-01-01

Reversible lysine acetylation is a widespread post-translational modification controlling the activity of proteins in different subcellular compartments. We previously demonstrated that a class II histone deacetylase (HDAC), HDAC4, and a histone acetyltransferase, p300/CREB-binding protein-associated factor, associate with cardiac sarcomeres and that a class I and II HDAC inhibitor, trichostatin A, enhances contractile activity of myofilaments. In this study we show that a class I HDAC, HDAC3, is also present at cardiac sarcomeres. By immunohistochemical and electron microscopic analyses, we found that HDAC3 was localized to A-band of sarcomeres and capable of deacetylating myosin heavy chain (MHC) isoforms. The motor domains of both cardiac α- and β-MHC isoforms were found to be reversibly acetylated. Biomechanical studies revealed that lysine acetylation significantly decreased the Km for the actin-activated ATPase activity of MHC isoforms. By in vitro motility assay, we found that lysine acetylation increased the actin-sliding velocity of α-myosin by 20% and β-myosin by 36% compared with their respective non-acetylated isoforms. Moreover, myosin acetylation was found to be sensitive to cardiac stress. During induction of hypertrophy, myosin isoform acetylation increased progressively with duration of stress stimuli independently of isoform shift, suggesting that lysine acetylation of myosin could be an early response of myofilaments to increase contractile performance of the heart. These studies provide the first evidence for localization of HDAC3 at myofilaments and uncover a novel mechanism modulating the motor activity of cardiac MHC isoforms. PMID:25911107

Left ventricular torsional mechanics and myocardial iron load in beta-thalassaemia major: a potential role of titin degradation.

PubMed

Chen, Mei-Pian; Li, Shu-Na; Lam, Wendy W M; Ho, Yuen-Chi; Ha, Shau-Yin; Chan, Godfrey C F; Cheung, Yiu-Fai

2014-04-12

Iron may damage sarcomeric proteins through oxidative stress. We explored the left ventricular (LV) torsional mechanics in patients with beta-thalassaemia major and its relationship to myocardial iron load. Using HL-1 cell and B6D2F1 mouse models, we further determined the impact of iron load on proteolysis of the giant sarcomeric protein titin. In 44 thalassaemia patients aged 25 ± 7 years and 38 healthy subjects, LV torsion and twisting velocities were determined at rest using speckle tracking echocardiography. Changes in LV torsional parameters during submaximal exercise testing were further assessed in 32 patients and 17 controls. Compared with controls, patients had significantly reduced LV apical rotation, torsion, systolic twisting velocity, and diastolic untwisting velocity. T2* cardiac magnetic resonance findings correlated with resting diastolic untwisting velocity. The increments from baseline and resultant LV torsion and systolic and diastolic untwisting velocities during exercise were significantly lower in patients than controls. Significant correlations existed between LV systolic torsion and diastolic untwisting velocities in patients and controls, both at rest and during exercise. In HL-1 cells and ventricular myocardium of B6D2F1 mice overloaded with iron, the titin-stained pattern of sarcomeric structure became disrupted. Gel electrophoresis of iron-overloaded mouse myocardial tissue further showed significant decrease in the amount of titin isoforms and increase in titin degradation products. Resting and dynamic LV torsional mechanics is impaired in patients with beta-thalassaemia major. Cell and animal models suggest a potential role of titin degradation in iron overload-induced alteration of LV torsional mechanics.

Spatial nonuniformity of contraction causes arrhythmogenic Ca2+ waves in rat cardiac muscle.

PubMed

Ter Keurs, Henk E D J; Wakayama, Yuji; Miura, Masahito; Stuyvers, Bruno D; Boyden, Penelope A; Landesberg, Amir

2005-06-01

Landesberg and Sideman's four state model of the cardiac cross-bridge (XB) hypothesizes a feedback of force development to Ca(2+) binding by troponin C (TnC). We have further modeled this behavior and observed that the force (F)-Ca(2+) relationship as well as the F-sarcomere length (SL) relationship and the time course of F and Ca(2+) transients in cardiac muscle can be reproduced faithfully by a single effect of F on deformation of the TnC-Ca complex and, thereby, on the dissociation rate of Ca(2+). Furthermore, this feedback predicts that rapid decline of F in the activated sarcomere causes release of Ca(2+) from TnC-Ca(2+), which is sufficient to initiate arrhythmogenic Ca(2+) release from the sarcoplasmic reticulum (SR). This work investigated the initiation of Ca(2+) waves underlying triggered propagated contractions (TPCs) in rat cardiac trabeculae under conditions that simulate functional nonuniformity caused by mechanical or ischemic local damage of the myocardium. A mechanical discontinuity along the trabeculae was created by exposing the preparation to a small constant flow jet of solution that reduces excitation-contraction coupling in myocytes within that segment. Force was measured, and SL as well as [Ca(2+)](i) were measured regionally. When the jet contained caffeine, 2,3-butanedione monoxime or low-[Ca(2+)], muscle-twitch F decreased and the sarcomeres in the exposed segment were stretched by shortening the normal regions outside the jet. During relaxation, the sarcomeres in the exposed segment shortened rapidly. Short trains of stimulation at 2.5 Hz reproducibly caused Ca(2+) waves to rise from the borders exposed to the jet. Ca(2+) waves started during F relaxation of the last stimulated twitch and propagated into segments both inside and outside of the jet. Arrhythmias, in the form of nondriven rhythmic activity, were triggered when the amplitude of the Ca(2+) wave increased by raising [Ca(2+)](o). The arrhythmias disappeared when the muscle uniformity was restored by turning the jet off. These results show that nonuniform contraction can cause Ca(2+) waves underlying TPCs, and suggest that Ca(2+) dissociated from myofilaments plays an important role in the initiation of arrhythmogenic Ca(2+) waves.

On the Distribution of Free Path Lengths for the Periodic Lorentz Gas III

NASA Astrophysics Data System (ADS)

Caglioti, Emanuele; Golse, François

For r(0,1), let Zr={xR2|dist(x,Z2)>r/2} and define τr(x,v)=inf{t>0|x+tv∂Zr}. Let Φr(t) be the probability that τr(x,v)>=t for x and v uniformly distributed in Zr and §1 respectively. We prove in this paper that as t-->+∞. This result improves upon the bounds on Φr in Bourgain-Golse-Wennberg [Commun. Math. Phys. 190, 491-508 (1998)]. We also discuss the applications of this result in the context of kinetic theory.

A Statistical Optimizing Navigation Procedure for Space Flight

DTIC Science & Technology

1961-09-01

E - _ _n) + an (w -Yn) (Wn Y and using Eq. (4.6) e - a) tr E - a n (WT y )(W_ + y T (4.8) so that 2 - n 2T n - ) e (W) + On tr (Yn _nT) (4.9) Thus...between the lines-of-sight to a star and the edge of a planet disc. From Fig. A-2 we have n " z =zcos(A + y ) (A. 11) 32 where A is the angle to be measured...It is shown in Appendix A that the devi- ation in position 6r of the spacecraft from the reference position is related- n to the deviation in angular

A Bridging Water Anchors the Tethered 5-(3-Aminopropyl)-2′-deoxyuridine Amine in the DNA Major Groove Proximate to the N+2 C·G Base Pair: Implications for Formation of Interstrand 5′-GNC-3′ Cross-Links by Nitrogen Mustards

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Feng; Li, Feng; Ganguly, Manjori

2008-11-14

Site-specific insertion of t-(3-aminopropyl)-2'-deoxyuridine (Z3dU) and 7-deaza-dG into the Dickerson-Drew dodecamers 5'-d(C{sup 1}G{sup 2}C{sup 3}G{sup 4}A{sup 5}A{sup 6}T{sup 7}T{sup 8}C{sup 9}{und Z}{sup 10}C{sup 11}G{sup 12})-3'{center_dot}5'-d (C{sup 13}G{sup 14}C{sup 15}G{sup 16}A{sup 17}A{sup 18}T{sup 19}T{sup 20}C{sup 21}{und Z}{sup 22}C{sup 23}G{sup 24})-3' (named DDD{sup Z10}) and 5'-d(C{sup 1}G{sup 2}C{sup 3}G{sup 4}A{sup 5}A{sup 6}T{sup 7}{und X}{sup 20}C{sup 21}{und Z}{sup 22}C{sup 23}G{sup 24})-3' (named DDD{sup 2+Z10}) (X = 73dU; Z = 7-deaza-dG) suggests a mechanism underlying the formation of interstrand N+2 DNA cross-links by nitrogen mustards, e.g., melphalan and mechlorethamine. Analysis of the DDD{sup 2+Z10} duplex reveals that the tethered cations at base pairs A{supmore » 5}{center_dot}X{sup 20} and X{sup 8}{center_dot}A{sup 17} extend within the major groove in the 3'-direction, toward conserved Mg{sup 2+} binding sites located adjacent to N+2 base pairs C{sup 3}{center_dot}Z{sup 22} and Z{sup 10}{center_dot}C{sup 15}. Bridging waters located between the tethered amines and either Z{sup 10} or Z{sup 22} O{sup 6} stabilize the tethered cations and allow interactions with the N + 2 base pairs without DNA bending. Incorporation of 7-deaza-dG into the DDD{sup 2+Z10} duplex weakens but does not eliminate electrostatic interactions between tethered amines and Z{sup 10} O{sup 6} and Z{sup 22} O{sup 6}. The results suggest a mechanism by which tethered N7-dG aziridinium ions, the active species involved in formation of interstrand 5'-GNC-3' cross-links by nitrogen mustards, modify the electrostatics of the major groove and position the aziridinium ions proximate to the major groove edge of the N+2 C{center_dot}G base pair, facilitating interstrand cross-linking.« less

Kinematics, turbulence, and star formation of z ˜ 1 strongly lensed galaxies seen with MUSE

NASA Astrophysics Data System (ADS)

Patrício, V.; Richard, J.; Carton, D.; Contini, T.; Epinat, B.; Brinchmann, J.; Schmidt, K. B.; Krajnović, D.; Bouché, N.; Weilbacher, P. M.; Pelló, R.; Caruana, J.; Maseda, M.; Finley, H.; Bauer, F. E.; Martinez, J.; Mahler, G.; Lagattuta, D.; Clément, B.; Soucail, G.; Wisotzki, L.

2018-06-01

We analyse a sample of eight highly magnified galaxies at redshift 0.6 < z < 1.5 observed with MUSE, exploring the resolved properties of these galaxies at sub-kiloparsec scales. Combining multiband HST photometry and MUSE spectra, we derive the stellar mass, global star formation rates (SFRs), extinction and metallicity from multiple nebular lines, concluding that our sample is representative of z ˜ 1 star-forming galaxies. We derive the 2D kinematics of these galaxies from the [O II ] emission and model it with a new method that accounts for lensing effects and fits multiple images simultaneously. We use these models to calculate the 2D beam-smearing correction and derive intrinsic velocity dispersion maps. We find them to be fairly homogeneous, with relatively constant velocity dispersions between 15 and 80 km s-1 and Gini coefficient of {≲ }0.3. We do not find any evidence for higher (or lower) velocity dispersions at the positions of bright star-forming clumps. We derive resolved maps of dust attenuation and attenuation-corrected SFRs from emission lines for two objects in the sample. We use this information to study the relation between resolved SFR and velocity dispersion. We find that these quantities are not correlated, and the high-velocity dispersions found for relatively low star-forming densities seems to indicate that, at sub-kiloparsec scales, turbulence in high-z discs is mainly dominated by gravitational instability rather than stellar feedback.

Selective CO2 conversion to formate conjugated with H2O oxidation utilizing semiconductor/complex hybrid photocatalysts.

PubMed

Sato, Shunsuke; Arai, Takeo; Morikawa, Takeshi; Uemura, Keiko; Suzuki, Tomiko M; Tanaka, Hiromitsu; Kajino, Tsutomu

2011-10-05

Photoelectrochemical reduction of CO(2) to HCOO(-) (formate) over p-type InP/Ru complex polymer hybrid photocatalyst was highly enhanced by introducing an anchoring complex into the polymer. By functionally combining the hybrid photocatalyst with TiO(2) for water oxidation, selective photoreduction of CO(2) to HCOO(-) was achieved in aqueous media, in which H(2)O was used as both an electron donor and a proton source. The so-called Z-scheme (or two-step photoexcitation) system operated with no external electrical bias. The selectivity for HCOO(-) production was >70%, and the conversion efficiency of solar energy to chemical energy was 0.03-0.04%.

What drives the kinematic evolution of star-forming galaxies?

NASA Astrophysics Data System (ADS)

Hung, Chao-Ling

2017-12-01

One important result from recent large integral field spectrograph (IFS) surveys is that the intrinsic velocity dispersion of galaxies increases with redshift. Massive, rotationdominated discs are already in place at z ∼ 2, but they are dynamically hotter than spiral galaxies in the local Universe. Although several plausible mechanisms for this elevated velocity dispersion (e.g. star formation feedback, elevated gas supply, or more frequent galaxy interactions) have been proposed, the fundamental driver of the velocity dispersion enhancement at high redshift remains unclear. We investigate the origin of this kinematic evolution using a suite of cosmological simulations from the FIRE (Feedback In Realistic Environments) project. These simulations reproduce the observed trends between intrinsic velocity dispersion (σ intr), SFR, and z. In both the observed and simulated galaxies, σ intr is positively correlated with SFR. σ intr increases with redshift out to z ∼ 1 and then flattens beyond that. In the FIRE simulations, σ intr can vary significantly on timescales of ≲ 100 Myr. These variations closely mirror the time evolution of the SFR and gas inflow rate ( Ṁ gas). By cross-correlating pairs of σ intr Ṁ gas, and SFR, we show that the increased gas inflow leads to subsequent enhanced star formation, and enhancements in σ intr tend to temporally coincide with increases in Ṁ gas and SFR.

Critical 2-D Percolation: Crossing Probabilities, Modular Forms and Factorization

NASA Astrophysics Data System (ADS)

Kleban, Peter

2007-03-01

We first consider crossing probabilities in critical 2-D percolation in rectangular geometries, derived via conformal field theory. These quantities are shown to exhibit interesting modular behavior [1], although the physical meaning of modular transformations in this context is not clear. We show that in many cases these functions are completely characterized by very simple transformation properties. In particular, Cardy's function for the percolation crossing probability (including the conformal dimension 1/3), follows from a simple modular argument. We next consider the probability of crossing between various points for percolation in the upper half-plane. For two points, with the point x an edge of the system, the probability is P(x,z)= k 1y^5/48 φ(x,z)^1/3 where φ is the potential at z of a 2-D dipole located at x, and k is a non-universal constant. For three points, one finds the exact and universal factorization [2,3] P(x1,x2,z)= C ; √P(x1,z)P(x2,z)P(x1,x2) with C= 8 √2; &5/2circ;3^3/4 ; γ(1/3)^9/2. These results are calculated by use of conformal field theory. Computer simulations verify them very precisely. Furthermore, simulations show that the same factorization holds asymptotically, with the same value of C, when one or both of the points xi are moved from the edge into the bulk.1.) Peter Kleban and Don Zagier, Crossing probabilities and modular forms, J. Stat. Phys. 113, 431-454 (2003) [arXiv: math-ph/0209023].2.) Peter Kleban, Jacob J. H. Simmons, and Robert M. Ziff, Anchored critical percolation clusters and 2-d electrostatics, Phys. Rev. Letters 97,115702 (2006) [arXiv: cond-mat/0605120].3.) Jacob J. H. Simmons and Peter Kleban, in preparation.

Cytoplasmic γ-actin and tropomodulin isoforms link to the sarcoplasmic reticulum in skeletal muscle fibers

PubMed Central

Gokhin, David S.

2011-01-01

The sarcoplasmic reticulum (SR) serves as the Ca2+ reservoir for muscle contraction. Tropomodulins (Tmods) cap filamentous actin (F-actin) pointed ends, bind tropomyosins (Tms), and regulate F-actin organization. In this paper, we use a genetic targeting approach to examine the effect of Tmod1 deletion on the organization of cytoplasmic γ-actin (γcyto-actin) in the SR of skeletal muscle. In wild-type muscle fibers, γcyto-actin and Tmod3 defined an SR microdomain that was distinct from another Z line–flanking SR microdomain containing Tmod1 and Tmod4. The γcyto-actin/Tmod3 microdomain contained an M line complex composed of small ankyrin 1.5 (sAnk1.5), γcyto-actin, Tmod3, Tm4, and Tm5NM1. Tmod1 deletion caused Tmod3 to leave its SR compartment, leading to mislocalization and destabilization of the Tmod3–γcyto-actin–sAnk1.5 complex. This was accompanied by SR morphological defects, impaired Ca2+ release, and an age-dependent increase in sarcomere misalignment. Thus, Tmod3 regulates SR-associated γcyto-actin architecture, mechanically stabilizes the SR via a novel cytoskeletal linkage to sAnk1.5, and maintains the alignment of adjacent myofibrils. PMID:21727195

Chemical chaperone ameliorates pathological protein aggregation in plectin-deficient muscle

PubMed Central

Winter, Lilli; Staszewska, Ilona; Mihailovska, Eva; Fischer, Irmgard; Goldmann, Wolfgang H.; Schröder, Rolf; Wiche, Gerhard

2014-01-01

The ubiquitously expressed multifunctional cytolinker protein plectin is essential for muscle fiber integrity and myofiber cytoarchitecture. Patients suffering from plectinopathy-associated epidermolysis bullosa simplex with muscular dystrophy (EBS-MD) and mice lacking plectin in skeletal muscle display pathological desmin-positive protein aggregation and misalignment of Z-disks, which are hallmarks of myofibrillar myopathies (MFMs). Here, we developed immortalized murine myoblast cell lines to examine the pathogenesis of plectinopathies at the molecular and single cell level. Plectin-deficient myotubes, derived from myoblasts, were fully functional and mirrored the pathological features of EBS-MD myofibers, including the presence of desmin-positive protein aggregates and a concurrent disarrangement of the myofibrillar apparatus. Using this cell model, we demonstrated that plectin deficiency leads to increased intermediate filament network and sarcomere dynamics, marked upregulation of HSPs, and reduced myotube resilience following mechanical stretch. Currently, no specific therapy or treatment is available to improve plectin-related or other forms of MFMs; therefore, we assessed the therapeutic potential of chemical chaperones to relieve plectinopathies. Treatment with 4-phenylbutyrate resulted in remarkable amelioration of the pathological phenotypes in plectin-deficient myotubes as well as in plectin-deficient mice. Together, these data demonstrate the biological relevance of the MFM cell model and suggest that this model has potential use for the development of therapeutic approaches for EBS-MD. PMID:24487589

The characterization of the distant blazar GB6 J1239+0443 from flaring and low activity periods

DOE PAGES

Pacciani, L.; Donnarumma, I.; Denney, K. D.; ...

2012-08-27

In 2008, AGILE and Fermi detected gamma-ray flaring activity from the unidentified EGRET source 3EG J1236+0457, recently associated with a flat spectrum radio quasar (GB6 J1239+0443) at z = 1.762. The optical counterpart of the gamma-ray source underwent a flux enhancement of a factor of 15–30 in six years, and of ~10 in six months. Here, we interpret this flare-up in terms of a transition from an accretion-disc-dominated emission to a synchrotron-jet-dominated one. We analysed a Sloan Digital Sky Survey (SDSS) archival optical spectrum taken during a period of low radio and optical activity of the source. We estimated themore » mass of the central black hole using the width of the C iv emission line. In our work, we have also investigated SDSS archival optical photometric data and ultraviolet GALEX observations to estimate the thermal disc emission contribution of GB6 J1239+0443. This analysis of the gamma-ray data taken during the flaring episodes indicates a flat gamma-ray spectrum, with an extension of up to 15 GeV, with no statistically relevant sign of absorption from the broad-line region, suggesting that the blazar zone is located beyond the broad-line region. Our result is confirmed by the modelling of the broad-band spectral energy distribution (well constrained by the available multiwavelength data) of the flaring activity periods and by the accretion disc luminosity and black hole mass estimated by us using archival data.« less

The SAMI Galaxy Survey: understanding observations of large-scale outflows at low redshift with EAGLE simulations

NASA Astrophysics Data System (ADS)

Tescari, E.; Cortese, L.; Power, C.; Wyithe, J. S. B.; Ho, I.-T.; Crain, R. A.; Bland-Hawthorn, J.; Croom, S. M.; Kewley, L. J.; Schaye, J.; Bower, R. G.; Theuns, T.; Schaller, M.; Barnes, L.; Brough, S.; Bryant, J. J.; Goodwin, M.; Gunawardhana, M. L. P.; Lawrence, J. S.; Leslie, S. K.; López-Sánchez, Á. R.; Lorente, N. P. F.; Medling, A. M.; Richards, S. N.; Sweet, S. M.; Tonini, C.

2018-01-01

This work presents a study of galactic outflows driven by stellar feedback. We extract main-sequence disc galaxies with stellar mass 109 ≤ M⋆/ M⊙ ≤ 5.7 × 1010 at redshift z = 0 from the highest resolution cosmological simulation of the Evolution and Assembly of GaLaxies and their Environments (EAGLE) set. Synthetic gas rotation velocity and velocity dispersion (σ) maps are created and compared to observations of disc galaxies obtained with the Sydney-AAO (Australian Astronomical Observatory) Multi-object Integral field spectrograph (SAMI), where σ-values greater than 150 km s-1 are most naturally explained by bipolar outflows powered by starburst activity. We find that the extension of the simulated edge-on (pixelated) velocity dispersion probability distribution depends on stellar mass and star formation rate surface density (ΣSFR), with low-M⋆/low-ΣSFR galaxies showing a narrow peak at low σ (∼30 km s-1) and more active, high-M⋆/high-ΣSFR galaxies reaching σ > 150 km s-1. Although supernova-driven galactic winds in the EAGLE simulations may not entrain enough gas with T <105 K compared to observed galaxies, we find that gas temperature is a good proxy for the presence of outflows. There is a direct correlation between the thermal state of the gas and its state of motion as described by the σ-distribution. The following equivalence relations hold in EAGLE: (i) low-σ peak ⇔ disc of the galaxy ⇔ gas with T <105 K; (ii) high-σ tail ⇔ galactic winds ⇔ gas with T ≥105 K.

Genetics Home Reference: early-onset myopathy with fatal cardiomyopathy

MedlinePlus

... they are made of proteins that generate the mechanical force needed for muscles to contract. Titin has several functions within sarcomeres. One of this protein's most important jobs is to provide structure, flexibility, and stability to these cell structures. Titin ...

Release of cell-free ice nuclei from Halomonas elongata expressing the ice nucleation gene inaZ of Pseudomonas syringae.

PubMed

Tegos, G; Vargas, C; Perysinakis, A; Koukkou, A I; Christogianni, A; Nieto, J J; Ventosa, A; Drainas, C

2000-11-01

Release of ice nuclei in the growth medium of recombinant Halomonas elongata cells expressing the inaZ gene of Pseudomonas syringae was studied in an attempt to produce cell-free active ice nuclei for biotechnological applications. Cell-free ice nuclei were not retained by cellulose acetate filters of 0.2 microm pore size. Highest activity of cell-free ice nuclei was obtained when cells were grown in low salinity (0.5-5% NaCl, w/v). Freezing temperature threshold, estimated to be below -7 degrees C indicating class C nuclei, was not affected by medium salinity. Their density, as estimated by Percoll density centrifugation, was 1.018 +/- 0.002 gml(-1) and they were found to be free of lipids. Ice nuclei are released in the growth medium of recombinant H. elongata cells probably because of inefficient anchoring of the ice-nucleation protein aggregates in the outer membrane. The ice+ recombinant H. elongata cells could be useful for future use as a source of active cell-free ice nucleation protein.

Preparation of Ultrahigh Molecular Weight Polyethylene/Graphene Nanocomposite In situ Polymerization via Spherical and Sandwich Structure Graphene/Sio2 Support

NASA Astrophysics Data System (ADS)

Su, Enqi; Gao, Wensheng; Hu, Xinjun; Zhang, Caicai; Zhu, Bochao; Jia, Junji; Huang, Anping; Bai, Yongxiao

2018-04-01

Reduced graphene oxide/SiO2 (RGO/SiO2) serving as a novel spherical support for Ziegler-Natta (Z-N) catalyst is reported. The surface and interior of the support has a porous architecture formed by RGO/SiO2 sandwich structure. The sandwich structure is like a brick wall coated with a graphene layer of concreted as skeleton which could withstand external pressures and endow the structure with higher support stabilities. After loading the Z-N catalyst, the active components anchor on the surface and internal pores of the supports. When the ethylene molecules meet the active centers, the molecular chains grow from the surface and internal catalytic sites in a regular and well-organized way. And the process of the nascent molecular chains filled in the sandwich structure polymerization could ensure the graphene disperse uniformly in the polymer matrix. Compared with traditional methods, the porous spherical graphene support of this strategy has far more advantages and could maintain an intrinsic graphene performance in the nanocomposites.

The KMOS Redshift One Spectroscopic Survey (KROSS): dynamical properties, gas and dark matter fractions of typical z ˜ 1 star-forming galaxies

NASA Astrophysics Data System (ADS)

Stott, John P.; Swinbank, A. M.; Johnson, Helen L.; Tiley, Alfie; Magdis, Georgios; Bower, Richard; Bunker, Andrew J.; Bureau, Martin; Harrison, Chris M.; Jarvis, Matt J.; Sharples, Ray; Smail, Ian; Sobral, David; Best, Philip; Cirasuolo, Michele

2016-04-01

The KMOS Redshift One Spectroscopic Survey (KROSS) is an ESO-guaranteed time survey of 795 typical star-forming galaxies in the redshift range z = 0.8-1.0 with the KMOS instrument on the Very Large Telescope. In this paper, we present resolved kinematics and star formation rates for 584 z ˜ 1 galaxies. This constitutes the largest near-infrared Integral Field Unit survey of galaxies at z ˜ 1 to date. We demonstrate the success of our selection criteria with 90 per cent of our targets found to be H α emitters, of which 81 per cent are spatially resolved. The fraction of the resolved KROSS sample with dynamics dominated by ordered rotation is found to be 83 ± 5 per cent. However, when compared with local samples these are turbulent discs with high gas to baryonic mass fractions, ˜35 per cent, and the majority are consistent with being marginally unstable (Toomre Q ˜ 1). There is no strong correlation between galaxy averaged velocity dispersion and the total star formation rate, suggesting that feedback from star formation is not the origin of the elevated turbulence. We postulate that it is the ubiquity of high (likely molecular) gas fractions and the associated gravitational instabilities that drive the elevated star formation rates in these typical z ˜ 1 galaxies, leading to the 10-fold enhanced star formation rate density. Finally, by comparing the gas masses obtained from inverting the star formation law with the dynamical and stellar masses, we infer an average dark matter to total mass fraction within 2.2re (9.5 kpc) of 65 ± 12 per cent, in agreement with the results from hydrodynamic simulations of galaxy formation.

Interference of HTLV-1 Tax Protein with Cell Polarity Regulators: Defining the Subcellular Localization of the Tax-DLG1 Interaction

PubMed Central

Marziali, Federico; Bugnon Valdano, Marina; Brunet Avalos, Clarisse; Moriena, Lucía; Cavatorta, Ana Laura; Gardiol, Daniela

2017-01-01

Human T cell leukemia virus (HTLV)-1 Tax (Tax) protein is very important in viral replication and cell transformation. Tax localizes in the nucleus and cytoplasm in association with organelles. Some activities of Tax depend on interactions with PDZ (PSD-95/Discs Large/Z0-1) domain–containing proteins such as Discs large protein 1 (DLG1) which is involved in cell polarity and proliferation. The DLG1 interaction results in a cytoplasmic co-localization pattern resembling vesicular aggregates, the nature of which is still unknown. To further explore the role of PDZ proteins in HTLV-1 cell transformation, we deeply investigated the Tax-DLG1 association. By fluorescence resonance energy transfer (FRET), we detected, for the first time, the direct binding of Tax to DLG1 within the cell. We showed that the interaction specifically affects the cellular distribution of not only DLG1, but also Tax. After studying different cell structures, we demonstrated that the aggregates distribute into the Golgi apparatus in spatial association with the microtubule-organizing center (MTOC). This study contributes to understand the biological significance of Tax-PDZ interactions. PMID:29168728

Interference of HTLV-1 Tax Protein with Cell Polarity Regulators: Defining the Subcellular Localization of the Tax-DLG1 Interaction.

PubMed

Marziali, Federico; Bugnon Valdano, Marina; Brunet Avalos, Clarisse; Moriena, Lucía; Cavatorta, Ana Laura; Gardiol, Daniela

2017-11-23

Human T cell leukemia virus (HTLV)-1 Tax (Tax) protein is very important in viral replication and cell transformation. Tax localizes in the nucleus and cytoplasm in association with organelles. Some activities of Tax depend on interactions with PDZ (PSD-95/Discs Large/Z0-1) domain-containing proteins such as Discs large protein 1 (DLG1) which is involved in cell polarity and proliferation. The DLG1 interaction results in a cytoplasmic co-localization pattern resembling vesicular aggregates, the nature of which is still unknown. To further explore the role of PDZ proteins in HTLV-1 cell transformation, we deeply investigated the Tax-DLG1 association. By fluorescence resonance energy transfer (FRET), we detected, for the first time, the direct binding of Tax to DLG1 within the cell. We showed that the interaction specifically affects the cellular distribution of not only DLG1, but also Tax. After studying different cell structures, we demonstrated that the aggregates distribute into the Golgi apparatus in spatial association with the microtubule-organizing center (MTOC). This study contributes to understand the biological significance of Tax-PDZ interactions.

Effects of accuracy motivation and anchoring on metacomprehension judgment and accuracy.

PubMed

Zhao, Qin

2012-01-01

The current research investigates how accuracy motivation impacts anchoring and adjustment in metacomprehension judgment and how accuracy motivation and anchoring affect metacomprehension accuracy. Participants were randomly assigned to one of six conditions produced by the between-subjects factorial design involving accuracy motivation (incentive or no) and peer performance anchor (95%, 55%, or no). Two studies showed that accuracy motivation did not impact anchoring bias, but the adjustment-from-anchor process occurred. Accuracy incentive increased anchor-judgment gap for the 95% anchor but not for the 55% anchor, which induced less certainty about the direction of adjustment. The findings offer support to the integrative theory of anchoring. Additionally, the two studies revealed a "power struggle" between accuracy motivation and anchoring in influencing metacomprehension accuracy. Accuracy motivation could improve metacomprehension accuracy in spite of anchoring effect, but if anchoring effect is too strong, it could overpower the motivation effect. The implications of the findings were discussed.

On the Theory of Ground Anchors

DTIC Science & Technology

1975-01-01

Reinart 46 American Electric Power Service anchor tests 47 Expandable land anchor 51 Anchorages in frozen ground 52 Foundation anchoring in thawed ground...Idealized configuration of Malone anchor 48 54. Standard grillage anchor and pyramid grillage anchor tested by the American Electric Power Service...Corporation 49 55. Configuration of bell anchors tested by the American Electric Power Service Corporation 50 56. Configuration of steel grillage - screw

Ground anchors and anchored systems

DOT National Transportation Integrated Search

1999-06-01

This document presents state-of-the-practice information on the design and installation of cement-grouted ground anchors and anchored systems for highway applications. The anchored systems discussed include flexible anchored walls, slopes supported u...

Anchoring Revisited: The Role of the Comparative Question

PubMed Central

Grau, Ina; Bohner, Gerd

2014-01-01

When people estimate a numeric value after judging whether it is larger or smaller than a high or low anchor value (comparative question), estimates are biased in the direction of the anchor. One explanation for this anchoring effect is that people selectively access knowledge consistent with the anchor value as part of a positive test strategy. Two studies (total N = 184) supported the alternative explanation that people access knowledge consistent with their own answer to the comparative question. Specifically, anchoring effects emerged when the answer to the comparative question was unexpected (lower than the low anchor or higher than the high anchor). For expected answers (lower than the high anchor or higher than the low anchor), however, anchoring effects were attenuated or reversed. The anchor value itself was almost never reported as an absolute estimate. PMID:24454953

Quantitative trait locus analysis of heterosis for plant height and ear height in an elite maize hybrid zhengdan 958 by design III.

PubMed

Li, Hongjian; Yang, Qingsong; Fan, Nannan; Zhang, Ming; Zhai, Huijie; Ni, Zhongfu; Zhang, Yirong

2017-04-17

Plant height (PH) and ear height (EH) are two important agronomic traits in maize selection breeding. F 1 hybrid exhibit significant heterosis for PH and EH as compared to their parental inbred lines. To understand the genetic basis of heterosis controlling PH and EH, we conducted quantitative trait locus (QTL) analysis using a recombinant inbreed line (RIL) based design III population derived from the elite maize hybrid Zhengdan 958 in five environments. A total of 14 environmentally stable QTLs were identified, and the number of QTLs for Z 1 and Z 2 populations was six and eight, respectively. Notably, all the eight environmentally stable QTLs for Z 2 were characterized by overdominance effect (OD), suggesting that overdominant QTLs were the most important contributors to heterosis for PH and EH. Furthermore, 14 environmentally stable QTLs were anchored on six genomic regions, among which four are trait-specific QTLs, suggesting that the genetic basis for PH and EH is partially different. Additionally, qPH.A-1.3, modifying about 10 centimeters of PH, was further validated in backcross populations. The genetic basis for PH and EH is partially different, and overdominant QTLs are important factors for heterosis of PH and EH. A major QTL qPH.A-1.3 may be a desired target for genetic improvement of maize plant height.

Constraining the Merging History of Massive Galaxies Since Redshift 3 Using Close Pairs. I. Major Pairs from Candels and the SDSS

NASA Astrophysics Data System (ADS)

Mantha, Kameswara Bharadwaj; McIntosh, Daniel H.; Brennan, Ryan; Cook, Joshua; Kodra, Dritan; Newman, Jeffrey; Somerville, Rachel S.; Barro, Guillermo; Behroozi, Peter; Conselice, Christopher; Dekel, Avishai; Faber, Sandra M.; Closson Ferguson, Henry; Finkelstein, Steven L.; Fontana, Adriano; Galametz, Audrey; Perez-Gonzalez, Pablo; Grogin, Norman A.; Guo, Yicheng; Hathi, Nimish P.; Hopkins, Philip F.; Kartaltepe, Jeyhan S.; Kocevski, Dale; Koekemoer, Anton M.; Koo, David C.; Lee, Seong-Kook; Lotz, Jennifer M.; Lucas, Ray A.; Nayyeri, Hooshang; Peth, Michael; Pforr, Janine; Primack, Joel R.; Santini, Paola; Simmons, Brooke D.; Stefanon, Mauro; Straughn, Amber; Snyder, Gregory F.; Wuyts, Stijn

2017-01-01

Major galaxy-galaxy merging can play an important role in the history of massive galaxies (stellar masses > 2E10 Msun) over cosmic time. An important way to measure the impact of major merging is to study close pairs of galaxies stellar mass or flux ratios between 1 and 4. We improve on the best recent efforts by probing merging of lower mass galaxies, anchoring evolutionary trends from five Hubble Space Telescope Legacy fields in the Cosmic Assembly Near-Infrared Deep Extragalactic Legacy Survey (CANDELS) to the nearby universe using Sloan Digital Sky Survey (SDSS) to measure the fraction of massive galaxies in such pairs during six epochs spanning 01.5. This implies that major merging may not be as important at high redshifts as previously thought, merger timescales may not be fully understood, or we may be missing evidence of mergers at z~2-3 owing to CANDELS selections effects. Next, we will analyze pair fractions and merging timescales within realistic mocks of CANDELS from state of the art Semi-Analytic Model (SAM) to better understand and calibrate our empirical results.

Root resorption of maxillary incisors retracted with and without skeletal anchorage.

PubMed

Barros, Sérgio Estelita; Janson, Guilherme; Chiqueto, Kelly; Baldo, Vitor Oliveira; Baldo, Taiana Oliveira

2017-02-01

Our objective was to compare root resorption degree of the maxillary central incisors retracted with and without skeletal anchorage. This nonrandomized historical control study included 37 patients requiring maximum anterior retraction and treated with extraction of 2 maxillary premolars. Group 1 consisted of 22 patients (11 male, 11 female) in whom anterior retraction was performed without skeletal anchorage, and group 2 included 15 patients (3 male, 12 female) treated with skeletally anchored anterior retraction. Periapical radiographs were used to evaluate root resorption degree by a scoring system. The groups were compared regarding the resorption score and resorption degree distribution with the Mann-Whitney U test, chi-square test, and Z test on proportions. There was no statistically significant intergroup difference regarding root resorption, but the number of patients with severe and extreme root resorption degrees was significantly greater in group 2. Although the root resorption degree of the skeletal anchorage group was not significantly different from the group without skeletal anchorage, the number of patients with severe to extreme resorption in the first group was significantly greater. Therefore, careful clinical monitoring of skeletally anchored anterior retraction is needed, especially when there are known root resorption predisposing factors. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Decisional Conflict in Parents Considering Bone-Anchored Hearing Devices in Children With Unilateral Aural Atresia.

PubMed

Graham, M Elise; Haworth, Rebecca; Chorney, Jill; Bance, Manohar; Hong, Paul

2015-12-01

The benefits of bone-anchored hearing devices (BAHD) in children with unilateral aural atresia are controversial. We sought to determine whether there is parental decisional conflict surrounding elective placement of BAHD for this indication. Caregivers of pediatric patients with unilateral aural atresia and normal contralateral ear undergoing percutaneous BAHD consultation were enrolled. All consultations were carried out by one pediatric otolaryngologist in a consistent manner. After consultation, the participants completed a demographics form and the Decisional Conflict Scale (DCS) questionnaire. Twenty-three caregivers of 15 male (65.2%) and 8 female (34.8%) children (mean age 5.65 years) participated. The overall median DCS score was 15.63 (standard error = 4.21). Significant decisional conflict (DCS score ≥ 25) was found in 10 participants (43.5%). The median DCS score in the group choosing surgery was 5.47, and it was 23.44 in those who did not choose surgery (Mann-Whitney U = 39, Z = -1.391, P = .164). The median DCS score for mothers and fathers was 25 and 3.91, respectively. Many parents experienced significant decisional conflict when considering percutaneous BAHD surgery in children with unilateral aural atresia in our study population. Future research should explore the impact of decisional conflict on health outcomes. © The Author(s) 2015.

Comprehensive Analysis of the COBRA-Like (COBL) Gene Family in Gossypium Identifies Two COBLs Potentially Associated with Fiber Quality

PubMed Central

Niu, Erli; Shang, Xiaoguang; Cheng, Chaoze; Bao, Jianghao; Zeng, Yanda; Cai, Caiping; Du, Xiongming; Guo, Wangzhen

2015-01-01

COBRA-Like (COBL) genes, which encode a plant-specific glycosylphosphatidylinositol (GPI) anchored protein, have been proven to be key regulators in the orientation of cell expansion and cellulose crystallinity status. Genome-wide analysis has been performed in A. thaliana, O. sativa, Z. mays and S. lycopersicum, but little in Gossypium. Here we identified 19, 18 and 33 candidate COBL genes from three sequenced cotton species, diploid cotton G. raimondii, G. arboreum and tetraploid cotton G. hirsutum acc. TM-1, respectively. These COBL members were anchored onto 10 chromosomes in G. raimondii and could be divided into two subgroups. Expression patterns of COBL genes showed highly developmental and spatial regulation in G. hirsutum acc. TM-1. Of them, GhCOBL9 and GhCOBL13 were preferentially expressed at the secondary cell wall stage of fiber development and had significantly co-upregulated expression with cellulose synthase genes GhCESA4, GhCESA7 and GhCESA8. Besides, GhCOBL9 Dt and GhCOBL13 Dt were co-localized with previously reported cotton fiber quality quantitative trait loci (QTLs) and the favorable allele types of GhCOBL9 Dt had significantly positive correlations with fiber quality traits, indicating that these two genes might play an important role in fiber development. PMID:26710066

New Details of the Human Corneal Limbus Revealed With Second Harmonic Generation Imaging.

PubMed

Park, Choul Yong; Lee, Jimmy K; Zhang, Cheng; Chuck, Roy S

2015-09-01

To report novel findings of the human corneal limbus by using second harmonic generation (SHG) imaging. Corneal limbus was imaged by using an inverted two-photon excitation fluorescence microscope. Laser (Ti:Sapphire) was tuned at 850 nm for two-photon excitation. Backscatter signals of SHG and autofluorescence (AF) were collected through a 425/30-nm emission filter and a 525/45-emission filter, respectively. Multiple, consecutive, and overlapping image stacks (z-stack) were acquired for the corneal limbal area. Two novel collagen structures were revealed by SHG imaging at the limbus: an anterior limbal cribriform layer and presumed anchoring fibers. Anterior limbal cribriform layer is an intertwined reticular collagen architecture just beneath the limbal epithelial niche and is located between the peripheral cornea and Tenon's/scleral tissue. Autofluorescence imaging revealed high vascularity in this structure. Central to the anterior limbal cribriform layer, radial strands of collagen were found to connect the peripheral cornea to the limbus. These presumed anchoring fibers have both collagen and elastin and were found more extensively in the superficial layers than deep layer and were absent in very deep limbus near Schlemm's canal. By using SHG imaging, new details of the collagen architecture of human corneal limbal area were elucidated. High resolution images with volumetric analysis revealed two novel collagen structures.

Kinetic coupling of phosphate release, force generation and rate-limiting steps in the cross-bridge cycle.

PubMed

Stehle, Robert; Tesi, Chiara

2017-08-01

A basic goal in muscle research is to understand how the cyclic ATPase activity of cross-bridges is converted into mechanical force. A direct approach to study the chemo-mechanical coupling between P i release and the force-generating step is provided by the kinetics of force response induced by a rapid change in [P i ]. Classical studies on fibres using caged-P i discovered that rapid increases in [P i ] induce fast force decays dependent on final [P i ] whose kinetics were interpreted to probe a fast force-generating step prior to P i release. However, this hypothesis was called into question by studies on skeletal and cardiac myofibrils subjected to P i jumps in both directions (increases and decreases in [P i ]) which revealed that rapid decreases in [P i ] trigger force rises with slow kinetics, similar to those of calcium-induced force development and mechanically-induced force redevelopment at the same [P i ]. A possible explanation for this discrepancy came from imaging of individual sarcomeres in cardiac myofibrils, showing that the fast force decay upon increase in [P i ] results from so-called sarcomere 'give'. The slow force rise upon decrease in [P i ] was found to better reflect overall sarcomeres cross-bridge kinetics and its [P i ] dependence, suggesting that the force generation coupled to P i release cannot be separated from the rate-limiting transition. The reasons for the different conclusions achieved in fibre and myofibril studies are re-examined as the recent findings on cardiac myofibrils have fundamental consequences for the coupling between P i release, rate-limiting steps and force generation. The implications from P i -induced force kinetics of myofibrils are discussed in combination with historical and recent models of the cross-bridge cycle.

Expression of a mutation causing hypertrophic cardiomyopathy disrupts sarcomere assembly in adult feline cardiac myocytes.

PubMed

Marian, A J; Yu, Q T; Mann, D L; Graham, F L; Roberts, R

1995-07-01

Mutations in the beta-myosin heavy chain (beta MyHC) induce hypertrophic cardiomyopathy (HCM), cardiac hypertrophy, and sarcomere disarray, with the latter being the characteristic hallmark. Thus, we sought to determine whether expression of mutant beta MyHC in adult feline cardiac myocytes, a species known to develop HCM with a phenotype identical to that in humans, induces sarcomere disarray. A full-length beta MyHC cDNA was cloned from a human heart cDNA library, and an HCM-causing mutation (Arg403Gln) was induced in the beta MyHC cDNA by site-directed mutagenesis using polymerase chain reaction (PCR). The normal and mutant beta MyHC cDNAs were cloned into p delta E1spIB shuttle vector, downstream from a cytomegalovirus (CMV) promoter. Replication-deficient recombinant adenoviral constructs (Ad5/CMV/beta MyHC-N and Ad5/CMV/beta MyHC-403) were generated through homologous recombination of p delta E1spIB/CMV/beta MyHC-N or Ad5/CMV/beta MyHC-403 and pBHG10 after cotransfection in 293 host cells. Infection of COS-1 cells with the beta MyHC construct resulted in the expression of a full-length myosin protein. Efficiency of infection of isolated adult cardiac myocytes was > 95%. Expression of the beta MyHC constructs into mRNA at 48 hours after infection of feline cardiac myocytes was confirmed by reverse transcription-PCR. The net total protein and beta-myosin synthesis were determined by using the amount of incorporation of [3H]phenylalanine into total protein and beta-myosin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Relative fascicle excursion effects on dynamic strength generation during gait in children with cerebral palsy.

PubMed

Martín Lorenzo, T; Lerma Lara, S; Martínez-Caballero, I; Rocon, E

2015-10-01

Evaluation of muscle structure gives us a better understanding of how muscles contribute to force generation which is significantly altered in children with cerebral palsy (CP). While most muscle structure parameters have shown to be significantly correlated to different expressions of strength development in children with CP and typically developing (TD) children, conflicting results are found for muscle fascicle length. Muscle fascicle length determines muscle excursion and velocity, and contrary to what might be expected, correlations of fascicle length to rate of force development have not been found for children with CP. The lack of correlation between muscle fascicle length and rate of force development in children with CP could be due, on the one hand, to the non-optimal joint position adopted for force generation on the isometric strength tests as compared to the position of TD children. On the other hand, the lack of correlation could be due to the erroneous assumption that muscle fascicle length is representative of sarcomere length. Thus, the relationship between muscle architecture parameters reflecting sarcomere length, such as relative fascicle excursions and dynamic power generation, should be assessed. Understanding of the underlying mechanisms of weakness in children with CP is key for individualized prescription and assessment of muscle-targeted interventions. Findings could imply the detection of children operating on the descending limb of the sarcomere length-tension curve, which in turn might be at greater risk of developing crouch gait. Furthermore, relative muscle fascicle excursions could be used as a predictive variable of outcomes related to crouch gait prevention treatments such as strength training. Copyright © 2015 Elsevier Ltd. All rights reserved.

In muscle lengthening surgery multiple aponeurotomy does not improve intended acute effects and may counter-indicate: an assessment by finite element modelling.

PubMed

Yucesoy, Can A; Seref-Ferlengez, Zeynep; Huijing, Peter A

2013-01-01

The goal was to assess the effects of multiple aponeurotomy on mechanics of muscle with extramuscular myofascial connections. Using finite element modelling, effects of combinations of the intervention carried out at a proximal (P), an intermediate (I) and a distal (D) location were studied: (1) Case P, (2) Case P-I, (3) Case P-D and (4) Case P-I-D. Compared to Case P, the effects of multiple interventions on muscle geometry and sarcomere lengths were sizable for the distal population of muscle fibres: e.g. at high muscle length (1) summed gap lengths between the cut ends of aponeurosis increased by 16, 25 and 27% for Cases P-I, P-D and P-I-D, respectively, (2) characteristic substantial sarcomere shortening became more pronounced (mean shortening was 26, 29, 30 and 31% for Cases P, P-I, P-D and P-I-D, respectively) and (3) fibre stresses decreased (mean stress equalled 0.49, 0.39, 0.38 and 0.33 for Cases P, P-I, P-D and P-I-D, respectively). In contrast, no appreciable effects were shown for the proximal population. The overall change in sarcomere length heterogeneity was limited. Consequently, the effects of multiple aponeurotomy on muscle length-force characteristics were marginal: (1) a limited reduction in active muscle force (maximal 'muscle weakening effect' remained between 5 and 11%) and (2) an even less pronounced change in slack to optimum length range of force exertion (maximal 'muscle lengthening effect' distally was 0.2% for Case P-I-D) were shown. The intended effects of the intervention were dominated by the one intervention carried out closer to the tendon suggesting that aponeurotomies done additionally to that may counter-indicated.

Sarcomere-length dependence of myosin filament structure in skeletal muscle fibres of the frog.

PubMed

Reconditi, Massimo; Brunello, Elisabetta; Fusi, Luca; Linari, Marco; Martinez, Manuel Fernandez; Lombardi, Vincenzo; Irving, Malcolm; Piazzesi, Gabriella

2014-03-01

X-ray diffraction patterns were recorded at beamline ID02 of the European Synchrotron Radiation Facility from small bundles of skeletal muscle fibres from Rana esculenta at sarcomere lengths between 2.1 and 3.5 μm at 4°C. The intensities of the X-ray reflections from resting fibres associated with the quasi-helical order of the myosin heads and myosin binding protein C (MyBP-C) decreased in the sarcomere length range 2.6-3.0 μm but were constant outside it, suggesting that an OFF conformation of the thick filament is maintained by an interaction between MyBP-C and the thin filaments. During active isometric contraction the intensity of the M3 reflection from the regular repeat of the myosin heads along the filaments decreased in proportion to the overlap between thick and thin filaments, with no change in its interference fine structure. Thus, myosin heads in the regions of the thick filaments that do not overlap with thin filaments are highly disordered during isometric contraction, in contrast to their quasi-helical order at rest. Heads in the overlap region that belong to two-headed myosin molecules that are fully detached from actin are also highly disordered, in contrast to the detached partners of actin-attached heads. These results provide strong support for the concept of a regulatory structural transition in the thick filament involving changes in both the organisation of the myosin heads on its surface and the axial periodicity of the myosin tails in its backbone, mediated by an interaction between MyBP-C and the thin filaments.

Nonlinear force-length relationship in the ADP-induced contraction of skeletal myofibrils.

PubMed

Shimamoto, Yuta; Kono, Fumiaki; Suzuki, Madoka; Ishiwata, Shin'ichi

2007-12-15

The regulatory mechanism of sarcomeric activity has not been fully clarified yet because of its complex and cooperative nature, which involves both Ca(2+) and cross-bridge binding to the thin filament. To reveal the mechanism of regulation mediated by the cross-bridges, separately from the effect of Ca(2+), we investigated the force-sarcomere length (SL) relationship in rabbit skeletal myofibrils (a single myofibril or a thin bundle) at SL > 2.2 microm in the absence of Ca(2+) at various levels of activation by exogenous MgADP (4-20 mM) in the presence of 1 mM MgATP. The individual SLs were measured by phase-contrast microscopy to confirm the homogeneity of the striation pattern of sarcomeres during activation. We found that at partial activation with 4-8 mM MgADP, the developed force nonlinearly depended on the length of overlap between the thick and the thin filaments; that is, contrary to the maximal activation, the maximal active force was generated at shorter overlap. Besides, the active force became larger, whereas this nonlinearity tended to weaken, with either an increase in [MgADP] or the lateral osmotic compression of the myofilament lattice induced by the addition of a macromolecular compound, dextran T-500. The model analysis, which takes into account the [MgADP]- and the lattice-spacing-dependent probability of cross-bridge formation, was successfully applied to account for the force-SL relationship observed at partial activation. These results strongly suggest that the cross-bridge works as a cooperative activator, the function of which is highly sensitive to as little as

A multi-scale cardiovascular system model can account for the load-dependence of the end-systolic pressure-volume relationship

PubMed Central

2013-01-01

Background The end-systolic pressure-volume relationship is often considered as a load-independent property of the heart and, for this reason, is widely used as an index of ventricular contractility. However, many criticisms have been expressed against this index and the underlying time-varying elastance theory: first, it does not consider the phenomena underlying contraction and second, the end-systolic pressure volume relationship has been experimentally shown to be load-dependent. Methods In place of the time-varying elastance theory, a microscopic model of sarcomere contraction is used to infer the pressure generated by the contraction of the left ventricle, considered as a spherical assembling of sarcomere units. The left ventricle model is inserted into a closed-loop model of the cardiovascular system. Finally, parameters of the modified cardiovascular system model are identified to reproduce the hemodynamics of a normal dog. Results Experiments that have proven the limitations of the time-varying elastance theory are reproduced with our model: (1) preload reductions, (2) afterload increases, (3) the same experiments with increased ventricular contractility, (4) isovolumic contractions and (5) flow-clamps. All experiments simulated with the model generate different end-systolic pressure-volume relationships, showing that this relationship is actually load-dependent. Furthermore, we show that the results of our simulations are in good agreement with experiments. Conclusions We implemented a multi-scale model of the cardiovascular system, in which ventricular contraction is described by a detailed sarcomere model. Using this model, we successfully reproduced a number of experiments that have shown the failing points of the time-varying elastance theory. In particular, the developed multi-scale model of the cardiovascular system can capture the load-dependence of the end-systolic pressure-volume relationship. PMID:23363818

Second harmonic generation imaging of skeletal muscle tissue and myofibrils

NASA Astrophysics Data System (ADS)

Campagnola, Paul J.; Mohler, William H.; Plotnikov, Sergey; Millard, Andrew C.

2006-02-01

Second Harmonic Generation (SHG) imaging microscopy is used to examine the morphology and structural properties of intact muscle tissue. Using biochemical and optical analysis, we characterize the molecular structure underlying SHG from the complex muscle sarcomere. We find that SHG from isolated myofibrils is abolished by extraction of myosin, but is unaffected by removal or addition of actin filaments. We thus determined that the SHG emission arises from domains of the sarcomere containing thick filaments. By fitting the SHG polarization anisotropy to theoretical response curves, we find an orientation for the harmonophore that corresponds well to the pitch angle of the myosin rod α-helix with respect to the thick filament axis. Taken together, these data indicate that myosin rod domains are the key structures giving rise to SHG from striated muscle. Using SHG imaging microscopy, we have also examined the effect of optical clearing with glycerol to achieve greater penetration into specimens of skeletal muscle tissue. We find that treatment with 50% glycerol results in a 2.5 fold increase in achievable SHG imaging depth. Fast Fourier Transform (FFT) analysis shows quantitatively that the periodicity of the sarcomere structure is unaltered by the clearing process. Also, comparison of the SHG angular polarization dependence shows no change in the supramolecular organization of acto-myosin complexes. We suggest that the primary mechanism of optical clearing in muscle with glycerol treatment results from the reduction of cytoplasmic protein concentration and concomitant decrease in the secondary inner filter effect on the SHG signal. The pronounced lack of dependence of glycerol concentration on the imaging depth indicates that refractive index matching plays only a minor role in the optical clearing of muscle.

Tenderness of pre- and post rigor lamb longissimus muscle.

PubMed

Geesink, Geert; Sujang, Sadi; Koohmaraie, Mohammad

2011-08-01

Lamb longissimus muscle (n=6) sections were cooked at different times post mortem (prerigor, at rigor, 1dayp.m., and 7 days p.m.) using two cooking methods. Using a boiling waterbath, samples were either cooked to a core temperature of 70 °C or boiled for 3h. The latter method was meant to reflect the traditional cooking method employed in countries where preparation of prerigor meat is practiced. The time postmortem at which the meat was prepared had a large effect on the tenderness (shear force) of the meat (P<0.01). Cooking prerigor and at rigor meat to 70 °C resulted in higher shear force values than their post rigor counterparts at 1 and 7 days p.m. (9.4 and 9.6 vs. 7.2 and 3.7 kg, respectively). The differences in tenderness between the treatment groups could be largely explained by a difference in contraction status of the meat after cooking and the effect of ageing on tenderness. Cooking pre and at rigor meat resulted in severe muscle contraction as evidenced by the differences in sarcomere length of the cooked samples. Mean sarcomere lengths in the pre and at rigor samples ranged from 1.05 to 1.20 μm. The mean sarcomere length in the post rigor samples was 1.44 μm. Cooking for 3 h at 100 °C did improve the tenderness of pre and at rigor prepared meat as compared to cooking to 70 °C, but not to the extent that ageing did. It is concluded that additional intervention methods are needed to improve the tenderness of prerigor cooked meat. Copyright © 2011 Elsevier B.V. All rights reserved.

Factors Influencing the Phenotypic Expression of Hypertrophic Cardiomyopathy in Genetic Carriers.

PubMed

Pérez-Sánchez, Inmaculada; Romero-Puche, Antonio José; García-Molina Sáez, Esperanza; Sabater-Molina, María; López-Ayala, José María; Muñoz-Esparza, Carmen; López-Cuenca, David; de la Morena, Gonzalo; Castro-García, Francisco José; Gimeno-Blanes, Juan Ramón

2018-03-01

Hypertrophic cardiomyopathy (HCM) is a disorder with variable expression. It is mainly caused by mutations in sarcomeric genes but the phenotype could be modulated by other factors. The aim of this study was to determine whether factors such as sex, systemic hypertension, or physical activity are modifiers of disease severity and to establish their role in age-related penetrance of HCM. We evaluated 272 individuals (mean age 49 ± 17 years, 57% males) from 72 families with causative mutations. The relationship between sex, hypertension, physical activity, and left ventricular hypertrophy was studied. The proportion of affected individuals increased with age. Men developed the disease 12.5 years earlier than women (adjusted median, 95%CI, -17.52 to -6.48; P < .001). Hypertensive patients were diagnosed with HCM later (10.8 years of delay) than normotensive patients (adjusted median, 95%CI, 6.28-17.09; P < .001). Individuals who performed physical activity were diagnosed with HCM significantly earlier (7.3 years, adjusted median, 95%CI, -14.49 to -1.51; P = .016). Sex, hypertension, and the degree of physical activity were not significantly associated with the severity of left ventricular hypertrophy. Adjusted survival both free from sudden death and from the combined event were not influenced by any of the exploratory variables. Men and athletes who are carriers of sarcomeric mutations are diagnosed earlier than women and sedentary individuals. Hypertensive carriers of sarcomeric mutations have a delayed diagnosis. Sex, hypertension, and physical activity are not associated with disease severity in carriers of HCM causative mutations. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Orientation of Myosin Binding Protein C in the Cardiac Muscle Sarcomere Determined by Domain-Specific Immuno-EM

PubMed Central

Lee, Kyounghwan; Harris, Samantha P.; Sadayappan, Sakthivel; Craig, Roger

2014-01-01

Myosin binding protein-C is a thick filament protein of vertebrate striated muscle. The cardiac isoform (cMyBP-C) is essential for normal cardiac function, and mutations in cMyBP-C cause cardiac muscle disease. The rod-shaped molecule is composed primarily of 11 immunoglobulin- or fibronectin-like domains, and is located at 9 sites, 43 nm apart, in each half of the A-band. To understand how cMyBP-C functions, it is important to know its structural organization in the sarcomere, as this will affect its ability to interact with other sarcomeric proteins. Several models have been proposed, in which cMyBP-C wraps around, extends radially from, or runs axially along the thick filament. Our goal was to define cMyBP-C orientation by determining the relative axial positions of different cMyBP-C domains. Immuno-electron microscopy was performed using mouse cardiac myofibrils labeled with antibodies specific to the N- and C-terminal domains and to the middle of cMyBP-C. Antibodies to all regions of the molecule, except the C-terminus, labeled at the same nine axial positions in each half A-band, consistent with a circumferential and/or radial rather than an axial orientation of the bulk of the molecule. The C-terminal antibody stripes were slightly displaced axially, demonstrating an axial orientation of the C-terminal 3 domains, with the C-terminus closer to the M-line. These results, combined with previous studies, suggest that the C-terminal domains of cMyBP-C run along the thick filament surface, while the N-terminus extends towards neighboring thin filaments. This organization provides a structural framework for understanding cMyBP-C’s modulation of cardiac muscle contraction. PMID:25451032

A rare missense mutation in MYH6 associates with non-syndromic coarctation of the aorta.

PubMed

Bjornsson, Thorsteinn; Thorolfsdottir, Rosa B; Sveinbjornsson, Gardar; Sulem, Patrick; Norddahl, Gudmundur L; Helgadottir, Anna; Gretarsdottir, Solveig; Magnusdottir, Audur; Danielsen, Ragnar; Sigurdsson, Emil L; Adalsteinsdottir, Berglind; Gunnarsson, Sverrir I; Jonsdottir, Ingileif; Arnar, David O; Helgason, Hrodmar; Gudbjartsson, Tomas; Gudbjartsson, Daniel F; Thorsteinsdottir, Unnur; Holm, Hilma; Stefansson, Kari

2018-03-24

Coarctation of the aorta (CoA) accounts for 4-8% of congenital heart defects (CHDs) and confers substantial morbidity despite treatment. It is increasingly recognized as a highly heritable condition. The aim of the study was to search for sequence variants that affect the risk of CoA. We performed a genome-wide association study of CoA among Icelanders (120 cases and 355 166 controls) based on imputed variants identified through whole-genome sequencing. We found association with a rare (frequency = 0.34%) missense mutation p.Arg721Trp in MYH6 (odds ratio = 44.2, P = 5.0 × 10-22), encoding the alpha-heavy chain subunit of cardiac myosin, an essential sarcomere protein. Approximately 20% of individuals with CoA in Iceland carry this mutation. We show that p.Arg721Trp also associates with other CHDs, in particular bicuspid aortic valve. We have previously reported broad effects of p.Arg721Trp on cardiac electrical function and strong association with sick sinus syndrome and atrial fibrillation. Through a population approach, we found that a rare missense mutation p.Arg721Trp in the sarcomere gene MYH6 has a strong effect on the risk of CoA and explains a substantial fraction of the Icelanders with CoA. This is the first mutation associated with non-familial or sporadic form of CoA at a population level. The p.Arg721Trp in MYH6 causes a cardiac syndrome with highly variable expressivity and emphasizes the importance of sarcomere integrity for cardiac development and function.

Dual function of the UNC-45b chaperone with myosin and GATA4 in cardiac development

PubMed Central

Chen, Daisi; Li, Shumin; Singh, Ram; Spinette, Sarah; Sedlmeier, Reinhard; Epstein, Henry F.

2012-01-01

Summary Cardiac development requires interplay between the regulation of gene expression and the assembly of functional sarcomeric proteins. We report that UNC-45b recessive loss-of-function mutations in C3H and C57BL/6 inbred mouse strains cause arrest of cardiac morphogenesis at the formation of right heart structures and failure of contractile function. Wild-type C3H and C57BL/6 embryos at the same stage, E9.5, form actively contracting right and left atria and ventricles. The known interactions of UNC-45b as a molecular chaperone are consistent with diminished accumulation of the sarcomeric myosins, but not their mRNAs, and the resulting decreased contraction of homozygous mutant embryonic hearts. The novel finding that GATA4 accumulation is similarly decreased at the protein but not mRNA levels is also consistent with the function of UNC-45b as a chaperone. The mRNAs of known downstream targets of GATA4 during secondary cardiac field development, the cardiogenic factors Hand1, Hand2 and Nkx-2.5, are also decreased, consistent with the reduced GATA4 protein accumulation. Direct binding studies show that the UNC-45b chaperone forms physical complexes with both the alpha and beta cardiac myosins and the cardiogenic transcription factor GATA4. Co-expression of UNC-45b with GATA4 led to enhanced transcription from GATA promoters in naïve cells. These novel results suggest that the heart-specific UNC-45b isoform functions as a molecular chaperone mediating contractile function of the sarcomere and gene expression in cardiac development. PMID:22553207

Sarcomere-length dependence of myosin filament structure in skeletal muscle fibres of the frog

PubMed Central

Reconditi, Massimo; Brunello, Elisabetta; Fusi, Luca; Linari, Marco; Martinez, Manuel Fernandez; Lombardi, Vincenzo; Irving, Malcolm; Piazzesi, Gabriella

2014-01-01

X-ray diffraction patterns were recorded at beamline ID02 of the European Synchrotron Radiation Facility from small bundles of skeletal muscle fibres from Rana esculenta at sarcomere lengths between 2.1 and 3.5 μm at 4°C. The intensities of the X-ray reflections from resting fibres associated with the quasi-helical order of the myosin heads and myosin binding protein C (MyBP-C) decreased in the sarcomere length range 2.6–3.0 μm but were constant outside it, suggesting that an OFF conformation of the thick filament is maintained by an interaction between MyBP-C and the thin filaments. During active isometric contraction the intensity of the M3 reflection from the regular repeat of the myosin heads along the filaments decreased in proportion to the overlap between thick and thin filaments, with no change in its interference fine structure. Thus, myosin heads in the regions of the thick filaments that do not overlap with thin filaments are highly disordered during isometric contraction, in contrast to their quasi-helical order at rest. Heads in the overlap region that belong to two-headed myosin molecules that are fully detached from actin are also highly disordered, in contrast to the detached partners of actin-attached heads. These results provide strong support for the concept of a regulatory structural transition in the thick filament involving changes in both the organisation of the myosin heads on its surface and the axial periodicity of the myosin tails in its backbone, mediated by an interaction between MyBP-C and the thin filaments. PMID:24344169

Motivated Use of Numerical Anchors for Judgments Relevant to the Self.

PubMed

Joel, Samantha; Spielmann, Stephanie S; MacDonald, Geoff

2017-07-01

The anchoring effect has been replicated so extensively that it is generally thought to be ubiquitous. However, anchoring has primarily been tested in domains in which people are motivated to reach accurate conclusions rather than biased conclusions. Is the anchoring effect robust even when the anchors are threatening? In three studies, participants made a series of probability judgments about their own futures paired with either optimistic anchors (e.g., "Do you think that the chances that your current relationship will last a lifetime are more or less than 95%?"), pessimistic anchors (e.g., "more or less than 10%?"), or no anchors. A fourth study experimentally manipulated motivation to ignore the anchor with financial incentives. Across studies, anchors that implied high probabilities of unwanted events occurring were ineffective. Together, these studies suggest that anchoring has an important boundary condition: Personally threatening anchors are ignored as a result of motivated reasoning processes.

Chemical composition and structural characteristics of Arabian camel (Camelus dromedarius) m. longissimus thoracis.

PubMed

Al-Owaimer, A N; Suliman, G M; Sami, A S; Picard, B; Hocquette, J F

2014-03-01

Saudi Arabian camels of four breeds (6 animals per breed) were used to evaluate characteristics and quality of their meat. Chemical composition, fibre cross sectional area, collagen content, muscle metabolism, cooking loss, pH at 24 h post mortem, colour values (except redness) and shear force of Longissimus thoracis (LT) muscle did not differ between the breeds. Elevated pH values and short sarcomeres reduced overall tenderisation, with a difference between myofibril fragmentation index (P<0.001) and sarcomere length (P<0.05) between breeds. A positive correlation was observed between the activities of the mitochondrial enzymes (r>0.49), between the glycolytic activities (PFK and LDH) (r=0.61) and between Myosin Heavy Chain IIa and LDH activity. The intramuscular fat content was positively associated with redness and muscle oxidative metabolism, whereas shear force had a slight positive association with collagen content and muscle glycolytic metabolism and a negative association with muscle oxidative metabolism and muscle fibre area. © 2013.

Rad-deletion Phenocopies Tonic Sympathetic Stimulation of the Heart.

PubMed

Levitan, Bryana M; Manning, Janet R; Withers, Catherine N; Smith, Jeffrey D; Shaw, Robin M; Andres, Douglas A; Sorrell, Vincent L; Satin, Jonathan

2016-12-01

Sympathetic stimulation modulates L-type calcium channel (LTCC) gating to contribute to increased systolic heart function. Rad is a monomeric G-protein that interacts with LTCC. Genetic deletion of Rad (Rad -/- ) renders LTCC in a sympathomimetic state. The study goal was to use a clinically inspired pharmacological stress echocardiography test, including analysis of global strain, to determine whether Rad -/- confers tonic positive inotropic heart function. Sarcomere dynamics and strain showed partial parallel isoproterenol (ISO) responsiveness for wild-type (WT) and for Rad -/- . Rad -/- basal inotropy was elevated compared to WT but was less responsiveness to ISO. Rad protein levels were lower in human patients with end-stage non-ischemic heart failure. These results show that Rad reduction provides a stable inotropic response rooted in sarcomere level function. Thus, reduced Rad levels in heart failure patients may be a compensatory response to need for increased output in the setting of HF. Rad deletion suggests a future therapeutic direction for inotropic support.

Do sarcomere length, collagen content, pH, intramuscular fat and desmin degradation explain variation in the tenderness of three ovine muscles?

PubMed

Starkey, Colin P; Geesink, Geert H; Collins, Damian; Hutton Oddy, V; Hopkins, David L

2016-03-01

The longissimus (n=118) (LL), semimembranosus (n=104) (SM) and biceps femoris (n=134) (BF) muscles were collected from lamb and sheep carcases and aged for 5days (LL and SM) and 14days (BF) to study the impact of muscle characteristics on tenderness as assessed by shear force (SF) and sensory evaluation. The impact of gender, animal age, collagen content, sarcomere length (SL), desmin degradation, ultimate pH and intramuscular fat (IMF) on tenderness was examined. The main factors which influenced SF of the LL were IMF, SL and desmin degradation, but for sensory tenderness, IMF, ultimate pH and gender were the main factors. The SF and sensory tenderness of the SM was best predicted by the degree of desmin degradation. For the BF soluble collagen and animal age both influenced SF. Different factors affect tenderness across muscles and not one prediction model applied across all muscles equally well. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rad-deletion Phenocopies Tonic Sympathetic Stimulation of the Heart

PubMed Central

Levitan, Bryana M.; Manning, Janet R.; Withers, Catherine N.; Smith, Jeffrey D.; Shaw, Robin M.; Andres, Douglas A.; Sorrell, Vincent L.

2016-01-01

Sympathetic stimulation modulates L-type calcium channel (LTCC) gating to contribute to increased systolic heart function. Rad is a monomeric G-protein that interacts with LTCC. Genetic deletion of Rad (Rad−/−) renders LTCC in a sympathomimetic state. The study goal was to use a clinically inspired pharmacological stress echocardiography test, including analysis of global strain, to determine whether Rad−/− confers tonic positive inotropic heart function. Sarcomere dynamics and strain showed partial parallel isoproterenol (ISO) responsiveness for wild-type (WT) and for Rad−/−. Rad−/− basal inotropy was elevated compared to WT but was less responsiveness to ISO. Rad protein levels were lower in human patients with end-stage non-ischemic heart failure. These results show that Rad reduction provides a stable inotropic response rooted in sarcomere level function. Thus, reduced Rad levels in heart failure patients may be a compensatory response to need for increased output in the setting of HF. Rad deletion suggests a future therapeutic direction for inotropic support. PMID:27798760

Thick Filament Protein Network, Functions, and Disease Association.

PubMed

Wang, Li; Geist, Janelle; Grogan, Alyssa; Hu, Li-Yen R; Kontrogianni-Konstantopoulos, Aikaterini

2018-03-13

Sarcomeres consist of highly ordered arrays of thick myosin and thin actin filaments along with accessory proteins. Thick filaments occupy the center of sarcomeres where they partially overlap with thin filaments. The sliding of thick filaments past thin filaments is a highly regulated process that occurs in an ATP-dependent manner driving muscle contraction. In addition to myosin that makes up the backbone of the thick filament, four other proteins which are intimately bound to the thick filament, myosin binding protein-C, titin, myomesin, and obscurin play important structural and regulatory roles. Consistent with this, mutations in the respective genes have been associated with idiopathic and congenital forms of skeletal and cardiac myopathies. In this review, we aim to summarize our current knowledge on the molecular structure, subcellular localization, interacting partners, function, modulation via posttranslational modifications, and disease involvement of these five major proteins that comprise the thick filament of striated muscle cells. © 2018 American Physiological Society. Compr Physiol 8:631-709, 2018. Copyright © 2018 American Physiological Society. All rights reserved.

Meat quality attributes of Agile Wallabies.

PubMed

Geesink, Geert H; van den Heuvel, Aaron; Hunt, Warren

2017-11-01

Meat quality traits of Agile Wallaby (Macropus agilis) M. longissimus (loin) and M. semimembranosus (topside) were investigated. Both muscles exhibited a relatively high pH (>5.7) and dark colour (L*-, a*-, and b*-values). Aging the loins from 2 to 21days p.m. had a significant effect on shear force. However, the results regarding shear force, myofibrillar fragmentation index (MFI) and degradation of desmin and troponin-T suggested that the aging response largely occurred within 2days p.m. Suspension of carcasses from one leg resulted in a side effect on shear force of the loin at 2 and 7days p.m., but not on sarcomere length or MFI. Topsides from the free hanging leg exhibited lower shear force values (33 vs 42N) and greater sarcomere lengths (2.51 vs 1.84μM). Tenderness, juiciness, flavour and overall liking were higher for loins than topsides. Sensory scores for the loin and topside were slightly lower and similar, respectively, to those reported for lamb. Copyright © 2017 Elsevier Ltd. All rights reserved.

Test Score Equating Using a Mini-Version Anchor and a Midi Anchor: A Case Study Using SAT[R] Data

ERIC Educational Resources Information Center

Liu, Jinghua; Sinharay, Sandip; Holland, Paul W.; Curley, Edward; Feigenbaum, Miriam

2011-01-01

This study explores an anchor that is different from the traditional miniature anchor in test score equating. In contrast to a traditional "mini" anchor that has the same spread of item difficulties as the tests to be equated, the studied anchor, referred to as a "midi" anchor (Sinharay & Holland), has a smaller spread of…

The Synergistic Effects of MoS2 and Liquid Lubrication

NASA Astrophysics Data System (ADS)

Buttery, M.; Roberts, E.; Stanley, S.; Murer, J.

2015-09-01

We present an overview of a three-stage program on the potential for hybrid lubrication of MoS2 and PFPE fluids (Fomblin Z25 & Braycote 601EF) performed at the European Space Tribology Laboratory (ESTL).Tests were performed using a spiral orbit tribometer (SOT) and a pin-on-disc tribometer (POD), demonstrating encouraging results. Hybrid lubrication allows for extended periods of in-air running of MoS2 with no detrimental effect to the subsequent in-vacuum lifetime. In addition, hybrid lubrication was shown to be synergistic, with the lifetime of the hybrid fluid/MoS2 lubrication extended in comparison to the individual constituents, with no detriment to the friction.

Galaxy Transformations In The Cosmic Web

NASA Astrophysics Data System (ADS)

Jablonka, Pascale

2017-06-01

In this talk, I present a new survey, the Spatial Extended EDisCS Survey (SEEDisCS), that aims at understanding how clusters assemble and the level at which galaxies are preprocessed before falling on the cluster cores. SEEDisCS therefore focusses on the changes in galaxy properties along the large scale structures surrounding a couple of z 0.5 medium mass clusters, I first describe how spiral disc stellar populations are affected by the environment,and how we can get constraints on the timescale of star formation quenching. I then present new NOEMA and ALMA CO observations that trace the fate of the galaxy cold gas content along the infalling paths towards the cluster cores.

Use of the ROC anchor in foot and ankle surgery. A retrospective study.

PubMed

Kuwada, G T

1999-05-01

A retrospective study was conducted on the use of the ROC (Radial Osteo Compression) soft-tissue anchor in foot and ankle surgery. This article describes how the anchor is deployed, problematic aspects of using the anchor, and complications and success rates associated with the anchor in ankle stabilizations, posterior tibial tendon reconstruction, peroneus brevis tendon reconstruction after fracture of the base of the fifth metatarsal, and detachment and reattachment of the Achilles tendon. The ROC anchor consists of the anchor with nonabsorbable suture attached to the shaft, the deployment handle, and drill bits. The anchor and shaft are snapped into the deployment handle and inserted into the drill hole. Compression of the trigger deploys the anchor into the hole. The ROC anchor was found to be reliable, useful, and relatively easy to deploy, with outcomes similar to those of other soft-tissue anchors.

Monogenean anchor morphometry: systematic value, phylogenetic signal, and evolution

PubMed Central

Soo, Oi Yoon Michelle; Tan, Wooi Boon; Lim, Lee Hong Susan

2016-01-01

Background. Anchors are one of the important attachment appendages for monogenean parasites. Common descent and evolutionary processes have left their mark on anchor morphometry, in the form of patterns of shape and size variation useful for systematic and evolutionary studies. When combined with morphological and molecular data, analysis of anchor morphometry can potentially answer a wide range of biological questions. Materials and Methods. We used data from anchor morphometry, body size and morphology of 13 Ligophorus (Monogenea: Ancyrocephalidae) species infecting two marine mugilid (Teleostei: Mugilidae) fish hosts: Moolgarda buchanani (Bleeker) and Liza subviridis (Valenciennes) from Malaysia. Anchor shape and size data (n = 530) were generated using methods of geometric morphometrics. We used 28S rRNA, 18S rRNA, and ITS1 sequence data to infer a maximum likelihood phylogeny. We discriminated species using principal component and cluster analysis of shape data. Adams’s Kmult was used to detect phylogenetic signal in anchor shape. Phylogeny-correlated size and shape changes were investigated using continuous character mapping and directional statistics, respectively. We assessed morphological constraints in anchor morphometry using phylogenetic regression of anchor shape against body size and anchor size. Anchor morphological integration was studied using partial least squares method. The association between copulatory organ morphology and anchor shape and size in phylomorphospace was used to test the Rohde-Hobbs hypothesis. We created monogeneaGM, a new R package that integrates analyses of monogenean anchor geometric morphometric data with morphological and phylogenetic data. Results. We discriminated 12 of the 13 Ligophorus species using anchor shape data. Significant phylogenetic signal was detected in anchor shape. Thus, we discovered new morphological characters based on anchor shaft shape, the length between the inner root point and the outer root point, and the length between the inner root point and the dent point. The species on M. buchanani evolved larger, more robust anchors; those on L. subviridis evolved smaller, more delicate anchors. Anchor shape and size were significantly correlated, suggesting constraints in anchor evolution. Tight integration between the root and the point compartments within anchors confirms the anchor as a single, fully integrated module. The correlation between male copulatory organ morphology and size with anchor shape was consistent with predictions from the Rohde-Hobbs hypothesis. Conclusions. Monogenean anchors are tightly integrated structures, and their shape variation correlates strongly with phylogeny, thus underscoring their value for systematic and evolutionary biology studies. Our MonogeneaGM R package provides tools for researchers to mine biological insights from geometric morphometric data of speciose monogenean genera. PMID:26966649

The host dark matter haloes of [O II] emitters at 0.5 < z < 1.5

NASA Astrophysics Data System (ADS)

Gonzalez-Perez, V.; Comparat, J.; Norberg, P.; Baugh, C. M.; Contreras, S.; Lacey, C.; McCullagh, N.; Orsi, A.; Helly, J.; Humphries, J.

2018-03-01

Emission line galaxies (ELGs) are used in several ongoing and upcoming surveys (SDSS-IV/eBOSS, DESI) as tracers of the dark matter distribution. Using a new galaxy formation model, we explore the characteristics of [O II] emitters, which dominate optical ELG selections at z ≃ 1. Model [O II] emitters at 0.5 < z < 1.5 are selected to mimic the DEEP2, VVDS, eBOSS and DESI surveys. The luminosity functions of model [O II] emitters are in reasonable agreement with observations. The selected [O II] emitters are hosted by haloes with Mhalo ≥ 1010.3h-1M⊙, with ˜90 per cent of them being central star-forming galaxies. The predicted mean halo occupation distributions of [O II] emitters have a shape typical of that inferred for star-forming galaxies, with the contribution from central galaxies, < N > _{[O II] cen}, being far from the canonical step function. The < N > _{[O II] cen}} can be described as the sum of an asymmetric Gaussian for discs and a step function for spheroids, which plateau below unity. The model [O II] emitters have a clustering bias close to unity, which is below the expectations for eBOSS and DESI ELGs. At z ˜ 1, a comparison with observed g-band-selected galaxy, which is expected to be dominated by [O II] emitters, indicates that our model produces too few [O II] emitters that are satellite galaxies. This suggests the need to revise our modelling of hot gas stripping in satellite galaxies.

Proposed rocket experiments to measure the profile and intensity of the solar He1584A resonance line

NASA Technical Reports Server (NTRS)

Judge, D. L.

1978-01-01

The intensity and profile of the helium resonance line at 584 A from the entire disc of the sun was investigated using a rocket-borne helium-filled spectrometer and a curve of growth technique. The line profile was found to be accurately represented by a Gaussian profile with full width at half maximum of 122 plus or minus 10m A while the integrated intensity was measured to be (2.6 plus or minus 1.3) x 10 to the 9th power/photons sec sq cm at solar levels of F sub 10.7 = 90.8 x 10 to the minus 22th power/sq m H sub z and R sub z = 27. The measured linewidth is in good agreement with previous spectrographic measurement but the integrated intensity is larger than most previous photoelectric measurements. However, the derived line center flux of (2.0 plus or minus 1.0) x 10 to the 10th power/photons sec sq cm A is in good agreement with values inferred from airglow measurements.

Precision of the anchor influences the amount of adjustment.

PubMed

Janiszewski, Chris; Uy, Dan

2008-02-01

The anchoring-and-adjustment heuristic has been used to account for a wide variety of numerical judgments. Five studies show that adjustment away from a numerical anchor is smaller if the anchor is precise than if it is rounded. Evidence suggests that precise anchors, compared with rounded anchors, are represented on a subjective scale with a finer resolution. If adjustment consists of a series of iterative mental movements along a subjective scale, then an adjustment from a precise anchor should result in a smaller overall correction than an adjustment from a rounded anchor.

International Space Station (ISS)

NASA Image and Video Library

2007-08-13

As the construction continued on the International Space Station (ISS), STS-118 astronaut and mission specialist, Dave Williams, representing the Canadian Space Agency, was anchored on the foot restraint of the Canadarm2 as he participated in the second session of Extra Vehicular Activity (EVA) for the mission. Assisting Williams was Rick Mastracchio (out of frame). During the 6 hour, 28 minute space walk, the two removed a faulty control moment gyroscope (CMG-3) and installed a new CMG into the Z1 truss. The failed CMG will remain in its temporary stowage location on the exterior of the station until it is returned to Earth on a later Shuttle mission. The new gyroscope is one of four CMGs that are used to control the orbital attitude of the station.