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Sample records for maximum contractile response

  1. Calcium-responsive contractility during fertilization in sea urchin eggs.

    Science.gov (United States)

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

    2006-04-01

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

  2. Endothelin-1 and endothelin-2 initiate and maintain contractile responses by different mechanisms in rat mesenteric and cerebral arteries

    DEFF Research Database (Denmark)

    Compeer, M. G.; Janssen, G. M. J.; De Mey, J. G. R.

    2013-01-01

    , but relaxed ET-1-induced contractions in MRA. A PLC inhibitor prevented contractile responses to ET-1 and ET-2 in MRA and BA, and relaxed ET-1- and ET-2-induced responses in MRA and ET-1 effects in BA. A Rho-kinase inhibitor did not modify sensitivity, maximum and maintenance of responses to both peptides...... in both arteries but relaxed ET-2, but not ET-1, effects in MRA and ET-1 effects in BA. Conclusions and ImplicationsPLC played a key role in arterial contractile responses to ETs, but ET-1 and ET-2 initiated and maintained vasoconstriction through different mechanisms, and these differed between MRA...

  3. Sex differences and the effects of ovariectomy on the β-adrenergic contractile response

    Science.gov (United States)

    McIntosh, Victoria J.; Chandrasekera, P. Charukeshi

    2011-01-01

    The presence of sex differences in myocardial β-adrenergic responsiveness is controversial, and limited studies have addressed the mechanism underlying these differences. Studies were performed using isolated perfused hearts from male, intact female and ovariectomized female mice to investigate sex differences and the effects of ovarian hormone withdrawal on β-adrenergic receptor function. Female hearts exhibited blunted contractile responses to the β-adrenergic receptor agonist isoproterenol (ISO) compared with males but not ovariectomized females. There were no sex differences in β1-adrenergic receptor gene or protein expression. To investigate the role of adenylyl cyclase, phosphodiesterase, and the cAMP-signaling cascade in generating sex differences in the β-adrenergic contractile response, dose-response studies were performed in isolated perfused male and female hearts using forskolin, 3-isobutyl-1-methylxanthine (IBMX), and 8-(4-chlorophenylthio)adenosine 3′,5′-cyclic monophosphate (CPT-cAMP). Males showed a modestly enhanced contractile response to forskolin at 300 nM and 5 μM compared with females, but there were no sex differences in the response to IBMX or CPT-cAMP. The role of the A1 adenosine receptor (A1AR) in antagonizing the β-adrenergic contractile response was investigated using both the A1AR agonist 2-chloro-N6-cyclopentyl-adenosine and A1AR knockout (KO) mice. Intact females showed an enhanced A1AR anti-adrenergic effect compared with males and ovariectomized females. The β-adrenergic contractile response was potentiated in both male and female A1ARKO hearts, with sex differences no longer present above 1 nM ISO. The β-adrenergic contractile response is greater in male hearts than females, and minor differences in the action of adenylyl cyclase or the A1AR may contribute to these sex differences. PMID:21685268

  4. Simulation of the contractile response of cells on an array of micro-posts.

    LENUS (Irish Health Repository)

    McGarry, J P

    2009-09-13

    A bio-chemo-mechanical model has been used to predict the contractile responses of smooth cells on a bed of micro-posts. Predictions obtained for smooth muscle cells reveal that, by converging onto a single set of parameters, the model captures all of the following responses in a self-consistent manner: (i) the scaling of the force exerted by the cells with the number of posts; (ii) actin distributions within the cells, including the rings of actin around the micro-posts; (iii) the curvature of the cell boundaries between the posts; and (iv) the higher post forces towards the cell periphery. Similar correspondences between predictions and measurements have been demonstrated for fibroblasts and mesenchymal stem cells once the maximum stress exerted by the stress fibre bundles has been recalibrated. Consistent with measurements, the model predicts that the forces exerted by the cells will increase with both increasing post stiffness and cell area (or equivalently, post spacing). In conjunction with previous assessments, these findings suggest that this framework represents an important step towards a complete model for the coupled bio-chemo-mechanical responses of cells.

  5. The importance of myocardial contractile reserve in predicting response to cardiac resynchronization therapy

    NARCIS (Netherlands)

    Kloosterman, Mariëlle; Damman, Kevin; Van Veldhuisen, Dirk J; Rienstra, Michiel; Maass, Alexander H

    AimTo perform a meta-analysis and systematic review of published data to assess the relationship between contractile reserve and response to cardiac resynchronization therapy (CRT) in patients with heart failure. Methods and resultsWe searched MEDLINE/PubMed and Cochrane for all papers published up

  6. PKA catalytic subunit compartmentation regulates contractile and hypertrophic responses to β-adrenergic signaling

    Science.gov (United States)

    Yang, Jason H.; Polanowska-Grabowska, Renata K.; Smith, Jeffrey S.; Shields, Charles W.; Saucerman, Jeffrey J.

    2014-01-01

    β-adrenergic signaling is spatiotemporally heterogeneous in the cardiac myocyte, conferring exquisite control to sympathetic stimulation. Such heterogeneity drives the formation of protein kinase A (PKA) signaling microdomains, which regulate Ca2+ handling and contractility. Here, we test the hypothesis that the nucleus independently comprises a PKA signaling microdomain regulating myocyte hypertrophy. Spatially-targeted FRET reporters for PKA activity identified slower PKA activation and lower isoproterenol sensitivity in the nucleus (t50 = 10.60±0.68 min; EC50 = 89.00 nmol/L) than in the cytosol (t50 = 3.71±0.25 min; EC50 = 1.22 nmol/L). These differences were not explained by cAMP or AKAP-based compartmentation. A computational model of cytosolic and nuclear PKA activity was developed and predicted that differences in nuclear PKA dynamics and magnitude are regulated by slow PKA catalytic subunit diffusion, while differences in isoproterenol sensitivity are regulated by nuclear expression of protein kinase inhibitor (PKI). These were validated by FRET and immunofluorescence. The model also predicted differential phosphorylation of PKA substrates regulating cell contractility and hypertrophy. Ca2+ and cell hypertrophy measurements validated these predictions and identified higher isoproterenol sensitivity for contractile enhancements (EC50 = 1.84 nmol/L) over cell hypertrophy (EC50 = 85.88 nmol/L). Over-expression of spatially targeted PKA catalytic subunit to the cytosol or nucleus enhanced contractile and hypertrophic responses, respectively. We conclude that restricted PKA catalytic subunit diffusion is an important PKA compartmentation mechanism and the nucleus comprises a novel PKA signaling microdomain, insulating hypertrophic from contractile β-adrenergic signaling responses. PMID:24225179

  7. Contractile Response of Bovine Lateral Saphenous Vein to Ergotamine Tartrate Exposed to Different Concentrations of Molecularly Imprinted Polymer

    Directory of Open Access Journals (Sweden)

    Manoj B. Kudupoje

    2018-01-01

    Full Text Available Ergot alkaloids, in their active isomeric form, affect animal health and performance, and adsorbents are used to mitigate toxicities by reducing bioavailability. Adsorbents with high specificity (molecularly imprinted polymers: MIP adsorb ergot alkaloids in vitro, but require evaluation for biological implications. Using ex vivo myography, synthetic polymers were evaluated for effects on the bioactivity of ergotamine tartrate (ETA. Polymers were first evaluated using isotherms. Lateral saphenous veins were collected from 17 steers for four independent studies: dose response of ETA, adsorbent dose response, validation of pre-myograph incubation conditions and MIP/ non-molecularly imprinted polymer (NIP comparison. Norepinephrine normalized percent contractile response to increasing ETA exhibited a sigmoidal dose response (max: 88.47 and log of the effective molar concentration (EC50 (−log [ETA] of 6.66 ± 0.17 M. Although sample preparation time affected contractile response (p < 0.001, pre-myograph incubation temperature (39 vs. 21 °C, 1 h had no effect (p > 0.05. Isothermal adsorption showed a maximum adsorption of 3.27E-008 moles·mg−1 and affinity between 0.51 and 0.57 mg (R2: 0.83–0.92 for both polymers, with no significant difference between polymers (p > 0.05. No significant differences in maximum inhibitory (p = 0.96 and IC50 responses (p = 0.163 between MIP and NIP were noticed. Normalized percent contraction could be predicted from the in vitro adsorption data (R2 = 0.87, p < 0.01, for both polymers. These studies indicate that synthetic polymers are potentially effective adsorbents to mitigate ergot toxicity caused by ergot alkaloids, with little evidence of significant differences between MIP and NIP in aqueous media.

  8. Measuring the Contractile Response of Isolated Tissue Using an Image Sensor

    Directory of Open Access Journals (Sweden)

    David Díaz-Martín

    2015-04-01

    Full Text Available Isometric or isotonic transducers have traditionally been used to study the contractile/relaxation effects of drugs on isolated tissues. However, these mechanical sensors are expensive and delicate, and they are associated with certain disadvantages when performing experiments in the laboratory. In this paper, a method that uses an image sensor to measure the contractile effect of drugs on blood vessel rings and other luminal organs is presented. The new method is based on an image-processing algorithm, and it provides a fast, easy and non-expensive way to analyze the effects of such drugs. In our tests, we have obtained dose-response curves from rat aorta rings that are equivalent to those achieved with classical mechanic sensors.

  9. Changes of contractile responses due to simulated weightlessness in rat soleus muscle

    Science.gov (United States)

    Elkhammari, A.; Noireaud, J.; Léoty, C.

    1994-08-01

    Some contractile and electrophysiological properties of muscle fibers isolated from the slow-twitch soleus (SOL) and fast-twitch extensor digitorum longus (EDL) muscles of rats were compared with those measured in SOL muscles from suspended rats. In suspendede SOL (21 days of tail-suspension) membrane potential (Em), intracellular sodium activity (aiNa) and the slope of the relationship between Em and log [K]o were typical of fast-twitch muscles. The relation between the maximal amplitude of K-contractures vs Em was steeper for control SOL than for EDL and suspended SOL muscles. After suspension, in SOL muscles the contractile threshold and the inactivation curves for K-contractures were shifted to more positive Em. Repriming of K-contractures was unaffected by suspencion. The exposure of isolated fibers to perchlorate (ClO4-)-containing (6-40 mM) solutions resulted ina similar concentration-dependent shift to more negative Em of activation curves for EDL and suspended SOL muscles. On exposure to a Na-free TEA solution, SOL from control and suspended rats, in contrast to EDL muscles, generated slow contractile responses. Suspended SOL showed a reduced sensitivity to the contracture-producing effect of caffeine compared to control muscles. These results suggested that the modification observed due to suspension could be encounted by changes in the characteristics of muscle fibers from slow to fast-twitch type.

  10. Adaptive responses of mouse skeletal muscle to contractile activity: The effect of age.

    Science.gov (United States)

    Vasilaki, A; McArdle, F; Iwanejko, L M; McArdle, A

    2006-11-01

    This study has characterised the time course of two major transcriptional adaptive responses to exercise (changes in antioxidant defence enzyme activity and heat shock protein (HSP) content) in muscles of adult and old male mice following isometric contractions and has examined the mechanisms involved in the age-related reduction in transcription factor activation. Muscles of B6XSJL mice were subjected to isometric contractions and analysed for antioxidant defence enzyme activities, heat shock protein content and transcription factor DNA binding activity. Data demonstrated a significant increase in superoxide dismutase (SOD) and catalase activity and HSP content of muscles of adult mice following contractile activity which was associated with increased activation of the transcription factors, nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) and heat shock factor (HSF) following contractions. Significant increases in SOD and catalase activity and heat shock cognate (HSC70) content were seen in quiescent muscles of old mice. The increase in antioxidant defence enzyme activity following contractile activity seen in muscles of adult mice was not seen in muscles of old mice and this was associated with a failure to fully activate NF-kappaB and AP-1 following contractions. In contrast, although the production of HSPs was also reduced in muscles of old mice following contractile activity compared with muscles of adult mice following contractions, this was not due to a gross reduction in the DNA binding activity of HSF.

  11. Effects of Silodosin and Tamsulosin on the Seminal Vesicle Contractile Response.

    Science.gov (United States)

    Hayashi, Tokumasa; Takeya, Mitsue; Nakamura, Kei-ichiro; Matsuoka, Kei

    2016-01-01

    To understand the mechanisms underlying ejaculation dysfunction caused by α1A-adrenocetor (AR) antagonists, the effects of α1A-AR antagonists on the contractile responses of the seminal vesicle were investigated. Isolated seminal vesicles from guinea pigs were cannulated and pressurized, and the changes in the intraluminal pressure were recorded. Periodic applications of electrical stimulation (ES) caused biphasic increase in the intraluminal pressure, that is, initial and subsequent contractions. The effects of silodosin and tamsulosin, α1A-AR antagonists, on the contractile responses were examined. The ES-induced biphasic contractions were blocked by tetrodotoxin (TTX). Silodosin and tamsulosin suppressed the initial contractions in a dose-dependent manner, while also exerting various inhibitory effects on the subsequent contractions. Increases in the intraluminal pressure facilitated spontaneous phasic contractions. The spontaneous contractions were not affected by TTX or α1A-AR antagonists, but were abolished by nifedipine. The initial contractions triggered by neuronal excitations were suppressed by silodosin and tamsulosin, suggesting that the ejaculation dysfunction may be attributed to the α1A-AR antagonist-mediated suppression of nerve-evoked contractions in the seminal vesicle. The subsequent contractions may be induced by mechanical stimulation associated with the initial, nerve-evoked contractions. Alternatively, other transmitters may be involved to various degrees in the neuromuscular transmission of the seminal vesicle. © 2014 Wiley Publishing Asia Pty Ltd.

  12. The effectiveness of two novel techniques in establishing the mechanical and contractile responses of biceps femoris

    International Nuclear Information System (INIS)

    Ditroilo, Massimiliano; De Vito, Giuseppe; Hunter, Angus M; Haslam, Samuel

    2011-01-01

    Portable tensiomyography (TMG) and myotonometry (MMT) devices have been developed to measure mechanical and contractile properties of skeletal muscle. The aim of this study was to explore the sensitivity of the aforementioned techniques in detecting a change in passive mechanical properties of the biceps femoris (BF) muscle as a result of change in knee joint angle (i.e. muscle length). BF responses were assessed in 16 young participants (23.4 ± 4.9 years), at three knee joint angles (0°, 45° and 90°), for maximal isometric torque (MIT) along with myo-electrical activity. Contractile and mechanical properties were measured in a relaxed state. Inter-day reliability of the TMG and MMT was also assessed. MIT changed significantly (p < 0.01) across the three angles, so did stiffness and other parameters measured with MMT (p < 0.01). Conversely, TMG could detect changes only at two knee angles (0° and 45°, p < 0.01), when there is enough tension in the muscle. Reliability was overall insufficient for TMG whilst absolute reliability was excellent (coefficient of variation < 5%) for MMT. The ability of MMT more than TMG to detect an inherent change in stiffness can be conceivably exploited in a number of clinical/therapeutic applications that have to do with unnatural changes in passive muscle stiffness

  13. Differential Kolaviron Attenuated Contractile Responses to Agonists on Isolated Rabbit Aorta in Na+-K+ Pump Blockade.

    Science.gov (United States)

    Uche, O K; Ofeimun, J O

    2017-12-30

    The mechanism of kolaviron-induced vascular smooth muscles (VSMs) responses has not been fullycharacterised. The present study investigated the effect and mode of action of kolaviron a biflavanoid-complex and majorcomponent of Garcinia Kola-fraction on differential contractile responses to agonists-[phenylephrine (PHE) and histamine(HIST)] on VSMs of rabbit isolated aortic rings in K+-free physiological salt solution (KFPSS). Cumulative concentrationresponses to PHE and HIST were examined on 2 mm ring segments of the thoracic aortae which were suspended in 20 mlorgan baths containing physiological salt solution (PSS) for measurement of isometric contractions, at 370C and pH 7.4. Themedium was bubbled with 95% O2, 5% CO2, and rings were given an initial load of 1g. Cumulative contractile responses tothe agonists were studied in normal PSS (control) and following 30 minutes exposure to K+-free PSS and/or 800µg/mLkolaviron. Contractile responses were expressed as percentage of 80 mM K+ contractions in normal PSS. Maximalcontractions (Emax) induced by PHE and HIST compared with high K+ contraction in the various preparations weredifferentially altered following exposure to K+-free or 800µg/mL kolaviron in both intact (+E) and endotheliumdenuded (-E) rings. Based on the efficacy (Emax) and potency (EC50) values for the dose-response curves of the agonists, it isconcluded that enhanced differential contractile responses elicited by agonists in K+-free PSS were significantly attenuatedby kolaviron concentration-dependently. This observation probably suggests the existence of another pathway of kolavironmode of action in vascular smooth muscle reactivity.

  14. Characterization of the anatomical structures involved in the contractile response of the rat lung periphery.

    Science.gov (United States)

    Salerno, F G; Kurosawa, H; Eidelman, D H; Ludwig, M S

    1996-06-01

    co-preincubation with propranolol (Prop). 6. These results suggest that during ACh and NA challenge, small vessels do not contribute substantially to the parenchymal strip response. The discrepancy between results in airways, vessels and strips when Atr was administered prior to AII implicates a direct contractile response in the parenchymal strip.

  15. Plasticity of TOM complex assembly in skeletal muscle mitochondria in response to chronic contractile activity.

    Science.gov (United States)

    Joseph, Anna-Maria; Hood, David A

    2012-03-01

    We investigated the assembly of the TOM complex within skeletal muscle under conditions of chronic contractile activity-induced mitochondrial biogenesis. Tom40 import into mitochondria was increased by chronic contractile activity, as was its time-dependent assembly into the TOM complex. These changes coincided with contractile activity-induced augmentations in the expression of key protein import machinery components Tim17, Tim23, and Tom22, as well as the cytosolic chaperone Hsp90. These data indicate the adaptability of the TOM protein import complex and suggest a regulatory role for the assembly of this complex in exercise-induced mitochondrial biogenesis. Copyright © 2011 Elsevier B.V. and Mitochondria Research Society. All rights reserved. All rights reserved.

  16. Sinoatrial tissue of crucian carp heart has only negative contractile responses to autonomic agonists

    Directory of Open Access Journals (Sweden)

    Hälinen Mervi

    2010-06-01

    Full Text Available Abstract Background In the anoxia-tolerant crucian carp (Carassius carassius cardiac activity varies according to the seasons. To clarify the role of autonomic nervous control in modulation of cardiac activity, responses of atrial contraction and heart rate (HR to carbacholine (CCh and isoprenaline (Iso were determined in fish acclimatized to winter (4°C, cold-acclimated, CA and summer (18°C, warm-acclimated, WA temperatures. Results Inhibitory action of CCh was much stronger on atrial contractility than HR. CCh reduced force of atrial contraction at an order of magnitude lower concentrations (EC50 2.75-3.5·10-8 M in comparison to its depressive effect on HR (EC50 1.23-2.02·10-7 M (P -8 M and 10-7 M CCh, respectively (P + current, IK,CCh, with an EC50 value of 3-4.5·10-7 M and inhibited Ca2+ current (ICa by 28 ± 8% and 51 ± 6% at 10-7 M and 10-6 M, respectively. These currents can explain the shortening of AP. Iso did not elicit any responses in crucian carp sinoatrial preparations nor did it have any effect on atrial ICa, probably due to the saturation of the β-adrenergic cascade in the basal state. Conclusion In the crucian carp, HR and force of atrial contraction show cardio-depressive responses to the cholinergic agonist, but do not have any responses to the β-adrenergic agonist. The scope of inhibitory regulation by CCh is increased by the high basal tone of the adenylate cyclase-cAMP cascade. Higher concentrations of CCh were required to induce IK,CCh and inhibit ICa than was needed for CCh's negative inotropic effect on atrial muscle suggesting that neither IK,CCh nor ICa alone can mediate CCh's actions but they might synergistically reduce AP duration and atrial force production. Autonomic responses were similar in CA winter fish and WA summer fish indicating that cardiac sensitivity to external modulation by the autonomic nervous system is not involved in seasonal acclimatization of the crucian carp heart to cold and anoxic

  17. Presenilin 1 mutation decreases both calcium and contractile responses in cerebral arteries.

    Science.gov (United States)

    Toussay, Xavier; Morel, Jean-Luc; Biendon, Nathalie; Rotureau, Lolita; Legeron, François-Pierre; Boutonnet, Marie-Charlotte; Cho, Yoon H; Macrez, Nathalie

    2017-10-01

    Mutations or upregulation in presenilin 1 (PS1) gene are found in familial early-onset Alzheimer's disease or sporadic late-onset Alzheimer's disease, respectively. PS1 has been essentially studied in neurons and its mutation was shown to alter intracellular calcium (Ca 2+ ) signals. Here, we showed that PS1 is expressed in smooth muscle cells (SMCs) of mouse cerebral arteries, and we assessed the effects of the deletion of exon 9 of PS1 (PS1dE9) on Ca 2+ signals and contractile responses of vascular SMC. Agonist-induced contraction of cerebral vessels was significantly decreased in PS1dE9 both in vivo and ex vivo. Spontaneous activity of Ca 2+ sparks through ryanodine-sensitive channels (RyR) was unchanged, whereas the RyR-mediated Ca 2+ -release activated by caffeine was shorter in PS1dE9 SMC when compared with control. Moreover, PS1dE9 mutation decreased the caffeine-activated capacitive Ca 2+ entry, and inhibitors of SERCA pumps reversed the effects of PS1dE9 on Ca 2+ signals. PS1dE9 mutation also leads to the increased expression of SERCA3, phospholamban, and RyR3. These results show that PS1 plays a crucial role in the cerebrovascular system and the vascular reactivity is decreased through altered Ca 2+ signals in PS1dE9 mutant mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Contractile responses to ergotamine and dihydroergotamine in the perfused middle cerebral artery of rat

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Nilsson, Elisabeth; Edvinsson, Lars

    2007-01-01

    mmHg and luminally perfused. All vessels used attained spontaneous contractile tone (34.9+/-1.8% of resting tone) and responded to luminal adenosine triphosphate (ATP) with dilatation (24.1+/-4.0%), which showed functioning endothelium. Luminally added ergotamine or DHE induced maximal contractions...

  19. Enhancement of S1P-induced contractile response in detrusor smooth muscle of rats having cystitis.

    Science.gov (United States)

    Anjum, Irfan; Denizalti, Merve; Kandilci, Hilmi Burak; Durlu-Kandilci, Nezahat Tugba; Sahin-Erdemli, Inci

    2017-11-05

    Interstitial cystitis is a chronic disease characterized by lower abdominal pain and some nonspecific symptoms including an increase in urinary frequency and urgency. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that controls smooth muscle tone via G-protein coupled receptors (S1P 1-3 receptors). S1P production is known to take place both in physiological states and some pathological situations, such as in overactive bladder syndrome. The intracellular mechanism of S1P-induced contractile response was investigated in β-escin permeabilized detrusor smooth muscle of rats having cyclophosphamide-induced cystitis. The bladder was isolated from rats and detrusor smooth muscle strips were permeabilized with β-escin. S1P (50µM)-induced contraction and calcium sensitization response were significantly increased in cystitis. S1P-induced augmented contractile response was inhibited by S1P 2 receptor antagonist JTE-013 and S1P 3 receptor antagonist suramin. S1P 2 receptor protein expressions were increased in cystitis, where no change was observed in S1P 3 expressions between control and cystitis groups. S1P-induced contraction was reduced by Rho kinase (ROCK) inhibitor Y-27632 and protein kinase C (PKC) inhibitor GF-109203X in both control and cystitis group. S1P-induced increased calcium sensitization response was decreased by ROCK inhibitor and PKC inhibitor in cystitis. Our findings provide the first evidence that interstitial cystitis triggers S1P-induced increase in intracellular calcium in permeabilized detrusor smooth muscle of female rats. Both S1P 2 and S1P 3 receptors are involved in S1P mediated enhanced contractile response. The augmentation in S1P-induced contraction in interstitial cystitis involves both PKC and ROCK pathways of calcium sensitization. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Fractalkine depresses cardiomyocyte contractility.

    Directory of Open Access Journals (Sweden)

    David Taube

    Full Text Available Our laboratory reported that male mice with cardiomyocyte-selective knockout of the prostaglandin E2 EP4 receptor sub-type (EP4 KO exhibit reduced cardiac function. Gene array on left ventricles (LV showed increased fractalkine, a chemokine implicated in heart failure. We therefore hypothesized that fractalkine is regulated by PGE2 and contributes to depressed contractility via alterations in intracellular calcium.Fractalkine was measured in LV of 28-32 week old male EP4 KO and wild type controls (WT by ELISA and the effect of PGE2 on fractalkine secretion was measured in cultured neonatal cardiomyocytes and fibroblasts. The effect of fractalkine on contractility and intracellular calcium was determined in Fura-2 AM-loaded, electrical field-paced cardiomyocytes. Cardiomyocytes (AVM from male C57Bl/6 mice were treated with fractalkine and responses measured under basal conditions and after isoproterenol (Iso stimulation.LV fractalkine was increased in EP4 KO mice but surprisingly, PGE2 regulated fractalkine secretion only in fibroblasts. Fractalkine treatment of AVM decreased both the speed of contraction and relaxation under basal conditions and after Iso stimulation. Despite reducing contractility after Iso stimulation, fractalkine increased the Ca(2+ transient amplitude but decreased phosphorylation of cardiac troponin I, suggesting direct effects on the contractile machinery.Fractalkine depresses myocyte contractility by mechanisms downstream of intracellular calcium.

  1. In Vitro Contractile Response of Rabbit Myometrium to BKCa and KATP Potassium Channel Openers

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    Soňa Fraňová

    2009-01-01

    Full Text Available The aim of the study was to evaluate the participation of ligand-sensitive potassium large conductance calcium-activated channels (BKCa and ATP-sensitive potassium channels in uterine smooth muscle reactivity during different stages of the experimentally induced proliferatory and secretory phase in the sexual cycle in ovariectomised rabbits in vitro. The myometrial reactivity to oxytocin (10-6 mol l-1 was investigated by an in vitro method in female rabbits 14 days after ovariectomy treated with 17β-estradiol - 1 mg/kg/day i.m. for 7 days, or with a combination of progesterone 2 mg/kg/day s.c. for 7 days and 17β-estradiol - 0.2 mg/ kg/day (day 3–7. The strips of myometrial smooth muscle were incubated with a specific opener (NS 1619 and an antagonist (TEA of potassium large conductance calcium-activated channel, or with a specific opener (pinacidil and an antagonist (glybenclamide of ATP-sensitive potassium channels before the administration of oxytocin. NS1619 produced more potent inhibition of the oxytocin-induced contraction during the gestagen dominance (experimental secretory phase than the one observed during the oestrogen dominance (experimental proliferatory phase. TEA antagonized the NS1619 induced inhibition of the myometrial contraction. In the matter of KATP potassium channels, after the administration of pinacidil we observed a similar situation in the changes of myometrial contractility. Pinacidil produced more pronounced inhibition of oxytocin-induced contraction during the secretory phase, and its effect was abolished by the selective inhibitor glybenclamide. Our experimental results indicate that both potassium large conductance calcium-activated channels and ATP-sensitive potassium channels significantly participate in the regulation of myometrial oxytocin-induced contractions and the activity of these channels is probably influenced by the levels of oestrogens and gestagens.

  2. Marginal Maximum Likelihood Estimation of Item Response Models in R

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    Matthew S. Johnson

    2007-02-01

    Full Text Available Item response theory (IRT models are a class of statistical models used by researchers to describe the response behaviors of individuals to a set of categorically scored items. The most common IRT models can be classified as generalized linear fixed- and/or mixed-effect models. Although IRT models appear most often in the psychological testing literature, researchers in other fields have successfully utilized IRT-like models in a wide variety of applications. This paper discusses the three major methods of estimation in IRT and develops R functions utilizing the built-in capabilities of the R environment to find the marginal maximum likelihood estimates of the generalized partial credit model. The currently available R packages ltm is also discussed.

  3. Maximum likelihood estimation for cytogenetic dose-response curves

    International Nuclear Information System (INIS)

    Frome, E.L.; DuFrain, R.J.

    1986-01-01

    In vitro dose-response curves are used to describe the relation between chromosome aberrations and radiation dose for human lymphocytes. The lymphocytes are exposed to low-LET radiation, and the resulting dicentric chromosome aberrations follow the Poisson distribution. The expected yield depends on both the magnitude and the temporal distribution of the dose. A general dose-response model that describes this relation has been presented by Kellerer and Rossi (1972, Current Topics on Radiation Research Quarterly 8, 85-158; 1978, Radiation Research 75, 471-488) using the theory of dual radiation action. Two special cases of practical interest are split-dose and continuous exposure experiments, and the resulting dose-time-response models are intrinsically nonlinear in the parameters. A general-purpose maximum likelihood estimation procedure is described, and estimation for the nonlinear models is illustrated with numerical examples from both experimental designs. Poisson regression analysis is used for estimation, hypothesis testing, and regression diagnostics. Results are discussed in the context of exposure assessment procedures for both acute and chronic human radiation exposure

  4. Consecutive bouts of diverse contractile activity alter acute responses in human skeletal muscle

    DEFF Research Database (Denmark)

    Coffey, Vernon G; Pilegaard, Henriette; Garnham, Andrew P

    2009-01-01

    -mTOR-S6 kinase phosphorylation 15 min after each bout of exercise was similar regardless of the exercise mode. The cumulative effect of combined exercise resulted in disparate mRNA responses. IGF-I mRNA content was reduced when cycling preceded resistance exercise (-42%), whereas muscle ring finger...

  5. Maximum likelihood estimation for cytogenetic dose-response curves

    International Nuclear Information System (INIS)

    Frome, E.L; DuFrain, R.J.

    1983-10-01

    In vitro dose-response curves are used to describe the relation between the yield of dicentric chromosome aberrations and radiation dose for human lymphocytes. The dicentric yields follow the Poisson distribution, and the expected yield depends on both the magnitude and the temporal distribution of the dose for low LET radiation. A general dose-response model that describes this relation has been obtained by Kellerer and Rossi using the theory of dual radiation action. The yield of elementary lesions is kappa[γd + g(t, tau)d 2 ], where t is the time and d is dose. The coefficient of the d 2 term is determined by the recovery function and the temporal mode of irradiation. Two special cases of practical interest are split-dose and continuous exposure experiments, and the resulting models are intrinsically nonlinear in the parameters. A general purpose maximum likelihood estimation procedure is described and illustrated with numerical examples from both experimental designs. Poisson regression analysis is used for estimation, hypothesis testing, and regression diagnostics. Results are discussed in the context of exposure assessment procedures for both acute and chronic human radiation exposure

  6. Maximum likelihood estimation for cytogenetic dose-response curves

    Energy Technology Data Exchange (ETDEWEB)

    Frome, E.L; DuFrain, R.J.

    1983-10-01

    In vitro dose-response curves are used to describe the relation between the yield of dicentric chromosome aberrations and radiation dose for human lymphocytes. The dicentric yields follow the Poisson distribution, and the expected yield depends on both the magnitude and the temporal distribution of the dose for low LET radiation. A general dose-response model that describes this relation has been obtained by Kellerer and Rossi using the theory of dual radiation action. The yield of elementary lesions is kappa(..gamma..d + g(t, tau)d/sup 2/), where t is the time and d is dose. The coefficient of the d/sup 2/ term is determined by the recovery function and the temporal mode of irradiation. Two special cases of practical interest are split-dose and continuous exposure experiments, and the resulting models are intrinsically nonlinear in the parameters. A general purpose maximum likelihood estimation procedure is described and illustrated with numerical examples from both experimental designs. Poisson regression analysis is used for estimation, hypothesis testing, and regression diagnostics. Results are discussed in the context of exposure assessment procedures for both acute and chronic human radiation exposure.

  7. Inhibitory effects of tiamulin on contractile and electrical responses in isolated thoracic aorta and cardiac muscle of guinea-pigs.

    Science.gov (United States)

    Nakajyo, S; Hara, Y; Hirano, S; Agata, N; Shimizu, K; Urakawa, N

    1992-09-01

    The inhibitory effect of tiamulin, an antibiotic produced by Pleurotus mutilis, on contractile and electrical responses in isolated thoracic aorta and cardiac muscle of guinea-pigs was studied. In the thoracic aorta, tiamulin with an IC50 of 9.7 x 10(-6) M inhibited sustained contractions induced by isosmotically added 60 mM KCl. The inhibitory effect of tiamulin on a Ca(2+)-induced contraction in a depolarized muscle was competitively antagonized by raising external Ca2+ concentration. Bay K 8644 (10(-7) M) antagonized tiamulin's inhibition of the Ca(2+)-induced contraction. Tiamulin (2 x 10(-5) M) decreased the elevated cytoplasmic Ca2+ level measured by the fura 2 AM method in the depolarized muscle. In high K(+)-isoprenaline-treated left atria, tiamulin (2 x 10(-5)-2 x 10(-4) M) produced negative inotropic effects. On the other hand in the membrane action potential of papillary muscles, tiamulin (2 x 10(-6)-2 x 10(-4) M) produced decreases in action potential and durations and 2 x 10(-4) M tiamulin depressed the slow response action potential in depolarized muscles. Tiamulin produced prolongations of the PR interval in ECG, negative chrono- and inotropic effects, and an increase in perfusion flow in guinea-pig isolated and perfused hearts. These effects of tiamulin on the aorta or cardiac muscle were similar to those of verapamil and nifedipine. These results suggest that both the inhibitory action of tiamulin on the high K(+)-induced contraction in the aorta and the negative inotropic effect of tiamulin on the cardiac muscle are due to an inhibition of Ca2+ entry through the voltage-dependent Ca2+ channels of cells of both these muscles.

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

    Science.gov (United States)

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

    2010-08-06

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

  9. Altered contractile responses of arteries from spontaneously hypertensive rat: The role of endogenous mediators and membrane depolarization

    Czech Academy of Sciences Publication Activity Database

    Bencze, Michal; Behuliak, Michal; Vavřínová, Anna; Zicha, Josef

    2016-01-01

    Roč. 166, Dec 1 (2016), s. 46-53 ISSN 0024-3205 R&D Projects: GA ČR(CZ) GAP304/12/0259; GA MZd(CZ) NV15-25396A Institutional support: RVO:67985823 Keywords : femoral artery * SHR * vascular contractility * adrenergic contraction * tyramine * propranolol * neuropeptide Y Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.936, year: 2016

  10. Cholesterol regulates contractility and inotropic response to β2-adrenoceptor agonist in the mouse atria: Involvement of Gi-protein-Akt-NO-pathway.

    Science.gov (United States)

    Odnoshivkina, Yulia G; Sytchev, Vaycheslav I; Petrov, Alexey M

    2017-06-01

    Majority of cardiac β2-adrenoceptors is located in cholesterol-rich microdomains. Here, we have investigated the underlying mechanisms by which a slight to moderate cholesterol depletion with methyl-β-cyclodextrin (MβCD, 1 and 5mM) interferes with contractility and inotropic effect of β2-adrenergic agonist (fenoterol, 50μM) in the mouse atria. Treatment with MβCD itself increased amplitude of Ca 2+ transient but did not change the contraction amplitude due to a clamping action of elevated NO. Cholesterol depletion significantly attenuated the positive inotropic response to fenoterol which is accompanied by increase in NO generation and decrease in Ca 2+ transient. Influence of 1mM MβCD on the fenoterol-driven changes in both contractility and NO level was strongly attenuated by inhibition of G i -protein (pertussis toxin), Akt (Akt 1/2 kinase inhibitor) or NO-synthase (L-NAME). After exposure to 5mM MβCD, pertussis toxin or Akt inhibitor could recover the β2-agonist effects on contractility, NO production and Ca 2+ transient, while L-NAME only reduced NO level. An adenylyl cyclase activator (forskolin, 50nM) had no influence on the MβCD-induced changes in the β2-agonist effects. Obtained results suggest that slight cholesterol depletion upregulates G i -protein/Akt/NO-synthase signaling that attenuates the positive inotropic response to β2-adrenergic stimulation without altering the Ca 2+ transient. Whilst moderate cholesterol depletion additionally could suppress the enhancement of the Ca 2+ transient amplitude caused by the β2-adrenergic agonist administration in G i -protein/Akt-dependent but NO-independent manner. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Alterations in Muscle Mass and Contractile Phenotype in Response to Unloading Models: Role of Transcriptional/Pretranslational Mechanisms

    Directory of Open Access Journals (Sweden)

    Kenneth M Baldwin

    2013-10-01

    Full Text Available Skeletal muscle is the largest organ system in mammalian organisms providing postural control and movement patterns of varying intensity. Through evolution, skeletal muscle fibers have evolved into three phenotype clusters defined as a muscle unit which consists of all muscle fibers innervated by a single motoneuron linking varying numbers of fibers of similar phenotype. This fundamental organization of the motor unit reflects the fact that there is a remarkable interdependence of gene regulation between the motoneurons and the muscle mainly via activity-dependent mechanisms. These fiber types can be classified via the primary type of myosin heavy chain (MHC gene expressed in the motor unit. Four MHC gene encoded proteins have been identified in striated muscle: slow type I MHC and three fast MHC types, IIa, IIx, and IIb. These MHCs dictate the intrinsic contraction speed of the myofiber with the type I generating the slowest and IIb the fastest contractile speed. Over the last ~35 years, a large body of knowledge suggests that altered loading state cause both fiber atrophy/wasting and a slow to fast shift in the contractile phenotype in the target muscle(s. Hence, this review will examine findings from three different animal models of unloading: 1 space flight (SF, i.e., microgravity; 2 hindlimb suspension (HS, a procedure that chronically eliminates weight bearing of the lower limbs; and 3 spinal cord isolation (SI, a surgical procedure that eliminates neural activation of the motoneurons and associated muscles while maintaining neurotrophic motoneuron-muscle connectivity. The collective findings demonstrate: 1 all three models show a similar pattern of fiber atrophy with differences mainly in the magnitude and kinetics of alteration; 2 transcriptional/pretranslational processes play a major role in both the atrophy process and phenotype shifts; and 3 signaling pathways impacting these alterations appear to be similar in each of the models

  12. Post-contractile BOLD contrast in skeletal muscle at 7 T reveals inter-individual heterogeneity in the physiological responses to muscle contraction.

    Science.gov (United States)

    Towse, Theodore F; Elder, Christopher P; Bush, Emily C; Klockenkemper, Samuel W; Bullock, Jared T; Dortch, Richard D; Damon, Bruce M

    2016-12-01

    Muscle blood oxygenation-level dependent (BOLD) contrast is greater in magnitude and potentially more influenced by extravascular BOLD mechanisms at 7 T than it is at lower field strengths. Muscle BOLD imaging of muscle contractions at 7 T could, therefore, provide greater or different contrast than at 3 T. The purpose of this study was to evaluate the feasibility of using BOLD imaging at 7 T to assess the physiological responses to in vivo muscle contractions. Thirteen subjects (four females) performed a series of isometric contractions of the calf muscles while being scanned in a Philips Achieva 7 T human imager. Following 2 s maximal isometric plantarflexion contractions, BOLD signal transients ranging from 0.3 to 7.0% of the pre-contraction signal intensity were observed in the soleus muscle. We observed considerable inter-subject variability in both the magnitude and time course of the muscle BOLD signal. A subset of subjects (n = 7) repeated the contraction protocol at two different repetition times (T R : 1000 and 2500 ms) to determine the potential of T 1 -related inflow effects on the magnitude of the post-contractile BOLD response. Consistent with previous reports, there was no difference in the magnitude of the responses for the two T R values (3.8 ± 0.9 versus 4.0 ± 0.6% for T R  = 1000 and 2500 ms, respectively; mean ± standard error). These results demonstrate that studies of the muscle BOLD responses to contractions are feasible at 7 T. Compared with studies at lower field strengths, post-contractile 7 T muscle BOLD contrast may afford greater insight into microvascular function and dysfunction. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Improved throughput traction microscopy reveals pivotal role for matrix stiffness in fibroblast contractility and TGF-β responsiveness

    Science.gov (United States)

    Marinković, Aleksandar; Mih, Justin D.; Park, Jin-Ah; Liu, Fei

    2012-01-01

    Lung fibroblast functions such as matrix remodeling and activation of latent transforming growth factor-β1 (TGF-β1) are associated with expression of the myofibroblast phenotype and are directly linked to fibroblast capacity to generate force and deform the extracellular matrix. However, the study of fibroblast force-generating capacities through methods such as traction force microscopy is hindered by low throughput and time-consuming procedures. In this study, we improved at the detail level methods for higher-throughput traction measurements on polyacrylamide hydrogels using gel-surface-bound fluorescent beads to permit autofocusing and automated displacement mapping, and transduction of fibroblasts with a fluorescent label to streamline cell boundary identification. Together these advances substantially improve the throughput of traction microscopy and allow us to efficiently compute the forces exerted by lung fibroblasts on substrates spanning the stiffness range present in normal and fibrotic lung tissue. Our results reveal that lung fibroblasts dramatically alter the forces they transmit to the extracellular matrix as its stiffness changes, with very low forces generated on matrices as compliant as normal lung tissue. Moreover, exogenous TGF-β1 selectively accentuates tractions on stiff matrices, mimicking fibrotic lung, but not on physiological stiffness matrices, despite equivalent changes in Smad2/3 activation. Taken together, these results demonstrate a pivotal role for matrix mechanical properties in regulating baseline and TGF-β1-stimulated contraction of lung fibroblasts and suggest that stiff fibrotic lung tissue may promote myofibroblast activation through contractility-driven events, whereas normal lung tissue compliance may protect against such feedback amplification of fibroblast activation. PMID:22659883

  14. Cell stiffness, contractile stress and the role of extracellular matrix

    International Nuclear Information System (INIS)

    An, Steven S.; Kim, Jina; Ahn, Kwangmi; Trepat, Xavier; Drake, Kenneth J.; Kumar, Sarvesh; Ling, Guoyu; Purington, Carolyn; Rangasamy, Tirumalai; Kensler, Thomas W.; Mitzner, Wayne; Fredberg, Jeffrey J.; Biswal, Shyam

    2009-01-01

    Here we have assessed the effects of extracellular matrix (ECM) composition and rigidity on mechanical properties of the human airway smooth muscle (ASM) cell. Cell stiffness and contractile stress showed appreciable changes from the most relaxed state to the most contracted state: we refer to the maximal range of these changes as the cell contractile scope. The contractile scope was least when the cell was adherent upon collagen V, followed by collagen IV, laminin, and collagen I, and greatest for fibronectin. Regardless of ECM composition, upon adherence to increasingly rigid substrates, the ASM cell positively regulated expression of antioxidant genes in the glutathione pathway and heme oxygenase, and disruption of a redox-sensitive transcription factor, nuclear erythroid 2 p45-related factor (Nrf2), culminated in greater contractile scope. These findings provide biophysical evidence that ECM differentially modulates muscle contractility and, for the first time, demonstrate a link between muscle contractility and Nrf2-directed responses.

  15. Cell stiffness, contractile stress and the role of extracellular matrix

    Energy Technology Data Exchange (ETDEWEB)

    An, Steven S., E-mail: san@jhsph.edu [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Kim, Jina [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Ahn, Kwangmi [Division of Biostatistics, Penn State College of Medicine, Hershey, PA 17033 (United States); Trepat, Xavier [CIBER, Enfermedades Respiratorias, 07110 Bunyola (Spain); Drake, Kenneth J. [Division of Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA 02115 (United States); Kumar, Sarvesh; Ling, Guoyu; Purington, Carolyn; Rangasamy, Tirumalai; Kensler, Thomas W.; Mitzner, Wayne [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Fredberg, Jeffrey J. [Division of Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA 02115 (United States); Biswal, Shyam [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205 (United States)

    2009-05-15

    Here we have assessed the effects of extracellular matrix (ECM) composition and rigidity on mechanical properties of the human airway smooth muscle (ASM) cell. Cell stiffness and contractile stress showed appreciable changes from the most relaxed state to the most contracted state: we refer to the maximal range of these changes as the cell contractile scope. The contractile scope was least when the cell was adherent upon collagen V, followed by collagen IV, laminin, and collagen I, and greatest for fibronectin. Regardless of ECM composition, upon adherence to increasingly rigid substrates, the ASM cell positively regulated expression of antioxidant genes in the glutathione pathway and heme oxygenase, and disruption of a redox-sensitive transcription factor, nuclear erythroid 2 p45-related factor (Nrf2), culminated in greater contractile scope. These findings provide biophysical evidence that ECM differentially modulates muscle contractility and, for the first time, demonstrate a link between muscle contractility and Nrf2-directed responses.

  16. Ginsenoside Rb1 Attenuates Agonist-Induced Contractile Response via Inhibition of Store-Operated Calcium Entry in Pulmonary Arteries of Normal and Pulmonary Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Rui-Xing Wang

    2015-03-01

    Full Text Available Background: Pulmonary hypertension (PH is characterized by sustained vasoconstriction, enhanced vasoreactivity and vascular remodeling, which leads to right heart failure and death. Despite several treatments are available, many forms of PH are still incurable. Ginsenoside Rb1, a principle active ingredient of Panax ginseng, exhibits multiple pharmacological effects on cardiovascular system, and suppresses monocrotaline (MCT-induced right heart hypertrophy. However, its effect on the pulmonary vascular functions related to PH is unknown. Methods: We examined the vasorelaxing effects of ginsenoside Rb1 on endothelin-1 (ET-1 induced contraction of pulmonary arteries (PAs and store-operated Ca2+ entry (SOCE in pulmonary arterial smooth muscle cells (PASMCs from chronic hypoxia (CH and MCT-induced PH. Results: Ginsenoside Rb1 elicited concentration-dependent relaxation of ET-1-induced PA contraction. The vasorelaxing effect was unaffected by nifedipine, but abolished by the SOCE blocker Gd3+. Ginsenoside Rb1 suppressed cyclopiazonic acid (CPA-induced PA contraction, and CPA-activated cation entry and Ca2+ transient in PASMCs. ET-1 and CPA-induced contraction, and CPA-activated cation entry and Ca2+ transients were enhanced in PA and PASMCs of CH and MCT-treated rats; the enhanced responses were abolished by ginsenoside Rb1. Conclusion: Ginsenoside Rb1 attenuates ET-1-induced contractile response via inhibition of SOCE, and it can effectively antagonize the enhanced pulmonary vasoreactivity in PH.

  17. Increased Contractile Response to Noradrenaline Induced By Factors Associated with the Metabolic Syndrome in Cultured Small Mesenteric Arteries

    DEFF Research Database (Denmark)

    Blædel, Martin; Sams, Anette; Boonen, Harrie C M

    2016-01-01

    UNLABELLED: This study investigated the effect of the metabolic syndrome associated risk factors hyperglycemia (glucose [Glc]), hyperinsulinemia (insulin [Ins]) and low-grade inflammation (tumor necrosis factor α [TNFα]) on the vasomotor responses of resistance arteries. Isolated small mesenteric...... arteries from 3-month-old Sprague-Dawley rats, were suspended for 21-23 h in tissue cultures containing either elevated Glc (30 mmol/l), Ins (100 nmol/l), TNFα (100 ng/ml) or combinations thereof. After incubation, the vascular response to noradrenaline (NA), phenylephrine, isoprenaline and NA...... in vascular tone....

  18. Genetic fuzzy system predicting contractile reactivity patterns of small arteries

    DEFF Research Database (Denmark)

    Tang, J; Sheykhzade, Majid; Clausen, B F

    2014-01-01

    strategies. Results show that optimized fuzzy systems (OFSs) predict contractile reactivity of arteries accurately. In addition, OFSs identified significant differences that were undetectable using conventional analysis in the responses of arteries between groups. We concluded that OFSs may be used...

  19. Evolutionary History Underlies Plant Physiological Responses to Global Change Since the Last Glacial Maximum

    Science.gov (United States)

    Becklin, K. M.; Medeiros, J. S.; Sale, K. R.; Ward, J. K.

    2014-12-01

    Assessing family and species-level variation in physiological responses to global change across geologic time is critical for understanding factors that underlie changes in species distributions and community composition. Ancient plant specimens preserved within packrat middens are invaluable in this context since they allow for comparisons between co-occurring plant lineages. Here we used modern and ancient plant specimens preserved within packrat middens from the Snake Range, NV to investigate the physiological responses of a mixed montane conifer community to global change since the last glacial maximum. We used a conceptual model to infer relative changes in stomatal conductance and maximum photosynthetic capacity from measures of leaf carbon isotopes, stomatal characteristics, and leaf nitrogen content. Our results indicate that most of the sampled taxa decreased stomatal conductance and/or photosynthetic capacity from glacial to modern times. However, plant families differed in the timing and magnitude of these physiological responses. Additionally, leaf-level responses were more similar within plant families than within co-occurring species assemblages. This suggests that adaptation at the level of leaf physiology may not be the main determinant of shifts in community composition, and that plant evolutionary history may drive physiological adaptation to global change over recent geologic time.

  20. Estimation method for first excursion probability of secondary system with impact and friction using maximum response

    International Nuclear Information System (INIS)

    Shigeru Aoki

    2005-01-01

    The secondary system such as pipings, tanks and other mechanical equipment is installed in the primary system such as building. The important secondary systems should be designed to maintain their function even if they are subjected to destructive earthquake excitations. The secondary system has many nonlinear characteristics. Impact and friction characteristic, which are observed in mechanical supports and joints, are common nonlinear characteristics. As impact damper and friction damper, impact and friction characteristic are used for reduction of seismic response. In this paper, analytical methods of the first excursion probability of the secondary system with impact and friction, subjected to earthquake excitation are proposed. By using the methods, the effects of impact force, gap size and friction force on the first excursion probability are examined. When the tolerance level is normalized by the maximum response of the secondary system without impact or friction characteristics, variation of the first excursion probability is very small for various values of the natural period. In order to examine the effectiveness of the proposed method, the obtained results are compared with those obtained by the simulation method. Some estimation methods for the maximum response of the secondary system with nonlinear characteristics have been developed. (author)

  1. A Maximum Likelihood Approach to Determine Sensor Radiometric Response Coefficients for NPP VIIRS Reflective Solar Bands

    Science.gov (United States)

    Lei, Ning; Chiang, Kwo-Fu; Oudrari, Hassan; Xiong, Xiaoxiong

    2011-01-01

    Optical sensors aboard Earth orbiting satellites such as the next generation Visible/Infrared Imager/Radiometer Suite (VIIRS) assume that the sensors radiometric response in the Reflective Solar Bands (RSB) is described by a quadratic polynomial, in relating the aperture spectral radiance to the sensor Digital Number (DN) readout. For VIIRS Flight Unit 1, the coefficients are to be determined before launch by an attenuation method, although the linear coefficient will be further determined on-orbit through observing the Solar Diffuser. In determining the quadratic polynomial coefficients by the attenuation method, a Maximum Likelihood approach is applied in carrying out the least-squares procedure. Crucial to the Maximum Likelihood least-squares procedure is the computation of the weight. The weight not only has a contribution from the noise of the sensor s digital count, with an important contribution from digitization error, but also is affected heavily by the mathematical expression used to predict the value of the dependent variable, because both the independent and the dependent variables contain random noise. In addition, model errors have a major impact on the uncertainties of the coefficients. The Maximum Likelihood approach demonstrates the inadequacy of the attenuation method model with a quadratic polynomial for the retrieved spectral radiance. We show that using the inadequate model dramatically increases the uncertainties of the coefficients. We compute the coefficient values and their uncertainties, considering both measurement and model errors.

  2. Dependency of maximum goitrogenic response on some minimal level of thyroid hormone production

    International Nuclear Information System (INIS)

    March, B.E.; Poon, R.

    1981-01-01

    Thyroidal activity was studied in chicks given dietary thiouracil in conjunction with daily doses of thyroxine and with diets adequate and deficient in iodine. DL-thyroxine administered at doses up to 1.0 microgram per day for 10 to 12 days had no effect or slightly increased thyroid weight. Both the epithelial and colloid components of the thyroid gland were increased in response to thiouracil and to thiouracil in combination with low dosages of exogenous thyroxine. Radioiodine uptake was increased above the control with thiouracil and with thiouracil in conjunction with .5 and 1.0 microgram DL-thyroxine given daily. Birds receiving thiouracil, with and without exogenous thyroxine, showed a different pattern of radioiodine uptake and release than the control birds. Thiouracil-treated birds showed a rapid uptake of iodine following its administration, which was followed by a rapid decline immediately after peak accumulation, whereas in control birds thyroidal radioiodine concentration reached a plateau at the maximum concentration attained. The goitrogenic response to thiouracil was much greater when the diet was supplemented with iodine than when the diet was iodine-deficient. Thyroids under iodine deficiency contained greater percentages of epithelial tissue than with iodine-supplemented diets. Thyroid glands of chicks given thiouracil in an iodine-supplemented diet contained much more colloid than glands from iodine-deficient chicks with or without thiouracil. DL-thyroxine at a dosage of .5 microgram per day to chicks given thiouracil in an iodine-adequate diet increased, whereas higher dosages decreased thyroidal colloid. It is concluded that some minimal concentration of thyroid hormone is required for maximum goitrogenic response. It is not clear whether the response is entirely due to an effect on thyrotropin production or whether there is an effect of thyroid hormone on the thyroid gland itself

  3. Actomyosin contractility rotates the cell nucleus.

    Science.gov (United States)

    Kumar, Abhishek; Maitra, Ananyo; Sumit, Madhuresh; Ramaswamy, Sriram; Shivashankar, G V

    2014-01-21

    The cell nucleus functions amidst active cytoskeletal filaments, but its response to their contractile stresses is largely unexplored. We study the dynamics of the nuclei of single fibroblasts, with cell migration suppressed by plating onto micro-fabricated patterns. We find the nucleus undergoes noisy but coherent rotational motion. We account for this observation through a hydrodynamic approach, treating the nucleus as a highly viscous inclusion residing in a less viscous fluid of orientable filaments endowed with active stresses. Lowering actin contractility selectively by introducing blebbistatin at low concentrations drastically reduced the speed and coherence of the angular motion of the nucleus. Time-lapse imaging of actin revealed a correlated hydrodynamic flow around the nucleus, with profile and magnitude consistent with the results of our theoretical approach. Coherent intracellular flows and consequent nuclear rotation thus appear to be an intrinsic property of cells.

  4. Response of spatial vegetation distribution in China to climate changes since the Last Glacial Maximum (LGM)

    Science.gov (United States)

    Wang, Siyang; Xu, Xiaoting; Shrestha, Nawal; Zimmermann, Niklaus E.; Tang, Zhiyao; Wang, Zhiheng

    2017-01-01

    Analyzing how climate change affects vegetation distribution is one of the central issues of global change ecology as this has important implications for the carbon budget of terrestrial vegetation. Mapping vegetation distribution under historical climate scenarios is essential for understanding the response of vegetation distribution to future climatic changes. The reconstructions of palaeovegetation based on pollen data provide a useful method to understand the relationship between climate and vegetation distribution. However, this method is limited in time and space. Here, using species distribution model (SDM) approaches, we explored the climatic determinants of contemporary vegetation distribution and reconstructed the distribution of Chinese vegetation during the Last Glacial Maximum (LGM, 18,000 14C yr BP) and Middle-Holocene (MH, 6000 14C yr BP). The dynamics of vegetation distribution since the LGM reconstructed by SDMs were largely consistent with those based on pollen data, suggesting that the SDM approach is a useful tool for studying historical vegetation dynamics and its response to climate change across time and space. Comparison between the modeled contemporary potential natural vegetation distribution and the observed contemporary distribution suggests that temperate deciduous forests, subtropical evergreen broadleaf forests, temperate deciduous shrublands and temperate steppe have low range fillings and are strongly influenced by human activities. In general, the Tibetan Plateau, North and Northeast China, and the areas near the 30°N in Central and Southeast China appeared to have experienced the highest turnover in vegetation due to climate change from the LGM to the present. PMID:28426780

  5. Structural comparison of contractile nanomachines

    Directory of Open Access Journals (Sweden)

    Sebastian Kube

    2015-05-01

    Full Text Available Contractile molecular machines are a common feature among bacteriophages and prokaryotes. Due to their stability and the large size, contractile-tailed bacteriophages are traditionally investigated by electron microscopic methods. Complemented by crystallographic studies, a molecular model of contraction for the T4 phage was developed. Lately, also related contractile structures like the Photorhabdus virulence cassette-like particles, the R-Type pyocins and the contractile tubule of the bacterial Type VI secretion system have been analyzed by cryo electron microscopy. Photorhabdus virulence cassette particles and R-Type pyocins are toxin complexes reminiscent of bacteriophage tails that are secreted by bacteria to kill their insect host or competing bacteria. In contrast, the Type VI secretion system is an intracellular apparatus for injection of effector proteins into bacterial and eukaryotic cells. Although it shares homology with other contractile systems, the Type VI secretion system is additionally equipped with a recycling function, which makes it suitable for multiple rounds of action. Starting from the 3D reconstructions, we compare these molecular machines structurally and functionally to their viral counterparts and summarize the current knowledge on their respective mode of action.

  6. Thermospheric response observed over Fritz peak, Colorado, during two large geomagnetic storms near solar cycle maximum

    International Nuclear Information System (INIS)

    Hernandez, G.; Roble, R.G.; Ridley, E.C.; Allen, J.H.

    1982-01-01

    Nightime thermospheric winds and temperatures have been measured over Fritz Peak Observatory, Colorado (39.9 0 N, 105.5 0 W), with a high resolution Fabry-Perot spectrometer. The winds and temperatures are obtained from the Doppler shifts and line profiles of the (O 1) 15,867K (630 nm) line emission. Measurements made during two large geomagnetic storm periods near solar cycle maximum reveal a thermospheric response to the heat and momentum sources associated with these storms that is more complex than the ones measured near solar cycle minimum. In the earlier measurements made during solar cycle minimum, the winds to the north of Fritz Peak Observatory had an enhanced equatorward component and the winds to the south were also equatorward, usually with smaller velocities. The winds measured to the east and west of the observatory both had an enhanced westward wind component. For the two large storms near the present solar cycle maximum period converging winds are observed in each of the cardinal directions from Fritz Peak Observatory. These converging winds with speeds of hundreds of meters per second last for several hours. The measured neutral gas temperature in each of the directions also increases several hundred degrees Kelvin. Numerical experiments done with the NCAR thermospheric general circulation model (TGCM) suggest that the winds to the east and north of the station are driven by high-latitude heating and enhanced westward ion drag associated with magnetospheric convection. The cause of the enhanced poleward and eastward winds measured to the south and west of Fritz Peak Observatory, respectively, is not known. During geomagnetic quiet conditions the circulation is typically from the soutwest toward the northeast in the evening hours

  7. Effects of lifting tempo on one repetition maximum and hormonal responses to a bench press protocol.

    Science.gov (United States)

    Headley, Samuel A; Henry, Kelley; Nindl, Bradley C; Thompson, Brian A; Kraemer, William J; Jones, Margaret T

    2011-02-01

    This study was carried out in 2 parts: part 1 was designed to measure the 1 repetition maximum (1RM) bench press with 2 different moderate-velocity tempos (2/0/2) vs. (2/0/4) in male lifters while part 2 compared the hormonal responses at the same tempos as described in part 1. In both parts 1 and 2, the 1RMs (lbs) were higher on the 2/0/2 tempo than on the 2/0/4 tempo. The change in plasma volume (PV) was greater after the 2/0/4 tempo (-5.7 ± 1.7% vs. 0.96 ± 1.2%, p < 0.05). All blood parameters were significantly (p < 0.05) higher post-exercise compared with baseline. With PV corrected, insulin-like growth factor 1 (IGF-1) (ng·mL⁻¹) was higher with the 2/0/2 tempo only (pre-exercise: 277.4 ± 21.8, post-exercise: 308.1 ± 22.9; 2/0/4 tempo pre-exercise: 277.2 ± 17.6, post-exercise: 284.8 ± 21.2). In conclusion, heavier loads can be lifted and more total work can be performed using a (2/0/2) tempo compared with a slower (2/0/4) tempo, but with the exception of IGF-1, the hormonal responses are similar. Individuals may get the same metabolic responses to training by using different tempos, but they will need to use less weight at a slower tempo.

  8. Productivity response of calcareous nannoplankton to Eocene Thermal Maximum 2 (ETM2

    Directory of Open Access Journals (Sweden)

    M. Dedert

    2012-05-01

    Full Text Available The Early Eocene Thermal Maximum 2 (ETM2 at ~53.7 Ma is one of multiple hyperthermal events that followed the Paleocene-Eocene Thermal Maximum (PETM, ~56 Ma. The negative carbon excursion and deep ocean carbonate dissolution which occurred during the event imply that a substantial amount (103 Gt of carbon (C was added to the ocean-atmosphere system, consequently increasing atmospheric CO2(pCO2. This makes the event relevant to the current scenario of anthropogenic CO2 additions and global change. Resulting changes in ocean stratification and pH, as well as changes in exogenic cycles which supply nutrients to the ocean, may have affected the productivity of marine phytoplankton, especially calcifying phytoplankton. Changes in productivity, in turn, may affect the rate of sequestration of excess CO2 in the deep ocean and sediments. In order to reconstruct the productivity response by calcareous nannoplankton to ETM2 in the South Atlantic (Site 1265 and North Pacific (Site 1209, we employ the coccolith Sr/Ca productivity proxy with analysis of well-preserved picked monogeneric populations by ion probe supplemented by analysis of various size fractions of nannofossil sediments by ICP-AES. The former technique of measuring Sr/Ca in selected nannofossil populations using the ion probe circumvents possible contamination with secondary calcite. Avoiding such contamination is important for an accurate interpretation of the nannoplankton productivity record, since diagenetic processes can bias the productivity signal, as we demonstrate for Sr/Ca measurements in the fine (<20 μm and other size fractions obtained from bulk sediments from Site 1265. At this site, the paleoproductivity signal as reconstructed from the Sr/Ca appears to be governed by cyclic changes, possibly orbital forcing, resulting in a 20–30% variability in Sr/Ca in dominant genera as obtained by ion probe. The ~13 to 21

  9. Blood pressure and the contractility of a human leg muscle.

    Science.gov (United States)

    Luu, Billy L; Fitzpatrick, Richard C

    2013-11-01

    These studies investigate the relationships between perfusion pressure, force output and pressor responses for the contracting human tibialis anterior muscle. Eight healthy adults were studied. Changing the height of tibialis anterior relative to the heart was used to control local perfusion pressure. Electrically stimulated tetanic force output was highly sensitive to physiological variations in perfusion pressure showing a proportionate change in force output of 6.5% per 10 mmHg. This perfusion-dependent change in contractility begins within seconds and is reversible with a 53 s time constant, demonstrating a steady-state equilibrium between contractility and perfusion pressure. These stimulated contractions did not produce significant cardiovascular responses, indicating that the muscle pressor response does not play a major role in cardiovascular regulation at these workloads. Voluntary contractions at forces that would require constant motor drive if perfusion pressure had remained constant generated a central pressor response when perfusion pressure was lowered. This is consistent with a larger cortical drive being required to compensate for the lost contractility with lower perfusion pressure. The relationship between contractility and perfusion for this large postural muscle was not different from that of a small hand muscle (adductor pollicis) and it responded similarly to passive peripheral and active central changes in arterial pressure, but extended over a wider operating range of pressures. If we consider that, in a goal-oriented motor task, muscle contractility determines central motor output and the central pressor response, these results indicate that muscle would fatigue twice as fast without a pressor response. From its extent, timing and reversibility we propose a testable hypothesis that this change in contractility arises through contraction- and perfusion-dependent changes in interstitial K(+) concentration.

  10. Recovery of Graded Response Model Parameters: A Comparison of Marginal Maximum Likelihood and Markov Chain Monte Carlo Estimation

    Science.gov (United States)

    Kieftenbeld, Vincent; Natesan, Prathiba

    2012-01-01

    Markov chain Monte Carlo (MCMC) methods enable a fully Bayesian approach to parameter estimation of item response models. In this simulation study, the authors compared the recovery of graded response model parameters using marginal maximum likelihood (MML) and Gibbs sampling (MCMC) under various latent trait distributions, test lengths, and…

  11. Effects of Crocetin Esters and Crocetin from Crocus sativus L. on Aortic Contractility in Rat Genetic Hypertension

    Directory of Open Access Journals (Sweden)

    Silvia Llorens

    2015-09-01

    Full Text Available Background: Endothelial dysfunction, characterized by an enhancement in vasoconstriction, is clearly associated with hypertension. Saffron (Crocus sativus L. bioactive compounds have been recognized to have hypotensive properties. Recently, we have reported that crocetin exhibits potent vasodilator effects on isolated aortic rings from hypertensive rats. In this work, we have aimed to analyze the anticontractile ability of crocetin or crocetin esters pool (crocins isolated from saffron. Thus, we have studied the effects of saffron carotenoids on endothelium-dependent and -independent regulation of smooth muscle contractility in genetic hypertension. Methods: We have measured the isometric responses of aortic segments with or without endothelium obtained from spontaneously hypertensive rats. The effects of carotenoids were studied by assessing the endothelial modulation of phenylephrine-induced contractions (10−9–10−5 M in the presence or absence of crocetin or crocins. The role of nitric oxide and prostanoids was analyzed by performing the experiments with L-NAME (NG-nitro-l-arginine methyl ester or indomethacin (both 10−5 M, respectively. Results: Crocetin, and to a minor extent crocins, diminished the maximum contractility of phenylephrine in intact rings, while crocins, but not crocetin, increased this contractility in de-endothelizated vessels. In the intact vessels, the effect of crocetin on contractility was unaffected by indomethacin but was abolished by L-NAME. However, crocetin but not crocins, lowered the already increased contractility caused by L-NAME. Conclusions: Saffron compounds, but especially crocetin have endothelium-dependent prorelaxing actions. Crocins have procontractile actions that take place via smooth muscle cell mechanisms. These results suggest that crocetin and crocins activate different mechanisms involved in the vasoconstriction pathway in hypertension.

  12. The response of the southern Greenland ice sheet to the Holocene thermal maximum

    DEFF Research Database (Denmark)

    Larsen, Nicolaj Krog; Kjaer, Kurt H.; Lecavalier, Benoit

    2015-01-01

    contribution of 0.16 m sea-level equivalent from the entire Greenland ice sheet, with a centennial ice loss rate of as much as 100 Gt/yr for several millennia during the Holocene thermal maximum. Our results provide an estimate of the long-term rates of volume loss that can be expected in the future...

  13. Geoarchaeological response to landscape changes of the Greek continental shelf since the Last Glacial Maximum

    Science.gov (United States)

    Kapsimalis, Vasilios; Pavlopoulos, Kosmas; Panagiotopoulos, Ioannis

    2010-05-01

    An overview of geological, sedimentological, palaeoclimatic, archaeological and mythological data is presented in order to detect the geomorphological changes of the Aegean and Ionian shelves during the last sea-level transgression, and comprehend the consequent prehistoric human adaptations. The irregular rise of sea level since the Last Glacial Maximum forced the Palaeolithic human to abandon its settlements located near the old (lower) coastlines and to move landward in new positions. Commonly, the coastline movement was very slow causing no significant impact on human activities; however in some cases, the transgression was very prompt causing human migration towards highlands. In some very gentle-dipped and wide regions, e.g. the North Aegean plateau, the sea-level rise caused a rapid coastline retreat (in some extreme case as fast as 10 m/yr) and inundation of an extended surface area. However, at the same time, in the steep parts of the Greek shelf, e.g. the Kyparissiakos Gulf and Crete, the coastline advanced landwards with a slow motion (commonly, a few cm/yr) covering small areas. In addition, coastal regions with particular geomorphologic characteristics, e.g. coastal paleo-lakes protected by a sill (gulfs of Corinth, Amvrakikos, Pagasitikos Evvoikos, Saronikos), were deluged by the sea during different periods and under different intensity, depending on the elevation of the sill and the manner of its overflow. Although the presence of Palaeolithic human in the Greek mainland has been confirmed by several archaeological excavations, there is no certain evidence for human settlement in the deep parts of Greek shelf. However, many archaeologists have suggested that some of Palaeolithic people lived on the shelf, when the sea level was lower than its present position. Nevertheless, some potential Palaeolithic migration routes can be indicated taking into account (a) the palaeogeographic reconstruction of Greek shelf over the Last Quaternary; (b

  14. Maximum in the middle: nonlinear response of microbial plankton to ultraviolet radiation and phosphorus.

    Directory of Open Access Journals (Sweden)

    Juan Manuel Medina-Sánchez

    Full Text Available The responses of heterotrophic microbial food webs (HMFW to the joint action of abiotic stressors related to global change have been studied in an oligotrophic high-mountain lake. A 2×5 factorial design field experiment performed with large mesocosms for >2 months was used to quantify the dynamics of the entire HMFW (bacteria, heterotrophic nanoflagellates, ciliates, and viruses after an experimental P-enrichment gradient which approximated or surpassed current atmospheric P pulses in the presence vs. absence of ultraviolet radiation. HMFW underwent a mid-term (<20 days acute development following a noticeable unimodal response to P enrichment, which peaked at intermediate P-enrichment levels and, unexpectedly, was more accentuated under ultraviolet radiation. However, after depletion of dissolved inorganic P, the HMFW collapsed and was outcompeted by a low-diversity autotrophic compartment, which constrained the development of HMFW and caused a significant loss of functional biodiversity. The dynamics and relationships among variables, and the response patterns found, suggest the importance of biotic interactions (predation/parasitism and competition in restricting HMFW development, in contrast to the role of abiotic factors as main drivers of autotrophic compartment. The response of HMFW may contribute to ecosystem resilience by favoring the maintenance of the peculiar paths of energy and nutrient-mobilization in these pristine ecosystems, which are vulnerable to threats by the joint action of abiotic stressors related to global change.

  15. An Alternative Estimator for the Maximum Likelihood Estimator for the Two Extreme Response Patterns.

    Science.gov (United States)

    1981-06-29

    is the item discrimination parameter and b is the g X g item response difficulty parameter which satisfies (2.3) - = b 0 < b1 < b 2 < ....... < b...Tuscon, AZ 85721 4833 Rugby Avenue Dr. John B. Carroll Bethesda, MD 20014 Psychometric Lab 1 Dr. Leonard Feldt Univ. of No. Carolina Lindquist Center for

  16. An iterative method applied to optimize the design of PIN photodiodes for enhanced radiation tolerance and maximum light response

    International Nuclear Information System (INIS)

    Cedola, A.P.; Cappelletti, M.A.; Casas, G.; Peltzer y Blanca, E.L.

    2011-01-01

    An iterative method based on numerical simulations was developed to enhance the proton radiation tolerance and the responsivity of Si PIN photodiodes. The method allows to calculate the optimal values of the intrinsic layer thickness and the incident light wavelength, in function of the light intensity and the maximum proton fluence to be supported by the device. These results minimize the effects of radiation on the total reverse current of the photodiode and maximize its response to light. The implementation of the method is useful in the design of devices whose operation point should not suffer variations due to radiation.

  17. Modulatory effects of taurine on jejunal contractility

    Directory of Open Access Journals (Sweden)

    Q.Y. Yao

    2014-12-01

    Full Text Available Taurine (2-aminoethanesulfonic acid is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.

  18. Modulatory effects of taurine on jejunal contractility

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Q.Y.; Chen, D.P.; Ye, D.M.; Diao, Y.P.; Lin, Y. [Dalian Medical University, Dalian, Liaoning (China)

    2014-10-14

    Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca{sup 2+} dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.

  19. Modulatory effects of taurine on jejunal contractility

    International Nuclear Information System (INIS)

    Yao, Q.Y.; Chen, D.P.; Ye, D.M.; Diao, Y.P.; Lin, Y.

    2014-01-01

    Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca 2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism

  20. Modulatory effects of taurine on jejunal contractility

    Science.gov (United States)

    Yao, Q.Y.; Chen, D.P.; Ye, D.M.; Diao, Y.P.; Lin, Y.

    2014-01-01

    Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism. PMID:25387674

  1. Maximum tech, minimum time. Response and cleanup of the Fidalgo Bay oil spill

    International Nuclear Information System (INIS)

    Pintler, L.R.

    1991-01-01

    A booster pump failure on a pipeline at Texaco's Anacortes refinery spilled more than 17,000 gallons of oil into Fidalgo Bay. A description is given of the spill control measures taken under Texaco's Spill Prevention and Control Countermeasures and facility contingency plans. The spill was addressed quickly, and containment booms were used to cordon off the spill. Vacuum trucks, rope mop machines and disk skimmers were used to collect the thickest concentrations of oil, and the oil and water collected was separated at the refinery's wastewater treatment centre. Nonwoven polypropylene sorbent pads, sweeps, booms and oil snares were used to clean up thinner concentrations of oil. Essential steps for a smooth spill response include the following: a comprehensive spill prevention and control countermeasures plan, training and regular drills and testing; immediate notification of appropriate regulatory agencies and company emergency response personnel; and the use of professional oil spill management contractors to assist in spill cleanup. 2 figs

  2. Maximum in the Middle: Nonlinear Response of Microbial Plankton to Ultraviolet Radiation and Phosphorus

    OpenAIRE

    Medina-S?nchez, Juan Manuel; Delgado-Molina, Jos? Antonio; Bratbak, Gunnar; Bullejos, Francisco Jos?; Villar-Argaiz, Manuel; Carrillo, Presentaci?n

    2013-01-01

    The responses of heterotrophic microbial food webs (HMFW) to the joint action of abiotic stressors related to global change have been studied in an oligotrophic high-mountain lake. A 2??5 factorial design field experiment performed with large mesocosms for >2 months was used to quantify the dynamics of the entire HMFW (bacteria, heterotrophic nanoflagellates, ciliates, and viruses) after an experimental P-enrichment gradient which approximated or surpassed current atmospheric P pulses in the ...

  3. Maximum in the middle: nonlinear response of microbial plankton to ultraviolet radiation and phosphorus.

    Science.gov (United States)

    Medina-Sánchez, Juan Manuel; Delgado-Molina, José Antonio; Bratbak, Gunnar; Bullejos, Francisco José; Villar-Argaiz, Manuel; Carrillo, Presentación

    2013-01-01

    The responses of heterotrophic microbial food webs (HMFW) to the joint action of abiotic stressors related to global change have been studied in an oligotrophic high-mountain lake. A 2×5 factorial design field experiment performed with large mesocosms for >2 months was used to quantify the dynamics of the entire HMFW (bacteria, heterotrophic nanoflagellates, ciliates, and viruses) after an experimental P-enrichment gradient which approximated or surpassed current atmospheric P pulses in the presence vs. absence of ultraviolet radiation. HMFW underwent a mid-term (ultraviolet radiation. However, after depletion of dissolved inorganic P, the HMFW collapsed and was outcompeted by a low-diversity autotrophic compartment, which constrained the development of HMFW and caused a significant loss of functional biodiversity. The dynamics and relationships among variables, and the response patterns found, suggest the importance of biotic interactions (predation/parasitism and competition) in restricting HMFW development, in contrast to the role of abiotic factors as main drivers of autotrophic compartment. The response of HMFW may contribute to ecosystem resilience by favoring the maintenance of the peculiar paths of energy and nutrient-mobilization in these pristine ecosystems, which are vulnerable to threats by the joint action of abiotic stressors related to global change.

  4. Maximum likelihood estimation of dose-response parameters for therapeutic operating characteristic (TOC) analysis of carcinoma of the nasopharynx

    International Nuclear Information System (INIS)

    Metz, C.E.; Tokars, R.P.; Kronman, H.B.; Griem, M.L.

    1982-01-01

    A Therapeutic Operating Characteristic (TOC) curve for radiation therapy plots, for all possible treatment doses, the probability of tumor ablation as a function of the probability of radiation-induced complication. Application of this analysis to actual therapeutic situation requires that dose-response curves for ablation and for complication be estimated from clinical data. We describe an approach in which ''maximum likelihood estimates'' of these dose-response curves are made, and we apply this approach to data collected on responses to radiotherapy for carcinoma of the nasopharynx. TOC curves constructed from the estimated dose-response curves are subject to moderately large uncertainties because of the limitations of available data.These TOC curves suggest, however, that treatment doses greater than 1800 rem may substantially increase the probability of tumor ablation with little increase in the risk of radiation-induced cervical myelopathy, especially for T1 and T2 tumors

  5. LPS from Porphyromonas gingivalis increases the sensitivity of contractile response mediated by endothelin-B (ET(B)) receptors in cultured endothelium-intact rat coronary arteries

    DEFF Research Database (Denmark)

    Ghorbani, Bahareh; Holmstrup, Palle; Edvinsson, Lars

    2010-01-01

    The purpose of our study was to examine if lipopolysaccharide (LPS) from Porphyromonas gingivalis (P.g.) modifies the vasomotor responses to Endothelin-1 (ET-1) and Sarafotoxin 6c (S6c) in rat coronary arteries. The arteries were studied directly or following organ culture for 24h in absence...

  6. Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

    Science.gov (United States)

    Ianuzzo, C. D.; Chen, V.

    1977-01-01

    Describes an experiment using rats that demonstrates contractile characteristics of normal and hypertrophied muscle. Compensatory hypertrophy of the plantaris muscle is induced by surgical removal of the synergistic gastrocnemium muscle. Includes methods for determination of contractile properties of normal and hypertrophied muscle and…

  7. Assessment of precast beam-column using capacity demand response spectrum subject to design basis earthquake and maximum considered earthquake

    Science.gov (United States)

    Ghani, Kay Dora Abd.; Tukiar, Mohd Azuan; Hamid, Nor Hayati Abdul

    2017-08-01

    Malaysia is surrounded by the tectonic feature of the Sumatera area which consists of two seismically active inter-plate boundaries, namely the Indo-Australian and the Eurasian Plates on the west and the Philippine Plates on the east. Hence, Malaysia experiences tremors from far distant earthquake occurring in Banda Aceh, Nias Island, Padang and other parts of Sumatera Indonesia. In order to predict the safety of precast buildings in Malaysia under near field ground motion the response spectrum analysis could be used for dealing with future earthquake whose specific nature is unknown. This paper aimed to develop of capacity demand response spectrum subject to Design Basis Earthquake (DBE) and Maximum Considered Earthquake (MCE) in order to assess the performance of precast beam column joint. From the capacity-demand response spectrum analysis, it can be concluded that the precast beam-column joints would not survive when subjected to earthquake excitation with surface-wave magnitude, Mw, of more than 5.5 Scale Richter (Type 1 spectra). This means that the beam-column joint which was designed using the current code of practice (BS8110) would be severely damaged when subjected to high earthquake excitation. The capacity-demand response spectrum analysis also shows that the precast beam-column joints in the prototype studied would be severely damaged when subjected to Maximum Considered Earthquake (MCE) with PGA=0.22g having a surface-wave magnitude of more than 5.5 Scale Richter, or Type 1 spectra.

  8. Altered contractile response due to increased beta3-adrenoceptor stimulation in diabetic cardiomyopathy: the role of nitric oxide synthase 1-derived nitric oxide.

    Science.gov (United States)

    Amour, Julien; Loyer, Xavier; Le Guen, Morgan; Mabrouk, Nejma; David, Jean-Stéphane; Camors, Emmanuel; Carusio, Nunzia; Vivien, Benoît; Andriantsitohaina, Ramaroson; Heymes, Christophe; Riou, Bruno

    2007-09-01

    In the diabetic heart, the positive inotropic response to beta-adrenoceptor stimulation is altered and beta1 and beta2 adrenoceptors are down-regulated, whereas beta3 adrenoceptor is up-regulated. In heart failure, beta3-adrenoceptor stimulation induces a negative inotropic effect that results from endothelial nitric oxide synthase (NOS3)-derived nitric oxide production. The objective of our study was to investigate the role of beta3-adrenoceptor in diabetic cardiomyopathy. beta-Adrenergic responses were investigated in vivo (dobutamine echocardiography) and in vitro (left ventricular papillary muscle) in healthy and streptozotocin-induced diabetic rats. The effect of beta3-adrenoceptor inhibition on the inotropic response was studied in vitro. Immunoblots and NOS activities were performed in heart homogenates (electron paramagnetic resonance) and isolated cardiomyocytes. Data are mean percentage of baseline +/- SD. The impaired positive inotropic effect was confirmed in diabetes both in vivo (121 +/- 15% vs. 160 +/- 16%; P < 0.05) and in vitro (112 +/- 5% vs. 179 +/- 15%; P < 0.05). In healthy rat, the positive inotropic effect was not significantly modified in presence of beta3-adrenoceptor antagonist (174 +/- 20%), nonselective NOS inhibitor (N -nitro-l-arginine methylester [l-NAME]; 183 +/- 19%), or selective NOS1 inhibitor (vinyl-l-N-5-(1-imino-3-butenyl)-l-ornithine [l-VNIO]; 172 +/- 13%). In diabetes, in parallel with the increase in beta3-adrenoceptor protein expression, the positive inotropic effect was partially restored by beta3-adrenoceptor antagonist (137 +/- 8%; P < 0.05), l-NAME (133 +/- 11%; P < 0.05), or l-VNIO (130 +/- 13%; P < 0.05). Nitric oxide was exclusively produced by NOS1 within diabetic cardiomyocytes. NOS2 and NOS3 proteins were undetectable. beta3-Adrenoceptor is involved in altered positive inotropic response to beta-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by NOS1-derived nitric oxide in diabetic

  9. Na(+)/Ca(2+) exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart.

    Science.gov (United States)

    Farkas, A S; Acsai, K; Nagy, N; Tóth, A; Fülöp, F; Seprényi, G; Birinyi, P; Nánási, P P; Forster, T; Csanády, M; Papp, J G; Varró, A; Farkas, A

    2008-05-01

    The Na(+)/Ca(2+) exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na(+) concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 microM SEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na(+) concentrations in rabbit and rat hearts. The concentration-dependent effects of SEA0400 on I(Na/Ca) were studied in rat and rabbit ventricular cardiomyocytes using a patch clamp technique. Starling curves were constructed for isolated, Langendorff-perfused rat and rabbit hearts. The cardiac sarcolemmal NCX protein densities of both species were compared by immunohistochemistry. SEA0400 inhibited I(Na/Ca) with similar efficacy in the two species; there was no difference between the inhibitions of the forward or reverse mode of the NCX in either species. SEA0400 increased the systolic and the developed pressure in the rat heart in a concentration-dependent manner, for example, 1.0 microM SEA0400 increased the maximum systolic pressures by 12% relative to the control, whereas it failed to alter the contractility in the rabbit heart. No interspecies difference was found in the cardiac sarcolemmal NCX protein densities. NCX inhibition exerted a positive inotropic effect in the rat heart, but it did not influence the contractility of the rabbit heart. This implies that the AP configuration and the intracellular Na(+) concentration may play an important role in the contractility response to NCX inhibition.

  10. Modifying influence of incorporated 137Cs upon the mechanisms of adrenergic control over contractile myucard function

    International Nuclear Information System (INIS)

    Lobanok, L.M.; Bulanova, K.Ya.; Gerasimovich, N.V.; Sineleva, M.V.; Milyutin, A.A.

    1994-01-01

    Incorporated 137 Cs (absorbed dose of 0.26 Gy) causes decrease of myocard's contractile function and intropic response to β-adrenagonists effect, isoproterenol-stimulated adenylate cyclase activity and β-adrenoreceptors affinity. Adrenergic effects, mediated by α-adrenergic structures on heart contractile function, on the contrary, become stronger, that is due to the increase of the receptors' dencity on sarcolemma surface

  11. Effects of hypoxia and hypercapnia on geniohyoid contractility and endurance.

    Science.gov (United States)

    Salmone, R J; Van Lunteren, E

    1991-08-01

    Sleep apnea and other respiratory diseases produce hypoxemia and hypercapnia, factors that adversely affect skeletal muscle performance. To examine the effects of these chemical alterations on force production by an upper airway dilator muscle, the contractile and endurance characteristics of the geniohyoid muscle were examined in situ during severe hypoxia (arterial PO2 less than 40 Torr), mild hypoxia (PO2 45-65 Torr), and hypercapnia (PCO2 55-80 Torr) and compared with hyperoxic-normocapnic conditions in anesthetized cats. Muscles were studied at optimal length, and contractile force was assessed in response to supramaximal electrical stimulation of the hypoglossal nerve (n = 7 cats) or geniohyoid muscle (n = 2 cats). There were no significant changes in the twitch kinetics or force-frequency curve of the geniohyoid muscle during hypoxia or hypercapnia. However, the endurance of the geniohyoid, as reflected in the fatigue index (ratio of force at 2 min to initial force in response to 40-Hz stimulation at a duty cycle 0.33), was significantly reduced by severe hypoxia but not by hypercapnia or mild hypoxia. In addition, the downward shift in the force-frequency curve after the repetitive stimulation protocol was greater during hypoxia than hyperoxia, especially at higher frequencies. In conclusion, the ability of the geniohyoid muscle to maintain force output during high levels of activation is adversely affected by severe hypoxia but not mild hypoxia or hypercapnia. However, none of these chemical perturbations affected muscle contractility acutely.

  12. Effects of endothelin, calcium channel blockade and EDRF inhibition on the contractility of human uteroplacental arteries.

    Science.gov (United States)

    Fried, G; Liu, Y A

    1994-08-01

    In order to examine the possibility that endothelin might be important in the regulation of placental blood flow, human uteroplacental vessels were superfused in vitro to study the contractile effect of endothelin as compared with a known strong contractor of placental blood vessels, serotonin (5-HT). The contractile responses were compared in the presence and absence of calcium channel blocking agents, as well as in the presence of L-NMA, an inhibitor of EDRF/nitric oxide. Endothelin (ET, 10(-10)-10(-6) M) and 5-HT (10(-8)-10(-4) M) induced contractions in the vessels. Maximal contractions in the presence of endothelin were elicited at 10(-7) M, whereas 5-HT elicited maximal contractions at 10(-5) M. At 10(-7) M, ET was more potent than 5-HT. The calcium-channel blocking agents nifedipine, diltiazem and NiCl2 relaxed the vessels by 5-15% from baseline. The contractile response to ET in the presence of nifedipine or diltiazem was reduced by 55 and 67%, respectively. The response of 5-HT in the presence of nifedipine was reduced by 58%. The contractile response to 5-HT as well as ET in the presence of both nifedipine and NiCl2 was not significantly lower than in the presence of nifedipine only. The EDRF-inhibiting agent L-NMA caused a small contractile response at concentrations of 10(-6)-10(-5) M. ET as well as 5-HT added after pretreatment with L-NMA produced a larger contractile response than ET or 5-HT alone. The results show that ET has a strong contractile effect on placental blood vessels at concentrations likely to occur during labor and delivery. The mechanism whereby ET as well as 5-HT contracts placental vessel smooth muscle appears to partly involve nifedipine- and diltiazem-sensitive calcium channels, but almost half of the response depends on mobilization of calcium through other means.

  13. A global, myosin light chain kinase-dependent increase in myosin II contractility accompanies the metaphase-anaphase transition in sea urchin eggs.

    Science.gov (United States)

    Lucero, Amy; Stack, Christianna; Bresnick, Anne R; Shuster, Charles B

    2006-09-01

    Myosin II is the force-generating motor for cytokinesis, and although it is accepted that myosin contractility is greatest at the cell equator, the temporal and spatial cues that direct equatorial contractility are not known. Dividing sea urchin eggs were placed under compression to study myosin II-based contractile dynamics, and cells manipulated in this manner underwent an abrupt, global increase in cortical contractility concomitant with the metaphase-anaphase transition, followed by a brief relaxation and the onset of furrowing. Prefurrow cortical contractility both preceded and was independent of astral microtubule elongation, suggesting that the initial activation of myosin II preceded cleavage plane specification. The initial rise in contractility required myosin light chain kinase but not Rho-kinase, but both signaling pathways were required for successful cytokinesis. Last, mobilization of intracellular calcium during metaphase induced a contractile response, suggesting that calcium transients may be partially responsible for the timing of this initial contractile event. Together, these findings suggest that myosin II-based contractility is initiated at the metaphase-anaphase transition by Ca2+-dependent myosin light chain kinase (MLCK) activity and is maintained through cytokinesis by both MLCK- and Rho-dependent signaling. Moreover, the signals that initiate myosin II contractility respond to specific cell cycle transitions independently of the microtubule-dependent cleavage stimulus.

  14. A Global, Myosin Light Chain Kinase-dependent Increase in Myosin II Contractility Accompanies the Metaphase–Anaphase Transition in Sea Urchin Eggs

    Science.gov (United States)

    Lucero, Amy; Stack, Christianna; Bresnick, Anne R.

    2006-01-01

    Myosin II is the force-generating motor for cytokinesis, and although it is accepted that myosin contractility is greatest at the cell equator, the temporal and spatial cues that direct equatorial contractility are not known. Dividing sea urchin eggs were placed under compression to study myosin II-based contractile dynamics, and cells manipulated in this manner underwent an abrupt, global increase in cortical contractility concomitant with the metaphase–anaphase transition, followed by a brief relaxation and the onset of furrowing. Prefurrow cortical contractility both preceded and was independent of astral microtubule elongation, suggesting that the initial activation of myosin II preceded cleavage plane specification. The initial rise in contractility required myosin light chain kinase but not Rho-kinase, but both signaling pathways were required for successful cytokinesis. Last, mobilization of intracellular calcium during metaphase induced a contractile response, suggesting that calcium transients may be partially responsible for the timing of this initial contractile event. Together, these findings suggest that myosin II-based contractility is initiated at the metaphase–anaphase transition by Ca2+-dependent myosin light chain kinase (MLCK) activity and is maintained through cytokinesis by both MLCK- and Rho-dependent signaling. Moreover, the signals that initiate myosin II contractility respond to specific cell cycle transitions independently of the microtubule-dependent cleavage stimulus. PMID:16837551

  15. Recently active contractile deformation in the forearc of southern Peru

    Science.gov (United States)

    Hall, S. R.; Farber, D.; Audin, L.; Finkel, R. C.

    2010-12-01

    In the Precordillera and Western Cordillera of southern Peru (14°-18°S), vast pediment surfaces have been abandoned through drainage diversion and river incision, with the major drainages carving deep canyons. Within this region, we have identified range-sub-parallel contractile structures that accommodate significant distributed crustal deformation. Young geomorphic features document both the presence and youthfulness of these contractile structures. Here, we determine exposure ages on geomorphic features such as pediment surfaces and fluvial terraces using in situ produced cosmogenic radionuclides, in conjunction with field and remote mapping. This chronologic data reveals that ancient surfaces have been preserved as a result of very low erosion rates. We measure this rate to be chronology and geomorphic mapping, we calculate a Pleistocene river incision rate of ~0.3mm/yr determined from data collected along exoreic rivers. This rate is consistent with longer-term incision rates measured in other localities along this margin. We suggest that, in this region of southern Peru, the steep western wedge of the Andean margin supports the high topography of the Altiplano through a combination of uplift along steeply dipping contractile west-vergent structures and isostatic responses to the focused removal of large amounts of crustal material through canyon incision. Further, that these range sub-parallel structures are related at depth to a thrust system that plays a role in not only the maintenance of the Andean margin, but potentially in its formation as well.

  16. Protein kinase Cα deletion causes hypotension and decreased vascular contractility.

    Science.gov (United States)

    Wynne, Brandi M; McCarthy, Cameron G; Szasz, Theodora; Molina, Patrick A; Chapman, Arlene B; Webb, R Clinton; Klein, Janet D; Hoover, Robert S

    2018-03-01

    Protein kinase Cα (PKCα) is a critical regulator of multiple cell signaling pathways including gene transcription, posttranslation modifications and activation/inhibition of many signaling kinases. In regards to the control of blood pressure, PKCα causes increased vascular smooth muscle contractility, while reducing cardiac contractility. In addition, PKCα has been shown to modulate nephron ion transport. However, the role of PKCα in modulating mean arterial pressure (MAP) has not been investigated. In this study, we used a whole animal PKCα knock out (PKC KO) to test the hypothesis that global PKCα deficiency would reduce MAP, by a reduction in vascular contractility. Radiotelemetry measurements of ambulatory blood pressure (day/night) were obtained for 18 h/day during both normal chow and high-salt (4%) diet feedings. PKCα mice had a reduced MAP, as compared with control, which was not normalized with high-salt diet (14 days). Metabolic cage studies were performed to determine urinary sodium excretion. PKC KO mice had a significantly lower diastolic, systolic and MAP as compared with control. No significant differences in urinary sodium excretion were observed between the PKC KO and control mice, whether fed normal chow or high-salt diet. Western blot analysis showed a compensatory increase in renal sodium chloride cotransporter expression. Both aorta and mesenteric vessels were removed for vascular reactivity studies. Aorta and mesenteric arteries from PKC KO mice had a reduced receptor-independent relaxation response, as compared with vessels from control. Vessels from PKC KO mice exhibited a decrease in maximal contraction, compared with controls. Together, these data suggest that global deletion of PKCα results in reduced MAP due to decreased vascular contractility.

  17. Shallow marine response to global climate change during the Paleocene-Eocene Thermal Maximum, Salisbury Embayment, USA

    Science.gov (United States)

    Self-Trail, Jean; Robinson, Marci M.; Bralower, Timothy J.; Sessa, Jocelyn A.; Hajek, Elizabeth A.; Kump, Lee R.; Trampush, Sheila M.; Willard, Debra A.; Edwards, Lucy E.; Powars, David S.; Wandless, Gregory A.

    2017-01-01

    The Paleocene-Eocene Thermal Maximum (PETM) was an interval of extreme warmth that caused disruption of marine and terrestrial ecosystems on a global scale. Here we examine the sediments, flora, and fauna from an expanded section at Mattawoman Creek-Billingsley Road (MCBR) in Maryland and explore the impact of warming at a nearshore shallow marine (30–100 m water depth) site in the Salisbury Embayment. Observations indicate that at the onset of the PETM, the site abruptly shifted from an open marine to prodelta setting with increased terrestrial and fresh water input. Changes in microfossil biota suggest stratification of the water column and low-oxygen bottom water conditions in the earliest Eocene. Formation of authigenic carbonate through microbial diagenesis produced an unusually large bulk carbon isotope shift, while the magnitude of the corresponding signal from benthic foraminifera is similar to that at other marine sites. This proves that the landward increase in the magnitude of the carbon isotope excursion measured in bulk sediment is not due to a near instantaneous release of 12C-enriched CO2. We conclude that the MCBR site records nearshore marine response to global climate change that can be used as an analog for modern coastal response to global warming.

  18. Shallow marine response to global climate change during the Paleocene-Eocene Thermal Maximum, Salisbury Embayment, USA

    Science.gov (United States)

    Self-Trail, Jean M.; Robinson, Marci M.; Bralower, Timothy J.; Sessa, Jocelyn A.; Hajek, Elizabeth A.; Kump, Lee R.; Trampush, Sheila M.; Willard, Debra A.; Edwards, Lucy E.; Powars, David S.; Wandless, Gregory A.

    2017-07-01

    The Paleocene-Eocene Thermal Maximum (PETM) was an interval of extreme warmth that caused disruption of marine and terrestrial ecosystems on a global scale. Here we examine the sediments, flora, and fauna from an expanded section at Mattawoman Creek-Billingsley Road (MCBR) in Maryland and explore the impact of warming at a nearshore shallow marine (30-100 m water depth) site in the Salisbury Embayment. Observations indicate that at the onset of the PETM, the site abruptly shifted from an open marine to prodelta setting with increased terrestrial and fresh water input. Changes in microfossil biota suggest stratification of the water column and low-oxygen bottom water conditions in the earliest Eocene. Formation of authigenic carbonate through microbial diagenesis produced an unusually large bulk carbon isotope shift, while the magnitude of the corresponding signal from benthic foraminifera is similar to that at other marine sites. This proves that the landward increase in the magnitude of the carbon isotope excursion measured in bulk sediment is not due to a near instantaneous release of 12C-enriched CO2. We conclude that the MCBR site records nearshore marine response to global climate change that can be used as an analog for modern coastal response to global warming.

  19. Self-reported sleep disturbances due to railway noise: exposure-response relationships for nighttime equivalent and maximum noise levels.

    Science.gov (United States)

    Aasvang, Gunn Marit; Moum, Torbjorn; Engdahl, Bo

    2008-07-01

    The objective of the present survey was to study self-reported sleep disturbances due to railway noise with respect to nighttime equivalent noise level (L(p,A,eq,night)) and maximum noise level (L(p,A,max)). A sample of 1349 people in and around Oslo in Norway exposed to railway noise was studied in a cross-sectional survey to obtain data on sleep disturbances, sleep problems due to noise, and personal characteristics including noise sensitivity. Individual noise exposure levels were determined outside of the bedroom facade, the most-exposed facade, and inside the respondents' bedrooms. The exposure-response relationships were analyzed by using logistic regression models, controlling for possible modifying factors including the number of noise events (train pass-by frequency). L(p,A,eq,night) and L(p,A,max) were significantly correlated, and the proportion of reported noise-induced sleep problems increased as both L(p,A,eq,night) and L(p,A,max) increased. Noise sensitivity, type of bedroom window, and pass-by frequency were significant factors affecting noise-induced sleep disturbances, in addition to the noise exposure level. Because about half of the study population did not use a bedroom at the most-exposed side of the house, the exposure-response curve obtained by using noise levels for the most-exposed facade underestimated noise-induced sleep disturbance for those who actually have their bedroom at the most-exposed facade.

  20. Reliability of contractile properties of the knee extensor muscles in individuals with post-polio syndrome.

    Directory of Open Access Journals (Sweden)

    Eric L Voorn

    Full Text Available To assess the reliability of contractile properties of the knee extensor muscles in 23 individuals with post-polio syndrome (PPS and 18 age-matched healthy individuals.Contractile properties of the knee extensors were assessed from repeated electrically evoked contractions on 2 separate days, with the use of a fixed dynamometer. Reliability was determined for fatigue resistance, rate of torque development (MRTD, and early and late relaxation time (RT50 and RT25, using the intraclass correlation coefficient (ICC and standard error of measurement (SEM, expressed as % of the mean.In both groups, reliability for fatigue resistance was good, with high ICCs (>0.90 and small SEM values (PPS: 7.1%, healthy individuals: 7.0%. Reliability for contractile speed indices varied, with the best values found for RT50 (ICCs>0.82, SEM values <2.8%. We found no systematic differences between test and retest occasions, except for RT50 in healthy subjects (p = 0.016.In PPS and healthy individuals, the reliability of fatigue resistance, as obtained from electrically evoked contractions is high. The reliability of contractile speed is only moderate, except for RT50 in PPS, demonstrating high reliability.This was the first study to examine the reliability of electrically evoked contractile properties in individuals with PPS. Our results demonstrate its potential to study mechanisms underlying muscle fatigue in PPS and to evaluate changes in contractile properties over time in response to interventions or from natural course.

  1. Effects of minoxidil and nitroprusside on reflex increases in myocardial contractility.

    Science.gov (United States)

    Robie, N W

    1978-01-01

    1 The effects of nitroprusside and minoxidil on increases in myocardial contractility resulting from carotid artery occlusion were investigated in anaesthetized dogs. The results were compared with those produced by intravenous influsion of noradrenaline. 2 Nitroprusside and minoxidil attenuated the pressor responses produced by carotid artery occlusion. 3 Nitroprusside, but not minoxidil, attenuated the maximal myocardial contractility resulting from carotid occlusion. 4 The pressor and contractility responses to noradrenaline infusion were unaffected by either agent. 5 Nitroprusside failed to alter the myocardial responses produced by dimethylphenylpiperazinium. 6 These results, in conjunction with those of other investigators who have demonstrated that nitroprusside does not affect the release of noradrenaline from adrenergic neurons, suggest that nitroprusside may inhibit sympathetic nervous system reflex activity via an afferent and/or central component. PMID:620094

  2. The role of voltage-gated potassium channels in the regulation of mouse uterine contractility

    Directory of Open Access Journals (Sweden)

    Abel Peter W

    2007-11-01

    Full Text Available Abstract Background Uterine smooth muscle cells exhibit ionic currents that appear to be important in the control of uterine contractility, but how these currents might produce the changes in contractile activity seen in pregnant myometrium has not been established. There are conflicting reports concerning the role of voltage-gated potassium (Kv channels and large-conductance, calcium-activated potassium (BK channels in the regulation of uterine contractility. In this study we provide molecular and functional evidence for a role for Kv channels in the regulation of spontaneous contractile activity in mouse myometrium, and also demonstrate a change in Kv channel regulation of contractility in pregnant mouse myometrium. Methods Functional assays which evaluated the effects of channel blockers and various contractile agonists were accomplished by quantifying contractility of isolated uterine smooth muscle obtained from nonpregnant mice as well as mice at various stages of pregnancy. Expression of Kv channel proteins in isolated uterine smooth muscle was evaluated by Western blots. Results The Kv channel blocker 4-aminopyridine (4-AP caused contractions in nonpregnant mouse myometrium (EC50 = 54 micromolar, maximal effect at 300 micromolar but this effect disappeared in pregnant mice; similarly, the Kv4.2/Kv4.3 blocker phrixotoxin-2 caused contractions in nonpregnant, but not pregnant, myometrium. Contractile responses to 4-AP were not dependent upon nerves, as neither tetrodotoxin nor storage of tissues at room temperature significantly altered these responses, nor were responses dependent upon the presence of the endometrium. Spontaneous contractions and contractions in response to 4-AP did not appear to be mediated by BK, as the BK channel-selective blockers iberiotoxin, verruculogen, or tetraethylammonium failed to affect either spontaneous contractions or 4-AP-elicited responses. A number of different Kv channel alpha subunit proteins were

  3. Effect of heat stress on contractility of tissue-engineered artificial skeletal muscle.

    Science.gov (United States)

    Takagi, Shunya; Nakamura, Tomohiro; Fujisato, Toshia

    2018-01-23

    The effects of heat stress on tissue like skeletal muscle have been widely studied. However, the mechanism responsible for the effect of heat stress is still unclear. A useful experimental tissue model is necessary because muscle function in cell culture may differ from native muscle and measuring its contractility is difficult. We previously reported three-dimensional tissue-engineered artificial skeletal muscle (TEM) that can be easily set in a measurement apparatus for quantitative evaluation of contractility. We have now applied TEM to the investigation of heat stress. We analyzed contractility immediately after thermal exposure at 39 °C for 24 or 48 h to evaluate the acute effects and after thermal exposure followed by normal culture to evaluate the aftereffects. Peak twitch contractile force and time-to-peak twitch were used as contractile parameters. Heat stress increased the TCF in the early stage (1 week) after normal culture; the TCF decreased temporarily in the middle to late stages (2-3 weeks). These results suggest that heat stress may affect both myoblast fusion and myotube differentiation in the early stage of TEM culture, but not myotube maturation in the late stage. The TCF increase rate with thermal exposure was significantly higher than that without thermal exposure. Although detailed analysis at the molecular level is necessary for further investigation, our artificial skeletal muscle may be a promising tool for heat stress investigation.

  4. Slack length reduces the contractile phenotype of the Swine carotid artery.

    Science.gov (United States)

    Rembold, Christopher M; Garvey, Sean M; Tejani, Ankit D

    2013-01-01

    Contraction is the primary function of adult arterial smooth muscle. However, in response to vessel injury or inflammation, arterial smooth muscle is able to phenotypically modulate from the contractile state to several 'synthetic' states characterized by proliferation, migration and/or increased cytokine secretion. We examined the effect of tissue length (L) on the phenotype of intact, isometrically held, initially contractile swine carotid artery tissues. Tissues were studied (1) without prolonged incubation at the optimal length for force generation (1.0 Lo, control), (2) with prolonged incubation for 17 h at 1.0 Lo, or (3) with prolonged incubation at slack length (0.6 Lo) for 16 h and then restoration to 1.0 Lo for 1 h. Prolonged incubation at 1.0 Lo minimally reduced the contractile force without substantially altering the mediators of contraction (crossbridge phosphorylation, shortening velocity or stimulated actin polymerization). Prolonged incubation of tissues at slack length (0.6 Lo), despite return of length to 1.0 Lo, substantially reduced contractile force, reduced crossbridge phosphorylation, nearly abolished crossbridge cycling (shortening velocity) and abolished stimulated actin polymerization. These data suggest that (1) slack length treatment significantly alters the contractile phenotype of arterial tissue, and (2) slack length treatment is a model to study acute phenotypic modulation of intact arterial smooth muscle. Copyright © 2013 S. Karger AG, Basel.

  5. Computing maximum likelihood estimates of loglinear models from marginal sums with special attention to loglinear item response theory

    NARCIS (Netherlands)

    Kelderman, Henk

    1991-01-01

    In this paper, algorithms are described for obtaining the maximum likelihood estimates of the parameters in log-linear models. Modified versions of the iterative proportional fitting and Newton-Raphson algorithms are described that work on the minimal sufficient statistics rather than on the usual

  6. Computing maximum likelihood estimates of loglinear models from marginal sums with special attention to loglinear item response theory

    NARCIS (Netherlands)

    Kelderman, Henk

    1992-01-01

    In this paper algorithms are described for obtaining the maximum likelihood estimates of the parameters in loglinear models. Modified versions of the iterative proportional fitting and Newton-Raphson algorithms are described that work on the minimal sufficient statistics rather than on the usual

  7. Spontaneous actin dynamics in contractile rings

    Science.gov (United States)

    Kruse, Karsten; Wollrab, Viktoria; Thiagarajan, Raghavan; Wald, Anne; Riveline, Daniel

    Networks of polymerizing actin filaments are known to be capable to self-organize into a variety of structures. For example, spontaneous actin polymerization waves have been observed in living cells in a number of circumstances, notably, in crawling neutrophils and slime molds. During later stages of cell division, they can also spontaneously form a contractile ring that will eventually cleave the cell into two daughter cells. We present a framework for describing networks of polymerizing actin filaments, where assembly is regulated by various proteins. It can also include the effects of molecular motors. We show that the molecular processes driven by these proteins can generate various structures that have been observed in contractile rings of fission yeast and mammalian cells. We discuss a possible functional role of each of these patterns. The work was supported by Agence Nationale de la Recherche, France, (ANR-10-LABX-0030-INRT) and by Deutsche Forschungsgemeinschaft through SFB1027.

  8. Effect of short-term outlet obstruction on rat bladder nerve density and contractility

    NARCIS (Netherlands)

    Barendrecht, M. M.; Chichester, P.; Michel, M. C.; Levin, R. M.

    2007-01-01

    1 The present study was designed to investigate the relationship between innervation density and contractile responses to field stimulation and exogenous agonists at early time points after induction of bladder outlet obstruction (BOO) in rats. 2 When compared with sham-operated animals, 1, 3 and 7

  9. Effect of a Carbohydrate-Rich Diet on Rat Detrusor Smooth Muscle Contractility: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Mustafa Suat Bolat

    2017-01-01

    Full Text Available Objectives. We aimed to investigate the effect of a carbohydrate-rich diet on detrusor contractility in rats. Materials and Methods. Sprague-Dawley rats were randomized into two groups. The control group received regular food and water. The study group received carbohydrate-rich diet for six weeks. The rats’ detrusor muscle was isolated for pharmacological and histopathological examinations. Results. In the control and study groups, mean body weights were 431.5 ± 27.6 g and 528.0 ± 36.2 g, respectively (p < 0.001. Electrical stimulation of the detrusor strips of the control group resulted in gradual contraction. A decreased contractile response was shown in the study group. Acetylcholine in 10-7-10-3 molar concentration produced a decreased contractile response in the study group, compared to the control group (p < 0.01. The study group showed marked subepithelial and intermuscular fibrosis in the bladder. Conclusion. Carbohydrate-rich diet causes marked subepithelial and extracellular fibrosis and changes in contractility in the detrusor within a six-week period. Changes have higher costs in therapeutic choices and correction of these changes remains difficult. Putting an end to carbohydrate-rich diet would seem to be more cost-effective than dealing with the effects of consuming it in high proportions which should be the national policy worldwide.

  10. Use of Maximum Likelihood-Mixed Models to select stable reference genes: a case of heat stress response in sheep

    Directory of Open Access Journals (Sweden)

    Salces Judit

    2011-08-01

    Full Text Available Abstract Background Reference genes with stable expression are required to normalize expression differences of target genes in qPCR experiments. Several procedures and companion software have been proposed to find the most stable genes. Model based procedures are attractive because they provide a solid statistical framework. NormFinder, a widely used software, uses a model based method. The pairwise comparison procedure implemented in GeNorm is a simpler procedure but one of the most extensively used. In the present work a statistical approach based in Maximum Likelihood estimation under mixed models was tested and compared with NormFinder and geNorm softwares. Sixteen candidate genes were tested in whole blood samples from control and heat stressed sheep. Results A model including gene and treatment as fixed effects, sample (animal, gene by treatment, gene by sample and treatment by sample interactions as random effects with heteroskedastic residual variance in gene by treatment levels was selected using goodness of fit and predictive ability criteria among a variety of models. Mean Square Error obtained under the selected model was used as indicator of gene expression stability. Genes top and bottom ranked by the three approaches were similar; however, notable differences for the best pair of genes selected for each method and the remaining genes of the rankings were shown. Differences among the expression values of normalized targets for each statistical approach were also found. Conclusions Optimal statistical properties of Maximum Likelihood estimation joined to mixed model flexibility allow for more accurate estimation of expression stability of genes under many different situations. Accurate selection of reference genes has a direct impact over the normalized expression values of a given target gene. This may be critical when the aim of the study is to compare expression rate differences among samples under different environmental

  11. Cadmium translocation by contractile roots differs from that in regular, non-contractile roots.

    Science.gov (United States)

    Lux, Alexander; Lackovič, Andrej; Van Staden, Johannes; Lišková, Desana; Kohanová, Jana; Martinka, Michal

    2015-06-01

    Contractile roots are known and studied mainly in connection with the process of shrinkage of their basal parts, which acts to pull the shoot of the plant deeper into the ground. Previous studies have shown that the specific structure of these roots results in more intensive water uptake at the base, which is in contrast to regular root types. The purpose of this study was to find out whether the basal parts of contractile roots are also more active in translocation of cadmium to the shoot. Plants of the South African ornamental species Tritonia gladiolaris were cultivated in vitro for 2 months, at which point they possessed well-developed contractile roots. They were then transferred to Petri dishes with horizontally separated compartments of agar containing 50 µmol Cd(NO3)2 in the region of the root base or the root apex. Seedlings of 4-d-old maize (Zea mays) plants, which do not possess contractile roots, were also transferred to similar Petri dishes. The concentrations of Cd in the leaves of the plants were compared after 10 d of cultivation. Anatomical analyses of Tritonia roots were performed using appropriately stained freehand cross-sections. The process of contraction required specific anatomical adaptation of the root base in Tritonia, with less lignified and less suberized tissues in comparison with the subapical part of the root. These unusual developmental characteristics were accompanied by more intensive translocation of Cd ions from the basal part of contractile roots to the leaves than from the apical-subapical root parts. The opposite effects were seen in the non-contractile roots of maize, with higher uptake and transport by the apical parts of the root and lower uptake and transport by the basal part. The specific characteristics of contractile roots may have a significant impact on the uptake of ions, including toxic metals from the soil surface layers. This may be important for plant nutrition, for example in the uptake of nutrients from

  12. The numerical simulation of the WWER-440/V-213 reactor pressure vessel internals response to maximum hypothetical large break loss of coolant accident

    International Nuclear Information System (INIS)

    Hermansky, P.; Krajcovic, M.

    2012-01-01

    The reactor internals are designed to ensure cooling of the fuel, to ensure the movement of emergency control assemblies under all operating conditions including accidents and facilitate removal of the fuel and of the internals following an accident This paper presents results of the numerical simulation of the WWER-440/V213 reactor vessel internals dynamic response to maximum hypothetical Large-Break Loss of Coolant Accident. The purpose of this analysis is to determine the reactor vessel internals response due to rapid depressurization and to prove no such deformations occur in the reactor vessel internals which would prevent timely and proper activation of the emergency control assemblies. (Authors)

  13. Contractility Dispersion in Long QT Syndrome

    Directory of Open Access Journals (Sweden)

    MH Nikoo

    2009-09-01

    Full Text Available Background: Previous studies, using M mode echocardiography, provided unexpected evidence of a mechanical alteration in patients with long QT syndrome. The aim of this study was to evaluate entire left ventricular (LV wall motion characteristics in patients with long QT syndrome using tissue Doppler imaging. Methods: We enrolled 17 patients with congenital long QT syndrome [11 female and 6 male], aged 21 to 45 years. 10 subjects without cardiac disease were also selected as a control group. Two-dimensional tissue Doppler imaging (TDI recording of the LV was obtained from the basal and mid-segments from apical four-chamber, two-chamber, and long-axis views. ‘Myocardial Contraction Duration’ [MCD] was defined as the time from start of R wave on ECG to end of S wave on TDI. MCD was measured in the six LV wall positions: septal, anteroseptal, lateral, inferior, posterior and anterior positions.Results: LV contractility dispersion was significantly greater in long QT syndrome patients compared to control group [0.051 ± 0.011 vs. 0.016 ± 0.06; P < 0.001]. Conclusion: Our study evaluated left ventricular dispersion of contractility duration in patients with long QT syndrome. This mechanical dispersion may be a reflection of the inhomogeneity of repolarisation in the long QT syndrome.

  14. Permanent Distal Occlusion of Middle Cerebral Artery in Rat Causes Local Increased ETB, 5-HT1B and AT1 Receptor-Mediated Contractility Downstream of Occlusion

    DEFF Research Database (Denmark)

    Rasmussen, Marianne N P; Hornbak, Malene; Larsen, Stine S

    2013-01-01

    Background/Aims: In response to experimental stroke, a characteristic functional and expressional upregulation of contractile G-protein-coupled receptors has been uncovered in the affected cerebral vasculature; however, the mechanism initiating this phenomenon remains unknown. Methods: Using...... a model of permanent distal occlusion of rat middle cerebral arteries, we investigated whether there was a regional difference in receptor-mediated contractility of segments located upstream and downstream of the occlusion site. The contractile response to endothelin, angiotensin and 5-hydroxytryptamine...... receptor stimulation was studied by sensitive wire myograph. Results: Only downstream segments exhibited an augmented contractile response to stimulation with each of the three ligands, with the response towards sarafotoxin 6c being especially augmented compared to sham, upstream and contralateral controls...

  15. In vitro contractile effects of agents used in the clinical management of postpartum haemorrhage.

    Science.gov (United States)

    Morrison, John J; Crosby, David A; Crankshaw, Denis J

    2016-10-15

    Uterine atony is a major cause of postpartum haemorrhage and maternal mortality. However, the comparative pharmacology of agents used to treat this condition is poorly understood. This study evaluates, using human pregnant myometrium in vitro, a range of contractile parameters for agents used in the clinical treatment of atonic postpartum haemorrhage. The effects of oxytocin, carbetocin, ergometrine, carboprost, syntometrine and misoprostol were investigated in 146 myometrial strips from 19 donors. The potency and maximal response values were obtained, and compared, using both maximal amplitude and mean contractile force as indices of contraction. Single, EC50 concentrations of the agents were administered and both force and contraction peak parameters were compared during a 15-min exposure. Differences were considered significant when Poxytocin and carbetocin being the most potent. The most important difference between the agents was in their ability to increase the mean contractile force, with oxytocin superior to all agents except syntometrine. In single dose experiments, mean contractile force was the parameter that separated the agents. In this respect, oxytocin was not statistically different from carboprost or syntometrine, but was superior to all other agents. These findings support a clear role for oxytocin as the first line agent for treatment of postpartum haemorrhage and raise doubts about the potential clinical usefulness of misoprostol. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Gene transfer of heterologous G protein-coupled receptors to cardiomyocytes: differential effects on contractility.

    Science.gov (United States)

    Laugwitz, K L; Weig, H J; Moretti, A; Hoffmann, E; Ueblacker, P; Pragst, I; Rosport, K; Schömig, A; Ungerer, M

    2001-04-13

    In heart failure, reduced cardiac contractility is accompanied by blunted cAMP responses to beta-adrenergic stimulation. Parathyroid hormone (PTH)-related peptide and arginine vasopressin are released from the myocardium in response to increased wall stress but do not stimulate contractility or adenylyl cyclase at physiological concentrations. To bypass the defective beta-adrenergic signaling cascade, recombinant P1 PTH/PTH-related peptide receptors (rPTH1-Rs) and V(2) vasopressin receptors (rV(2)-Rs), which are normally not expressed in the myocardium and which are both strongly coupled to adenylyl cyclase, and recombinant beta(2)-adrenergic receptors (rbeta(2)-ARs) were overexpressed in cardiomyocytes by viral gene transfer. The capacity of endogenous hormones to increase contractility via the heterologous, recombinant receptors was compared. Whereas V(2)-Rs are uniquely coupled to Gs, PTH1-Rs and beta(2)-ARs are also coupled to other G proteins. Gene transfer of rPTH1-Rs or rbeta(2)-ARs to adult cardiomyocytes resulted in maximally increased basal contractility, which could not be further stimulated by adding receptor agonists. Agonists at rPTH1-Rs induced increased cAMP formation and phospholipase C activity. In contrast, healthy or failing rV(2)-R-expressing cardiomyocytes showed unaltered basal contractility. Their contractility and cAMP formation increased only at agonist exposure, which did not activate phospholipase C. In summary, we found that gene transfer of PTH1-Rs to cardiomyocytes results in constitutive activity of the transgene, as does that of beta(2)-ARS: In the absence of receptor agonists, rPTH1-Rs and rbeta(2)-ARs increase basal contractility, coupling to 2 G proteins simultaneously. In contrast, rV(2)-Rs are uniquely coupled to Gs and are not constitutively active, retaining their property to be activated exclusively on agonist stimulation. Therefore, gene transfer of V(2)-Rs might be more suited to test the effects of c

  17. Matching of sarcoplasmic reticulum and contractile properties in rat fast- and slow-twitch muscle fibres.

    Science.gov (United States)

    Trinh, Huong H; Lamb, Graham D

    2006-07-01

    1. The twitch characteristics (fast-twitch or slow-twitch) of skeletal muscle fibres are determined not only by the contractile apparatus properties of the fibre, but also by the time-course of Ca2+ release and re-uptake by the sarcoplasmic reticulum (SR). The present study examined, in individual fibres from non-transforming muscle of the rat, whether particular SR properties are matched to the contractile apparatus properties of the fibre, in particular in the case of fibres with fast-twitch contractile apparatus located in a slow-twitch muscle, namely the soleus. 2. Force was recorded in single, mechanically skinned fibres from extensor digitorum longus (EDL), gastrocnemius, peroneus longus and soleus muscles. Using repeated cycles in which the SR was emptied of all releasable Ca2+ and then reloaded, it was possible to determine the relative amount of Ca2+ present in the SR endogenously, the maximum SR capacity and the rate of Ca2+ loading. The sensitivity of the contractile apparatus to Ca2+ and Sr2+ was used to classify the fibres as fast-twitch (FT), slow-twitch (ST) or mixed (fibres examined) and thereby identify the likely troponin C and myosin heavy chain types present. 3. There was no significant difference in SR properties between the groups of FT fibres obtained from the four different muscles, including soleus. Despite some overlap in the SR properties of individual fibres between the FT and ST groups, the properties of the FT fibres in all four muscles studied were significantly different from those of the ST and mixed fibres. 4. In general, in FT fibres the SR had a larger capacity and the endogenous Ca2+ content was a relatively lower percentage of maximum compared with ST fibres. Importantly, in terms of their SR properties, FT fibres from soleus muscle more closely resembled FT fibres from other muscles than they did ST fibres from soleus muscle.

  18. Contractile injection systems of bacteriophages and related systems

    DEFF Research Database (Denmark)

    Taylor, Nicholas M I; van Raaij, Mark J; Leiman, Petr G

    2018-01-01

    Contractile tail bacteriophages, or myobacteriophages, use a sophisticated biomolecular structure to inject their genome into the bacterial host cell. This structure consists of a contractile sheath enveloping a rigid tube that is sharpened by a spike-shaped protein complex at its tip. The spike ...

  19. Genome sequence of Haloplasma contractile, an unusual contractile bacterium from a deep-sea anoxic brine lake.

    KAUST Repository

    Antunes, Andre; Alam, Intikhab; El Dorry, Hamza; Siam, Rania; Robertson, Anthony J.; Bajic, Vladimir B.; Stingl, Ulrich

    2011-01-01

    We present the draft genome of Haloplasma contractile, isolated from a deep-sea brine and representing a new order between Firmicutes and Mollicutes. Its complex morphology with contractile protrusions might be strongly influenced by the presence of seven MreB/Mbl homologs, which appears to be the highest copy number ever reported.

  20. Genome sequence of Haloplasma contractile, an unusual contractile bacterium from a deep-sea anoxic brine lake.

    KAUST Repository

    Antunes, Andre

    2011-09-01

    We present the draft genome of Haloplasma contractile, isolated from a deep-sea brine and representing a new order between Firmicutes and Mollicutes. Its complex morphology with contractile protrusions might be strongly influenced by the presence of seven MreB/Mbl homologs, which appears to be the highest copy number ever reported.

  1. Considerations for Contractile Electroactive Materials and Actuators

    Energy Technology Data Exchange (ETDEWEB)

    Lenore Rasmussen, David Schramm, Paul Rasmussen, Kevin Mullaly, Ras Labs, LLC, Intelligent Materials for Prosthetics & Automation, Lewis D. Meixler, Daniel Pearlman and Alice Kirk

    2011-05-23

    Ras Labs produces contractile electroactive polymer (EAP) based materials and actuators that bend, swell, ripple, and contract (new development) with low electric input. In addition, Ras Labs produces EAP materials that quickly contract and expand, repeatedly, by reversing the polarity of the electric input, which can be cycled. This phenomenon was explored using molecular modeling, followed by experimentation. Applied voltage step functions were also investigated. High voltage steps followed by low voltage steps produced a larger contraction followed by a smaller contraction. Actuator control by simply adjusting the electric input is extremely useful for biomimetic applications. Muscles are able to partially contract. If muscles could only completely contract, nobody could hold an egg, for example, without breaking it. A combination of high and low voltage step functions could produce gross motor function and fine manipulation within the same actuator unit. Plasma treated electrodes with various geometries were investigated as a means of providing for more durable actuation.

  2. Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum.

    Science.gov (United States)

    Lupia, Enrico; Spatola, Tiziana; Cuccurullo, Alessandra; Bosco, Ornella; Mariano, Filippo; Pucci, Angela; Ramella, Roberta; Alloatti, Giuseppe; Montrucchio, Giuseppe

    2010-09-01

    Thrombopoietin (TPO) is a humoral growth factor that has been shown to increase platelet activation in response to several agonists. Patients with sepsis have increased circulating TPO levels, which may enhance platelet activation, potentially participating to the pathogenesis of multi-organ failure. Aim of this study was to investigate whether TPO affects myocardial contractility and participates to depress cardiac function during sepsis. We showed the expression of the TPO receptor c-Mpl on myocardial cells and tissue by RT-PCR, immunofluorescence and western blotting. We then evaluated the effect of TPO on the contractile function of rat papillary muscle and isolated heart. TPO did not change myocardial contractility in basal conditions, but, when followed by epinephrine (EPI) stimulation, it blunted the enhancement of contractile force induced by EPI both in papillary muscle and isolated heart. An inhibitor of TPO prevented TPO effect on cardiac inotropy. Treatment of papillary muscle with pharmacological inhibitors of phosphatidylinositol 3-kinase, NO synthase, and guanilyl cyclase abolished TPO effect, indicating NO as the final mediator. We finally studied the role of TPO in the negative inotropic effect exerted by human septic shock (HSS) serum and TPO cooperation with TNF-alpha and IL-1beta. Pre-treatment with the TPO inhibitor prevented the decrease in contractile force induced by HSS serum. Moreover, TPO significantly amplified the negative inotropic effect induced by TNF-alpha and IL-1beta in papillary muscle. In conclusion, TPO negatively modulates cardiac inotropy in vitro and contributes to the myocardial depressing activity of septic shock serum.

  3. New insights into roles of acidocalcisomes and contractile vacuole complex in osmoregulation in protists.

    Science.gov (United States)

    Docampo, Roberto; Jimenez, Veronica; Lander, Noelia; Li, Zhu-Hong; Niyogi, Sayantanee

    2013-01-01

    While free-living protists are usually subjected to hyposmotic environments, parasitic protists are also in contact with hyperosmotic habitats. Recent work in one of these parasites, Trypanosoma cruzi, has revealed that its contractile vacuole complex, which usually collects and expels excess water as a mechanism of regulatory volume decrease after hyposmotic stress, has also a role in cell shrinking when the cells are submitted to hyperosmotic stress. Trypanosomes also have an acidic calcium store rich in polyphosphate (polyP), named the acidocalcisome, which is involved in their response to osmotic stress. Here, we review newly emerging insights on the role of acidocalcisomes and the contractile vacuole complex in the cellular response to hyposmotic and hyperosmotic stresses. We also review the current state of knowledge on the composition of these organelles and their other roles in calcium homeostasis and protein trafficking. © 2013, Elsevier Inc. All Rights Reserved.

  4. New Insights into the Roles of Acidocalcisomes and the Contractile Vacuole Complex in Osmoregulation in Protists

    Science.gov (United States)

    Docampo, Roberto; Jimenez, Veronica; Lander, Noelia; Li, Zhu-Hong; Niyogi, Sayantanee

    2013-01-01

    While free-living protists are usually subjected to hyposmotic environments, parasitic protists are also in contact with hyperosmotic habitats. Recent work in one of these parasites, Trypanosoma cruzi, has revealed that its contractile vacuole complex, which usually collects and expels excess water as a mechanism of regulatory volume decrease after hyposmotic stress, has also a role in cell shrinking when the cells are submitted to hyperosmotic stress. Trypanosomes also have an acidic calcium store rich in polyphosphate (polyP), named the acidocalcisome, which is involved in their response to osmotic stress. Here, we review newly emerging insights on the role of acidocalcisomes and the contractile vacuole complex in the cellular response to hyposmotic and hyperosmotic stresses. We also review the current state of knowledge on the composition of these organelles and their other roles in calcium homeostasis and protein trafficking. PMID:23890380

  5. Robust gap repair in the contractile ring ensures timely completion of cytokinesis.

    OpenAIRE

    Silva, AM; Osório, DS; Pereira, AJ; Maiato, H; Pinto, IM; Rubinstein, B; Gassmann, R; Telley, IA; Carvalho, AX

    2016-01-01

    Cytokinesis in animal cells requires the constriction of an actomyosin contractile ring, whose architecture and mechanism remain poorly understood. We use laser microsurgery to explore the biophysical properties of constricting rings in Caenorhabditis elegans embryos. Laser cutting causes rings to snap open. However, instead of disintegrating, ring topology recovers and constriction proceeds. In response to severing, a finite gap forms and is repaired by recruitment of new material in an acti...

  6. A note on the relationships between multiple imputation, maximum likelihood and fully Bayesian methods for missing responses in linear regression models.

    Science.gov (United States)

    Chen, Qingxia; Ibrahim, Joseph G

    2014-07-01

    Multiple Imputation, Maximum Likelihood and Fully Bayesian methods are the three most commonly used model-based approaches in missing data problems. Although it is easy to show that when the responses are missing at random (MAR), the complete case analysis is unbiased and efficient, the aforementioned methods are still commonly used in practice for this setting. To examine the performance of and relationships between these three methods in this setting, we derive and investigate small sample and asymptotic expressions of the estimates and standard errors, and fully examine how these estimates are related for the three approaches in the linear regression model when the responses are MAR. We show that when the responses are MAR in the linear model, the estimates of the regression coefficients using these three methods are asymptotically equivalent to the complete case estimates under general conditions. One simulation and a real data set from a liver cancer clinical trial are given to compare the properties of these methods when the responses are MAR.

  7. ATP-induced changes in rat skeletal muscle contractility.

    Science.gov (United States)

    Gabdrakhmanov, A I; Khayrullin, A E; Grishin, C H; Ziganshin, A U

    2015-01-01

    considered as typical effects of ATP and other purines on skeletal muscles and could not be extrapolated to all warm-blooded animals. Furthermore the role of ATP and its derivatives in the accumulation of vertebrate muscular effort has not been investigated.It is known that in physiological conditions vertebrates may mobilize only up to a third of the maximum muscle force. Why the two-thirds of muscular strength are not used normally but may be used at stress, remains unknown.It is known that the body's adaptive response to stress is a change in the activity of the endocrine system. The leading role in this is given to catechol amines and glucocorticoids, mobilized in significant quantities in blood under stress.We have found previously that incubation of frog sartorius muscle with hydrocortisone resulted in a decrease of contraction amplitude. However, when hydrocortisone was used in combination with ATP, its inhibitory effect on contractile responses disappeared. It is interesting that hydrocortisone had no effect on the inhibitory effect of adenosine. In the following experiments, assessing the effect of hydrocortisone on rat soleus muscle, it was established that hydrocortisone and purines had similar inhibitory effect. When ATP and hydrocortisone were given together the same oppression occurred. To study the effects of ATP and adenosine on contraction parameters of rat skeletal muscle and assess the impact of the catechol amines on these processes. Contractions of rat soleus muscles were recorded isometrically by mechanical sensor Linton FSG-01 (UK) according to standard procedures. The average of muscle parameters received within 30 seconds (30 responses) was treated as one result. Amplitude and time characteristics of the curve reductions were estimated. During all experiments standard Krebs solution flowed through the bath continuously to which agents were added at necessary concentrations. All experimental animals were maintained and prepared for dissection under

  8. Cellular Architecture Regulates Collective Calcium Signaling and Cell Contractility.

    Directory of Open Access Journals (Sweden)

    Jian Sun

    2016-05-01

    Full Text Available A key feature of multicellular systems is the ability of cells to function collectively in response to external stimuli. However, the mechanisms of intercellular cell signaling and their functional implications in diverse vascular structures are poorly understood. Using a combination of computational modeling and plasma lithography micropatterning, we investigate the roles of structural arrangement of endothelial cells in collective calcium signaling and cell contractility. Under histamine stimulation, endothelial cells in self-assembled and microengineered networks, but not individual cells and monolayers, exhibit calcium oscillations. Micropatterning, pharmacological inhibition, and computational modeling reveal that the calcium oscillation depends on the number of neighboring cells coupled via gap junctional intercellular communication, providing a mechanistic basis of the architecture-dependent calcium signaling. Furthermore, the calcium oscillation attenuates the histamine-induced cytoskeletal reorganization and cell contraction, resulting in differential cell responses in an architecture-dependent manner. Taken together, our results suggest that endothelial cells can sense and respond to chemical stimuli according to the vascular architecture via collective calcium signaling.

  9. Regional gastrointestinal contractility parameters using the wireless motility capsule

    DEFF Research Database (Denmark)

    Farmer, A D; Wegeberg, A-M L; Brock, B

    2018-01-01

    BACKGROUND: The wireless motility capsule concurrently measures temperature, pH and pressure as it traverses the gastrointestinal tract. AIMS: To describe normative values for motility/contractility parameters across age, gender and testing centres. METHODS: Healthy participants underwent...

  10. Considerations for Contractile Electroactive Materials and Actuators

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, Lenore; Erickson, Carl J.; Meixler, Lewis D.; Ascione, George; Gentile, Charles A.; Tilson, Carl; Bernasek, Stephen L.; Abelev, Esta

    2010-02-19

    Ras Labs produces electroactive polymer (EAP) based materials and actuators that bend, swell, ripple and now contract (new development) with low electric input. This is an important attribute because of the ability of contraction to produce life-like motion. The mechanism of contraction is not well understood. Radionuclide-labeled experiments were conducted to follow the movement of electrolytes and water in these EAPs when activated. Extreme temperature experiments were performed on the contractile EAPs with very favorable results. One of the biggest challenges in developing these actuators, however, is the electrode-EAP interface because of the pronounced movement of the EAP. Plasma treatments of metallic electrodes were investigated in order to improve the attachment of the embedded electrodes to the EAP material. Surface analysis, adhesive testing, and mechanical testing were conducted to test metal surfaces and metal-polymer interfaces. The nitrogen plasma treatment of titanium produced a strong metal-polymer interface; however, oxygen plasma treatment of both stainless steel and titanium produced even stronger metal-polymer interfaces. Plasma treatment of the electrodes allows for the embedded electrodes and the EAP material of the actuator to work and move as a unit, with no detachment, by significantly improving the metal-polymer interface.

  11. Effect of a crude sulfated polysaccharide from Halymenia floresia (Rhodophyta on gastrointestinal smooth muscle contractility

    Directory of Open Access Journals (Sweden)

    José Ronaldo Vasconcelos Graça

    2011-10-01

    Full Text Available The aim of this work was to study the effect of Halymenia floresia (Hf on duodenum contractility, and on experimental protocols of gastric compliance (GC in rats. Fraction Hf2s exhibited a concentration-dependent myocontractile effect (EC50 12.48 µg/ml, and an inhibitory effect after consecutive washing. The contractile response promoted by Hf2s in the duodenum strips was completely inhibited by verapamil, and the effects were prevented in the presence of Ca2+-free medium. The pretreatment with atropine prevented the Hf2s myocontractile effect. Hf2s was also capable to decrease the GC (from 3.8±0.06 to 3.4±0.13 ml, P<0.05, which did not return to basal levels after more 50 min of observation. These results indicated that the algal polysaccharide possessed in vitro and in vivo gastrointestinal effects.

  12. Operative contractility: a functional concept of the inotropic state.

    Science.gov (United States)

    Curiel, Roberto; Perez-Gonzalez, Juan; Torres, Edwar; Landaeta, Ruben; Cerrolaza, Miguel

    2005-10-01

    1. Initial unsuccessful attempts to evaluate ventricular function in terms of the 'heart as a pump' led to focusing on the 'heart as a muscle' and to the concept of myocardial contractility. However, no clinically ideal index exists to assess the contractile state. The aim of the present study was to develop a mathematical model to assess cardiac contractility. 2. A tri-axial system was conceived for preload (PL), afterload (AL) and contractility, where stroke volume (SV) was represented as the volume of the tetrahedron. Based on this model, 'operative' contractility ('OperCon') was calculated from the readily measured values of PL, AL and SV. The model was tested retrospectively under a variety of different experimental and clinical conditions, in 71 studies in humans and 29 studies in dogs. A prospective echocardiographic study was performed in 143 consecutive subjects to evaluate the ability of the model to assess contractility when SV and PL were measured volumetrically (mL) or dimensionally (cm). 3. With inotropic interventions, OperCon changes were comparable to those of ejection fraction (EF), velocity of shortening (Vcf) and dP/dt-max. Only with positive inotropic interventions did elastance (Ees) show significantly larger changes. With load manipulations, OperCon showed significantly smaller changes than EF and Ees and comparable changes to Vcf and dP/dt-max. Values of OperCon were similar when AL was represented by systolic blood pressure or wall stress and when volumetric or dimensional values were used. 4. Operative contractility is a reliable, simple and versatile method to assess cardiac contractility.

  13. The Effect of Cleft Palate Repair on Contractile Properties of Single Permeabilized Muscle Fibers From Congenitally Cleft Goats Palates

    Science.gov (United States)

    A cleft palate goat model was used to study the contractile properties of the levator veli palatini (LVP) muscle which is responsible for the movement of the soft palate. In 15-25% of patients that undergo palatoplasty, residual velopharyngeal insufficiency (VPI) remains a problem and often require...

  14. The effect of exercise hypertrophy and disuse atrophy on muscle contractile properties: a mechanomyographic analysis.

    Science.gov (United States)

    Than, Christian; Tosovic, Danijel; Seidl, Laura; Mark Brown, J

    2016-12-01

    To determine whether mechanomyographic (MMG) determined contractile properties of the biceps brachii change during exercise-induced hypertrophy and subsequent disuse atrophy. Healthy subjects (mean ± SD, 23.7 ± 2.6 years, BMI 21.8 ± 2.4, n = 19) performed unilateral biceps curls (9 sets × 12 repetitions, 5 sessions per week) for 8 weeks (hypertrophic phase) before ceasing exercise (atrophic phase) for the following 8 weeks (non-dominant limb; treatment, dominant limb; control). MMG measures of muscle contractile properties (contraction time; T c , maximum displacement; D max , contraction velocity; V c ), electromyographic (EMG) measures of muscle fatigue (median power frequency; MPF), strength measures (maximum voluntary contraction; MVC) and measures of muscle thickness (ultrasound) were obtained. Two-way repeated measures ANOVA showed significant differences (P muscle thickness was greater than control, reflecting gross hypertrophy. MMG variables Dmax (weeks 2, 7) and Vc (weeks 7, 8) declined. During the atrophic phase, MVC (weeks 9-12) and muscle thickness (weeks 9, 10) initially remained high before declining to control levels, reflecting gross atrophy. MMG variables D max (weeks 9, 14) and V c (weeks 9, 14, 15) also declined during the atrophic phase. No change in T c was found throughout the hypertrophic or atrophic phases. MMG detects changes in contractile properties during stages of exercise-induced hypertrophy and disuse atrophy suggesting its applicability as a clinical tool in musculoskeletal rehabilitation.

  15. Modeling the dispersion effects of contractile fibers in smooth muscles

    Science.gov (United States)

    Murtada, Sae-Il; Kroon, Martin; Holzapfel, Gerhard A.

    2010-12-01

    Micro-structurally based models for smooth muscle contraction are crucial for a better understanding of pathological conditions such as atherosclerosis, incontinence and asthma. It is meaningful that models consider the underlying mechanical structure and the biochemical activation. Hence, a simple mechanochemical model is proposed that includes the dispersion of the orientation of smooth muscle myofilaments and that is capable to capture available experimental data on smooth muscle contraction. This allows a refined study of the effects of myofilament dispersion on the smooth muscle contraction. A classical biochemical model is used to describe the cross-bridge interactions with the thin filament in smooth muscles in which calcium-dependent myosin phosphorylation is the only regulatory mechanism. A novel mechanical model considers the dispersion of the contractile fiber orientations in smooth muscle cells by means of a strain-energy function in terms of one dispersion parameter. All model parameters have a biophysical meaning and may be estimated through comparisons with experimental data. The contraction of the middle layer of a carotid artery is studied numerically. Using a tube the relationships between the internal pressure and the stretches are investigated as functions of the dispersion parameter, which implies a strong influence of the orientation of smooth muscle myofilaments on the contraction response. It is straightforward to implement this model in a finite element code to better analyze more complex boundary-value problems.

  16. Impact of tamsulosin and nifedipine on contractility of pregnant rat ureters in vitro.

    Science.gov (United States)

    Haddad, Lisette; Corriveau, Stéphanie; Rousseau, Eric; Blouin, Simon; Pasquier, Jean-Charles; Ponsot, Yves; Roy-Lacroix, Marie-Ève

    2018-01-01

    To evaluate the in vitro effect of tamsulosin and nifedipine on the contractility of pregnant rat ureters and to perform quantitative analysis of the pharmacological effects. Medical expulsive therapy (MET) is commonly used to treat urolithiasis. However, this treatment is seldom used in pregnant women since no studies support this practice. This was an in vitro study on animal tissue derived from pregnant Sprague-Dawley rats. A total of 124 ureteral segments were mounted in an organ bath system and contractile response to methacholine (MCh) was assessed. Tamsulosin or nifedipine were added at cumulative concentrations (0.001-1 μM). The area under the curve (AUC) from isometric tension measurements was calculated. The effect of pharmacological agents and the respective controls were assessed by calculating the AUC for each 5-min interval. Statistical analyses were performed using the Mann-Whitney-Wilcoxon nonparametric test. Both drugs displayed statistically significant inhibitory activity at concentrations of 0.1 and 1 μM for tamsulosin and 1 μM for nifedipine when calculated as the AUC as compared to DMSO controls. Tamsulosin and nifedipine directly inhibit MCh-induced contractility of pregnant rat ureters. Further work is needed to determine the clinical efficacy of these medications for MET in pregnancy.

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

    Science.gov (United States)

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

    2014-10-16

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

  18. Cellular contractility and substrate elasticity: a numerical investigation of the actin cytoskeleton and cell adhesion.

    Science.gov (United States)

    Ronan, William; Deshpande, Vikram S; McMeeking, Robert M; McGarry, J Patrick

    2014-04-01

    Numerous experimental studies have established that cells can sense the stiffness of underlying substrates and have quantified the effect of substrate stiffness on stress fibre formation, focal adhesion area, cell traction, and cell shape. In order to capture such behaviour, the current study couples a mixed mode thermodynamic and mechanical framework that predicts focal adhesion formation and growth with a material model that predicts stress fibre formation, contractility, and dissociation in a fully 3D implementation. Simulations reveal that SF contractility plays a critical role in the substrate-dependent response of cells. Compliant substrates do not provide sufficient tension for stress fibre persistence, causing dissociation of stress fibres and lower focal adhesion formation. In contrast, cells on stiffer substrates are predicted to contain large amounts of dominant stress fibres. Different levels of cellular contractility representative of different cell phenotypes are found to alter the range of substrate stiffness that cause the most significant changes in stress fibre and focal adhesion formation. Furthermore, stress fibre and focal adhesion formation evolve as a cell spreads on a substrate and leading to the formation of bands of fibres leading from the cell periphery over the nucleus. Inhibiting the formation of FAs during cell spreading is found to limit stress fibre formation. The predictions of this mutually dependent material-interface framework are strongly supported by experimental observations of cells adhered to elastic substrates and offer insight into the inter-dependent biomechanical processes regulating stress fibre and focal adhesion formation.

  19. Robust gap repair in the contractile ring ensures timely completion of cytokinesis.

    Science.gov (United States)

    Silva, Ana M; Osório, Daniel S; Pereira, Antonio J; Maiato, Helder; Pinto, Inês Mendes; Rubinstein, Boris; Gassmann, Reto; Telley, Ivo Andreas; Carvalho, Ana Xavier

    2016-12-19

    Cytokinesis in animal cells requires the constriction of an actomyosin contractile ring, whose architecture and mechanism remain poorly understood. We use laser microsurgery to explore the biophysical properties of constricting rings in Caenorhabditis elegans embryos. Laser cutting causes rings to snap open. However, instead of disintegrating, ring topology recovers and constriction proceeds. In response to severing, a finite gap forms and is repaired by recruitment of new material in an actin polymerization-dependent manner. An open ring is able to constrict, and rings repair from successive cuts. After gap repair, an increase in constriction velocity allows cytokinesis to complete at the same time as controls. Our analysis demonstrates that tension in the ring increases while net cortical tension at the site of ingression decreases throughout constriction and suggests that cytokinesis is accomplished by contractile modules that assemble and contract autonomously, enabling local repair of the actomyosin network. Consequently, cytokinesis is a highly robust process impervious to discontinuities in contractile ring structure. © 2016 Silva et al.

  20. Microtubule depolymerization normalizes in vivo myocardial contractile function in dogs with pressure-overload left ventricular hypertrophy

    Science.gov (United States)

    Koide, M.; Hamawaki, M.; Narishige, T.; Sato, H.; Nemoto, S.; DeFreyte, G.; Zile, M. R.; Cooper G, I. V.; Carabello, B. A.

    2000-01-01

    BACKGROUND: Because initially compensatory myocardial hypertrophy in response to pressure overloading may eventually decompensate to myocardial failure, mechanisms responsible for this transition have long been sought. One such mechanism established in vitro is densification of the cellular microtubule network, which imposes a viscous load that inhibits cardiocyte contraction. METHODS AND RESULTS: In the present study, we extended this in vitro finding to the in vivo level and tested the hypothesis that this cytoskeletal abnormality is important in the in vivo contractile dysfunction that occurs in experimental aortic stenosis in the adult dog. In 8 dogs in which gradual stenosis of the ascending aorta had caused severe left ventricular (LV) pressure overloading (gradient, 152+/-16 mm Hg) with contractile dysfunction, LV function was measured at baseline and 1 hour after the intravenous administration of colchicine. Cardiocytes obtained by biopsy before and after in vivo colchicine administration were examined in tandem. Microtubule depolymerization restored LV contractile function both in vivo and in vitro. CONCLUSIONS: These and additional corroborative data show that increased cardiocyte microtubule network density is an important mechanism for the ventricular contractile dysfunction that develops in large mammals with adult-onset pressure-overload-induced cardiac hypertrophy.

  1. An Idle-State Detection Algorithm for SSVEP-Based Brain-Computer Interfaces Using a Maximum Evoked Response Spatial Filter.

    Science.gov (United States)

    Zhang, Dan; Huang, Bisheng; Wu, Wei; Li, Siliang

    2015-11-01

    Although accurate recognition of the idle state is essential for the application of brain-computer interfaces (BCIs) in real-world situations, it remains a challenging task due to the variability of the idle state. In this study, a novel algorithm was proposed for the idle state detection in a steady-state visual evoked potential (SSVEP)-based BCI. The proposed algorithm aims to solve the idle state detection problem by constructing a better model of the control states. For feature extraction, a maximum evoked response (MER) spatial filter was developed to extract neurophysiologically plausible SSVEP responses, by finding the combination of multi-channel electroencephalogram (EEG) signals that maximized the evoked responses while suppressing the unrelated background EEGs. The extracted SSVEP responses at the frequencies of both the attended and the unattended stimuli were then used to form feature vectors and a series of binary classifiers for recognition of each control state and the idle state were constructed. EEG data from nine subjects in a three-target SSVEP BCI experiment with a variety of idle state conditions were used to evaluate the proposed algorithm. Compared to the most popular canonical correlation analysis-based algorithm and the conventional power spectrum-based algorithm, the proposed algorithm outperformed them by achieving an offline control state classification accuracy of 88.0 ± 11.1% and idle state false positive rates (FPRs) ranging from 7.4 ± 5.6% to 14.2 ± 10.1%, depending on the specific idle state conditions. Moreover, the online simulation reported BCI performance close to practical use: 22.0 ± 2.9 out of the 24 control commands were correctly recognized and the FPRs achieved as low as approximately 0.5 event/min in the idle state conditions with eye open and 0.05 event/min in the idle state condition with eye closed. These results demonstrate the potential of the proposed algorithm for implementing practical SSVEP BCI systems.

  2. Controls on seasonal patterns of maximum ecosystem carbon uptake and canopy-scale photosynthetic light response: contributions from both temperature and photoperiod.

    Science.gov (United States)

    Stoy, Paul C; Trowbridge, Amy M; Bauerle, William L

    2014-02-01

    Most models of photosynthetic activity assume that temperature is the dominant control over physiological processes. Recent studies have found, however, that photoperiod is a better descriptor than temperature of the seasonal variability of photosynthetic physiology at the leaf scale. Incorporating photoperiodic control into global models consequently improves their representation of the seasonality and magnitude of atmospheric CO2 concentration. The role of photoperiod versus that of temperature in controlling the seasonal variability of photosynthetic function at the canopy scale remains unexplored. We quantified the seasonal variability of ecosystem-level light response curves using nearly 400 site years of eddy covariance data from over eighty Free Fair-Use sites in the FLUXNET database. Model parameters describing maximum canopy CO2 uptake and the initial slope of the light response curve peaked after peak temperature in about 2/3 of site years examined, emphasizing the important role of temperature in controlling seasonal photosynthetic function. Akaike's Information Criterion analyses indicated that photoperiod should be included in models of seasonal parameter variability in over 90% of the site years investigated here, demonstrating that photoperiod also plays an important role in controlling seasonal photosynthetic function. We also performed a Granger causality analysis on both gross ecosystem productivity (GEP) and GEP normalized by photosynthetic photon flux density (GEP n ). While photoperiod Granger-caused GEP and GEP n in 99 and 92% of all site years, respectively, air temperature Granger-caused GEP in a mere 32% of site years but Granger-caused GEP n in 81% of all site years. Results demonstrate that incorporating photoperiod may be a logical step toward improving models of ecosystem carbon uptake, but not at the expense of including enzyme kinetic-based temperature constraints on canopy-scale photosynthesis.

  3. Contractile profile of esophageal and gastric fundus strips in experimental doxorubicin-induced esophageal atresia

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    F.A. Capeto

    2015-05-01

    Full Text Available Esophageal atresia (EA is characterized by esophageal and gastric motility changes secondary to developmental and postsurgical damage. This study evaluated the in vitro contractile profile of the distal esophagus and gastric fundus in an experimental model of EA induced by doxorubicin (DOXO. Wistar pregnant rats received DOXO 2.2 mg/kg on the 8th and 9th gestational days. On day 21.5, fetuses were collected, sacrificed, and divided into groups: control, DOXO without EA (DOXO-EA, and DOXO with EA (DOXO+EA. Strips from the distal esophagus and gastric fundus were mounted on a wire myograph and isolated organ-bath system, respectively, and subjected to increasing concentrations of carbamylcholine chloride (carbachol, CCh. The isolated esophagus was also stimulated with increasing concentrations of KCl. In esophagus, the concentration-effect curves were reduced in response to CCh in the DOXO+EA and DOXO-EA groups compared to the control group (P0.05. In response to KCl, the distal esophagus samples in the three groups were not statistically different with regard to Emax or EC50 values (P>0.05. No significant difference was noted for EC50 or Emax values in fundic strips stimulated with CCh (P>0.05. In conclusion, exposure of dams to DOXO during gestation inhibited the contractile behavior of esophageal strips from offspring in response to CCh but not KCl, regardless of EA induction. The gastric fundus of DOXO-exposed offspring did not have altered contractile responsiveness to cholinergic stimulation.

  4. Changes in muscle fiber contractility and extracellular matrix production during skeletal muscle hypertrophy.

    Science.gov (United States)

    Mendias, Christopher L; Schwartz, Andrew J; Grekin, Jeremy A; Gumucio, Jonathan P; Sugg, Kristoffer B

    2017-03-01

    Skeletal muscle can adapt to increased mechanical loads by undergoing hypertrophy. Transient reductions in whole muscle force production have been reported during the onset of hypertrophy, but contractile changes in individual muscle fibers have not been previously studied. Additionally, the extracellular matrix (ECM) stores and transmits forces from muscle fibers to tendons and bones, and determining how the ECM changes during hypertrophy is important in understanding the adaptation of muscle tissue to mechanical loading. Using the synergist ablation model, we sought to measure changes in muscle fiber contractility, collagen content, and cross-linking, and in the expression of several genes and activation of signaling proteins that regulate critical components of myogenesis and ECM synthesis and remodeling during muscle hypertrophy. Tissues were harvested 3, 7, and 28 days after induction of hypertrophy, and nonoverloaded rats served as controls. Muscle fiber specific force (sF o ), which is the maximum isometric force normalized to cross-sectional area, was reduced 3 and 7 days after the onset of mechanical overload, but returned to control levels by 28 days. Collagen abundance displayed a similar pattern of change. Nearly a quarter of the transcriptome changed over the course of overload, as well as the activation of signaling pathways related to hypertrophy and atrophy. Overall, this study provides insight into fundamental mechanisms of muscle and ECM growth, and indicates that although muscle fibers appear to have completed remodeling and regeneration 1 mo after synergist ablation, the ECM continues to be actively remodeling at this time point. NEW & NOTEWORTHY This study utilized a rat synergist ablation model to integrate changes in single muscle fiber contractility, extracellular matrix composition, activation of important signaling pathways in muscle adaption, and corresponding changes in the muscle transcriptome to provide novel insight into the basic

  5. Comparison of contractile and extensile pneumatic artificial muscles

    Science.gov (United States)

    Pillsbury, Thomas E.; Wereley, Norman M.; Guan, Qinghua

    2017-09-01

    Pneumatic artificial muscles (PAMs) are used in robotic and prosthetic applications due to their high power to weight ratio, controllable compliance, and simple design. Contractile PAMs are typically used in traditional hard robotics in place of heavy electric motors. As the field of soft robotics grows, extensile PAMs are beginning to have increased usage. This work experimentally tests, models, and compares contractile and extensile PAMs to demonstrate the advantages and disadvantages of each type of PAM and applications for which they are best suited.

  6. Effect of cadmium on myocardial contractility and calcium fluxes

    International Nuclear Information System (INIS)

    Pilati, C.F.

    1979-01-01

    The effect of cadmium on myocardial mechanical performance and calcium fluxes was studied in kitten isometric papillary muscles and in isovolumic Langendorff-perfused rabbit hearts. Therefore, it is concluded that cadmium-induced decreases in contractility are not primarily the result of cadmium interference with ATP metabolic processes. Furthermore, these results imply that cadmium causes no structural alterations of the contractile proteins. These data suggest that cadmium may be competing with the calcium needed for excitation-contraction coupling. During experiments using radioisotopic calcium, a statistically significant cellular influx of calcium was observed following the onset of 100 μM Cd ++ perfusion of isolated, Langendorff-prepared rabbit hearts

  7. Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury

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    Han-Bin Lin

    2014-01-01

    Full Text Available Matrix metalloproteinases (MMPs significantly contribute to ischemia reperfusion (I/R injury, namely, by the degradation of contractile proteins. However, due to the experimental models adopted and lack of isoform specificity of MMP inhibitors, the cellular source and identity of the MMP(s involved in I/R injury remain to be elucidated. Using isolated adult rat cardiomyocytes, subjected to chemically induced I/R-like injury, we show that specific inhibition of MMP-2 expression and activity using MMP-2 siRNA significantly protected cardiomyocyte contractility from I/R-like injury. This was also associated with increased expression of myosin light chains 1 and 2 (MLC1/2 in comparison to scramble siRNA transfection. Moreover, the positive effect of MMP-2 siRNA transfection on cardiomyocyte contractility and MLC1/2 expression levels was also observed under control conditions, suggesting an important additional role for MMP-2 in physiological sarcomeric protein turnover. This study clearly demonstrates that intracellular expression of MMP-2 plays a significant role in sarcomeric protein turnover, such as MLC1 and MLC2, under aerobic (physiological conditions. In addition, this study identifies intracellular/autocrine, cardiomyocyte-produced MMP-2, rather than paracrine/extracellular, as responsible for the degradation of MLC1/2 and consequent contractile dysfunction in cardiomyocytes subjected to I/R injury.

  8. Prognostic impact of initial maximum standardized uptake value of 18F-FDG PET/CT on treatment response in patients with metastatic lung adenocarcinoma treated with erlotinib

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    Kus T

    2015-12-01

    5.26, respectively. Thirty-one of 60 patients had SUVmax values ≤11. The PFS rates for 3, 6, and 12 months were 70.5%/28% (P=0.001, OR=9.0; 95% CI: 2.79–29.04, 61.7%/8% (P<0.001, OR=28.35; 95% CI: 5.5–143, and 52.9%/8% (P<0.001, OR=18.69; 95% CI: 3.76–92.9 for low SUVmax (≤11 group/high SUVmax (>11 group, respectively.Conclusion: Initial SUVmax value on 18F-FDG PET/CT is found to be a prognostic factor anticipating the response to erlotinib for 3, 6, and 12-month rates of PFS in both EGFR-sensitizing mutation and wild-type tumor group. Keywords: lung adenocarcinoma, erlotinib, 18F-fluorodeoxyglucose positron emission tomography/computed tomography, maximum standardized uptake value, treatment response, prognosis

  9. Large-scale glacitectonic deformation in response to active ice sheet retreat across Dogger Bank (southern central North Sea) during the Last Glacial Maximum

    Science.gov (United States)

    Phillips, Emrys; Cotterill, Carol; Johnson, Kirstin; Crombie, Kirstin; James, Leo; Carr, Simon; Ruiter, Astrid

    2018-01-01

    High resolution seismic data from the Dogger Bank in the central southern North Sea has revealed that the Dogger Bank Formation records a complex history of sedimentation and penecontemporaneous, large-scale, ice-marginal to proglacial glacitectonic deformation. These processes led to the development of a large thrust-block moraine complex which is buried beneath a thin sequence of Holocene sediments. This buried glacitectonic landsystem comprises a series of elongate, arcuate moraine ridges (200 m up to > 15 km across; over 40-50 km long) separated by low-lying ice marginal to proglacial sedimentary basins and/or meltwater channels, preserving the shape of the margin of this former ice sheet. The moraines are composed of highly deformed (folded and thrust) Dogger Bank Formation with the lower boundary of the deformed sequence (up to 40-50 m thick) being marked by a laterally extensive décollement. The ice-distal parts of the thrust moraine complex are interpreted as a "forward" propagating imbricate thrust stack developed in response to S/SE-directed ice-push. The more complex folding and thrusting within the more ice-proximal parts of the thrust-block moraines record the accretion of thrust slices of highly deformed sediment as the ice repeatedly reoccupied this ice marginal position. Consequently, the internal structure of the Dogger Bank thrust-moraine complexes can be directly related to ice sheet dynamics, recording the former positions of a highly dynamic, oscillating Weichselian ice sheet margin as it retreated northwards at the end of the Last Glacial Maximum.

  10. The last glacial maximum

    Science.gov (United States)

    Clark, P.U.; Dyke, A.S.; Shakun, J.D.; Carlson, A.E.; Clark, J.; Wohlfarth, B.; Mitrovica, J.X.; Hostetler, S.W.; McCabe, A.M.

    2009-01-01

    We used 5704 14C, 10Be, and 3He ages that span the interval from 10,000 to 50,000 years ago (10 to 50 ka) to constrain the timing of the Last Glacial Maximum (LGM) in terms of global ice-sheet and mountain-glacier extent. Growth of the ice sheets to their maximum positions occurred between 33.0 and 26.5 ka in response to climate forcing from decreases in northern summer insolation, tropical Pacific sea surface temperatures, and atmospheric CO2. Nearly all ice sheets were at their LGM positions from 26.5 ka to 19 to 20 ka, corresponding to minima in these forcings. The onset of Northern Hemisphere deglaciation 19 to 20 ka was induced by an increase in northern summer insolation, providing the source for an abrupt rise in sea level. The onset of deglaciation of the West Antarctic Ice Sheet occurred between 14 and 15 ka, consistent with evidence that this was the primary source for an abrupt rise in sea level ???14.5 ka.

  11. Basal and β-Adrenergic Cardiomyocytes Contractility Dysfunction Induced by Dietary Protein Restriction is Associated with Downregulation of SERCA2a Expression and Disturbance of Endoplasmic Reticulum Ca2+ Regulation in Rats

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    Arlete R. Penitente

    2014-07-01

    Full Text Available Background: The mechanisms responsible for the cardiac dysfunction associated with dietary protein restriction (PR are poorly understood. Thus, this study was designed to evaluate the effects of PR on calcium kinetics, basal and β-adrenergic contractility in murine ventricular cardiomyocytes. Methods: After breastfeeding male Fisher rats were distributed into a control group (CG, n = 20 and a protein-restricted group (PRG, n = 20, receiving isocaloric diets for 35 days containing 15% and 6% protein, respectively. Biometric and hemodynamic variables were measured. After euthanasia left ventricles (LV were collected for histopathological evaluation, SERCA2a expression, cardiomyocytes contractility and Ca2+sparks analysis. Results: PRG animals showed reduced general growth, increased heart rate and arterial pressure. These animals presented extracellular matrix expansion and disorganization, cardiomyocytes hypotrophy, reduced amplitudes of shortening and maximum velocity of contraction and relaxation at baseline and after β-adrenergic stimulation. Reduced SERCA2a expression as well as higher frequency and lower amplitude of Ca2+sparks were observed in PRG cardiomyocytes. Conclusion: The observations reveal that protein restriction induces marked myocardial morphofunctional damage. The pathological changes of cardiomyocyte mechanics suggest the potential involvement of the β-adrenergic system, which is possibly associated with changes in SERCA2a expression and disturbances in Ca2+ intracellular kinetics.

  12. Izalpinin from fruits of Alpinia oxyphylla with antagonistic activity against the rat bladder contractility.

    Science.gov (United States)

    Yuan, Yuan; Tan, Yin-Feng; Xu, Peng; Li, Hailong; Li, Yong-Hui; Chen, Wen-Ya; Zhang, Jun-Qing; Chen, Feng; Huang, Guo-Jun

    2014-01-01

    Alpinia oxyphylla (Zingiberaceae), an herbaceous perennial plant, its capsular fruit is commonly used in traditional Chinese medicine for the treatment of different urinary incontinence symptoms including frequency, urgency and nocturia. These symptoms are similar to the overactive bladder syndrome. In our lab, we found that the 95% ethanol extract of the capsular fruits exhibited significant anti-muscarinic activity. Some constituents in capsular fruits including flavonoids (e.g., izalpinin and tectochrysin), diarylheptanoids (e.g., yakuchinone A and yakuchinone B) and sesquiterpenes (e.g., nootkatone), are regarded as representative chemicals with putative pharmacological activities. This study aimed to evaluate the in vitro antagonistic actions of izalpinin on carbachol-induced contraction of the rat detrusor muscle. In vitro inhibition of rat detrusor contractile response to carbachol was used to study the functional activity of izalpinin. The isolated detrusor strips of rats were mounted in organ baths containing oxygenated Krebs' solution. The cumulative consecutive concentration-response curves to carbachol-evoked contractions in strips of rat bladder were obtained. Carbachol induced concentration-dependent contractions of isolated rat bladder detrusor strips. The vehicle DMSO had no impact on the contraction response. The contraction effects were concentration-dependently antagonized by izalpinin, with a mean EC50 value of 0.35 µM. The corresponding cumulative agonist concentration-response curves shifted right-ward. Izalpinin exhibits inhibitory role of muscarinic receptor-related detrusor contractile activity, and it may be a promising lead compound to treat overactive bladder.

  13. Myocardial contractility in the echo lab: molecular, cellular and pathophysiological basis

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    Bombardini Tonino

    2005-09-01

    Full Text Available Abstract In the standard accepted concept, contractility is the intrinsic ability of heart muscle to generate force and to shorten, independently of changes in the preload or afterload with fixed heart rates. At molecular level the crux of the contractile process lies in the changing concentrations of Ca2+ ions in the myocardial cytosol. Ca2+ ions enter through the calcium channel that opens in response to the wave of depolarization that travels along the sarcolemma. These Ca2+ ions "trigger" the release of more calcium from the sarcoplasmic reticulum (SR and thereby initiate a contraction-relaxation cycle. In the past, several attempts were made to transfer the pure physiological concept of contractility, expressed in the isolated myocardial fiber by the maximal velocity of contraction of unloaded muscle fiber (Vmax, to the in vivo beating heart. Suga and Sagawa achieved this aim by measuring pressure/volume loops in the intact heart: during a positive inotropic intervention, the pressure volume loop reflects a smaller end-systolic volume and a higher end-systolic pressure, so that the slope of the pressure volume relationship moves upward and to the left. The pressure volume relationship is the most reliable index for assessing myocardial contractility in the intact circulation and is almost insensitive to changes in preload and after load. This is widely used in animal studies and occasionally clinically. The limit of the pressure volume relationship is that it fails to take into account the frequency-dependent regulation of contractility: the frequency-dependent control of transmembrane Ca2+ entry via voltage-gated Ca2+ channels provides cardiac cells with a highly sophisticated short-term system for the regulation of intracellular Ca2+ homeostasis. An increased stimulation rate increases the force of contraction: the explanation is repetitive Ca2+ entry with each depolarization and, hence, an accumulation of cytosolic calcium. As the heart

  14. Dependence of intramyocardial pressure and coronary flow on ventricular loading and contractility: a model study.

    Science.gov (United States)

    Bovendeerd, Peter H M; Borsje, Petra; Arts, Theo; van De Vosse, Frans N

    2006-12-01

    The phasic coronary arterial inflow during the normal cardiac cycle has been explained with simple (waterfall, intramyocardial pump) models, emphasizing the role of ventricular pressure. To explain changes in isovolumic and low afterload beats, these models were extended with the effect of three-dimensional wall stress, nonlinear characteristics of the coronary bed, and extravascular fluid exchange. With the associated increase in the number of model parameters, a detailed parameter sensitivity analysis has become difficult. Therefore we investigated the primary relations between ventricular pressure and volume, wall stress, intramyocardial pressure and coronary blood flow, with a mathematical model with a limited number of parameters. The model replicates several experimental observations: the phasic character of coronary inflow is virtually independent of maximum ventricular pressure, the amplitude of the coronary flow signal varies about proportionally with cardiac contractility, and intramyocardial pressure in the ventricular wall may exceed ventricular pressure. A parameter sensitivity analysis shows that the normalized amplitude of coronary inflow is mainly determined by contractility, reflected in ventricular pressure and, at low ventricular volumes, radial wall stress. Normalized flow amplitude is less sensitive to myocardial coronary compliance and resistance, and to the relation between active fiber stress, time, and sarcomere shortening velocity.

  15. Inhalation of Budesonide/Formoterol Increases Diaphragm Muscle Contractility

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    Chiyohiko Shindoh

    2012-01-01

    Conclusions: BUD/FORM inhalation has an inotropic effect on diaphragm muscle, protects diaphragm muscle deterioration after endotoxin injection, and inhibits NO production. Increments in muscle contractility with BUD/FORM inhalation are induced through a synergistic effect of an anti-inflammatory agent and 02-agonist.

  16. Clinical Relationship between Steatocholecystitis and Gallbladder Contractility Measured by Cholescintigraphy

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    Chang Seok Bang

    2015-01-01

    Full Text Available Objective. Contractility of gallbladder is known to be decreased in fatty gallbladder diseases. However, clinical estimation data about this relationship is still lacking. The aim of this study was to investigate the association between steatocholecystitis and contractility of gallbladder. Methods. Patients with cholecystitis (steatocholecystitis versus nonsteatocholecystitis who underwent cholescintigraphy before cholecystectomy were retrospectively evaluated in a single teaching hospital of Korea. The association of steatocholecystitis with contractility of gallbladder, measured by preoperative cholescintigraphy, was assessed by univariable and multivariable analysis. Results. A total of 432 patients were finally enrolled (steatocholecystitis versus nonsteatocholecystitis; 75 versus 357, calculous versus acalculous cholecystitis; 316 versus 116. In the multivariable analysis, age (OR: 0.94, 95% CI: 0.90–0.99, P=0.01 and total serum cholesterol (OR: 1.02, 95% CI: 1.01–1.04, P=0.04 were related to steatocholecystitis in patients with acalculous cholecystitis. Only age (OR: 0.97, 95% CI: 0.94–0.99, P=0.004 was significantly related to steatocholecystitis in patients with calculous cholecystitis. However, ejection fraction of gallbladder reflecting contractility measured by cholescintigraphy was not related to steatocholecystitis irrespective of presence of gallbladder stone in patients with cholecystitis. Conclusion. Ejection fraction of gallbladder measured by cholescintigraphy cannot be used for the detection or confirmation of steatocholecystitis.

  17. Myocardial contractile function in survived neonatal piglets after cardiopulmonary bypass

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    Popov Aron-Frederik

    2010-11-01

    Full Text Available Abstract Background Hemodynamic function may be depressed in the early postoperative stages after cardiac surgery. The aim of this study was the analysis of the myocardial contractility in neonates after cardiopulmonary bypass (CPB and mild hypothermia. Methods Three indices of left ventricular myocardial contractile function (dP/dt, (dP/dt/P, and wall thickening were studied up to 6 hours after CPB in neonatal piglets (CPB group; n = 4. The contractility data were analysed and then compared to the data of newborn piglets who also underwent median thoracotomy and instrumentation for the same time intervals but without CPB (non-CPB group; n = 3. Results Left ventricular dP/dtmax and (dP/dtmax/P remained stable in CPB group, while dP/dtmax decreased in non-CPB group 5 hours postoperatively (1761 ± 205 mmHg/s at baseline vs. 1170 ± 205 mmHg/s after 5 h; p max and (dP/dtmax/P there were no statistically significant differences between the two groups. Comparably, although myocardial thickening decreased in the non-CPB group the differences between the two groups were not statistically significant. Conclusions The myocardial contractile function in survived neonatal piglets remained stable 6 hours after cardiopulmonary bypass and mild hypothermia probably due to regional hypercontractility.

  18. Stalk-length-dependence of the contractility of Vorticella convallaria

    Science.gov (United States)

    Gul Chung, Eun; Ryu, Sangjin

    2017-12-01

    Vorticella convallaria is a sessile protozoan of which the spasmoneme contracts on a millisecond timescale. Because this contraction is induced and powered by the binding of calcium ions (Ca2+), the spasmoneme showcases Ca2+-powered cellular motility. Because the isometric tension of V. convallaria increases linearly with its stalk length, it is hypothesized that the contractility of V. convallaria during unhindered contraction depends on the stalk length. In this study, the contractile force and energetics of V. convallaria cells of different stalk lengths were evaluated using a fluid dynamic drag model which accounts for the unsteadiness and finite Reynolds number of the water flow caused by contracting V. convallaria and the wall effect of the no-slip substrate. It was found that the contraction displacement, peak contraction speed, peak contractile force, total mechanical work, and peak power depended on the stalk length. The observed stalk-length-dependencies were simulated using a damped spring model, and the model estimated that the average spring constant of the contracting stalk was 1.34 nN µm-1. These observed length-dependencies of Vorticella’s key contractility parameters reflect the biophysical mechanism of the spasmonemal contraction, and thus they should be considered in developing a theoretical model of the Vorticella spasmoneme.

  19. Approximate maximum parsimony and ancestral maximum likelihood.

    Science.gov (United States)

    Alon, Noga; Chor, Benny; Pardi, Fabio; Rapoport, Anat

    2010-01-01

    We explore the maximum parsimony (MP) and ancestral maximum likelihood (AML) criteria in phylogenetic tree reconstruction. Both problems are NP-hard, so we seek approximate solutions. We formulate the two problems as Steiner tree problems under appropriate distances. The gist of our approach is the succinct characterization of Steiner trees for a small number of leaves for the two distances. This enables the use of known Steiner tree approximation algorithms. The approach leads to a 16/9 approximation ratio for AML and asymptotically to a 1.55 approximation ratio for MP.

  20. Protective effects of anisodamine on cigarette smoke extract-induced airway smooth muscle cell proliferation and tracheal contractility

    International Nuclear Information System (INIS)

    Xu, Guang-Ni; Yang, Kai; Xu, Zu-Peng; Zhu, Liang; Hou, Li-Na; Qi, Hong; Chen, Hong-Zhuan; Cui, Yong-Yao

    2012-01-01

    Anisodamine, an antagonist of muscarinic acetylcholine receptors (mAChRs), has been used therapeutically to improve smooth muscle function, including microvascular, intestinal and airway spasms. Our previous studies have revealed that airway hyper-reactivity could be prevented by anisodamine. However, whether anisodamine prevents smoking-induced airway smooth muscle (ASM) cell proliferation remained unclear. In this study, a primary culture of rat ASM cells was used to evaluate an ASM phenotype through the ability of the cells to proliferate and express contractile proteins in response to cigarette smoke extract (CSE) and intervention of anisodamine. Our results showed that CSE resulted in an increase in cyclin D1 expression concomitant with the G0/G1-to-S phase transition, and high expression of M2 and M3. Functional studies showed that tracheal hyper-contractility accompanied contractile marker α-SMA high-expression. These changes, which occur only after CSE stimulation, were prevented and reversed by anisodamine, and CSE-induced cyclin D1 expression was significantly inhibited by anisodamine and the specific inhibitor U0126, BAY11-7082 and LY294002. Thus, we concluded that the protective and reversal effects and mechanism of anisodamine on CSE-induced events might involve, at least partially, the ERK, Akt and NF-κB signaling pathways associated with cyclin D1 via mAChRs. Our study validated that anisodamine intervention on ASM cells may contribute to anti-remodeling properties other than bronchodilation. -- Highlights: ► CSE induces tracheal cell proliferation, hyper-contractility and α-SMA expression. ► Anisodamine reverses CSE-induced tracheal hyper-contractility and cell proliferation. ► ERK, PI3K, and NF-κB pathways and cyclin D1 contribute to the reversal effect.

  1. Parasympathetic neurons in the cranial medial ventricular fat pad on the dog heart selectively decrease ventricular contractility.

    Science.gov (United States)

    Dickerson, L W; Rodak, D J; Fleming, T J; Gatti, P J; Massari, V J; McKenzie, J C; Gillis, R A

    1998-05-28

    We hypothesized that selective control of ventricular contractility might be mediated by postganglionic parasympathetic neurons in the cranial medial ventricular (CMV) ganglion plexus located in a fat pad at the base of the aorta. Sinus rate, atrioventricular (AV) conduction (ventricular rate during atrial pacing), and left ventricular contractile force (LV dP/dt during right ventricular pacing) were measured in eight chloralose-anesthetized dogs both before and during bilateral cervical vagus stimulation (20-30 V, 0.5 ms pulses, 15-20 Hz). Seven of these dogs were tested under beta-adrenergic blockade (propranolol, 0.8 mg kg(-1) i.v.). Control responses included sinus node bradycardia or arrest during spontaneous rhythm, high grade AV block or complete heart block, and a 30% decrease in contractility from 2118 +/- 186 to 1526 +/- 187 mm Hg s(-1) (P 0.05) decrease in contractility but still elicited the same degree of sinus bradycardia and AV block (N = 8, P < 0.05). Five dogs were re-tested 3 h after trimethaphan fat pad injection, at which time blockade of vagally-induced negative inotropy was partially reversed, as vagal stimulation decreased LV dP/dt by 19%. The same dose of trimethaphan given either locally into other fat pads (PVFP or IVC-ILA) or systemically (i.v.) had no effect on vagally-induced negative inotropy. Thus, parasympathetic ganglia located in the CMV fat pad mediated a decrease in ventricular contractility during vagal stimulation. Blockade of the CMV fat pad had no effect on vagally-mediated slowing of sinus rate or AV conduction.

  2. Maximum permissible dose

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    This chapter presents a historic overview of the establishment of radiation guidelines by various national and international agencies. The use of maximum permissible dose and maximum permissible body burden limits to derive working standards is discussed

  3. Upregulation of contractile endothelin type B receptors by lipid-soluble cigarette smoking particles in rat cerebral arteries via activation of MAPK

    International Nuclear Information System (INIS)

    Sandhu, Hardip; Xu, Cang Bao; Edvinsson, Lars

    2010-01-01

    Cigarette smoke exposure increases the risk of stroke. However, the underlying molecular mechanisms are poorly understood. Endothelin system plays key roles in the pathogenesis of stroke. The present study was designed to examine if lipid-soluble (dimethyl sulfoxide-soluble) cigarette smoke particles (DSP) induces upregulation of contractile endothelin type B (ET B ) receptors in rat cerebral arteries and if activation of mitogen activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) mediate the upregulation of contractile endothelin receptors in the cerebral arteries. Rat middle cerebral arteries were isolated and organ cultured in serum free medium for 24 h in the presence of DSP with or without specific inhibitors: MEK specific (U0126), p38 specific (SB202190), JNK specific (SP600125), NF-κB specific (BMS-345541) or (IMD-0354), transcription inhibitor (actinomycin D), or translation blocker (cycloheximide). Contractile responses to the ET B receptor agonist sarafotoxin 6c were investigated by a sensitive myograph. The expression of the ET B receptors were studied at mRNA and protein levels using quantitative real time PCR and immunohistochemistry, respectively. Results show that organ culture per se induced transcriptional upregulation of contractile ET B receptors in the cerebral vascular smooth muscle cells. This upregulation was further increased at the translational level by addition of DSP to the organ culture, but this increase was not seen by addition of nicotine or water-soluble cigarette smoke particles to the organ culture. The increased upregulation of contractile ET B receptors by DSP was abrogated by U0126, SP600125, actinomycin D, and cycloheximide, suggesting that the underlying molecular mechanisms involved in this process include activation of MEK and JNK MAPK-mediated transcription and translation of new contractile ET B receptors. Thus, the MAPK-mediated upregulation of contractile ET B receptors in cerebral arteries might be a

  4. Clebopride enhances contractility of the guinea pig stomach by blocking peripheral D2 dopamine receptor and alpha-2 adrenoceptor.

    Science.gov (United States)

    Takeda, K; Taniyama, K; Kuno, T; Sano, I; Ishikawa, T; Ohmura, I; Tanaka, C

    1991-05-01

    The mechanism of action of clebopride on the motility of guinea pig stomach was examined by the receptor binding assay for bovine brain membrane and by measuring gastric contractility and the release of acetylcholine from the stomach. The receptor binding assay revealed that clebopride bound to the D2 dopamine receptor with a high affinity and to the alpha-2 adrenoceptor and 5-HT2 serotonin receptor with relatively lower affinity, and not to D1 dopamine, alpha-1 adrenergic, muscarinic acetylcholine, H1 histamine, or opioid receptor. In strips of the stomach, clebopride at 10(-8) M to 10(-5) M enhanced the electrical transmural stimulation-evoked contraction and the release of acetylcholine. This enhancement was attributed to the blockade of the D2 dopamine receptor and alpha-2 adrenoceptor because: 1) Maximum responses obtained with specific D2 dopamine receptor antagonist, domperidone, and with specific alpha-2 adrenoceptor antagonist, yohimbine, were smaller than that with clebopride, and the sum of the effects of these two specific receptor antagonists is approximately equal to the effect of clebopride. 2) The facilitatory effect of clebopride was partially eliminated by pretreatment of the sample with domperidone or yohimbine, and the facilitatory effect of clebopride was not observed in preparations treated with the combination of domperidone and yohimbine. Clebopride also antagonized the inhibitory effects of dopamine and clonidine on the electrical transmural stimulation-evoked responses. These results indicate that clebopride acts on post ganglionic cholinergic neurons at D2 and alpha-2 receptors in this preparation to enhance enteric nervous system stimulated motility.

  5. Clebopride enhances contractility of the guinea pig stomach by blocking peripheral D2 dopamine receptor and alpha-2 adrenoceptor

    International Nuclear Information System (INIS)

    Takeda, K.; Taniyama, K.; Kuno, T.; Sano, I.; Ishikawa, T.; Ohmura, I.; Tanaka, C.

    1991-01-01

    The mechanism of action of clebopride on the motility of guinea pig stomach was examined by the receptor binding assay for bovine brain membrane and by measuring gastric contractility and the release of acetylcholine from the stomach. The receptor binding assay revealed that clebopride bound to the D2 dopamine receptor with a high affinity and to the alpha-2 adrenoceptor and 5-HT2 serotonin receptor with relatively lower affinity, and not to D1 dopamine, alpha-1 adrenergic, muscarinic acetylcholine, H1 histamine, or opioid receptor. In strips of the stomach, clebopride at 10 - 8 M to 10 - 5 M enhanced the electrical transmural stimulation-evoked contraction and the release of acetylcholine. This enhancement was attributed to the blockade of the D2 dopamine receptor and alpha-2 adrenoceptor because: (1) Maximum responses obtained with specific D2 dopamine receptor antagonist, domperidone, and with specific alpha-2 adrenoceptor antagonist, yohimbine, were smaller than that with clebopride, and the sum of the effects of these two specific receptor antagonists is approximately equal to the effect of clebopride. (2) The facilitatory effect of clebopride was partially eliminated by pretreatment of the sample with domperidone or yohimbine, and the facilitatory effect of clebopride was not observed in preparations treated with the combination of domperidone and yohimbine. Clebopride also antagonized the inhibitory effects of dopamine and clonidine on the electrical transmural stimulation-evoked responses. These results indicate that clebopride acts on post ganglionic cholinergic neurons at D2 and alpha-2 receptors in this preparation to enhance enteric nervous system stimulated motility

  6. Response of methane emissions from wetlands to the Last Glacial Maximum and an idealized Dansgaard-Oeschger climate event: insights from two models of different complexity

    NARCIS (Netherlands)

    Ringeval, B.; Hopcroft, P.O.; Valdes, P.J.; Ciais, P.; Ramstein, G.; Dolman, A.J.; Kageyama, M.

    2013-01-01

    The role of different sources and sinks of CH4 in changes in atmospheric methane ([CH4]) concentration during the last 100 000 yr is still not fully understood. In particular, the magnitude of the change in wetland CH4 emissions at the Last Glacial Maximum (LGM) relative to the pre-industrial period

  7. Acute exposure to lead increases myocardial contractility independent of hypertension development

    International Nuclear Information System (INIS)

    Fioresi, M.; Furieri, L.B.; Simões, M.R.; Ribeiro, R.F. Junior; Meira, E.F.; Fernandes, A.A.; Stefanon, I.; Vassallo, D.V.

    2013-01-01

    We studied the effects of the acute administration of small doses of lead over time on hemodynamic parameters in anesthetized rats to determine if myocardial contractility changes are dependent or not on the development of hypertension. Male Wistar rats received 320 µg/kg lead acetate iv once, and their hemodynamic parameters were measured for 2 h. Cardiac contractility was evaluated in vitro using left ventricular papillary muscles as were Na + ,K + -ATPase and myosin Ca 2+ -ATPase activities. Lead increased left- (control: 112 ± 3.7 vs lead: 129 ± 3.2 mmHg) and right-ventricular systolic pressures (control: 28 ± 1.2 vs lead: 34 ± 1.2 mmHg) significantly without modifying heart rate. Papillary muscles were exposed to 8 µM lead acetate and evaluated 60 min later. Isometric contractions increased (control: 0.546 ± 0.07 vs lead: 0.608 ± 0.06 g/mg) and time to peak tension decreased (control: 268 ± 13 vs lead: 227 ± 5.58 ms), but relaxation time was unchanged. Post-pause potentiation was similar between groups (n = 6 per group), suggesting no change in sarcoplasmic reticulum activity, evaluated indirectly by this protocol. After 1-h exposure to lead acetate, the papillary muscles became hyperactive in response to a β-adrenergic agonist (10 µM isoproterenol). In addition, post-rest contractions decreased, suggesting a reduction in sarcolemmal calcium influx. The heart samples treated with 8 µM lead acetate presented increased Na + ,K + -ATPase (approximately 140%, P < 0.05 for control vs lead) and myosin ATPase (approximately 30%, P < 0.05 for control vs lead) activity. Our results indicated that acute exposure to low lead concentrations produces direct positive inotropic and lusitropic effects on myocardial contractility and increases the right and left ventricular systolic pressure, thus potentially contributing to the early development of hypertension

  8. Facilitated ethanol metabolism promotes cardiomyocyte contractile dysfunction through autophagy in murine hearts.

    Science.gov (United States)

    Guo, Rui; Hu, Nan; Kandadi, Machender R; Ren, Jun

    2012-04-01

    Chronic drinking leads to myocardial contractile dysfunction where ethanol metabolism plays an essential role. Acetaldehyde, the main ethanol metabolite, mediates alcohol-induced cell injury although the underlying mechanism is still elusive. This study was designed to examine the mechanism involved in accelerated ethanol metabolism-induced cardiac defect with a focus on autophagy. Wild-type FVB and cardiac-specific overexpression of alcohol dehydrogenase mice were placed on a 4% nutrition-balanced alcohol diet for 8 weeks. Myocardial histology, immunohistochemistry, autophagy markers and signal molecules were examined. Expression of micro RNA miR-30a, a potential target of Beclin 1, was evaluated by real-time PCR. Chronic alcohol intake led to cardiac acetaldehyde accumulation, hypertrophy and overt autophagosome accumulation (LC3-II and Atg7), the effect of which was accentuated by ADH. Signaling molecules governing autophagy initiation including class III PtdIns3K, phosphorylation of mTOR and p70S6K were enhanced and dampened, respectively, following alcohol intake. These alcohol-induced signaling responses were augmented by ADH. ADH accentuated or unmasked alcohol-induced downregulation of Bcl-2, Bcl-xL and MiR-30a. Interestingly, ADH aggravated alcohol-induced p62 accumulation. Autophagy inhibition using 3-MA abolished alcohol-induced cardiomyocyte contractile anomalies. Moreover, acetaldehyde led to cardiomyocyte contractile dysfunction and autophagy induction, which was ablated by 3-MA. Ethanol or acetaldehyde increased GFP-LC3 puncta in H9c2 cells, the effect of which was ablated by 3-MA but unaffected by lysosomal inhibition using bafilomycin A(1), E64D and pepstatin A. In summary, these data suggested that facilitated acetaldehyde production via ADH following alcohol intake triggered cardiac autophagosome formation along with impaired lysosomal degradation, en route to myocardial defect.

  9. Dynamics of myosin II organization into cortical contractile networks and fibers

    Science.gov (United States)

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

    2014-03-01

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

  10. Influence of metabolism modifiers of cyclic nucleotides on contractility of right ventricle of rat heart with intact and removed endocardial endothelium

    Directory of Open Access Journals (Sweden)

    Savić Slađana

    2010-01-01

    Full Text Available Introduction. Endocardial endothelium, a natural biological barrier between circulating blood in heart ventricle and cells, creates a complex yet finely tuned balance of interactions with the immediate environment. Objective. We investigated the roles of theophylline, nonspecific phosphodiesterase inhibitor, and imidazole, an activator of phosphodiesterase on contractility of the right ventricle of rat heart, with intact and removed endocardial endothelium. Methods. Adult rats, of both sexes, type Wistar albino, were used in this experiment. All experiments were conducted on the preparations of the right ventricle using two experimental models. In the first experimental model, an endocardial endothelium (EE was preserved, and in the second model, an endocardial endothelium (-EE was removed using 1% solution Triton X-100. Results. Theophylline (1x10-2 mol/l expressed the positive inotropic effect on the heart, regardless of the presence of the endocardial endothelium. Inotropic response as multiple process can be induced by inhibition of phosphodiesterase, accumulation of cyclic nucleotides and activation of Ca2+ channels. Imidazole (2x10-3 mol/l increased the contractility of the right ventricle of the heart with EE. The modulator effect of endocardial endothelium on contractility of imidazole proved to be significant. As imidazole influenced the contractility of the right ventricle only in the presence of the endocardial endothelium, it is assumed that its effect is mediated via deliverance of endothelial mediators with positive inotropic effect. Conclusion. An intact endocardial endothelium is necessary for completion of contractile performance of the heart.

  11. Climatic responses to the shortwave and longwave direct radiative effects of sea salt aerosol in present day and the last glacial maximum

    Energy Technology Data Exchange (ETDEWEB)

    Yue, Xu [Chinese Academy of Sciences (CAS), Climate Change Research Center (CCRC), Beijing (China); Chinese Academy of Sciences (CAS), Nansen-Zhu International Research Center, Institute of Atmospheric Physics (IAP), Beijing (China); Harvard University, School of Engineering and Applied Sciences, Cambridge, MA (United States); Liao, Hong [Chinese Academy of Sciences (CAS), State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry (LAPC), Institute of Atmospheric Physics (IAP), P.O. Box 9804, Beijing (China)

    2012-12-15

    We examine the climatic responses to the shortwave (SW) and longwave (LW) direct radiative effects (RE) of sea salt aerosol in present day and the last glacial maximum (LGM) using a general circulation model with online simulation of sea salt cycle. The 30-year control simulation predicts a present-day annual emission of sea salt of 4,253 Tg and a global burden of 8.1 Tg for the particles with dry radii smaller than 10 {mu}m. Predicted annual and global mean SW and LW REs of sea salt are, respectively, -1.06 and +0.14 W m{sup -2} at the top of atmosphere (TOA), and -1.10 and +0.54 W m{sup -2} at the surface. The LW warming of sea salt is found to decrease with altitude, which leads to a stronger net sea salt cooling in the upper troposphere. The changes in global mean air temperature by the present-day sea salt are simulated to be -0.55, -0.63, -0.86, and -0.91 K at the surface, 850, 500a, and 200 hPa, respectively. The emission of sea salt at the LGM is estimated to be 4,075 Tg year{sup -1}. Relative to present day, the LGM sea salt emission is higher by about 18% over the tropical and subtropical oceans, and is lower by about 35% in the mid- and high-latitudes in both hemispheres because of the expansion of sea ice. As a result of the weakened LGM water cycle, the LGM annual and global mean burden of sea salt is predicted to be higher by 4% as compared to the present-day value. Compared with the climatic effect of sea salt in present day, the sea-salt-induced reductions in surface air temperature at the LGM have similar magnitude in the tropics but are weakened by about 0.18 and 0.14 K in the high latitudes of the Southern and Northern Hemispheres, respectively. We also perform a sensitivity study to explore the upper limit of the climatic effect of the LGM sea salt. We assume an across-the-board 30% increase in the glacial wind speed and consider sea salt emissions over sea ice, so that the model can reproduce the ratio of sea salt deposition between the LGM and

  12. Contractile properties of motor units and expression of myosin heavy chain isoforms in rat fast-type muscle after volitional weight-lifting training.

    Science.gov (United States)

    Łochyński, Dawid; Kaczmarek, Dominik; Mrówczyński, Włodzimierz; Warchoł, Wojciech; Majerczak, Joanna; Karasiński, Janusz; Korostyński, Michał; Zoladz, Jerzy A; Celichowski, Jan

    2016-10-01

    Dynamic resistance training increases the force and speed of muscle contraction, but little is known about modifications to the contractile properties of the main physiological types of motor units (MUs) that contribute to these muscle adaptations. Although the contractile profile of MU muscle fibers is tightly coupled to myosin heavy chain (MyHC) protein expression, it is not well understood if MyHC transition is a prerequisite for modifications to the contractile characteristics of MUs. In this study, we examined MU contractile properties, the mRNA expression of MyHC, parvalbumin, and sarcoendoplasmic reticulum Ca 2+ pump isoforms, as well as the MyHC protein content after 5 wk of volitional progressive weight-lifting training in the medial gastrocnemius muscle in rats. The training had no effect on MyHC profiling or Ca 2+ -handling protein gene expression. Maximum force increased in slow (by 49%) and fast (by 21%) MUs. Within fast MUs, the maximum force increased in most fatigue-resistant and intermediate but not most fatigable MUs. Twitch contraction time was shortened in slow and fast fatigue-resistant MUs. Twitch half-relaxation was shortened in fast most fatigue-resistant and intermediate MUs. The force-frequency curve shifted rightward in fast fatigue-resistant MUs. Fast fatigable MUs fatigued less within the initial 15 s while fast fatigue-resistant units increased the ability to potentiate the force within the first minute of the standard fatigue test. In conclusion, at the early stage of resistance training, modifications to the contractile characteristics of MUs appear in the absence of MyHC transition and the upregulation of Ca 2+ -handling genes. Copyright © 2016 the American Physiological Society.

  13. A comparison of the contractile properties of smooth muscle from pig urethra and internal anal sphincter.

    Science.gov (United States)

    Ramalingam, Thanesan; Durlu-Kandilci, N Tugba; Brading, Alison F

    2010-09-01

    Smooth muscles from the urethra and internal anal sphincter (IAS) play an essential role in the maintenance of urinary and fecal continence. Any damage in these muscles may cause serious problems. The aim of this study was to directly compare the contractile properties of pig urethra and IAS taken from the same animal. Smooth muscle strips of urethra and IAS dissected from the same pig were transferred to organ baths superfused with Krebs' solution, loaded with 1 g tension and equilibrated for 1 hr. Carbachol and phenylephrine response curves and EFS responses were elicited in the absence and presence of inhibitors. Both tissues developed tone during the 1 hr equilibration period. Carbachol (3 × 10(-6)-10(-3) M) contracted urethra whilst relaxing IAS. Guanethidine (10(-6) M) inhibited the carbachol responses in both tissues. L-NOARG (10(-4) M) decreased carbachol responses in IAS, but not in urethra. Phenylephrine (3 × 10(-6)-10(-2) M) contracted both tissues. EFS (1-40 Hz) induced a contractile response in urethra which was decreased with guanethidine (10(-6) M) and further blocked by atropine (10(-6) M). In the presence of both, a relaxation response was observed that is sensitive to NOS inhibitors especially at low frequencies. EFS induced a relaxation followed by a contraction in IAS strips. This contraction was blocked by guanethidine but not by atropine, and the remaining relaxation at 20 Hz was decreased with L-NOARG and increased with L-arginine. There are differences between urethra and IAS in terms of muscarinic activation and neural innervation, relevant for pharmacotherapy. © 2010 Wiley-Liss, Inc.

  14. Cerebral artery alpha-1 AR subtypes: high altitude long-term acclimatization responses.

    Directory of Open Access Journals (Sweden)

    Ravi Goyal

    Full Text Available In response to hypoxia and other stress, the sympathetic (adrenergic nervous system regulates arterial contractility and blood flow, partly through differential activities of the alpha1 (α1 - adrenergic receptor (AR subtypes (α1A-, α1B-, and α1D-AR. Thus, we tested the hypothesis that with acclimatization to long-term hypoxia (LTH, contractility of middle cerebral arteries (MCA is regulated by changes in expression and activation of the specific α1-AR subtypes. We conducted experiments in MCA from adult normoxic sheep maintained near sea level (300 m and those exposed to LTH (110 days at 3801 m. Following acclimatization to LTH, ovine MCA showed a 20% reduction (n = 5; P<0.05 in the maximum tension achieved by 10-5 M phenylephrine (PHE. LTH-acclimatized cerebral arteries also demonstrated a statistically significant (P<0.05 inhibition of PHE-induced contractility in the presence of specific α1-AR subtype antagonists. Importantly, compared to normoxic vessels, there was significantly greater (P<0.05 α1B-AR subtype mRNA and protein levels in LTH acclimatized MCA. Also, our results demonstrate that extracellular regulated kinase 1 and 2 (ERK1/2-mediated negative feedback regulation of PHE-induced contractility is modulated by α1B-AR subtype. Overall, in ovine MCA, LTH produces profound effects on α1-AR subtype expression and function.

  15. Dietary nitrate increases tetanic [Ca2+]i and contractile force in mouse fast-twitch muscle.

    Science.gov (United States)

    Hernández, Andrés; Schiffer, Tomas A; Ivarsson, Niklas; Cheng, Arthur J; Bruton, Joseph D; Lundberg, Jon O; Weitzberg, Eddie; Westerblad, Håkan

    2012-08-01

    Dietary inorganic nitrate has profound effects on health and physiological responses to exercise. Here, we examined if nitrate, in doses readily achievable via a normal diet, could improve Ca(2+) handling and contractile function using fast- and slow-twitch skeletal muscles from C57bl/6 male mice given 1 mm sodium nitrate in water for 7 days. Age matched controls were provided water without added nitrate. In fast-twitch muscle fibres dissected from nitrate treated mice, myoplasmic free [Ca(2+)] was significantly greater than in Control fibres at stimulation frequencies from 20 to 150 Hz, which resulted in a major increase in contractile force at ≤ 50 Hz. At 100 Hz stimulation, the rate of force development was ∼35% faster in the nitrate group. These changes in nitrate treated mice were accompanied by increased expression of the Ca(2+) handling proteins calsequestrin 1 and the dihydropyridine receptor. No changes in force or calsequestrin 1 and dihydropyridine receptor expression were measured in slow-twitch muscles. In conclusion, these results show a striking effect of nitrate supplementation on intracellular Ca(2+) handling in fast-twitch muscle resulting in increased force production. A new mechanism is revealed by which nitrate can exert effects on muscle function with applications to performance and a potential therapeutic role in conditions with muscle weakness.

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

    Science.gov (United States)

    Nie, Wei

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

  17. Maximum Acceleration Recording Circuit

    Science.gov (United States)

    Bozeman, Richard J., Jr.

    1995-01-01

    Coarsely digitized maximum levels recorded in blown fuses. Circuit feeds power to accelerometer and makes nonvolatile record of maximum level to which output of accelerometer rises during measurement interval. In comparison with inertia-type single-preset-trip-point mechanical maximum-acceleration-recording devices, circuit weighs less, occupies less space, and records accelerations within narrower bands of uncertainty. In comparison with prior electronic data-acquisition systems designed for same purpose, circuit simpler, less bulky, consumes less power, costs and analysis of data recorded in magnetic or electronic memory devices. Circuit used, for example, to record accelerations to which commodities subjected during transportation on trucks.

  18. Effect of lead on cholinergic contractile function in the forestomach, ileum and colon of the male Wistar rat

    International Nuclear Information System (INIS)

    Ryden, E.B.

    1986-01-01

    Gastrointestinal symptoms, including colic, are signs of lead poisoning in man, but the mechanism of these effects has not been elucidated. In order to understand the effects of lead on acetylcholine (ACh)-mediated responses, studies were undertaken to determine the isometric contractile response to methacholine, KCl and electric field stimulation in rat forestomach, ileum and colon under conditions of in vitro and in vivo treatment with lead acetate. Rats were dosed with 4% lead acetate in their diet, NIH-07, for 7 weeks, which resulted in renal and hematologic toxicity and blood lead levels of 180-389 ug/dl (1.2 x 10 -5 M). Tissues from in vivo treated rats were exposed to 1.2 x 10 -5 M lead acetate during in vitro contractile studies. E/sub max/ or ED 50 methacholine was not affected by 1.2 x 10 -5 M lead acetate, administered in vitro to control tissue. In the forestomach, a 10-fold higher concentration of lead (16 x 10 -5 M), administered in vitro, increased baseline tension and inhibition response to methacholine. However, in vivo lead treatment potentiated response to methacholine in the forestomach and increased baseline tension in the presence of physostigmine. The EFS response, attributable to ACh release, was not affected in the forestomach or ileum by 1.2 x 10 -5 M in vitro lead treatment. These data indicate that lead, administered in vivo in concentrations which cause renal and hematologic toxicity, does not impair cholinergic contractile response in gastrointestinal smooth muscle. Instead, the response to methacholine may be potentiated in the forestomach. Possible mechanisms of lead-induced potentiation of baseline or evoked tension include increased levels of non-elicited ACh release, inhibition of acetylcholinesterase or sensitization of muscarinic receptors

  19. Contractile function and motor unit firing rates of the human hamstrings.

    Science.gov (United States)

    Kirk, Eric A; Rice, Charles L

    2017-01-01

    Neuromuscular properties of the lower limb in health, aging, and disease are well described for major lower limb muscles comprising the quadriceps, triceps surae, and dorsiflexors, with the notable exception of the posterior thigh (hamstrings). The purpose of this study was to further characterize major muscles of the lower limb by comprehensively exploring contractile properties in relation to spinal motor neuron output expressed as motor unit firing rates (MUFRs) in the hamstrings of 11 (26.5 ± 3.8) young men. Maximal isometric voluntary contraction (MVC), voluntary activation, stimulated contractile properties including a force-frequency relationship, and MUFRs from submaximal to maximal voluntary contractile intensities were assessed in the hamstrings. Strength and MUFRs were assessed at two presumably different muscle lengths by varying the knee joint angles (90° and 160°). Knee flexion MVCs were 60-70% greater in the extended position (160°). The frequency required to elicit 50% of maximum tetanic torque was 16-17 Hz. Mean MUFRs at 25-50% MVC were 9-31% less in the biceps femoris compared with the semimembranosus-semitendinosus group. Knee joint angle (muscle length) influenced MUFRs such that mean MUFRs were greater in the shortened (90°) position at 50% and 100% MVC. Compared with previous reports, mean maximal MUFRs in the hamstrings are greater than those in the quadriceps and triceps surae and somewhat less than those in the tibialis anterior. Mean maximal MUFRs in the hamstrings are influenced by changes in knee joint angle, with lower firing rates in the biceps femoris compared with the semimembranosus-semitendinosus muscle group. We studied motor unit firing rates (MUFRs) at various voluntary contraction intensities in the hamstrings, one of the only major lower limb muscles to have MUFRs affected by muscle length changes. Within the hamstrings muscle-specific differences have greater impact on MUFRs than length changes, with the biceps femoris

  20. Maximum Quantum Entropy Method

    OpenAIRE

    Sim, Jae-Hoon; Han, Myung Joon

    2018-01-01

    Maximum entropy method for analytic continuation is extended by introducing quantum relative entropy. This new method is formulated in terms of matrix-valued functions and therefore invariant under arbitrary unitary transformation of input matrix. As a result, the continuation of off-diagonal elements becomes straightforward. Without introducing any further ambiguity, the Bayesian probabilistic interpretation is maintained just as in the conventional maximum entropy method. The applications o...

  1. Maximum power demand cost

    International Nuclear Information System (INIS)

    Biondi, L.

    1998-01-01

    The charging for a service is a supplier's remuneration for the expenses incurred in providing it. There are currently two charges for electricity: consumption and maximum demand. While no problem arises about the former, the issue is more complicated for the latter and the analysis in this article tends to show that the annual charge for maximum demand arbitrarily discriminates among consumer groups, to the disadvantage of some [it

  2. The growth hormone/insulin-like growth factor-I axis hormones and bone markers in elite athletes in response to a maximum exercise test

    DEFF Research Database (Denmark)

    Ehrnborg, C.; Lange, K.H.; Dall, R.

    2003-01-01

    -53 yr) from Denmark, the United Kingdom, Italy, and Sweden participated in the study. The serum concentrations of total GH, GH22 kDa, IGF-I, IGF binding protein (IGFBP)-2, IGFBP-3, acid-labile subunit, procollagen type III (P-III-P), and the bone markers osteocalcin, carboxy-terminal cross......-linked telopeptide of type I collagen (ICTP), and carboxy-terminal propeptide of type I procollagen were measured. The maximum exercise test showed, in both genders, a peak concentration of total GH (P ... in both genders, with a peak value in the direct post-exercise phase and a subsequent decrease to baseline levels or below within 120 min. The osteocalcin and propeptide of type I procollagen values did not change during the exercise test. Specific reference ranges for each variable in the GH/IGF-I axis...

  3. Intramural Injection with Botulinum Toxin Type A in Piglet Esophagus. The Influencer on Maximum Load and Elongation: A Dose Response Study.

    Science.gov (United States)

    Ellebæk, Mark Bremholm; Qvist, Niels; Schrøder, Henrik Daa; Rasmussen, Lars

    2016-06-01

    Introduction The treatment of esophageal atresia (OA) is challenging. The main goal is to achieve primary anastomosis. We have previously demonstrated in a pig model that intramural injection of botulinum toxin type A (BTX-A) resulted in significant elongation of the esophagus during tensioning until bursting point. The objectives of the present study were to investigate the influence of different amounts of intramural BTX-A on the stretch-tension characteristics and histological changes of the esophagus in piglets. Materials and Methods A total of 52 piglets were randomized to four groups receiving 2, 4, or 8 units/kg of BTX-A or isotonic saline (placebo). After a 1-hour of rest the esophagus was harvested and subjected to a stretch-tension test and histological examination to assess changes in the density of presynaptic vesicles in the nerve cells. Results Overall, 9 of the 52 animals were excluded from analysis due to problems with the stretch-tension test or death from anesthesia. The maximum loads were higher in the BTX-A groups (2 units/kg: +2.1 N; 4 units/kg: +1.3 N; 8 units/kg: +1.9 N) than the placebo (p = 0.046). There were no significant differences in percentage elongation, or histology. Conclusions This study demonstrated that injection of 2 units/kg BTX-A into a nonanastomosed esophageal wall resulted in a modest increase in the maximum load achieved before bursting; this may be due to the muscle-relaxant effect of BTX-A. BTX-A injection produced no significant effects on elongation or esophageal histology. The clinical usefulness of BTX-A in treatment of OA is still unclear. Georg Thieme Verlag KG Stuttgart · New York.

  4. The effect of N-acetylcysteine on cardiac contractility to dobutamine in rats with streptozotocin-induced diabetes.

    Science.gov (United States)

    Cheng, Xing; Xia, Zhengyuan; Leo, Joyce M; Pang, Catherine C Y

    2005-09-05

    We examined if myocardial depression at the acute phase of diabetes (3 weeks after injection of streptozotocin, 60 mg/kg i.v.) is due to activation of inducible nitric oxide synthase and production of peroxynitrite, and if treatment with N-acetylcysteine (1.2 g/day/kg for 3 weeks, antioxidant) improves cardiac function. Four groups of rats were used: control, N-acetylcysteine-treated control, diabetic and N-acetylcysteine-treated diabetic. Pentobarbital-anaesthetized diabetic rats, relative to the controls, had reduced left ventricular contractility to dobutamine (1-57 microg/min/kg). The diabetic rats also had increased myocardial levels of thiobarbituric acid reactive substances, immunostaining of inducible nitric oxide synthase and nitrotyrosine, and similar baseline 15-F2t-isoprostane. N-acetylcysteine did not affect responses in the control rats; but increased cardiac contractility to dobutamine, reduced myocardial immunostaining of inducible nitric oxide synthase and nitrotyrosine and level of 15-F2t-isoprostane, and increased cardiac contractility to dobutamine in the diabetic rats. Antioxidant supplementation in diabetes reduces oxidative stress and improves cardiac function.

  5. Beta adrenergic overstimulation impaired vascular contractility via actin-cytoskeleton disorganization in rabbit cerebral artery.

    Directory of Open Access Journals (Sweden)

    Hyoung Kyu Kim

    Full Text Available BACKGROUND AND PURPOSE: Beta adrenergic overstimulation may increase the vascular damage and stroke. However, the underlying mechanisms of beta adrenergic overstimulation in cerebrovascular dysfunctions are not well known. We investigated the possible cerebrovascular dysfunction response to isoproterenol induced beta-adrenergic overstimulation (ISO in rabbit cerebral arteries (CAs. METHODS: ISO was induced in six weeks aged male New Zealand white rabbit (0.8-1.0 kg by 7-days isoproterenol injection (300 μg/kg/day. We investigated the alteration of protein expression in ISO treated CAs using 2DE proteomics and western blot analysis. Systemic properties of 2DE proteomics result were analyzed using bioinformatics software. ROS generation and following DNA damage were assessed to evaluate deteriorative effect of ISO on CAs. Intracellular Ca(2+ level change and vascular contractile response to vasoactive drug, angiotensin II (Ang II, were assessed to evaluate functional alteration of ISO treated CAs. Ang II-induced ROS generation was assessed to evaluated involvement of ROS generation in CA contractility. RESULTS: Proteomic analysis revealed remarkably decreased expression of cytoskeleton organizing proteins (e.g. actin related protein 1A and 2, α-actin, capping protein Z beta, and vimentin and anti-oxidative stress proteins (e.g. heat shock protein 9A and stress-induced-phosphoprotein 1 in ISO-CAs. As a cause of dysregulation of actin-cytoskeleton organization, we found decreased level of RhoA and ROCK1, which are major regulators of actin-cytoskeleton organization. As functional consequences of proteomic alteration, we found the decreased transient Ca(2+ efflux and constriction response to angiotensin II and high K(+ in ISO-CAs. ISO also increased basal ROS generation and induced oxidative damage in CA; however, it decreased the Ang II-induced ROS generation rate. These results indicate that ISO disrupted actin cytoskeleton proteome network

  6. An increased rectal maximum tolerable volume and long anal canal are associated with poor short-term response to biofeedback therapy for patients with anismus with decreased bowel frequency and normal colonic transit time.

    Science.gov (United States)

    Rhee, P L; Choi, M S; Kim, Y H; Son, H J; Kim, J J; Koh, K C; Paik, S W; Rhee, J C; Choi, K W

    2000-10-01

    Biofeedback is an effective therapy for a majority of patients with anismus. However, a significant proportion of patients still failed to respond to biofeedback, and little has been known about the factors that predict response to biofeedback. We evaluated the factors associated with poor response to biofeedback. Biofeedback therapy was offered to 45 patients with anismus with decreased bowel frequency (less than three times per week) and normal colonic transit time. Any differences in demographics, symptoms, and parameters of anorectal physiologic tests were sought between responders (in whom bowel frequency increased up to three times or more per week after biofeedback) and nonresponders (in whom bowel frequency remained less than three times per week). Thirty-one patients (68.9 percent) responded to biofeedback and 14 patients (31.1 percent) did not. Anal canal length was longer in nonresponders than in responders (4.53 +/- 0.5 vs. 4.08 +/- 0.56 cm; P = 0.02), and rectal maximum tolerable volume was larger in nonresponders than in responders. (361 +/- 87 vs. 302 +/- 69 ml; P = 0.02). Anal canal length and rectal maximum tolerable volume showed significant differences between responders and nonresponders on multivariate analysis (P = 0.027 and P = 0.034, respectively). This study showed that a long anal canal and increased rectal maximum tolerable volume are associated with poor short-term response to biofeedback for patients with anismus with decreased bowel frequency and normal colonic transit time.

  7. Enhanced basal contractility but reduced excitation-contraction coupling efficiency and beta-adrenergic reserve of hearts with increased Cav1.2 activity.

    Science.gov (United States)

    Tang, Mingxin; Zhang, Xiaoying; Li, Yingxin; Guan, Yinzheng; Ai, Xiaojie; Szeto, Christopher; Nakayama, Hiroyuki; Zhang, Hongyu; Ge, Shuping; Molkentin, Jeffery D; Houser, Steven R; Chen, Xiongwen

    2010-08-01

    Cardiac remodeling during heart failure development induces a significant increase in the activity of the L-type Ca(2+) channel (Cav1.2). However, the effects of enhanced Cav1.2 activity on myocyte excitation-contraction (E-C) coupling, cardiac contractility, and its regulation by the beta-adrenergic system are not clear. To recapitulate the increased Cav1.2 activity, a double transgenic (DTG) mouse model overexpressing the Cavbeta2a subunit in a cardiac-specific and inducible manner was established. We studied cardiac (in vivo) and myocyte (in vitro) contractility at baseline and upon beta-adrenergic stimulation. E-C coupling efficiency was evaluated in isolated myocytes as well. The following results were found: 1) in DTG myocytes, L-type Ca(2+) current (I(Ca,L)) density, myocyte fractional shortening (FS), peak Ca(2+) transients, and sarcoplasmic reticulum (SR) Ca(2+) content (caffeine-induced Ca(2+) transient peak) were significantly increased (by 100.8%, 48.8%, 49.8%, and 46.8%, respectively); and 2) cardiac contractility evaluated with echocardiography [ejection fraction (EF) and (FS)] and invasive intra-left ventricular pressure (maximum dP/dt and -dP/dt) measurements were significantly greater in DTG mice than in control mice. However, 1) the cardiac contractility (EF, FS, dP/dt, and -dP/dt)-enhancing effect of the beta-adrenergic agonist isoproterenol (2 microg/g body wt ip) was significantly reduced in DTG mice, which could be attributed to the loss of beta-adrenergic stimulation on contraction, Ca(2+) transients, I(Ca,L), and SR Ca(2+) content in DTG myocytes; and 2) E-C couplng efficiency was significantly lower in DTG myocytes. In conclusion, increasing Cav1.2 activity by promoting its high-activity mode enhances cardiac contractility but decreases E-C coupling efficiency and the adrenergic reserve of the heart.

  8. Introduction of non-linear elasticity models for characterization of shape and deformation statistics: application to contractility assessment of isolated adult cardiocytes.

    Science.gov (United States)

    Bazan, Carlos; Hawkins, Trevor; Torres-Barba, David; Blomgren, Peter; Paolini, Paul

    2011-08-22

    We are exploring the viability of a novel approach to cardiocyte contractility assessment based on biomechanical properties of the cardiac cells, energy conservation principles, and information content measures. We define our measure of cell contraction as being the distance between the shapes of the contracting cell, assessed by the minimum total energy of the domain deformation (warping) of one cell shape into another. To guarantee a meaningful vis-à-vis correspondence between the two shapes, we employ both a data fidelity term and a regularization term. The data fidelity term is based on nonlinear features of the shapes while the regularization term enforces the compatibility between the shape deformations and that of a hyper-elastic material. We tested the proposed approach by assessing the contractile responses in isolated adult rat cardiocytes and contrasted these measurements against two different methods for contractility assessment in the literature. Our results show good qualitative and quantitative agreements with these methods as far as frequency, pacing, and overall behavior of the contractions are concerned. We hypothesize that the proposed methodology, once appropriately developed and customized, can provide a framework for computational cardiac cell biomechanics that can be used to integrate both theory and experiment. For example, besides giving a good assessment of contractile response of the cardiocyte, since the excitation process of the cell is a closed system, this methodology can be employed in an attempt to infer statistically significant model parameters for the constitutive equations of the cardiocytes.

  9. Automated Video-Based Analysis of Contractility and Calcium Flux in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Cultured over Different Spatial Scales.

    Science.gov (United States)

    Huebsch, Nathaniel; Loskill, Peter; Mandegar, Mohammad A; Marks, Natalie C; Sheehan, Alice S; Ma, Zhen; Mathur, Anurag; Nguyen, Trieu N; Yoo, Jennie C; Judge, Luke M; Spencer, C Ian; Chukka, Anand C; Russell, Caitlin R; So, Po-Lin; Conklin, Bruce R; Healy, Kevin E

    2015-05-01

    Contractile motion is the simplest metric of cardiomyocyte health in vitro, but unbiased quantification is challenging. We describe a rapid automated method, requiring only standard video microscopy, to analyze the contractility of human-induced pluripotent stem cell-derived cardiomyocytes (iPS-CM). New algorithms for generating and filtering motion vectors combined with a newly developed isogenic iPSC line harboring genetically encoded calcium indicator, GCaMP6f, allow simultaneous user-independent measurement and analysis of the coupling between calcium flux and contractility. The relative performance of these algorithms, in terms of improving signal to noise, was tested. Applying these algorithms allowed analysis of contractility in iPS-CM cultured over multiple spatial scales from single cells to three-dimensional constructs. This open source software was validated with analysis of isoproterenol response in these cells, and can be applied in future studies comparing the drug responsiveness of iPS-CM cultured in different microenvironments in the context of tissue engineering.

  10. Maximum mutual information regularized classification

    KAUST Repository

    Wang, Jim Jing-Yan

    2014-09-07

    In this paper, a novel pattern classification approach is proposed by regularizing the classifier learning to maximize mutual information between the classification response and the true class label. We argue that, with the learned classifier, the uncertainty of the true class label of a data sample should be reduced by knowing its classification response as much as possible. The reduced uncertainty is measured by the mutual information between the classification response and the true class label. To this end, when learning a linear classifier, we propose to maximize the mutual information between classification responses and true class labels of training samples, besides minimizing the classification error and reducing the classifier complexity. An objective function is constructed by modeling mutual information with entropy estimation, and it is optimized by a gradient descend method in an iterative algorithm. Experiments on two real world pattern classification problems show the significant improvements achieved by maximum mutual information regularization.

  11. Maximum mutual information regularized classification

    KAUST Repository

    Wang, Jim Jing-Yan; Wang, Yi; Zhao, Shiguang; Gao, Xin

    2014-01-01

    In this paper, a novel pattern classification approach is proposed by regularizing the classifier learning to maximize mutual information between the classification response and the true class label. We argue that, with the learned classifier, the uncertainty of the true class label of a data sample should be reduced by knowing its classification response as much as possible. The reduced uncertainty is measured by the mutual information between the classification response and the true class label. To this end, when learning a linear classifier, we propose to maximize the mutual information between classification responses and true class labels of training samples, besides minimizing the classification error and reducing the classifier complexity. An objective function is constructed by modeling mutual information with entropy estimation, and it is optimized by a gradient descend method in an iterative algorithm. Experiments on two real world pattern classification problems show the significant improvements achieved by maximum mutual information regularization.

  12. Maximum likely scale estimation

    DEFF Research Database (Denmark)

    Loog, Marco; Pedersen, Kim Steenstrup; Markussen, Bo

    2005-01-01

    A maximum likelihood local scale estimation principle is presented. An actual implementation of the estimation principle uses second order moments of multiple measurements at a fixed location in the image. These measurements consist of Gaussian derivatives possibly taken at several scales and/or ...

  13. Robust Maximum Association Estimators

    NARCIS (Netherlands)

    A. Alfons (Andreas); C. Croux (Christophe); P. Filzmoser (Peter)

    2017-01-01

    textabstractThe maximum association between two multivariate variables X and Y is defined as the maximal value that a bivariate association measure between one-dimensional projections αX and αY can attain. Taking the Pearson correlation as projection index results in the first canonical correlation

  14. Response of methane emissions from wetlands to the Last Glacial Maximum and an idealized Dansgaard–Oeschger climate event: insights from two models of different complexity

    Directory of Open Access Journals (Sweden)

    B. Ringeval

    2013-01-01

    Full Text Available The role of different sources and sinks of CH4 in changes in atmospheric methane ([CH4] concentration during the last 100 000 yr is still not fully understood. In particular, the magnitude of the change in wetland CH4 emissions at the Last Glacial Maximum (LGM relative to the pre-industrial period (PI, as well as during abrupt climatic warming or Dansgaard–Oeschger (D–O events of the last glacial period, is largely unconstrained. In the present study, we aim to understand the uncertainties related to the parameterization of the wetland CH4 emission models relevant to these time periods by using two wetland models of different complexity (SDGVM and ORCHIDEE. These models have been forced by identical climate fields from low-resolution coupled atmosphere–ocean general circulation model (FAMOUS simulations of these time periods. Both emission models simulate a large decrease in emissions during LGM in comparison to PI consistent with ice core observations and previous modelling studies. The global reduction is much larger in ORCHIDEE than in SDGVM (respectively −67 and −46%, and whilst the differences can be partially explained by different model sensitivities to temperature, the major reason for spatial differences between the models is the inclusion of freezing of soil water in ORCHIDEE and the resultant impact on methanogenesis substrate availability in boreal regions. Besides, a sensitivity test performed with ORCHIDEE in which the methanogenesis substrate sensitivity to the precipitations is modified to be more realistic gives a LGM reduction of −36%. The range of the global LGM decrease is still prone to uncertainty, and here we underline its sensitivity to different process parameterizations. Over the course of an idealized D–O warming, the magnitude of the change in wetland CH4 emissions simulated by the two models at global scale is very similar at around 15 Tg yr−1, but this is only around 25% of the ice-core measured

  15. Troglitazone stimulates β-arrestin-dependent cardiomyocyte contractility via the angiotensin II type 1A receptor

    International Nuclear Information System (INIS)

    Tilley, Douglas G.; Nguyen, Anny D.; Rockman, Howard A.

    2010-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) agonists are commonly used to treat cardiovascular diseases, and are reported to have several effects on cardiovascular function that may be due to PPARγ-independent signaling events. Select angiotensin receptor blockers (ARBs) interact with and modulate PPARγ activity, thus we hypothesized that a PPARγ agonist may exert physiologic effects via the angiotensin II type 1 A receptor (AT1 A R). In AT1 A R-overexpressing HEK 293 cells, both angiotensin II (Ang II) and the PPARγ agonist troglitazone (Trog) enhanced AT1 A R internalization and recruitment of endogenous β-arrestin1/2 (βarr1/2) to the AT1 A R. A fluorescence assay to measure diacylglycerol (DAG) accumulation showed that although Ang II induced AT1 A R-G q protein-mediated DAG accumulation, Trog had no impact on DAG generation. Trog-mediated recruitment of βarr1/2 was selective to AT1 A R as the response was prevented by an ARB- and Trog-mediated βarr1/2 recruitment to β1-adrenergic receptor (β1AR) was not observed. In isolated mouse cardiomyocytes, Trog increased both % and rate of cell shortening to a similar extent as Ang II, effects which were blocked with an ARB. Additionally, these effects were found to be βarr2-dependent, as cardiomyocytes isolated from βarr2-KO mice showed blunted contractile responses to Trog. These findings show for the first time that the PPARγ agonist Trog acts at the AT1 A R to simultaneously block G q protein activation and induce the recruitment of βarr1/2, which leads to an increase in cardiomyocyte contractility.

  16. Resolving the role of actoymyosin contractility in cell microrheology.

    Directory of Open Access Journals (Sweden)

    Christopher M Hale

    2009-09-01

    Full Text Available Einstein's original description of Brownian motion established a direct relationship between thermally-excited random forces and the transport properties of a submicron particle in a viscous liquid. Recent work based on reconstituted actin filament networks suggests that nonthermal forces driven by the motor protein myosin II can induce large non-equilibrium fluctuations that dominate the motion of particles in cytoskeletal networks. Here, using high-resolution particle tracking, we find that thermal forces, not myosin-induced fluctuating forces, drive the motion of submicron particles embedded in the cytoskeleton of living cells. These results resolve the roles of myosin II and contractile actomyosin structures in the motion of nanoparticles lodged in the cytoplasm, reveal the biphasic mechanical architecture of adherent cells-stiff contractile stress fibers interdigitating in a network at the cell cortex and a soft actin meshwork in the body of the cell, validate the method of particle tracking-microrheology, and reconcile seemingly disparate atomic force microscopy (AFM and particle-tracking microrheology measurements of living cells.

  17. Atomic Structure of Type VI Contractile Sheath from Pseudomonas aeruginosa.

    Science.gov (United States)

    Salih, Osman; He, Shaoda; Planamente, Sara; Stach, Lasse; MacDonald, James T; Manoli, Eleni; Scheres, Sjors H W; Filloux, Alain; Freemont, Paul S

    2018-02-06

    Pseudomonas aeruginosa has three type VI secretion systems (T6SSs), H1-, H2-, and H3-T6SS, each belonging to a distinct group. The two T6SS components, TssB/VipA and TssC/VipB, assemble to form tubules that conserve structural/functional homology with tail sheaths of contractile bacteriophages and pyocins. Here, we used cryoelectron microscopy to solve the structure of the H1-T6SS P. aeruginosa TssB1C1 sheath at 3.3 Å resolution. Our structure allowed us to resolve some features of the T6SS sheath that were not resolved in the Vibrio cholerae VipAB and Francisella tularensis IglAB structures. Comparison with sheath structures from other contractile machines, including T4 phage and R-type pyocins, provides a better understanding of how these systems have conserved similar functions/mechanisms despite evolution. We used the P. aeruginosa R2 pyocin as a structural template to build an atomic model of the TssB1C1 sheath in its extended conformation, allowing us to propose a coiled-spring-like mechanism for T6SS sheath contraction. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Effect of serotonin on small intestinal contractility in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, M.B.; Arif, F.; Gregersen, H.

    2008-01-01

    The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro-duodeno-jejunal contrac......The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro......-duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet......-depleted plasma levels of serotonin, blood pressure, heart rate and electrocardiogram were evaluated. All subjects showed similar results. Intravenous serotonin increased migrating motor complex phase In frequency 3-fold and migrating velocity 2-fold. Intraluminal infusion of serotonin did not change contractile...

  19. Acute exposure to lead increases myocardial contractility independent of hypertension development

    Energy Technology Data Exchange (ETDEWEB)

    Fioresi, M. [Programa de Pós-Graduação em Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Departamento de Enfermagem, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Furieri, L.B.; Simões, M.R.; Ribeiro, R.F. Junior; Meira, E.F.; Fernandes, A.A.; Stefanon, I. [Programa de Pós-Graduação em Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Vassallo, D.V. [Programa de Pós-Graduação em Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Centro de Ciências da Saúde de Vitória, Escola Superior de Ciências da Santa Casa de Misericórdia de Vitória, Vitória, ES (Brazil)

    2013-02-01

    We studied the effects of the acute administration of small doses of lead over time on hemodynamic parameters in anesthetized rats to determine if myocardial contractility changes are dependent or not on the development of hypertension. Male Wistar rats received 320 µg/kg lead acetate iv once, and their hemodynamic parameters were measured for 2 h. Cardiac contractility was evaluated in vitro using left ventricular papillary muscles as were Na{sup +},K{sup +}-ATPase and myosin Ca{sup 2+}-ATPase activities. Lead increased left- (control: 112 ± 3.7 vs lead: 129 ± 3.2 mmHg) and right-ventricular systolic pressures (control: 28 ± 1.2 vs lead: 34 ± 1.2 mmHg) significantly without modifying heart rate. Papillary muscles were exposed to 8 µM lead acetate and evaluated 60 min later. Isometric contractions increased (control: 0.546 ± 0.07 vs lead: 0.608 ± 0.06 g/mg) and time to peak tension decreased (control: 268 ± 13 vs lead: 227 ± 5.58 ms), but relaxation time was unchanged. Post-pause potentiation was similar between groups (n = 6 per group), suggesting no change in sarcoplasmic reticulum activity, evaluated indirectly by this protocol. After 1-h exposure to lead acetate, the papillary muscles became hyperactive in response to a β-adrenergic agonist (10 µM isoproterenol). In addition, post-rest contractions decreased, suggesting a reduction in sarcolemmal calcium influx. The heart samples treated with 8 µM lead acetate presented increased Na{sup +},K{sup +}-ATPase (approximately 140%, P < 0.05 for control vs lead) and myosin ATPase (approximately 30%, P < 0.05 for control vs lead) activity. Our results indicated that acute exposure to low lead concentrations produces direct positive inotropic and lusitropic effects on myocardial contractility and increases the right and left ventricular systolic pressure, thus potentially contributing to the early development of hypertension.

  20. Midlatitude ionospheric F2-layer response to eruptive solar events-caused geomagnetic disturbances over Hungary during the maximum of the solar cycle 24: A case study

    Science.gov (United States)

    Berényi, K. A.; Barta, V.; Kis, Á.

    2018-03-01

    In our study we analyze and compare the response and behavior of the ionospheric F2 and of the sporadic E-layer during three strong (i.e., Dst art digital ionosonde of the Széchenyi István Geophysical Observatory located at midlatitude, Nagycenk, Hungary (IAGA code: NCK, geomagnetic latitude: 46.17° geomagnetic longitude: 98.85°). The local time of the sudden commencement (SC) was used to characterize the type of the ionospheric storm (after Mendillo and Narvaez, 2010). This way two regular positive phase (RPP) ionospheric storms and one no-positive phase (NPP) storm have been analyzed. In all three cases a significant increase in electron density of the foF2 layer can be observed at dawn/early morning (around 6:00 UT, 07:00 LT). Also we can observe the fade-out of the ionospheric layers at night during the geomagnetically disturbed time periods. Our results suggest that the fade-out effect is not connected to the occurrence of the sporadic E-layers.

  1. Maximum power point tracking

    International Nuclear Information System (INIS)

    Enslin, J.H.R.

    1990-01-01

    A well engineered renewable remote energy system, utilizing the principal of Maximum Power Point Tracking can be m ore cost effective, has a higher reliability and can improve the quality of life in remote areas. This paper reports that a high-efficient power electronic converter, for converting the output voltage of a solar panel, or wind generator, to the required DC battery bus voltage has been realized. The converter is controlled to track the maximum power point of the input source under varying input and output parameters. Maximum power point tracking for relative small systems is achieved by maximization of the output current in a battery charging regulator, using an optimized hill-climbing, inexpensive microprocessor based algorithm. Through practical field measurements it is shown that a minimum input source saving of 15% on 3-5 kWh/day systems can easily be achieved. A total cost saving of at least 10-15% on the capital cost of these systems are achievable for relative small rating Remote Area Power Supply systems. The advantages at larger temperature variations and larger power rated systems are much higher. Other advantages include optimal sizing and system monitor and control

  2. Efeitos do propofol na resposta contrátil do miocárdio à dopamina e dobutamina: estudo experimental em corações isolados de ratos Effects of the propofol in the myocardial contractile response to dopamine and dobutamine in isolated rat's heart

    Directory of Open Access Journals (Sweden)

    José Carlos Dorsa Pontes

    1996-12-01

    (95% and CO2 (5%, under constant pressure of 90 cm H2O and at 37ºC. After stabilization of the heart activity during 15 minutes, the control values were obtained. The following groups were considered: Group I (control - 10 hearts perfused only with the Krebs-Hensleit solution during 11 minutes after the control values registration. Group II (dopamine-propofol-dopamine -10 hearts with the following sequency of drug injections and results values registration: dopamine (50 mcg/ml, 1.3 and 5 minutes registration; propofol (25 mcg/ml, 1 minute period registration; dopamine again in the same dosis, 1.3 and 5 minutes values registration. Group III (dobutamine-propofol-dobutamine -10 hearts with the following sequency of drug injections and results values registration: dobutamine (50 mcg/ml, 1.3 and 5 minutes registration: propofol (25 mcg/ml, 1 minute period registration; dobutamine again in the same dose and 1.3 and 5 minutes of registration. RESULTS: In Group I hearts, the dT/dt mean values changed only from 39.57 ± 3.97 to 39.37 ± 3.44 g.seg-1 (p>0.05. In Group II after propofol and dopamine the dT/dt fell 17.61 % (p0.050 in the 1 st min; 3.62% (p0.05 in the 5th min, over the values from isolated dobutamine injections. CONCLUSIONS: The myocardial contractile response to dopamine (50 mcg-ml-1 was partially inhibited; by propofol (25 mcg/ml-1 action was not altered.

  3. Contractility of the guinea pig bladder measured in situ and in vitro

    NARCIS (Netherlands)

    J.M. Groen (Jan); R. van Mastrigt (Ron); J.L.H.R. Bosch (Ruud)

    1994-01-01

    textabstractTo study the relative importance of neurogenic factors in detrusor contractility and to relate a total bladder in vitro contractility model to a previously described bladder wall strip model, active intravesical pressure values were compared in situ and in vitro in eight male guinea

  4. Free radicals in hypoxic rat diaphragm contractility: no role for xanthine oxidase.

    NARCIS (Netherlands)

    Heunks, L.M.A.; Machiels, H.A.; Abreu, R.A. de; Zhu, X.; Heijden, E. van der; Dekhuijzen, P.N.R.

    2001-01-01

    Recent evidence indicates that hypoxia enhances the generation of oxidants. Little is known about the role of free radicals in contractility of the rat diaphragm during hypoxia. We hypothesized that antioxidants improve contractility of the hypoxic rat diaphragm and that xanthine oxidase (XO) is an

  5. Effects of ageing on single muscle fibre contractile function following short-term immobilisation

    DEFF Research Database (Denmark)

    Hvid, Lars G; Ørtenblad, Niels; Aagaard, Per

    2011-01-01

    Very little attention has been given to the combined effect of healthy ageing and short-term disuse on the contractile function of human single muscle fibres. Therefore, the present study investigated the effects of 2 weeks of lower limb cast immobilisation (i.e. disuse) on selected contractile...

  6. Transient impairments in single muscle fibre contractile function after prolonged cycling in elite endurance athletes

    DEFF Research Database (Denmark)

    Hvid, L G; Gejl, Kasper Degn; Bech, R D

    2013-01-01

    Prolonged muscle activity impairs whole-muscle performance and function. However, little is known about the effects of prolonged muscle activity on the contractile function of human single muscle fibres. The purpose of this study was to investigate the effects of prolonged exercise and subsequent...... recovery on the contractile function of single muscle fibres obtained from elite athletes....

  7. Pretreatment with remifentanil protects against the reduced-intestinal contractility related to the ischemia and reperfusion injury in rat

    Directory of Open Access Journals (Sweden)

    Hale Sayan-Ozacmak

    2015-12-01

    Full Text Available BACKGROUND AND OBJECTIVES: Serious functional and structural alterations of gastrointestinal tract are observed in failure of blood supply, leading to gastrointestinal dismotility. Activation of opioid receptors provides cardioprotective effect against ischemia-reperfusion (I/R injury. The aim of the present study was to determine whether or not remifentanil could reduce I/R injury of small intestine. METHODS: Male Wistar Albino rats were subjected to mesenteric ischemia (30 min followed by reperfusion (3 h. Four groups were designed: sham control; remifentanil alone; I/R control; and remifentanil + I/R. Animals in remifentanil + I/R group were subjected to infusion of remifentanil (2 ug kg-1 min-1 for 60 min, half of which started before inducing ischemia. Collecting the ileum tissues, evaluation of damage was based on contractile responses to carbachol, levels of lipid peroxidation and neutrophil infiltration, and observation of histopathological features in intestinal tissue. RESULTS: Following reperfusion, a significant decrease in carbachol-induced contractile response, a remarkable increase in both lipid peroxidation and neutrophil infiltration, and a significant injury in mucosa were observed. An average contractile response of remifentanil + I/R group was significantly different from that of the I/R group. Lipid peroxidation and neutrophil infiltration were also significantly suppressed by the treatment. The tissue samples of the I/R group were grade 4 in histopathological evaluation. In remifentanil + I/R group, on the other hand, the mucosal damage was moderate, staging as grade 1. CONCLUSIONS: The pretreatment with remifentanil can attenuate the intestinal I/R injury at a remarkable degree possibly by lowering lipid peroxidation and leukocyte infiltration.

  8. Detecting cardiac contractile activity in the early mouse embryo using multiple modalities

    Directory of Open Access Journals (Sweden)

    Chiann-mun eChen

    2015-01-01

    Full Text Available The heart is one of the first organs to develop during mammalian embryogenesis. In the mouse, it starts to form shortly after gastrulation, and is derived primarily from embryonic mesoderm. The embryonic heart is unique in having to perform a mechanical contractile function while undergoing complex morphogenetic remodelling. Approaches to imaging the morphogenesis and contractile activity of the developing heart are important in understanding not only how this remodelling is controlled but also the origin of congenital heart defects. Here, we describe approaches for visualising contractile activity in the developing mouse embryo, using brightfield time lapse microscopy and confocal microscopy of calcium transients. We describe an algorithm for enhancing this image data and quantifying contractile activity from it. Finally we describe how atomic force microscopy can be used to record contractile activity prior to it being microscopically visible.

  9. [Role of sialic acid loss in the myocardium in depressing the contractile function of the heart muscle during stress].

    Science.gov (United States)

    Meerson, F Z; Saulia, A I; Gudumak, V S

    1985-01-01

    Under conditions of stress a time-dependent decrease in content of sialic acids was found in adult rats; within 9 hrs of the animal immobilization the sialic acid content was decreased by 40% as compared with controls. At the same time, activities of trypsin and LDHI were increased in blood serum. The data obtained suggest that activation of proteases occurring during the stress led to increased hydrolysis of base components of glycocalyx and to impairment of the cardiomyocyte sarcolemma. These phenomena appear to be responsible for the post-stress deterioration of heart muscle contractile functions.

  10. Exposure to low mercury concentration in vivo impairs myocardial contractile function

    International Nuclear Information System (INIS)

    Furieri, Lorena Barros; Fioresi, Mirian; Junior, Rogerio Faustino Ribeiro; Bartolome, Maria Visitacion; Fernandes, Aurelia Araujo; Cachofeiro, Victoria; Lahera, Vicente; Salaices, Mercedes; Stefanon, Ivanita; Vassallo, Dalton Valentim

    2011-01-01

    Increased cardiovascular risk after mercury exposure has been described but cardiac effects resulting from controlled chronic treatment are not yet well explored. We analyzed the effects of chronic exposure to low mercury concentrations on hemodynamic and ventricular function of isolated hearts. Wistar rats were treated with HgCl 2 (1st dose 4.6 μg/kg, subsequent dose 0.07 μg/kg/day, im, 30 days) or vehicle. Mercury treatment did not affect blood pressure (BP) nor produced cardiac hypertrophy or changes of myocyte morphometry and collagen content. This treatment: 1) in vivo increased left ventricle end diastolic pressure (LVEDP) without changing left ventricular systolic pressure (LVSP) and heart rate; 2) in isolated hearts reduced LV isovolumic systolic pressure and time derivatives, and β-adrenergic response; 3) increased myosin ATPase activity; 4) reduced Na + -K + ATPase (NKA) activity; 5) reduced protein expression of SERCA and phosphorylated phospholamban on serine 16 while phospholamban expression increased; as a consequence SERCA/phospholamban ratio reduced; 6) reduced sodium/calcium exchanger (NCX) protein expression and α-1 isoform of NKA, whereas α-2 isoform of NKA did not change. Chronic exposure for 30 days to low concentrations of mercury does not change BP, heart rate or LVSP but produces small but significant increase of LVEDP. However, in isolated hearts mercury treatment promoted contractility dysfunction as a result of the decreased NKA activity, reduction of NCX and SERCA and increased PLB protein expression. These findings offer further evidence that mercury chronic exposure, even at small concentrations, is an environmental risk factor affecting heart function. - Highlights: → Unchanges blood pressure, heart rate, systolic pressure. → Increases end diastolic pressure. → Promotes cardiac contractility dysfunction. → Decreases NKA activity, NCX and SERCA, increases PLB protein expression. → Small concentrations constitutes

  11. Maximum entropy methods

    International Nuclear Information System (INIS)

    Ponman, T.J.

    1984-01-01

    For some years now two different expressions have been in use for maximum entropy image restoration and there has been some controversy over which one is appropriate for a given problem. Here two further entropies are presented and it is argued that there is no single correct algorithm. The properties of the four different methods are compared using simple 1D simulations with a view to showing how they can be used together to gain as much information as possible about the original object. (orig.)

  12. Repeated stimulation, inter-stimulus interval and inter-electrode distance alters muscle contractile properties as measured by Tensiomyography.

    Directory of Open Access Journals (Sweden)

    Hannah V Wilson

    Full Text Available The influence of methodological parameters on the measurement of muscle contractile properties using Tensiomyography (TMG has not been published.To investigate the; (1 reliability of stimulus amplitude needed to elicit maximum muscle displacement (Dm, (2 effect of changing inter-stimulus interval on Dm (using a fixed stimulus amplitude and contraction time (Tc, (3 the effect of changing inter-electrode distance on Dm and Tc.Within subject, repeated measures.10 participants for each objective.Dm and Tc of the rectus femoris, measured using TMG.The coefficient of variance (CV and the intra-class correlation (ICC of stimulus amplitude needed to elicit maximum Dm was 5.7% and 0.92 respectively. Dm was higher when using an inter-electrode distance of 7cm compared to 5cm [P = 0.03] and when using an inter-stimulus interval of 10s compared to 30s [P = 0.017]. Further analysis of inter-stimulus interval data, found that during 10 repeated stimuli Tc became faster after the 5th measure when compared to the second measure [P<0.05]. The 30s inter-stimulus interval produced the most stable Tc over 10 measures compared to 10s and 5s respectively.Our data suggest that the stimulus amplitude producing maximum Dm of the rectus femoris is reliable. Inter-electrode distance and inter-stimulus interval can significantly influence Dm and/ or Tc. Our results support the use of a 30s inter-stimulus interval over 10s or 5s. Future studies should determine the influence of methodological parameters on muscle contractile properties in a range of muscles.

  13. Repeated stimulation, inter-stimulus interval and inter-electrode distance alters muscle contractile properties as measured by Tensiomyography

    Science.gov (United States)

    Johnson, Mark I.; Francis, Peter

    2018-01-01

    Context The influence of methodological parameters on the measurement of muscle contractile properties using Tensiomyography (TMG) has not been published. Objective To investigate the; (1) reliability of stimulus amplitude needed to elicit maximum muscle displacement (Dm), (2) effect of changing inter-stimulus interval on Dm (using a fixed stimulus amplitude) and contraction time (Tc), (3) the effect of changing inter-electrode distance on Dm and Tc. Design Within subject, repeated measures. Participants 10 participants for each objective. Main outcome measures Dm and Tc of the rectus femoris, measured using TMG. Results The coefficient of variance (CV) and the intra-class correlation (ICC) of stimulus amplitude needed to elicit maximum Dm was 5.7% and 0.92 respectively. Dm was higher when using an inter-electrode distance of 7cm compared to 5cm [P = 0.03] and when using an inter-stimulus interval of 10s compared to 30s [P = 0.017]. Further analysis of inter-stimulus interval data, found that during 10 repeated stimuli Tc became faster after the 5th measure when compared to the second measure [P<0.05]. The 30s inter-stimulus interval produced the most stable Tc over 10 measures compared to 10s and 5s respectively. Conclusion Our data suggest that the stimulus amplitude producing maximum Dm of the rectus femoris is reliable. Inter-electrode distance and inter-stimulus interval can significantly influence Dm and/ or Tc. Our results support the use of a 30s inter-stimulus interval over 10s or 5s. Future studies should determine the influence of methodological parameters on muscle contractile properties in a range of muscles. PMID:29451885

  14. Cardiac contractility, central haemodynamics and blood pressure regulation during semistarvation

    DEFF Research Database (Denmark)

    Stokholm, K H; Breum, L; Astrup, A

    1991-01-01

    pressure (BP) declined. The fall in BP was caused by the reduction in cardiac output as the total peripheral resistance was unchanged. Finally, the decline in total blood volume was not significant. These findings together with a reduction in heart rate indicated that a reduced sympathetic tone via......Eight obese patients were studied before and after 2 weeks of treatment by a very-low-calorie diet (VLCD). Cardiac output and central blood volume (pulmonary blood volume and left atrial volume) were determined by indicator dilution (125I-albumin) and radionuclide angiocardiography (first pass...... and equilibrium technique by [99Tcm]red blood cells). Cardiac output decreased concomitantly with the reduction in oxygen uptake as the calculated systemic arteriovenous difference of oxygen was unaltered. There were no significant decreases in left ventricular contractility indices, i.e. the ejection fraction...

  15. Matrix elasticity regulates the optimal cardiac myocyte shape for contractility

    Science.gov (United States)

    McCain, Megan L.; Yuan, Hongyan; Pasqualini, Francesco S.; Campbell, Patrick H.

    2014-01-01

    Concentric hypertrophy is characterized by ventricular wall thickening, fibrosis, and decreased myocyte length-to-width aspect ratio. Ventricular thickening is considered compensatory because it reduces wall stress, but the functional consequences of cell shape remodeling in this pathological setting are unknown. We hypothesized that decreases in myocyte aspect ratio allow myocytes to maximize contractility when the extracellular matrix becomes stiffer due to conditions such as fibrosis. To test this, we engineered neonatal rat ventricular myocytes into rectangles mimicking the 2-D profiles of healthy and hypertrophied myocytes on hydrogels with moderate (13 kPa) and high (90 kPa) elastic moduli. Actin alignment was unaffected by matrix elasticity, but sarcomere content was typically higher on stiff gels. Microtubule polymerization was higher on stiff gels, implying increased intracellular elastic modulus. On moderate gels, myocytes with moderate aspect ratios (∼7:1) generated the most peak systolic work compared with other cell shapes. However, on stiffer gels, low aspect ratios (∼2:1) generated the most peak systolic work. To compare the relative contributions of intracellular vs. extracellular elasticity to contractility, we developed an analytical model and used our experimental data to fit unknown parameters. Our model predicted that matrix elasticity dominates over intracellular elasticity, suggesting that the extracellular matrix may potentially be a more effective therapeutic target than microtubules. Our data and model suggest that myocytes with lower aspect ratios have a functional advantage when the elasticity of the extracellular matrix decreases due to conditions such as fibrosis, highlighting the role of the extracellular matrix in cardiac disease. PMID:24682394

  16. Usefulness of BMIPP SPECT to evaluate myocardial viability, contractile reserve and coronary stenotic progression after reperfusion in acute myocardial infarction

    International Nuclear Information System (INIS)

    Katsunuma, Eita; Kurokawa, Shingo; Takahashi, Motoi; Fukuda, Naoto; Kurosawa, Toshiro; Izumi, Tohru

    2001-01-01

    Using combined 123 I-BMIPP (BMIPP), 201 Tl (Tl) and 99m Tc-PYP (PYP) myocardial SPECT imaging, risk areas of acute myocardial infarction were documented in the acute stage, and then these images were evaluated for how well they reflected muscle viability, contractile reserve and coronary stenotic progression subsequent to reperfusion therapy. Patients who only experienced a first attack of myocardial infarction were enrolled. In total, 36 cases who had had the occluded artery successfully reperfused were examined during the past year. They had no significant vessel disease except for the culprit single artery. The patients were comprised of 32 men and 4 women. The mean age was 59.5 years. All patients underwent coronary angiography and left ventricular (LV) angiography in the emergency room. BMIPP/Tl and PYP myocardial SPECT were conducted in the acute stage and chronic stage. In the chronic stage LV angiography was repeated to assess the improvement of LV wall motion. The response to postextrasystolic potentiation (PESP) testing was performed to estimate myocardial contractile reserve. The risk area of acute myocardial infarction (AMI) was documented by reduced BMIPP accumulation. The size of reduced BMIPP accumulation was larger than that of PYP accumulation. A BMIPP/Tl discrepancy and PYP accumulation were documented to assess myocardial viability. Both improvement in LV wall motion and augmentation of PESP response were more closely related to a BMIPP/Tl discrepancy in the presence or absence of PYP accumulation. Therefore, it would be possible to evaluate myocardial viability and contractile reserve by the BMIPP/Tl discrepancy. In patients with good viability, it is important to predict whether there is coronary stenotic progression or not. In this study, we demonstrated that most patients with improved BMIPP images had no significant progression at the site of intervention. Serial observation of BMIPP images from the acute stage to the chronic stage might

  17. AB286. SPR-13 Sex differences and participation of Toll-like receptor 4 to rat bladder contractile function

    Science.gov (United States)

    Szasz, Theodora; Burgess, Beth; Webb, R. Clinton

    2016-01-01

    Objective Innate immune mechanisms have been implicated in the pathophysiology of chronic sterile conditions such as hypertension and diabetes. We have recently demonstrated that Toll-like receptor 4 (TLR4) activation by endogenous molecules such as high mobility group box-1 (HMGB1) contributes to hypertrophy and hypercontractility in diabetic bladder dysfunction. It has been reported that women have a higher frequency of overactive bladder symptoms, while men have higher detrusor overactivity. We hypothesized that sex differences in the contribution of TLR4 to bladder contraction may underlie the sex differences observed clinically. Methods Female and male rat bladder contractile responses to carbacholine (CCh) and electrical field stimulation (EFS) were measured in the presence and absence of TLR4 inhibitor CLI-095 and in the presence and absence of urothelium. Results We observed that contractile responses to both CCh and EFS were higher in the male than the female bladder segments in both the presence and absence of urothelium [CCh Emax (mN): male + urothelium =84.3±1.2, male – urothelium =83.7±1.2, female + urothelium =49.8±0.8, female – urothelium =59.2±1.1; EFS 32 Hz (mN): male + urothelium= 84.9±7.1, male – urothelium =66.8±5.2, female + urothelium =57.8±5.9, female – urothelium =54.5±3.5]. Incubation of bladder segments with the TLR4 inhibitor CLI-095 significantly decreased contractile responses to both CCh and EFS in both sexes, irrespective of the presence of urothelium [CCh Emax (mN): male + urothelium =91.1±0.8, male – urothelium =75.4±1.8, female + urothelium =42.9±1.1, female – urothelium =52.5±1.1; EFS 32 Hz (mN): male + urothelium =80.8±7.9, male – urothelium =59.6±10.6, female + urothelium =43.3±2.6, female – urothelium =46.4±1.9]. Conclusions Our data suggest that although there are sex differences in the contractile function of the rat bladder in basal conditions, the participation of TLR4 to bladder contraction

  18. Maximum Entropy Fundamentals

    Directory of Open Access Journals (Sweden)

    F. Topsøe

    2001-09-01

    Full Text Available Abstract: In its modern formulation, the Maximum Entropy Principle was promoted by E.T. Jaynes, starting in the mid-fifties. The principle dictates that one should look for a distribution, consistent with available information, which maximizes the entropy. However, this principle focuses only on distributions and it appears advantageous to bring information theoretical thinking more prominently into play by also focusing on the "observer" and on coding. This view was brought forward by the second named author in the late seventies and is the view we will follow-up on here. It leads to the consideration of a certain game, the Code Length Game and, via standard game theoretical thinking, to a principle of Game Theoretical Equilibrium. This principle is more basic than the Maximum Entropy Principle in the sense that the search for one type of optimal strategies in the Code Length Game translates directly into the search for distributions with maximum entropy. In the present paper we offer a self-contained and comprehensive treatment of fundamentals of both principles mentioned, based on a study of the Code Length Game. Though new concepts and results are presented, the reading should be instructional and accessible to a rather wide audience, at least if certain mathematical details are left aside at a rst reading. The most frequently studied instance of entropy maximization pertains to the Mean Energy Model which involves a moment constraint related to a given function, here taken to represent "energy". This type of application is very well known from the literature with hundreds of applications pertaining to several different elds and will also here serve as important illustration of the theory. But our approach reaches further, especially regarding the study of continuity properties of the entropy function, and this leads to new results which allow a discussion of models with so-called entropy loss. These results have tempted us to speculate over

  19. Probable maximum flood control

    International Nuclear Information System (INIS)

    DeGabriele, C.E.; Wu, C.L.

    1991-11-01

    This study proposes preliminary design concepts to protect the waste-handling facilities and all shaft and ramp entries to the underground from the probable maximum flood (PMF) in the current design configuration for the proposed Nevada Nuclear Waste Storage Investigation (NNWSI) repository protection provisions were furnished by the United States Bureau of Reclamation (USSR) or developed from USSR data. Proposed flood protection provisions include site grading, drainage channels, and diversion dikes. Figures are provided to show these proposed flood protection provisions at each area investigated. These areas are the central surface facilities (including the waste-handling building and waste treatment building), tuff ramp portal, waste ramp portal, men-and-materials shaft, emplacement exhaust shaft, and exploratory shafts facility

  20. Introduction to maximum entropy

    International Nuclear Information System (INIS)

    Sivia, D.S.

    1988-01-01

    The maximum entropy (MaxEnt) principle has been successfully used in image reconstruction in a wide variety of fields. We review the need for such methods in data analysis and show, by use of a very simple example, why MaxEnt is to be preferred over other regularizing functions. This leads to a more general interpretation of the MaxEnt method, and its use is illustrated with several different examples. Practical difficulties with non-linear problems still remain, this being highlighted by the notorious phase problem in crystallography. We conclude with an example from neutron scattering, using data from a filter difference spectrometer to contrast MaxEnt with a conventional deconvolution. 12 refs., 8 figs., 1 tab

  1. Solar maximum observatory

    International Nuclear Information System (INIS)

    Rust, D.M.

    1984-01-01

    The successful retrieval and repair of the Solar Maximum Mission (SMM) satellite by Shuttle astronauts in April 1984 permitted continuance of solar flare observations that began in 1980. The SMM carries a soft X ray polychromator, gamma ray, UV and hard X ray imaging spectrometers, a coronagraph/polarimeter and particle counters. The data gathered thus far indicated that electrical potentials of 25 MeV develop in flares within 2 sec of onset. X ray data show that flares are composed of compressed magnetic loops that have come too close together. Other data have been taken on mass ejection, impacts of electron beams and conduction fronts with the chromosphere and changes in the solar radiant flux due to sunspots. 13 references

  2. Introduction to maximum entropy

    International Nuclear Information System (INIS)

    Sivia, D.S.

    1989-01-01

    The maximum entropy (MaxEnt) principle has been successfully used in image reconstruction in a wide variety of fields. The author reviews the need for such methods in data analysis and shows, by use of a very simple example, why MaxEnt is to be preferred over other regularizing functions. This leads to a more general interpretation of the MaxEnt method, and its use is illustrated with several different examples. Practical difficulties with non-linear problems still remain, this being highlighted by the notorious phase problem in crystallography. He concludes with an example from neutron scattering, using data from a filter difference spectrometer to contrast MaxEnt with a conventional deconvolution. 12 refs., 8 figs., 1 tab

  3. Functional Maximum Autocorrelation Factors

    DEFF Research Database (Denmark)

    Larsen, Rasmus; Nielsen, Allan Aasbjerg

    2005-01-01

    MAF outperforms the functional PCA in concentrating the interesting' spectra/shape variation in one end of the eigenvalue spectrum and allows for easier interpretation of effects. Conclusions. Functional MAF analysis is a useful methods for extracting low dimensional models of temporally or spatially......Purpose. We aim at data where samples of an underlying function are observed in a spatial or temporal layout. Examples of underlying functions are reflectance spectra and biological shapes. We apply functional models based on smoothing splines and generalize the functional PCA in......\\verb+~+\\$\\backslash\\$cite{ramsay97} to functional maximum autocorrelation factors (MAF)\\verb+~+\\$\\backslash\\$cite{switzer85,larsen2001d}. We apply the method to biological shapes as well as reflectance spectra. {\\$\\backslash\\$bf Methods}. MAF seeks linear combination of the original variables that maximize autocorrelation between...

  4. Regularized maximum correntropy machine

    KAUST Repository

    Wang, Jim Jing-Yan; Wang, Yunji; Jing, Bing-Yi; Gao, Xin

    2015-01-01

    In this paper we investigate the usage of regularized correntropy framework for learning of classifiers from noisy labels. The class label predictors learned by minimizing transitional loss functions are sensitive to the noisy and outlying labels of training samples, because the transitional loss functions are equally applied to all the samples. To solve this problem, we propose to learn the class label predictors by maximizing the correntropy between the predicted labels and the true labels of the training samples, under the regularized Maximum Correntropy Criteria (MCC) framework. Moreover, we regularize the predictor parameter to control the complexity of the predictor. The learning problem is formulated by an objective function considering the parameter regularization and MCC simultaneously. By optimizing the objective function alternately, we develop a novel predictor learning algorithm. The experiments on two challenging pattern classification tasks show that it significantly outperforms the machines with transitional loss functions.

  5. Regularized maximum correntropy machine

    KAUST Repository

    Wang, Jim Jing-Yan

    2015-02-12

    In this paper we investigate the usage of regularized correntropy framework for learning of classifiers from noisy labels. The class label predictors learned by minimizing transitional loss functions are sensitive to the noisy and outlying labels of training samples, because the transitional loss functions are equally applied to all the samples. To solve this problem, we propose to learn the class label predictors by maximizing the correntropy between the predicted labels and the true labels of the training samples, under the regularized Maximum Correntropy Criteria (MCC) framework. Moreover, we regularize the predictor parameter to control the complexity of the predictor. The learning problem is formulated by an objective function considering the parameter regularization and MCC simultaneously. By optimizing the objective function alternately, we develop a novel predictor learning algorithm. The experiments on two challenging pattern classification tasks show that it significantly outperforms the machines with transitional loss functions.

  6. Progesterone Metabolites Produced by Cytochrome P450 3A Modulate Uterine Contractility in a Murine Model

    Science.gov (United States)

    Patil, Avinash S.; Swamy, Geeta K.; Murtha, Amy P.; Heine, R. Phillips; Zheng, Xiaomei; Grotegut, Chad A.

    2015-01-01

    Objective: We seek to characterize the effect of progesterone metabolites on spontaneous and oxytocin-induced uterine contractility. Study Design: Spontaneous contractility was studied in mouse uterine horns after treatment with progesterone, 2α-hydroxyprogesterone, 6β-hydroxyprogesterone (6β-OHP), 16α-hydroxyprogesterone (16α-OHP), or 17-hydroxyprogesterone caproate (17-OHPC) at 10−9 to 10−6 mol/L. Uterine horns were exposed to progestins (10−6 mol/L), followed by increasing concentrations of oxytocin (1-100 nmol/L) to study oxytocin-induced contractility. Contraction parameters were compared for each progestin and matched vehicle control using repeated measures 2-way analysis of variance. In vitro metabolism of progesterone by recombinant cytochrome P450 3A (CYP3A) microsomes (3A5, 3A5, and 3A7) identified major metabolites. Results: Oxytocin-induced contractile frequency was decreased by 16α-OHP (P = .03) and increased by 6β-OHP (P = .05). Progesterone and 17-OHPC decreased oxytocin-induced contractile force (P = .02 and P = .04, respectively) and frequency (P = .02 and P = .03, respectively). Only progesterone decreased spontaneous contractile force (P = .02). Production of 16α-OHP and 6β-OHP metabolites were confirmed in all CYP3A isoforms tested. Conclusion: Progesterone metabolites produced by maternal or fetal CYP3A enzymes influence uterine contractility. PMID:26037300

  7. Controlled chaos: three-dimensional kinematics, fiber histochemistry, and muscle contractile dynamics of autotomized lizard tails.

    Science.gov (United States)

    Higham, Timothy E; Lipsett, Kathryn R; Syme, Douglas A; Russell, Anthony P

    2013-01-01

    The ability to shed an appendage occurs in both vertebrates and invertebrates, often as a tactic to avoid predation. The tails of lizards, unlike most autotomized body parts of animals, exhibit complex and vigorous movements once disconnected from the body. Despite the near ubiquity of autotomy across groups of lizards and the fact that this is an extraordinary event involving the self-severing of the spinal cord, our understanding of why and how tails move as they do following autotomy is sparse. We herein explore the histochemistry and physiology of the tail muscles of the leopard gecko (Eublepharis macularius), a species that exhibits vigorous and variable tail movements following autotomy. To confirm that the previously studied tail movements of this species are generally representative of geckos and therefore suitable for in-depth muscle studies, we quantified the three-dimensional kinematics of autotomized tails in three additional species. The movements of the tails of all species were generally similar and included jumps, flips, and swings. Our preliminary analyses suggest that some species of gecko exhibit short but high-frequency movements, whereas others exhibit larger-amplitude but lower-frequency movements. We then compared the ATPase and oxidative capacity of muscle fibers and contractile dynamics of isolated muscle bundles from original tails, muscle from regenerate tails, and fast fibers from an upper limb muscle (iliofibularis) of the leopard gecko. Histochemical analysis revealed that more than 90% of the fibers in original and regenerate caudal muscles had high ATPase but possessed a superficial layer of fibers with low ATPase and high oxidative capacity. We found that contraction kinetics, isometric force, work, power output, and the oscillation frequency at which maximum power was generated were lowest in the original tail, followed by the regenerate tail and then the fast fibers of the iliofibularis. Muscle from the original tail exhibited

  8. Global and Regional Left Ventricular Contractile Impairment In Patients With Wolff-Parkinson-White Syndrome

    Directory of Open Access Journals (Sweden)

    Sony Jacob

    2009-07-01

    Full Text Available Background: To assess regional systolic function and global contractile function in patients with WPW Syndrome.Method: Eleven cases with manifest Wolff-Parkinson-White (WPW syndrome in sinus rhythm were compared to 11 age matched controls. 2D strain analysis was performed and peak segmental radial strain (pRS values obtained from basal ventricular parasternal short-axis images (70 ± 5 frames/sec using a dedicated software package. Heterogeneity of radial strain pattern in six circumferential basal left ventricular segments was measured in terms of standard deviations of peak RS (SDpRS or range (difference between maximum and minimum peak RS i.e. RangepRS. Spectral Doppler (continuous wave measurements were acquired through the left ventricular outflow tract to determine Pre Ejection Period (PEP, Left Ventricular Ejection Time (LVET and measures of left ventricular systolic performance. Results: LV segmental radial strain was profoundly heterogeneous in WPW cases in contrast to fairly homogenous strain pattern in normal subjects. Wide SDpRS values 17.5 ± 8.9 vs 3.3 ± 1.4, p<0.001 and RangepRS 42.7 ± 20.8 vs.8.5 ± 3.6 , p<0.001 were observed among WPW and healthy subjects respectively. PEP (132.4 ± 14.7 vs 4.7 ± 0.5ms, p<0.001 and corrected PEP (76.1 ± 8.0 vs 2.7 ± 0.4ms, p<0.001 were significantly longer in WPW patients compared to controls. The PEP/LVET ratio was also significantly greater in WPW cohort (0.49 ± 0.04 vs. 0.28 ± 0.05, p <0.001 suggesting global systolic dysfunction. Conclusion: Patients with manifest preexcitation (predominantly those with right-sided pathways have regional and global contractile dysfunction resulting from aberrant impulse propagation inherent to the preexcited state.

  9. Solar maximum mission

    International Nuclear Information System (INIS)

    Ryan, J.

    1981-01-01

    By understanding the sun, astrophysicists hope to expand this knowledge to understanding other stars. To study the sun, NASA launched a satellite on February 14, 1980. The project is named the Solar Maximum Mission (SMM). The satellite conducted detailed observations of the sun in collaboration with other satellites and ground-based optical and radio observations until its failure 10 months into the mission. The main objective of the SMM was to investigate one aspect of solar activity: solar flares. A brief description of the flare mechanism is given. The SMM satellite was valuable in providing information on where and how a solar flare occurs. A sequence of photographs of a solar flare taken from SMM satellite shows how a solar flare develops in a particular layer of the solar atmosphere. Two flares especially suitable for detailed observations by a joint effort occurred on April 30 and May 21 of 1980. These flares and observations of the flares are discussed. Also discussed are significant discoveries made by individual experiments

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

    Science.gov (United States)

    Price, Kari L; Rose, Lesilee S

    2017-09-01

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

  11. Alterations in serotonin receptor-induced contractility of bovine lateral saphenous vein in cattle grazing endophyte-infected tall fescue.

    Science.gov (United States)

    Klotz, J L; Brown, K R; Xue, Y; Matthews, J C; Boling, J A; Burris, W R; Bush, L P; Strickland, J R

    2012-02-01

    As part of a 2-yr study documenting the physiologic impact of grazing endophyte-infected tall fescue on growing cattle, 2 experiments were conducted to characterize and evaluate effects of grazing 2 levels of toxic endophyte-infected tall fescue pastures on vascular contractility and serotonin receptors. Experiment 1 examined vasoconstrictive activities of 5-hydroxytryptamine (5HT), α-methylserotonin (ME5HT; a 5HT(2) receptor agonist), d-lysergic acid (LSA), and ergovaline (ERV) on lateral saphenous veins collected from steers immediately removed from a high-endophyte-infected tall fescue pasture (HE) or a low-endophyte-infected mixed-grass (LE) pasture. Using the same pastures, Exp. 2 evaluated effects of grazing 2 levels of toxic endophyte-infected tall fescue on vasoconstrictive activities of (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), BW 723C86 (BW7), CGS-12066A (CGS), and 5-carboxamidotryptamine hemiethanolate maleate (5CT), agonists for 5HT(2A),( 2B), 5HT(1B), and 5HT(7) receptors, respectively. One-half of the steers in Exp. 2 were slaughtered immediately after removal from pasture, and the other one-half were fed finishing diets for >91 d before slaughter. For Exp. 1, maximal contractile intensities were greater (P 91 d. Experiment 1 demonstrated that grazing of HE pastures for 89 to 105 d induces functional alterations in blood vessels, as evidenced by reduced contractile capacity and altered serotonergic receptor activity. Experiment 2 demonstrated that grazing HE pastures alters vascular responses, which may be mediated through altered serotonin receptor activities, and these alterations may be ameliorated by the removal of ergot alkaloid exposure as demonstrated by the absence of differences in finished steers.

  12. α,β-Unsaturated aldehyde pollutant acrolein suppresses cardiomyocyte contractile function: Role of TRPV1 and oxidative stress.

    Science.gov (United States)

    Wu, Zhenbiao; He, Emily Y; Scott, Glenda I; Ren, Jun

    2015-01-01

    Air pollution is associated with an increased prevalence of heart disease and is known to trigger a proinflammatory response via stimulation of transient receptor potential vanilloid cation channels (TRPV1, also known as the capsaicin receptor). This study was designed to examine the effect of acrolein, an essential α,β-unsaturated aldehyde pollutant, on myocardial contractile function and the underlying mechanism involved with a focus on TRPV1 and oxidative stress. Cardiomyocyte mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix MyoCam® system including peak shortening (PS), maximal velocity of shortening/relengthening (± dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR90 ), fura-2 fluorescence intensity (FFI) and intracellular Ca(2+) decay. Changes in apoptosis and TRPV1 were evaluated using Western blot analysis. The degree of oxidative stress was assessed using the ratio between reduced and oxidized glutathione. Results obtained revealed that exposure of cardiomyocytes to acrolein acutely compromised contractile and intracellular Ca(2+) properties including depressed PS, ± dL/dt and ΔFFI, as well as prolonged TR90 and intracellular Ca(2+) decay. In addition, acrolein exposure upregulated TRPV1 associated with an increase in both apoptosis and oxidative stress. However, the acrolein-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, as well as apoptosis (as evidenced by Bcl-2, Bax, FasL, Caspase-3 and -8), were negated by the reactive oxygen species (ROS) scavenger glutathione or the TRPV1 antagonist capsazepine. Collectively these data suggest that the α,β-unsaturated aldehyde pollutant acrolein may play a role in the pathogenesis and sequelae of air pollution-induced heart disease via a TRPV1- and oxidative stress-dependent mechanism. © 2013 Wiley Periodicals, Inc.

  13. Removal of urothelium affects bladder contractility and release of ATP but not release of NO in rat urinary bladder

    Directory of Open Access Journals (Sweden)

    Boone Timothy B

    2010-05-01

    Full Text Available Abstract Background The objective of our work was to investigate both the contractile function and the release of ATP and NO from strips of bladder tissue after removal of the urothelium. Methods The method of removal was a gentle swabbing motion rather than a sharp surgical cutting to separate the urothelium from the smooth muscle. The contractile response and ATP and NO release were measured in intact as well as on swabbed preparations. The removal of the urothelial layer was affirmed microscopically. Results After the swabbing, the smaller contractions were evoked by electrical as well as by chemical stimulation (50 μM carbachol or 50 μM α, β meATP. Electrical stimulation, carbachol and substance P (5 μM evoked lower release of ATP in the swabbed strips than in intact strips. Although release of NO evoked by electrical stimulation or substance P was not changed, release of NO evoked by carbachol was significantly less in the swabbed preparations. Conclusion Since swabbing removes only the urothelium, the presence of the suburothelial layer may explain the difference between our findings and those of others who found an increase in contractility. Evoked release of ATP is reduced in swabbed strips, indicating that ATP derives solely from the urothelium. On the other hand, electrical stimulation and substance P evoke identical degrees of NO release in both intact and swabbed preparations, suggesting that NO can be released from the suburothelium. Conversely, carbachol-induced release of NO is lower in swabbed strips, implying that the cholinergic receptors (muscarinic or nicotinic are located in the upper layer of the urothelium.

  14. Differences in Contractile Function of Myofibrils within Human Embryonic Stem Cell-Derived Cardiomyocytes vs. Adult Ventricular Myofibrils Are Related to Distinct Sarcomeric Protein Isoforms

    Directory of Open Access Journals (Sweden)

    Bogdan Iorga

    2018-01-01

    Full Text Available 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

  15. Scintillation counter, maximum gamma aspect

    International Nuclear Information System (INIS)

    Thumim, A.D.

    1975-01-01

    A scintillation counter, particularly for counting gamma ray photons, includes a massive lead radiation shield surrounding a sample-receiving zone. The shield is disassembleable into a plurality of segments to allow facile installation and removal of a photomultiplier tube assembly, the segments being so constructed as to prevent straight-line access of external radiation through the shield into radiation-responsive areas. Provisions are made for accurately aligning the photomultiplier tube with respect to one or more sample-transmitting bores extending through the shield to the sample receiving zone. A sample elevator, used in transporting samples into the zone, is designed to provide a maximum gamma-receiving aspect to maximize the gamma detecting efficiency. (U.S.)

  16. [The cardioprotective action of the anticonvulsant preparation sodium valproate in disorders of cardiac contractile function caused by acute myocardial infarct in rats].

    Science.gov (United States)

    Belkina, L M; Korchazhkina, N B; Kamskova, Iu G; Fomin, N A

    1997-01-01

    The preventive and therapeutical effects of sodium valproate (SV), 200 mg/kg, on cardiac contractile disorders (developed pressure, rate-pressure products, dp/dt) were studied in rats having 2-day myocardial infarction (MI). The postinfarction rather than preinfarction use of SV substantially restricted the depressed resting left ventricular function. Given by two regimens, SV increased cardiac resistance to the maximum isometric load induced by 60-sec ligation of the ascending aorta. The cardioprotective effect of the drug was shown due to its positive chronotropic action rather than its inotropic one. Thus, SV may be used as an effective drug for the prevention and treatment of postinfarct cardiac dysfunctions.

  17. Maximum-Likelihood Detection Of Noncoherent CPM

    Science.gov (United States)

    Divsalar, Dariush; Simon, Marvin K.

    1993-01-01

    Simplified detectors proposed for use in maximum-likelihood-sequence detection of symbols in alphabet of size M transmitted by uncoded, full-response continuous phase modulation over radio channel with additive white Gaussian noise. Structures of receivers derived from particular interpretation of maximum-likelihood metrics. Receivers include front ends, structures of which depends only on M, analogous to those in receivers of coherent CPM. Parts of receivers following front ends have structures, complexity of which would depend on N.

  18. Quantifying esophagogastric junction contractility with a novel HRM topographic metric, the EGJ-Contractile Integral: normative values and preliminary evaluation in PPI non-responders.

    Science.gov (United States)

    Nicodème, F; Pipa-Muniz, M; Khanna, K; Kahrilas, P J; Pandolfino, J E

    2014-03-01

    Despite its obvious pathophysiological relevance, the clinical utility of measures of esophagogastric junction (EGJ) contractility is unsubstantiated. High-resolution manometry (HRM) may improve upon this with its inherent ability to integrate the magnitude of contractility over time and length of the EGJ. This study aimed to develop a novel HRM metric summarizing EGJ contractility and test its ability distinguish among subgroups of proton pump inhibitor non-responders (PPI-NRs). 75 normal controls and 88 PPI-NRs were studied. All underwent HRM. PPI-NRs underwent pH-impedance monitoring on PPI therapy scored in terms of acid exposure, number of reflux events, and reflux-symptom correlation and grouped as meeting all criteria, some criteria, or no criteria of abnormality. Control HRM studies were used to establish normal values for candidate EGJ contractility metrics, which were then compared in their ability to differentiate among PPI-NR subgroups. The EGJ contractile integral (EGJ-CI), a metric integrating contractility across the EGJ for three respiratory cycles, best distinguished the All Criteria PPI-NR subgroup from controls and other PPI-NR subgroups. Normal values (median, [IQR]) for this measure were 39 mmHg-cm [25-55 mmHg-cm]. The correlation between the EGJ-CI and a previously proposed metric, the lower esophageal sphincter-pressure integral, that used a fixed 10 s time frame and an atmospheric as opposed to gastric pressure reference was weak. Among HRM metrics tested, the EGJ-CI was best in distinguishing PPI-NRs meeting all criteria of abnormality on pH-impedance testing. Future prospective studies are required to explore its utility in management of broader groups of gastroesophageal reflux disease patients. © 2013 John Wiley & Sons Ltd.

  19. Adipose-derived stem cells inhibit the contractile myofibroblast in Dupuytren's disease.

    NARCIS (Netherlands)

    Verhoekx, J.S.; Mudera, V.; Walbeehm, E.T.; Hovius, S.E.

    2013-01-01

    BACKGROUND: In an attempt to provide minimally invasive treatment for Dupuytren's disease, percutaneous disruption of the affected tissue followed by lipografting is being tested. Contractile myofibroblasts drive this fibroproliferative disorder, whereas stem cells have recently been implicated in

  20. Considerations for Contractile Electroactive Polymeric Materials and Actuators

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, Lenore; Erickson, Carl J.; Meixler, Lewis D.; Ascione, George; Gentile, Charles A.; Tilson, Charles; Bernasek, Stephen L.; Abelev, Esta

    2009-06-16

    Ras Labs produces electroactive polymer (EAP) based materials and actuators that bend, swell, ripple and now contract (new development) with low electric input. This is an important attribute because of the ability of contraction to produce life-like motion. The mechanism of contraction is not well understood. Radionuclide-labeled experiments were conducted to follow the movement of electrolytes and water in these EAPs when activated. Extreme temperature experiments were performed on the contractile EAPs with very favorable results. One of the biggest challenges in developing these actuators, however, is the electrode-EAP interface because of the pronounced movement of the EAP. Plasma treatments of metallic electrodes were investigated in order to improve the attachment of the embedded electrodes to the EAP material. Surface analysis, adhesive testing, and mechanical testing were conducted to test metal surfaces and metal-polymer interfaces. The nitrogen plasma treatment of titanium produced a strong metal-polymer interface; however, oxygen plasma treatment of both stainless steel and titanium produced even stronger metal-polymer interfaces. Plasma treatment of the electrodes allows for the embedded electrodes and the EAP material of the actuator to work and move as a unit, with no detachment, by significantly improving the metal-polymer interface.

  1. Mechanism of action of ethanol on heart contractility

    International Nuclear Information System (INIS)

    Oquendo-Muriente, I.; De Mello, W.C.

    1986-01-01

    Ethanol depresses heart contractility. To investigate the mechanism of the negative inotropic action of ethanol, rat ventricular strips were dissected and mounted vertically in a transparent chamber. The preparation was superfused initially with normal oxygenated Tyrode solution (32.5 0 C) and electrically stimulated (1 Hz). After 1 hour of equilibration, contractures were elicited by exposing the muscle strips to high K + (100 mM) solution. Studies on the influence of (Ca 2+ ) 0 on K + contractures showed that the first rapid component of the contracture (58 mg/sec - S.E. +/- 8; n = 8) was greatly dependent upon (Ca 2+ ) 0 while the second slow component (20 mg/sec - S.E. +/- 5; n = 8) was slightly altered. The addition of ethanol (400 mg/100 ml) to high K solution abolished the fast component and reduced the amplitude of the second phase of K contractures. Similar results were obtained with verapamil (10 -5 M). These results, as well as studies on the effect of the drug on 45 Ca fluxes support the view that ethanol decreases the permeability of the heart cell membrane to Ca

  2. Mechanism of action of ethanol on heart contractility

    Energy Technology Data Exchange (ETDEWEB)

    Oquendo-Muriente, I.; De Mello, W.C.

    1986-03-05

    Ethanol depresses heart contractility. To investigate the mechanism of the negative inotropic action of ethanol, rat ventricular strips were dissected and mounted vertically in a transparent chamber. The preparation was superfused initially with normal oxygenated Tyrode solution (32.5/sup 0/C) and electrically stimulated (1 Hz). After 1 hour of equilibration, contractures were elicited by exposing the muscle strips to high K/sup +/ (100 mM) solution. Studies on the influence of (Ca/sup 2 +/)/sub 0/ on K/sup +/ contractures showed that the first rapid component of the contracture (58 mg/sec - S.E. +/- 8; n = 8) was greatly dependent upon (Ca/sup 2 +/)/sub 0/ while the second slow component (20 mg/sec - S.E. +/- 5; n = 8) was slightly altered. The addition of ethanol (400 mg/100 ml) to high K solution abolished the fast component and reduced the amplitude of the second phase of K contractures. Similar results were obtained with verapamil (10/sup -5/ M). These results, as well as studies on the effect of the drug on /sup 45/Ca fluxes support the view that ethanol decreases the permeability of the heart cell membrane to Ca.

  3. Contractile Force of Human Extraocular Muscle: A Theoretical Analysis

    Directory of Open Access Journals (Sweden)

    Hongmei Guo

    2016-01-01

    Full Text Available Aim. The length-contractile force relationships of six human extraocular muscles (EOMs in primary innervations should be determined during eye movement modeling and surgery of clinical EOMs. This study aims to investigate these relationships. Method. The proposal is based on the assumption that six EOMs have similar constitutive relationships, with the eye suspended in the primary position. The constitutive relationships of EOMs are obtained by optimizing from previous experimental data and the theory of mechanical equilibrium using traditional model. Further, simulate the existing experiment of resistance force, and then compare the simulated results with the existing experimental results. Finally, the mechanical constitutive relationships of EOMs are obtained. Results. The results show that the simulated resistance forces from the other four EOMs except for the horizontal recti well agree with previous experimental results. Conclusion. The mechanical constitutive relationships of six EOMs in primary innervations are obtained, and the rationality of the constitutive relationships is verified. Whereafter, the active stress-strain relationships of the six EOMs in the primary innervations are obtained. The research results can improve the eye movement model to predict the surgical amounts of EOMs before EOM surgery more precisely.

  4. Postextrasystolic potentiation and contractile reserve: requirements and restrictions.

    Science.gov (United States)

    Lust, R M; Lutherer, L O; Gardner, M E; Cooper, M W

    1982-12-01

    These studies were conducted to examine the basic characteristics of postextrasystolic potentiation (PESP) and the relationship of loading effects to PESP. Measurements of left ventricular (LV) and aortic pressures, the rate of pressure rise, and echocardiographically determined LV dimensions were made in anesthetized open-chest dogs. The hearts were paced, and timed extrasystoles were introduced that were followed by postextrasystoles (PES). PES's were elicited after an interval equal to either a full compensatory pause or a time when the diastolic properties of the LV could not be distinguished from control (isolength). Potentiation of contraction for the PES's introduced after an isolength pause was dependent on both the heart rate and the extrasystolic interval, whereas the PES's that occurred after a full pause showed no dependence on either of these intervals. PESP elicited during the isolength period was not dependent on either preload and afterload. It is concluded that PESP depends on the combination of heart rate and extrasystolic and postextrasystolic intervals. Further, PESP may be inaccurate in assessing contractile reserve unless the heart rate and extrasystolic interval are known and the PES is introduced after an isolength pause.

  5. Considerations for Contractile Electroactive Polymeric Materials and Actuators

    International Nuclear Information System (INIS)

    Rasmussen, L.; Erickson, Carl J.; Meixler, Lewis D.; Ascione, G.; Gentile, Charles A.; Tilson, C.; Bernasek, Stephen L.; Abelev, E.

    2009-01-01

    Ras Labs produces electroactive polymer (EAP) based materials and actuators that bend, swell, ripple and now contract (new development) with low electric input. This is an important attribute because of the ability of contraction to produce life-like motion. The mechanism of contraction is not well understood. Radionuclide-labeled experiments were conducted to follow the movement of electrolytes and water in these EAPs when activated. Extreme temperature experiments were performed on the contractile EAPs with very favorable results. One of the biggest challenges in developing these actuators, however, is the electrode-EAP interface because of the pronounced movement of the EAP. Plasma treatments of metallic electrodes were investigated in order to improve the attachment of the embedded electrodes to the EAP material. Surface analysis, adhesive testing, and mechanical testing were conducted to test metal surfaces and metal-polymer interfaces. The nitrogen plasma treatment of titanium produced a strong metal-polymer interface; however, oxygen plasma treatment of both stainless steel and titanium produced even stronger metal-polymer interfaces. Plasma treatment of the electrodes allows for the embedded electrodes and the EAP material of the actuator to work and move as a unit, with no detachment, by significantly improving the metal-polymer interface

  6. Maximum Credible Incidents

    CERN Document Server

    Strait, J

    2009-01-01

    Following the incident in sector 34, considerable effort has been made to improve the systems for detecting similar faults and to improve the safety systems to limit the damage if a similar incident should occur. Nevertheless, even after the consolidation and repairs are completed, other faults may still occur in the superconducting magnet systems, which could result in damage to the LHC. Such faults include both direct failures of a particular component or system, or an incorrect response to a “normal” upset condition, for example a quench. I will review a range of faults which could be reasonably expected to occur in the superconducting magnet systems, and which could result in substantial damage and down-time to the LHC. I will evaluate the probability and the consequences of such faults, and suggest what mitigations, if any, are possible to protect against each.

  7. Pre-treatment with Toll-like receptor 4 antagonist inhibits lipopolysaccharide-induced preterm uterine contractility, cytokines, and prostaglandins in rhesus monkeys

    Science.gov (United States)

    Adams Waldorf, Kristina M.; Persing, David; Novy, Miles J.; Sadowsky, Drew W.; Gravett, Michael G.

    2009-01-01

    Intra-uterine infection, which occurs in the majority of early preterm births, triggers an immune response culminating in preterm labor. We hypothesized that blockade of lipopolysaccharide (LPS)-induced immune responses by a Toll-like receptor 4 antagonist (TLR4A) would prevent elevations in amniotic fluid (AF) cytokines, prostaglandins, and uterine contractility. Chronically catheterized rhesus monkeys at 128-147 days gestation received intra-amniotic infusions of either: 1) saline (n=6), 2) LPS (0.15-10μg; n=4), or 3) TLR4A pre-treatment with LPS (10 μg) one hour later (n=4). AF cytokines, prostaglandins, and uterine contractility were compared using oneway ANOVA with Bonferroni-adjusted pairwise comparisons. Compared to saline controls, LPS induced significant elevations in AF IL-8, TNF-α, PGE2, PGF2α, and uterine contractility (p<0.05). In contrast, TLR4A pre-treatment inhibited LPS-induced uterine activity and was associated with significantly lower AF IL-8, TNF-α, PGE2, and PGF2α versus LPS alone (p<0.05). Toll-like receptor antagonists, together with antibiotics, may delay or prevent infection-associated preterm birth. PMID:18187405

  8. Administration of imatinib mesylate in rats impairs the neonatal development of intramuscular interstitial cells in bladder and results in altered contractile properties.

    Science.gov (United States)

    Gevaert, Thomas; Hutchings, Graham; Everaerts, Wouter; Prenen, Hans; Roskams, Tania; Nilius, Bernd; De Ridder, Dirk

    2014-04-01

    The KIT receptor is considered as a reliable marker for a subpopulation of interstitial cells (IC), and by persistent neonatal inhibition of KIT we have investigated the role of this receptor in the development of IC-networks in bladder and we have observed the functional consequences of this inhibition. Newborn rat pups were treated daily with the KIT inhibitor imatinib mesylate (IM). After 7 days animals were sacrificed and bladder samples were dissected for morphological and functional studies. Morphological research consisted of immunohistochemistry with IC specific antigens (KIT and vimentin) and electron microscopy. The functional studies were based on isolated bladder strips in organ baths, in which spontaneous bladder contractility and the response to a non-subtype selective muscarinic agonist was evaluated. Suburothelial and intramuscular IC were found and characterized in neonatal rat bladder. IM-treatment induced a significant decrease in numbers of IC based on specific immunohistochemical markers, and electron microscopy revealed evidence of IC cell injury. These morphological alterations were observed on intramuscular IC only and not on IC in the suburothelium. Isolated muscle strips from IM-treated animals had a lower contractile frequency and an altered response to muscarinic agonists. The present study shows the presence of regional subpopulations of IC in neonatal rat bladder, provides evidence for a dependence on KIT of the development of intramuscular IC and supports the hypothesis that a poor development of networks of intramuscular IC might have repercussions on spontaneous and muscarinic-induced bladder contractility. © 2013 Wiley Periodicals, Inc.

  9. Thick filament length and isoform composition determine self-organized contractile units in actomyosin bundles.

    Science.gov (United States)

    Thoresen, Todd; Lenz, Martin; Gardel, Margaret L

    2013-02-05

    Diverse myosin II isoforms regulate contractility of actomyosin bundles in disparate physiological processes by variations in both motor mechanochemistry and the extent to which motors are clustered into thick filaments. Although the role of mechanochemistry is well appreciated, the extent to which thick filament length regulates actomyosin contractility is unknown. Here, we study the contractility of minimal actomyosin bundles formed in vitro by mixtures of F-actin and thick filaments of nonmuscle, smooth, and skeletal muscle myosin isoforms with varied length. Diverse myosin II isoforms guide the self-organization of distinct contractile units within in vitro bundles with shortening rates similar to those of in vivo myofibrils and stress fibers. The tendency to form contractile units increases with the thick filament length, resulting in a bundle shortening rate proportional to the length of constituent myosin thick filament. We develop a model that describes our data, providing a framework in which to understand how diverse myosin II isoforms regulate the contractile behaviors of disordered actomyosin bundles found in muscle and nonmuscle cells. These experiments provide insight into physiological processes that use dynamic regulation of thick filament length, such as smooth muscle contraction. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  10. A comparative study of contractility of the heart ventricle in some ectothermic vertebrates

    Directory of Open Access Journals (Sweden)

    Sergey Kharin

    2009-07-01

    Full Text Available The purpose of this study was to analyze contractility of the heart ventricle in selected reptilian and amphibian species having the same ventricular excitation pattern. Systolic time intervals and indices of contractility of the heart ventricle were measured in anaesthetized frogs, snakes, and tortoises by use of polycardiography. The electromechanical delay was significantly shorter in tortoises compared with the other two species. The isovolumetric contraction time in frogs was approximately twofold longer than in reptiles. The pre-ejection period was the longest in frogs and the shortest in tortoises, whereas snakes were intermediate. The ejection time was slightly longer in tortoises compared with the other two species. The greatest isovolumetric contraction index and the smallest myocardial tension index corresponded to the frog and tortoise heart ventricle, respectively. The intrasystolic index in tortoises was significantly greater than in frogs, whereas quite similar to that in snakes. The frog ventricle had lower contractility compared with the reptilian one. Although ventricular contractility tended to be lower in snakes compared with tortoises, this difference was not statistically significant. Possible causes for these differences are discussed. We suppose a large variety in ventricular contractility among amphibian and reptilian species having the same ventricular activation pattern. This variety may be conditioned by heart anatomy, intracardiac shunting, lifestyles, and habitats. It can only be hypothesized that on the average, ventricular contractility is higher in reptiles compared with amphibians and in chelonians compared with snakes.

  11. Improvement of cardiac contractile function by peptide-based inhibition of NF-κB in the utrophin/dystrophin-deficient murine model of muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Guttridge Denis C

    2011-05-01

    Full Text Available Abstract Background Duchenne muscular dystrophy (DMD is an inherited and progressive disease causing striated muscle deterioration. Patients in their twenties generally die from either respiratory or cardiac failure. In order to improve the lifespan and quality of life of DMD patients, it is important to prevent or reverse the progressive loss of contractile function of the heart. Recent studies by our labs have shown that the peptide NBD (Nemo Binding Domain, targeted at blunting Nuclear Factor κB (NF-κB signaling, reduces inflammation, enhances myofiber regeneration, and improves contractile deficits in the diaphragm in dystrophin-deficient mdx mice. Methods To assess whether cardiac function in addition to diaphragm function can be improved, we investigated physiological and histological parameters of cardiac muscle in mice deficient for both dystrophin and its homolog utrophin (double knockout = dko mice treated with NBD peptide. These dko mice show classic pathophysiological hallmarks of heart failure, including myocyte degeneration, an impaired force-frequency response and a severely blunted β-adrenergic response. Cardiac contractile function at baseline and frequencies and pre-loads throughout the in vivo range as well as β-adrenergic reserve was measured in isolated cardiac muscle preparations. In addition, we studied histopathological and inflammatory markers in these mice. Results At baseline conditions, active force development in cardiac muscles from NBD treated dko mice was more than double that of vehicle-treated dko mice. NBD treatment also significantly improved frequency-dependent behavior of the muscles. The increase in force in NBD-treated dko muscles to β-adrenergic stimulation was robustly restored compared to vehicle-treated mice. However, histological features, including collagen content and inflammatory markers were not significantly different between NBD-treated and vehicle-treated dko mice. Conclusions We conclude

  12. The effects of RSR13 on microvascular Po2 kinetics and muscle contractile performance in the rat arterial ligation model of peripheral arterial disease.

    Science.gov (United States)

    Watanabe, Aiko; Poole, David C; Kano, Yutaka

    2017-10-01

    Exercise intolerance and claudication are symptomatic of peripheral arterial disease. There is a close relationship between muscle O 2 delivery, microvascular oxygen partial pressure (P mv O 2 ), and contractile performance. We therefore hypothesized that a reduction of hemoglobin-oxygen affinity via RSR13 would maintain a higher P mv O 2 and enhance blood-muscle O 2 transport and contractile function. In male Wistar rats (12 wk of age), we created hindlimb ischemia via right-side iliac artery ligation (AL). The contralateral (left) muscle served as control (CONT). Seven days after AL, phosphorescence-quenching techniques were used to measure P mv O 2 at rest and during contractions (electrical stimulation; 1 Hz, 300 s) in tibialis anterior muscle (TA) under saline ( n = 10) or RSR13 ( n = 10) conditions. RSR13 at rest increased TA P mv O 2 in CONT (13.9 ± 1.6 to 19.3 ± 1.9 Torr, P < 0.05) and AL (9.0 ± 0.5 to 9.9 ± 0.7 Torr, P < 0.05). Furthermore, RSR13 extended maintenance of the initial TA force (i.e., improved contractile performance) such that force was not decreased significantly until contraction 240 vs. 150 in CONT and 80 vs. 20 in AL. This improved muscle endurance with RSR13 was accompanied by a greater ΔP mv O 2 (P mv O 2 decrease from baseline) (CONT, 7.4 ± 1.0 to 11.2 ± 1.3; AL, 6.9 ± 0.5 to 8.6 ± 0.6 Torr, both P < 0.05). Whereas RSR13 did not alter the kinetics profile of P mv O 2 (i.e., mean response time) substantially during contractions, muscle force was elevated, and the ratio of muscle force to P mv O 2 increased. In conclusion, reduction of hemoglobin-oxygen affinity via RSR13 in AL increased P mv O 2 and improved muscle contractile performance most likely via enhanced blood-muscle O 2 diffusion. NEW & NOTEWORTHY This is the first investigation to examine the effect of RSR13 (erythrocyte allosteric effector) on skeletal muscle microvascular oxygen partial pressure kinetics and contractile function using an arterial ligation model of

  13. Action of ouabain and an amino-cardenolide on Na+-pump function and contractility of isolated canine heart cells

    International Nuclear Information System (INIS)

    Porterfield, L.M.; Songu-Mize, E.; Chryssanthis, T.; Caldwell, R.W.

    1986-01-01

    Viable, rod-shaped, Ca ++ -tolerant cells were isolated from the cardiac ventricle of adult mongrel dogs, a digitalis-sensitive species. These cells do not contract spontaneously but contractions were driven by electrical field stimulation. Changes in contractile amplitude were assessed by computer-assisted analysis of recorded phase contrast images. Addition of a polar aminocardenolide (AC), ASI-222, produced a dose-related increase in contractility with a concentration producing a 50% maximal response (RC 50 ) of 4 x 10 -8 M. For ouabain (OB) the RC 50 was 7 x 10 -7 M. Cellular Na + -pump (NaP) function was determined as digitalis-sensitive 86 Rb + -uptake. Addition of AC and OB to these cells produced a dose-related decrease in 86 Rb + -uptake; concentrations which produced a 50% inhibition (IC 50 ) of NaP function were of 6 x 10 -8 M and 1.2 x 10 -6 M for AC and OB, respectively. Their data indicates that in isolated dog heart cells AC is both a more potent inotropic agent and an inhibitor of NaP function by 15-20 fold than OB. The RC 50 and IC 50 for these processes correlate for each glycoside

  14. The Mitochondrial Calcium Uniporter Selectively Matches Metabolic Output to Acute Contractile Stress in the Heart

    Directory of Open Access Journals (Sweden)

    Jennifer Q. Kwong

    2015-07-01

    Full Text Available In the heart, augmented Ca2+ fluxing drives contractility and ATP generation through mitochondrial Ca2+ loading. Pathologic mitochondrial Ca2+ overload with ischemic injury triggers mitochondrial permeability transition pore (MPTP opening and cardiomyocyte death. Mitochondrial Ca2+ uptake is primarily mediated by the mitochondrial Ca2+ uniporter (MCU. Here, we generated mice with adult and cardiomyocyte-specific deletion of Mcu, which produced mitochondria refractory to acute Ca2+ uptake, with impaired ATP production, and inhibited MPTP opening upon acute Ca2+ challenge. Mice lacking Mcu in the adult heart were also protected from acute ischemia-reperfusion injury. However, resting/basal mitochondrial Ca2+ levels were normal in hearts of Mcu-deleted mice, and mitochondria lacking MCU eventually loaded with Ca2+ after stress stimulation. Indeed, Mcu-deleted mice were unable to immediately sprint on a treadmill unless warmed up for 30 min. Hence, MCU is a dedicated regulator of short-term mitochondrial Ca2+ loading underlying a “fight-or-flight” response that acutely matches cardiac workload with ATP production.

  15. Functional Loss of Bmsei Causes Thermosensitive Epilepsy in Contractile Mutant Silkworm, Bombyx mori

    Science.gov (United States)

    Nie, Hongyi; Cheng, Tingcai; Huang, Xiaofeng; Zhou, Mengting; Zhang, Yinxia; Dai, Fangyin; Mita, Kazuei; Xia, Qingyou; Liu, Chun

    2015-07-01

    The thermoprotective mechanisms of insects remain largely unknown. We reported the Bombyx mori contractile (cot) behavioral mutant with thermo-sensitive seizures phenotype. At elevated temperatures, the cot mutant exhibit seizures associated with strong contractions, rolling, vomiting, and a temporary lack of movement. We narrowed a region containing cot to ~268 kb by positional cloning and identified the mutant gene as Bmsei which encoded a potassium channel protein. Bmsei was present in both the cell membrane and cytoplasm in wild-type ganglia but faint in cot. Furthermore, Bmsei was markedly decreased upon high temperature treatment in cot mutant. With the RNAi method and injecting potassium channel blockers, the wild type silkworm was induced the cot phenotype. These results demonstrated that Bmsei was responsible for the cot mutant phenotype and played an important role in thermoprotection in silkworm. Meanwhile, comparative proteomic approach was used to investigate the proteomic differences. The results showed that the protein of Hsp-1 and Tn1 were significantly decreased and increased on protein level in cot mutant after thermo-stimulus, respectively. Our data provide insights into the mechanism of thermoprotection in insect. As cot phenotype closely resembles human epilepsy, cot might be a potential model for the mechanism of epilepsy in future.

  16. Roles of calcium and IP3 in impaired colon contractility of rats following multiple organ dysfunction syndrome

    Directory of Open Access Journals (Sweden)

    C. Zheyu

    2007-10-01

    Full Text Available The purpose of the present study was to explore changes in rat colon motility, and determine the roles of calcium and inositol (1,4,5-triphosphate (IP3 in colon dysmotility induced by multiple organ dysfunction syndrome (MODS caused by bacteria peritonitis. The number of stools, the contractility of the muscle strips and the length of smooth muscle cells (SMC in the colon, the concentration of calcium and IP3 in SMC, and serum nitric oxide were measured. Number of stools, fecal weight, IP3 concentration in SMC and serum nitric oxide concentration were 0.77 ± 0.52 pellets, 2.51 ± 0.39 g, 4.14 ± 2.07 pmol/tube, and 113.95 ± 37.89 µmol/L, respectively, for the MODS group (N = 11 vs 1.54 ± 0.64 pellets, 4.32 ± 0.57 g, 8.19 ± 3.11 pmol/tube, and 37.42 ± 19.56 µmol/L for the control group (N = 20; P < 0.05. After treatment with 0.1 mM acetylcholine and 0.1 M potassium chloride, the maximum contraction stress of smooth muscle strips, the length of SMC and the changes of calcium concentration were 593 ± 81 and 458 ± 69 g/cm³, 48.1 ± 11.8 and 69.2 ± 15.7 µM, 250 ± 70 and 167 ± 48%, respectively, for the control group vs 321 ± 53 and 284 ± 56 g/cm³, 65.1 ± 18.5 and 87.2 ± 23.7 µM, 127 ± 35 and 112 ± 35% for the MODS group (P < 0.05. Thus, colon contractility was decreased in MODS, a result possibly related to reduced calcium concentration and IP3 in SMC.

  17. The Functional Lumen Imaging Probe Detects Esophageal Contractility not Observed with Manometry in Patients with Achalasia

    Science.gov (United States)

    Carlson, Dustin A.; Lin, Zhiyue; Kahrilas, Peter J.; Sternbach, Joel; Donnan, Erica N.; Friesen, Laurel; Listernick, Zoe; Mogni, Benjamin; Pandolfino, John E.

    2015-01-01

    Background & Aims The functional lumen imaging probe (FLIP) could improve characterization of achalasia subtypes by detecting non-occlusive esophageal contractions not observed with standard manometry. We aimed to evaluate for esophageal contractions during volumetric distention in patients with achalasia using FLIP topography. Methods Fifty one treatment-naïve patients with achalasia, defined and sub-classified by high-resolution esophageal pressure topography, and 10 asymptomatic individuals (controls) were evaluated with the FLIP during endoscopy. During stepwise distension, simultaneous intra-bag pressures and 16 channels of cross-sectional areas were measured; data were exported to software that generated FLIP topography plots. Esophageal contractility was identified by noting periods of reduced luminal diameter. Esophageal contractions were further characterized by propagation direction, repetitiveness, and based on whether they were occluding or non-occluding. Results Esophageal contractility was detected in all 10 controls: 8/10 had repetitive, antegrade, contractions and 9/10 had occluding contractions. Contractility was detected in 27% (4/15) of patients with type I achalasia and 65% (18/26, including 9 with occluding contractions) of patients with type II achalasia. Contractility was detected in all 10 patients with type III achalasia; 8 of these patients had a pattern of contractility not observed in controls (repetitive, retrograde contractions). Conclusions Esophageal contractility not observed with manometry can be detected in patients with achalasia using FLIP topography. The presence and patterns of contractility detected with FLIP topography may represent variations in pathophysiology, such as mechanisms of pan-esophageal pressurization in patients with type II achalasia. These findings could have implications for additional sub-classification to supplement prediction of the achalasia disease course. PMID:26278501

  18. Stress and strain in the contractile and cytoskeletal filaments of airway smooth muscle.

    Science.gov (United States)

    Deng, Linhong; Bosse, Ynuk; Brown, Nathan; Chin, Leslie Y M; Connolly, Sarah C; Fairbank, Nigel J; King, Greg G; Maksym, Geoffrey N; Paré, Peter D; Seow, Chun Y; Stephen, Newman L

    2009-10-01

    Stress and strain are omnipresent in the lung due to constant lung volume fluctuation associated with respiration, and they modulate the phenotype and function of all cells residing in the airways including the airway smooth muscle (ASM) cell. There is ample evidence that the ASM cell is very sensitive to its physical environment, and can alter its structure and/or function accordingly, resulting in either desired or undesired consequences. The forces that are either conferred to the ASM cell due to external stretching or generated inside the cell must be borne and transmitted inside the cytoskeleton (CSK). Thus, maintaining appropriate levels of stress and strain within the CSK is essential for maintaining normal function. Despite the importance, the mechanisms regulating/dysregulating ASM cytoskeletal filaments in response to stress and strain remained poorly understood until only recently. For example, it is now understood that ASM length and force are dynamically regulated, and both can adapt over a wide range of length, rendering ASM one of the most malleable living tissues. The malleability reflects the CSK's dynamic mechanical properties and plasticity, both of which strongly interact with the loading on the CSK, and all together ultimately determines airway narrowing in pathology. Here we review the latest advances in our understanding of stress and strain in ASM cells, including the organization of contractile and cytoskeletal filaments, range and adaptation of functional length, structural and functional changes of the cell in response to mechanical perturbation, ASM tone as a mediator of strain-induced responses, and the novel glassy dynamic behaviors of the CSK in relation to asthma pathophysiology.

  19. The influence of D2O, perchlorate, and variation in temperature on the potential-dependent contractile function of frog skeletal muscle

    International Nuclear Information System (INIS)

    Foulks, J.G.; Morishita, L.

    1985-01-01

    D 2 O and perchlorate manifest opposing effects on the contractile function of skeletal muscle (amplitude of twitches and maximum K contractures, potential dependence of contraction and inactivation), and when combined the influence of one may effectively antagonize that of the other. The ratio of perchlorate concentrations required to produce effects of equal intensity, (e.g., twitch enhancement and restoration of maximum K contractures in media lacking divalent cations or containing a depressant concentration of a cationic amphipath) in H 2 O and D 2 O solutions was generally rather constant. These findings are compatible with the view that both agents can influence contractile function by virtue of their effects on solvent structure. In the absence of divalent cations, the effects of reduced temperature resemble those of D 2 O whereas the effects of increased temperature resemble those of the chaotropic anion. However, in other media, variation in temperature was found to result in additional nonsolvent effects so that low temperature could oppose rather than enhance the effects of D 2 O. These observations are discussed in terms of a model which postulates a role for solvent influences on the kinetics of two separate potential-dependent conformational transitions of membrane proteins which mediate the activation and inactivation of contraction in skeletal muscle

  20. Credal Networks under Maximum Entropy

    OpenAIRE

    Lukasiewicz, Thomas

    2013-01-01

    We apply the principle of maximum entropy to select a unique joint probability distribution from the set of all joint probability distributions specified by a credal network. In detail, we start by showing that the unique joint distribution of a Bayesian tree coincides with the maximum entropy model of its conditional distributions. This result, however, does not hold anymore for general Bayesian networks. We thus present a new kind of maximum entropy models, which are computed sequentially. ...

  1. 17 alpha-hydroxyprogesterone caproate vehicle, castor oil, enhances the contractile effect of oxytocin in human myometrium in pregnancy.

    Science.gov (United States)

    O'Sullivan, Michael D; Hehir, Mark P; O'Brien, Yvonne M; Morrison, John J

    2010-05-01

    The possibility exists that the vehicle for 17-alpha-hydroxyprogesterone caproate, castor oil, exerts an effect on human uterine contractility. The aim of this study was to evaluate its effects on contractility of myometrial preparations that were obtained during pregnancy. Myometrial strips were suspended under isometric conditions. Contractility was induced with oxytocin. Strips were incubated in castor oil or physiologic salt solution and suspended for a further oxytocin challenge. Contractile integrals were compared between both groups. Strips that were exposed to castor oil demonstrated increased contractile activity that was elicited by oxytocin (mean contractility value, 165.53%+/-17.03%; n=8; P=.004), compared with control strips (mean contractility value, 72.57%+/-7.48%; n=8; P=.003). There was a significant increase in contractile activity of the castor oil-exposed strips, compared with those that were exposed to physiologic salt solution (n=8; Pcastor oil results in enhanced oxytocin-induced contractility. Copyright (c) 2010 Mosby, Inc. All rights reserved.

  2. Impact of Cardiac Contractility during Cerebral Blood Flow in Ischemia

    Directory of Open Access Journals (Sweden)

    Silver, Brian

    2011-05-01

    Full Text Available Objective: In cerebral regions affected by ischemia, intrinsic vascular autoregulation is often lost. Blood flow delivery depends upon cardiac function and may be influenced by neuro-endocrine mediated myocardial suppression. Our objective is to evaluate the relation between ejection fraction (EF and transcranial doppler (TCD peak systolic velocities (PSV in patients with cerebral ischemic events.Methods: We conducted a retrospective cohort study from an existing TCD registry. We evaluated patients admitted within 24 hours of onset of a focal neurological deficit who had an echocardiogram and TCD performed within 72 hours of admission.Results: We identified 58 patients from March to October 2003. Eighty-one percent (n=47 had a hospital discharge diagnosis of ischemic stroke and 18.9% (n=11 had a diagnosis of transient ischemic attack. Fourteen patients had systolic dysfunction (EF50% compared to those with systolic dysfunction (EF<50% was as follows: middle cerebral artery 62.0 + 28.6 cm/s vs. 51.0 + 23.3 cm/s, p=0.11; anterior cerebral artery 52.1 + 21.6 cm/s vs. 45.9 + 22.7 cm/s, p=0.28; internal carotid artery 56.5 + 20.1 cm/s vs. 46.4 + 18.4 cm/s, p=0.04; ophthalmic artery 18.6 + 7.2 cm/s vs. 15.3 + 5.2 cm/s, p=0.11; vertebral artery 34.0 + 13.9 cm/s vs. 31.6 + 15.0 cm/s, p=0.44.Conclusion: Cerebral blood flow in the internal carotid artery territory appears to be higher in cerebral ischemia patients with preserved left ventricular contractility. Our study was unable to differentiate pre-existing cardiac dysfunction from neuro-endocrine mediated myocardial stunning. Future research is necessary to better understand heart-brain interactions in this setting and to further explore the underlying mechanisms and consequences of neuro-endocrine mediated cardiac dysfunction. [West J Emerg Med. 2011;12(2:227-232.

  3. Inhibition of isolated human myometrium contractility by minoxidil and reversal by glibenclamide.

    Science.gov (United States)

    Prabhakaran, S S; Dhanasekar, K R; Thomas, E; Jose, R; Peedicayil, J; Samuel, P

    2010-03-01

    This study investigated the ability of the antihypertensive drug minoxidil to inhibit potassium chloride (KCl)-induced contractility of the isolated human myometrium. Twelve strips of myometrium obtained from 12 patients who underwent hysterectomy were triggered to contract with 55 mM KCl before and after incubation with 3 concentrations (1, 3 and 10 microM) of minoxidil. The percent inhibition by minoxidil on the extent of contraction, and the area under the contractile curve of KCl-induced contraction of the myometrial strips was determined. Furthermore, the effect of 10 microM glibenclamide on the inhibition generated by 3 microM minoxidil on KCl-induced contractility was studied. It was found that minoxidil produced a concentration-dependent inhibition of KCl-induced contractility of the myometrium and that glibenclamide reversed this inhibitory effect. These results suggest that the inhibitory effect of minoxidil on isolated human myometrium contractility may prove useful in clinical conditions requiring relaxation of the myometrium. 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

  4. [Contractile function of the heart and myocardium antioxidant system in rats of August and Wistar strains during ischemia and reperfusion].

    Science.gov (United States)

    Sazontova, T G; Belkina, L M; Zhukova, A G; Kirillina, T N; Arkhipenko, Iu V

    2004-01-01

    In August rats, local myocardial ischemia caused by 30-min occlusion of the coronary artery induced a slight depression of the contractile function of the heart; the latter was restored after 15-min reperfusion more rapidly than in Wistar rats. In August rats, the activities of antioxidant protection enzymes were lower than in Wistar rats. In comparison with Wistar rats, these enzyme activities were decreased in a lesser degree under ischemia and were restored in a greater degree under reperfusion. It may thus be concluded that the higher stability of antiradical protection parameters in August rats is one of the mechanisms responsible for the enhanced resistance of the heart to ischemia- and reperfusion-induced injuries.

  5. Effect of spaceflight on the isotonic contractile properties of single skeletal muscle fibers in the rhesus monkey

    Science.gov (United States)

    Fitts, R. H.; Romatowski, J. G.; Blaser, C.; De La Cruz, L.; Gettelman, G. J.; Widrick, J. J.

    2000-01-01

    Experiments from both Cosmos and Space Shuttle missions have shown weightlessness to result in a rapid decline in the mass and force of rat hindlimb extensor muscles. Additionally, despite an increased maximal shortening velocity, peak power was reduced in rat soleus muscle post-flight. In humans, declines in voluntary peak isometric ankle extensor torque ranging from 15-40% have been reported following long- and short-term spaceflight and prolonged bed rest. Complete understanding of the cellular events responsible for the fiber atrophy and the decline in force, as well as the development of effective countermeasures, will require detailed knowledge of how the physiological and biochemical processes of muscle function are altered by spaceflight. The specific purpose of this investigation was to determine the extent to which the isotonic contractile properties of the slow- and fast-twitch fiber types of the soleus and gastrocnemius muscles of rhesus monkeys (Macaca mulatta) were altered by a 14-day spaceflight.

  6. Effects of high-altitude exercise training on contractile function of rat skinned cardiomyocyte.

    Science.gov (United States)

    Cazorla, O; Aït Mou, Y; Goret, L; Vassort, G; Dauzat, M; Lacampagne, A; Tanguy, S; Obert, P

    2006-09-01

    Previous studies have questioned whether there is an improved cardiac function after high-altitude training. Accordingly, the present study was designed specifically to test whether this apparent blunted response of the whole heart to training can be accounted for by altered mechanical properties at the cellular level. Adult rats were trained for 5 weeks under normoxic (N, NT for sedentary and trained animals, respectively) or hypobaric hypoxic (H, HT) conditions. Cardiac morphology and function were evaluated by echocardiography. Calcium Ca2+ sensitivity of the contractile machinery was estimated in skinned cardiomyocytes isolated from the left ventricular (LV) sub-epicardium (Epi) and sub-endocardium (Endo) at short and long sarcomere lengths (SL). Cardiac remodelling was harmonious (increase in wall thickness with chamber dilatation) in NT rats and disharmonious (hypertrophy without chamber dilatation) in HT rats. Contrary to NT rats, HT rats did not exhibit enhancement in global cardiac performance evaluated by echocardiography. Stretch- dependent Ca2+ sensitization of the myofilaments (cellular index of the Frank-Starling mechanism) increased from Epi to Endo in N rats. Training in normoxic conditions further increased this stretch-dependent Ca2+ sensitization. Chronic hypoxia did not significantly affect myofibrilar Ca2+ sensitivity. In contrast, high-altitude training decreased Ca2+ sensitivity of the myofilaments at both SL, mostly in Endo cells, resulting in a loss of the transmural gradient of the stretch-dependent Ca2+ sensitization. Expression of myosin heavy chain isoforms was affected both by training and chronic hypoxia but did not correlate with mechanical data. Training at sea level increased the transmural gradient of stretch-dependent Ca2+ sensitization of the myofilaments, accounting for an improved Frank-Starling mechanism. High-altitude training depressed myofilament response to Ca2+, especially in the Endo layer. This led to a reduction in

  7. High-dose benfotiamine rescues cardiomyocyte contractile dysfunction in streptozotocin-induced diabetes mellitus.

    Science.gov (United States)

    Ceylan-Isik, Asli F; Wu, Shan; Li, Qun; Li, Shi-Yan; Ren, Jun

    2006-01-01

    Diabetic cardiomyopathy is characterized by cardiac dysfunction. This study was designed to examine the effect of benfotiamine, a lipophilic derivative of thiamine, on streptozotocin (STZ)-induced cardiac contractile dysfunction in mouse cardiomyocytes. Adult male FVB mice were made diabetic with a single injection of STZ (200 mg/kg ip). Fourteen days later, control and diabetic (fasting plasma glucose > 13.9 mM) mice were put on benfotiamine therapy (100 mg.kg(-1).day(-1) ip) for another 14 days. Mechanical and intracellular Ca2+ properties were evaluated in left ventricular myocytes using an IonOptix MyoCam system. The following indexes were evaluated: peak shortening (PS), time to PS (TPS), time to 90% relengthening (TR90), maximal velocity of shortening/relengthening, resting and rise of intracellular Ca2+ in response to electrical stimulus, sarcoplasmic reticulum (SR) Ca2+ load, and intracellular Ca2+ decay rate (tau). Two- or four-week STZ treatment led to hyperglycemia, prolonged TPS and TR90, reduced SR Ca2+ load, elevated resting intracellular Ca2+ level and prolonged tau associated with normal PS, maximal velocity of shortening/relengthening, and intracellular Ca2+ rise in response to electrical stimulus. Benfotiamine treatment abolished prolongation in TPS, TR90, and tau, as well as reduction in SR Ca2+ load without affecting hyperglycemia and elevated resting intracellular Ca2+. Diabetes triggered oxidative stress, measured by GSH-to-GSSG ratio and formation of advanced glycation end product (AGE) in the hearts. Benfotiamine treatment alleviated oxidative stress without affecting AGE or protein carbonyl formation. Collectively, our results indicated that benfotiamine may rescue STZ-induced cardiomyocyte dysfunction but not AGE formation in short-term diabetes.

  8. Density estimation by maximum quantum entropy

    International Nuclear Information System (INIS)

    Silver, R.N.; Wallstrom, T.; Martz, H.F.

    1993-01-01

    A new Bayesian method for non-parametric density estimation is proposed, based on a mathematical analogy to quantum statistical physics. The mathematical procedure is related to maximum entropy methods for inverse problems and image reconstruction. The information divergence enforces global smoothing toward default models, convexity, positivity, extensivity and normalization. The novel feature is the replacement of classical entropy by quantum entropy, so that local smoothing is enforced by constraints on differential operators. The linear response of the estimate is proportional to the covariance. The hyperparameters are estimated by type-II maximum likelihood (evidence). The method is demonstrated on textbook data sets

  9. Sodium Glucose Cotransporter 2 (SGLT2 Plays as a Physiological Glucose Sensor and Regulates Cellular Contractility in Rat Mesangial Cells.

    Directory of Open Access Journals (Sweden)

    Masanori Wakisaka

    Full Text Available Mesangial cells play an important role in regulating glomerular filtration by altering their cellular tone. We report the presence of a sodium glucose cotransporter (SGLT in rat mesangial cells. This study in rat mesangial cells aimed to evaluate the expression and role of SGLT2.The SGLT2 expression in rat mesangial cells was assessed by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR. Changes in the mesangial cell surface area at different glucose concentrations and the effects of extracellular Na+ and Ca2+ and of SGLT and Na+/Ca2+ exchanger (NCX inhibitors on cellular size were determined. The cellular sizes and the contractile response were examined during a 6-day incubation with high glucose with or without phlorizin, an SGLT inhibitor.Western blotting revealed an SGLT2 band, and RT-PCR analysis of SGLT2 revealed the predicted 422-bp band in both rat mesangial and renal proximal tubular epithelial cells. The cell surface area changed according to the extracellular glucose concentration. The glucose-induced contraction was abolished by the absence of either extracellular Na+ or Ca2+ and by SGLT and NCX inhibitors. Under the high glucose condition, the cell size decreased for 2 days and increased afterwards; these cells did not contract in response to angiotensin II, and the SGLT inhibitor restored the abolished contraction.These data suggest that SGLT2 is expressed in rat mesangial cells, acts as a normal physiological glucose sensor and regulates cellular contractility in rat mesangial cells.

  10. Insoluble elastin reduces collagen scaffold stiffness, improves viscoelastic properties, and induces a contractile phenotype in smooth muscle cells.

    Science.gov (United States)

    Ryan, Alan J; O'Brien, Fergal J

    2015-12-01

    Biomaterials with the capacity to innately guide cell behaviour while also displaying suitable mechanical properties remain a challenge in tissue engineering. Our approach to this has been to utilise insoluble elastin in combination with collagen as the basis of a biomimetic scaffold for cardiovascular tissue engineering. Elastin was found to markedly alter the mechanical and biological response of these collagen-based scaffolds. Specifically, during extensive mechanical assessment elastin was found to reduce the specific tensile and compressive moduli of the scaffolds in a concentration dependant manner while having minimal effect on scaffold microarchitecture with both scaffold porosity and pore size still within the ideal ranges for tissue engineering applications. However, the viscoelastic properties were significantly improved with elastin addition with a 3.5-fold decrease in induced creep strain, a 6-fold increase in cyclical strain recovery, and with a four-parameter viscoelastic model confirming the ability of elastin to confer resistance to long term deformation/creep. Furthermore, elastin was found to result in the modulation of SMC phenotype towards a contractile state which was determined via reduced proliferation and significantly enhanced expression of early (α-SMA), mid (calponin), and late stage (SM-MHC) contractile proteins. This allows the ability to utilise extracellular matrix proteins alone to modulate SMC phenotype without any exogenous factors added. Taken together, the ability of elastin to alter the mechanical and biological response of collagen scaffolds has led to the development of a biomimetic biomaterial highly suitable for cardiovascular tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Contractile properties are disrupted in Becker muscular dystrophy, but not in limb girdle type 2I.

    Science.gov (United States)

    Løkken, Nicoline; Hedermann, Gitte; Thomsen, Carsten; Vissing, John

    2016-09-01

    We investigated whether a linear relationship between muscle strength and cross-sectional area (CSA) is preserved in calf muscles of patients with Becker muscular dystrophy (BMD, n = 14) and limb-girdle type 2I muscular dystrophy (LGMD2I, n = 11), before and after correcting for muscle fat infiltration. The Dixon magnetic resonance imaging technique was used to quantify fat and calculate a fat-free contractile CSA. Strength was assessed by dynamometry. Muscle strength/CSA relationships were significantly lower in patients versus controls. The strength/contractile-CSA relationship was still severely lowered in BMD, but was almost normalized in LGMD2I. Our findings suggest close to intact contractile properties in LGMD2I, which are severely disrupted in BMD. Ann Neurol 2016;80:466-471. © 2016 American Neurological Association.

  12. Suppression of guinea pig ileum induced contractility by plasma albumin of hibernators

    Science.gov (United States)

    Bruce, David S.; Ambler, Douglas L.; Henschel, Timothy M.; Oeltgen, Peter R.; Nilekani, Sita P.; Amstrup, Steven C.

    1992-01-01

    Previous studies suggest that hibernation may be regulated by internal opioids and that the putative “hibernation induction trigger” (HIT) may itself be an opioid. This study examined the effect of plasma albumin (known to bind HIT) on induced contractility of the guinea pig ileum muscle strip. Morphine (400 nM) depressed contractility and 100 nM naloxone restored it. Ten milligrams of lyophilized plasma albumin fractions from hibernating ground squirrels, woodchucks, black bears, and polar bears produced similar inhibition, with partial reversal by naloxone. Five hundredths mg of d-Ala2-d-Leu5-enkephalin (DADLE) also inhibited contractility and naloxone reversed it. Conclusions are that hibernating individuals of these species contain an HIT substance that is opioid in nature and summer animals do not; an endogenous opioid similar to leu-enkephalin may be the HIT compound or give rise to it.

  13. Mechanobiological induction of long-range contractility by diffusing biomolecules and size scaling in cell assemblies

    Science.gov (United States)

    Dasbiswas, K.; Alster, E.; Safran, S. A.

    2016-06-01

    Mechanobiological studies of cell assemblies have generally focused on cells that are, in principle, identical. Here we predict theoretically the effect on cells in culture of locally introduced biochemical signals that diffuse and locally induce cytoskeletal contractility which is initially small. In steady-state, both the concentration profile of the signaling molecule as well as the contractility profile of the cell assembly are inhomogeneous, with a characteristic length that can be of the order of the system size. The long-range nature of this state originates in the elastic interactions of contractile cells (similar to long-range “macroscopic modes” in non-living elastic inclusions) and the non-linear diffusion of the signaling molecules, here termed mechanogens. We suggest model experiments on cell assemblies on substrates that can test the theory as a prelude to its applicability in embryo development where spatial gradients of morphogens initiate cellular development.

  14. Respostas morfológicas do capim-Tanzânia (Panicum maximum Jacq. cv. Tanzânia-1 irrigado à intensidade de desfolha sob lotação rotacionada Morphological responses of irrigated Tanzaniagrass (Panicum Maximum Jacq. cv. Tanzania-1 to grazing intensity under rotational stocking

    Directory of Open Access Journals (Sweden)

    Alexandre Carneiro Leão de Mello

    2004-04-01

    Full Text Available Objetivando quantificar respostas morfológicas de dosséis de capim-Tanzânia (Panicum maximum Jacq. cv. Tanzânia-1 sob três intensidades de pastejo, lotação rotacionada e irrigação, foi conduzido um experimento em delineamento experimental de blocos completos casualizados com quatro repetições. Os tratamentos foram três intensidades de pastejo, representados pelas quantidades de massa seca verde residual pós-pastejo (T1=1000; T2=2500 e T3=4000 kg MSV/ha. Durante oito ciclos de pastejo (rebrotas de 33 dias após três dias de pastejo em cada ciclo, foram realizadas avaliações de altura média do dossel, índice de área foliar (IAF, interceptação luminosa (IL e ângulos foliares médios, em quatro dias dentro do período de rebrota (1, 11, 22 e 33 dias após a saída dos animais. A análise de correlações parciais indicou correlações entre altura e IL, bem como entre IAF e IL. Com o progresso da estação de pastejo, da primavera-verão para outono-inverno, houve reduções nos valores de IAF médio. Valores médios de IAF crítico (95% IL de 3,6 (T1, 4,0 (T2 e 4,5 (T3, foram alcançados por volta do 22º dia das rebrotas. A maior intensidade de pastejo (menor resíduo alterou a estrutura da pastagem no que diz respeito à arquitetura do dossel, evidenciada pela redução nos ângulos foliares médios (folhas mais horizontais ao longo das estações, com plantas passando a interceptar mais luz por unidade de área foliar. Os IAFs críticos medidos sugerem a necessidade de períodos de descanso menores que 33 dias em pastos de capim-Tanzânia, quando submetido a pastejo intensivo sob lotação rotacionada e irrigação.The objective of this research was to quantify morphological responses of Tanzania grass (Panicum maximum Jacq. cv. Tanzania-1 under three grazing intensities in an irrigated, rotationally stocked setting. Treatments consisted of three grazing intensities represented by three post-graze forage masses (T1=1,000; T

  15. Clinical Characteristics and Associated Systemic Diseases in Patients With Esophageal "Absent Contractility"-A Clinical Algorithm.

    Science.gov (United States)

    Laique, Sobia; Singh, Tavankit; Dornblaser, David; Gadre, Abhishek; Rangan, Vikram; Fass, Ronnie; Kirby, Donald; Chatterjee, Soumya; Gabbard, Scott

    2018-01-19

    This study was carried out to assess the clinical characteristics and associated systemic diseases seen in patients diagnosed with absent contractility as per the Chicago Classification version 3.0, allowing us to propose a diagnostic algorithm for their etiologic testing. The Chicago Classification version 3.0 has redefined major and minor esophageal motility disorders using high-resolution esophageal manometry. There is a dearth of publications based on research on absent contractility, which historically has been associated with myopathic processes such as systemic sclerosis (SSc). We conducted a retrospective, multicenter study. Data of patients diagnosed with absent contractility were pooled from Cleveland Clinic, Cleveland, OH (January 2006 to July 2016) and Metrohealth Medical Center, Cleveland, OH (July 2014 to July 2016) and included: age, gender, associated medical conditions, surgical history, medications, and specific antibody testing. A total of 207 patients, including 57 male individuals and 150 female individuals, with mean age of 56.1 and 60.0 years, respectively, were included. Disease distribution was as follows: SSc (diffuse or limited cutaneous) 132, overlap syndromes 7, systemic lupus erythematosus17, Sjögren syndrome 4, polymyositis 3, and dermatomyositis 3. Various other etiologies including gastroesophageal reflux disease, postradiation esophagitis, neuromuscular disorders, and surgical complications were seen in the remaining cohort. Most practitioners use the term "absent contractility" interchangeably with "scleroderma esophagus"; however, only 63% of patients with absent contractility had SSc. Overall, 20% had another systemic autoimmune rheumatologic disease and 16% had a nonrheumatologic etiology for absent contractility. Therefore, alternate diagnosis must be sought in these patients. We propose an algorithm for their etiologic evaluation.

  16. Accessory left atrial diverticulae: contractile properties depicted with 64-slice cine-cardiac CT.

    LENUS (Irish Health Repository)

    Killeen, Ronan P

    2012-02-01

    To assess the contractility of accessory left atrial appendages (LAAs) using multiphasic cardiac CT. We retrospectively analyzed the presence, location, size and contractile properties of accessory LAAs using multiphasic cardiac 64-slice CT in 102 consecutive patients (63 males, 39 females, mean age 57). Multiplanar reformats were used to create image planes in axial oblique, sagittal oblique and coronal oblique planes. For all appendages with an orifice diameter >or= 10 mm, axial and sagittal diameters and appendage volumes were recorded in atrial diastole and systole. Regression analysis was performed to assess which imaging appearances best predicted accessory appendage contractility. Twenty-three (23%) patients demonstrated an accessory LAA, all identified along the anterior LA wall. Dimensions for axial oblique (AOD) and sagittal oblique (SOD) diameters and sagittal oblique length (SOL) were 6.3-19, 3.4-20 and 5-21 mm, respectively. All appendages (>or=10 mm) demonstrated significant contraction during atrial systole (greatest diameter reduction was AOD [3.8 mm, 27%]). Significant correlations were noted between AOD-contraction and AOD (R = 0.57, P < 0.05) and SOD-contraction and AOD, SOD and SOL (R = 0.6, P < 0.05). Mean diverticulum volume in atrial diastole was 468.4 +\\/- 493 mm(3) and in systole was 171.2 +\\/- 122 mm(3), indicating a mean change in volume of 297.2 +\\/- 390 mm(3), P < 0.0001. Stepwise multiple regression analysis revealed SOL to be the strongest independent predictor of appendage contractility (R(2) = 0.86, P < 0.0001) followed by SOD (R(2) = 0.91, P < 0.0001). Accessory LAAs show significant contractile properties on cardiac CT. Those accessory LAAs with a large sagittal height or depth should be evaluated for contractile properties, and if present should be examined for ectopic activity during electrophysiological studies.

  17. Validation of an in vitro contractility assay using canine ventricular myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Harmer, A.R., E-mail: alex.harmer@astrazeneca.com; Abi-Gerges, N.; Morton, M.J.; Pullen, G.F.; Valentin, J.P.; Pollard, C.E.

    2012-04-15

    Measurement of cardiac contractility is a logical part of pre-clinical safety assessment in a drug discovery project, particularly if a risk has been identified or is suspected based on the primary- or non-target pharmacology. However, there are limited validated assays available that can be used to screen several compounds in order to identify and eliminate inotropic liability from a chemical series. We have therefore sought to develop an in vitro model with sufficient throughput for this purpose. Dog ventricular myocytes were isolated using a collagenase perfusion technique and placed in a perfused recording chamber on the stage of a microscope at ∼ 36 °C. Myocytes were stimulated to contract at a pacing frequency of 1 Hz and a digital, cell geometry measurement system (IonOptix™) was used to measure sarcomere shortening in single myocytes. After perfusion with vehicle (0.1% DMSO), concentration–effect curves were constructed for each compound in 4–30 myocytes taken from 1 or 2 dog hearts. The validation test-set was 22 negative and 8 positive inotropes, and 21 inactive compounds, as defined by their effect in dog, cynolomolgous monkey or humans. By comparing the outcome of the assay to the known in vivo contractility effects, the assay sensitivity was 81%, specificity was 75%, and accuracy was 78%. With a throughput of 6–8 compounds/week from 1 cell isolation, this assay may be of value to drug discovery projects to screen for direct contractility effects and, if a hazard is identified, help identify inactive compounds. -- Highlights: ► Cardiac contractility is an important physiological function of the heart. ► Assessment of contractility is a logical part of pre-clinical drug safety testing. ► There are limited validated assays that predict effects of compounds on contractility. ► Using dog myocytes, we have developed an in vitro cardiac contractility assay. ► The assay predicted the in vivo contractility with a good level of accuracy.

  18. Spontaneous and α-adrenoceptor-induced contractility in human collecting lymphatic vessels require chloride

    DEFF Research Database (Denmark)

    Mohanakumar, Sheyanth; Majgaard, Jens; Telinius, Niklas

    2018-01-01

    - with the impermeant anion aspartate and inhibition of Cl- transport and channels with the clinical diuretics furosemide and bendroflumethiazide, as well as DIDS and NPPB. The molecular expression of calcium-activated chloride channels was investigated by RT-PCR and proteins localized using immunoreactivity....... Spontaneous and norepinephrine-induced contractility in human lymphatic vessels was highly abrogated after Cl- substitution with aspartate. 100‒300µM DIDS or NPPB inhibited spontaneous contractile behavior. Norepinephrine-stimulated tone was furthermore markedly abrogated by 200µM DIDS. Furosemide lowered...

  19. 2-Deoxyadenosine triphosphate restores the contractile function of cardiac myofibril from adult dogs with naturally occurring dilated cardiomyopathy

    OpenAIRE

    Cheng, Yuanhua; Hogarth, Kaley A.; O'Sullivan, M. Lynne; Regnier, Michael; Pyle, W. Glen

    2015-01-01

    1) First report to characterize and define the contractile kinetics and defects associated with naturally occurring dilated cardiomyopathy (DCM) in dogs. 2) Novel findings that dATP is able to reverse the contractile defects associated with naturally occurring canine DCM.

  20. Modification of abomasum contractility by flavonoids present in ruminants diet: in vitro study.

    Science.gov (United States)

    Mendel, M; Chłopecka, M; Dziekan, N; Karlik, W

    2016-09-01

    Flavonoid supplementation is likely to be beneficial in improving rumen fermentation and in reducing the incidence of rumen acidosis and bloat. Flavonoids are also said to increase the metabolic performance during the peripartum period. Ruminants are constantly exposed to flavonoids present in feed. However, it is not clear if these phytochemicals can affect the activity of the gut smooth muscle. Therefore, the aim of the study was to verify the effect of three flavonoids on bovine isolated abomasum smooth muscle. The study was carried out on bovine isolated circular and longitudinal abomasal smooth muscle specimens. All experiments were conducted under isometric conditions. The effect of apigenin, luteolin and quercetin (0.001 to 100 µM) was evaluated on acetylcholine-precontracted preparations. The effect of multiple, but not cumulative, treatment and single treatment with each flavonoid on abomasum strips was compared. Apigenin (0.1 to 100 µM) dose-dependently showed myorelaxation effects. Luteolin and quercetin applied in low doses increased the force of the ACh-evoked reaction. However, if used in high doses in experiments testing a wide range of concentrations, their contractile effect either declined (luteolin) or was replaced by an antispasmodic effect (quercetin). Surprisingly, the reaction induced by flavonoids after repeated exposure to the same phytochemical was not reproducible in experiments testing only single exposure of abomasum strips to the same flavonoid used in a high concentration. Taking into account the physicochemical properties of flavonoids, this data suggests the ability of flavonoids to interfere with cell membranes and, subsequently, to modify their responsiveness. Assuming ruminant supplementation with luteolin or quercetin or their presence in daily pasture, a reduction of the likelihood of abomasum dysmotility should be expected.

  1. Adaptation of motor unit contractile properties in rat medial gastrocnemius to treadmill endurance training: Relationship to muscle mitochondrial biogenesis.

    Science.gov (United States)

    Kryściak, Katarzyna; Majerczak, Joanna; Kryściak, Jakub; Łochyński, Dawid; Kaczmarek, Dominik; Drzymała-Celichowska, Hanna; Krutki, Piotr; Gawedzka, Anna; Guzik, Magdalena; Korostynski, Michał; Szkutnik, Zbigniew; Pyza, Elżbieta; Jarmuszkiewicz, Wiesława; Zoladz, Jerzy A; Celichowski, Jan

    2018-01-01

    This study aimed at investigating the effects of 2, 4 and 8 weeks of endurance training on the contractile properties of slow (S), fast fatigue resistant (FR) and fast fatigable (FF) motor units (MUs) in rat medial gastrocnemius (MG) in relation to the changes in muscle mitochondrial biogenesis. The properties of functionally isolated MUs were examined in vivo. Mitochondrial biogenesis was judged based on the changes in mitochondrial DNA copy number (mtDNA), the content of the electron transport chain (ETC) proteins and PGC-1α in the MG. Moreover, the markers of mitochondria remodeling mitofusins (Mfn1, Mfn2) and dynamin-like protein (Opa1) were studied using qPCR. A proportion of FR MUs increased from 37.9% to 50.8% and a proportion of FF units decreased from 44.7% to 26.6% after 8 weeks of training. The increased fatigue resistance, shortened twitch duration, and increased ability to potentiate force were found as early as after 2 weeks of endurance training, predominantly in FR MUs. Moreover, just after 2 weeks of the training an enhancement of the mitochondrial network remodeling was present as judged by an increase in expression of Mfn1, Opa1 and an increase in PGC-1α in the slow part of MG. Interestingly, no signs of intensification of mitochondrial biogenesis assessed by ETC proteins content and mtDNA in slow and fast parts of gastrocnemius were found at this stage of the training. Nevertheless, after 8 weeks of training an increase in the ETC protein content was observed, but mainly in the slow part of gastrocnemius. Concluding, the functional changes in MUs' contractile properties leading to the enhancement of muscle performance accompanied by an activation of signalling that controls the muscle mitochondrial network reorganisation and mitochondrial biogenesis belong to an early muscle adaptive responses that precede an increase in mitochondrial ETC protein content.

  2. Cold stress accentuates pressure overload-induced cardiac hypertrophy and contractile dysfunction: role of TRPV1/AMPK-mediated autophagy.

    Science.gov (United States)

    Lu, Songhe; Xu, Dezhong

    2013-12-06

    Severe cold exposure and pressure overload are both known to prompt oxidative stress and pathological alterations in the heart although the interplay between the two remains elusive. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel activated in response to a variety of exogenous and endogenous physical and chemical stimuli including heat and capsaicin. The aim of this study was to examine the impact of cold exposure on pressure overload-induced cardiac pathological changes and the mechanism involved. Adult male C57 mice were subjected to abdominal aortic constriction (AAC) prior to exposure to cold temperature (4 °C) for 4 weeks. Cardiac geometry and function, levels of TRPV1, mitochondrial, and autophagy-associated proteins including AMPK, mTOR, LC3B, and P62 were evaluated. Sustained cold stress triggered cardiac hypertrophy, compromised depressed myocardial contractile capacity including lessened fractional shortening, peak shortening, and maximal velocity of shortening/relengthening, enhanced ROS production, and mitochondrial injury, the effects of which were negated by the TRPV1 antagonist SB366791. Western blot analysis revealed upregulated TRPV1 level and AMPK phosphorylation, enhanced ratio of LC3II/LC3I, and downregulated P62 following cold exposure. Cold exposure significantly augmented AAC-induced changes in TRPV1, phosphorylation of AMPK, LC3 isoform switch, and p62, the effects of which were negated by SB366791. In summary, these data suggest that cold exposure accentuates pressure overload-induced cardiac hypertrophy and contractile defect possibly through a TRPV1 and autophagy-dependent mechanism. Copyright © 2013. Published by Elsevier Inc.

  3. Role of glycolysis in maintenance of the action potential duration and contractile activity in isolated perfused rat heart.

    Science.gov (United States)

    Opie, L H; Tuschmidt, R; Bricknell, O; Girardier, L

    1980-01-01

    1. Changing substrates from glucose to pyruvate in paced isolated rat hearts, perfused by the Langendorff technique at 65 cm H2O with a Krebs-Henseleit bicarbonate buffer, produced effects which are opposite to those of ouabain treatment: negative inotropy, decreased work efficiency, hyperpolarization, increased maximum rate of rise and amplitude of the action potential, increased conduction velocity. 2. All the effects resulting from perfusion with pyruvate can be reversed by adding ouabain at a concentration of 100 microM. 3. The correlation between various tissue metabolises and change in contractile force (delta F), rate of tension development [maximum + (dF/dt)] and rate of relaxation [maximum -(dF/dt)] was studied by multiple linear regression. No significant correlation was found with either glycogen content and tissue lactate or with cAMP and cGMP. A weak negative correlation was found with ATP and phosphocreatine. The strongest correlation was found 76 to 807 nM/g in passing from glucose- to pyruvate-containing perfusion solution. 4. In vitro tests performed with a solution containing high energy phosphates and magnesium at concentrations equal to their calculated values in the cytosol (pH 7.0) showed that a significant negative correlation exists between citrate concentration (range: 1 and 1500 M) and free calcium concentration in the micromole range. 5. It is concluded that the effects of pyruvate (non glucose substrate) perfusion could be mediated by a decrease in cytosolic-free calcium resulting from an increase in intracellular citrate. The observation that all these effects can be reversed by ouabain is taken as a circumstantial evidence of a common mechanism.

  4. Max dD/Dt: A Novel Parameter to Assess Fetal Cardiac Contractility and a Substitute for Max dP/Dt.

    Science.gov (United States)

    Fujita, Yasuyuki; Kiyokoba, Ryo; Yumoto, Yasuo; Kato, Kiyoko

    2018-07-01

    Aortic pulse waveforms are composed of a forward wave from the heart and a reflection wave from the periphery. We focused on this forward wave and suggested a new parameter, the maximum slope of aortic pulse waveforms (max dD/dt), for fetal cardiac contractility. Max dD/dt was calculated from fetal aortic pulse waveforms recorded with an echo-tracking system. A normal range of max dD/dt was constructed in 105 healthy fetuses using linear regression analysis. Twenty-two fetuses with suspected fetal cardiac dysfunction were divided into normal and decreased max dD/dt groups, and their clinical parameters were compared. Max dD/dt of aortic pulse waveforms increased linearly with advancing gestational age (r = 0.93). The decreased max dD/dt was associated with abnormal cardiotocography findings and short- and long-term prognosis. In conclusion, max dD/dt calculated from the aortic pulse waveforms in fetuses can substitute for max dP/dt, an index of cardiac contractility in adults. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

  5. Smoothelin-B deficiency results in reduced arterial contractility, hypertension, and cardiac hypertrophy in mice

    NARCIS (Netherlands)

    Rensen, Sander S.; Niessen, Petra M.; van Deursen, Jan M.; Janssen, Ben J.; Heijman, Edwin; Hermeling, Evelien; Meens, Merlijn; Lie, Natascha; Gijbels, Marion J.; Strijkers, Gustav J.; Doevendans, Pieter A.; Hofker, Marten H.; de Mey, Jo G. R.; van Eys, Guillaume J.

    2008-01-01

    Smoothelins are actin-binding proteins that are abundantly expressed in healthy visceral (smoothelin-A) and vascular (smoothelin-B) smooth muscle. Their expression is strongly associated with the contractile phenotype of smooth muscle cells. Analysis of mice lacking both smoothelins (Smtn-A/B(-/-)

  6. Acute hypoxia limits endurance but does not affect muscle contractile properties.

    NARCIS (Netherlands)

    Degens, H.; Sanchez Horneros, J.M.; Hopman, M.T.E.

    2006-01-01

    Acute hypoxia causes skeletal muscle dysfunction in vitro, but little is known about its effect on muscle function in vivo. In 10 healthy male subjects, isometric contractile properties and fatigue resistance of the quadriceps muscle were determined during normoxia and hypoxia using electrically

  7. Prolonged ischemic heart disease and coronary artery bypass - relation to contractile reserve

    DEFF Research Database (Denmark)

    Kofoed, Klaus F; Bangsgaard, Regitze; Carstensen, Steen

    2002-01-01

    OBJECTIVE: A major effect of coronary artery bypass grafting (CABG) in patients with ischemic heart disease and impaired left ventricular (LV) contractile function is believed to be an improvement in LV function due to recovery of dysfunctional, but viable myocardium. However, recent studies have...

  8. Gallbladder contractility and mucus secretion after cholesterol feeding in the prairie dog

    NARCIS (Netherlands)

    Li, Y. F.; Moody, F. G.; Weisbrodt, N. W.; Zalewsky, C. A.; Coelho, J. C.; Senninger, N.; Gouma, D.

    1986-01-01

    The purpose of our study was to evaluate changes in gallbladder contractility and mucus secretion in vitro during the early stages of gallstone formation in prairie dogs. Thirty-two animals were divided into five groups. Control animals were fed a trace cholesterol diet. Experimental animals were

  9. Hydrogen ion changes and contractile behavior in the perfused rat heart

    NARCIS (Netherlands)

    Cingolani, H.E.; Maas, A.H.J.; Zimmerman, A.N.E.; Meijler, F.L.

    1975-01-01

    The effect of acid-base alterations was analyzed using isolated rat hearts perfused at constant coronary perfusion pressure, and stimulated to contract at constant rate. The amount of shortening in the major axis and its derivative were measured to assess myocardial contractility. Both the

  10. Maximum Entropy in Drug Discovery

    Directory of Open Access Journals (Sweden)

    Chih-Yuan Tseng

    2014-07-01

    Full Text Available Drug discovery applies multidisciplinary approaches either experimentally, computationally or both ways to identify lead compounds to treat various diseases. While conventional approaches have yielded many US Food and Drug Administration (FDA-approved drugs, researchers continue investigating and designing better approaches to increase the success rate in the discovery process. In this article, we provide an overview of the current strategies and point out where and how the method of maximum entropy has been introduced in this area. The maximum entropy principle has its root in thermodynamics, yet since Jaynes’ pioneering work in the 1950s, the maximum entropy principle has not only been used as a physics law, but also as a reasoning tool that allows us to process information in hand with the least bias. Its applicability in various disciplines has been abundantly demonstrated. We give several examples of applications of maximum entropy in different stages of drug discovery. Finally, we discuss a promising new direction in drug discovery that is likely to hinge on the ways of utilizing maximum entropy.

  11. Predicting changes in cardiac myocyte contractility during early drug discovery with in vitro assays

    Energy Technology Data Exchange (ETDEWEB)

    Morton, M.J., E-mail: michael.morton@astrazeneca.com [Discovery Sciences, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Armstrong, D.; Abi Gerges, N. [Drug Safety and Metabolism, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Bridgland-Taylor, M. [Discovery Sciences, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Pollard, C.E.; Bowes, J.; Valentin, J.-P. [Drug Safety and Metabolism, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom)

    2014-09-01

    Cardiovascular-related adverse drug effects are a major concern for the pharmaceutical industry. Activity of an investigational drug at the L-type calcium channel could manifest in a number of ways, including changes in cardiac contractility. The aim of this study was to define which of the two assay technologies – radioligand-binding or automated electrophysiology – was most predictive of contractility effects in an in vitro myocyte contractility assay. The activity of reference and proprietary compounds at the L-type calcium channel was measured by radioligand-binding assays, conventional patch-clamp, automated electrophysiology, and by measurement of contractility in canine isolated cardiac myocytes. Activity in the radioligand-binding assay at the L-type Ca channel phenylalkylamine binding site was most predictive of an inotropic effect in the canine cardiac myocyte assay. The sensitivity was 73%, specificity 83% and predictivity 78%. The radioligand-binding assay may be run at a single test concentration and potency estimated. The least predictive assay was automated electrophysiology which showed a significant bias when compared with other assay formats. Given the importance of the L-type calcium channel, not just in cardiac function, but also in other organ systems, a screening strategy emerges whereby single concentration ligand-binding can be performed early in the discovery process with sufficient predictivity, throughput and turnaround time to influence chemical design and address a significant safety-related liability, at relatively low cost. - Highlights: • The L-type calcium channel is a significant safety liability during drug discovery. • Radioligand-binding to the L-type calcium channel can be measured in vitro. • The assay can be run at a single test concentration as part of a screening cascade. • This measurement is highly predictive of changes in cardiac myocyte contractility.

  12. Retosiban Prevents Stretch-Induced Human Myometrial Contractility and Delays Labor in Cynomolgus Monkeys.

    Science.gov (United States)

    Aye, Irving L M H; Moraitis, Alexandros A; Stanislaus, Dinesh; Charnock-Jones, D Stephen; Smith, Gordon C S

    2018-03-01

    Stretch of the myometrium promotes its contractility and is believed to contribute to the control of parturition at term and to the increased risk of preterm birth in multiple pregnancies. To determine the effects of the putative oxytocin receptor (OTR) inverse agonist retosiban on (1) the contractility of human myometrial explants and (2) labor in nonhuman primates. Human myometrial biopsies were obtained at planned term cesarean, and explants were exposed to stretch in the presence and absence of a range of drugs, including retosiban. The in vivo effects of retosiban were determined in cynomolgus monkeys. Prolonged mechanical stretch promoted myometrial extracellular signal-regulated kinase (ERK)1/2 phosphorylation. Moreover, stretch-induced stimulation of myometrial contractility was prevented by ERK1/2 inhibitors. Retosiban (10 nM) prevented stretch-induced stimulation of myometrial contractility and phosphorylation of ERK1/2. Moreover, the inhibitory effect of retosiban on stretch-induced ERK1/2 phosphorylation was prevented by coincubation with a 100-fold excess of a peptide OTR antagonist, atosiban. Compared with vehicle-treated cynomolgus monkeys, treatment with oral retosiban (100 to 150 days of gestational age) reduced the risk of spontaneous delivery (hazard ratio = 0.07, 95% confidence interval 0.01 to 0.60, P = 0.015). The OTR acts as a uterine mechanosensor, whereby stretch increases myometrial contractility through agonist-free activation of the OTR. Retosiban prevents this through inverse agonism of the OTR and, in vivo, reduced the likelihood of spontaneous labor in nonhuman primates. We hypothesize that retosiban may be an effective preventative treatment of preterm birth in high-risk multiple pregnancies, an area of unmet clinical need.

  13. Dynamic MR cholangiography after fatty meal loading. Cystic contractility and dynamic evaluation of biliary stasis

    International Nuclear Information System (INIS)

    Omata, Takayuki; Saito, Kazuhiro; Kotake, Fumio; Mizokami, Yuji; Matsuoka, Takeshi; Abe, Kimihiko

    2002-01-01

    Dynamic MR cholangiography was conducted on patients with cholelithiasis or choledocholithiasis who had consumed a fatty test meal (Molyork) and the cystic contractility and dynamics of biliary stasis was evaluated. The subjects were 25 with intracystic cholelithiasis, 10 with choledocholithiasis and 10 normal controls. For an imaging sequence, the rapid acquisition with relaxation enhancement (RARE) method was employed and imaging was conducted for 40 min (every 30 s following Molyork administration) without breath-holding. The gallbladder contraction ratio was computed and the contractile ratio for the common bile duct was calculated. To determine the bile flow to the duodenum, the high-intensity signal, indicating the flow from the lower common bile duct, and perfusion of the duodenum were observed in dynamic mode on the monitor with the naked eye and interpreted as positive bile flow. The frequency of this flow was visually monitored. The gallbladder contractile ratio was significantly reduced in patients with cholelithiasis or choledocholithiasis compared with the controls. In a comparison with the normal controls, no sequential changes were noted in the mean contractile ratio of the common bile duct of the patients with cholelithiasis or choledocholithiasis. The mean frequency of bile flow observed for each 40 min period was 13±2.4, 6±2.2, and 4±1.3 times for the controls, those with intracystic cholelithiasis, and those with choledocholithiasis, respectively. Compared with the controls, the latter two patient groups showed evident reductions in the frequency of bile flow to the duodenum (p<0.001). Dynamic MRC combined with Molyork loading makes it possible to compute cystic contractile ratios and perform a dynamic examination of bile flow under non-invasive, near-physiological conditions. (author)

  14. Changes in contractile activation characteristics of rat fast and slow skeletal muscle fibres during regeneration.

    Science.gov (United States)

    Gregorevic, Paul; Plant, David R; Stupka, Nicole; Lynch, Gordon S

    2004-07-15

    Damaged skeletal muscle fibres are replaced with new contractile units via muscle regeneration. Regenerating muscle fibres synthesize functionally distinct isoforms of contractile and regulatory proteins but little is known of their functional properties during the regeneration process. An advantage of utilizing single muscle fibre preparations is that assessment of their function is based on the overall characteristics of the contractile apparatus and regulatory system and as such, these preparations are sensitive in revealing not only coarse, but also subtle functional differences between muscle fibres. We examined the Ca(2+)- and Sr(2+)-activated contractile characteristics of permeabilized fibres from rat fast-twitch (extensor digitorum longus) and slow-twitch (soleus) muscles at 7, 14 and 21 days following myotoxic injury, to test the hypothesis that fibres from regenerating fast and slow muscles have different functional characteristics to fibres from uninjured muscles. Regenerating muscle fibres had approximately 10% of the maximal force producing capacity (P(o)) of control (uninjured) fibres, and an altered sensitivity to Ca(2+) and Sr(2+) at 7 days post-injury. Increased force production and a shift in Ca(2+) sensitivity consistent with fibre maturation were observed during regeneration such that P(o) was restored to 36-45% of that in control fibres by 21 days, and sensitivity to Ca(2+) and Sr(2+) was similar to that of control (uninjured) fibres. The findings support the hypothesis that regenerating muscle fibres have different contractile activation characteristics compared with mature fibres, and that they adopt properties of mature fast- or slow-twitch muscle fibres in a progressive manner as the regeneration process is completed.

  15. Predicting changes in cardiac myocyte contractility during early drug discovery with in vitro assays

    International Nuclear Information System (INIS)

    Morton, M.J.; Armstrong, D.; Abi Gerges, N.; Bridgland-Taylor, M.; Pollard, C.E.; Bowes, J.; Valentin, J.-P.

    2014-01-01

    Cardiovascular-related adverse drug effects are a major concern for the pharmaceutical industry. Activity of an investigational drug at the L-type calcium channel could manifest in a number of ways, including changes in cardiac contractility. The aim of this study was to define which of the two assay technologies – radioligand-binding or automated electrophysiology – was most predictive of contractility effects in an in vitro myocyte contractility assay. The activity of reference and proprietary compounds at the L-type calcium channel was measured by radioligand-binding assays, conventional patch-clamp, automated electrophysiology, and by measurement of contractility in canine isolated cardiac myocytes. Activity in the radioligand-binding assay at the L-type Ca channel phenylalkylamine binding site was most predictive of an inotropic effect in the canine cardiac myocyte assay. The sensitivity was 73%, specificity 83% and predictivity 78%. The radioligand-binding assay may be run at a single test concentration and potency estimated. The least predictive assay was automated electrophysiology which showed a significant bias when compared with other assay formats. Given the importance of the L-type calcium channel, not just in cardiac function, but also in other organ systems, a screening strategy emerges whereby single concentration ligand-binding can be performed early in the discovery process with sufficient predictivity, throughput and turnaround time to influence chemical design and address a significant safety-related liability, at relatively low cost. - Highlights: • The L-type calcium channel is a significant safety liability during drug discovery. • Radioligand-binding to the L-type calcium channel can be measured in vitro. • The assay can be run at a single test concentration as part of a screening cascade. • This measurement is highly predictive of changes in cardiac myocyte contractility

  16. Revisiting the slow force response: the role of the PKG signaling pathway in the normal and the ischemic heart.

    Science.gov (United States)

    Castro-Ferreira, Ricardo; Neves, João Sérgio; Ladeiras-Lopes, Ricardo; Leite-Moreira, André M; Neiva-Sousa, Manuel; Almeida-Coelho, João; Ferreira-Martins, João; F Leite-Moreira, Adelino

    2014-09-01

    The myocardial response to acute stretch consists of a two-phase increase in contractility: an acute increase by the Frank-Starling mechanism and a gradual and time-dependent increase in force generated known as the slow force response (SFR). The SFR is actively modulated by different signaling pathways, but the role of protein kinase G (PKG) signaling is unknown. In this study we aim to characterize the role of the PKG signaling pathway in the SFR under normal and ischemic conditions. Rabbit papillary muscles were stretched from 92 to 100% of maximum length (Lmax) under basal conditions, in the absence (1) or presence of: a PKG agonist (2) and a PKG inhibitor (3); under ischemic conditions in the absence (4) or presence of: a PKG agonist (5); a nitric oxide (NO) donor (6) and a phosphodiesterase 5 (PDE5) inhibitor (7). Under normoxia, the SFR was significantly attenuated by inhibition of PKG and remained unaltered with PKG activation. Ischemia induced a progressive decrease in myocardial contractility after stretch. Neither the PKG agonist nor the NO donor altered the myocardial response to stretch under ischemic conditions. However, the use of a PDE5 inhibitor in ischemia partially reversed the progressive deterioration in contractility. PKG activity is essential for the SFR. During ischemia, a progressive decline in the force is observed in response to acute myocardial stretch. This dysfunctional response can be partially reversed by the use of PDE5 inhibitors. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  17. Maximum stellar iron core mass

    Indian Academy of Sciences (India)

    60, No. 3. — journal of. March 2003 physics pp. 415–422. Maximum stellar iron core mass. F W GIACOBBE. Chicago Research Center/American Air Liquide ... iron core compression due to the weight of non-ferrous matter overlying the iron cores within large .... thermal equilibrium velocities will tend to be non-relativistic.

  18. Maximum entropy beam diagnostic tomography

    International Nuclear Information System (INIS)

    Mottershead, C.T.

    1985-01-01

    This paper reviews the formalism of maximum entropy beam diagnostic tomography as applied to the Fusion Materials Irradiation Test (FMIT) prototype accelerator. The same formalism has also been used with streak camera data to produce an ultrahigh speed movie of the beam profile of the Experimental Test Accelerator (ETA) at Livermore. 11 refs., 4 figs

  19. Maximum entropy beam diagnostic tomography

    International Nuclear Information System (INIS)

    Mottershead, C.T.

    1985-01-01

    This paper reviews the formalism of maximum entropy beam diagnostic tomography as applied to the Fusion Materials Irradiation Test (FMIT) prototype accelerator. The same formalism has also been used with streak camera data to produce an ultrahigh speed movie of the beam profile of the Experimental Test Accelerator (ETA) at Livermore

  20. A portable storage maximum thermometer

    International Nuclear Information System (INIS)

    Fayart, Gerard.

    1976-01-01

    A clinical thermometer storing the voltage corresponding to the maximum temperature in an analog memory is described. End of the measurement is shown by a lamp switch out. The measurement time is shortened by means of a low thermal inertia platinum probe. This portable thermometer is fitted with cell test and calibration system [fr

  1. Neutron spectra unfolding with maximum entropy and maximum likelihood

    International Nuclear Information System (INIS)

    Itoh, Shikoh; Tsunoda, Toshiharu

    1989-01-01

    A new unfolding theory has been established on the basis of the maximum entropy principle and the maximum likelihood method. This theory correctly embodies the Poisson statistics of neutron detection, and always brings a positive solution over the whole energy range. Moreover, the theory unifies both problems of overdetermined and of underdetermined. For the latter, the ambiguity in assigning a prior probability, i.e. the initial guess in the Bayesian sense, has become extinct by virtue of the principle. An approximate expression of the covariance matrix for the resultant spectra is also presented. An efficient algorithm to solve the nonlinear system, which appears in the present study, has been established. Results of computer simulation showed the effectiveness of the present theory. (author)

  2. Inotropic responses of the frog ventricle to adenosine triphosphate and related changes in endogenous cyclic nucleotides.

    Science.gov (United States)

    Flitney, F W; Singh, J

    1980-07-01

    1. A study has been made of a well documented but poorly understood response of the isolated frog ventricle to treatment with exogenous adenosine 5' triphosphate (ATP). Measurements of membrane potential, isometric twitch tension and levels of endogenous 3',5'-cyclic nucleotides have been made at various times during the ATP-induced response. 2. ATP elicits a characteristic triphasic response, which comprises an initial, abrupt increase in contractility, rising to a maximum within a few beats (first phase); followed by a period when the twitch amplitude falls, sometimes to below the control level (second phase); and superceded by a more slowly developing and longer-lasting increase in contractile force (third phase). The response is unaffected by atropine, propranolol or phentolamine. However, the prostaglandin synthetase inhibitor indomethacin depresses the first phase and entirely suppresses the third phase. 3. The inotropic effects of ATP are accompanied by changes in the shape of the action potential. These effects are dose-related. The duration of the action potential (D-30mV) and its positive overshoot (O) are increased during all phases of the response, for [ATP]o's up to 10(-5) M. However, at higher [ATP]o's, D-30mV and O ar both reduced during the second phase (but not the first or third phase), when isometric twitch tension is also depressed. The relationship between action potential duration and twitch tension (P) for different [ATP]o's is linear for all three phases of the response, but the slopes of the curves (delta P/delta D) are markedly different, indicating that the sensitivity of the contractile system to membrane depolarization is not constant, but varies continuously throughout the response. 4. ATP has a potent stimulatory effect on the metabolism of endogenous 3',5'-cyclic nucleotides. The time courses of the changes in adenosine 3','5-cyclic monophosphate (3',5'-cyclic AMP) and guanosine 3',5'-cyclic monophosphate (3',5'-cyclic GMP) are

  3. Contractile Changes in the Vasculature After Subchronic Smoking

    DEFF Research Database (Denmark)

    Haanes, Kristian Agmund; Kruse, Lars Schack; Johansson, Helle Wulf

    2016-01-01

    clearance in the lungs and knock-out (KO) mice for this protein develop emphysema. SP-D is also weakly expressed in the vasculature. We aimed to investigate whether SP-D was important in the cardiovascular response to cigarette smoke exposure (CSE), by utilizing SP-D KO mice and a myograph setup. METHODS...

  4. Inhibition of PKC-dependent extracellular Ca2+ entry contributes to the depression of contractile activity in long-term pressure-overloaded endothelium-denuded rat aortas

    International Nuclear Information System (INIS)

    Padilla, J.; López, R.M.; López, P.; Castillo, M.C.; Querejeta, E.; Ruiz, A.; Castillo, E.F.

    2014-01-01

    We examined the contractile responsiveness of rat thoracic aortas under pressure overload after long-term suprarenal abdominal aortic coarctation (lt-Srac). Endothelium-dependent angiotensin II (ANG II) type 2 receptor (AT 2 R)-mediated depression of contractions to ANG II has been reported in short-term (1 week) pressure-overloaded rat aortas. Contractility was evaluated in the aortic rings of rats subjected to lt-Srac or sham surgery (Sham) for 8 weeks. ANG I and II levels and AT 2 R protein expression in the aortas of lt-Srac and Sham rats were also evaluated. lt-Srac attenuated the contractions of ANG II and phenylephrine in the aortas in an endothelium-independent manner. However, lt-Srac did not influence the transient contractions induced in endothelium-denuded aortic rings by ANG II, phenylephrine, or caffeine in Ca 2+ -free medium or the subsequent tonic constrictions induced by the addition of Ca 2+ in the absence of agonists. Thus, the contractions induced by Ca 2+ release from intracellular stores and Ca 2+ influx through stored-operated channels were not inhibited in the aortas of lt-Srac rats. Potassium-elicited contractions in endothelium-denuded aortic rings of lt-Srac rats remained unaltered compared with control tissues. Consequently, the contractile depression observed in aortic tissues of lt-Srac rats cannot be explained by direct inhibition of voltage-operated Ca 2+ channels. Interestingly, 12-O-tetradecanoylphorbol-13-acetate-induced contractions in endothelium-denuded aortic rings of lt-Srac rats were depressed in the presence but not in the absence of extracellular Ca 2+ . Neither levels of angiotensins nor of AT 2 R were modified in the aortas after lt-Srac. The results suggest that, in rat thoracic aortas, lt-Srac selectively inhibited protein kinase C-mediated activation of contraction that is dependent on extracellular Ca 2+ entry

  5. Apelin and APJ orchestrate complex tissue-specific control of cardiomyocyte hypertrophy and contractility in the hypertrophy-heart failure transition.

    Science.gov (United States)

    Parikh, Victoria Nicole; Liu, Jing; Shang, Ching; Woods, Christopher; Chang, Alex Chia Yu; Zhao, Mingming; Charo, David N; Grunwald, Zachary; Huang, Yong; Seo, Kinya; Tsao, Philip S; Bernstein, Daniel; Ruiz-Lozano, Pilar; Quertermous, Thomas; Ashley, Euan A

    2018-05-18

    The G protein coupled receptor APJ is a promising therapeutic target for heart failure. Constitutive deletion of APJ in the mouse is protective against the hypertrophy-heart failure transition via elimination of ligand-independent, β-arrestin dependent stretch transduction. However, the cellular origin of this stretch transduction and the details of its interaction with apelin signaling remain unknown. We generated mice with conditional elimination of APJ in the endothelium (APJ endo-/- ) and myocardium (APJ myo-/- ). No baseline difference was observed in LV function in APJ endo-/- , APJ myo-/- or controls (APJ endo+/+ , APJ myo+/+ ). After exposure to transaortic constriction (TAC), APJ endo-/- animals developed left ventricular failure while APJ myo-/- were protected. At the cellular level, carbon fiber stretch of freshly isolated single cardiomyocytes demonstrated decreased contractile response to stretch in APJ -/- cardiomyocytes compared to APJ +/+ cardiomyocytes. Calcium transient did not change with stretch in either APJ -/- or APJ +/+ cardiomyocytes. Application of apelin to APJ +/+ cardiomyocytes resulted in decreased calcium transient. Further, hearts of mice treated with apelin exhibited decreased phosphorylation at Troponin I (cTnI) N-terminal residues (Ser 22,23), consistent with increased calcium sensitivity. These data establish that APJ stretch transduction is mediated specifically by myocardial APJ, that APJ is necessary for stretch-induced increases in contractility, and that apelin opposes APJ's stretch-mediated hypertrophy signaling by lowering calcium transient while maintaining contractility through myofilament calcium sensitization. These findings underscore apelin's unique potential as a therapeutic agent that can simultaneously support cardiac function and protect against the hypertrophy-heart failure transition.

  6. The "sticking period" in a maximum bench press.

    Science.gov (United States)

    van den Tillaar, Roland; Ettema, Gertjan

    2010-03-01

    The purpose of this study was to examine muscle activity and three-dimensional kinematics in the ascending phase of a successful one-repetition maximum attempt in bench press for 12 recreational weight-training athletes, with special attention to the sticking period. The sticking period was defined as the first period of deceleration of the upward movement (i.e. from the highest barbell velocity until the first local lowest barbell velocity). All participants showed a sticking period during the upward movement that started about 0.2 s after the initial upward movement, and lasted about 0.9 s. Electromyography revealed that the muscle activity of the prime movers changed significantly from the pre-sticking to the sticking and post-sticking periods. A possible mechanism for the existence of the sticking period is the diminishing potentiation of the contractile elements during the upward movement together with the limited activity of the pectoral and deltoid muscles during this period.

  7. [Gallbladder contractility in children with functional abdominal pain or irritable bowel syndrome].

    Science.gov (United States)

    Iwańczak, Franciszek; Siedlecka-Dawidko, Jolanta; Iwanczak, Barbara

    2013-07-01

    III Rome Criteria of functional gastrointestinal disorders in children, distinguished the disturbances with abdominal pain, to which irritable bowel syndrome, functional abdominal pains, functional dyspepsia and abdominal migraine were included. THE AIM OF THE STUDY was sonographic assessment of the gallbladder and its contractility in functional abdominal pain and irritable bowel syndrome in children. The study comprised 96 children aged 6 to 18 years, 59 girls and 37 boys. Depending on diagnosis, the children were divided into three groups. 38 children with functional abdominal pain constituted the first group, 26 children with irritable bowel syndrome were included to the second group, the third group consisted of 32 healthy children (control group). Diagnosis of functional abdominal pain and irritable bowel syndrome was made based on the III Rome Criteria. In irritable bowel syndrome both forms with diarrhea (13) and with constipation (13) were observed. Anatomy and contractility of the gallbladder were assessed by ultrasound examination. The presence of septum, wall thickness, thick bile, vesicle volume in fasting state and 30th and 60th minute after test meal were taken into consideration. Test meal comprised about 15% of caloric requirement of moderate metabolism. Children with bile stones and organic diseases were excluded from the study. Thickened vesicle wall and thick bile were present more frequently in children with irritable bowel syndrome and functional abdominal pain than in control group (p functional abdominal pain than in irritable bowel syndrome and control group (p = 0.003, p = 0.05). Vesicle contractility after test meal was greatest in children with functional abdominal pain. Evaluation of diminished (smaller than 30%) and enlarged (greater then 80%) gallbladder contractility at 30th and 60th minute after test meal demonstrated disturbances of contractility in children with irritable bowel syndrome and functional abdominal pain. In children

  8. On Maximum Entropy and Inference

    Directory of Open Access Journals (Sweden)

    Luigi Gresele

    2017-11-01

    Full Text Available Maximum entropy is a powerful concept that entails a sharp separation between relevant and irrelevant variables. It is typically invoked in inference, once an assumption is made on what the relevant variables are, in order to estimate a model from data, that affords predictions on all other (dependent variables. Conversely, maximum entropy can be invoked to retrieve the relevant variables (sufficient statistics directly from the data, once a model is identified by Bayesian model selection. We explore this approach in the case of spin models with interactions of arbitrary order, and we discuss how relevant interactions can be inferred. In this perspective, the dimensionality of the inference problem is not set by the number of parameters in the model, but by the frequency distribution of the data. We illustrate the method showing its ability to recover the correct model in a few prototype cases and discuss its application on a real dataset.

  9. Maximum Water Hammer Sensitivity Analysis

    OpenAIRE

    Jalil Emadi; Abbas Solemani

    2011-01-01

    Pressure waves and Water Hammer occur in a pumping system when valves are closed or opened suddenly or in the case of sudden failure of pumps. Determination of maximum water hammer is considered one of the most important technical and economical items of which engineers and designers of pumping stations and conveyance pipelines should take care. Hammer Software is a recent application used to simulate water hammer. The present study focuses on determining significance of ...

  10. Maximum Gene-Support Tree

    Directory of Open Access Journals (Sweden)

    Yunfeng Shan

    2008-01-01

    Full Text Available Genomes and genes diversify during evolution; however, it is unclear to what extent genes still retain the relationship among species. Model species for molecular phylogenetic studies include yeasts and viruses whose genomes were sequenced as well as plants that have the fossil-supported true phylogenetic trees available. In this study, we generated single gene trees of seven yeast species as well as single gene trees of nine baculovirus species using all the orthologous genes among the species compared. Homologous genes among seven known plants were used for validation of the finding. Four algorithms—maximum parsimony (MP, minimum evolution (ME, maximum likelihood (ML, and neighbor-joining (NJ—were used. Trees were reconstructed before and after weighting the DNA and protein sequence lengths among genes. Rarely a gene can always generate the “true tree” by all the four algorithms. However, the most frequent gene tree, termed “maximum gene-support tree” (MGS tree, or WMGS tree for the weighted one, in yeasts, baculoviruses, or plants was consistently found to be the “true tree” among the species. The results provide insights into the overall degree of divergence of orthologous genes of the genomes analyzed and suggest the following: 1 The true tree relationship among the species studied is still maintained by the largest group of orthologous genes; 2 There are usually more orthologous genes with higher similarities between genetically closer species than between genetically more distant ones; and 3 The maximum gene-support tree reflects the phylogenetic relationship among species in comparison.

  11. Characterization of the adenosine receptor in cultured embryonic chick atrial myocytes: Coupling to modulation of contractility and adenylate cyclase activity and identification by direct radioligand binding

    International Nuclear Information System (INIS)

    Liang, B.T.

    1989-01-01

    Adenosine receptors in a spontaneously contracting atrial myocyte culture from 14-day chick embryos were characterized by radioligand binding studies and by examining the involvement of G-protein in coupling these receptors to a high-affinity state and to the adenylate cyclase and the myocyte contractility. Binding of the antagonist radioligand [3H]-8-cyclopentyl-1,3-diproylxanthine ([3H]CPX) was rapid, reversible and saturable and was to a homogeneous population of sites with a Kd value of 2.1 +/- 0.2 nM and an apparent maximum binding of 26.2 +/- 3 fmol/mg of protein (n = 10, +/- S.E.). Guanyl-5-yl-(beta, gamma-imido)diphosphate had no effect on either the Kd or the maximum binding and CPX reversed the N6-R-phenyl-2-propyladenosine-induced inhibition of adenylate cyclase activity and contractility, indicating that [3H] CPX is an antagonist radioligand. Competition curves for [3H] CPX binding by a series of reference adenosine agonists were consistent with labeling of an A1 adenosine receptor and were better fit by a two-site model than by a one-site model. ADP-ribosylation of the G-protein by the endogenous NAD+ in the presence of pertussis toxin shifted the competition curves from bi to monophasic with Ki values similar to those of the KL observed in the absence of prior pertussis intoxication. The adenosine agonists were capable of inhibiting both the adenylate cyclase activity and myocyte contractility in either the absence or the presence of isoproterenol. The A1 adenosine receptor-selective antagonist CPX reversed these agonist effects. The order of ability of the reference adenosine receptor agonists in causing these inhibitory effects was similar to the order of potency of the same agonists in inhibiting the specific [3H]CPX binding (N6-R-phenyl-2-propyladenosine greater than N6-S-phenyl-2-propyladenosine or N-ethyladenosine-5'-uronic acid)

  12. LCLS Maximum Credible Beam Power

    International Nuclear Information System (INIS)

    Clendenin, J.

    2005-01-01

    The maximum credible beam power is defined as the highest credible average beam power that the accelerator can deliver to the point in question, given the laws of physics, the beam line design, and assuming all protection devices have failed. For a new accelerator project, the official maximum credible beam power is determined by project staff in consultation with the Radiation Physics Department, after examining the arguments and evidence presented by the appropriate accelerator physicist(s) and beam line engineers. The definitive parameter becomes part of the project's safety envelope. This technical note will first review the studies that were done for the Gun Test Facility (GTF) at SSRL, where a photoinjector similar to the one proposed for the LCLS is being tested. In Section 3 the maximum charge out of the gun for a single rf pulse is calculated. In Section 4, PARMELA simulations are used to track the beam from the gun to the end of the photoinjector. Finally in Section 5 the beam through the matching section and injected into Linac-1 is discussed

  13. Pharmacological radionuclide ventriculography for detection of myocardial contractile reserve in patients after myocardial infarction: head-to-head comparison of low dose dobutamine and low dose dypiridamole

    International Nuclear Information System (INIS)

    Petrasinovic, Z.; Ostojic, M.; Beleslin, B.; Stojkovic, S.; Nedeljkovic, M.; Stankovic, G.; Dikic, A.; Pavlovic, S.; Sobic, D.

    2002-01-01

    Background. Low dose pharmacological stress echocardiography with either dobutamine or dipyridamole infusion has been proposed for recognition of myocardial viability. However, dependence on adequate acoustic window, observer experience, and the mild degree of wall motion changes make the viability assessment by stress echocardiography especially bothersome. The objective of the study was to evaluate the ability of low dose dobutamine and low dose dipyridamole radionuclide ventriculography to detect contractile reserve in patients after myocardial infarction and functional recovery after coronary angioplasty. Methods. The study group consisted of 20 consecutive patients (52±10 years, 17 male) with previous myocardial infarction and resting regional dyssynergy, in whom diagnostic cardiac catheterization revealed significant one-vessel coronary artery stenosis suitable for angioplasty. Each patient underwent equilibrium 99m-Tc radionuclide ventriculography which was performed at rest and during low dose dipyridamole (0.28 mg/kg over 2 minutes) and low dose dobutamine infusion (up to 10 mcg/kg/min). Left ventricular global and regional ejection fractions were determined. Increase of regional ejection fraction for >5% (inferoapical and posterolateral regions) or >10% (anteroseptal regions) during low dose dobutamine and dipyridamole in infarcted regions, as well as in the follow up period, was considered as index of contractile reserve. After 8 weeks of successful angioplasty, resting radionuclide ventriculography was repeated in all patients in order to identify functional recovery of the infarct zone. Results. Out of the 180 analyzed segments (20x9), 90 regional ejection fractions have shown depressed contractility. The mean of the regional ejection fractions showing depressed contractility increased from the resting value of 34±12% to 42±14% in the follow-up period (p=0.06). Of the 90 with baseline dyssynergy, 46 were responders during low-dose dobutamine (51

  14. Effect of changes in contractility on the index of myocardial performance in the dysfunctional left ventricle

    Directory of Open Access Journals (Sweden)

    Lavine Steven J

    2006-11-01

    Full Text Available Abstract Background The index of myocardial performance has prognostic power in patients with cardiomyopathy and following myocardial infarction. As the index of myocardial performance has been shown to be preload and afterload dependent, the effect of altering contractility on IMP and its components with left ventricular dysfunction has been incompletely delineated. Methods Chronic left ventricular dysfunction was induced in 10 canines using coronary microsphere embolization. Each dog was instrumented and imaged with 2D echo and Doppler. At the same atrially paced rate, contractility was increased with a dobutamine infusion and then following 4 weeks of oral digoxin. Results With chronic left ventricular dysfunction, a reduced left ventricular ejection fraction (42 ± 3%, p Conclusion Increased inotropy with digoxin and dobutamine reduced the index of myocardial performance in dogs with left ventricular dysfunction. Shortened isovolumic contraction time, increased diastolic filling period, and reduced left ventricular end diastolic pressure with digoxin may provide insight into its efficacy in heart failure.

  15. An Estimating Method of Contractile State Changes Come From Continuous Isometric Contraction of Skeletal Muscle

    Energy Technology Data Exchange (ETDEWEB)

    Park, H.J.; Lee, S.J. [Wonkwang University, Iksan (Korea)

    2003-01-01

    In this study was proposed that a new estimating method for investigation of contractile state changes which generated from continuous isometric contraction of skeletal muscle. The physiological changes (EMG, ECG) and the psychological changes by CNS(central nervous system) were measured by experiments, while the muscle of subjects contracted continuously with isometric contraction in constant load. The psychological changes were represented as three-step-change named 'fatigue', 'pain' and 'sick(greatly pain)' from oral test, and the method which compared physiological change with psychological change on basis of these three steps was developed. The result of analyzing the physiological signals, EMG and ECG signal changes were observed at the vicinity of judging point in time of psychological changes. Namely, it is supposed that contractile states have three kind of states pattern (stable, fatigue, pain) instead of two states (stable, fatigue). (author). 24 refs., 7 figs.

  16. Numerical investigation of perforated polymer microcantilever sensor for contractile behavior of cardiomyocytes

    Science.gov (United States)

    Khoa Nguyen, Trieu; Lee, Dong-Weon; Lee, Bong-Kee

    2017-06-01

    In this study, a numerical investigation of microcantilever sensors for detecting the contractile behavior of cardiomyocytes (CMs) was performed. Recently, a novel surface-patterned perforated SU-8 microcantilever sensor has been developed for the preliminary screening of cardiac toxicity. From the contractile motion of the CMs cultured on the microcantilever surface, a macroscopic bending of the microcantilever was obtained, which is considered to reflect a physiological change. As a continuation of the previous research, a novel numerical method based on a surface traction model was proposed and verified to further understand the bending behavior of the microcantilevers. Effects of various factors, including surface traction magnitude, focal area of CMs, and stiffness of microcantilever, on the bending displacement were investigated. From static and transient analyses, the focal area was found to be the most crucial factor. In addition, the current result can provide a design guideline for various micromechanical devices based on the same principle.

  17. Cell density and actomyosin contractility control the organization of migrating collectives within an epithelium

    Science.gov (United States)

    Loza, Andrew J.; Koride, Sarita; Schimizzi, Gregory V.; Li, Bo; Sun, Sean X.; Longmore, Gregory D.

    2016-01-01

    The mechanisms underlying collective migration are important for understanding development, wound healing, and tumor invasion. Here we focus on cell density to determine its role in collective migration. Our findings show that increasing cell density, as might be seen in cancer, transforms groups from broad collectives to small, narrow streams. Conversely, diminishing cell density, as might occur at a wound front, leads to large, broad collectives with a distinct leader–follower structure. Simulations identify force-sensitive contractility as a mediator of how density affects collectives, and guided by this prediction, we find that the baseline state of contractility can enhance or reduce organization. Finally, we test predictions from these data in an in vivo epithelium by using genetic manipulations to drive collective motion between predicted migratory phases. This work demonstrates how commonly altered cellular properties can prime groups of cells to adopt migration patterns that may be harnessed in health or exploited in disease. PMID:27605707

  18. Effects of ageing on single muscle fibre contractile function following short-term immobilisation

    DEFF Research Database (Denmark)

    Hvid, Lars G; Ortenblad, Niels; Aagaard, Per

    2011-01-01

    Very little attention has been given to the combined effects of healthy ageing and short-term disuse on the contractile function of human single muscle fibres. Therefore, the present study investigated the effects of 2 weeks of lower limb cast immobilisation (i.e. disuse) on selected contractile...... IIa: young 18% and old 25%; P selective decrease in Ca(2+) sensitivity in MHC IIa fibres of young (P ....05), respectively. In conclusion, 2 weeks of lower limb immobilisation caused greater impairments in single muscle fibre force and specific force in MHC IIa than MHC I fibres independently of age. In contrast, immobilisation-induced changes in Ca(2+) sensitivity that were dependent on age and MHC isoform....

  19. Levothyroxine treatment generates an abnormal uterine contractility patterns in an in vitro animal model.

    Science.gov (United States)

    Corriveau, Stéphanie; Blouin, Simon; Raiche, Évelyne; Nolin, Marc-Antoine; Rousseau, Éric; Pasquier, Jean-Charles

    2015-12-01

    Abnormal uterine contraction patterns were recently demonstrated in uterine strips from pregnant women treated with Levothyroxine (T4). These abnormalities were correlated with an increased risk of C-section delivery and associated surgical complications. To date, no study has investigated whether uterine contractility is modified by hypothyroidism or T4 treatment. Herein, we analyze the physiological role of T4 on uterine contractions. Female non-pregnant Sprague-Dawley rats ( N  = 22) were used and divided into four groups: 1) control, 2) hypothyroidism, 3) hypothyroidism treated with low T4 doses (20 μg/kg/day) and 4) with high T4 doses (100 μg/kg/day). Hypothyroidism was induced by an iodine-deficient diet. Isometric tension measurements were performed in vitro on myometrium tissues in isolated organ baths. Contractile activity parameters were quantified (amplitude, duration, frequency and area under the curve) using pharmacological tools to assess their effect. Screening of thyroid function confirmed a hypothyroid state for all rats under iodine-free diet to which T4 was subsequently administered to counterbalance hypothyroidism. Results demonstrate that hypothyroidism significantly decreased contractile duration (-17%) and increased contractile frequency (+26%), while high doses of T4 increased duration (+200%) and decreased frequency (-51%). These results thus mimic the pattern of abnormal contractions previously observed in uterine tissue from T4-treated hypothyroid pregnant women. Our data suggest that changes in myometrial reactivity are induced by T4 treatment. Thus, in conjunction with our previous observations on human myometrial strips, management of hypothyroidism should be improved to reduce the rate of C-sections in this group of patients.

  20. Functions of nonmuscle myosin II in assembly of the cellular contractile system.

    Directory of Open Access Journals (Sweden)

    Maria Shutova

    Full Text Available The contractile system of nonmuscle cells consists of interconnected actomyosin networks and bundles anchored to focal adhesions. The initiation of the contractile system assembly is poorly understood structurally and mechanistically, whereas system's maturation heavily depends on nonmuscle myosin II (NMII. Using platinum replica electron microscopy in combination with fluorescence microscopy, we characterized the structural mechanisms of the contractile system assembly and roles of NMII at early stages of this process. We show that inhibition of NMII by a specific inhibitor, blebbistatin, in addition to known effects, such as disassembly of stress fibers and mature focal adhesions, also causes transformation of lamellipodia into unattached ruffles, loss of immature focal complexes, loss of cytoskeleton-associated NMII filaments and peripheral accumulation of activated, but unpolymerized NMII. After blebbistatin washout, assembly of the contractile system begins with quick and coordinated recovery of lamellipodia and focal complexes that occurs before reappearance of NMII bipolar filaments. The initial formation of focal complexes and subsequent assembly of NMII filaments preferentially occurred in association with filopodial bundles and concave actin bundles formed by filopodial roots at the lamellipodial base. Over time, accumulating NMII filaments help to transform the precursor structures, focal complexes and associated thin bundles, into stress fibers and mature focal adhesions. However, semi-sarcomeric organization of stress fibers develops at much slower rate. Together, our data suggest that activation of NMII motor activity by light chain phosphorylation occurs at the cell edge and is uncoupled from NMII assembly into bipolar filaments. We propose that activated, but unpolymerized NMII initiates focal complexes, thus providing traction for lamellipodial protrusion. Subsequently, the mechanical resistance of focal complexes activates a

  1. Influence of genotype on contractile protein differentiation in different bovine muscles during foetal life

    OpenAIRE

    Gagnière , Hélène; Ménissier , François; Geay , Yves; Picard , Brigitte

    2000-01-01

    International audience; The purpose of this work was to compare muscle fibre differentiation in two genetic types: "normal charolais" and double-muscled (DM) "INRA 95" cattles displaying muscle hypertrophy. Six muscles with different contractile and metabolic characteristics in adult animal: Masseter, Diaphragma (Di), Biceps femoris (BF), Longissimus thoracis, Semitendinosus and Cutaneus trunci (CT) were excised from 60 to 260-day-old fœtuses of both genotypes. These muscles present different...

  2. Chronic clenbuterol treatment compromises force production without directly altering skeletal muscle contractile machinery

    Science.gov (United States)

    Py, G; Ramonatxo, C; Sirvent, P; Sanchez, A M J; Philippe, A G; Douillard, A; Galbès, O; Lionne, C; Bonnieu, A; Chopard, A; Cazorla, O; Lacampagne, A; Candau, R B

    2015-01-01

    Clenbuterol is a β2-adrenergic receptor agonist known to induce skeletal muscle hypertrophy and a slow-to-fast phenotypic shift. The aim of the present study was to test the effects of chronic clenbuterol treatment on contractile efficiency and explore the underlying mechanisms, i.e. the muscle contractile machinery and calcium-handling ability. Forty-three 6-week-old male Wistar rats were randomly allocated to one of six groups that were treated with either subcutaneous equimolar doses of clenbuterol (4 mg kg−1 day−1) or saline solution for 9, 14 or 21 days. In addition to the muscle hypertrophy, although an 89% increase in absolute maximal tetanic force (Po) was noted, specific maximal tetanic force (sPo) was unchanged or even depressed in the slow twitch muscle of the clenbuterol-treated rats (P muscle contraction and relaxation force kinetics indicated that clenbuterol treatment significantly reduced the rate constant of force development and the slow and fast rate constants of relaxation in extensor digitorum longus muscle (P fast rate constant of relaxation in soleus muscle (P fibres (fast twitch fibres) from clenbuterol-treated animals demonstrated decreased amplitude after 14 days (−19%, P < 0.01) and 21 days (−25%, P < 0.01). In conclusion, we showed that chronic clenbuterol treatment reduces contractile efficiency, with altered contraction and relaxation kinetics, but without directly altering the contractile machinery. Lower Ca2+ release during contraction could partially explain these deleterious effects. PMID:25656230

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

    Science.gov (United States)

    Bunda, Jordan; Gittings, William; Vandenboom, Rene

    2018-01-30

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

  4. Cardiac-specific overexpression of catalase attenuates lipopolysaccharide-induced myocardial contractile dysfunction: role of autophagy.

    Science.gov (United States)

    Turdi, Subat; Han, Xuefeng; Huff, Anna F; Roe, Nathan D; Hu, Nan; Gao, Feng; Ren, Jun

    2012-09-15

    Lipopolysaccharide (LPS) from gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complications in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis, and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity, and carbonyl formation. A Kaplan-Meier curve was constructed for survival after LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice after LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O(2)(-), and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury after LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by the antioxidant N-acetylcysteine and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

    OpenAIRE

    Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

    2012-01-01

    Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged ...

  6. A thermodynamical model for stress-fiber organization in contractile cells

    OpenAIRE

    Foucard, Louis; Vernerey, Franck J.

    2012-01-01

    Cell mechanical adaptivity to external stimuli is vital to many of its biological functions. A critical question is therefore to understand the formation and organization of the stress fibers from which emerge the cell’s mechanical properties. By accounting for the mechanical aspects and the viscoelastic behavior of stress fibers, we here propose a thermodynamic model to predict the formation and orientation of stress fibers in contractile cells subjected to constant or cyclic stretch and dif...

  7. Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

    Science.gov (United States)

    Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

    2012-01-01

    Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity and carbonyl formation. Kaplan-Meier curve was constructed for survival following LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice following LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O2−, and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury following LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by antioxidant NAC and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. PMID:22902401

  8. Cardiac myofibrillar contractile properties during the progression from hypertension to decompensated heart failure.

    Science.gov (United States)

    Hanft, Laurin M; Emter, Craig A; McDonald, Kerry S

    2017-07-01

    Heart failure arises, in part, from a constellation of changes in cardiac myocytes including remodeling, energetics, Ca 2+ handling, and myofibrillar function. However, little is known about the changes in myofibrillar contractile properties during the progression from hypertension to decompensated heart failure. The aim of the present study was to provide a comprehensive assessment of myofibrillar functional properties from health to heart disease. A rodent model of uncontrolled hypertension was used to test the hypothesis that myocytes in compensated hearts exhibit increased force, higher rates of force development, faster loaded shortening, and greater power output; however, with progression to overt heart failure, we predicted marked depression in these contractile properties. We assessed contractile properties in skinned cardiac myocyte preparations from left ventricles of Wistar-Kyoto control rats and spontaneous hypertensive heart failure (SHHF) rats at ~3, ~12, and >20 mo of age to evaluate the time course of myofilament properties associated with normal aging processes compared with myofilaments from rats with a predisposition to heart failure. In control rats, the myofilament contractile properties were virtually unchanged throughout the aging process. Conversely, in SHHF rats, the rate of force development, loaded shortening velocity, and power all increased at ~12 mo and then significantly fell at the >20-mo time point, which coincided with a decrease in left ventricular fractional shortening. Furthermore, these changes occurred independent of changes in β-myosin heavy chain but were associated with depressed phosphorylation of myofibrillar proteins, and the fall in loaded shortening and peak power output corresponded with the onset of clinical signs of heart failure. NEW & NOTEWORTHY This novel study systematically examined the power-generating capacity of cardiac myofilaments during the progression from hypertension to heart disease. Previously

  9. Changes in contractile properties of muscles receiving repeat injections of botulinum toxin (Botox).

    Science.gov (United States)

    Fortuna, Rafael; Vaz, Marco Aurélio; Youssef, Aliaa Rehan; Longino, David; Herzog, Walter

    2011-01-04

    Botulinum toxin type A (BTX-A) is a frequently used therapeutic tool to denervate muscles in the treatment of neuromuscular disorders. Although considered safe by the US Food and Drug Administration, BTX-A can produce adverse effects in target and non-target muscles. With an increased use of BTX-A for neuromuscular disorders, the effects of repeat injections of BTX-A on strength, muscle mass and structure need to be known. Therefore, the purpose of this study was to investigate the changes in strength, muscle mass and contractile material in New Zealand White (NZW) rabbits. Twenty NZW rabbits were divided into 4 groups: control and 1, 3 and 6 months of unilateral, repeat injections of BTX-A into the quadriceps femoris. Outcome measures included knee extensor torque, muscle mass and the percentage of contractile material in the quadriceps muscles of the target and non-injected contralateral hindlimbs. Strength in the injected muscles was reduced by 88%, 89% and 95% in the 1, 3 and 6 months BTX-A injected hindlimbs compared to controls. Muscle mass was reduced by 50%, 42% and 31% for the vastus lateralis (VL), rectus femoris (RF) and vastus medialis (VM), respectively, at 1 month, by 68%, 51% and 50% at 3 months and by 76%, 44% and 13% at 6 months. The percentage of contractile material was reduced for the 3 and 6 months animals to 80-64%, respectively, and was replaced primarily by fat. Similar, but less pronounced results were also observed for the quadriceps muscles of the contralateral hindlimbs, suggesting that repeat BTX-A injections cause muscle atrophy and loss of contractile tissue in target muscles and also in non-target muscles that are far removed from the injection site. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Generic maximum likely scale selection

    DEFF Research Database (Denmark)

    Pedersen, Kim Steenstrup; Loog, Marco; Markussen, Bo

    2007-01-01

    in this work is on applying this selection principle under a Brownian image model. This image model provides a simple scale invariant prior for natural images and we provide illustrative examples of the behavior of our scale estimation on such images. In these illustrative examples, estimation is based......The fundamental problem of local scale selection is addressed by means of a novel principle, which is based on maximum likelihood estimation. The principle is generally applicable to a broad variety of image models and descriptors, and provides a generic scale estimation methodology. The focus...

  11. PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility

    Directory of Open Access Journals (Sweden)

    Ana E. González Wusener

    2016-01-01

    Full Text Available Cell contractility and migration by integrins depends on precise regulation of protein tyrosine kinase and Rho-family GTPase activities in specific spatiotemporal patterns. Here we show that protein tyrosine phosphatase PTP1B cooperates with β3 integrin to activate the Src/FAK signalling pathway which represses RhoA-myosin-dependent contractility. Using PTP1B null (KO cells and PTP1B reconstituted (WT cells, we determined that some early steps following cell adhesion to fibronectin and vitronectin occurred robustly in WT cells, including aggregation of β3 integrins and adaptor proteins, and activation of Src/FAK-dependent signalling at small puncta in a lamellipodium. However, these events were significantly impaired in KO cells. We established that cytoskeletal strain and cell contractility was highly enhanced at the periphery of KO cells compared to WT cells. Inhibition of the Src/FAK signalling pathway or expression of constitutive active RhoA in WT cells induced a KO cell phenotype. Conversely, expression of constitutive active Src or myosin inhibition in KO cells restored the WT phenotype. We propose that this novel function of PTP1B stimulates permissive conditions for adhesion and lamellipodium assembly at the protruding edge during cell spreading and migration.

  12. PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility

    Science.gov (United States)

    González Wusener, Ana E.; González, Ángela; Nakamura, Fumihiko; Arregui, Carlos O.

    2016-01-01

    ABSTRACT Cell contractility and migration by integrins depends on precise regulation of protein tyrosine kinase and Rho-family GTPase activities in specific spatiotemporal patterns. Here we show that protein tyrosine phosphatase PTP1B cooperates with β3 integrin to activate the Src/FAK signalling pathway which represses RhoA-myosin-dependent contractility. Using PTP1B null (KO) cells and PTP1B reconstituted (WT) cells, we determined that some early steps following cell adhesion to fibronectin and vitronectin occurred robustly in WT cells, including aggregation of β3 integrins and adaptor proteins, and activation of Src/FAK-dependent signalling at small puncta in a lamellipodium. However, these events were significantly impaired in KO cells. We established that cytoskeletal strain and cell contractility was highly enhanced at the periphery of KO cells compared to WT cells. Inhibition of the Src/FAK signalling pathway or expression of constitutive active RhoA in WT cells induced a KO cell phenotype. Conversely, expression of constitutive active Src or myosin inhibition in KO cells restored the WT phenotype. We propose that this novel function of PTP1B stimulates permissive conditions for adhesion and lamellipodium assembly at the protruding edge during cell spreading and migration. PMID:26700725

  13. A human in vitro model of Duchenne muscular dystrophy muscle formation and contractility.

    Science.gov (United States)

    Nesmith, Alexander P; Wagner, Matthew A; Pasqualini, Francesco S; O'Connor, Blakely B; Pincus, Mark J; August, Paul R; Parker, Kevin Kit

    2016-10-10

    Tongue weakness, like all weakness in Duchenne muscular dystrophy (DMD), occurs as a result of contraction-induced muscle damage and deficient muscular repair. Although membrane fragility is known to potentiate injury in DMD, whether muscle stem cells are implicated in deficient muscular repair remains unclear. We hypothesized that DMD myoblasts are less sensitive to cues in the extracellular matrix designed to potentiate structure-function relationships of healthy muscle. To test this hypothesis, we drew inspiration from the tongue and engineered contractile human muscle tissues on thin films. On this platform, DMD myoblasts formed fewer and smaller myotubes and exhibited impaired polarization of the cell nucleus and contractile cytoskeleton when compared with healthy cells. These structural aberrations were reflected in their functional behavior, as engineered tongues from DMD myoblasts failed to achieve the same contractile strength as healthy tongue structures. These data suggest that dystrophic muscle may fail to organize with respect to extracellular cues necessary to potentiate adaptive growth and remodeling. © 2016 Nesmith et al.

  14. A contractile and counterbalancing adhesion system controls the 3D shape of crawling cells.

    Science.gov (United States)

    Burnette, Dylan T; Shao, Lin; Ott, Carolyn; Pasapera, Ana M; Fischer, Robert S; Baird, Michelle A; Der Loughian, Christelle; Delanoe-Ayari, Helene; Paszek, Matthew J; Davidson, Michael W; Betzig, Eric; Lippincott-Schwartz, Jennifer

    2014-04-14

    How adherent and contractile systems coordinate to promote cell shape changes is unclear. Here, we define a counterbalanced adhesion/contraction model for cell shape control. Live-cell microscopy data showed a crucial role for a contractile meshwork at the top of the cell, which is composed of actin arcs and myosin IIA filaments. The contractile actin meshwork is organized like muscle sarcomeres, with repeating myosin II filaments separated by the actin bundling protein α-actinin, and is mechanically coupled to noncontractile dorsal actin fibers that run from top to bottom in the cell. When the meshwork contracts, it pulls the dorsal fibers away from the substrate. This pulling force is counterbalanced by the dorsal fibers' attachment to focal adhesions, causing the fibers to bend downward and flattening the cell. This model is likely to be relevant for understanding how cells configure themselves to complex surfaces, protrude into tight spaces, and generate three-dimensional forces on the growth substrate under both healthy and diseased conditions.

  15. Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions

    Science.gov (United States)

    Doyle, Andrew D.; Carvajal, Nicole; Jin, Albert; Matsumoto, Kazue; Yamada, Kenneth M.

    2015-11-01

    The physical properties of two-dimensional (2D) extracellular matrices (ECMs) modulate cell adhesion dynamics and motility, but little is known about the roles of local microenvironmental differences in three-dimensional (3D) ECMs. Here we generate 3D collagen gels of varying matrix microarchitectures to characterize their regulation of 3D adhesion dynamics and cell migration. ECMs containing bundled fibrils demonstrate enhanced local adhesion-scale stiffness and increased adhesion stability through balanced ECM/adhesion coupling, whereas highly pliable reticular matrices promote adhesion retraction. 3D adhesion dynamics are locally regulated by ECM rigidity together with integrin/ECM association and myosin II contractility. Unlike 2D migration, abrogating contractility stalls 3D migration regardless of ECM pore size. We find force is not required for clustering of activated integrins on 3D native collagen fibrils. We propose that efficient 3D migration requires local balancing of contractility with ECM stiffness to stabilize adhesions, which facilitates the detachment of activated integrins from ECM fibrils.

  16. EXERCISE PERFORMANCE AND MUSCLE CONTRACTILE PROPERTIES AFTER CREATINE MONOHYDRATE SUPPLEMENTATION IN AEROBIC-ANAEROBIC TRAINING RATS

    Directory of Open Access Journals (Sweden)

    Nickolay Boyadjiev

    2007-12-01

    Full Text Available The purpose of this study was to investigate the effects of creatine monohydrate supplementation on exercise performance and contractile variables in aerobic-anaerobic training rats. Twenty 90-day-old male Sprague Dawley rats were divided into two groups - creatine (Cr and controls (K. The creatine group received creatine monohydrate as a nutritional supplement, whereas the control group was given placebo. Both groups were trained 5 days a week on a treadmill for 20 days in a mixed (aerobic-anaerobic metabolic working regimen (27 m·min-1, 15% elevation for 40 min. The exercise performance (sprint-test, contractile properties (m. tibialis anterior, oxidative enzyme activity (SDH, LDH, NADH2 in m. soleus and blood hematological and chemical variables were assessed in the groups at the end of the experiment. It was found out that creatine supplementation improved the exercise performance after 20 days of administration in a dose of 60 mg per day on the background of a mixed (aerobic-anaerobic exercise training. At the end of the trial the Cr-group demonstrated better values for the variables which characterize the contractile properties of m. tibialis anterior containing predominantly types IIA and IIB muscle fibers. On the other hand, a higher oxidative capacity was found out in m. soleus (type I muscle fibers as a result of 20-day creatine supplementation. No side effects of creatine monohydrate supplementation were assessed by the hematological and blood biochemical indices measured in this study

  17. Galectin-3 and fibulin-1 in systolic heart failure - relation to glucose metabolism and left ventricular contractile reserve

    OpenAIRE

    Holmager, Pernille; Egstrup, Michael; Gustafsson, Ida; Schou, Morten; Dahl, Jordi S.; Rasmussen, Lars Melholt; M?ller, Jacob E.; Tuxen, Christian; Faber, Jens; Kistorp, Caroline

    2017-01-01

    Background: Heart failure (HF) patients with diabetes (DM) have an adverse prognosis and reduced functional capacity, which could be associated with cardiac fibrosis, increased chamber stiffness and reduced left ventricular (LV) contractile reserve. Galectin-3 (Gal-3) and fibulin-1 are circulating biomarkers potentially reflecting cardiac fibrosis. We hypothesize that plasma levels of Gal-3 and fibulin-1 are elevated in HF patients with DM and are associated with reduced LV contractile reserv...

  18. Extreme Maximum Land Surface Temperatures.

    Science.gov (United States)

    Garratt, J. R.

    1992-09-01

    There are numerous reports in the literature of observations of land surface temperatures. Some of these, almost all made in situ, reveal maximum values in the 50°-70°C range, with a few, made in desert regions, near 80°C. Consideration of a simplified form of the surface energy balance equation, utilizing likely upper values of absorbed shortwave flux (1000 W m2) and screen air temperature (55°C), that surface temperatures in the vicinity of 90°-100°C may occur for dry, darkish soils of low thermal conductivity (0.1-0.2 W m1 K1). Numerical simulations confirm this and suggest that temperature gradients in the first few centimeters of soil may reach 0.5°-1°C mm1 under these extreme conditions. The study bears upon the intrinsic interest of identifying extreme maximum temperatures and yields interesting information regarding the comfort zone of animals (including man).

  19. In vitro study on the effects of some selected agonists and antagonists of alpha(1)-adrenergic receptors on the contractility of the aneurysmally-changed aortic smooth muscle in humans.

    Science.gov (United States)

    Gnus, J; Czerski, A; Ferenc, S; Zawadzki, W; Witkiewicz, W; Hauzer, W; Rusiecka, A; Bujok, J

    2012-02-01

    The study included 18 sections of the aneurysmally-changed abdominal aortas, obtained from patients of the Provincial Specialist Hospital in Wroclaw and 18 sections of normal abdominal aortas obtained from swine. The collected samples were placed horizontally in the incubation chamber. Changes in their transverse section area were registered. They were stretched to a tension of 5 mN. Krebs-Henseleit buffer was used as the incubatory environment. Incubation of the sections was performed at a temperature of 37°C, in the gaseous mixture of oxygen and carbon dioxide used in the following proportion: 95% of O(2) and 5% of CO(2). Contractions of the aorta were registered with isotonic transducers (Letica Scientific Instruments). In the studies, we examined the influence of α(1)-adrenergic receptors (and their subtypes α(1A), α(1B), α(1D)) on the contractility of the aortic muscle in humans and swine by their stimulation or inhibition with some selected agonists or antagonists. This time, it was shown that the stimulation of α(1)-adrenergic receptors leads to contractions of the human and swine aortic muscle; the observed increase in the muscle tone may follow from the stimulation of all subtypes of alpha-1 receptor (α(1A), α(1B), α(1D)). All three subtypes of 1-adrenergic receptor are engaged in vasoconstriction, especially of α(1A) and α(1D) subtypes; the α(1B) subtype is less significant for aortic contractility. The contractile response of the aneurysmally-changed abdominal aorta in humans to agonists of α-adrenergic receptors was significantly less intense than that of the normal porcine aorta. It can be concluded that aneurysms influence the contractile response of the aorta.

  20. The Masticatory Contractile Load Induced Expression and Activation of Akt1/PKBα in Muscle Fibers at the Myotendinous Junction within Muscle-Tendon-Bone Unit

    Directory of Open Access Journals (Sweden)

    Yüksel Korkmaz

    2010-01-01

    Full Text Available The cell specific detection of enzyme activation in response to the physiological contractile load within muscle-tendon-bone unit is essential for understanding of the mechanical forces transmission from muscle cells via tendon to the bone. The hypothesis that the physiological mechanical loading regulates activation of Akt1/PKBα at Thr308 and at Ser473 in muscle fibers within muscle-tendon-bone unit was tested using quantitative immunohistochemistry, confocal double fluorescence analysis, and immunoblot analysis. In comparison to the staining intensities in peripheral regions of the muscle fibers, Akt1/PKBα was detected with a higher staining intensity in muscle fibers at the myotendinous junction (MTJ areas. In muscle fibers at the MTJ areas, Akt1/PKBα is dually phosphorylated at Thr308 and Ser473. The immunohistochemical results were confirmed by immunoblot analysis. We conclude that contractile load generated by masticatory muscles induces local domain-dependent expression of Akt1/PKBα as well as activation by dually phosphorylation at Thr308 and Ser473 in muscle fibers at the MTJ areas within muscle-tendon-bone unit.

  1. Contractile recovery of microtissues after giant shear events

    Science.gov (United States)

    Morley, Cameron; Bhattacharjee, Tapomoy; Ellison, Sarah; Sawyer, W.; Angelini, Thomas

    Cells are often dispersed in extracellular matrix (ECM) gels like collagen and Matrigel as minimal tissue models. Generally, large-scale contraction of these constructs is observed, in which the degree of contraction of the entire system correlates with cell density and ECM concentration. The freedom to perform diverse mechanical experiments on these contracting constructs is limited by the challenges of handling and supporting these delicate samples. Here, we present a method to create simple cell-ECM constructs that can be manipulated with significantly reduced experimental limitations. We 3D print mixtures of MCF10A cells and ECM (collagen-I and Matrigel) into a 3D growth medium made from jammed microgels. With this approach, we are able to apply shear stresses to the cell constructs times after printing and observe the collective response. Preliminary results reveal that, following shear deformations that exceed 300% and dramatically smear cells and matrix in space, the cells actively re-contract the construct toward the un-sheared construct. These results suggest that new principles of collective recovery can be employed for tissue engineering applications using jammed microgels as a re-configurable support medium.

  2. Regulatory Forum Opinion Piece*: Retrospective Evaluation of Doses in the 26-week Tg.rasH2 Mice Carcinogenicity Studies: Recommendation to Eliminate High Doses at Maximum Tolerated Dose in Future Studies. A Response to the Counterpoints.

    Science.gov (United States)

    Paranjpe, Madhav G; Denton, Melissa D; Vidmar, Tom J; Elbekai, Reem H

    2016-01-01

    We recently conducted a retrospective analysis of data collected from 29 Tg.rasH2 carcinogenicity studies conducted at our facility to determine how successful was the strategy of choosing the high dose of the 26-week studies based on an estimated maximum tolerated dose (MTD). As a result of our publication, 2 counterviews were expressed. Both counterviews illustrate very valid points in their interpretation of our data. In this article, we would like to highlight clarifications based on several points and issues they have raised in their papers, namely, the dose-level selection, determining if MTD was exceeded in 26-week studies, and a discussion on the number of dose groups to be used in the studies. © The Author(s) 2015.

  3. System for memorizing maximum values

    Science.gov (United States)

    Bozeman, Richard J., Jr.

    1992-08-01

    The invention discloses a system capable of memorizing maximum sensed values. The system includes conditioning circuitry which receives the analog output signal from a sensor transducer. The conditioning circuitry rectifies and filters the analog signal and provides an input signal to a digital driver, which may be either linear or logarithmic. The driver converts the analog signal to discrete digital values, which in turn triggers an output signal on one of a plurality of driver output lines n. The particular output lines selected is dependent on the converted digital value. A microfuse memory device connects across the driver output lines, with n segments. Each segment is associated with one driver output line, and includes a microfuse that is blown when a signal appears on the associated driver output line.

  4. Remarks on the maximum luminosity

    Science.gov (United States)

    Cardoso, Vitor; Ikeda, Taishi; Moore, Christopher J.; Yoo, Chul-Moon

    2018-04-01

    The quest for fundamental limitations on physical processes is old and venerable. Here, we investigate the maximum possible power, or luminosity, that any event can produce. We show, via full nonlinear simulations of Einstein's equations, that there exist initial conditions which give rise to arbitrarily large luminosities. However, the requirement that there is no past horizon in the spacetime seems to limit the luminosity to below the Planck value, LP=c5/G . Numerical relativity simulations of critical collapse yield the largest luminosities observed to date, ≈ 0.2 LP . We also present an analytic solution to the Einstein equations which seems to give an unboundedly large luminosity; this will guide future numerical efforts to investigate super-Planckian luminosities.

  5. Alteration in contractile G-protein coupled receptor expression by moist snuff and nicotine in rat cerebral arteries

    DEFF Research Database (Denmark)

    Sandhu, Hardip; Xu, Cang-Bao; Edvinsson, Lars

    2011-01-01

    The cardiovascular risk for users of use of Swedish snus/American snuff (moist tobacco) has been debated for a long time. The present study was designed to examine the effects of water- or lipid-soluble (DMSO-soluble) snus and nicotine, the most important substance in tobacco, on the expression...... kinases (MAPK). However, the effects of moist tobacco on the expression of GPCR are less studied. Rat middle cerebral arteries were isolated and organ cultured in serum-free medium for 24h in the presence of water-soluble snus (WSS), DMSO-soluble snus (DSS), or nicotine. The dose of snus and nicotine...... was kept at plasma level of snus users (25ng nicotine/ml). A high dose (250ng nicotine/ml) was also included due to the previous results showing alteration in the GPCR expression by nicotine at this concentration. Contractile responses to the ET(B) receptor agonist sarafotoxin 6c, 5-HT(1B) receptor agonist...

  6. PGE2 maintains the tone of the guinea pig trachea through a balance between activation of contractile EP1 receptors and relaxant EP2 receptors

    Science.gov (United States)

    Säfholm, J; Dahlén, S-E; Delin, I; Maxey, K; Stark, K; Cardell, L-O; Adner, M

    2013-01-01

    Background and Purpose The guinea pig trachea (GPT) is commonly used in airway pharmacology. The aim of this study was to define the expression and function of EP receptors for PGE2 in GPT as there has been ambiguity concerning their role. Experimental Approach Expression of mRNA for EP receptors and key enzymes in the PGE2 pathway were assessed by real-time PCR using species-specific primers. Functional studies of GPT were performed in tissue organ baths. Key Results Expression of mRNA for the four EP receptors was found in airway smooth muscle. PGE2 displayed a bell-shaped concentration–response curve, where the initial contraction was inhibited by the EP1 receptor antagonist ONO-8130 and the subsequent relaxation by the EP2 receptor antagonist PF-04418948. Neither EP3 (ONO-AE5-599) nor EP4 (ONO-AE3-208) selective receptor antagonists affected the response to PGE2. Expression of COX-2 was greater than COX-1 in GPT, and the spontaneous tone was most effectively abolished by selective COX-2 inhibitors. Furthermore, ONO-8130 and a specific PGE2 antibody eliminated the spontaneous tone, whereas the EP2 antagonist PF-04418948 increased it. Antagonists of other prostanoid receptors had no effect on basal tension. The relaxant EP2 response to PGE2 was maintained after long-term culture, whereas the contractile EP1 response showed homologous desensitization to PGE2, which was prevented by COX-inhibitors. Conclusions and Implications Endogenous PGE2, synthesized predominantly by COX-2, maintains the spontaneous tone of GPT by a balance between contractile EP1 receptors and relaxant EP2 receptors. The model may be used to study interactions between EP receptors. PMID:22934927

  7. Insulin Preconditioning Elevates p-Akt and Cardiac Contractility after Reperfusion in the Isolated Ischemic Rat Heart

    Directory of Open Access Journals (Sweden)

    Tamaki Sato

    2014-01-01

    Full Text Available Insulin induces cardioprotection partly via an antiapoptotic effect. However, the optimal timing of insulin administration for the best quality cardioprotection remains unclear. We tested the hypothesis that insulin administered prior to ischemia provides better cardioprotection than insulin administration after ischemia. Isolated rat hearts were prepared using Langendorff method and divided into three groups. The Pre-Ins group (Pre-Ins received 0.5 U/L insulin prior to 15 min no-flow ischemia for 20 min followed by 20 min of reperfusion. The Post-Ins group (Post-Ins received 0.5 U/L insulin during the reperfusion period only. The control group (Control was perfused with KH buffer throughout. The maximum of left ventricular derivative of pressure development (dP/dt(max was recorded continuously. Measurements of TNF-α and p-Akt in each time point were assayed by ELISA. After reperfusion, dP/dt(max in Pre-Ins was elevated, compared with Post-Ins at 10 minutes after reperfusion and Control at all-time points. TNF-α levels at 5 minutes after reperfusion in the Pre-Ins were lower than the others. After 5 minutes of reperfusion, p-Akt was elevated in Pre-Ins compared with the other groups. Insulin administration prior to ischemia provides better cardioprotection than insulin administration only at reperfusion. TNF-α suppression is possibly mediated via p-Akt leading to a reduction in contractile myocardial dysfunction.

  8. Maximum entropy and Bayesian methods

    International Nuclear Information System (INIS)

    Smith, C.R.; Erickson, G.J.; Neudorfer, P.O.

    1992-01-01

    Bayesian probability theory and Maximum Entropy methods are at the core of a new view of scientific inference. These 'new' ideas, along with the revolution in computational methods afforded by modern computers allow astronomers, electrical engineers, image processors of any type, NMR chemists and physicists, and anyone at all who has to deal with incomplete and noisy data, to take advantage of methods that, in the past, have been applied only in some areas of theoretical physics. The title workshops have been the focus of a group of researchers from many different fields, and this diversity is evident in this book. There are tutorial and theoretical papers, and applications in a very wide variety of fields. Almost any instance of dealing with incomplete and noisy data can be usefully treated by these methods, and many areas of theoretical research are being enhanced by the thoughtful application of Bayes' theorem. Contributions contained in this volume present a state-of-the-art overview that will be influential and useful for many years to come

  9. The Functional Lumen Imaging Probe Detects Esophageal Contractility Not Observed With Manometry in Patients With Achalasia.

    Science.gov (United States)

    Carlson, Dustin A; Lin, Zhiyue; Kahrilas, Peter J; Sternbach, Joel; Donnan, Erica N; Friesen, Laurel; Listernick, Zoe; Mogni, Benjamin; Pandolfino, John E

    2015-12-01

    The functional lumen imaging probe (FLIP) could improve the characterization of achalasia subtypes by detecting nonocclusive esophageal contractions not observed with standard manometry. We aimed to evaluate esophageal contractions during volumetric distention in patients with achalasia using FLIP topography. Fifty-one treatment-naive patients with achalasia, defined and subclassified by high-resolution esophageal pressure topography, and 10 asymptomatic individuals (controls) were evaluated with the FLIP during endoscopy. During stepwise distension, simultaneous intrabag pressures and 16 channels of cross-sectional areas were measured; data were exported to software that generated FLIP topography plots. Esophageal contractility was identified by noting periods of reduced luminal diameter. Esophageal contractions were characterized further by propagation direction, repetitiveness, and based on whether they were occluding or nonoccluding. Esophageal contractility was detected in all 10 controls: 8 of 10 had repetitive antegrade contractions and 9 of 10 had occluding contractions. Contractility was detected in 27% (4 of 15) of patients with type I achalasia and in 65% (18 of 26, including 9 with occluding contractions) of patients with type II achalasia. Contractility was detected in all 10 patients with type III achalasia; 8 of these patients had a pattern of contractility that was not observed in controls (repetitive retrograde contractions). Esophageal contractility not observed with manometry can be detected in patients with achalasia using FLIP topography. The presence and patterns of contractility detected with FLIP topography may represent variations in pathophysiology, such as mechanisms of panesophageal pressurization in patients with type II achalasia. These findings could have implications for additional subclassification to supplement prediction of the achalasia disease course. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights

  10. Changes of cytosolic calcium and contractility of young rat vas deferens by acute treatment with amphetamine, fluoxetine or sibutramine.

    Science.gov (United States)

    Jurkiewicz, Neide Hyppolito; da Silva Júnior, Edilson Dantas; de Souza, Bruno Palmieri; Ferreira Verde, Luciana; Drawanz Pereira, Janaina; Mendes Sobrinho, Cairo; Soubhi Smaili, Soraya; Caricati-Neto, Afonso; Miranda-Ferreira, Regiane; Jurkiewicz, Aron

    2012-09-15

    Previous studies conducted in our laboratory indicated that administration of amphetamine, fluoxetine or sibutramine affects the sympathetic nervous system of the rat vas deferens. Therefore, our goal was to verify the role of calcium in vasa deferentia from young rats pretreated with a single dose of these drugs. Young 40-day-old male Wistar rats were pretreated with amphetamine 3 mg/kg, fluoxetine 10 mg/kg or sibutramine 6 mg/kg for 4 h before the experiments. CaCl(2) (10 mM) was used to induce contraction through time-effect curves in calcium-free solution to measure phasic and tonic components. We also evaluated the calcium-induced fluorescence of vas deferens cut into thin slices. In rats pretreated with amphetamine, we found an increase of the tonic contraction component which was reduced by verapamil. The phasic and tonic responses were increased in the group treated with fluoxetine, but only the tonic response was more sensitive to the antagonism by verapamil. The group treated with sibutramine showed an increase of phasic response whereas the tonic component was decreased. In this group an increase of the affinity for verapamil antagonism was found. In the calcium fluorescence study it was observed that the group treated with amphetamine, fluoxetine or sibutramine showed higher basal Ca(2+) fluorescence after stimulus with KCl (70 mM), noradrenaline (10(-4)M) or acetylcholine (10(-4)M). In all pretreated groups the calcium fluorescence was diminished by nifedipine 10(-7)M. Therefore, the pretreatment with amphetamine, fluoxetine or sibutramine seems to affect the calcium contractility and homeostasis in young rat vas deferens. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Maximum entropy principal for transportation

    International Nuclear Information System (INIS)

    Bilich, F.; Da Silva, R.

    2008-01-01

    In this work we deal with modeling of the transportation phenomenon for use in the transportation planning process and policy-impact studies. The model developed is based on the dependence concept, i.e., the notion that the probability of a trip starting at origin i is dependent on the probability of a trip ending at destination j given that the factors (such as travel time, cost, etc.) which affect travel between origin i and destination j assume some specific values. The derivation of the solution of the model employs the maximum entropy principle combining a priori multinomial distribution with a trip utility concept. This model is utilized to forecast trip distributions under a variety of policy changes and scenarios. The dependence coefficients are obtained from a regression equation where the functional form is derived based on conditional probability and perception of factors from experimental psychology. The dependence coefficients encode all the information that was previously encoded in the form of constraints. In addition, the dependence coefficients encode information that cannot be expressed in the form of constraints for practical reasons, namely, computational tractability. The equivalence between the standard formulation (i.e., objective function with constraints) and the dependence formulation (i.e., without constraints) is demonstrated. The parameters of the dependence-based trip-distribution model are estimated, and the model is also validated using commercial air travel data in the U.S. In addition, policy impact analyses (such as allowance of supersonic flights inside the U.S. and user surcharge at noise-impacted airports) on air travel are performed.

  12. Ndrg2 is a PGC-1α/ERRα target gene that controls protein synthesis and expression of contractile-type genes in C2C12 myotubes.

    Science.gov (United States)

    Foletta, Victoria C; Brown, Erin L; Cho, Yoshitake; Snow, Rod J; Kralli, Anastasia; Russell, Aaron P

    2013-12-01

    The stress-responsive, tumor suppressor N-myc downstream-regulated gene 2 (Ndrg2) is highly expressed in striated muscle. In response to anabolic and catabolic signals, Ndrg2 is suppressed and induced, respectively, in mouse C2C12 myotubes. However, little is known about the mechanisms regulating Ndrg2 expression in muscle, as well as the biological role for Ndrg2 in differentiated myotubes. Here, we show that Ndrg2 is a target of a peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and estrogen-related receptor alpha (ERRα) transcriptional program and is induced in response to endurance exercise, a physiological stress known also to increase PGC-1α/ERRα activity. Analyses of global gene and protein expression profiles in C2C12 myotubes with reduced levels of NDRG2, suggest that NDRG2 affects muscle growth, contractile properties, MAPK signaling, ion and vesicle transport and oxidative phosphorylation. Indeed, suppression of NDRG2 in myotubes increased protein synthesis and the expression of fast glycolytic myosin heavy chain isoforms, while reducing the expression of embryonic myosin Myh3, other contractile-associated genes and the MAPK p90 RSK1. Conversely, enhanced expression of NDRG2 reduced protein synthesis, and furthermore, partially blocked the increased protein synthesis rates elicited by a constitutively active form of ERRα. In contrast, suppressing or increasing levels of NDRG2 did not affect mRNA expression of genes involved in mitochondrial biogenesis that are regulated by PGC-1α or ERRα. This study shows that in C2C12 myotubes Ndrg2 is a novel PGC-1α/ERRα transcriptional target, which influences protein turnover and the regulation of genes involved in muscle contraction and function. © 2013 Elsevier B.V. All rights reserved.

  13. Isolation and maintenance-free culture of contractile myotubes from Manduca sexta embryos.

    Directory of Open Access Journals (Sweden)

    Amanda L Baryshyan

    Full Text Available Skeletal muscle tissue engineering has the potential to treat tissue loss and degenerative diseases. However, these systems are also applicable for a variety of devices where actuation is needed, such as microelectromechanical systems (MEMS and robotics. Most current efforts to generate muscle bioactuators are focused on using mammalian cells, which require exacting conditions for survival and function. In contrast, invertebrate cells are more environmentally robust, metabolically adaptable and relatively autonomous. Our hypothesis is that the use of invertebrate muscle cells will obviate many of the limitations encountered when mammalian cells are used for bioactuation. We focus on the tobacco hornworm, Manduca sexta, due to its easy availability, large size and well-characterized muscle contractile properties. Using isolated embryonic cells, we have developed culture conditions to grow and characterize contractile M. sexta muscles. The insect hormone 20-hydroxyecdysone was used to induce differentiation in the system, resulting in cells that stained positive for myosin, contract spontaneously for the duration of the culture, and do not require media changes over periods of more than a month. These cells proliferate under normal conditions, but the application of juvenile hormone induced further proliferation and inhibited differentiation. Cellular metabolism under normal and low glucose conditions was compared for C2C12 mouse and M. sexta myoblast cells. While differentiated C2C12 cells consumed glucose and produced lactate over one week as expected, M. sexta muscle did not consume significant glucose, and lactate production exceeded mammalian muscle production on a per cell basis. Contractile properties were evaluated using index of movement analysis, which demonstrated the potential of these cells to perform mechanical work. The ability of cultured M. sexta muscle to continuously function at ambient conditions without medium replenishment

  14. Myocardial mitochondrial and contractile function are preserved in mice lacking adiponectin.

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    Martin Braun

    Full Text Available Adiponectin deficiency leads to increased myocardial infarct size following ischemia reperfusion and to exaggerated cardiac hypertrophy following pressure overload, entities that are causally linked to mitochondrial dysfunction. In skeletal muscle, lack of adiponectin results in impaired mitochondrial function. Thus, it was our objective to investigate whether adiponectin deficiency impairs mitochondrial energetics in the heart. At 8 weeks of age, heart weight-to-body weight ratios were not different between adiponectin knockout (ADQ-/- mice and wildtypes (WT. In isolated working hearts, cardiac output, aortic developed pressure and cardiac power were preserved in ADQ-/- mice. Rates of fatty acid oxidation, glucose oxidation and glycolysis were unchanged between groups. While myocardial oxygen consumption was slightly reduced (-24% in ADQ-/- mice in isolated working hearts, rates of maximal ADP-stimulated mitochondrial oxygen consumption and ATP synthesis in saponin-permeabilized cardiac fibers were preserved in ADQ-/- mice with glutamate, pyruvate or palmitoyl-carnitine as a substrate. In addition, enzymatic activity of respiratory complexes I and II was unchanged between groups. Phosphorylation of AMP-activated protein kinase and SIRT1 activity were not decreased, expression and acetylation of PGC-1α were unchanged, and mitochondrial content of OXPHOS subunits was not decreased in ADQ-/- mice. Finally, increasing energy demands due to prolonged subcutaneous infusion of isoproterenol did not differentially affect cardiac contractility or mitochondrial function in ADQ-/- mice compared to WT. Thus, mitochondrial and contractile function are preserved in hearts of mice lacking adiponectin, suggesting that adiponectin may be expendable in the regulation of mitochondrial energetics and contractile function in the heart under non-pathological conditions.

  15. Separate effects of ischemia, hypoxia, and contractility on thallium-201 kinetics in rabbit myocardium

    International Nuclear Information System (INIS)

    Leppo, J.A.; Macneil, P.B.; Moring, A.F.; Apstein, C.S.

    1986-01-01

    The effects of hypoxia and ischemia, as well as altered contractility, on thallium-201 ( 201 TI) kinetics were evaluated in 42 isolated isovolumetrically contracting rabbit hearts. In Group A, three subgroups (n = 7 each) were studied that had either normal flow and oxygenation, hypoxia and normal flow, or ischemic flow and normal perfusate oxygen content. In Group B, three subgroups (n = 7 each) were studied and all hearts had normal flow but the contractile state was either enhanced with isoproterenol or impaired by hypocalcemia. A hemoglobin-free buffer perfusate was used in all experiments and multiple timed collections of arterial and coronary sinus effluent were used to model myocardial isotope activity during 30 min of constant uptake followed by 30 min of tracer clearance. During ischemia, hypoxia and hypocalcemia peak developed pressure and peak positive and negative dP/dt were all significantly reduced when compared to normal hemodynamic parameters (p less than 0.01). As expected, isoproterenol significantly elevated these parameters (p less than 0.04). Myocardial 201 TI kinetics were adequately described utilizing a bi-exponential model having a fast and slow component. Only ischemic hearts had significantly lower rate constants for 201 TI uptake and clearance than normal hearts (p less than 0.001). The mean (+/- s.d.) myocardial uptake and clearance rates for 201 TI (%/min) varied between 4.86 +/- 0.87 and 7.18 +/- 1.45 for the remaining groups of hearts. Therefore, myocardial 201 TI kinetics appear to be dominated by coronary flow and may not reflect marked alterations in the metabolic and contractile state. These data suggest that normal 201 TI uptake in impaired or hypercontractile cells, receiving normal flow, may not represent normal cellular function

  16. Opportunities to Target Specific Contractile Abnormalities with Smooth Muscle Protein Kinase Inhibitors

    Directory of Open Access Journals (Sweden)

    Annegret Ulke-Lemée

    2010-05-01

    Full Text Available Smooth muscle is a major component of most hollow organ systems (e.g., airways, vasculature, bladder and gut/gastrointestine; therefore, the coordinated regulation of contraction is a key property of smooth muscle. When smooth muscle functions normally, it contributes to general health and wellness, but its dysfunction is associated with morbidity and mortality. Rho-associated protein kinase (ROCK is central to calcium-independent, actomyosin-mediated contractile force generation in the vasculature, thereby playing a role in smooth muscle contraction, cell motility and adhesion. Recent evidence supports an important role for ROCK in the increased vasoconstriction and remodeling observed in various models of hypertension. This review will provide a commentary on the development of specific ROCK inhibitors and their clinical application. Fasudil will be discussed as an example of bench-to-bedside development of a clinical therapeutic that is used to treat conditions of vascular hypercontractility. Due to the wide spectrum of biological processes regulated by ROCK, many additional clinical indications might also benefit from ROCK inhibition. Apart from the importance of ROCK in smooth muscle contraction, a variety of other protein kinases are known to play similar roles in regulating contractile force. The zipper-interacting protein kinase (ZIPK and integrin-linked kinase (ILK are two well-described regulators of contraction. The relative contribution of each kinase to contraction depends on the muscle bed as well as hormonal and neuronal stimulation. Unfortunately, specific inhibitors for ZIPK and ILK are still in the development phase, but the success of fasudil suggests that inhibitors for these other kinases may also have valuable clinical applications. Notably, the directed inhibition of ZIPK with a pseudosubstrate molecule shows unexpected effects on the contractility of gastrointestinal smooth muscle.

  17. The role of apical contractility in determining cell morphology in multilayered epithelial sheets and tubes

    Science.gov (United States)

    Zhen Tan, Rui; Lai, Tanny; Chiam, K.-H.

    2017-08-01

    A multilayered epithelium is made up of individual cells that are stratified in an orderly fashion, layer by layer. In such tissues, individual cells can adopt a wide range of shapes ranging from columnar to squamous. From histological images, we observe that, in flat epithelia such as the skin, the cells in the top layer are squamous while those in the middle and bottom layers are columnar, whereas in tubular epithelia, the cells in all layers are columnar. We develop a computational model to understand how individual cell shape is governed by the mechanical forces within multilayered flat and curved epithelia. We derive the energy function for an epithelial sheet of cells considering intercellular adhesive and intracellular contractile forces. We determine computationally the cell morphologies that minimize the energy function for a wide range of cellular parameters. Depending on the dominant adhesive and contractile forces, we find four dominant cell morphologies for the multilayered-layered flat sheet and three dominant cell morphologies for the two-layered curved sheet. We study the transitions between the dominant cell morphologies for the two-layered flat sheet and find both continuous and discontinuous transitions and also the presence of multistable states. Matching our computational results with histological images, we conclude that apical contractile forces from the actomyosin belt in the epithelial cells is the dominant force determining cell shape in multilayered epithelia. Our computational model can guide tissue engineers in designing artificial multilayered epithelia, in terms of figuring out the cellular parameters needed to achieve realistic epithelial morphologies.

  18. Contractility-afterload mismatch in patients with protein-losing enteropathy after the Fontan operation.

    Science.gov (United States)

    Ozawa, Hideto; Ueno, Takayoshi; Iwai, Shigemitsu; Kawata, Hiroaki; Nishigaki, Kyouichi; Kishimoto, Hidefumi; Sawa, Yoshiki

    2014-10-01

    This study aimed to clarify the relationship between onset of protein-losing enteropathy (PLE) and Fontan circulation, with special reference to the development of contractility-afterload mismatch. The PLE group comprised 9 patients who experienced PLE after undergoing the Fontan operation, and the control group consisted of 32 patients had did not experienced PLE more than 10 years after the Fontan operation. The study compared the pre- and postoperative values of arterial elastance (Ea), end-systolic elastance (Ees), and contractility-afterload mismatch (Ea/Ees). Furthermore, the variations in the values were examined during the preoperative, postoperative, and midterm postoperative periods in seven PLE patients who underwent cardiac catheterization at the onset of PLE and during the pre- and postintervention periods in three PLE patients who underwent surgical intervention to improve the Fontan circulation after the onset of PLE. Comparison of the values obtained before and after Fontan operations showed that the Ea values increased significantly in the PLE group. However, the pre- and postoperative Ees values did not differ in the two groups. During the postoperative period, Ea/Ees increased significantly, and the Ea and Ea/Ees values increased continuously until the onset of PLE in the PLE group. In the patients who underwent surgical intervention to improve the Fontan circulation after the onset of PLE, the Ea/Ees decreased significantly, and the serum albumin levels improved after the intervention. Contractility-afterload mismatch, mainly caused by the increase in the afterload of the systemic ventricle, may have an important role in the development of PLE after the Fontan operation.

  19. Altered Ca fluxes and contractile state during pH changes in cultured heart cells

    International Nuclear Information System (INIS)

    Kim, D.; Smith, T.W.

    1987-01-01

    The authors studied mechanisms underlying changes in myocardial contractile state produced by intracellular (pH/sub i/) or extracellular (pH 0 ) changes in pH using cultured chick embryo ventricular cells. A change in pH 0 of HEPES-buffered medium from 7.4 to 6.0 or to 8.8 changed the amplitude of cell motion by -85 or +60%, and 45 Ca uptake at 10 s by -29 or +22%, respectively. The pH 0 induced change in Ca uptake was not sensitive to nifedipine but was Na gradient dependent. Changes in pH/sub i/ produced by NH 4 Cl or preincubation in media at pH values ranging from 6.0 to 8.8 failed to alter significantly 45 Ca uptake or efflux. However, larger changes in pH/sub i/ were associated with altered Ca uptake. Changes in pH 0 from 7.5 to 6.0 or to 8.8 were associated with initial changes in 45 Ca efflux by +17 or -18%, respectively, and these effects were not Na dependent. Exposure of cells to 20 mM NH 4 Cl produced intracellular alkalinization and a positive inotropic effect, whereas subsequent removal of NH 4 Cl caused intracellular acidification and a negative inotropic effect. There was, however, a lack of close temporal relationships between pH/sub i/ and contractile state. These results indicated that pH 0 -induced changes in contractile state in cultured heart cells are closely correlated with altered transarcolemmal Ca movements and presumably are due to these Ca flux changes

  20. Pulmonary artery radiocardiography and rheography in the diagnosis of hemodynamic and contractile function impairments of the right ventricle in patients with obstructive bronchitis

    International Nuclear Information System (INIS)

    Paleev, N.P.; Cherejskaya, N.K.; Tsar'kova, L.N.; Baklykova, S.N.; Novoderezhkina, L.B.; Oblovatskaya, O.G.; Dubinina, E.B.

    1990-01-01

    Radiocardiography and rheography of the pulmonary artery were used to examine impairments in hemodynamics and contractile function of the right ventricle in 40 patients with chronic obstructive bronchitis complicated with persistent hypertension. Right ventricular hemodynamic and contractile impairments were shown to be not equivalent with similar clinical and functional signs of pulmonary hypertension. This fact indicates that the use of special techiques is of practical value in the determination of right ventricular hemodynamics and myocardial contractility in patients with chronic obstructive bronchitis. Radiocardiography and rheography of the pulmonary artery are sufficiently reliable noninvasive techniques for examining the hemodynamics and contractile function of the right ventricular myocardium

  1. Bladder contractility is modulated by Kv7 channels in pig detrusor

    DEFF Research Database (Denmark)

    Svalø, Julie; Bille, Michala; Parameswaran Theepakaran, Neeraja

    2013-01-01

    Kv7 channels are involved in smooth muscle relaxation, and accordingly we believe that they constitute potential targets for the treatment of overactive bladder syndrome. We have therefore used myography to examine the function of Kv7 channels in detrusor, i.e. pig bladder, with a view...... relaxation, suggesting that Kv7.2 and/or Kv7.4 channels constitute the subtypes that are relevant to bladder contractility. The effects of retigabine and ML213 were attenuated by pre-incubation with 10µM XE991 (Kv7.1-7.5 channel blocker) (P...

  2. A thermodynamical model for stress-fiber organization in contractile cells.

    Science.gov (United States)

    Foucard, Louis; Vernerey, Franck J

    2012-01-02

    Cell mechanical adaptivity to external stimuli is vital to many of its biological functions. A critical question is therefore to understand the formation and organization of the stress fibers from which emerge the cell's mechanical properties. By accounting for the mechanical aspects and the viscoelastic behavior of stress fibers, we here propose a thermodynamic model to predict the formation and orientation of stress fibers in contractile cells subjected to constant or cyclic stretch and different substrate stiffness. Our results demonstrate that the stress fibers viscoelastic behavior plays a crucial role in their formation and organization and shows good consistency with various experiments.

  3. Last Glacial Maximum Salinity Reconstruction

    Science.gov (United States)

    Homola, K.; Spivack, A. J.

    2016-12-01

    It has been previously demonstrated that salinity can be reconstructed from sediment porewater. The goal of our study is to reconstruct high precision salinity during the Last Glacial Maximum (LGM). Salinity is usually determined at high precision via conductivity, which requires a larger volume of water than can be extracted from a sediment core, or via chloride titration, which yields lower than ideal precision. It has been demonstrated for water column samples that high precision density measurements can be used to determine salinity at the precision of a conductivity measurement using the equation of state of seawater. However, water column seawater has a relatively constant composition, in contrast to porewater, where variations from standard seawater composition occur. These deviations, which affect the equation of state, must be corrected for through precise measurements of each ion's concentration and knowledge of apparent partial molar density in seawater. We have developed a density-based method for determining porewater salinity that requires only 5 mL of sample, achieving density precisions of 10-6 g/mL. We have applied this method to porewater samples extracted from long cores collected along a N-S transect across the western North Atlantic (R/V Knorr cruise KN223). Density was determined to a precision of 2.3x10-6 g/mL, which translates to salinity uncertainty of 0.002 gms/kg if the effect of differences in composition is well constrained. Concentrations of anions (Cl-, and SO4-2) and cations (Na+, Mg+, Ca+2, and K+) were measured. To correct salinities at the precision required to unravel LGM Meridional Overturning Circulation, our ion precisions must be better than 0.1% for SO4-/Cl- and Mg+/Na+, and 0.4% for Ca+/Na+, and K+/Na+. Alkalinity, pH and Dissolved Inorganic Carbon of the porewater were determined to precisions better than 4% when ratioed to Cl-, and used to calculate HCO3-, and CO3-2. Apparent partial molar densities in seawater were

  4. Maximum Parsimony on Phylogenetic networks

    Science.gov (United States)

    2012-01-01

    Background Phylogenetic networks are generalizations of phylogenetic trees, that are used to model evolutionary events in various contexts. Several different methods and criteria have been introduced for reconstructing phylogenetic trees. Maximum Parsimony is a character-based approach that infers a phylogenetic tree by minimizing the total number of evolutionary steps required to explain a given set of data assigned on the leaves. Exact solutions for optimizing parsimony scores on phylogenetic trees have been introduced in the past. Results In this paper, we define the parsimony score on networks as the sum of the substitution costs along all the edges of the network; and show that certain well-known algorithms that calculate the optimum parsimony score on trees, such as Sankoff and Fitch algorithms extend naturally for networks, barring conflicting assignments at the reticulate vertices. We provide heuristics for finding the optimum parsimony scores on networks. Our algorithms can be applied for any cost matrix that may contain unequal substitution costs of transforming between different characters along different edges of the network. We analyzed this for experimental data on 10 leaves or fewer with at most 2 reticulations and found that for almost all networks, the bounds returned by the heuristics matched with the exhaustively determined optimum parsimony scores. Conclusion The parsimony score we define here does not directly reflect the cost of the best tree in the network that displays the evolution of the character. However, when searching for the most parsimonious network that describes a collection of characters, it becomes necessary to add additional cost considerations to prefer simpler structures, such as trees over networks. The parsimony score on a network that we describe here takes into account the substitution costs along the additional edges incident on each reticulate vertex, in addition to the substitution costs along the other edges which are

  5. Hydrologic Cycle Response to the Paleocene-Eocene Thermal Maximum at Austral, High-Latitude Site 690 as Revealed by In Situ Measurements of Foraminiferal Oxygen Isotope and Mg/Ca Ratios

    Science.gov (United States)

    Kozdon, R.; Kelly, D.; Fournelle, J.; Valley, J. W.

    2012-12-01

    Earth surface temperatures warmed by ~5°C during an ancient (~55.5 Ma) global warming event termed the Paleocene-Eocene thermal maximum (PETM). This transient (~200 ka) "hyperthermal" climate state had profound consequences for the planet's surficial processes and biosphere, and is widely touted as being an ancient analog for climate change driven by human activities. Hallmarks of the PETM are pervasive carbonate dissolution in the ocean basins and a negative carbon isotope excursion (CIE) recorded in variety of substrates including soil and marine carbonates. Together these lines of evidence signal the rapid (≤30 ka) release of massive quantities (≥2000 Gt) of 13C-depleted carbon into the exogenic carbon cycle. Paleoenvironmental reconstructions based on pedogenic features in paleosols, clay mineralogy and sedimentology of coastal and continental deposits, and land-plant communities indicate that PETM warmth was accompanied by a major perturbation to the hydrologic cycle. Micropaleontological evidence and n-alkane hydrogen isotope records indicate that increased poleward moisture transport reduced sea-surface salinities (SSSs) in the central Arctic Ocean during the PETM. Such findings are broadly consistent with predictions of climate model simulations. Here we reassess a well-studied PETM record from the Southern Ocean (ODP Site 690) in light of new δ18O and Mg/Ca data obtained from planktic foraminiferal shells by secondary ion mass spectrometry (SIMS) and electron microprobe analysis (EMPA), respectively. The unparalleled spatial resolution of these in situ techniques permits extraction of more reliable δ18O and Mg/Ca data by targeting of minute (≤10 μm spots), biogenic domains within individual planktic foraminifera that retain the original shell chemistry (Kozdon et al. 2011, Paleocean.). In general, the stratigraphic profile and magnitude of the δ18O decrease (~2.2‰) delimiting PETM warming in our SIMS-generated record are similar to those of

  6. A stepwise procedure to test contractility and susceptibility to injury for the rodent quadriceps muscle

    Directory of Open Access Journals (Sweden)

    Stephen J.P. Pratt

    2014-07-01

    Full Text Available In patients with muscle injury or muscle disease, assessment of muscle damage is typically limited to clinical signs, such as tenderness, strength, range of motion, and more recently, imaging studies.  Biological markers can also be used in measuring muscle injury, such as increased creatine kinase levels in the blood, but these are not always correlated with loss in muscle function (i.e. loss of force production.  This is even true of histological findings from animals, which provide a “direct measure” of damage, but do not account for loss of function.  The most comprehensive measure of the overall health of the muscle is contractile force.  To date, animal models testing contractile force have been limited to the muscle groups moving the ankle.  Here we describe an in vivo animal model for the quadriceps, with abilities to measure torque, produce a reliable muscle injury, and follow muscle recovery within the same animal over time.  We also describe a second model used for direct measurement of force from an isolated quadriceps muscle in situ. 

  7. Influence of intracellular acidosis on contractile function in the working rat heart

    International Nuclear Information System (INIS)

    Jeffrey, F.M.H.; Malloy, C.R.; Radda, G.K.

    1987-01-01

    The decrease in myocardial contractility during ischemia, hypoxia, and extracellular acidosis has been attributed to intracellular acidosis. Previous studies of the relationship between pH and contractile state have utilized respiratory or metabolic acidosis to alter intracellular pH. The authors developed a model in the working perfused rat heart to study the effects of intracellular acidosis with normal external pH and optimal O 2 delivery. Intracellular pH and high-energy phosphates were monitored by 31 P nuclear magnetic resonance spectroscopy. Hearts were perfused to a steady state with a medium containing 10 mM NH 4 Cl. Acidosis induced a substantial decrease in aortic flow and stroke volume which was associated with little change in peak systolic pressure. It was concluded that (1) for the same intracellular acidosis the influence on tension development was more pronounced with a combined extra- and intracellular acidosis than with an isolated intracellular acidosis, and (2) stroke volume at constant preload was impaired by intracellular acidosis even though changes in developed pressure were minimal. These observations suggest that isolated intracellular acidosis has adverse effects on diastolic compliance and/or relaxation

  8. Oscillatory behaviors and hierarchical assembly of contractile structures in intercalating cells

    International Nuclear Information System (INIS)

    Fernandez-Gonzalez, Rodrigo; Zallen, Jennifer A

    2011-01-01

    Fluctuations in the size of the apical cell surface have been associated with apical constriction and tissue invagination. However, it is currently not known if apical oscillatory behaviors are a unique property of constricting cells or if they constitute a universal feature of the force balance between cells in multicellular tissues. Here, we set out to determine whether oscillatory cell behaviors occur in parallel with cell intercalation during the morphogenetic process of axis elongation in the Drosophila embryo. We applied multi-color, time-lapse imaging of living embryos and SIESTA, an integrated tool for automated and semi-automated cell segmentation, tracking, and analysis of image sequences. Using SIESTA, we identified cycles of contraction and expansion of the apical surface in intercalating cells and characterized them at the molecular, cellular, and tissue scales. We demonstrate that apical oscillations are anisotropic, and this anisotropy depends on the presence of intact cell–cell junctions and spatial cues provided by the anterior–posterior patterning system. Oscillatory cell behaviors during axis elongation are associated with the hierarchical assembly and disassembly of contractile actomyosin structures at the medial cortex of the cell, with actin localization preceding myosin II and with the localization of both proteins preceding changes in cell shape. We discuss models to explain how the architecture of cytoskeletal networks regulates their contractile behavior and the mechanisms that give rise to oscillatory cell behaviors in intercalating cells

  9. Modulation of cardiac contractility by the phospholamban/SERCA2a regulatome.

    Science.gov (United States)

    Kranias, Evangelia G; Hajjar, Roger J

    2012-06-08

    Heart disease remains the leading cause of death and disability in the Western world. Current therapies aim at treating the symptoms rather than the subcellular mechanisms, underlying the etiology and pathological remodeling in heart failure. A universal characteristic, contributing to the decreased contractile performance in human and experimental failing hearts, is impaired calcium sequestration into the sarcoplasmic reticulum (SR). SR calcium uptake is mediated by a Ca(2+)-ATPase (SERCA2), whose activity is reversibly regulated by phospholamban (PLN). Dephosphorylated PLN is an inhibitor of SERCA and phosphorylation of PLN relieves this inhibition. However, the initial simple view of a PLN/SERCA regulatory complex has been modified by our recent identification of SUMO, S100 and the histidine-rich Ca-binding protein as regulators of SERCA activity. In addition, PLN activity is regulated by 2 phosphoproteins, the inhibitor-1 of protein phosphatase 1 and the small heat shock protein 20, which affect the overall SERCA-mediated Ca-transport. This review will highlight the regulatory mechanisms of cardiac contractility by the multimeric SERCA/PLN-ensemble and the potential for new therapeutic avenues targeting this complex by using small molecules and gene transfer methods.

  10. Evolutionarily conserved sites in yeast tropomyosin function in cell polarity, transport and contractile ring formation

    Directory of Open Access Journals (Sweden)

    Susanne Cranz-Mileva

    2015-08-01

    Full Text Available Tropomyosin is a coiled-coil protein that binds and regulates actin filaments. The tropomyosin gene in Schizosaccharomyces pombe, cdc8, is required for formation of actin cables, contractile rings, and polar localization of actin patches. The roles of conserved residues were investigated in gene replacement mutants. The work validates an evolution-based approach to identify tropomyosin functions in living cells and sites of potential interactions with other proteins. A cdc8 mutant with near-normal actin affinity affects patch polarization and vacuole fusion, possibly by affecting Myo52p, a class V myosin, function. The presence of labile residual cell attachments suggests a delay in completion of cell division and redistribution of cell patches following cytokinesis. Another mutant with a mild phenotype is synthetic negative with GFP-fimbrin, inferring involvement of the mutated tropomyosin sites in interaction between the two proteins. Proteins that assemble in the contractile ring region before actin do so in a mutant cdc8 strain that cannot assemble condensed actin rings, yet some cells can divide. Of general significance, LifeAct-GFP negatively affects the actin cytoskeleton, indicating caution in its use as a biomarker for actin filaments.

  11. EFFECT OF HYDROGEN SULFIDE ON ATRIUM CONTRACTILITY IN CONTROL AND DIABETHIC MICE

    Directory of Open Access Journals (Sweden)

    A. S. Lifanova

    2014-01-01

    Full Text Available Hydrogen sulfide (H2S is endogenously synthesized gasotransmitter that has a regulatory effect in cardiovascular system. Diabetes mellitus leads to an increased risk of hypertension and cardiovascular diseases, so the purpose of the study was to analyze the contractility of the atria mice after application of L-cysteine and H2S. Contractile activity of the myocardium was investigated in the experiment on isolated mouse atria. Alloxan was used for modeling diabetes. Intraperitoneal injection of alloxan resulted in a significant increase of glucose concentration in blood, whereas the concentration of glucose didn’t change at the injection of physiological solution. In control, the addition of NaHS resulted in a significant dose-dependent decrease of the amplitude of contraction of the myocardium, whereas the negative inotropic effect of NaHS was significantly lower in terms of modeling diabetes compare to control conditions. In the control, L-cysteine reduced the amplitude contractions significantly, whereas L-cysteine did not lead to significant changes in the amplitude of contractions in terms of modeling diabetes. These data indicate that the sensitivity of mice’s atria reduced for H2S and L-cysteine in diabetes mellitus.

  12. Scintigraphic measurement of the contractile activity of the gastric antrum using factor analysis

    International Nuclear Information System (INIS)

    Bergmann, H.; Hoebart, J.; Kugi, A.; Stacher, G.; Granser, G.V.

    1990-01-01

    The motor activity of the gastric antrum is difficult to record by manometric means and scintigraphic methods have proved unsatisfactory so far as no consistent relationship between antral contractile activity and gastric emptying rate could be detected. We investigated, using data recorded in 16 healthy human subjects after the ingestion of a semisolid standard meal, whether a newly developed method employing factor analysis would yield more meaningful and reproducible results. Factor analysis was applied to sequential scintigraphic images (3-s frame time) of gastric antrum. The computed factor images and the respective factor curves are representative of distinct dynamic structures of the antrum. From the more or less sinusoidal excursions of the factor curves, which exhibited the 3 cycles per minute frequency characteristic for the stomach, amplitude, frequency and propagation velocity of antral contractions can be calculated. The amplitudes of the factor curves were used to calculate a contraction index. This contraction index was found to be correlated significantly negatively with the gastric half-emptying time of the ingested meal. The employed factor analytical approach thus seems a promising tool to further investigate the role of antral contractility in the process of gastric emptying. (Authors)

  13. PPARγ Ligands Regulate Noncontractile and Contractile Functions of Airway Smooth Muscle: Implications for Asthma Therapy

    Directory of Open Access Journals (Sweden)

    Chantal Donovan

    2012-01-01

    Full Text Available In asthma, the increase in airway smooth muscle (ASM can contribute to inflammation, airway wall remodeling and airway hyperresponsiveness (AHR. Targetting peroxisome proliferator-activated receptor γ (PPARγ, a receptor upregulated in ASM in asthmatic airways, may provide a novel approach to regulate these contributions. This review summarises experimental evidence that PPARγ ligands, such as rosiglitazone (RGZ and pioglitazone (PGZ, inhibit proliferation and inflammatory cytokine production from ASM in vitro. In addition, inhaled administration of these ligands reduces inflammatory cell infiltration and airway remodelling in mouse models of allergen-induced airways disease. PPARγ ligands can also regulate ASM contractility, with acute treatment eliciting relaxation of mouse trachea in vitro through a PPARγ-independent mechanism. Chronic treatment can protect against the loss of bronchodilator sensitivity to β2-adrenoceptor agonists and inhibit the development of AHR associated with exposure to nicotine in utero or following allergen challenge. Of particular interest, a small clinical trial has shown that oral RGZ treatment improves lung function in smokers with asthma, a group that is generally unresponsive to conventional steroid treatment. These combined findings support further investigation of the potential for PPARγ agonists to target the noncontractile and contractile functions of ASM to improve outcomes for patients with poorly controlled asthma.

  14. Long-term vascular contractility assay using genipin-modified muscular thin films

    International Nuclear Information System (INIS)

    Hald, Eric S; Steucke, Kerianne E; Reeves, Jack A; Win, Zaw; Alford, Patrick W

    2014-01-01

    Vascular disease is a leading cause of death globally and typically manifests chronically due to long-term maladaptive arterial growth and remodeling. To date, there is no in vitro technique for studying vascular function over relevant disease time courses that both mimics in vivo-like tissue structure and provides a simple readout of tissue stress. We aimed to extend tissue viability in our muscular thin film contractility assay by modifying the polydimethylsiloxane (PDMS) substrate with micropatterned genipin, allowing extracellular matrix turnover without cell loss. To achieve this, we developed a microfluidic delivery system to pattern genipin and extracellular matrix proteins on PDMS prior to cell seeding. Tissues constructed using this method showed improved viability and maintenance of in vivo-like lamellar structure. Functional contractility of tissues fabricated on genipin-modified substrates remained consistent throughout two weeks in culture. These results suggest that muscular thin films with genipin-modified PDMS substrates are a viable method for conducting functional studies of arterial growth and remodeling in vascular diseases. (paper)

  15. Two-dimensional maximum entropy image restoration

    International Nuclear Information System (INIS)

    Brolley, J.E.; Lazarus, R.B.; Suydam, B.R.; Trussell, H.J.

    1977-07-01

    An optical check problem was constructed to test P LOG P maximum entropy restoration of an extremely distorted image. Useful recovery of the original image was obtained. Comparison with maximum a posteriori restoration is made. 7 figures

  16. Efficiency of autonomous soft nanomachines at maximum power.

    Science.gov (United States)

    Seifert, Udo

    2011-01-14

    We consider nanosized artificial or biological machines working in steady state enforced by imposing nonequilibrium concentrations of solutes or by applying external forces, torques, or electric fields. For unicyclic and strongly coupled multicyclic machines, efficiency at maximum power is not bounded by the linear response value 1/2. For strong driving, it can even approach the thermodynamic limit 1. Quite generally, such machines fall into three different classes characterized, respectively, as "strong and efficient," "strong and inefficient," and "balanced." For weakly coupled multicyclic machines, efficiency at maximum power has lost any universality even in the linear response regime.

  17. Receiver function estimated by maximum entropy deconvolution

    Institute of Scientific and Technical Information of China (English)

    吴庆举; 田小波; 张乃铃; 李卫平; 曾融生

    2003-01-01

    Maximum entropy deconvolution is presented to estimate receiver function, with the maximum entropy as the rule to determine auto-correlation and cross-correlation functions. The Toeplitz equation and Levinson algorithm are used to calculate the iterative formula of error-predicting filter, and receiver function is then estimated. During extrapolation, reflective coefficient is always less than 1, which keeps maximum entropy deconvolution stable. The maximum entropy of the data outside window increases the resolution of receiver function. Both synthetic and real seismograms show that maximum entropy deconvolution is an effective method to measure receiver function in time-domain.

  18. Maximum Power from a Solar Panel

    Directory of Open Access Journals (Sweden)

    Michael Miller

    2010-01-01

    Full Text Available Solar energy has become a promising alternative to conventional fossil fuel sources. Solar panels are used to collect solar radiation and convert it into electricity. One of the techniques used to maximize the effectiveness of this energy alternative is to maximize the power output of the solar collector. In this project the maximum power is calculated by determining the voltage and the current of maximum power. These quantities are determined by finding the maximum value for the equation for power using differentiation. After the maximum values are found for each time of day, each individual quantity, voltage of maximum power, current of maximum power, and maximum power is plotted as a function of the time of day.

  19. Enhanced contractile force generation by artificial skeletal muscle tissues using IGF-I gene-engineered myoblast cells.

    Science.gov (United States)

    Sato, Masanori; Ito, Akira; Kawabe, Yoshinori; Nagamori, Eiji; Kamihira, Masamichi

    2011-09-01

    The aim of this study was to investigate whether insulin-like growth factor (IGF)-I gene delivery to myoblast cells promotes the contractile force generated by hydrogel-based tissue-engineered skeletal muscles in vitro. Two retroviral vectors allowing doxycycline (Dox)-inducible expression of the IGF-I gene were transduced into mouse myoblast C2C12 cells to evaluate the effects of IGF-I gene expression on these cells. IGF-I gene expression stimulated the proliferation of C2C12 cells, and a significant increase in the growth rate was observed for IGF-I-transduced C2C12 cells with Dox addition, designated C2C12/IGF (Dox+) cells. Quantitative morphometric analyses showed that the myotubes induced from C2C12/IGF (Dox+) cells had a larger area and a greater width than control myotubes induced from normal C2C12 cells. Artificial skeletal muscle tissues were prepared from the respective cells using hydrogels composed of type I collagen and Matrigel. Western blot analyses revealed that the C2C12/IGF (Dox+) tissue constructs showed activation of a skeletal muscle hypertrophy marker (Akt) and enhanced expression of muscle-specific markers (myogenin, myosin heavy chain and tropomyosin). Moreover, the creatine kinase activity was increased in the C2C12/IGF (Dox+) tissue constructs. The C2C12/IGF (Dox+) tissue constructs contracted in response to electrical pulses, and generated a significantly higher physical force than the control C2C12 tissue constructs. These findings indicate that IGF-I gene transfer has the potential to yield functional skeletal muscle substitutes that are capable of in vivo restoration of the load-bearing function of injured muscle or acting as in vitro electrically-controlled bio-actuators. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  20. Changes in contractile properties and action potentials of motor units in the rat medial gastrocnemius muscle during maturation.

    Science.gov (United States)

    Dobrzynska, Z; Celichowski, J

    2016-02-01

    The early phase of development of muscles stops following the disappearance of embryonic and neonatal myosin and the elimination of polyneuronal innervation of muscle fibres with the formation of motor units (MUs), but later the muscle mass still considerably increases. It is unknown whether the three types are visible among newly formed MUs soon after the early postnatal period and whether their proportion is similar to that in adult muscle. Moreover, the processes responsible for MU-force regulation by changes in motoneuronal firing rate as well as properties of motor unit action potentials (MUAPs) during maturation are unknown. Three groups of Wistar rats were investigated - 1 month old, 2 months old and the adult, 9 months old. The basic contractile properties and action potentials of MUs in the medial gastrocnemius (MG) muscle were analysed. The three types of MUs were distinguishable in all age groups, but higher proportion of slow MUs was noticed in young rats (29%, 18% and 11% in 1, 2 and 9 months rats, respectively). The fatigue index for fast fatigable MUs in 1 month old rats was about 2 times higher than in 9 months old rats. The twitch time parameters of fast MUs were shortened during the maturation; for these units, the force-frequency curves in young rats were shifted towards lower frequencies, which suggested that fast motoneurons of young animals generate lower firing rates. Higher twitch-to-tetanus ratios noted for the three MU types in young rats suggested the smaller role of rate coding in force regulation processes, and the higher role of MU recruitment in young rats. No significant differences in MUAP parameters between two groups of young and adult animals were observed. Concluding, the maturation process evokes deeper changes in fast MUs than in slow ones.

  1. IGF-1 Alleviates High Fat Diet-Induced Myocardial Contractile Dysfunction: Role of Insulin Signaling and Mitochondrial Function

    Science.gov (United States)

    Zhang, Yingmei; Yuan, Ming; Bradley, Katherine M.; Dong, Feng; Anversa, Piero; Ren, Jun

    2012-01-01

    Obesity is often associated with reduced plasma IGF-1 levels, oxidative stress, mitochondrial damage and cardiac dysfunction. This study was designed to evaluate the impact of IGF-1 on high fat diet-induced oxidative, myocardial, geometric and mitochondrial responses. FVB and cardiomyocyte-specific IGF-1 overexpression transgenic mice were fed a low (10%) or high fat (45%) diet to induce obesity. High fat diet feeding led to glucose intolerance, elevated plasma levels of leptin, interleukin-6, insulin and triglyceride as well as reduced circulating IGF-1 levels. Echocardiography revealed reduced fractional shortening, increased end systolic and diastolic diameter, increased wall thickness, and cardiac hypertrophy in high fat-fed FVB mice. High fat diet promoted ROS generation, apoptosis, protein and mitochondrial damage, reduced ATP content, cardiomyocyte cross-sectional area, contractile and intracellular Ca2+ dysregulation, including depressed peak shortening and maximal velocity of shortening/relengthening, prolonged duration of relengthening, and dampened intracellular Ca2+ rise and clearance. Western blot analysis revealed disrupted phosphorylation of insulin receptor, post-receptor signaling molecules IRS-1 (tyrosine/serine phosphorylation), Akt, GSK3β, Foxo3a, mTOR, as well as downregulated expression of mitochondrial proteins PPARγ coactivator 1α (PGC1α) and UCP-2. Intriguingly, IGF-1 mitigated high fat diet feeding-induced alterations in ROS, protein and mitochondrial damage, ATP content, apoptosis, myocardial contraction, intracellular Ca2+ handling and insulin signaling, but not whole body glucose intolerance and cardiac hypertrophy. Exogenous IGF-1 treatment also alleviated high fat diet-induced cardiac dysfunction. Our data revealed that IGF-1 alleviates high fat diet-induced cardiac dysfunction despite persistent cardiac remodeling, possibly due to preserved cell survival, mitochondrial function and insulin signaling. PMID:22275536

  2. Novel insights on the relationship between T-tubular defects and contractile dysfunction in a mouse model of hypertrophic cardiomyopathy.

    Science.gov (United States)

    Crocini, C; Ferrantini, C; Scardigli, M; Coppini, R; Mazzoni, L; Lazzeri, E; Pioner, J M; Scellini, B; Guo, A; Song, L S; Yan, P; Loew, L M; Tardiff, J; Tesi, C; Vanzi, F; Cerbai, E; Pavone, F S; Sacconi, L; Poggesi, C

    2016-02-01

    Abnormalities of cardiomyocyte Ca(2+) homeostasis and excitation-contraction (E-C) coupling are early events in the pathogenesis of hypertrophic cardiomyopathy (HCM) and concomitant determinants of the diastolic dysfunction and arrhythmias typical of the disease. T-tubule remodelling has been reported to occur in HCM but little is known about its role in the E-C coupling alterations of HCM. Here, the role of T-tubule remodelling in the electro-mechanical dysfunction associated to HCM is investigated in the Δ160E cTnT mouse model that expresses a clinically-relevant HCM mutation. Contractile function of intact ventricular trabeculae is assessed in Δ160E mice and wild-type siblings. As compared with wild-type, Δ160E trabeculae show prolonged kinetics of force development and relaxation, blunted force-frequency response with reduced active tension at high stimulation frequency, and increased occurrence of spontaneous contractions. Consistently, prolonged Ca(2+) transient in terms of rise and duration are also observed in Δ160E trabeculae and isolated cardiomyocytes. Confocal imaging in cells isolated from Δ160E mice reveals significant, though modest, remodelling of T-tubular architecture. A two-photon random access microscope is employed to dissect the spatio-temporal relationship between T-tubular electrical activity and local Ca(2+) release in isolated cardiomyocytes. In Δ160E cardiomyocytes, a significant number of T-tubules (>20%) fails to propagate action potentials, with consequent delay of local Ca(2+) release. At variance with wild-type, we also observe significantly increased variability of local Ca(2+) transient rise as well as higher Ca(2+)-spark frequency. Although T-tubule structural remodelling in Δ160E myocytes is modest, T-tubule functional defects determine non-homogeneous Ca(2+) release and delayed myofilament activation that significantly contribute to mechanical dysfunction. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All

  3. Food allergy alters jejunal circular muscle contractility and induces local inflammatory cytokine expression in a mouse model

    Directory of Open Access Journals (Sweden)

    Kovanen Petri T

    2009-05-01

    Full Text Available Abstract Background We hypothesized that food allergy causes a state of non-specific jejunal dysmotility. This was tested in a mouse model. Methods Balb/c mice were epicutaneously sensitized with ovalbumin and challenged with 10 intragastric ovalbumin administrations every second day. Smooth muscle contractility of isolated circular jejunal sections was studied in organ bath with increasing concentrations of carbamylcholine chloride (carbachol. Smooth muscle layer thickness and mast cell protease-1 (MMCP-1 positive cell density were assayed histologically. Serum MMCP-1 and immunoglobulins were quantified by ELISA, and mRNA expressions of IFN-γ, IL-4, IL-6 and TGFβ-1 from jejunal and ileal tissue segments were analyzed with quantitative real-time PCR. Results Ovalbumin-specific serum IgE correlated with jejunal MMCP-1+ cell density. In the allergic mice, higher concentrations of carbachol were required to reach submaximal muscular stimulation, particularly in preparations derived from mice with diarrhoea. Decreased sensitivity to carbachol was associated with increased expression of IL-4 and IL-6 mRNA in jejunum. Smooth muscle layer thickness, as well as mRNA of IFN-γ and TGF-β1 remained unchanged. Conclusion In this mouse model of food allergy, we demonstrated a decreased response to a muscarinic agonist, and increased levels of proinflammatory IL-6 and Th2-related IL-4, but not Th1-related IFN-γ mRNAs in jejunum. IgE levels in serum correlated with the number of jejunal MMCP-1+ cells, and predicted diarrhoea. Overall, these changes may reflect a protective mechanism of the gut in food allergy.

  4. Na+,K+-pump stimulation improves contractility in isolated muscles of mice with hyperkalemic periodic paralysis.

    Science.gov (United States)

    Clausen, Torben; Nielsen, Ole Bækgaard; Clausen, Johannes D; Pedersen, Thomas Holm; Hayward, Lawrence J

    2011-07-01

    In patients with hyperkalemic periodic paralysis (HyperKPP), attacks of muscle weakness or paralysis are triggered by K(+) ingestion or rest after exercise. Force can be restored by muscle work or treatment with β(2)-adrenoceptor agonists. A missense substitution corresponding to a mutation in the skeletal muscle voltage-gated Na(+) channel (Na(v)1.4, Met1592Val) causing human HyperKPP was targeted into the mouse SCN4A gene (mutants). In soleus muscles prepared from these mutant mice, twitch, tetanic force, and endurance were markedly reduced compared with soleus from wild type (WT), reflecting impaired excitability. In mutant soleus, contractility was considerably more sensitive than WT soleus to inhibition by elevated [K(+)](o). In resting mutant soleus, tetrodotoxin (TTX)-suppressible (22)Na uptake and [Na(+)](i) were increased by 470 and 58%, respectively, and membrane potential was depolarized (by 16 mV, P Na(+),K(+) pump-mediated (86)Rb uptake was 83% larger than in WT. Salbutamol stimulated (86)Rb uptake and reduced [Na(+)](i) both in mutant and WT soleus. Stimulating Na(+),K(+) pumps with salbutamol restored force in mutant soleus and extensor digitorum longus (EDL). Increasing [Na(+)](i) with monensin also restored force in soleus. In soleus, EDL, and tibialis anterior muscles of mutant mice, the content of Na(+),K(+) pumps was 28, 62, and 33% higher than in WT, respectively, possibly reflecting the stimulating effect of elevated [Na(+)](i) on the synthesis of Na(+),K(+) pumps. The results confirm that the functional disorders of skeletal muscles in HyperKPP are secondary to increased Na(+) influx and show that contractility can be restored by acute stimulation of the Na(+),K(+) pumps. Calcitonin gene-related peptide (CGRP) restored force in mutant soleus but caused no detectable increase in (86)Rb uptake. Repeated excitation and capsaicin also restored contractility, possibly because of the release of endogenous CGRP from nerve endings in the isolated

  5. Muscle contractility decrement and correlated morphology during the pathogenesis of streptozotocin-diabetic mice.

    Science.gov (United States)

    Fahim, M A; el-Sabban, F; Davidson, N

    1998-06-01

    Peripheral neuropathy of both motor and sensory nerves has been well documented in diabetes mellitus, but the evidence for physiological and correlated morphological changes during the pathogenesis of myopathy is scarce. In the present report, we have chosen the dorsiflexor muscle of adult male mice as a model for studying in situ muscle contraction and neuromuscular ultrastructure during the pathogenesis of streptozotocin-induced diabetes. Thirty mice (30 g bodyweight) were injected once i.p. with streptozotocin solution (200 mg/Kg) to induce experimental diabetes mellitus. Comparative analyses of in situ muscle isometric contractile characteristics were studied (at 1 Hz, 5 Hz and 30 Hz nerve stimulation) in urethane-anesthetized (2 mg/g, i.p.) control and diabetic mice at three time points, 2 weeks, 4 weeks, and 8 weeks postinjection. Synaptic delay was also recorded in diabetic and age-matched control mice. There was a significant increase in synaptic delay in both 4-week and 8-week diabetic mice compared with control mice (8.9 +/- 1.2 msec and 7.6 +/- 0.6 msec, respectively, compared with 6.1 +/- 0.5 msec). At all three stimulation frequencies, diabetes did not affect muscle contractile speed but significantly reduced the twitch tension after 8 weeks, with no changes at 2 weeks or 4 weeks. The recorded single-twitch tension values were 2.6 +/- 0.3 g, 2.1 +/- 0.6 g, 2.2 +/- 0.7 g, and 1.2 +/- 0.1 g for control, 2 weeks, 4 weeks, and 8 weeks, respectively. At 30 Hz, the recorded tension values were 4.6 +/- 1.6 g, 3.1 +/- 1.2 g, 3.1 +/- 1.1 g, and 2.1 +/- 1.0 g for control, 2 weeks, 4 weeks, and 8 weeks, respectively. Ultrastructural changes in neuromuscular junctions were similar to those that have been described in disuse and aging. These changes were observed after 8 weeks and included serve loss of synaptic vesicles, electron-dense bodies, and myelin-like figures as well as degeneration of mitochondria. The results reveal that streptozotocin-induced diabetes

  6. Reduced Mechanical Stretch Induces Enhanced Endothelin B Receptor-mediated Contractility via Activation of Focal Adhesion Kinase and Extra Cellular-regulated Kinase 1/2 in Cerebral Arteries from Rat

    DEFF Research Database (Denmark)

    Spray, Stine; Rasmussen, Marianne N P; Skovsted, Gry F

    2016-01-01

    that rapid and sustained reduction in wall tension/stretch is a possible trigger mechanism for this vascular remodelling. Isolated rat middle cerebral artery (MCA) segments were incubated in a wire-myograph with or without mechanical stretch, prior to assessment of their contractile response to the selective...... expression to SMC expression and 2) an increased calcium sensitivity of the SMCs due to an increased expression of the calcium channel transient receptor potential canonical 1. Collectively, our results present a possible mechanism linking lack of vessel wall stretch/tension to changes in ETB receptor...

  7. Contractile effects and binding properties of endothelins/sarafotoxins in the guinea pig ileum.

    Science.gov (United States)

    Wollberg, Z; Bdolah, A; Galron, R; Sokolovsky, M; Kochva, E

    1991-05-30

    Seven of the eight known isopeptides of the endothelin/sarafotoxin (ET/SRTX) family were tested on the isolated guinea pig ileum and found to cause a concentration-dependent increase in basal tone. The rate or the amplitude of the spontaneous rhythmic contractions of the ileal smooth muscle were essentially not affected by any of the peptides. The maximum contraction elicited by vasoactive intestinal contractor (VIC) was slightly stronger than that induced by endothelin-1 (ET-1) or sarafotoxin-b (SRTX-b), and significantly stronger than the maximal contractions elicited by sarafotoxin-a (SRTX-a), sarafotoxin-c (SRTX-c), or endothelin-3 (ET-3). Sarafotoxin-d (SRTX-d) caused, essentially, no contraction but a rather marked relaxation. The potencies of the various peptides to induce the increase in tension, in terms of EC50 values (cumulative effective concentrations that induce half-maximum response), ranged between 6 and 95 nM depending on the peptide. VIC, ET-1, SRTX-b and SRTX-a had similar potencies and were significantly more potent than SRTX-c and ET-3. A high concentration of SRTX-b elicited no additional response when applied to the organ bath after one of the other peptides had shown a maximal effect. Binding experiments with ileal membranes revealed similar binding properties for the various peptides. Competition with iodinated SRTX-b showed no meaningful differences between the various peptides. It is concluded that all the ET/SRTX peptides compete for the same receptor subtype in the ileum. In terms of efficacy, VIC can be considered as a full agonist of this receptor, SRTX-d is probably an antagonist, while all the other peptides behave as partial agonists.

  8. Reduced Contractility and Motility of Prostatic Cancer-Associated Fibroblasts after Inhibition of Heat Shock Protein 90

    Directory of Open Access Journals (Sweden)

    Alex Henke

    2016-08-01

    Full Text Available Background: Prostate cancer-associated fibroblasts (CAF can stimulate malignant progression and invasion of prostatic tumour cells via several mechanisms including those active in extracellular matrix; Methods: We isolated CAF from prostate cancer patients of Gleason Score 6–10 and confirmed their cancer-promoting activity using an in vivo tumour reconstitution assay comprised of CAF and BPH1 cells. We tested the effects of heat shock protein 90 (HSP90 inhibitors upon reconstituted tumour growth in vivo. Additionally, CAF contractility was measured in a 3D collagen contraction assay and migration was measured by scratch assay; Results: HSP90 inhibitors dipalmitoyl-radicicol and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG reduced tumour size and proliferation in CAF/BPH1 reconstituted tumours in vivo. We observed that the most contractile CAF were derived from patients with lower Gleason Score and of younger age compared with the least contractile CAF. HSP90 inhibitors radicicol and 17-DMAG inhibited contractility and reduced the migration of CAF in scratch assays. Intracellular levels of HSP70 and HSP90 were upregulated upon treatment with HSP90 inhibitors. Inhibition of HSP90 also led to a specific increase in transforming growth factor beta 2 (TGFβ2 levels in CAF; Conclusions: We suggest that HSP90 inhibitors act not only upon tumour cells, but also on CAF in the tumour microenvironment.

  9. Investigating Cardiac MRI Based Right Ventricular Contractility As A Novel Non-Invasive Metric of Pulmonary Arterial Pressure

    Science.gov (United States)

    Menon, Prahlad G; Adhypak, Srilakshmi M; Williams, Ronald B; Doyle, Mark; Biederman, Robert WW

    2014-01-01

    BACKGROUND We test the hypothesis that cardiac magnetic resonance (CMR) imaging-based indices of four-dimensional (4D) (three dimensions (3D) + time) right ventricle (RV) function have predictive values in ascertaining invasive pulmonary arterial systolic pressure (PASP) measurements from right heart catheterization (RHC) in patients with pulmonary arterial hypertension (PAH). METHODS We studied five patients with idiopathic PAH and two age and sex-matched controls for RV function using a novel contractility index (CI) for amplitude and phase to peak contraction established from analysis of regional shape variation in the RV endocardium over 20 cardiac phases, segmented from CMR images in multiple orientations. RESULTS The amplitude of RV contractility correlated inversely with RV ejection fraction (RVEF; R2 = 0.64, P = 0.03) and PASP (R2 = 0.71, P = 0.02). Phase of peak RV contractility also correlated inversely to RVEF (R2 = 0.499, P = 0.12) and PASP (R2 = 0.66, P = 0.04). CONCLUSIONS RV contractility analyzed from CMR offers promising non-invasive metrics for classification of PAH, which are congruent with invasive pressure measurements. PMID:25624777

  10. 5-HT4 receptors mediating enhancement of contractility in canine stomach; an in vitro and in vivo study

    NARCIS (Netherlands)

    Prins, NH; van der Grijn, A; Lefebvre, RA; Akkermans, LMA; Schuurkes, JAJ

    1 We aimed to study 5-HT4 receptors in canine stomach contractility both in vivo and in vitro. 2 In anaesthetized Beagle dogs, the selective 5-HT4 receptor agonist prucalopride (i.v.) induced dose-dependent tonic stomach contractions under isobaric conditions, an effect that was antagonized by the

  11. Effect of Propafenone on the Contractile Activity of Latissimus Dorsi Muscle Isolated in an Organ Chamber: Experimental Study in Rats

    Directory of Open Access Journals (Sweden)

    Ricardo Simões

    2002-03-01

    Full Text Available OBJECTIVE: To study the effect of propafenone on the contractile function of latissimus dorsi muscle isolated from rats in an organ chamber. METHODS: We studied 20 latissimus dorsi muscles of Wistar rats and divided them into 2 groups: group I (n=10, or control group - we studied the feasibility of muscle contractility; group II (n=10, in which the contralateral muscles were grouped - we analyzed the effect of propafenone on muscle contractility. After building a muscle ring, 8 periods of sequential 2-minute baths were performed, with intervals of preprogrammed electrical stimulation using a pacemaker of 50 stimuli/min. In group II, propafenone, at the concentration of 9.8 µg/mL, was added to the bath in period 2 and withdrawn in period 4. RESULTS: In group I, no significant depression in muscle contraction occurred up to period 5 (p>0.05. In group II, a significant depression occurred in all periods, except between the last 2 periods (p0.05. CONCLUSION: Propafenone had a depressing effect on the contractile function of latissimus dorsi muscle isolated from rats and studied in an organ chamber.

  12. Effect of acute and chronic simvastatin treatment on post-ischemic contractile dysfunction in isolated rat heart

    Czech Academy of Sciences Publication Activity Database

    Szárszoi, Ondrej; Malý, J.; Ošťádal, P.; Netuka, I.; Bešík, J.; Kolář, František; Ošťádal, Bohuslav

    2008-01-01

    Roč. 57, č. 5 (2008), s. 793-796 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : simvastatin * contractile dysfunction * protection Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.653, year: 2008

  13. [A basis for application of cardiac contractility variability in the Evaluation and assessment of exercise and fitness].

    Science.gov (United States)

    Bu, Bin; Wang, Aihua; Han, Haijun; Xiao, Shouzhong

    2010-06-01

    Cardiac contractility variability (CCV) is a new concept which is introduced in the research field of cardiac contractility in recent years, that is to say, there are some disparities between cardiac contractilities when heart contracts. The changing signals of cardiac contractility contain a plenty of information on the cardiovascular function and disorder. In order to collect and analyze the message, we could quantitatively evaluate the tonicity and equilibrium of cardiac sympathetic nerve and parasympathetic nerve, and the effects of bio-molecular mechanism on the cardiovascular activities. By analyzing CCV, we could further understand the background of human being's heritage characteristics, nerve types, the adjusting mechanism, the molecular biology, and the adjustment of cardiac automatic nerve. With the development of the computing techniques, the digital signal processing method and its application in medical field, this analysis has been progressing greatly. By now, the assessment of CCV, just like the analysis of heart rate variability, is mainly via time domain and frequency domain analysis. CCV is one of the latest research fields in human cardiac signals being scarcely reported in the field of sports medicine; however, its research progresses are of important value for cardiac physiology and pathology in sports medicine and rehabilitation medicine.

  14. Effects of testosterone on contractile properties of sexually dimorphic forelimb muscles in male bullfrogs (Rana catesbeiana, Shaw 1802

    Directory of Open Access Journals (Sweden)

    Aaron R. Kampe

    2013-07-01

    This study examined the effects of testosterone (T on the contractile properties of two sexually dimorphic forelimb muscles and one non-dimorphic muscle in male bullfrogs (Rana catesbeiana, Shaw 1802. The dimorphic muscles in castrated males with testosterone replacement (T+ achieved higher forces and lower fatigability than did castrated males without replaced testosterone (T0 males, but the magnitude of the differences was low and many of the pair-wise comparisons of each muscle property were not statistically significant. However, when taken as a whole, the means of seven contractile properties varied in the directions expected of masculine values in T+ animals in the sexually dimorphic muscles. Moreover, these data, compared with previous data on male and female bullfrogs, show that values for T+ males are similar to normal males and are significantly different from females. The T0 males tended to be intermediate in character between T+ males and females, generally retaining masculine values. This suggests that the exposure of young males to T in their first breeding season produces a masculinizing effect on the sexually dimorphic muscles that is not reversed between breeding seasons when T levels are low. The relatively minor differences in contractile properties between T+ and T0 males may indicate that as circulating T levels rise during breeding season in normal males, contractile properties can be enhanced rapidly to maximal functional levels for breeding success.

  15. Effect of a Periodized Power Training Program on the Functional Performances and Contractile Properties of the Quadriceps in Sprinters

    Science.gov (United States)

    Kamandulis, Sigitas; Skurvydas, Albertas; Brazaitis, Marius; Stanislovaitis, Aleksas; Duchateau, Jacques; Stanislovaitiene, Jurate

    2012-01-01

    Our purpose was to compare the effect of a periodized preparation consisting of power endurance training and high-intensity power training on the contractile properties of the quadriceps muscle and functional performances in well trained male sprinters (n = 7). After 4 weeks of high-intensity power training, 60-m sprint running time improved by an…

  16. Alterations in serotonin receptor-induced contractility of bovine lateral saphenous vein in cattle grazing endophyte-infected tall fescue

    Science.gov (United States)

    As part of a large 2-year study documenting the physiologic impact of grazing endophyte-infected tall fescue on growing cattle, 2 experiments were conducted to characterize and evaluate the effects of grazing 2 levels of toxic endophyte-infected tall fescue pastures on vascular contractility and ser...

  17. Bidirectional Interplay between Vimentin Intermediate Filaments and Contractile Actin Stress Fibers

    Directory of Open Access Journals (Sweden)

    Yaming Jiu

    2015-06-01

    Full Text Available The actin cytoskeleton and cytoplasmic intermediate filaments contribute to cell migration and morphogenesis, but the interplay between these two central cytoskeletal elements has remained elusive. Here, we find that specific actin stress fiber structures, transverse arcs, interact with vimentin intermediate filaments and promote their retrograde flow. Consequently, myosin-II-containing arcs are important for perinuclear localization of the vimentin network in cells. The vimentin network reciprocally restricts retrograde movement of arcs and hence controls the width of flat lamellum at the leading edge of the cell. Depletion of plectin recapitulates the vimentin organization phenotype of arc-deficient cells without affecting the integrity of vimentin filaments or stress fibers, demonstrating that this cytoskeletal cross-linker is required for productive interactions between vimentin and arcs. Collectively, our results reveal that plectin-mediated interplay between contractile actomyosin arcs and vimentin intermediate filaments controls the localization and dynamics of these two cytoskeletal systems and is consequently important for cell morphogenesis.

  18. Transcellular tunnel dynamics: Control of cellular dewetting by actomyosin contractility and I-BAR proteins.

    Science.gov (United States)

    Lemichez, Emmanuel; Gonzalez-Rodriguez, David; Bassereau, Patricia; Brochard-Wyart, Françoise

    2013-03-01

    Dewetting is the spontaneous withdrawal of a liquid film from a non-wettable surface by nucleation and growth of dry patches. Two recent reports now propose that the principles of dewetting explain the physical phenomena underpinning the opening of transendothelial cell macroaperture (TEM) tunnels, referred to as cellular dewetting. This was discovered by studying a group of bacterial toxins endowed with the property of corrupting actomyosin cytoskeleton contractility. For both liquid and cellular dewetting, the growth of holes is governed by a competition between surface forces and line tension. We also discuss how the dynamics of TEM opening and closure represent remarkable systems to investigate actin cytoskeleton regulation by sensors of plasma membrane curvature and investigate the impact on membrane tension and the role of TEM in vascular dysfunctions. Copyright © 2013 Soçiété Française des Microscopies and Soçiété de Biologie Cellulaire de France.

  19. Nonequilibrium phase transitions, fluctuations and correlations in an active contractile polar fluid.

    Science.gov (United States)

    Gowrishankar, Kripa; Rao, Madan

    2016-02-21

    We study the patterning, fluctuations and correlations of an active polar fluid consisting of contractile polar filaments on a two-dimensional substrate, using a hydrodynamic description. The steady states generically consist of arrays of inward pointing asters and show a continuous transition from a moving lamellar phase, a moving aster street, to a stationary aster lattice with no net polar order. We next study the effect of spatio-temporal athermal noise, parametrized by an active temperature TA, on the stability of the ordered phases. In contrast to its equilibrium counterpart, we find that the active crystal shows true long range order at low TA. On increasing TA, the asters dynamically remodel, concomitantly we find novel phase transitions characterized by bond-orientational and polar order upon "heating".

  20. Image Processing Techniques for Assessing Contractility in Isolated Adult Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Carlos Bazan

    2009-01-01

    The physiologic application of the methodology is evaluated by assessing overall contraction in enzymatically dissociated adult rat cardiocytes. Our results demonstrate the effectiveness of the proposed approach in characterizing the true, two-dimensional, “shortening” in the contraction process of adult cardiocytes. We compare the performance of the proposed method to that of a popular edge detection system in the literature. The proposed method not only provides a more comprehensive assessment of the myocyte contraction process but also can potentially eliminate historical concerns and sources of errors caused by myocyte rotation or translation during contraction. Furthermore, the versatility of the image processing techniques makes the method suitable for determining myocyte shortening in cells that usually bend or move during contraction. The proposed method can be utilized to evaluate changes in contractile behavior resulting from drug intervention, disease modeling, transgeneity, or other common applications to mammalian cardiocytes.

  1. A new strain gage method for measuring the contractile strain ratio of Zircaloy tubing

    International Nuclear Information System (INIS)

    Hwang, S.K.; Sabol, G.P.

    1988-01-01

    An improved strain gage method for determining the contractile strain ratio (CSR) of Zircaloy tubing was developed. The new method consists of a number of load-unload cyclings at approximately 0.2% plastic strain interval. With this method the CSR of Zircaloy-4 tubing could be determined accurately because it was possible to separate the plastic strains from the elastic strain involvement. The CSR values determined by use of the new method were in good agreement with those calculated from conventional post-test manual measurements. The CSR of the tubing was found to decrease with the amount of deformation during testing because of uneven plastic flow in the gage section. A new technique of inscribing gage marks by use of a YAG laser is discussed. (orig.)

  2. Gamma-ray spectra deconvolution by maximum-entropy methods

    International Nuclear Information System (INIS)

    Los Arcos, J.M.

    1996-01-01

    A maximum-entropy method which includes the response of detectors and the statistical fluctuations of spectra is described and applied to the deconvolution of γ-ray spectra. Resolution enhancement of 25% can be reached for experimental peaks and up to 50% for simulated ones, while the intensities are conserved within 1-2%. (orig.)

  3. Optimal item discrimination and maximum information for logistic IRT models

    NARCIS (Netherlands)

    Veerkamp, W.J.J.; Veerkamp, Wim J.J.; Berger, Martijn P.F.; Berger, Martijn

    1999-01-01

    Items with the highest discrimination parameter values in a logistic item response theory model do not necessarily give maximum information. This paper derives discrimination parameter values, as functions of the guessing parameter and distances between person parameters and item difficulty, that

  4. Leucine elicits myotube hypertrophy and enhances maximal contractile force in tissue engineered skeletal muscle in vitro.

    Science.gov (United States)

    Martin, Neil R W; Turner, Mark C; Farrington, Robert; Player, Darren J; Lewis, Mark P

    2017-10-01

    The amino acid leucine is thought to be important for skeletal muscle growth by virtue of its ability to acutely activate mTORC1 and enhance muscle protein synthesis, yet little data exist regarding its impact on skeletal muscle size and its ability to produce force. We utilized a tissue engineering approach in order to test whether supplementing culture medium with leucine could enhance mTORC1 signaling, myotube growth, and muscle function. Phosphorylation of the mTORC1 target proteins 4EBP-1 and rpS6 and myotube hypertrophy appeared to occur in a dose dependent manner, with 5 and 20 mM of leucine inducing similar effects, which were greater than those seen with 1 mM. Maximal contractile force was also elevated with leucine supplementation; however, although this did not appear to be enhanced with increasing leucine doses, this effect was completely ablated by co-incubation with the mTOR inhibitor rapamycin, showing that the augmented force production in the presence of leucine was mTOR sensitive. Finally, by using electrical stimulation to induce chronic (24 hr) contraction of engineered skeletal muscle constructs, we were able to show that the effects of leucine and muscle contraction are additive, since the two stimuli had cumulative effects on maximal contractile force production. These results extend our current knowledge of the efficacy of leucine as an anabolic nutritional aid showing for the first time that leucine supplementation may augment skeletal muscle functional capacity, and furthermore validates the use of engineered skeletal muscle for highly-controlled investigations into nutritional regulation of muscle physiology. © 2017 The Authors. Journal of Cellular Physiology Published by wiley periodicals, Inc.

  5. Tension cost correlates with mechanical and biochemical parameters in different myocardial contractility conditions

    Directory of Open Access Journals (Sweden)

    Cleci M. Moreira

    2012-01-01

    Full Text Available OBJECTIVES: Tension cost, the ratio of myosin ATPase activity to tension, reflects the economy of tension development in the myocardium. To evaluate the mechanical advantage represented by the tension cost, we studied papillary muscle contractility and the activity of myosin ATPase in the left ventricles in normal and pathophysiological conditions. METHODS: Experimental protocols were performed using rat left ventricles from: (1 streptozotocin-induced diabetic and control Wistar rats; (2 N-nitro-L-arginine methyl ester (L-NAME hypertensive and untreated Wistar rats; (3 deoxycorticosterone acetate (DOCA salt-treated, nephrectomized and salt- and DOCA-treated rats; (4 spontaneous hypertensive rats (SHR and Wistar Kyoto (WKY rats; (5 rats with myocardial infarction and shamoperated rats. The isometric force, tetanic tension, and the activity of myosin ATPase were measured. RESULTS: The results obtained from infarcted, diabetic, and deoxycorticosterone acetate-salt-treated rats showed reductions in twitch and tetanic tension compared to the control and sham-operated groups. Twitch and tetanic tension increased in the N-nitro-L-arginine methyl ester-treated rats compared with the Wistar rats. Myosin ATPase activity was depressed in the infarcted, diabetic, and deoxycorticosterone acetate salt-treated rats compared with control and sham-operated rats and was increased in N-nitro-L-arginine methyl ester-treated rats. These parameters did not differ between SHR and WKY rats. In the studied conditions (e.g., post-myocardial infarction, deoxycorticosterone acetate salt-induced hypertension, chronic N-nitro-L-arginine methyl ester treatment, and streptozotocin-induced diabetes, a positive correlation between force or plateau tetanic tension and myosin ATPase activity was observed. CONCLUSION: Our results suggest that the myocardium adapts to force generation by increasing or reducing the tension cost to maintain myocardial contractility with a better

  6. Perfusion-induced changes in cardiac contractility depend on capillary perfusion.

    Science.gov (United States)

    Dijkman, M A; Heslinga, J W; Sipkema, P; Westerhof, N

    1998-02-01

    The perfusion-induced increase in cardiac contractility (Gregg phenomenon) is especially found in heart preparations that lack adequate coronary autoregulation and thus protection of changes in capillary pressure. We determined in the isolated perfused papillary muscle of the rat whether cardiac muscle contractility is related to capillary perfusion. Oxygen availability of this muscle is independent of internal perfusion, and perfusion may be varied or even stopped without loss of function. Muscles contracted isometrically at 27 degrees C (n = 7). During the control state stepwise increases in perfusion pressure resulted in all muscles in a significant increase in active tension. Muscle diameter always increased with increased perfusion pressure, but muscle segment length was unaffected. Capillary perfusion was then obstructed by plastic microspheres (15 microns). Flow, at a perfusion pressure of 66.6 +/- 26.2 cmH2O, reduced from 17.6 +/- 5.4 microliters/min in the control state to 3.2 +/- 1.3 microliters/min after microspheres. Active tension developed by the muscle in the unperfused condition before microspheres and after microspheres did not differ significantly (-12.8 +/- 29.4% change). After microspheres similar perfusion pressure steps as in control never resulted in an increase in active tension. Even at the two highest perfusion pressures (89.1 +/- 28.4 and 106.5 +/- 31.7 cmH2O) that were applied a significant decrease in active tension was found. We conclude that the Gregg phenomenon is related to capillary perfusion.

  7. Pentamidine rescues contractility and rhythmicity in a Drosophila model of myotonic dystrophy heart dysfunction

    Directory of Open Access Journals (Sweden)

    Mouli Chakraborty

    2015-12-01

    Full Text Available Up to 80% of individuals with myotonic dystrophy type 1 (DM1 will develop cardiac abnormalities at some point during the progression of their disease, the most common of which is heart blockage of varying degrees. Such blockage is characterized by conduction defects and supraventricular and ventricular tachycardia, and carries a high risk of sudden cardiac death. Despite its importance, very few animal model studies have focused on the heart dysfunction in DM1. Here, we describe the characterization of the heart phenotype in a Drosophila model expressing pure expanded CUG repeats under the control of the cardiomyocyte-specific driver GMH5-Gal4. Morphologically, expression of 250 CUG repeats caused abnormalities in the parallel alignment of the spiral myofibrils in dissected fly hearts, as revealed by phalloidin staining. Moreover, combined immunofluorescence and in situ hybridization of Muscleblind and CUG repeats, respectively, confirmed detectable ribonuclear foci and Muscleblind sequestration, characteristic features of DM1, exclusively in flies expressing the expanded CTG repeats. Similarly to what has been reported in humans with DM1, heart-specific expression of toxic RNA resulted in reduced survival, increased arrhythmia, altered diastolic and systolic function, reduced heart tube diameters and reduced contractility in the model flies. As a proof of concept that the fly heart model can be used for in vivo testing of promising therapeutic compounds, we fed flies with pentamidine, a compound previously described to improve DM1 phenotypes. Pentamidine not only released Muscleblind from the CUG RNA repeats and reduced ribonuclear formation in the Drosophila heart, but also rescued heart arrhythmicity and contractility, and improved fly survival in animals expressing 250 CUG repeats.

  8. Low thermal dependence of the contractile properties of a wing muscle in the bat Carollia perspicillata.

    Science.gov (United States)

    Rummel, Andrea D; Swartz, Sharon M; Marsh, Richard L

    2018-05-29

    Temperature affects contractile rate properties in muscle, which may affect locomotor performance. Endotherms are known to maintain high core body temperatures, but temperatures in the periphery of the body can fluctuate. Such a phenomenon occurs in bats, whose wing musculature is relatively poorly insulated, resulting in substantially depressed temperatures in the distal wing. We examined a wing muscle in the small-bodied tropical bat Carollia perspicillata and a hindlimb muscle in the laboratory mouse at 5°C intervals from 22 to 42°C to determine the thermal dependence of the contractile properties of both muscles. We found that the bat ECRL had low thermal dependence from near body temperature to 10°C lower, with Q 10 values of less than 1.5 for relaxation from contraction and shortening velocities in that interval, and with no significant difference in some rate properties in the interval between 32 and 37°C. In contrast, for all temperature intervals below 37°C, Q 10 values for the mouse EDL were 1.5 or higher, and rate properties differed significantly across successive temperature intervals from 37 to 22°C. An ANCOVA analysis found that the thermal dependencies of all measured isometric and isotonic rate processes were significantly different between the bat and mouse muscles. The relatively low thermal dependence of the bat muscle likely represents a downward shift of its optimal temperature and may be functionally significant in light of the variable operating temperatures of bat wing muscles. © 2018. Published by The Company of Biologists Ltd.

  9. Improved sphincter contractility after allogenic muscle-derived progenitor cell injection into the denervated rat urethra.

    Science.gov (United States)

    Cannon, Tracy W; Lee, Ji Youl; Somogyi, George; Pruchnic, Ryan; Smith, Christopher P; Huard, Johnny; Chancellor, Michael B

    2003-11-01

    To study the physiologic outcome of allogenic transplant of muscle-derived progenitor cells (MDPCs) in the denervated female rat urethra. MDPCs were isolated from muscle biopsies of normal 6-week-old Sprague-Dawley rats and purified using the preplate technique. Sciatic nerve-transected rats were used as a model of stress urinary incontinence. The experimental group was divided into three subgroups: control, denervated plus 20 microL saline injection, and denervated plus allogenic MDPCs (1 to 1.5 x 10(6) cells) injection. Two weeks after injection, urethral muscle strips were prepared and underwent electrical field stimulation. The pharmacologic effects of d-tubocurare, phentolamine, and tetrodotoxin on the urethral strips were assessed by contractions induced by electrical field stimulation. The urethral tissues also underwent immunohistochemical staining for fast myosin heavy chain and CD4-activated lymphocytes. Urethral denervation resulted in a significant decrease of the maximal fast-twitch muscle contraction amplitude to only 8.77% of the normal urethra and partial impairment of smooth muscle contractility. Injection of MDPCs into the denervated sphincter significantly improved the fast-twitch muscle contraction amplitude to 87.02% of normal animals. Immunohistochemistry revealed a large amount of new skeletal muscle fiber formation at the injection site of the urethra with minimal inflammation. CD4 staining showed minimal lymphocyte infiltration around the MDPC injection sites. Urethral denervation resulted in near-total abolishment of the skeletal muscle and partial impairment of smooth muscle contractility. Allogenic MDPCs survived 2 weeks in sciatic nerve-transected urethra with minimal inflammation. This is the first report of the restoration of deficient urethral sphincter function through muscle-derived progenitor cell tissue engineering. MDPC-mediated cellular urethral myoplasty warrants additional investigation as a new method to treat stress urinary

  10. Paving the road to maximum productivity.

    Science.gov (United States)

    Holland, C

    1998-01-01

    "Job security" is an oxymoron in today's environment of downsizing, mergers, and acquisitions. Workers find themselves living by new rules in the workplace that they may not understand. How do we cope? It is the leader's charge to take advantage of this chaos and create conditions under which his or her people can understand the need for change and come together with a shared purpose to effect that change. The clinical laboratory at Arkansas Children's Hospital has taken advantage of this chaos to down-size and to redesign how the work gets done to pave the road to maximum productivity. After initial hourly cutbacks, the workers accepted the cold, hard fact that they would never get their old world back. They set goals to proactively shape their new world through reorganizing, flexing staff with workload, creating a rapid response laboratory, exploiting information technology, and outsourcing. Today the laboratory is a lean, productive machine that accepts change as a way of life. We have learned to adapt, trust, and support each other as we have journeyed together over the rough roads. We are looking forward to paving a new fork in the road to the future.

  11. Maximum permissible voltage of YBCO coated conductors

    Energy Technology Data Exchange (ETDEWEB)

    Wen, J.; Lin, B.; Sheng, J.; Xu, J.; Jin, Z. [Department of Electrical Engineering, Shanghai Jiao Tong University, Shanghai (China); Hong, Z., E-mail: zhiyong.hong@sjtu.edu.cn [Department of Electrical Engineering, Shanghai Jiao Tong University, Shanghai (China); Wang, D.; Zhou, H.; Shen, X.; Shen, C. [Qingpu Power Supply Company, State Grid Shanghai Municipal Electric Power Company, Shanghai (China)

    2014-06-15

    Highlights: • We examine three kinds of tapes’ maximum permissible voltage. • We examine the relationship between quenching duration and maximum permissible voltage. • Continuous I{sub c} degradations under repetitive quenching where tapes reaching maximum permissible voltage. • The relationship between maximum permissible voltage and resistance, temperature. - Abstract: Superconducting fault current limiter (SFCL) could reduce short circuit currents in electrical power system. One of the most important thing in developing SFCL is to find out the maximum permissible voltage of each limiting element. The maximum permissible voltage is defined as the maximum voltage per unit length at which the YBCO coated conductors (CC) do not suffer from critical current (I{sub c}) degradation or burnout. In this research, the time of quenching process is changed and voltage is raised until the I{sub c} degradation or burnout happens. YBCO coated conductors test in the experiment are from American superconductor (AMSC) and Shanghai Jiao Tong University (SJTU). Along with the quenching duration increasing, the maximum permissible voltage of CC decreases. When quenching duration is 100 ms, the maximum permissible of SJTU CC, 12 mm AMSC CC and 4 mm AMSC CC are 0.72 V/cm, 0.52 V/cm and 1.2 V/cm respectively. Based on the results of samples, the whole length of CCs used in the design of a SFCL can be determined.

  12. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy.

    Science.gov (United States)

    Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun

    2012-11-07

    Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Wild type (WT) and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.)). Cardiomyocyte contractile and intracellular Ca(2+) properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca(2+) handling), the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, possibly through regulation of autophagy and mitochondrial function.

  13. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

    Directory of Open Access Journals (Sweden)

    Kandadi Machender R

    2012-11-01

    Full Text Available Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.. Cardiomyocyte contractile and intracellular Ca2+ properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Results Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca2+ handling, the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Conclusions Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca2+ anomalies, possibly through regulation of autophagy and mitochondrial function.

  14. A tropospheric ozone maximum over the equatorial Southern Indian Ocean

    Directory of Open Access Journals (Sweden)

    L. Zhang

    2012-05-01

    Full Text Available We examine the distribution of tropical tropospheric ozone (O3 from the Microwave Limb Sounder (MLS and the Tropospheric Emission Spectrometer (TES by using a global three-dimensional model of tropospheric chemistry (GEOS-Chem. MLS and TES observations of tropospheric O3 during 2005 to 2009 reveal a distinct, persistent O3 maximum, both in mixing ratio and tropospheric column, in May over the Equatorial Southern Indian Ocean (ESIO. The maximum is most pronounced in 2006 and 2008 and less evident in the other three years. This feature is also consistent with the total column O3 observations from the Ozone Mapping Instrument (OMI and the Atmospheric Infrared Sounder (AIRS. Model results reproduce the observed May O3 maximum and the associated interannual variability. The origin of the maximum reflects a complex interplay of chemical and dynamic factors. The O3 maximum is dominated by the O3 production driven by lightning nitrogen oxides (NOx emissions, which accounts for 62% of the tropospheric column O3 in May 2006. We find the contribution from biomass burning, soil, anthropogenic and biogenic sources to the O3 maximum are rather small. The O3 productions in the lightning outflow from Central Africa and South America both peak in May and are directly responsible for the O3 maximum over the western ESIO. The lightning outflow from Equatorial Asia dominates over the eastern ESIO. The interannual variability of the O3 maximum is driven largely by the anomalous anti-cyclones over the southern Indian Ocean in May 2006 and 2008. The lightning outflow from Central Africa and South America is effectively entrained by the anti-cyclones followed by northward transport to the ESIO.

  15. Revealing the Maximum Strength in Nanotwinned Copper

    DEFF Research Database (Denmark)

    Lu, L.; Chen, X.; Huang, Xiaoxu

    2009-01-01

    boundary–related processes. We investigated the maximum strength of nanotwinned copper samples with different twin thicknesses. We found that the strength increases with decreasing twin thickness, reaching a maximum at 15 nanometers, followed by a softening at smaller values that is accompanied by enhanced...

  16. Modelling maximum canopy conductance and transpiration in ...

    African Journals Online (AJOL)

    There is much current interest in predicting the maximum amount of water that can be transpired by Eucalyptus trees. It is possible that industrial waste water may be applied as irrigation water to eucalypts and it is important to predict the maximum transpiration rates of these plantations in an attempt to dispose of this ...

  17. Response

    Science.gov (United States)

    Higgins, Chris

    2012-01-01

    This article presents the author's response to the reviews of his book, "The Good Life of Teaching: An Ethics of Professional Practice." He begins by highlighting some of the main concerns of his book. He then offers a brief response, doing his best to address the main criticisms of his argument and noting where the four reviewers (Charlene…

  18. S-glutathionylation of troponin I (fast) increases contractile apparatus Ca2+ sensitivity in fast-twitch muscle fibres of rats and humans.

    Science.gov (United States)

    Mollica, J P; Dutka, T L; Merry, T L; Lamboley, C R; McConell, G K; McKenna, M J; Murphy, R M; Lamb, G D

    2012-03-15

    Oxidation can decrease or increase the Ca2+ sensitivity of the contractile apparatus in rodent fast-twitch (type II) skeletal muscle fibres, but the reactions and molecular targets involved are unknown. This study examined whether increased Ca2+ sensitivity is due to S-glutathionylation of particular cysteine residues. Skinned muscle fibres were directly activated in heavily buffered Ca2+ solutions to assess contractile apparatus Ca2+ sensitivity. Rat type II fibres were subjected to S-glutathionylation by successive treatments with 2,2′-dithiodipyridine (DTDP) and glutathione (GSH), and displayed a maximal increase in pCa50 (−log10 [Ca2+] at half-maximal force) of ∼0.24 pCa units, with little or no effect on maximum force or Hill coefficient. Partial similar effect was produced by exposure to oxidized gluthathione (GSSG, 10 mM) for 10 min at pH 7.1, and near-maximal effect by GSSG treatment at pH 8.5. None of these treatments significantly altered Ca2+ sensitivity in rat type I fibres. Western blotting showed that both the DTDP–GSH and GSSG–pH 8.5 treatments caused marked S-glutathionylation of the fast troponin I isoform (TnI(f)) present in type II fibres, but not of troponin C (TnC) or myosin light chain 2. Both the increased Ca2+ sensitivity and glutathionylation of TnI(f) were blocked by N-ethylmaleimide (NEM). S-nitrosoglutathione (GSNO) also increased Ca2+ sensitivity, but only in conditions where it caused S-glutathionylation of TnI(f). In human type II fibres from vastus lateralis muscle, DTDP–GSH treatment also caused similar increased Ca2+ sensitivity and S-glutathionylation of TnI(f). When the slow isoform of TnI in type I fibres of rat was partially substituted (∼30%) with TnI(f), DTDP–GSH treatment caused a significant increase in Ca2+ sensitivity (∼0.08 pCa units). TnIf in type II fibres from toad and chicken muscle lack Cys133 present in mammalian TnIf, and such fibres showed no change in Ca2+ sensitivity with DTDP–GSH nor any S

  19. Nitric Oxide Synthase 1 Modulates Basal and β-Adrenergic-Stimulated Contractility by Rapid and Reversible Redox-Dependent S-Nitrosylation of the Heart

    Science.gov (United States)

    Vielma, Alejandra Z.; León, Luisa; Fernández, Ignacio C.; González, Daniel R.

    2016-01-01

    S-nitrosylation of several Ca2+ regulating proteins in response to β-adrenergic stimulation was recently described in the heart; however the specific nitric oxide synthase (NOS) isoform and signaling pathways responsible for this modification have not been elucidated. NOS-1 activity increases inotropism, therefore, we tested whether β-adrenergic stimulation induces NOS-1-dependent S-nitrosylation of total proteins, the ryanodine receptor (RyR2), SERCA2 and the L-Type Ca2+ channel (LTCC). In the isolated rat heart, isoproterenol (10 nM, 3-min) increased S-nitrosylation of total cardiac proteins (+46±14%) and RyR2 (+146±77%), without affecting S-nitrosylation of SERCA2 and LTCC. Selective NOS-1 blockade with S-methyl-L-thiocitrulline (SMTC) and Nω-propyl-l-arginine decreased basal contractility and relaxation (−25–30%) and basal S-nitrosylation of total proteins (−25–60%), RyR2, SERCA2 and LTCC (−60–75%). NOS-1 inhibition reduced (−25–40%) the inotropic response and protein S-nitrosylation induced by isoproterenol, particularly that of RyR2 (−85±7%). Tempol, a superoxide scavenger, mimicked the effects of NOS-1 inhibition on inotropism and protein S-nitrosylation; whereas selective NOS-3 inhibitor L-N5-(1-Iminoethyl)ornithine had no effect. Inhibition of NOS-1 did not affect phospholamban phosphorylation, but reduced its oligomerization. Attenuation of contractility was abolished by PKA blockade and unaffected by guanylate cyclase inhibition. Additionally, in isolated mouse cardiomyocytes, NOS-1 inhibition or removal reduced the Ca2+-transient amplitude and sarcomere shortening induced by isoproterenol or by direct PKA activation. We conclude that 1) normal cardiac performance requires basal NOS-1 activity and S-nitrosylation of the calcium-cycling machinery; 2) β-adrenergic stimulation induces rapid and reversible NOS-1 dependent, PKA and ROS-dependent, S-nitrosylation of RyR2 and other proteins, accounting for about one third of its

  20. MXLKID: a maximum likelihood parameter identifier

    International Nuclear Information System (INIS)

    Gavel, D.T.

    1980-07-01

    MXLKID (MaXimum LiKelihood IDentifier) is a computer program designed to identify unknown parameters in a nonlinear dynamic system. Using noisy measurement data from the system, the maximum likelihood identifier computes a likelihood function (LF). Identification of system parameters is accomplished by maximizing the LF with respect to the parameters. The main body of this report briefly summarizes the maximum likelihood technique and gives instructions and examples for running the MXLKID program. MXLKID is implemented LRLTRAN on the CDC7600 computer at LLNL. A detailed mathematical description of the algorithm is given in the appendices. 24 figures, 6 tables

  1. Dietary fat influences the expression of contractile and metabolic genes in rat skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Wataru Mizunoya

    Full Text Available Dietary fat plays a major role in obesity, lipid metabolism, and cardiovascular diseases. To determine whether the intake of different types of dietary fats affect the muscle fiber types that govern the metabolic and contractile properties of the skeletal muscle, we fed male Wistar rats with a 15% fat diet derived from different fat sources. Diets composed of soybean oil (n-6 polyunsaturated fatty acids (PUFA-rich, fish oil (n-3 PUFA-rich, or lard (low in PUFAs were administered to the rats for 4 weeks. Myosin heavy chain (MyHC isoforms were used as biomarkers to delineate the skeletal muscle fiber types. Compared with soybean oil intake, fish oil intake showed significantly lower levels of the fast-type MyHC2B and higher levels of the intermediate-type MyHC2X composition in the extensor digitorum longus (EDL muscle, which is a fast-type dominant muscle. Concomitantly, MyHC2X mRNA levels in fish oil-fed rats were significantly higher than those observed in the soybean oil-fed rats. The MyHC isoform composition in the lard-fed rats was an intermediate between that of the fish oil and soybean oil-fed rats. Mitochondrial uncoupling protein 3, pyruvate dehydrogenase kinase 4, and porin mRNA showed significantly upregulated levels in the EDL of fish oil-fed rats compared to those observed in soybean oil-fed and lard-fed rats, implying an activation of oxidative metabolism. In contrast, no changes in the composition of MyHC isoforms was observed in the soleus muscle, which is a slow-type dominant muscle. Fatty acid composition in the serum and the muscle was significantly influenced by the type of dietary fat consumed. In conclusion, dietary fat affects the expression of genes related to the contractile and metabolic properties in the fast-type dominant skeletal muscle, where the activation of oxidative metabolism is more pronounced after fish oil intake than that after soybean oil intake.

  2. Maximum neutron flux in thermal reactors

    International Nuclear Information System (INIS)

    Strugar, P.V.

    1968-12-01

    Direct approach to the problem is to calculate spatial distribution of fuel concentration if the reactor core directly using the condition of maximum neutron flux and comply with thermal limitations. This paper proved that the problem can be solved by applying the variational calculus, i.e. by using the maximum principle of Pontryagin. Mathematical model of reactor core is based on the two-group neutron diffusion theory with some simplifications which make it appropriate from maximum principle point of view. Here applied theory of maximum principle are suitable for application. The solution of optimum distribution of fuel concentration in the reactor core is obtained in explicit analytical form. The reactor critical dimensions are roots of a system of nonlinear equations and verification of optimum conditions can be done only for specific examples

  3. Maximum allowable load on wheeled mobile manipulators

    International Nuclear Information System (INIS)

    Habibnejad Korayem, M.; Ghariblu, H.

    2003-01-01

    This paper develops a computational technique for finding the maximum allowable load of mobile manipulator during a given trajectory. The maximum allowable loads which can be achieved by a mobile manipulator during a given trajectory are limited by the number of factors; probably the dynamic properties of mobile base and mounted manipulator, their actuator limitations and additional constraints applied to resolving the redundancy are the most important factors. To resolve extra D.O.F introduced by the base mobility, additional constraint functions are proposed directly in the task space of mobile manipulator. Finally, in two numerical examples involving a two-link planar manipulator mounted on a differentially driven mobile base, application of the method to determining maximum allowable load is verified. The simulation results demonstrates the maximum allowable load on a desired trajectory has not a unique value and directly depends on the additional constraint functions which applies to resolve the motion redundancy

  4. Maximum phytoplankton concentrations in the sea

    DEFF Research Database (Denmark)

    Jackson, G.A.; Kiørboe, Thomas

    2008-01-01

    A simplification of plankton dynamics using coagulation theory provides predictions of the maximum algal concentration sustainable in aquatic systems. These predictions have previously been tested successfully against results from iron fertilization experiments. We extend the test to data collect...

  5. Size dependence of efficiency at maximum power of heat engine

    KAUST Repository

    Izumida, Y.; Ito, N.

    2013-01-01

    We perform a molecular dynamics computer simulation of a heat engine model to study how the engine size difference affects its performance. Upon tactically increasing the size of the model anisotropically, we determine that there exists an optimum size at which the model attains the maximum power for the shortest working period. This optimum size locates between the ballistic heat transport region and the diffusive heat transport one. We also study the size dependence of the efficiency at the maximum power. Interestingly, we find that the efficiency at the maximum power around the optimum size attains a value that has been proposed as a universal upper bound, and it even begins to exceed the bound as the size further increases. We explain this behavior of the efficiency at maximum power by using a linear response theory for the heat engine operating under a finite working period, which naturally extends the low-dissipation Carnot cycle model [M. Esposito, R. Kawai, K. Lindenberg, C. Van den Broeck, Phys. Rev. Lett. 105, 150603 (2010)]. The theory also shows that the efficiency at the maximum power under an extreme condition may reach the Carnot efficiency in principle.© EDP Sciences Società Italiana di Fisica Springer-Verlag 2013.

  6. Size dependence of efficiency at maximum power of heat engine

    KAUST Repository

    Izumida, Y.

    2013-10-01

    We perform a molecular dynamics computer simulation of a heat engine model to study how the engine size difference affects its performance. Upon tactically increasing the size of the model anisotropically, we determine that there exists an optimum size at which the model attains the maximum power for the shortest working period. This optimum size locates between the ballistic heat transport region and the diffusive heat transport one. We also study the size dependence of the efficiency at the maximum power. Interestingly, we find that the efficiency at the maximum power around the optimum size attains a value that has been proposed as a universal upper bound, and it even begins to exceed the bound as the size further increases. We explain this behavior of the efficiency at maximum power by using a linear response theory for the heat engine operating under a finite working period, which naturally extends the low-dissipation Carnot cycle model [M. Esposito, R. Kawai, K. Lindenberg, C. Van den Broeck, Phys. Rev. Lett. 105, 150603 (2010)]. The theory also shows that the efficiency at the maximum power under an extreme condition may reach the Carnot efficiency in principle.© EDP Sciences Società Italiana di Fisica Springer-Verlag 2013.

  7. Non-linear elasticity of extracellular matrices enables contractile cells to communicate local position and orientation.

    Directory of Open Access Journals (Sweden)

    Jessamine P Winer

    2009-07-01

    Full Text Available Most tissue cells grown in sparse cultures on linearly elastic substrates typically display a small, round phenotype on soft substrates and become increasingly spread as the modulus of the substrate increases until their spread area reaches a maximum value. As cell density increases, individual cells retain the same stiffness-dependent differences unless they are very close or in molecular contact. On nonlinear strain-stiffening fibrin gels, the same cell types become maximally spread even when the low strain elastic modulus would predict a round morphology, and cells are influenced by the presence of neighbors hundreds of microns away. Time lapse microscopy reveals that fibroblasts and human mesenchymal stem cells on fibrin deform the substrate by several microns up to five cell lengths away from their plasma membrane through a force limited mechanism. Atomic force microscopy and rheology confirm that these strains locally and globally stiffen the gel, depending on cell density, and this effect leads to long distance cell-cell communication and alignment. Thus cells are acutely responsive to the nonlinear elasticity of their substrates and can manipulate this rheological property to induce patterning.

  8. Contractile Activity Is Necessary to Trigger Intermittent Hypobaric Hypoxia-Induced Fiber Size and Vascular Adaptations in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    David Rizo-Roca

    2018-05-01

    Full Text Available Altitude training has become increasingly popular in recent decades. Its central and peripheral effects are well-described; however, few studies have analyzed the effects of intermittent hypobaric hypoxia (IHH alone on skeletal muscle morphofunctionality. Here, we studied the effects of IHH on different myofiber morphofunctional parameters, investigating whether contractile activity is required to elicit hypoxia-induced adaptations in trained rats. Eighteen male Sprague-Dawley rats were trained 1 month and then divided into three groups: (1 rats in normobaria (trained normobaric inactive, TNI; (2 rats subjected daily to a 4-h exposure to hypobaric hypoxia equivalent to 4,000 m (trained hypobaric inactive, THI; and (3 rats subjected daily to a 4-h exposure to hypobaric hypoxia just before performing light exercise (trained hypobaric active, THA. After 2 weeks, the tibialis anterior muscle (TA was excised. Muscle cross-sections were stained for: (1 succinate dehydrogenase to identify oxidative metabolism; (2 myosin-ATPase to identify slow- and fast-twitch fibers; and (3 endothelial-ATPase to stain capillaries. Fibers were classified as slow oxidative (SO, fast oxidative glycolytic (FOG, fast intermediate glycolytic (FIG or fast glycolytic (FG and the following parameters were measured: fiber cross-sectional area (FCSA, number of capillaries per fiber (NCF, NCF per 1,000 μm2 of FCSA (CCA, fiber and capillary density (FD and CD, and the ratio between CD and FD (C/F. THI rats did not exhibit significant changes in most of the parameters, while THA animals showed reduced fiber size. Compared to TNI rats, FOG fibers from the lateral/medial fields, as well as FIG and FG fibers from the lateral region, had smaller FCSA in THA rats. Moreover, THA rats had increased NCF in FG fibers from all fields, in medial and posterior FIG fibers and in posterior FOG fibers. All fiber types from the three analyzed regions (except the posterior FG fibers displayed a

  9. 3,5-Diiodo-l-Thyronine Increases Glucose Consumption in Cardiomyoblasts Without Affecting the Contractile Performance in Rat Heart

    Directory of Open Access Journals (Sweden)

    Ginevra Sacripanti

    2018-05-01

    Full Text Available 3,5-diiodo-l-thyronine (T2 is an endogenous derivative of thyroid hormone that has been suggested to regulate energy expenditure, resting metabolic rate and oxygen consumption with a mechanism that involves the activation of mitochondrial function. In this study, we focused on the cardiac effects of T2, which have been poorly investigated so far, by using both in vitro and ex vivo models. As a comparison, the response to T3 and T4 was also determined. Rat cardiomyoblasts (H9c2 cells were used to determine T2, T3, and T4 uptake by high-performance liquid chromatography–tandem mass spectrometry. In the same experimental model, MTT test, crystal violet staining, and glucose consumption were investigated, using T2 concentrations ranging from 0.1 to 10 µM. To assess cardiac functional effects, isolated working rat hearts were perfused with T2, T3, or T4 in Krebs-Ringer buffer, and the hemodynamic variables were recorded. T2 was taken up by cardiomyoblasts, and in cell lysate T2 levels increased slowly over time, reaching higher concentrations than in the incubation medium. T2 significantly decreased MTT staining at 0.5–10 µM concentration (P < 0.05. Crystal violet staining confirmed a reduction of cell viability only upon treatment with 10 µM T2, while equimolar T3 and T4 did not share this effect. Glucose consumption was also significantly affected as indicated by glucose uptake being increased by 24 or 35% in cells exposed to 0.1 or 1.0 µM T2 (P < 0.05 in both cases. On the contrary, T3 did not affect glucose consumption which, in turn, was significantly reduced by 1 and 10 µM T4 (−24 and −41% vs control, respectively, P < 0.05 and P < 0.01. In the isolated perfused rat heart, 10 µM T2 produced a slight and transient reduction in cardiac output, while T3 and T4 did not produce any hemodynamic effect. Our findings indicate that T2 is taken up by cardiomyoblasts, and at 0.1–1.0 µM concentration it can

  10. Abnormal glucose metabolism is associated with reduced left ventricular contractile reserve and exercise intolerance in patients with chronic heart failure

    DEFF Research Database (Denmark)

    Egstrup, M; Kistorp, C N; Schou, M

    2013-01-01

    AIMS: To investigate the associations between glucose metabolism, left ventricular (LV) contractile reserve, and exercise capacity in patients with chronic systolic heart failure (HF). METHODS AND RESULTS: From an outpatient HF clinic, 161 patients with systolic HF were included (mean age 70 ± 10...... or new DM. All patients completed low-dose dobutamine echocardiography (LDDE) and 154 patients a 6-min walking distance test (6MWD). Compared with patients with NGT, patients with known DM had lower resting LVEF (33.4 vs. 39.1%, P ... in LVEF could be observed in all glycemic groups (mean 8.2% absolute increase), but the contractile reserve was lower in patients with known DM (-5.4%, P = 0.001) and new DM (-3.5%, P = 0.035) compared to patients with NGT. 6MWD was lower in known DM (349 m) and new DM (379 m) compared with NGT (467 m) (P...

  11. Integrated Analysis of Contractile Kinetics, Force Generation, and Electrical Activity in Single Human Stem Cell-Derived Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Jan David Kijlstra

    2015-12-01

    Full Text Available The quantitative analysis of cardiomyocyte function is essential for stem cell-based approaches for the in vitro study of human cardiac physiology and pathophysiology. We present a method to comprehensively assess the function of single human pluripotent stem cell-derived cardiomyocyte (hPSC-CMs through simultaneous quantitative analysis of contraction kinetics, force generation, and electrical activity. We demonstrate that statistical analysis of movies of contracting hPSC-CMs can be used to quantify changes in cellular morphology over time and compute contractile kinetics. Using a biomechanical model that incorporates substrate stiffness, we calculate cardiomyocyte force generation at single-cell resolution and validate this approach with conventional traction force microscopy. The addition of fluorescent calcium indicators or membrane potential dyes allows the simultaneous analysis of contractility and calcium handling or action potential morphology. Accordingly, our approach has the potential for broad application in the study of cardiac disease, drug discovery, and cardiotoxicity screening.

  12. Hydrogen sulfide-mediated regulation of contractility in the mouse ileum with electrical stimulation: roles of L-cysteine, cystathionine β-synthase, and K+ channels.

    Science.gov (United States)

    Yamane, Satoshi; Kanno, Toshio; Nakamura, Hiroyuki; Fujino, Hiromichi; Murayama, Toshihiko

    2014-10-05

    Hydrogen sulfide (H2S) is considered to be a signaling molecule. The precise mechanisms underlying H2S-related events, including the producing enzymes and target molecules in gastrointestinal tissues, have not been elucidated in detail. We herein examined the involvement of H2S in contractions induced by repeated electrical stimulations (ES). ES-induced contractions were neurotoxin-sensitive and increased by aminooxyacetic acid, an inhibitor of cystathionine β-synthase (CBS) and cystathionine γ-lyase, but not by D,L-propargylglycine, a selective inhibitor of cystathionine γ-lyase, in an ES trial-dependent manner. ES-induced contractions were markedly decreased in the presence of L-cysteine. This response was inhibited by aminooxyacetic acid and an antioxidant, and accelerated by L-methionine, an activator of CBS. The existence of CBS was confirmed. NaHS transiently inhibited ES- and acetylcholine-induced contractions, and sustainably decreased basal tone for at least 20 min after its addition. The treatment with glibenclamide, an ATP-sensitive K+ channel blocker, reduced both the L-cysteine response and NaHS-induced inhibition of contractions. The NaHS-induced decrease in basal tone was inhibited by apamin, a small conductance Ca2+-activated K+ channel blocker. These results suggest that H2S may be endogenously produced via CBS in ES-activated enteric neurons, and regulates contractility via multiple K+ channels in the ileum. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Effect of chronic and acute cigarette smoking on the pharyngo-upper oesophageal sphincter contractile reflex and reflexive pharyngeal swallow

    OpenAIRE

    Dua, K; Bardan, E; Ren, J; Sui, Z; Shaker, R

    1998-01-01

    Background—Cigarette smoking is known to affect adversely the defence mechanisms against gastro-oesophageal reflux. The effect of smoking on the supraoesophageal reflexes that prevent aspiration of gastric contents has not been previously studied. 
Aims—To elucidate the effect of cigarette smoking on two of the supraoesophageal reflexes: the pharyngo-upper oesophageal sphincter (UOS) contractile reflex; and the reflexive pharyngeal swallow. 
Methods—Ten chronic smokers and 10 non-...

  14. Moderate ethanol administration accentuates cardiomyocyte contractile dysfunction and mitochondrial injury in high fat diet-induced obesity.

    Science.gov (United States)

    Yuan, Fang; Lei, Yonghong; Wang, Qiurong; Esberg, Lucy B; Huang, Zaixing; Scott, Glenda I; Li, Xue; Ren, Jun

    2015-03-18

    Light to moderate drinking confers cardioprotection although it remains unclear with regards to the role of moderate drinking on cardiac function in obesity. This study was designed to examine the impact of moderate ethanol intake on myocardial function in high fat diet intake-induced obesity and the mechanism(s) involved with a focus on mitochondrial integrity. C57BL/6 mice were fed low or high fat diet for 16 weeks prior to ethanol challenge (1g/kg/d for 3 days). Cardiac contractile function, intracellular Ca(2+) homeostasis, myocardial histology, and mitochondrial integrity [aconitase activity and the mitochondrial proteins SOD1, UCP-2 and PPARγ coactivator 1α (PGC-1α)] were assessed 24h after the final ethanol challenge. Fat diet intake compromised cardiomyocyte contractile and intracellular Ca(2+) properties (depressed peak shortening and maximal velocities of shortening/relengthening, prolonged duration of relengthening, dampened intracellular Ca(2+) rise and clearance without affecting duration of shortening). Although moderate ethanol challenge failed to alter cardiomyocyte mechanical property under low fat diet intake, it accentuated high fat diet intake-induced changes in cardiomyocyte contractile function and intracellular Ca(2+) handling. Moderate ethanol challenge failed to affect fat diet intake-induced cardiac hypertrophy as evidenced by H&E staining. High fat diet intake reduced myocardial aconitase activity, downregulated levels of mitochondrial protein UCP-2, PGC-1α, SOD1 and interrupted intracellular Ca(2+) regulatory proteins, the effect of which was augmented by moderate ethanol challenge. Neither high fat diet intake nor moderate ethanol challenge affected protein or mRNA levels as well as phosphorylation of Akt and GSK3β in mouse hearts. Taken together, our data revealed that moderate ethanol challenge accentuated high fat diet-induced cardiac contractile and intracellular Ca(2+) anomalies as well as mitochondrial injury. Copyright

  15. Stochastic Ratcheting on a Funneled Energy Landscape Is Necessary for Highly Efficient Contractility of Actomyosin Force Dipoles

    Science.gov (United States)

    Komianos, James E.; Papoian, Garegin A.

    2018-04-01

    Current understanding of how contractility emerges in disordered actomyosin networks of nonmuscle cells is still largely based on the intuition derived from earlier works on muscle contractility. In addition, in disordered networks, passive cross-linkers have been hypothesized to percolate force chains in the network, hence, establishing large-scale connectivity between local contractile clusters. This view, however, largely overlooks the free energy of cross-linker binding at the microscale, which, even in the absence of active fluctuations, provides a thermodynamic drive towards highly overlapping filamentous states. In this work, we use stochastic simulations and mean-field theory to shed light on the dynamics of a single actomyosin force dipole—a pair of antiparallel actin filaments interacting with active myosin II motors and passive cross-linkers. We first show that while passive cross-linking without motor activity can produce significant contraction between a pair of actin filaments, driven by thermodynamic favorability of cross-linker binding, a sharp onset of kinetic arrest exists at large cross-link binding energies, greatly diminishing the effectiveness of this contractility mechanism. Then, when considering an active force dipole containing nonmuscle myosin II, we find that cross-linkers can also serve as a structural ratchet when the motor dissociates stochastically from the actin filaments, resulting in significant force amplification when both molecules are present. Our results provide predictions of how actomyosin force dipoles behave at the molecular level with respect to filament boundary conditions, passive cross-linking, and motor activity, which can explicitly be tested using an optical trapping experiment.

  16. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

    OpenAIRE

    Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun

    2012-01-01

    Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT) and cardiac-specific catalase overexpression mice were challenged...

  17. The neuromechanical functional contractile properties of the thigh muscles measured using tensiomyography in male athletes and non-athletes

    Directory of Open Access Journals (Sweden)

    Toskić Lazar

    2016-01-01

    Full Text Available Involuntary neuromechanical muscle contractile properties, especially of the extensor muscles and knee joint flexors as the largest muscle groups of the caudal part of the body, play an important role in both everyday movement and sport. Based on these data we can obtain important information on the functional properties of muscles. The basic means of evaluation of the functional involuntary neuromechanical muscles contractile properties is the non-invasive tensiomyographic method (TMG. The aim of this study was to determine the differences between the involuntary neuromechanical contractile properties of the thigh muscles measured using the TMG method on a sample of male athletes and non-athletes. The sample of participants was made up of 17 athletes and 10 non-athletes. By applying the multivariate analysis of variance (MANOVA and the t-test, we achieved results which indicate that of the overall 30 variables, a difference was determined among 13 of them. Most of the differences were determined for the extensor muscles of the right knee, especially of the rectus femoris muscle. It was also shown that in addition to the main knee joint extensor muscle (rectus femoris the main knee joint flexor muscle (biceps femoris also takes part in the definition of the difference between athletes and non-athletes. The results have shown that the following variables: contraction time (Tc and delay contraction time (Td are the functional parameters for which the highest difference between athletes and non-athletes were determined (from t = -2.284, p < 0.05 for the vastus lateralis of the right leg to t = -4.018, p < 0.01 for the rectus femoris of the left leg. These results have shown that it is possible to determine the differences in the functional involuntary neuromechanical contractile properties of the thigh muscles among trained and untrained individuals using the tensiomyographic method, but at the same time indicated that these differences were very

  18. Stochastic Ratcheting on a Funneled Energy Landscape Is Necessary for Highly Efficient Contractility of Actomyosin Force Dipoles

    Directory of Open Access Journals (Sweden)

    James E. Komianos

    2018-04-01

    Full Text Available Current understanding of how contractility emerges in disordered actomyosin networks of nonmuscle cells is still largely based on the intuition derived from earlier works on muscle contractility. In addition, in disordered networks, passive cross-linkers have been hypothesized to percolate force chains in the network, hence, establishing large-scale connectivity between local contractile clusters. This view, however, largely overlooks the free energy of cross-linker binding at the microscale, which, even in the absence of active fluctuations, provides a thermodynamic drive towards highly overlapping filamentous states. In this work, we use stochastic simulations and mean-field theory to shed light on the dynamics of a single actomyosin force dipole—a pair of antiparallel actin filaments interacting with active myosin II motors and passive cross-linkers. We first show that while passive cross-linking without motor activity can produce significant contraction between a pair of actin filaments, driven by thermodynamic favorability of cross-linker binding, a sharp onset of kinetic arrest exists at large cross-link binding energies, greatly diminishing the effectiveness of this contractility mechanism. Then, when considering an active force dipole containing nonmuscle myosin II, we find that cross-linkers can also serve as a structural ratchet when the motor dissociates stochastically from the actin filaments, resulting in significant force amplification when both molecules are present. Our results provide predictions of how actomyosin force dipoles behave at the molecular level with respect to filament boundary conditions, passive cross-linking, and motor activity, which can explicitly be tested using an optical trapping experiment.

  19. Contribution of contractile state of the non-infarcted area to global ventricular performance after acute myocardial infarction

    International Nuclear Information System (INIS)

    Nishimura, Tsunehiko; Yasuda, Tsunehiro; Gold, H.K.; Leinbach, R.C.; Boucher, C.A.; McKusick, K.A.; Strauss, H.W.

    1986-01-01

    To evaluate the regional contractile state of the non-infarcted zone and to determine the contribution of this area to left ventricular (LV) performance, 112 patients (42 anterior and 70 inferior infarction) with their first acute myocardial infarction were investigated by radionuclide ventriculography at admission and 10 days after admission. Wall motion at the non-infarcted area was defined as hyperkinetic, normal, or hypokinetic, if radial chord shortening had above normal, normal, or below normal values, respectively, by quantitative wall motion analysis. Hyperkinetic, normal, and hypokinetic wall motion of the non-infarcted area were observed in three (7 %), 12 (29 %), and 27 (64 %) patients in anterior infarction and 14 (20 %), 28 (40 %), and 28 (40 %) in inferior infarction, respectively. In the patients with hypokinetic wall motion at the non-infarcted area, the infarct involved more than 30 % of the left ventricle manifesting akinetic contractile segment (ACS), radial chord shortening in the infarcted area was severely depressed, and the incidence of multi-vessel involvement was higher compared with those with hyperkinetic or normal wall motion. In serial measurements, radial chord shortening in the infarcted and non-infarcted area, percent ACS, left ventricular ejection fraction, and left ventricular end-diastolic volume index did not change significantly from acute to follow-up study in any group. In conclusion, our data indicated that the non-infarcted area following acute infarction had various contractile states and these conditions were determined primarily by the severity and extent of infarct and underlying coronary artery disease. Furthermore, the contractile state of the non-infarcted area has a supplemental role in determination of LV function following acute infarction. (author)

  20. Inhibition of CYP2E1 attenuates chronic alcohol intake-induced myocardial contractile dysfunction and apoptosis.

    Science.gov (United States)

    Zhang, Rong-Huai; Gao, Jian-Yuan; Guo, Hai-Tao; Scott, Glenda I; Eason, Anna R; Wang, Xiao-Ming; Ren, Jun

    2013-01-01

    Alcohol intake is associated with myocardial contractile dysfunction and apoptosis although the precise mechanism is unclear. This study was designed to examine the effect of the cytochrome P450 enzyme CYP2E1 inhibition on ethanol-induced cardiac dysfunction. Adult male mice were fed a 4% ethanol liquid or pair-fed control diet for 6weeks. Following 2weeks of diet feeding, a cohort of mice started to receive the CYP2E1 inhibitor diallyl sulfide (100mg/kg/d, i.p.) for the remaining feeding duration. Cardiac function was assessed using echocardiographic and IonOptix systems. Western blot analysis was used to evaluate CYP2E1, heme oxygenase-1 (HO-1), iNOS, the intracellular Ca(2+) regulatory proteins sarco(endo)plasmic reticulum Ca(2+)-ATPase, Na(+)Ca(2+) exchanger and phospholamban, pro-apoptotic protein cleaved caspase-3, Bax, c-Jun-NH(2)-terminal kinase (JNK) and apoptosis signal-regulating kinase (ASK-1). Ethanol led to elevated levels of CYP2E1, iNOS and phospholamban, decreased levels of HO-1 and Na(+)Ca(2+) exchanger, cardiac contractile and intracellular Ca(2+) defects, cardiac fibrosis, overt O(2)(-) production, and apoptosis accompanied with increased phosphorylation of JNK and ASK-1, the effects were significantly attenuated or ablated by diallyl sulfide. Inhibitors of JNK and ASK-1 but not HO-1 inducer or iNOS inhibitor obliterated ethanol-induced cardiomyocyte contractile dysfunction, substantiating a role for JNK and ASK-1 signaling in ethanol-induced myocardial injury. Taken together, these findings suggest that ethanol metabolism through CYP2E1 may contribute to the pathogenesis of alcoholic cardiomyopathy including myocardial contractile dysfunction, oxidative stress and apoptosis, possibly through activation of JNK and ASK-1 signaling. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Enhancement of contractile force generation of artificial skeletal muscle tissues by mild and transient heat treatment.

    Science.gov (United States)

    Sato, Masanori; Ikeda, Kazushi; Kanno, Shota; Ito, Akira; Kawabe, Yoshinori; Kamihira, Masamichi

    2014-01-01

    Artificial skeletal muscle tissues composed of cells are expected to be used for applications of regenerative medicine and drug screening. Generally, however, the physical forces generated by tissue-engineered skeletal muscle are lower than those of skeletal muscle tissues found in the body. Local hyperthermia is used for many diseases including muscle injuries. It was recently reported that mild heat treatment improved skeletal muscle functions. In this study, we investigated the effects of mild heat treatment on the tissue-engineered skeletal muscle tissues in vitro. We used magnetite cationic liposomes to label C2C12 myoblast cells magnetically, and constructed densely packed artificial skeletal muscle tissues by using magnetic force. Cell culture at 39°C promoted the differentiation of myoblast cells into myotubes. Moreover, the mild and transient heat treatment improved the contractile properties of artificial skeletal muscle tissue constructs. These findings indicate that the culture method using heat treatment is a useful approach to enhance functions of artificial skeletal muscle tissue.

  2. Bidirectional Interplay between Vimentin Intermediate Filaments and Contractile Actin Stress Fibers.

    Science.gov (United States)

    Jiu, Yaming; Lehtimäki, Jaakko; Tojkander, Sari; Cheng, Fang; Jäälinoja, Harri; Liu, Xiaonan; Varjosalo, Markku; Eriksson, John E; Lappalainen, Pekka

    2015-06-16

    The actin cytoskeleton and cytoplasmic intermediate filaments contribute to cell migration and morphogenesis, but the interplay between these two central cytoskeletal elements has remained elusive. Here, we find that specific actin stress fiber structures, transverse arcs, interact with vimentin intermediate filaments and promote their retrograde flow. Consequently, myosin-II-containing arcs are important for perinuclear localization of the vimentin network in cells. The vimentin network reciprocally restricts retrograde movement of arcs and hence controls the width of flat lamellum at the leading edge of the cell. Depletion of plectin recapitulates the vimentin organization phenotype of arc-deficient cells without affecting the integrity of vimentin filaments or stress fibers, demonstrating that this cytoskeletal cross-linker is required for productive interactions between vimentin and arcs. Collectively, our results reveal that plectin-mediated interplay between contractile actomyosin arcs and vimentin intermediate filaments controls the localization and dynamics of these two cytoskeletal systems and is consequently important for cell morphogenesis. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. [Effects of genistein on contractility of isolated right ventricular muscles in guinea pig].

    Science.gov (United States)

    Wu, Jin-xia; Li, Hong-fang; Liu, Chong-bin; Tian, Zhi-feng

    2008-11-01

    To study the effect of genistein (GEN) on contractility of isolated right ventricular muscles in guinea pig and its mechanisms. Isolated guinea pig ventricular muscles were suspended in organ baths containing K-H solution.After an equilibration period, the effect of GEN on contraction of myocardium was observed. GEN and isoprenaline hydrochloride had the positive inotropic effects on contractity of myocardium. Meanwhile, the effect of GEN (1-100 micromol x L(-1)) was in dose-dependent manner. Propranolol (1 micromol x L(-1)) and verapamil hydrochloride (0.5 micromol x L(-1)) attenuated the positive inotropic effect of isoprenaline hydrochloride (1 micromol x L(-1)), but did not change the effect of GEN (50 micromol x L(-1)). Further more, the enhancement of the contraction induced by elevation of extracellular Ca2+ concentration in ventricular muscles had no change after pretreatment with GEN (1.10 micromol x L(-1)). In addition,the positive inotropic effect of GEN was inhibited partially by tamoxifen (1 micromol x L(-1)) and SQ22536 (1 micromol x L(-1)), also, could be attenuated by bpV (1 micromol x L(-1)). GEN has the positive inotropic effect on guinea pig ventricular muscles, which is not related to the activation of beta adrenoceptor, Ca2+ channel on cell membrane,but may involve in cAMP of intracellular signal transduction and tyrosine kinase pathway.

  4. Shortening actin filaments cause force generation in actomyosin network to change from contractile to extensile

    Science.gov (United States)

    Kumar, Nitin; Gardel, Margaret

    Motor proteins in conjunction with filamentous proteins convert biochemical energy into mechanical energy which serves a number of cellular processes including cell motility, force generation and intracellular cargo transport. In-vitro experiments suggest that the forces generated by kinesin motors on microtubule bundles are extensile in nature whereas myosin motors on actin filaments are contractile. It is not clear how qualitatively similar systems can show completely different behaviors in terms of the nature of force generation. In order to answer this question, we carry out in vitro experiments where we form quasi 2D filamentous actomyosin networks and vary the length of actin filaments by adding capping protein. We show that when filaments are much shorter than their typical persistence length (approximately 10 microns), the forces generated are extensile and we see active nematic defect propagation, as seen in the microtubule-kinesin system. Based on this observation, we claim that the rigidity of rods plays an important role in dictating the nature of force generation in such systems. In order to understand this transition, we selectively label individual filaments and find that longer filaments show considerable bending and buckling, making them difficult to slide and extend along their length.

  5. An Equatorial Contractile Mechanism Drives Cell Elongation but not Cell Division

    Science.gov (United States)

    Denker, Elsa; Bhattachan, Punit; Deng, Wei; Mathiesen, Birthe T.; Jiang, Di

    2014-01-01

    Cell shape changes and proliferation are two fundamental strategies for morphogenesis in animal development. During embryogenesis of the simple chordate Ciona intestinalis, elongation of individual notochord cells constitutes a crucial stage of notochord growth, which contributes to the establishment of the larval body plan. The mechanism of cell elongation is elusive. Here we show that although notochord cells do not divide, they use a cytokinesis-like actomyosin mechanism to drive cell elongation. The actomyosin network forming at the equator of each notochord cell includes phosphorylated myosin regulatory light chain, α-actinin, cofilin, tropomyosin, and talin. We demonstrate that cofilin and α-actinin are two crucial components for cell elongation. Cortical flow contributes to the assembly of the actomyosin ring. Similar to cytokinetic cells, membrane blebs that cause local contractions form at the basal cortex next to the equator and participate in force generation. We present a model in which the cooperation of equatorial actomyosin ring-based constriction and bleb-associated contractions at the basal cortex promotes cell elongation. Our results demonstrate that a cytokinesis-like contractile mechanism is co-opted in a completely different developmental scenario to achieve cell shape change instead of cell division. We discuss the occurrences of actomyosin rings aside from cell division, suggesting that circumferential contraction is an evolutionally conserved mechanism to drive cell or tissue elongation. PMID:24503569

  6. Multiple effects of sibutramine on ejaculation and on vas deferens and seminal vesicle contractility.

    Science.gov (United States)

    Nojimoto, Fernanda D; Piffer, Renata C; Kiguti, Luiz Ricardo de A; Lameu, Claudiana; de Camargo, Antônio C M; Pereira, Oduvaldo C M; Pupo, André S

    2009-09-15

    Sibutramine is an inhibitor of norepinephrine and 5-HT reuptake largely used in the management of obesity. Although a fairly safe drug, postmarketing adverse effects of sibutramine were reported including abnormal ejaculation in men. This study investigates the effects of sibutramine on ejaculation and vas deferens and seminal vesicle contractility. Adult male rats received sibutramine (5; 20; or 50 mg kg(-1), ip) and after 60 min were exposed to receptive females for determination of ejaculation parameters. The vasa deferentia and seminal vesicles of untreated rats were mounted in isolated organ baths for recording of isometric contractions and HEK293 cells loaded with fluorescent calcium indicator were used to measure intracellular Ca(2+) transients. Sibutramine 5 and 20 mg kg(-1) reduced ejaculation latency whereas 50 mg kg(-1) increased ejaculation latency. Sibutramine 3 to 30 microM greatly increased the sensitivity of the seminal vesicle and vas deferens to norepinephrine, but at concentrations higher than 10 microM there were striking depressions of maximal contractions induced by norepinephrine, carbachol and CaCl(2). In HEK293 cells, sibutramine 10 to 100 microM inhibited intracellular Ca(2+) transients induced by carbachol. Depending on the doses, sibutramine either facilitates or inhibits ejaculation. Apart from its actions in the central nervous system, facilitation of ejaculation may result from augmented sensitivity of smooth muscles to norepinephrine while reductions of intracellular Ca(2+) may be involved in the delayed ejaculation observed with high doses of sibutramine.

  7. Multiple effects of sibutramine on ejaculation and on vas deferens and seminal vesicle contractility

    International Nuclear Information System (INIS)

    Nojimoto, Fernanda D.; Piffer, Renata C.; Kiguti, Luiz Ricardo de A.; Lameu, Claudiana; Camargo, Antonio C.M. de; Pereira, Oduvaldo C.M.; Pupo, Andre S.

    2009-01-01

    Sibutramine is an inhibitor of norepinephrine and 5-HT reuptake largely used in the management of obesity. Although a fairly safe drug, postmarketing adverse effects of sibutramine were reported including abnormal ejaculation in men. This study investigates the effects of sibutramine on ejaculation and vas deferens and seminal vesicle contractility. Adult male rats received sibutramine (5; 20; or 50 mg kg -1 , ip) and after 60 min were exposed to receptive females for determination of ejaculation parameters. The vasa deferentia and seminal vesicles of untreated rats were mounted in isolated organ baths for recording of isometric contractions and HEK293 cells loaded with fluorescent calcium indicator were used to measure intracellular Ca 2+ transients. Sibutramine 5 and 20 mg kg -1 reduced ejaculation latency whereas 50 mg kg -1 increased ejaculation latency. Sibutramine 3 to 30 μM greatly increased the sensitivity of the seminal vesicle and vas deferens to norepinephrine, but at concentrations higher than 10 μM there were striking depressions of maximal contractions induced by norepinephrine, carbachol and CaCl 2 . In HEK293 cells, sibutramine 10 to 100 μM inhibited intracellular Ca 2+ transients induced by carbachol. Depending on the doses, sibutramine either facilitates or inhibits ejaculation. Apart from its actions in the central nervous system, facilitation of ejaculation may result from augmented sensitivity of smooth muscles to norepinephrine while reductions of intracellular Ca 2+ may be involved in the delayed ejaculation observed with high doses of sibutramine.

  8. Human embryonic stem cell derived mesenchymal progenitors express cardiac markers but do not form contractile cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Christophe M Raynaud

    Full Text Available Mesenchymal progenitors or stromal cells have shown promise as a therapeutic strategy for a range of diseases including heart failure. In this context, we explored the growth and differentiation potential of mesenchymal progenitors (MPs derived in vitro from human embryonic stem cells (hESCs. Similar to MPs isolated from bone marrow, hESC derived MPs (hESC-MPs efficiently differentiated into archetypical mesenchymal derivatives such as chondrocytes and adipocytes. Upon treatment with 5-Azacytidine or TGF-β1, hESC-MPs modified their morphology and up-regulated expression of key cardiac transcription factors such as NKX2-5, MEF2C, HAND2 and MYOCD. Nevertheless, NKX2-5+ hESC-MP derivatives did not form contractile cardiomyocytes, raising questions concerning the suitability of these cells as a platform for cardiomyocyte replacement therapy. Gene profiling experiments revealed that, although hESC-MP derived cells expressed a suite of cardiac related genes, they lacked the complete repertoire of genes associated with bona fide cardiomyocytes. Our results suggest that whilst agents such as TGF-β1 and 5-Azacytidine can induce expression of cardiac related genes, but treated cells retain a mesenchymal like phenotype.

  9. Pharmacological characterization and chemical fractionation of a liposterolic extract of saw palmetto (Serenoa repens): effects on rat prostate contractility.

    Science.gov (United States)

    Chua, Thiam; Eise, Nicole T; Simpson, Jamie S; Ventura, Sabatino

    2014-03-14

    Saw palmetto (Serenoa repens) was first used medicinally by native American Indians to treat urological disorders. Nowadays, saw palmetto extracts are widely used in Europe and North America to treat the urinary symptoms associated with benign prostatic hyperplasia even though its mechanisms of action are poorly understood. This study aimed to characterize the bioactive constituents of a lipid extract of saw palmetto that are able to affect contractility of the rat prostate gland. The mechanism of action will also be investigated. A commercially available lipid extract of saw palmetto was subjected to fractionation using normal phase column chromatography. Composition of fractions was assessed by proton nuclear magnetic resonance spectroscopy ((1)H NMR) and mass spectrometry (MS). Contractile activities of these fractions were evaluated pharmacologically using isolated preparations of rat prostate gland and compared to the activity of the crude extract. Saw palmetto extract inhibited contractions of the rat prostate gland which were consistent with smooth muscle relaxant activity. Only the ethyl acetate fraction resulting from chromatography inhibited contractions of isolated rat prostates similarly to the inhibition produced by the crude lipid extract. Comparison with authentic samples and analysis of NMR data revealed that this bioactivity was due to the fatty acid components present in the ethyl acetate fraction. Bioassay using various pharmacological tools identified multiple contractile mechanisms which were affected by the bioactive constituents. A fatty acid component of saw palmetto extract causes inhibition of prostatic smooth muscle contractions via a non-specific mechanism. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. The effects of space flight on the contractile apparatus of antigravity muscles: implications for aging and deconditioning

    Science.gov (United States)

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

    1994-01-01

    Previous studies have shown that the unloading of skeletal muscle, as occurring during exposure to space flight, exerts a profound effect on both the mass (cross sectional area) of skeletal muscle fibers and the relative expression of protein isoforms comprising the contractile system. Available information suggests that slow (type I) fibers, comprising chiefly the antigravity muscles of experimental animals, in addition to atrophying, undergo alterations in the type of myosin heavy chain (MHC) expressed such that faster isoforms become concomitantly expressed in a sub-population of slow fibers when insufficient force-bearing activity is maintained on the muscle. Consequently, these transformations in both mass and myosin heavy chain phenotype could exert a significant impact on the functional properties of skeletal muscle as manifest in the strength, contractile speed, and endurance scope of the muscle. To further explore these issues, a study was performed in which young adult male rats were exposed to zero gravity for six days, following which, the antigravity soleus muscle was examined for a) contractile properties, determined in situ and b) isomyosin expression, as studied using biochemical, molecular biology, and histochemical/immunohistochemical techniques.

  11. Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation.

    Directory of Open Access Journals (Sweden)

    Daniel Biermann

    Full Text Available The long-term outcome of patients with single ventricles improved over time, but remains poor compared to other congenital heart lesions with biventricular circulation. Main cause for this unfavourable outcome is the unphysiological hemodynamic of the Fontan circulation, such as subnormal systemic cardiac output and increased systemic-venous pressure. To overcome this limitation, we are developing the concept of a contractile extracardiac Fontan-tunnel. In this study, we evaluated the survival and structural development of a tissue-engineered conduit under in vivo conditions. Engineered heart tissue was generated from ventricular heart cells of neonatal Wistar rats, fibrinogen and thrombin. Engineered heart tissues started beating around day 8 in vitro and remained contractile in vivo throughout the experiment. After culture for 14 days constructs were implanted around the right superior vena cava of Wistar rats (n = 12. Animals were euthanized after 7, 14, 28 and 56 days postoperatively. Hematoxylin and eosin staining showed cardiomyocytes arranged in thick bundles within the engineered heart tissue-conduit. Immunostaining of sarcomeric actin, alpha-actin and connexin 43 revealed a well -developed cardiac myocyte structure. Magnetic resonance imaging (d14, n = 3 revealed no constriction or stenosis of the superior vena cava by the constructs. Engineered heart tissues survive and contract for extended periods after implantation around the superior vena cava of rats. Generation of larger constructs is warranted to evaluate functional benefits of a contractile Fontan-conduit.

  12. Contractile Defect Caused by Mutation in MYBPC3 Revealed under Conditions Optimized for Human PSC-Cardiomyocyte Function

    Directory of Open Access Journals (Sweden)

    Matthew J. Birket

    2015-10-01

    Full Text Available Maximizing baseline function of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs is essential for their effective application in models of cardiac toxicity and disease. Here, we aimed to identify factors that would promote an adequate level of function to permit robust single-cell contractility measurements in a human induced pluripotent stem cell (hiPSC model of hypertrophic cardiomyopathy (HCM. A simple screen revealed the collaborative effects of thyroid hormone, IGF-1 and the glucocorticoid analog dexamethasone on the electrophysiology, bioenergetics, and contractile force generation of hPSC-CMs. In this optimized condition, hiPSC-CMs with mutations in MYBPC3, a gene encoding myosin-binding protein C, which, when mutated, causes HCM, showed significantly lower contractile force generation than controls. This was recapitulated by direct knockdown of MYBPC3 in control hPSC-CMs, supporting a mechanism of haploinsufficiency. Modeling this disease in vitro using human cells is an important step toward identifying therapeutic interventions for HCM.

  13. Effects of Using Tricaine Methanesulfonate and Metomidate before Euthanasia on the Contractile Properties of Rainbow Trout (Oncorhynchus mykiss) Myocardium.

    Science.gov (United States)

    Roberts, Jordan C; Syme, Douglas A

    2016-01-01

    Because many anesthetics work through depressing cell excitability, unanesthetized euthanasia has become common for research involving excitable tissues (for example muscle and nerve) to avoid these depressive effects. However, anesthetic use during euthanasia may be indicated for studies involving isolated tissues if the potential depressive effects of brief anesthetic exposure dissipate after subsequent tissue isolation, washout, and saline perfusion. We explore this here by measuring whether, when applied prior to euthanasia, standard immersion doses of 2 fish anesthetics, tricaine methanesulfonate (TMS; 100 mg/L, n = 6) and methyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate (metomidate, 10 mg/L, n = 6), have residual effects on the contractile properties (force and work output) of isolated and saline-perfused ventricular compact myocardium from rainbow trout (Oncorhynchus mykiss). Results suggest that direct exposure of muscle to immersion doses of TMS-but not metomidate-impairs muscle contractile performance. However, brief exposure (2 to 3 min) to either anesthetic during euthanasia only-providing that the agent is washed out prior to tissue experimentation-does not have an effect on the contractile properties of the myocardium. Therefore, the use of TMS, metomidate, and perhaps other anesthetics that depress cell excitability during euthanasia may be indicated when conducting research on isolated and rinsed tissues.

  14. Generation of Functional Cardiomyocytes from Efficiently Generated Human iPSCs and a Novel Method of Measuring Contractility.

    Directory of Open Access Journals (Sweden)

    Sheeja Rajasingh

    Full Text Available Human induced pluripotent stem cells (iPSCs derived cardiomyocytes (iCMCs would provide an unlimited cell source for regenerative medicine and drug discoveries. The objective of our study is to generate functional cardiomyocytes from human iPSCs and to develop a novel method of measuring contractility of CMCs. In a series of experiments, adult human skin fibroblasts (HSF and human umbilical vein endothelial cells (HUVECs were treated with a combination of pluripotent gene DNA and mRNA under specific conditions. The iPSC colonies were identified and differentiated into various cell lineages, including CMCs. The contractile activity of CMCs was measured by a novel method of frame-by-frame cross correlation (particle image velocimetry-PIV analysis. Our treatment regimen transformed 4% of HSFs into iPSC colonies at passage 0, a significantly improved efficiency compared with use of either DNA or mRNA alone. The iPSCs were capable of differentiating both in vitro and in vivo into endodermal, ectodermal and mesodermal cells, including CMCs with >88% of cells being positive for troponin T (CTT and Gata4 by flow cytometry. We report a highly efficient combination of DNA and mRNA to generate iPSCs and functional iCMCs from adult human cells. We also report a novel approach to measure contractility of iCMCs.

  15. Generation of Functional Cardiomyocytes from Efficiently Generated Human iPSCs and a Novel Method of Measuring Contractility.

    Science.gov (United States)

    Rajasingh, Sheeja; Thangavel, Jayakumar; Czirok, Andras; Samanta, Saheli; Roby, Katherine F; Dawn, Buddhadeb; Rajasingh, Johnson

    2015-01-01

    Human induced pluripotent stem cells (iPSCs) derived cardiomyocytes (iCMCs) would provide an unlimited cell source for regenerative medicine and drug discoveries. The objective of our study is to generate functional cardiomyocytes from human iPSCs and to develop a novel method of measuring contractility of CMCs. In a series of experiments, adult human skin fibroblasts (HSF) and human umbilical vein endothelial cells (HUVECs) were treated with a combination of pluripotent gene DNA and mRNA under specific conditions. The iPSC colonies were identified and differentiated into various cell lineages, including CMCs. The contractile activity of CMCs was measured by a novel method of frame-by-frame cross correlation (particle image velocimetry-PIV) analysis. Our treatment regimen transformed 4% of HSFs into iPSC colonies at passage 0, a significantly improved efficiency compared with use of either DNA or mRNA alone. The iPSCs were capable of differentiating both in vitro and in vivo into endodermal, ectodermal and mesodermal cells, including CMCs with >88% of cells being positive for troponin T (CTT) and Gata4 by flow cytometry. We report a highly efficient combination of DNA and mRNA to generate iPSCs and functional iCMCs from adult human cells. We also report a novel approach to measure contractility of iCMCs.

  16. Na+/Ca2+ exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart

    OpenAIRE

    Farkas, A S; Acsai, K; Nagy, N; Tóth, A; Fülöp, F; Seprényi, G; Birinyi, P; Nánási, P P; Forster, T; Csanády, M; Papp, J G; Varró, A; Farkas, A

    2008-01-01

    Background and purpose: The Na+/Ca2+ exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na+ concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 μM SEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na+ concentrations in rabbit and rat hearts.

  17. Regulation of myofibrillar accumulation in chick muscle cultures - Evidence for the involvement of calcium and lysosomes in non-uniform turnover of contractile proteins

    Science.gov (United States)

    Silver, Geri; Etlinger, Joseph D.

    1985-01-01

    The effects of calcium on the synthesis and the degradation of individual myofibrillar proteins were investigated using primary chick-leg skeletal muscle cultures labeled with S-35-methionine (for protein accumulation experiments) or Ca(2+)-45 (for calcium efflux experiments). It was found that the turnover of individual contractile proteins is regulated nonuniformly by a calcium-dependent mechanism involving lysosomes. The results also indicate that contractile proteins are released from the myofibril before their breakdown to amino acids.

  18. Regulation of glycogen synthesis in rat skeletal muscle after glycogen-depleting contractile activity: effects of adrenaline on glycogen synthesis and activation of glycogen synthase and glycogen phosphorylase.

    OpenAIRE

    Franch, J; Aslesen, R; Jensen, J

    1999-01-01

    We investigated the effects of insulin and adrenaline on the rate of glycogen synthesis in skeletal muscles after electrical stimulation in vitro. The contractile activity decreased the glycogen concentration by 62%. After contractile activity, the glycogen stores were fully replenished at a constant and high rate for 3 h when 10 m-i.u./ml insulin was present. In the absence of insulin, only 65% of the initial glycogen stores was replenished. Adrenaline decreased insulin-stimulated glycogen s...

  19. Maximum gravitational redshift of white dwarfs

    International Nuclear Information System (INIS)

    Shapiro, S.L.; Teukolsky, S.A.

    1976-01-01

    The stability of uniformly rotating, cold white dwarfs is examined in the framework of the Parametrized Post-Newtonian (PPN) formalism of Will and Nordtvedt. The maximum central density and gravitational redshift of a white dwarf are determined as functions of five of the nine PPN parameters (γ, β, zeta 2 , zeta 3 , and zeta 4 ), the total angular momentum J, and the composition of the star. General relativity predicts that the maximum redshifts is 571 km s -1 for nonrotating carbon and helium dwarfs, but is lower for stars composed of heavier nuclei. Uniform rotation can increase the maximum redshift to 647 km s -1 for carbon stars (the neutronization limit) and to 893 km s -1 for helium stars (the uniform rotation limit). The redshift distribution of a larger sample of white dwarfs may help determine the composition of their cores

  20. Role of contractile prostaglandins and Rho-kinase in growth factor-induced airway smooth muscle contraction

    Directory of Open Access Journals (Sweden)

    Zaagsma Johan

    2005-07-01

    Full Text Available Abstract Background In addition to their proliferative and differentiating effects, several growth factors are capable of inducing a sustained airway smooth muscle (ASM contraction. These contractile effects were previously found to be dependent on Rho-kinase and have also been associated with the production of eicosanoids. However, the precise mechanisms underlying growth factor-induced contraction are still unknown. In this study we investigated the role of contractile prostaglandins and Rho-kinase in growth factor-induced ASM contraction. Methods Growth factor-induced contractions of guinea pig open-ring tracheal preparations were studied by isometric tension measurements. The contribution of Rho-kinase, mitogen-activated protein kinase (MAPK and cyclooxygenase (COX to these reponses was established, using the inhibitors Y-27632 (1 μM, U-0126 (3 μM and indomethacin (3 μM, respectively. The Rho-kinase dependency of contractions induced by exogenously applied prostaglandin F2α (PGF2α and prostaglandin E2 (PGE2 was also studied. In addition, the effects of the selective FP-receptor antagonist AL-8810 (10 μM and the selective EP1-antagonist AH-6809 (10 μM on growth factor-induced contractions were investigated, both in intact and epithelium-denuded preparations. Growth factor-induced PGF2α-and PGE2-release in the absence and presence of Y-27632, U-0126 and indomethacin, was assessed by an ELISA-assay. Results Epidermal growth factor (EGF-and platelet-derived growth factor (PDGF-induced contractions of guinea pig tracheal smooth muscle preparations were dependent on Rho-kinase, MAPK and COX. Interestingly, growth factor-induced PGF2α-and PGE2-release from tracheal rings was significantly reduced by U-0126 and indomethacin, but not by Y-27632. Also, PGF2α-and PGE2-induced ASM contractions were largely dependent on Rho-kinase, in contrast to other contractile agonists like histamine. The FP-receptor antagonist AL-8810 (10 μM significantly

  1. Maximum entropy analysis of EGRET data

    DEFF Research Database (Denmark)

    Pohl, M.; Strong, A.W.

    1997-01-01

    EGRET data are usually analysed on the basis of the Maximum-Likelihood method \\cite{ma96} in a search for point sources in excess to a model for the background radiation (e.g. \\cite{hu97}). This method depends strongly on the quality of the background model, and thus may have high systematic unce...... uncertainties in region of strong and uncertain background like the Galactic Center region. Here we show images of such regions obtained by the quantified Maximum-Entropy method. We also discuss a possible further use of MEM in the analysis of problematic regions of the sky....

  2. The Maximum Resource Bin Packing Problem

    DEFF Research Database (Denmark)

    Boyar, J.; Epstein, L.; Favrholdt, L.M.

    2006-01-01

    Usually, for bin packing problems, we try to minimize the number of bins used or in the case of the dual bin packing problem, maximize the number or total size of accepted items. This paper presents results for the opposite problems, where we would like to maximize the number of bins used...... algorithms, First-Fit-Increasing and First-Fit-Decreasing for the maximum resource variant of classical bin packing. For the on-line variant, we define maximum resource variants of classical and dual bin packing. For dual bin packing, no on-line algorithm is competitive. For classical bin packing, we find...

  3. Shower maximum detector for SDC calorimetry

    International Nuclear Information System (INIS)

    Ernwein, J.

    1994-01-01

    A prototype for the SDC end-cap (EM) calorimeter complete with a pre-shower and a shower maximum detector was tested in beams of electrons and Π's at CERN by an SDC subsystem group. The prototype was manufactured from scintillator tiles and strips read out with 1 mm diameter wave-length shifting fibers. The design and construction of the shower maximum detector is described, and results of laboratory tests on light yield and performance of the scintillator-fiber system are given. Preliminary results on energy and position measurements with the shower max detector in the test beam are shown. (authors). 4 refs., 5 figs

  4. Topics in Bayesian statistics and maximum entropy

    International Nuclear Information System (INIS)

    Mutihac, R.; Cicuttin, A.; Cerdeira, A.; Stanciulescu, C.

    1998-12-01

    Notions of Bayesian decision theory and maximum entropy methods are reviewed with particular emphasis on probabilistic inference and Bayesian modeling. The axiomatic approach is considered as the best justification of Bayesian analysis and maximum entropy principle applied in natural sciences. Particular emphasis is put on solving the inverse problem in digital image restoration and Bayesian modeling of neural networks. Further topics addressed briefly include language modeling, neutron scattering, multiuser detection and channel equalization in digital communications, genetic information, and Bayesian court decision-making. (author)

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

    Directory of Open Access Journals (Sweden)

    Xinhua Zhang

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

  6. 17β-Estradiol-induced interaction of estrogen receptor α and human atrial essential myosin light chain modulates cardiac contractile function.

    Science.gov (United States)

    Duft, Karolin; Schanz, Miriam; Pham, Hang; Abdelwahab, Ahmed; Schriever, Cindy; Kararigas, Georgios; Dworatzek, Elke; Davidson, Mercy M; Regitz-Zagrosek, Vera; Morano, Ingo; Mahmoodzadeh, Shokoufeh

    2017-01-01

    Chronic increased workload of the human heart causes ventricular hypertrophy, re-expression of the atrial essential myosin light chain (hALC-1), and improved contractile function. Although hALC-1 is an important positive inotropic regulator of the human heart, little is known about its regulation. Therefore, we investigated the role of the sex hormone 17β-estradiol (E2) on hALC-1 gene expression, the underlying molecular mechanisms, and the impact of this regulatory process on cardiac contractile function. We showed that E2 attenuated hALC-1 expression in human atrial tissues of both sexes and in human ventricular AC16 cells. E2 induced the nuclear translocation of estrogen receptor alpha (ERα) and hALC-1 in AC16 cells, where they cooperatively regulate the transcriptional activity of hALC-1 gene promoter. E2-activated ERα required the estrogen response element (ERE) motif within the hALC-1 gene promoter to reduce its transcriptional activity (vehicle: 15.55 ± 4.80 vs. E2: 6.51 ± 3.69; ~2 fold). This inhibitory effect was potentiated in the presence of hALC-1 (vehicle: 11.13 ± 3.66 vs. E2: 2.18 ± 1.10; ~5 fold), and thus, hALC-1 acts as a co-repressor of ERα-mediated transcription. Yeast two-hybrid screening of a human heart cDNA library revealed that ERα interacts physically with hALC-1 in the presence of E2. This interaction was confirmed by Co-Immunoprecipitation and immunofluorescence in human atrium. As a further novel effect, we showed that chronic E2-treatment of adult mouse cardiomyocytes overexpressing hALC-1 resulted in reduced cell-shortening amplitude and twitching kinetics of these cells independent of Ca 2+ activation levels. Together, our data showed that the expression of hALC-1 gene is, at least partly, regulated by E2/ERα, while hALC-1 acts as a co-repressor. The inotropic effect of hALC-1 overexpression in cardiomyocytes can be significantly repressed by E2.

  7. IMAGE-BASED IN VIVO QUANTITATIVE ASSESSMENT OF HUMAN AIRWAY OPENING AND CONTRACTILITY BY FIBER OPTICAL NASOPHARYNGOSCOPY IN HEALTHY AND ASTHMATIC SUBJECTS

    Directory of Open Access Journals (Sweden)

    LINHONG DENG

    2013-04-01

    Full Text Available Assessment of human airway lumen opening is important in diagnosing and understanding the mechanisms of airway dysfunctions such as the excessive airway narrowing in asthma and chronic obstructive pulmonary disease (COPD. Although there are indirect methods to evaluate the airway calibre, direct in vivo measurement of the airway calibre has not been commonly available. With recent advent of the flexible fiber optical nasopharyngoscope with video recording it has become possible to directly visualize the passages of upper and lower airways. However, quantitative analysis of the recorded video images has been technically challenging. Here, we describe an automatic image processing and analysis method that allows for batch analysis of the images recorded during the endoscopic procedure, thus facilitates image-based quantification of the airway opening. Video images of the airway lumen of volunteer subject were acquired using a fiber optical nasopharyngoscope, and subsequently processed using Gaussian smoothing filter, threshold segmentation, differentiation, and Canny image edge detection, respectively. Thus the area of the open airway lumen was identified and computed using a predetermined converter of the image scale to true dimension of the imaged object. With this method we measured the opening/narrowing of the glottis during tidal breathing with or without making "Hee" sound or cough. We also used this method to measure the opening/narrowing of the primary bronchus of either healthy or asthmatic subjects in response to histamine and/or albuterol treatment, which also provided an indicator of the airway contractility. Our results demonstrate that the image-based method accurately quantified the area change waveform of either the glottis or the bronchus as observed by using the optical nasopharygoscope. Importantly, the opening/narrowing of the airway lumen generally correlated with the airflow and resistance of the airways, and could

  8. Nonsymmetric entropy and maximum nonsymmetric entropy principle

    International Nuclear Information System (INIS)

    Liu Chengshi

    2009-01-01

    Under the frame of a statistical model, the concept of nonsymmetric entropy which generalizes the concepts of Boltzmann's entropy and Shannon's entropy, is defined. Maximum nonsymmetric entropy principle is proved. Some important distribution laws such as power law, can be derived from this principle naturally. Especially, nonsymmetric entropy is more convenient than other entropy such as Tsallis's entropy in deriving power laws.

  9. Maximum speed of dewetting on a fiber

    NARCIS (Netherlands)

    Chan, Tak Shing; Gueudre, Thomas; Snoeijer, Jacobus Hendrikus

    2011-01-01

    A solid object can be coated by a nonwetting liquid since a receding contact line cannot exceed a critical speed. We theoretically investigate this forced wetting transition for axisymmetric menisci on fibers of varying radii. First, we use a matched asymptotic expansion and derive the maximum speed

  10. Maximum potential preventive effect of hip protectors

    NARCIS (Netherlands)

    van Schoor, N.M.; Smit, J.H.; Bouter, L.M.; Veenings, B.; Asma, G.B.; Lips, P.T.A.M.

    2007-01-01

    OBJECTIVES: To estimate the maximum potential preventive effect of hip protectors in older persons living in the community or homes for the elderly. DESIGN: Observational cohort study. SETTING: Emergency departments in the Netherlands. PARTICIPANTS: Hip fracture patients aged 70 and older who

  11. Maximum gain of Yagi-Uda arrays

    DEFF Research Database (Denmark)

    Bojsen, J.H.; Schjær-Jacobsen, Hans; Nilsson, E.

    1971-01-01

    Numerical optimisation techniques have been used to find the maximum gain of some specific parasitic arrays. The gain of an array of infinitely thin, equispaced dipoles loaded with arbitrary reactances has been optimised. The results show that standard travelling-wave design methods are not optimum....... Yagi–Uda arrays with equal and unequal spacing have also been optimised with experimental verification....

  12. correlation between maximum dry density and cohesion

    African Journals Online (AJOL)

    HOD

    represents maximum dry density, signifies plastic limit and is liquid limit. Researchers [6, 7] estimate compaction parameters. Aside from the correlation existing between compaction parameters and other physical quantities there are some other correlations that have been investigated by other researchers. The well-known.

  13. Weak scale from the maximum entropy principle

    Science.gov (United States)

    Hamada, Yuta; Kawai, Hikaru; Kawana, Kiyoharu

    2015-03-01

    The theory of the multiverse and wormholes suggests that the parameters of the Standard Model (SM) are fixed in such a way that the radiation of the S3 universe at the final stage S_rad becomes maximum, which we call the maximum entropy principle. Although it is difficult to confirm this principle generally, for a few parameters of the SM, we can check whether S_rad actually becomes maximum at the observed values. In this paper, we regard S_rad at the final stage as a function of the weak scale (the Higgs expectation value) vh, and show that it becomes maximum around vh = {{O}} (300 GeV) when the dimensionless couplings in the SM, i.e., the Higgs self-coupling, the gauge couplings, and the Yukawa couplings are fixed. Roughly speaking, we find that the weak scale is given by vh ˜ T_{BBN}2 / (M_{pl}ye5), where ye is the Yukawa coupling of electron, T_BBN is the temperature at which the Big Bang nucleosynthesis starts, and M_pl is the Planck mass.

  14. The maximum-entropy method in superspace

    Czech Academy of Sciences Publication Activity Database

    van Smaalen, S.; Palatinus, Lukáš; Schneider, M.

    2003-01-01

    Roč. 59, - (2003), s. 459-469 ISSN 0108-7673 Grant - others:DFG(DE) XX Institutional research plan: CEZ:AV0Z1010914 Keywords : maximum-entropy method, * aperiodic crystals * electron density Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.558, year: 2003

  15. Achieving maximum sustainable yield in mixed fisheries

    NARCIS (Netherlands)

    Ulrich, Clara; Vermard, Youen; Dolder, Paul J.; Brunel, Thomas; Jardim, Ernesto; Holmes, Steven J.; Kempf, Alexander; Mortensen, Lars O.; Poos, Jan Jaap; Rindorf, Anna

    2017-01-01

    Achieving single species maximum sustainable yield (MSY) in complex and dynamic fisheries targeting multiple species (mixed fisheries) is challenging because achieving the objective for one species may mean missing the objective for another. The North Sea mixed fisheries are a representative example

  16. 5 CFR 534.203 - Maximum stipends.

    Science.gov (United States)

    2010-01-01

    ... maximum stipend established under this section. (e) A trainee at a non-Federal hospital, clinic, or medical or dental laboratory who is assigned to a Federal hospital, clinic, or medical or dental... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY UNDER OTHER SYSTEMS Student...

  17. Minimal length, Friedmann equations and maximum density

    Energy Technology Data Exchange (ETDEWEB)

    Awad, Adel [Center for Theoretical Physics, British University of Egypt,Sherouk City 11837, P.O. Box 43 (Egypt); Department of Physics, Faculty of Science, Ain Shams University,Cairo, 11566 (Egypt); Ali, Ahmed Farag [Centre for Fundamental Physics, Zewail City of Science and Technology,Sheikh Zayed, 12588, Giza (Egypt); Department of Physics, Faculty of Science, Benha University,Benha, 13518 (Egypt)

    2014-06-16

    Inspired by Jacobson’s thermodynamic approach, Cai et al. have shown the emergence of Friedmann equations from the first law of thermodynamics. We extend Akbar-Cai derivation http://dx.doi.org/10.1103/PhysRevD.75.084003 of Friedmann equations to accommodate a general entropy-area law. Studying the resulted Friedmann equations using a specific entropy-area law, which is motivated by the generalized uncertainty principle (GUP), reveals the existence of a maximum energy density closed to Planck density. Allowing for a general continuous pressure p(ρ,a) leads to bounded curvature invariants and a general nonsingular evolution. In this case, the maximum energy density is reached in a finite time and there is no cosmological evolution beyond this point which leaves the big bang singularity inaccessible from a spacetime prospective. The existence of maximum energy density and a general nonsingular evolution is independent of the equation of state and the spacial curvature k. As an example we study the evolution of the equation of state p=ωρ through its phase-space diagram to show the existence of a maximum energy which is reachable in a finite time.

  18. Swimming exercise reverses aging-related contractile abnormalities of female heart by improving structural alterations.

    Science.gov (United States)

    Ozturk, Nihal; Olgar, Yusuf; Er, Hakan; Kucuk, Murathan; Ozdemir, Semir

    2017-01-01

    The objective of this study was to examine the effect of swimming exercise on aging-related Ca2+ handling alterations and structural abnormalities of female rat heart. For this purpose, 4-month and 24-month old female rats were used and divided into three following groups: sedentary young (SY), sedentary old (SO), and exercised old (Ex-O). Swimming exercise was performed for 8 weeks (60 min/day, 5 days/week). Myocyte shortening, L-type Ca2+ currents and associated Ca2+ transients were measured from ventricular myocytes at 36 ± 1°C. NOX-4 levels, aconitase activity, glutathione measurements and ultrastructural examination by electron microscopy were conducted in heart tissue. Swimming exercise reversed the reduced shortening and slowed kinetics of aged cardiomyocytes. Although the current density was similar for all groups, Ca2+ transients were higher in SO and Ex-O myocytes with respect to the SY group. Caffeine-induced Ca2+ transients and the integrated NCX current were lower in cardiomyocytes of SY rats compared with other groups, suggesting an increased sarcoplasmic reticulum Ca2+ content in an aged heart. Aging led to upregulated cardiac NOX-4 along with declined aconitase activity. Although it did not reverse these oxidative parameters, swimming exercise achieved a significant increase in glutathione levels and improved structural alterations of old rats' hearts. We conclude that swimming exercise upregulates antioxidant defense capacity and improves structural abnormalities of senescent female rat heart, although it does not change Ca2+ handling alterations further. Thereby, it improves contractile function of aged myocardium by mitigating detrimental effects of oxidative stress.

  19. Deletion of Dicer in smooth muscle affects voiding pattern and reduces detrusor contractility and neuroeffector transmission.

    Directory of Open Access Journals (Sweden)

    Mardjaneh Karbalaei Sadegh

    Full Text Available MicroRNAs have emerged as important regulators of smooth muscle phenotype and may play important roles in pathogenesis of various smooth muscle related disease states. The aim of this study was to investigate the role of miRNAs for urinary bladder function. We used an inducible and smooth muscle specific Dicer knockout (KO mouse which resulted in significantly reduced levels of miRNAs, including miR-145, miR-143, miR-22, miR125b-5p and miR-27a, from detrusor preparations without mucosa. Deletion of Dicer resulted in a disturbed micturition pattern in vivo and reduced depolarization-induced pressure development in the isolated detrusor. Furthermore, electrical field stimulation revealed a decreased cholinergic but maintained purinergic component of neurogenic activation in Dicer KO bladder strips. The ultrastructure of detrusor smooth muscle cells was well maintained, and the density of nerve terminals was similar. Western blotting demonstrated reduced contents of calponin and desmin. Smooth muscle α-actin, SM22α and myocardin were unchanged. Activation of strips with exogenous agonists showed that depolarization-induced contraction was preferentially reduced; ATP- and calyculin A-induced contractions were unchanged. Quantitative real time PCR and western blotting demonstrated reduced expression of Cav1.2 (Cacna1c. It is concluded that smooth muscle miRNAs play an important role for detrusor contractility and voiding pattern of unrestrained mice. This is mediated in part via effects on expression of smooth muscle differentiation markers and L-type Ca(2+ channels in the detrusor.

  20. β-Citronellol, an alcoholic monoterpene with inhibitory properties on the contractility of rat trachea

    Directory of Open Access Journals (Sweden)

    T.B. Vasconcelos

    2016-01-01

    Full Text Available β-Citronellol is an alcoholic monoterpene found in essential oils such Cymbopogon citratus (a plant with antihypertensive properties. β-Citronellol can act against pathogenic microorganisms that affect airways and, in virtue of the popular use of β-citronellol-enriched essential oils in aromatherapy, we assessed its pharmacologic effects on the contractility of rat trachea. Contractions of isolated tracheal rings were recorded isometrically through a force transducer connected to a data-acquisition device. β-Citronellol relaxed sustained contractions induced by acetylcholine or high extracellular potassium, but half-maximal inhibitory concentrations (IC50 for K+-elicited stimuli were smaller than those for cholinergic contractions. It also inhibited contractions induced by electrical field stimulation or sodium orthovanadate with pharmacologic potency equivalent to that seen against acetylcholine-induced contractions. When contractions were evoked by selective recruitment of Ca2+ from the extracellular medium, β-citronellol preferentially inhibited contractions that involved voltage-operated (but not receptor-operated pathways. β-Citronellol (but not verapamil inhibited contractions induced by restoration of external Ca2+ levels after depleting internal Ca2+ stores with the concomitant presence of thapsigargin and recurrent challenge with acetylcholine. Treatment of tracheal rings with L-NAME, indomethacin or tetraethylammonium did not change the relaxing effects of β-citronellol. Inhibition of transient receptor potential vanilloid subtype 1 (TRPV1 or transient receptor potential ankyrin 1 (TRPA1 receptors with selective antagonists caused no change in the effects of β-citronellol. In conclusion, β-citronellol exerted inhibitory effects on rat tracheal rings, with predominant effects on contractions that recruit Ca2+ inflow towards the cytosol by voltage-gated pathways, whereas it appears less active against contractions elicited by

  1. The Effect of Substrate Elasticity and Actomyosin Contractility on Different Forms of Endocytosis

    Science.gov (United States)

    Missirlis, Dimitris

    2014-01-01

    Substrate mechanical properties have emerged as potent determinants of cell functions and fate. We here tested the hypothesis that different forms of endocytosis are regulated by the elasticity of the synthetic hydrogels cells are cultured on. Towards this objective, we quantified cell-associated fluorescence of the established endocytosis markers transferrin (Tf) and cholera toxin subunit B (CTb) using a flow-cytometry based protocol, and imaged marker internalization using microscopy techniques. Our results demonstrated that clathrin-mediated endocytosis of Tf following a 10-minute incubation with a fibroblast cell line was lower on the softer substrates studied (5 kPa) compared to those with elasticities of 40 and 85 kPa. This effect was cancelled after 1-hour incubation revealing that intracellular accumulation of Tf at this time point did not depend on substrate elasticity. Lipid-raft mediated endocytosis of CTb, on the other hand, was not affected by substrate elasticity in the studied range of time and substrate elasticity. The use of pharmacologic contractility inhibitors revealed inhibition of endocytosis for both Tf and CTb after a 10-minute incubation and a dissimilar effect after 1 hour depending on the inhibitor type. Further, the internalization of fluorescent NPs, used as model drug delivery systems, showed a dependence on substrate elasticity, while transfection efficiency was unaffected by it. Finally, an independence on substrate elasticity of Tf and CTb association with HeLa cells indicated that there are cell-type differences in this respect. Overall, our results suggest that clathrin-mediated but not lipid-raft mediated endocytosis is potentially influenced by substrate mechanics at the cellular level, while intracellular trafficking and accumulation show a more complex dependence. Our findings are discussed in the context of previous work on how substrate mechanics affect the fundamental process of endocytosis and highlight important

  2. Chelidonium majus and its effects on uterine contractility in a perfusion model.

    Science.gov (United States)

    Kuenzel, Julian; Geisler, Klaudija; Strahl, Olga; Grundtner, Philipp; Beckmann, Matthias W; Dittrich, Ralf

    2013-07-01

    The herbal agent celandine is thought to have mainly spasmolytic effects, but in the uterus it is regarded as promoting contractions, which can offer promising and innovative options for optimizing artificial reproduction. The aim of the present study was to investigate the effect of celandine on the uterine muscle, using a perfusion model of swine uteri. Sixteen swine uteri were perfused with Krebs-Ringer solution. Celandine (Chelidonium, Paverysat; Johannes Bürger Ysatfabrik Ltd., Bad Harzburg, Germany) was administered at increasing dosages. Intrauterine pressure (IUP) was recorded using an intrauterine double-chip microcatheter (Urobar 8 DS-F, Raumedic, Rehau AG & Co., Rehau, Germany). Differences in pressure (ΔP) and area under the curve (ΔAUC) after drug administration in the uterine body and uterine horn in the various dilution series were noted. A paired Student's t-test was used to evaluate differences between groups, with significance set at P<0.05. A significant initial increase in uterine activity was visible at each dosage. Inhibition of uterine activity was seen over longer periods of 5 and 10 min, particularly for a medium-dose range of 1-2mg/ml. At a dosage of 2mg/ml in particular, celandine almost always led to significant values. Following intra-arterial administration in a swine uterus perfusion model, celandine initially causes a significant increase in contractility, which is followed over time by a relaxation phase. This suggests interesting hypotheses on whether Chelidonium majus might be used to promote targeted sperm transport. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. The effects of watermelon (Citrullus lanatus) extracts and L-citrulline on rat uterine contractility.

    Science.gov (United States)

    Munglue, Phukphon; Eumkep, Graingsak; Wray, Susan; Kupittayanant, Sajeera

    2013-04-01

    In uterine smooth muscle, the effects of watermelon and its citrulline content are unknown. The aims of this study were therefore, to determine the effects of watermelon extract and citrulline on the myometrium and to investigate their mechanisms of action. The effects of extracts of watermelon flesh and rind and L-citrulline (64 μmol/L) were evaluated on 3 types of contractile activity; spontaneous, those elicited by potassium chloride (KCl) depolarization, or oxytocin (10 nmol/L) application in isolated rat uterus. Inhibitors of nitric oxide (NO) and its mechanisms of action, N ω-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 μmol/L), LY83583 (1 μmol/L), and tetraethylamonium chloride (5 mmol/L), as well as Ca signaling pathways, were determined. Both flesh and rind extracts significantly decreased the force produced by all 3 mechanisms, in a dose-dependent manner. The extracts could also significantly decrease the force under conditions of sustained high Ca levels (depolarization and agonist) and when the force was produced only by sarcoplasmic reticulum (SR) Ca release. L-citrulline produced the same effects on force as watermelon extracts. With submaximal doses of extract, the additive effects of L-citrulline were found. The inhibitory effects of extracts and L-citrulline were reversed upon the addition of NO inhibitors, and pretreatment of tissues with these inhibitors prevented the actions of both extracts and L-citrulline. Thus, these data show that watermelon and citrulline are potent tocolytics, decreasing the force produced by calcium entry and SR release and arising by different pathways, including oxytocin stimulation. Their major mechanism is to stimulate the NO-cyclic guanosine monophosphate (cGMP) relaxant pathway.

  4. Contractile properties and sarcoplasmic reticulum calcium content in type I and type II skeletal muscle fibres in active aged humans.

    Science.gov (United States)

    Lamboley, C R; Wyckelsma, V L; Dutka, T L; McKenna, M J; Murphy, R M; Lamb, G D

    2015-06-01

    Muscle weakness in old age is due in large part to an overall loss of skeletal muscle tissue, but it remains uncertain how much also stems from alterations in the properties of the individual muscle fibres. This study examined the contractile properties and amount of stored intracellular calcium in single muscle fibres of Old (70 ± 4 years) and Young (22 ± 3 years) adults. The maximum level of force production (per unit cross-sectional area) in fast twitch fibres in Old subjects was lower than in Young subjects, and the fibres were also less sensitive to activation by calcium. The amount of calcium stored inside muscle fibres and available to trigger contraction was also lower in both fast- and slow-twitch muscle fibres in the Old subjects. These findings indicate that muscle weakness in old age stems in part from an impaired capacity for force production in the individual muscle fibres. This study examined the contractile properties and sarcoplasmic reticulum (SR) Ca(2+) content in mechanically skinned vastus lateralis muscle fibres of Old (70 ± 4 years) and Young (22 ± 3 years) humans to investigate whether changes in muscle fibre properties contribute to muscle weakness in old age. In type II fibres of Old subjects, specific force was reduced by ∼17% and Ca(2+) sensitivity was also reduced (pCa50 decreased ∼0.05 pCa units) relative to that in Young. S-Glutathionylation of fast troponin I (TnIf ) markedly increased Ca(2+) sensitivity in type II fibres, but the increase was significantly smaller in Old versus Young (+0.136 and +0.164 pCa unit increases, respectively). Endogenous and maximal SR Ca(2+) content were significantly smaller in both type I and type II fibres in Old subjects. In fibres of Young, the SR could be nearly fully depleted of Ca(2+) by a combined caffeine and low Mg(2+) stimulus, whereas in fibres of Old the amount of non-releasable Ca(2+) was significantly increased (by > 12% of endogenous Ca(2+) content). Western

  5. Chinese Herbal Medicine Treatment Improves the Overall Survival Rate of Individuals with Hypertension among Type 2 Diabetes Patients and Modulates In Vitro Smooth Muscle Cell Contractility

    Science.gov (United States)

    Yeh, Yi-Chun; Cheng, Chi-Fung; Shiao, Yi-Tzone; Wang, Chang-Bi; Chien, Wen-Kuei; Chen, Jin-Hua; Liu, Xiang; Tsang, Hsinyi; Lin, Ting-Hsu; Liao, Chiu-Chu; Huang, Shao-Mei; Li, Ju-Pi; Lin, Cheng-Wen; Pang, Hao-Yu; Lin, Jaung-Geng; Lan, Yu-Ching; Liu, Yu-Huei; Chen, Shih-Yin; Tsai, Fuu-Jen; Liang, Wen-Miin

    2015-01-01

    Type 2 diabetes (T2D) is a chronic, multifactorial, and metabolic disorder accounting for 90% diabetes cases worldwide. Among them, almost half of T2D have hypertension, which is responsible for cardiovascular disease, morbidity, and mortality in these patients. The Chinese herbal medicine (CHM) prescription patterns of hypertension individuals among T2D patients have yet to be characterized. This study, therefore, aimed to determine their prescription patterns and evaluate the CHM effect. A cohort of one million randomly sampled cases from the National Health Insurance Research Database (NHIRD) was used to investigate the overall survival rate of CHM users, and prescription patterns. After matching CHM and non-CHM users for age, gender and date of diagnosis of hypertension, 980 subjects for each group were selected. The CHM users were characterized with slightly longer duration time from diabetes to hypertension, and more cases for hyperlipidaemia. The cumulative survival probabilities were higher in CHM users than in non-CHM users. Among these top 12 herbs, Liu-Wei-Di-Huang-Wan, Jia-Wei-Xiao-Yao-San, Dan-Shen, and Ge-Gen were the most common herbs and inhibited in vitro smooth muscle cell contractility. Our study also provides a CHM comprehensive list that may be useful in future investigation of the safety and efficacy for individuals with hypertension among type 2 diabetes patients. PMID:26699542

  6. Benefits of the maximum tolerated dose (MTD) and maximum tolerated concentration (MTC) concept in aquatic toxicology

    International Nuclear Information System (INIS)

    Hutchinson, Thomas H.; Boegi, Christian; Winter, Matthew J.; Owens, J. Willie

    2009-01-01

    There is increasing recognition of the need to identify specific sublethal effects of chemicals, such as reproductive toxicity, and specific modes of actions of the chemicals, such as interference with the endocrine system. To achieve these aims requires criteria which provide a basis to interpret study findings so as to separate these specific toxicities and modes of action from not only acute lethality per se but also from severe inanition and malaise that non-specifically compromise reproductive capacity and the response of endocrine endpoints. Mammalian toxicologists have recognized that very high dose levels are sometimes required to elicit both specific adverse effects and present the potential of non-specific 'systemic toxicity'. Mammalian toxicologists have developed the concept of a maximum tolerated dose (MTD) beyond which a specific toxicity or action cannot be attributed to a test substance due to the compromised state of the organism. Ecotoxicologists are now confronted by a similar challenge and must develop an analogous concept of a MTD and the respective criteria. As examples of this conundrum, we note recent developments in efforts to validate protocols for fish reproductive toxicity and endocrine screens (e.g. some chemicals originally selected as 'negatives' elicited decreases in fecundity or changes in endpoints intended to be biomarkers for endocrine modes of action). Unless analogous criteria can be developed, the potentially confounding effects of systemic toxicity may then undermine the reliable assessment of specific reproductive effects or biomarkers such as vitellogenin or spiggin. The same issue confronts other areas of aquatic toxicology (e.g., genotoxicity) and the use of aquatic animals for preclinical assessments of drugs (e.g., use of zebrafish for drug safety assessment). We propose that there are benefits to adopting the concept of an MTD for toxicology and pharmacology studies using fish and other aquatic organisms and the

  7. Maximum Power Point Tracking Based on Sliding Mode Control

    Directory of Open Access Journals (Sweden)

    Nimrod Vázquez

    2015-01-01

    Full Text Available Solar panels, which have become a good choice, are used to generate and supply electricity in commercial and residential applications. This generated power starts with the solar cells, which have a complex relationship between solar irradiation, temperature, and output power. For this reason a tracking of the maximum power point is required. Traditionally, this has been made by considering just current and voltage conditions at the photovoltaic panel; however, temperature also influences the process. In this paper the voltage, current, and temperature in the PV system are considered to be a part of a sliding surface for the proposed maximum power point tracking; this means a sliding mode controller is applied. Obtained results gave a good dynamic response, as a difference from traditional schemes, which are only based on computational algorithms. A traditional algorithm based on MPPT was added in order to assure a low steady state error.

  8. Maximum concentrations at work and maximum biologically tolerable concentration for working materials 1991

    International Nuclear Information System (INIS)

    1991-01-01

    The meaning of the term 'maximum concentration at work' in regard of various pollutants is discussed. Specifically, a number of dusts and smokes are dealt with. The valuation criteria for maximum biologically tolerable concentrations for working materials are indicated. The working materials in question are corcinogeneous substances or substances liable to cause allergies or mutate the genome. (VT) [de

  9. 75 FR 43840 - Inflation Adjustment of the Ordinary Maximum and Aggravated Maximum Civil Monetary Penalties for...

    Science.gov (United States)

    2010-07-27

    ...-17530; Notice No. 2] RIN 2130-ZA03 Inflation Adjustment of the Ordinary Maximum and Aggravated Maximum... remains at $250. These adjustments are required by the Federal Civil Penalties Inflation Adjustment Act [email protected] . SUPPLEMENTARY INFORMATION: The Federal Civil Penalties Inflation Adjustment Act of 1990...

  10. Zipf's law, power laws and maximum entropy

    International Nuclear Information System (INIS)

    Visser, Matt

    2013-01-01

    Zipf's law, and power laws in general, have attracted and continue to attract considerable attention in a wide variety of disciplines—from astronomy to demographics to software structure to economics to linguistics to zoology, and even warfare. A recent model of random group formation (RGF) attempts a general explanation of such phenomena based on Jaynes' notion of maximum entropy applied to a particular choice of cost function. In the present paper I argue that the specific cost function used in the RGF model is in fact unnecessarily complicated, and that power laws can be obtained in a much simpler way by applying maximum entropy ideas directly to the Shannon entropy subject only to a single constraint: that the average of the logarithm of the observable quantity is specified. (paper)

  11. Maximum-entropy description of animal movement.

    Science.gov (United States)

    Fleming, Chris H; Subaşı, Yiğit; Calabrese, Justin M

    2015-03-01

    We introduce a class of maximum-entropy states that naturally includes within it all of the major continuous-time stochastic processes that have been applied to animal movement, including Brownian motion, Ornstein-Uhlenbeck motion, integrated Ornstein-Uhlenbeck motion, a recently discovered hybrid of the previous models, and a new model that describes central-place foraging. We are also able to predict a further hierarchy of new models that will emerge as data quality improves to better resolve the underlying continuity of animal movement. Finally, we also show that Langevin equations must obey a fluctuation-dissipation theorem to generate processes that fall from this class of maximum-entropy distributions when the constraints are purely kinematic.

  12. Pareto versus lognormal: a maximum entropy test.

    Science.gov (United States)

    Bee, Marco; Riccaboni, Massimo; Schiavo, Stefano

    2011-08-01

    It is commonly found that distributions that seem to be lognormal over a broad range change to a power-law (Pareto) distribution for the last few percentiles. The distributions of many physical, natural, and social events (earthquake size, species abundance, income and wealth, as well as file, city, and firm sizes) display this structure. We present a test for the occurrence of power-law tails in statistical distributions based on maximum entropy. This methodology allows one to identify the true data-generating processes even in the case when it is neither lognormal nor Pareto. The maximum entropy approach is then compared with other widely used methods and applied to different levels of aggregation of complex systems. Our results provide support for the theory that distributions with lognormal body and Pareto tail can be generated as mixtures of lognormally distributed units.

  13. Maximum likelihood estimation for integrated diffusion processes

    DEFF Research Database (Denmark)

    Baltazar-Larios, Fernando; Sørensen, Michael

    We propose a method for obtaining maximum likelihood estimates of parameters in diffusion models when the data is a discrete time sample of the integral of the process, while no direct observations of the process itself are available. The data are, moreover, assumed to be contaminated...... EM-algorithm to obtain maximum likelihood estimates of the parameters in the diffusion model. As part of the algorithm, we use a recent simple method for approximate simulation of diffusion bridges. In simulation studies for the Ornstein-Uhlenbeck process and the CIR process the proposed method works...... by measurement errors. Integrated volatility is an example of this type of observations. Another example is ice-core data on oxygen isotopes used to investigate paleo-temperatures. The data can be viewed as incomplete observations of a model with a tractable likelihood function. Therefore we propose a simulated...

  14. A Maximum Radius for Habitable Planets.

    Science.gov (United States)

    Alibert, Yann

    2015-09-01

    We compute the maximum radius a planet can have in order to fulfill two constraints that are likely necessary conditions for habitability: 1- surface temperature and pressure compatible with the existence of liquid water, and 2- no ice layer at the bottom of a putative global ocean, that would prevent the operation of the geologic carbon cycle to operate. We demonstrate that, above a given radius, these two constraints cannot be met: in the Super-Earth mass range (1-12 Mearth), the overall maximum that a planet can have varies between 1.8 and 2.3 Rearth. This radius is reduced when considering planets with higher Fe/Si ratios, and taking into account irradiation effects on the structure of the gas envelope.

  15. Maximum parsimony on subsets of taxa.

    Science.gov (United States)

    Fischer, Mareike; Thatte, Bhalchandra D

    2009-09-21

    In this paper we investigate mathematical questions concerning the reliability (reconstruction accuracy) of Fitch's maximum parsimony algorithm for reconstructing the ancestral state given a phylogenetic tree and a character. In particular, we consider the question whether the maximum parsimony method applied to a subset of taxa can reconstruct the ancestral state of the root more accurately than when applied to all taxa, and we give an example showing that this indeed is possible. A surprising feature of our example is that ignoring a taxon closer to the root improves the reliability of the method. On the other hand, in the case of the two-state symmetric substitution model, we answer affirmatively a conjecture of Li, Steel and Zhang which states that under a molecular clock the probability that the state at a single taxon is a correct guess of the ancestral state is a lower bound on the reconstruction accuracy of Fitch's method applied to all taxa.

  16. Maximum entropy analysis of liquid diffraction data

    International Nuclear Information System (INIS)

    Root, J.H.; Egelstaff, P.A.; Nickel, B.G.

    1986-01-01

    A maximum entropy method for reducing truncation effects in the inverse Fourier transform of structure factor, S(q), to pair correlation function, g(r), is described. The advantages and limitations of the method are explored with the PY hard sphere structure factor as model input data. An example using real data on liquid chlorine, is then presented. It is seen that spurious structure is greatly reduced in comparison to traditional Fourier transform methods. (author)

  17. A Maximum Resonant Set of Polyomino Graphs

    Directory of Open Access Journals (Sweden)

    Zhang Heping

    2016-05-01

    Full Text Available A polyomino graph P is a connected finite subgraph of the infinite plane grid such that each finite face is surrounded by a regular square of side length one and each edge belongs to at least one square. A dimer covering of P corresponds to a perfect matching. Different dimer coverings can interact via an alternating cycle (or square with respect to them. A set of disjoint squares of P is a resonant set if P has a perfect matching M so that each one of those squares is M-alternating. In this paper, we show that if K is a maximum resonant set of P, then P − K has a unique perfect matching. We further prove that the maximum forcing number of a polyomino graph is equal to the cardinality of a maximum resonant set. This confirms a conjecture of Xu et al. [26]. We also show that if K is a maximal alternating set of P, then P − K has a unique perfect matching.

  18. Automatic maximum entropy spectral reconstruction in NMR

    International Nuclear Information System (INIS)

    Mobli, Mehdi; Maciejewski, Mark W.; Gryk, Michael R.; Hoch, Jeffrey C.

    2007-01-01

    Developments in superconducting magnets, cryogenic probes, isotope labeling strategies, and sophisticated pulse sequences together have enabled the application, in principle, of high-resolution NMR spectroscopy to biomolecular systems approaching 1 megadalton. In practice, however, conventional approaches to NMR that utilize the fast Fourier transform, which require data collected at uniform time intervals, result in prohibitively lengthy data collection times in order to achieve the full resolution afforded by high field magnets. A variety of approaches that involve nonuniform sampling have been proposed, each utilizing a non-Fourier method of spectrum analysis. A very general non-Fourier method that is capable of utilizing data collected using any of the proposed nonuniform sampling strategies is maximum entropy reconstruction. A limiting factor in the adoption of maximum entropy reconstruction in NMR has been the need to specify non-intuitive parameters. Here we describe a fully automated system for maximum entropy reconstruction that requires no user-specified parameters. A web-accessible script generator provides the user interface to the system

  19. maximum neutron flux at thermal nuclear reactors

    International Nuclear Information System (INIS)

    Strugar, P.

    1968-10-01

    Since actual research reactors are technically complicated and expensive facilities it is important to achieve savings by appropriate reactor lattice configurations. There is a number of papers, and practical examples of reactors with central reflector, dealing with spatial distribution of fuel elements which would result in higher neutron flux. Common disadvantage of all the solutions is that the choice of best solution is done starting from the anticipated spatial distributions of fuel elements. The weakness of these approaches is lack of defined optimization criteria. Direct approach is defined as follows: determine the spatial distribution of fuel concentration starting from the condition of maximum neutron flux by fulfilling the thermal constraints. Thus the problem of determining the maximum neutron flux is solving a variational problem which is beyond the possibilities of classical variational calculation. This variational problem has been successfully solved by applying the maximum principle of Pontrjagin. Optimum distribution of fuel concentration was obtained in explicit analytical form. Thus, spatial distribution of the neutron flux and critical dimensions of quite complex reactor system are calculated in a relatively simple way. In addition to the fact that the results are innovative this approach is interesting because of the optimization procedure itself [sr

  20. An Iterative Maximum a Posteriori Estimation of Proficiency Level to Detect Multiple Local Likelihood Maxima

    Science.gov (United States)

    Magis, David; Raiche, Gilles

    2010-01-01

    In this article the authors focus on the issue of the nonuniqueness of the maximum likelihood (ML) estimator of proficiency level in item response theory (with special attention to logistic models). The usual maximum a posteriori (MAP) method offers a good alternative within that framework; however, this article highlights some drawbacks of its…

  1. Palmitate diet-induced loss of cardiac caveolin-3: a novel mechanism for lipid-induced contractile dysfunction.

    Directory of Open Access Journals (Sweden)

    Catherine J Knowles

    Full Text Available Obesity is associated with an increased risk of cardiomyopathy, and mechanisms linking the underlying risk and dietary factors are not well understood. We tested the hypothesis that dietary intake of saturated fat increases the levels of sphingolipids, namely ceramide and sphingomyelin in cardiac cell membranes that disrupt caveolae, specialized membrane micro-domains and important for cellular signaling. C57BL/6 mice were fed two high-fat diets: palmitate diet (21% total fat, 47% is palmitate, and MCT diet (21% medium-chain triglycerides, no palmitate. We established that high-palmitate feeding for 12 weeks leads to 40% and 50% increases in ceramide and sphingomyelin, respectively, in cellular membranes. Concomitant with sphingolipid accumulation, we observed a 40% reduction in systolic contractile performance. To explore the relationship of increased sphingolipids with caveolins, we analyzed caveolin protein levels and intracellular localization in isolated cardiomyocytes. In normal cardiomyocytes, caveolin-1 and caveolin-3 co-localize at the plasma membrane and the T-tubule system. However, mice maintained on palmitate lost 80% of caveolin-3, mainly from the T-tubule system. Mice maintained on MCT diet had a 90% reduction in caveolin-1. These data show that caveolin isoforms are sensitive to the lipid environment. These data are further supported by similar findings in human cardiac tissue samples from non-obese, obese, non-obese cardiomyopathic, and obese cardiomyopathic patients. To further elucidate the contractile dysfunction associated with the loss of caveolin-3, we determined the localization of the ryanodine receptor and found lower expression and loss of the striated appearance of this protein. We suggest that palmitate-induced loss of caveolin-3 results in cardiac contractile dysfunction via a defect in calcium-induced calcium release.

  2. Assessment of drug-induced arrhythmic risk using limit cycle and autocorrelation analysis of human iPSC-cardiomyocyte contractility

    Energy Technology Data Exchange (ETDEWEB)

    Kirby, R. Jason [Sanford Burnham Prebys Medical Discovery Institute, Conrad Prebys Center for Chemical Genomics, 6400 Sanger Rd, Orlando, FL 32827 (United States); Qi, Feng [Sanford Burnham Prebys Medical Discovery Institute, Applied Bioinformatics Facility, 6400 Sanger Rd, Orlando, FL 32827 (United States); Phatak, Sharangdhar; Smith, Layton H. [Sanford Burnham Prebys Medical Discovery Institute, Conrad Prebys Center for Chemical Genomics, 6400 Sanger Rd, Orlando, FL 32827 (United States); Malany, Siobhan, E-mail: smalany@sbpdiscovery.org [Sanford Burnham Prebys Medical Discovery Institute, Conrad Prebys Center for Chemical Genomics, 6400 Sanger Rd, Orlando, FL 32827 (United States)

    2016-08-15

    Cardiac safety assays incorporating label-free detection of human stem-cell derived cardiomyocyte contractility provide human relevance and medium throughput screening to assess compound-induced cardiotoxicity. In an effort to provide quantitative analysis of the large kinetic datasets resulting from these real-time studies, we applied bioinformatic approaches based on nonlinear dynamical system analysis, including limit cycle analysis and autocorrelation function, to systematically assess beat irregularity. The algorithms were integrated into a software program to seamlessly generate results for 96-well impedance-based data. Our approach was validated by analyzing dose- and time-dependent changes in beat patterns induced by known proarrhythmic compounds and screening a cardiotoxicity library to rank order compounds based on their proarrhythmic potential. We demonstrate a strong correlation for dose-dependent beat irregularity monitored by electrical impedance and quantified by autocorrelation analysis to traditional manual patch clamp potency values for hERG blockers. In addition, our platform identifies non-hERG blockers known to cause clinical arrhythmia. Our method provides a novel suite of medium-throughput quantitative tools for assessing compound effects on cardiac contractility and predicting compounds with potential proarrhythmia and may be applied to in vitro paradigms for pre-clinical cardiac safety evaluation. - Highlights: • Impedance-based monitoring of human iPSC-derived cardiomyocyte contractility • Limit cycle analysis of impedance data identifies aberrant oscillation patterns. • Nonlinear autocorrelation function quantifies beat irregularity. • Identification of hERG and non-hERG inhibitors with known risk of arrhythmia • Automated software processes limit cycle and autocorrelation analyses of 96w data.

  3. 2-Deoxyadenosine triphosphate restores the contractile function of cardiac myofibril from adult dogs with naturally occurring dilated cardiomyopathy.

    Science.gov (United States)

    Cheng, Yuanhua; Hogarth, Kaley A; O'Sullivan, M Lynne; Regnier, Michael; Pyle, W Glen

    2016-01-01

    Dilated cardiomyopathy (DCM) is a major type of heart failure resulting from loss of systolic function. Naturally occurring canine DCM is a widely accepted experimental paradigm for studying human DCM. 2-Deoxyadenosine triphosphate (dATP) can be used by myosin and is a superior energy substrate over ATP for cross-bridge formation and increased systolic function. The objective of this study was to evaluate the beneficial effect of dATP on contractile function of cardiac myofibrils from dogs with naturally occurring DCM. We measured actomyosin NTPase activity and contraction/relaxation properties of isolated myofibrils from nonfailing (NF) and DCM canine hearts. NTPase assays indicated replacement of ATP with dATP significantly increased myofilament activity in both NF and DCM samples. dATP significantly improved maximal tension of DCM myofibrils to the NF sample level. dATP also restored Ca(2+) sensitivity of tension that was reduced in DCM samples. Similarly, dATP increased the kinetics of contractile activation (kACT), with no impact on the rate of cross-bridge tension redevelopment (kTR). Thus, the activation kinetics (kACT/kTR) that were reduced in DCM samples were restored for dATP to NF sample levels. dATP had little effect on relaxation. The rate of early slow-phase relaxation was slightly reduced with dATP, but its duration was not, nor was the fast-phase relaxation or times to 50 and 90% relaxation. Our findings suggest that myosin utilization of dATP improves cardiac myofibril contractile properties of naturally occurring DCM canine samples, restoring them to NF levels, without compromising relaxation. This suggests elevation of cardiac dATP is a promising approach for the treatment of DCM. Copyright © 2016 the American Physiological Society.

  4. Assessment of drug-induced arrhythmic risk using limit cycle and autocorrelation analysis of human iPSC-cardiomyocyte contractility

    International Nuclear Information System (INIS)

    Kirby, R. Jason; Qi, Feng; Phatak, Sharangdhar; Smith, Layton H.; Malany, Siobhan

    2016-01-01

    Cardiac safety assays incorporating label-free detection of human stem-cell derived cardiomyocyte contractility provide human relevance and medium throughput screening to assess compound-induced cardiotoxicity. In an effort to provide quantitative analysis of the large kinetic datasets resulting from these real-time studies, we applied bioinformatic approaches based on nonlinear dynamical system analysis, including limit cycle analysis and autocorrelation function, to systematically assess beat irregularity. The algorithms were integrated into a software program to seamlessly generate results for 96-well impedance-based data. Our approach was validated by analyzing dose- and time-dependent changes in beat patterns induced by known proarrhythmic compounds and screening a cardiotoxicity library to rank order compounds based on their proarrhythmic potential. We demonstrate a strong correlation for dose-dependent beat irregularity monitored by electrical impedance and quantified by autocorrelation analysis to traditional manual patch clamp potency values for hERG blockers. In addition, our platform identifies non-hERG blockers known to cause clinical arrhythmia. Our method provides a novel suite of medium-throughput quantitative tools for assessing compound effects on cardiac contractility and predicting compounds with potential proarrhythmia and may be applied to in vitro paradigms for pre-clinical cardiac safety evaluation. - Highlights: • Impedance-based monitoring of human iPSC-derived cardiomyocyte contractility • Limit cycle analysis of impedance data identifies aberrant oscillation patterns. • Nonlinear autocorrelation function quantifies beat irregularity. • Identification of hERG and non-hERG inhibitors with known risk of arrhythmia • Automated software processes limit cycle and autocorrelation analyses of 96w data

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

    Science.gov (United States)

    Gittings, William; Bunda, Jordan; Vandenboom, Rene

    2018-01-30

    Skeletal myosin light chain kinase (skMLCK)-catalyzed phosphorylation of the myosin regulatory light chain (RLC) increases (i.e. potentiates) mechanical work output of fast skeletal muscle. The influence of this event on contractile economy (i.e. energy cost/work performed) remains controversial, however. Our purpose was to quantify contractile economy of potentiated extensor digitorum longus (EDL) muscles from mouse skeletal muscles with (wild-type, WT) and without (skMLCK ablated, skMLCK -/- ) the ability to phosphorylate the RLC. Contractile economy was calculated as the ratio of total work performed to high-energy phosphate consumption (HEPC) during a period of repeated isovelocity contractions that followed a potentiating stimulus (PS). Consistent with genotype, the PS increased RLC phosphorylation measured during, before and after isovelocity contractions in WT but not in skMLCK -/- muscles (i.e. 0.65 and 0.05 mol phosphate mol -1 RLC, respectively). In addition, although the PS enhanced work during repeated isovelocity contractions in both genotypes, the increase was significantly greater in WT than in skMLCK -/- muscles (1.51±0.03 versus 1.10±0.05, respectively; all data P economy calculated for WT muscles was similar to that calculated for skMLCK -/- muscles (i.e. 5.74±0.67 and 4.61±0.71 J kg -1  μmol -1 P, respectively ( P economy. © 2018. Published by The Company of Biologists Ltd.

  6. Acute effects of sulfur dioxide on the circulation of animals as well as on the contractility of isolated blood vessels

    Energy Technology Data Exchange (ETDEWEB)

    Laszt, L; Schaad, R

    1974-01-01

    In support of earlier work on exhaust gases experiments were carried out to determine the acute effects of sulphur dioxide on the circulation of the cat and dog. Inhalation of SO/sub 2/ during 30 min at concentrations of up to 1000 ppm caused no circulatory reaction. Such a reaction first appeared after infusion of larger quantities of SO/sub 2/. The action of sulphur dioxide on systemic and pulmonar circulation is different. A difference was also observed for the contractility of the corresponding isolated vessels.

  7. Interleukin-6 downregulated vascular smooth muscle cell contractile proteins via ATG4B-mediated autophagy in thoracic aortic dissection.

    Science.gov (United States)

    An, Zhao; Qiao, Fan; Lu, Qijue; Ma, Ye; Liu, Yang; Lu, Fanglin; Xu, Zhiyun

    2017-12-01

    Interleukin-6 (IL-6) overexpression played an important role in the pathogenesis of thoracic aortic dissection (TAD). Our previous study found enhanced autophagy accompanying with contractile proteins α smooth muscle actin (α-SMA) and smooth muscle 22α (SM22α) degradation in TAD aortic vascular smooth muscle cells (VSMCs). Autophagy is an important way for intracellular proteins degradation, while IL-6 has been found as a contributing factor of autophagy in some cancers. These indicated IL-6 might contribute to the occurrence of TAD by promoting autophagy-induced contractile proteins degradation, which has not been investigated. The aim of the present study is to verify this hypothesis and investigate the mechanism of it. We collected 10 TAD and 10 control aortic specimens from patients underwent TAD surgical repair and coronary artery bypass grafting, respectively. Quantitative real-time polymerase chain reaction was used to detect mRNA expression. Protein expression level was assessed