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.

Spontaneous Plasticity of Multineuronal Activity Patterns in Activated Hippocampal Networks

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Atsushi Usami

2008-01-01

Full Text Available Using functional multineuron imaging with single-cell resolution, we examined how hippocampal networks by themselves change the spatiotemporal patterns of spontaneous activity during the course of emitting spontaneous activity. When extracellular ionic concentrations were changed to those that mimicked in vivo conditions, spontaneous activity was increased in active cell number and activity frequency. When ionic compositions were restored to the control conditions, the activity level returned to baseline, but the weighted spatial dispersion of active cells, as assessed by entropy-based metrics, did not. Thus, the networks can modify themselves by altering the internal structure of their correlated activity, even though they as a whole maintained the same level of activity in space and time.

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

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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.

Active hippocampal networks undergo spontaneous synaptic modification.

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Masako Tsukamoto-Yasui

Full Text Available The brain is self-writable; as the brain voluntarily adapts itself to a changing environment, the neural circuitry rearranges its functional connectivity by referring to its own activity. How the internal activity modifies synaptic weights is largely unknown, however. Here we report that spontaneous activity causes complex reorganization of synaptic connectivity without any external (or artificial stimuli. Under physiologically relevant ionic conditions, CA3 pyramidal cells in hippocampal slices displayed spontaneous spikes with bistable slow oscillations of membrane potential, alternating between the so-called UP and DOWN states. The generation of slow oscillations did not require fast synaptic transmission, but their patterns were coordinated by local circuit activity. In the course of generating spontaneous activity, individual neurons acquired bidirectional long-lasting synaptic modification. The spontaneous synaptic plasticity depended on a rise in intracellular calcium concentrations of postsynaptic cells, but not on NMDA receptor activity. The direction and amount of the plasticity varied depending on slow oscillation patterns and synapse locations, and thus, they were diverse in a network. Once this global synaptic refinement occurred, the same neurons now displayed different patterns of spontaneous activity, which in turn exhibited different levels of synaptic plasticity. Thus, active networks continuously update their internal states through ongoing synaptic plasticity. With computational simulations, we suggest that with this slow oscillation-induced plasticity, a recurrent network converges on a more specific state, compared to that with spike timing-dependent plasticity alone.

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

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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

Spatial diversity of spontaneous activity in the cortex

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Andrew Yong-Yi Tan

2015-09-01

Full Text Available The neocortex is a layered sheet across which a basic organization is thought to widely apply. The variety of spontaneous activity patterns is similar throughout the cortex, consistent with the notion of a basic cortical organization. However, the basic organization is only an outline which needs adjustments and additions to account for the structural and functional diversity across cortical layers and areas. Such diversity suggests that spontaneous activity is spatially diverse in any particular behavioral state. Accordingly, this review summarizes the laminar and areal diversity in cortical activity during fixation and slow oscillations, and the effects of attention, anesthesia and plasticity on the cortical distribution of spontaneous activity. Among questions that remain open, characterizing the spatial diversity in spontaneous membrane potential may help elucidate how differences in circuitry among cortical regions supports their varied functions. More work is also needed to understand whether cortical spontaneous activity not only reflects cortical circuitry, but also contributes to determining the outcome of plasticity, so that it is itself a factor shaping the functional diversity of the cortex.

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

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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.

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

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...

Associative memory model with spontaneous neural activity

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Kurikawa, Tomoki; Kaneko, Kunihiko

2012-05-01

We propose a novel associative memory model wherein the neural activity without an input (i.e., spontaneous activity) is modified by an input to generate a target response that is memorized for recall upon the same input. Suitable design of synaptic connections enables the model to memorize input/output (I/O) mappings equaling 70% of the total number of neurons, where the evoked activity distinguishes a target pattern from others. Spontaneous neural activity without an input shows chaotic dynamics but keeps some similarity with evoked activities, as reported in recent experimental studies.

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

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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.

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)

New Perspectives on Spontaneous Brain Activity: Dynamic Networks and Energy Matter.

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Tozzi, Arturo; Zare, Marzieh; Benasich, April A

2016-01-01

Spontaneous brain activity has received increasing attention as demonstrated by the exponential rise in the number of published article on this topic over the last 30 years. Such "intrinsic" brain activity, generated in the absence of an explicit task, is frequently associated with resting-state or default-mode networks (DMN)s. The focus on characterizing spontaneous brain activity promises to shed new light on questions concerning the structural and functional architecture of the brain and how they are related to "mind". However, many critical questions have yet to be addressed. In this review, we focus on a scarcely explored area, specifically the energetic requirements and constraints of spontaneous activity, taking into account both thermodynamical and informational perspectives. We argue that the "classical" definitions of spontaneous activity do not take into account an important feature, that is, the critical thermodynamic energetic differences between spontaneous and evoked brain activity. Spontaneous brain activity is associated with slower oscillations compared with evoked, task-related activity, hence it exhibits lower levels of enthalpy and "free-energy" (i.e., the energy that can be converted to do work), thus supporting noteworthy thermodynamic energetic differences between spontaneous and evoked brain activity. Increased spike frequency during evoked activity has a significant metabolic cost, consequently, brain functions traditionally associated with spontaneous activity, such as mind wandering, require less energy that other nervous activities. We also review recent empirical observations in neuroscience, in order to capture how spontaneous brain dynamics and mental function can be embedded in a non-linear dynamical framework, which considers nervous activity in terms of phase spaces, particle trajectories, random walks, attractors and/or paths at the edge of the chaos. This takes us from the thermodynamic free-energy, to the realm of "variational

Behavioral Modulation by Spontaneous Activity of Dopamine Neurons

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Toshiharu Ichinose

2017-12-01

Full Text Available Dopamine modulates a variety of animal behaviors that range from sleep and learning to courtship and aggression. Besides its well-known phasic firing to natural reward, a substantial number of dopamine neurons (DANs are known to exhibit ongoing intrinsic activity in the absence of an external stimulus. While accumulating evidence points at functional implications for these intrinsic “spontaneous activities” of DANs in cognitive processes, a causal link to behavior and its underlying mechanisms has yet to be elucidated. Recent physiological studies in the model organism Drosophila melanogaster have uncovered that DANs in the fly brain are also spontaneously active, and that this activity reflects the behavioral/internal states of the animal. Strikingly, genetic manipulation of basal DAN activity resulted in behavioral alterations in the fly, providing critical evidence that links spontaneous DAN activity to behavioral states. Furthermore, circuit-level analyses have started to reveal cellular and molecular mechanisms that mediate or regulate spontaneous DAN activity. Through reviewing recent findings in different animals with the major focus on flies, we will discuss potential roles of this physiological phenomenon in directing animal behaviors.

Vision drives correlated activity without patterned spontaneous activity in developing Xenopus retina.

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Demas, James A; Payne, Hannah; Cline, Hollis T

2012-04-01

Developing amphibians need vision to avoid predators and locate food before visual system circuits fully mature. Xenopus tadpoles can respond to visual stimuli as soon as retinal ganglion cells (RGCs) innervate the brain, however, in mammals, chicks and turtles, RGCs reach their central targets many days, or even weeks, before their retinas are capable of vision. In the absence of vision, activity-dependent refinement in these amniote species is mediated by waves of spontaneous activity that periodically spread across the retina, correlating the firing of action potentials in neighboring RGCs. Theory suggests that retinorecipient neurons in the brain use patterned RGC activity to sharpen the retinotopy first established by genetic cues. We find that in both wild type and albino Xenopus tadpoles, RGCs are spontaneously active at all stages of tadpole development studied, but their population activity never coalesces into waves. Even at the earliest stages recorded, visual stimulation dominates over spontaneous activity and can generate patterns of RGC activity similar to the locally correlated spontaneous activity observed in amniotes. In addition, we show that blocking AMPA and NMDA type glutamate receptors significantly decreases spontaneous activity in young Xenopus retina, but that blocking GABA(A) receptor blockers does not. Our findings indicate that vision drives correlated activity required for topographic map formation. They further suggest that developing retinal circuits in the two major subdivisions of tetrapods, amphibians and amniotes, evolved different strategies to supply appropriately patterned RGC activity to drive visual circuit refinement. Copyright © 2011 Wiley Periodicals, Inc.

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)

Opioid mediated activity and expression of mu and delta opioid receptors in isolated human term non-labouring myometrium.

LENUS (Irish Health Repository)

Fanning, Rebecca A

2013-01-05

The existence of opioid receptors in mammalian myometrial tissue is now widely accepted. Previously enkephalin degrading enzymes have been shown to be elevated in pregnant rat uterus and a met-enkephalin analogue has been shown to alter spontaneous contractility of rat myometrium. Here we have undertaken studies to determine the effects of met-enkephalin on in vitro human myometrial contractility and investigate the expression of opioid receptors in pregnant myometrium. Myometrial biopsies were taken from women undergoing elective caesarean delivery at term. Organ bath experiments were used to investigate the effect of the met-enkephalin analogue [d-Ala 2, d-met 5] enkephalin (DAMEA) on spontaneous contractility. A confocal immunofluorescent technique and real time PCR were used to determine the expression of protein and mRNA, respectively for two opioid receptor subtypes, mu and delta. DAMEA had a concentration dependent inhibitory effect on contractile activity (1 × 10(-7)M-1 × 10(-4)M; 54% reduction in contractile activity, P<0.001 at 1 × 10(-4)M concentration). Mu and delta opioid receptor protein sub-types and their respective mRNA were identified in all tissues sampled. This is the first report of opioid receptor expression and of an opioid mediated uterorelaxant action in term human non-labouring myometrium in vitro.

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

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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

Learning shapes spontaneous activity itinerating over memorized states.

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Tomoki Kurikawa

Full Text Available Learning is a process that helps create neural dynamical systems so that an appropriate output pattern is generated for a given input. Often, such a memory is considered to be included in one of the attractors in neural dynamical systems, depending on the initial neural state specified by an input. Neither neural activities observed in the absence of inputs nor changes caused in the neural activity when an input is provided were studied extensively in the past. However, recent experimental studies have reported existence of structured spontaneous neural activity and its changes when an input is provided. With this background, we propose that memory recall occurs when the spontaneous neural activity changes to an appropriate output activity upon the application of an input, and this phenomenon is known as bifurcation in the dynamical systems theory. We introduce a reinforcement-learning-based layered neural network model with two synaptic time scales; in this network, I/O relations are successively memorized when the difference between the time scales is appropriate. After the learning process is complete, the neural dynamics are shaped so that it changes appropriately with each input. As the number of memorized patterns is increased, the generated spontaneous neural activity after learning shows itineration over the previously learned output patterns. This theoretical finding also shows remarkable agreement with recent experimental reports, where spontaneous neural activity in the visual cortex without stimuli itinerate over evoked patterns by previously applied signals. Our results suggest that itinerant spontaneous activity can be a natural outcome of successive learning of several patterns, and it facilitates bifurcation of the network when an input is provided.

Cardiac tolerance to ischemia in neonatal spontaneously hypertensive rats

Czech Academy of Sciences Publication Activity Database

Charvátová, Z.; Ošťádalová, Ivana; Zicha, Josef; Kuneš, Jaroslav; Maxová, H.; Ošťádal, Bohuslav

2012-01-01

Roč. 61, Suppl.1 (2012), S145-S153 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : neonatal spontaneously hypertensive rats * contractile function * ischemic preconditioning * chronic hypoxia Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.531, year: 2012

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.

Tension cost correlates with mechanical and biochemical parameters in different myocardial contractility conditions

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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

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".

Why eicosanoids could represent a new class of tocolytics on uterine activity in pregnant women.

Science.gov (United States)

Corriveau, Stéphanie; Berthiaume, Maryse; Rousseau, Eric; Pasquier, Jean-Charles

2009-10-01

The purpose of this study was to assess the effects of exogenous eicosanoids on spontaneous uterine contractile activity. Eight uterine biopsies were performed from women who were undergoing elective cesarean delivery. Tension measurements were performed in vitro on myometrial strips. Contractile activities were quantified by the calculation of the area under the curve. The effects of eicosanoids and specific enzyme inhibitors were assessed. Fractions from various uterine tissues were analyzed by Western blot. Data demonstrate the presence, in some tested tissues, of cytochrome P-450 epoxygenase and soluble epoxide hydrolase, which respectively produce and degrade epoxyeicosatrienoic acid regioisomers. Inhibition of soluble epoxide hydrolase with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid or omega-hydroxylase with N-methylsulfonyl-12,12-dibromododec-11-enamide resulted in a tocolytic effect; N-methylsulfonyl-6-[2-propargyloxyphenyl] hexanamide, which is an epoxygenase inhibitor, had no effect. Exogenous epoxyeicosatrienoic acids displayed significant tocolytic effects on spontaneous contractile activities. Epoxy- and hydroxyeicosanoids represent new bioactive, arachidonic acid by-products with in vitro tocolytic activities. These findings suggest that cytochrome P-450 isozymes may represent relevant pharmacologic targets under physiopathologic conditions.

Synaptic model for spontaneous activity in developing networks

DEFF Research Database (Denmark)

Lerchner, Alexander; Rinzel, J.

2005-01-01

Spontaneous rhythmic activity occurs in many developing neural networks. The activity in these hyperexcitable networks is comprised of recurring "episodes" consisting of "cycles" of high activity that alternate with "silent phases" with little or no activity. We introduce a new model of synaptic...... dynamics that takes into account that only a fraction of the vesicles stored in a synaptic terminal is readily available for release. We show that our model can reproduce spontaneous rhythmic activity with the same general features as observed in experiments, including a positive correlation between...

The influence of spontaneous activity on stimulus processing in primary visual cortex.

Science.gov (United States)

Schölvinck, M L; Friston, K J; Rees, G

2012-02-01

Spontaneous activity in the resting human brain has been studied extensively; however, how such activity affects the local processing of a sensory stimulus is relatively unknown. Here, we examined the impact of spontaneous activity in primary visual cortex on neuronal and behavioural responses to a simple visual stimulus, using functional MRI. Stimulus-evoked responses remained essentially unchanged by spontaneous fluctuations, combining with them in a largely linear fashion (i.e., with little evidence for an interaction). However, interactions between spontaneous fluctuations and stimulus-evoked responses were evident behaviourally; high levels of spontaneous activity tended to be associated with increased stimulus detection at perceptual threshold. Our results extend those found in studies of spontaneous fluctuations in motor cortex and higher order visual areas, and suggest a fundamental role for spontaneous activity in stimulus processing. Copyright © 2011. Published by Elsevier Inc.

Spontaneous neutrophil activation in HTLV-1 infected patients

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Jaqueline B. Guerreiro

Full Text Available Human T cell lymphotropic Virus type-1 (HTLV-1 induces lymphocyte activation and proliferation, but little is known about the innate immune response due to HTLV-1 infection. We evaluated the percentage of neutrophils that metabolize Nitroblue tetrazolium (NBT to formazan in HTLV-1 infected subjects and the association between neutrophil activation and IFN-gamma and TNF-alpha levels. Blood was collected from 35 HTLV-1 carriers, from 8 patients with HAM/TSP (HTLV-1- associated myelopathy; 22 healthy individuals were evaluated for spontaneous and lipopolysaccharide (LPS-stimulated neutrophil activity (reduction of NBT to formazan. The production of IFN-gamma and TNF-alpha by unstimulated mononuclear cells was determined by ELISA. Spontaneous NBT levels, as well as spontaneous IFN-gamma and TNF-alpha production, were significantly higher (p<0.001 in HTLV-1 infected subjects than in healthy individuals. A trend towards a positive correlation was noted, with increasing percentage of NBT positive neutrophils and levels of IFN-gamma. The high IFN-gamma producing HTLV-1 patient group had significantly greater NBT than healthy controls, 43±24% and 17±4.8% respectively (p< 0.001, while no significant difference was observed between healthy controls and the low IFN-gamma-producing HTLV-1 patient group (30±20%. Spontaneous neutrophil activation is another marker of immune perturbation resulting from HTLV-1 infection. In vivo activation of neutrophils observed in HTLV-1 infected subjects is likely to be the same process that causes spontaneous IFN-gamma production, or it may partially result from direct IFN-gamma stimulation.

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.

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.

Fractalkine depresses cardiomyocyte contractility.

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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.

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

Recently active contractile deformation in the forearc of southern Peru

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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.

Antioxidant Phytochemicals of Opuntia ficus-indica (L.) Mill. Cladodes with Potential Anti-spasmodic Activity.

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Lanuzza, Francesco; Occhiuto, Francesco; Monforte, Maria Teresa; Tripodo, Maria Marcella; D'Angelo, Valeria; Galati, Enza Maria

2017-10-01

Opuntia ficus-indica (OFI) (L.) Mill. (Cactaceae), a plant widespread in dry regions of the world, shows interesting biological activities (cicatrizant, antiulcer, anti-inflammatory, and hypolipidemic) and is widely used in traditional medicine. Phytochemical analysis and antispasmodic effect of wild OFI cladodes were carried out. Polyphenols and Vitamin E occurrence, in antioxidant pool of OFI cladodes, were quantified by high-performance liquid chromatography. The antispasmodic effect of OFI cladodes was assessed in isolated rabbit smooth muscle tissues. The experiments were carried out with preparations of rabbit jejunum and uterus with the spontaneous contractile activity, to evaluate the effect of cumulative concentrations of the extract on basal tone, amplitude, and frequency of contractions. Catechin, quercetin, kaempferol, isorhamnetin and chlorogenic, ferulic, and p-coumaric acid were identified. α-, β-, and γ-tocopherols have been highlighted and α-tocopherol is the major component. OFI cladodes contain significant amount of polyphenols and tocopherols that are effective radical scavengers and inhibited ethanol 1,1-diphenyl-2-picrylhydrazyl formation by 50%. OFI cladodes caused a light inhibition of amplitude and frequency of spontaneous contractions and a marked decrease in muscle basal tone of rabbit jejunum preparations. On spontaneously contracting uterus preparations, the addition of increasing concentrations of cladode extract caused uterine muscle relaxation. The contraction of smooth muscle preparations depends on an increase in cytoplasmic free calcium ion concentration, which activates the contractile elements. The flavonoids may suppress the contractility of smooth myocytes, by an inhibition of availability of Ca 2+ for muscle contraction. Opuntia ficus-indica (OFI) cladodes contain significant amount of polyphenols and tocopherols that are effective radical scavengers and inhibited ethanol 1,1-diphenyl-2-picrylhydrazyl formation by 50

Antioxidant Phytochemicals of Opuntia ficus-indica (L.) Mill. Cladodes with Potential Anti-spasmodic Activity

Science.gov (United States)

Lanuzza, Francesco; Occhiuto, Francesco; Monforte, Maria Teresa; Tripodo, Maria Marcella; D’Angelo, Valeria; Galati, Enza Maria

2017-01-01

Background: Opuntia ficus-indica (OFI) (L.) Mill. (Cactaceae), a plant widespread in dry regions of the world, shows interesting biological activities (cicatrizant, antiulcer, anti-inflammatory, and hypolipidemic) and is widely used in traditional medicine. Objectives: Phytochemical analysis and antispasmodic effect of wild OFI cladodes were carried out. Material and Methods: Polyphenols and Vitamin E occurrence, in antioxidant pool of OFI cladodes, were quantified by high-performance liquid chromatography. The antispasmodic effect of OFI cladodes was assessed in isolated rabbit smooth muscle tissues. The experiments were carried out with preparations of rabbit jejunum and uterus with the spontaneous contractile activity, to evaluate the effect of cumulative concentrations of the extract on basal tone, amplitude, and frequency of contractions. Results: Catechin, quercetin, kaempferol, isorhamnetin and chlorogenic, ferulic, and p-coumaric acid were identified. α-, β-, and γ-tocopherols have been highlighted and α-tocopherol is the major component. OFI cladodes contain significant amount of polyphenols and tocopherols that are effective radical scavengers and inhibited ethanol 1,1-diphenyl-2-picrylhydrazyl formation by 50%. OFI cladodes caused a light inhibition of amplitude and frequency of spontaneous contractions and a marked decrease in muscle basal tone of rabbit jejunum preparations. On spontaneously contracting uterus preparations, the addition of increasing concentrations of cladode extract caused uterine muscle relaxation. Conclusion: The contraction of smooth muscle preparations depends on an increase in cytoplasmic free calcium ion concentration, which activates the contractile elements. The flavonoids may suppress the contractility of smooth myocytes, by an inhibition of availability of Ca2+ for muscle contraction. SUMMARY Opuntia ficus-indica (OFI) cladodes contain significant amount of polyphenols and tocopherols that are effective radical

Structural comparison of contractile nanomachines

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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.

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.

Mechanisms of morphine enhancement of spontaneous seizure activity.

Science.gov (United States)

Saboory, Ehsan; Derchansky, Miron; Ismaili, Mohammed; Jahromi, Shokrollah S; Brull, Richard; Carlen, Peter L; El Beheiry, Hossam

2007-12-01

High-dose opioid therapy can precipitate seizures; however, the mechanism of such a dangerous adverse effect remains poorly understood. The aim of our study was to determine whether the neuroexcitatory activity of high-dose morphine is mediated by selective stimulation of opioid receptors. Mice hippocampi were resected intact and bathed in low magnesium artificial cerebrospinal fluid to induce spontaneous seizure-like events recorded from CA1 neurons. Application of morphine had a biphasic effect on the recorded spontaneous seizure-like events. In a low concentration (10 microM), morphine depressed electrographic seizure activity. Higher morphine concentrations (30 and 100 microM) enhanced seizure activity in an apparent dose-dependent manner. Naloxone, a nonselective opiate antagonist blocked the proconvulsant action of morphine. Selective mu and kappa opiate receptor agonists and antagonists enhanced and suppressed the spontaneous seizure activity, respectively. On the contrary, delta opioid receptor ligands did not have an effect. The proseizure effect of morphine is mediated through selective stimulation of mu and kappa opiate receptors but not the activation of the delta receptor system. The observed dose-dependent mechanism of morphine neuroexcitation underscores careful adjustment and individualized opioid dosing in the clinical setting.

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

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

Which nerve conduction parameters can predict spontaneous electromyographic activity in carpal tunnel syndrome?

Science.gov (United States)

Chang, Chia-Wei; Lee, Wei-Ju; Liao, Yi-Chu; Chang, Ming-Hong

2013-11-01

We investigate electrodiagnostic markers to determine which parameters are the best predictors of spontaneous electromyographic (EMG) activity in carpal tunnel syndrome (CTS). We enrolled 229 patients with clinically proven and nerve conduction study (NCS)-proven CTS, as well as 100 normal control subjects. All subjects were evaluated using electrodiagnostic techniques, including median distal sensory latencies (DSLs), sensory nerve action potentials (SNAPs), distal motor latencies (DMLs), compound muscle action potentials (CMAPs), forearm median nerve conduction velocities (FMCVs) and wrist-palm motor conduction velocities (W-P MCVs). All CTS patients underwent EMG examination of the abductor pollicis brevis (APB) muscle, and the presence or absence of spontaneous EMG activities was recorded. Normal limits were determined by calculating the means ± 2 standard deviations from the control data. Associations between parameters from the NCS and EMG findings were investigated. In patients with clinically diagnosed CTS, abnormal median CMAP amplitudes were the best predictors of spontaneous activity during EMG examination (p95% (positive predictive rate >95%). If the median CMAP amplitude was higher than the normal limit (>4.9 mV), the rate of no spontaneous EMG activity was >94% (negative predictive rate >94%). An abnormal SNAP amplitude was the second best predictor of spontaneous EMG activity (p<0.001; OR 4.13; 95% CI 2.16-7.90), and an abnormal FMCV was the third best predictor (p=0.01; OR 2.10; 95% CI 1.20-3.67). No other nerve conduction parameters had significant power to predict spontaneous activity upon EMG examination. The CMAP amplitudes of the APB are the most powerful predictors of the occurrence of spontaneous EMG activity. Low CMAP amplitudes are strongly associated with spontaneous activity, whereas high CMAP amplitude are less associated with spontaneous activity, implying that needle EMG examination should be recommended for the detection of

Spontaneous emission from active dielectric microstructures

DEFF Research Database (Denmark)

Søndergaard, Thomas; Tromborg, Bjarne

2001-01-01

and engineered due to the dependence of the emission rate on the location and polarisation of the emitters in the structure. This paper addresses the methods of quantum electrodynamics of dielectric media which enable calculation of the local rate of spontaneous emission in active microstructures....

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....

Fullerenol C{sub 60}(OH){sub 24} nanoparticles decrease relaxing effects of dimethyl sulfoxide on rat uterus spontaneous contraction

Energy Technology Data Exchange (ETDEWEB)

Slavic, Marija, E-mail: marija17@ibiss.bg.ac.rs [University of Belgrade, Department for Physiology, Institute for Biological Research ' Sinisa Stankovic' (IBISS) (Serbia); Djordjevic, Aleksandar [University of Novi Sad, Department of Chemistry, Biochemistry and the Environment, Faculty of Sciences (Serbia); Radojicic, Ratko [University of Belgrade, Faculty of Biology (Serbia); Milovanovic, Slobodan [University of East Sarajevo, Department of Pharmacology, Faculty of Medicine at Foca (Bosnia and Herzegowina); Orescanin-Dusic, Zorana [University of Belgrade, Department for Physiology, Institute for Biological Research ' Sinisa Stankovic' (IBISS) (Serbia); Rakocevic, Zlatko [University of Belgrade, Institute for Nuclear Sciences ' Vinca' (Serbia); Spasic, Mihajlo B.; Blagojevic, Dusko [University of Belgrade, Department for Physiology, Institute for Biological Research ' Sinisa Stankovic' (IBISS) (Serbia)

2013-05-15

Dimethyl sulfoxide (DMSO) is a widely used solvent and cryoprotectant that can cause impaired blood flow, reduction in intracranial pressure, tissue edema, inflammatory reactions, inhibition of vascular smooth muscle cell migration and proliferation, processes which can lead to atherosclerosis of the coronary, peripheral and cerebral circulation. Although the adverse effects are rare when DMSO is administered in clinically established concentrations, there is no safe antagonist for an overdose. In this work, we treated isolated spontaneous and calcium-induced contractile active rat uteri (Wistar, virgo intacta), with DMSO and fullerenol C{sub 60}(OH){sub 24} nanoparticle (FNP) in DMSO. FNP is a water-soluble derivative of fullerene C{sub 60}. Its size is a 1.1 nm in diameter and is a very promising candidate for a drug carrier in nanomedicine. FNP also displays free radical scavenging activity. DMSO decreased both spontaneous and calcium-induced contractions. In contrast, FNP only decreased spontaneous contraction. FNP decreased copper-zinc superoxide dismutase activity and prevented the DMSO-induced increase in glutathione reductase activity. Atomic force microscopy detected that FNP aggregated with calcium ions. Our results indicate that FNP has properties that make it a good candidate to be a modulator of DMSO activity which could minimize side effects of the latter.

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.

Spontaneous Gamma Activity in Schizophrenia.

Science.gov (United States)

Hirano, Yoji; Oribe, Naoya; Kanba, Shigenobu; Onitsuka, Toshiaki; Nestor, Paul G; Spencer, Kevin M

2015-08-01

A major goal of translational neuroscience is to identify neural circuit abnormalities in neuropsychiatric disorders that can be studied in animal models to facilitate the development of new treatments. Oscillations in the gamma band (30-100 Hz) of the electroencephalogram have received considerable interest as the basic mechanisms underlying these oscillations are understood, and gamma abnormalities have been found in schizophrenia (SZ). Animal models of SZ based on hypofunction of the N-methyl-d-aspartate receptor (NMDAR) demonstrate increased spontaneous broadband gamma power, but this phenomenon has not been identified clearly in patients with SZ. To examine spontaneous gamma power and its relationship to evoked gamma oscillations in the auditory cortex of patients with SZ. We performed a cross-sectional study including 24 patients with chronic SZ and 24 matched healthy control participants at the Veterans Affairs Boston Healthcare System from January 1, 2009, through December 31, 2012. Electroencephalograms were obtained during auditory steady-state stimulation at multiple frequencies (20, 30, and 40 Hz) and during a resting state in 18 participants in each group. Electroencephalographic activity in the auditory cortex was estimated using dipole source localization. Auditory steady-state response (ASSR) measures included the phase-locking factor and evoked power. Spontaneous gamma power was measured as induced (non-phase-locked) gamma power in the ASSR data and as total gamma power in the resting-state data. The ASSR phase-locking factor was reduced significantly in patients with SZ compared with controls for the 40-Hz stimulation (mean [SD], 0.075 [0.028] vs 0.113 [0.065]; F1,46 = 6.79 [P = .012]) but not the 20- or the 30-Hz stimulation (0.042 [0.038] vs 0.043 [0.034]; F1,46 = 0.006 [P = .938] and 0.084 [0.040] vs 0.098 [0.050]; F1,46 = 1.605 [P = .212], respectively), repeating previous findings. The mean [SD] broadband-induced (30

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.

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

Innexin gap junctions in nerve cells coordinate spontaneous contractile behavior in Hydra polyps

KAUST Repository

Takaku, Yasuharu; Hwang, Jung Shan; Wolf, Alexander; Bö ttger, Angelika; Shimizu, Hiroshi; David, Charles N.; Gojobori, Takashi

2014-01-01

Nerve cells and spontaneous coordinated behavior first appeared near the base of animal evolution in the common ancestor of cnidarians and bilaterians. Experiments on the cnidarian Hydra have demonstrated that nerve cells are essential

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.

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.

Integrated Analysis of Contractile Kinetics, Force Generation, and Electrical Activity in Single Human Stem Cell-Derived Cardiomyocytes

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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.

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

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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

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

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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.

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

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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

The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the Activity of Antioxidant Enzymes

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Zorana Oreščanin-Dušić

2018-01-01

Full Text Available Ibogaine is an indole alkaloid originally extracted from the root bark of the African rainforest shrub Tabernanthe iboga. It has been explored as a treatment for substance abuse because it interrupts drug addiction and relieves withdrawal symptoms. However, it has been shown that ibogaine treatment leads to a sharp and transient fall in cellular ATP level followed by an increase of cellular respiration and ROS production. Since contractile tissues are sensitive to changes in the levels of ATP and ROS, here we investigated an ibogaine-mediated link between altered redox homeostasis and uterine contractile activity. We found that low concentrations of ibogaine stimulated contractile activity in spontaneously active uteri, but incremental increase of doses inhibited it. Inhibitory concentrations of ibogaine led to decreased SOD1 and elevated GSH-Px activity, but doses that completely inhibited contractions increased CAT activity. Western blot analyses showed that changes in enzyme activities were not due to elevated enzyme protein concentrations but posttranslational modifications. Changes in antioxidant enzyme activities point to a vast concentration-dependent increase in H2O2 level. Knowing that extracellular ATP stimulates isolated uterus contractility, while H2O2 has an inhibitory effect, this concentration-dependent stimulation/inhibition could be linked to ibogaine-related alterations in ATP level and redox homeostasis.

Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity.

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Yeves, A M; Burgos, J I; Medina, A J; Villa-Abrille, M C; Ennis, I L

2018-05-13

Myocardial Na + /H + exchanger-1 (NHE-1) hyperactivity and oxidative stress are interrelated phenomena playing pivotal roles in the development of pathological cardiac hypertrophy and heart failure. Exercise training is effective to convert pathological into physiological hypertrophy in the spontaneously hypertensive rats (SHR), and IGF-1-key humoral mediator of exercise training-inhibits myocardial NHE-1, at least in normotensive rats. Therefore, we hypothesize that IGF-1 by hampering NHE-1 hyperactivity and oxidative stress should exert a cardioprotective effect in the SHR. NHE-1 activity [proton efflux (JH+) mmol L -1  min -1 ], expression and phosphorylation; H 2 O 2 production; superoxide dismutase (SOD) activity; contractility and calcium transients were measured in SHR hearts in the presence/absence of IGF-1. IGF-1 significantly decreased NHE-1 activity (JH+ at pH i 6.95: 1.39 ± 0.32, n = 9 vs C 3.27 ± 0.3, n = 20, P IGF-1 receptor (2.7 ± 0.4, n = 7); by the PI3K inhibitor wortmannin (3.14 ± 0.41, n = 7); and the AKT inhibitor MK2206 (3.37 ± 0.43, n = 14). Moreover, IGF-1 exerted an antioxidant effect revealed by a significant reduction in H 2 O 2 production accompanied by an increase in SOD activity. In addition, IGF-1 improved cardiomyocyte contractility as evidenced by an increase in sarcomere shortening and a decrease in the relaxation constant, underlined by an increase in the amplitude and rate of decay of the calcium transients. IGF-1 exerts a cardioprotective role on the hypertrophied hearts of the SHR, in which the inhibition of NHE-1 hyperactivity, as well as the positive inotropic and antioxidant effects, emerges as key players. © 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

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

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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.

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

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

2015-01-01

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

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

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R. D. Labyntseva,

2015-12-01

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

Innexin gap junctions in nerve cells coordinate spontaneous contractile behavior in Hydra polyps

KAUST Repository

Takaku, Yasuharu

2014-01-07

Nerve cells and spontaneous coordinated behavior first appeared near the base of animal evolution in the common ancestor of cnidarians and bilaterians. Experiments on the cnidarian Hydra have demonstrated that nerve cells are essential for this behavior, although nerve cells in Hydra are organized in a diffuse network and do not form ganglia. Here we show that the gap junction protein innexin-2 is expressed in a small group of nerve cells in the lower body column of Hydra and that an anti-innexin-2 antibody binds to gap junctions in the same region. Treatment of live animals with innexin-2 antibody eliminates gap junction staining and reduces spontaneous body column contractions. We conclude that a small subset of nerve cells, connected by gap junctions and capable of synchronous firing, act as a pacemaker to coordinate the contraction of the body column in the absence of ganglia.

Noise-induced effects on multicellular biopacemaker spontaneous activity: Differences between weak and strong pacemaker cells

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Aghighi, Alireza; Comtois, Philippe

2017-09-01

Self-organization of spontaneous activity of a network of active elements is important to the general theory of reaction-diffusion systems as well as for pacemaking activity to initiate beating of the heart. Monolayer cultures of neonatal rat ventricular myocytes, consisting of resting and pacemaker cells, exhibit spontaneous activation of their electrical activity. Similarly, one proposed approach to the development of biopacemakers as an alternative to electronic pacemakers for cardiac therapy is based on heterogeneous cardiac cells with resting and spontaneously beating phenotypes. However, the combined effect of pacemaker characteristics, density, and spatial distribution of the pacemaker cells on spontaneous activity is unknown. Using a simple stochastic pattern formation algorithm, we previously showed a clear nonlinear dependency of spontaneous activity (occurrence and amplitude of spontaneous period) on the spatial patterns of pacemaker cells. In this study, we show that this behavior is dependent on the pacemaker cell characteristics, with weaker pacemaker cells requiring higher density and larger clusters to sustain multicellular activity. These multicellular structures also demonstrated an increased sensitivity to voltage noise that favored spontaneous activity at lower density while increasing temporal variation in the period of activity. This information will help researchers overcome the current limitations of biopacemakers.

Do β3-adrenergic receptors play a role in guinea pig detrusor smooth muscle excitability and contractility?

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Afeli, Serge A. Y.; Hristov, Kiril L.

2012-01-01

In many species, β3-adrenergic receptors (β3-ARs) have been reported to play a primary role in pharmacologically induced detrusor smooth muscle (DSM) relaxation. However, their role in guinea pig DSM remains controversial. The aim of this study was to investigate whether β3-ARs are expressed in guinea pig DSM and to evaluate how BRL37344 and L-755,507, two selective β3-AR agonists, modulate guinea pig DSM excitability and contractility. We used a combined experimental approach including RT-PCR, patch-clamp electrophysiology, and isometric DSM tension recordings. β3-AR mRNA message was detected in freshly isolated guinea pig DSM single cells. BRL37344 but not L-755,507 caused a slight decrease in DSM spontaneous phasic contraction amplitude and frequency in a concentration-dependent manner. In the presence of atropine (1 μM), only the spontaneous phasic contractions frequency was inhibited by BRL37344 at higher concentrations. Both BRL37344 and L-755,507 significantly decreased DSM carbachol-induced phasic and tonic contractions in a concentration-dependent manner. However, only BRL37344 inhibitory effect was partially antagonized by SR59230A (10 μM), a β3-AR antagonist. In the presence of atropine, BRL37344 and L-755,507 had no inhibitory effect on electrical field stimulation-induced contractions. Patch-clamp experiments showed that BRL37344 (100 μM) did not affect the DSM cell resting membrane potential and K+ conductance. Although β3-ARs are expressed at the mRNA level, they play a minor to no role in guinea pig DSM spontaneous contractility without affecting cell excitability. However, BRL37344 and L-755,507 have pronounced inhibitory effects on guinea pig DSM carbachol-induced contractions. The study outlines important DSM β3-ARs species differences. PMID:21993887

Ongoing spontaneous activity controls access to consciousness: a neuronal model for inattentional blindness.

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Stanislas Dehaene

2005-05-01

Full Text Available Even in the absence of sensory inputs, cortical and thalamic neurons can show structured patterns of ongoing spontaneous activity, whose origins and functional significance are not well understood. We use computer simulations to explore the conditions under which spontaneous activity emerges from a simplified model of multiple interconnected thalamocortical columns linked by long-range, top-down excitatory axons, and to examine its interactions with stimulus-induced activation. Simulations help characterize two main states of activity. First, spontaneous gamma-band oscillations emerge at a precise threshold controlled by ascending neuromodulator systems. Second, within a spontaneously active network, we observe the sudden "ignition" of one out of many possible coherent states of high-level activity amidst cortical neurons with long-distance projections. During such an ignited state, spontaneous activity can block external sensory processing. We relate those properties to experimental observations on the neural bases of endogenous states of consciousness, and particularly the blocking of access to consciousness that occurs in the psychophysical phenomenon of "inattentional blindness," in which normal subjects intensely engaged in mental activity fail to notice salient but irrelevant sensory stimuli. Although highly simplified, the generic properties of a minimal network may help clarify some of the basic cerebral phenomena underlying the autonomy of consciousness.

Ongoing spontaneous activity controls access to consciousness: a neuronal model for inattentional blindness.

Science.gov (United States)

Dehaene, Stanislas; Changeux, Jean-Pierre

2005-05-01

Even in the absence of sensory inputs, cortical and thalamic neurons can show structured patterns of ongoing spontaneous activity, whose origins and functional significance are not well understood. We use computer simulations to explore the conditions under which spontaneous activity emerges from a simplified model of multiple interconnected thalamocortical columns linked by long-range, top-down excitatory axons, and to examine its interactions with stimulus-induced activation. Simulations help characterize two main states of activity. First, spontaneous gamma-band oscillations emerge at a precise threshold controlled by ascending neuromodulator systems. Second, within a spontaneously active network, we observe the sudden "ignition" of one out of many possible coherent states of high-level activity amidst cortical neurons with long-distance projections. During such an ignited state, spontaneous activity can block external sensory processing. We relate those properties to experimental observations on the neural bases of endogenous states of consciousness, and particularly the blocking of access to consciousness that occurs in the psychophysical phenomenon of "inattentional blindness," in which normal subjects intensely engaged in mental activity fail to notice salient but irrelevant sensory stimuli. Although highly simplified, the generic properties of a minimal network may help clarify some of the basic cerebral phenomena underlying the autonomy of consciousness.

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

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

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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

Uncovering intrinsic modular organization of spontaneous brain activity in humans.

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Yong He

Full Text Available The characterization of topological architecture of complex brain networks is one of the most challenging issues in neuroscience. Slow (<0.1 Hz, spontaneous fluctuations of the blood oxygen level dependent (BOLD signal in functional magnetic resonance imaging are thought to be potentially important for the reflection of spontaneous neuronal activity. Many studies have shown that these fluctuations are highly coherent within anatomically or functionally linked areas of the brain. However, the underlying topological mechanisms responsible for these coherent intrinsic or spontaneous fluctuations are still poorly understood. Here, we apply modern network analysis techniques to investigate how spontaneous neuronal activities in the human brain derived from the resting-state BOLD signals are topologically organized at both the temporal and spatial scales. We first show that the spontaneous brain functional networks have an intrinsically cohesive modular structure in which the connections between regions are much denser within modules than between them. These identified modules are found to be closely associated with several well known functionally interconnected subsystems such as the somatosensory/motor, auditory, attention, visual, subcortical, and the "default" system. Specifically, we demonstrate that the module-specific topological features can not be captured by means of computing the corresponding global network parameters, suggesting a unique organization within each module. Finally, we identify several pivotal network connectors and paths (predominantly associated with the association and limbic/paralimbic cortex regions that are vital for the global coordination of information flow over the whole network, and we find that their lesions (deletions critically affect the stability and robustness of the brain functional system. Together, our results demonstrate the highly organized modular architecture and associated topological properties in

Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

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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…

Isolation and maintenance-free culture of contractile myotubes from Manduca sexta embryos.

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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

Embedding responses in spontaneous neural activity shaped through sequential learning.

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Tomoki Kurikawa

Full Text Available Recent experimental measurements have demonstrated that spontaneous neural activity in the absence of explicit external stimuli has remarkable spatiotemporal structure. This spontaneous activity has also been shown to play a key role in the response to external stimuli. To better understand this role, we proposed a viewpoint, "memories-as-bifurcations," that differs from the traditional "memories-as-attractors" viewpoint. Memory recall from the memories-as-bifurcations viewpoint occurs when the spontaneous neural activity is changed to an appropriate output activity upon application of an input, known as a bifurcation in dynamical systems theory, wherein the input modifies the flow structure of the neural dynamics. Learning, then, is a process that helps create neural dynamical systems such that a target output pattern is generated as an attractor upon a given input. Based on this novel viewpoint, we introduce in this paper an associative memory model with a sequential learning process. Using a simple hebbian-type learning, the model is able to memorize a large number of input/output mappings. The neural dynamics shaped through the learning exhibit different bifurcations to make the requested targets stable upon an increase in the input, and the neural activity in the absence of input shows chaotic dynamics with occasional approaches to the memorized target patterns. These results suggest that these dynamics facilitate the bifurcations to each target attractor upon application of the corresponding input, which thus increases the capacity for learning. This theoretical finding about the behavior of the spontaneous neural activity is consistent with recent experimental observations in which the neural activity without stimuli wanders among patterns evoked by previously applied signals. In addition, the neural networks shaped by learning properly reflect the correlations of input and target-output patterns in a similar manner to those designed in

Presbycusis Disrupts Spontaneous Activity Revealed by Resting-State Functional MRI

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Yu-Chen Chen

2018-03-01

Full Text Available Purpose: Presbycusis, age-related hearing loss, is believed to involve neural changes in the central nervous system, which is associated with an increased risk of cognitive impairment. The goal of this study was to determine if presbycusis disrupted spontaneous neural activity in specific brain areas involved in auditory processing, attention and cognitive function using resting-state functional magnetic resonance imaging (fMRI approach.Methods: Hearing and resting-state fMRI measurements were obtained from 22 presbycusis patients and 23 age-, sex- and education-matched healthy controls. To identify changes in spontaneous neural activity associated with age-related hearing loss, we compared the amplitude of low-frequency fluctuations (ALFF and regional homogeneity (ReHo of fMRI signals in presbycusis patients vs. controls and then determined if these changes were linked to clinical measures of presbycusis.Results: Compared with healthy controls, presbycusis patients manifested decreased spontaneous activity mainly in the superior temporal gyrus (STG, parahippocampal gyrus (PHG, precuneus and inferior parietal lobule (IPL as well as increased neural activity in the middle frontal gyrus (MFG, cuneus and postcentral gyrus (PoCG. A significant negative correlation was observed between ALFF/ReHo activity in the STG and average hearing thresholds in presbycusis patients. Increased ALFF/ReHo activity in the MFG was positively correlated with impaired Trail-Making Test B (TMT-B scores, indicative of impaired cognitive function involving the frontal lobe.Conclusions: Presbycusis patients have disrupted spontaneous neural activity reflected by ALFF and ReHo measurements in several brain regions; these changes are associated with specific cognitive performance and speech/language processing. These findings mainly emphasize the crucial role of aberrant resting-state ALFF/ReHo patterns in presbycusis patients and will lead to a better understanding of the

Presbycusis Disrupts Spontaneous Activity Revealed by Resting-State Functional MRI.

Science.gov (United States)

Chen, Yu-Chen; Chen, Huiyou; Jiang, Liang; Bo, Fan; Xu, Jin-Jing; Mao, Cun-Nan; Salvi, Richard; Yin, Xindao; Lu, Guangming; Gu, Jian-Ping

2018-01-01

Purpose : Presbycusis, age-related hearing loss, is believed to involve neural changes in the central nervous system, which is associated with an increased risk of cognitive impairment. The goal of this study was to determine if presbycusis disrupted spontaneous neural activity in specific brain areas involved in auditory processing, attention and cognitive function using resting-state functional magnetic resonance imaging (fMRI) approach. Methods : Hearing and resting-state fMRI measurements were obtained from 22 presbycusis patients and 23 age-, sex- and education-matched healthy controls. To identify changes in spontaneous neural activity associated with age-related hearing loss, we compared the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) of fMRI signals in presbycusis patients vs. controls and then determined if these changes were linked to clinical measures of presbycusis. Results : Compared with healthy controls, presbycusis patients manifested decreased spontaneous activity mainly in the superior temporal gyrus (STG), parahippocampal gyrus (PHG), precuneus and inferior parietal lobule (IPL) as well as increased neural activity in the middle frontal gyrus (MFG), cuneus and postcentral gyrus (PoCG). A significant negative correlation was observed between ALFF/ReHo activity in the STG and average hearing thresholds in presbycusis patients. Increased ALFF/ReHo activity in the MFG was positively correlated with impaired Trail-Making Test B (TMT-B) scores, indicative of impaired cognitive function involving the frontal lobe. Conclusions : Presbycusis patients have disrupted spontaneous neural activity reflected by ALFF and ReHo measurements in several brain regions; these changes are associated with specific cognitive performance and speech/language processing. These findings mainly emphasize the crucial role of aberrant resting-state ALFF/ReHo patterns in presbycusis patients and will lead to a better understanding of the

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.

Endogenous activation of adenosine A(1) receptors accelerates ischemic suppression of spontaneous electrocortical activity

DEFF Research Database (Denmark)

Ilie, Andrei; Ciocan, Dragos; Zagrean, Ana-Maria

2006-01-01

Cerebral ischemia induces a rapid suppression of spontaneous brain rhythms prior to major alterations in ionic homeostasis. It was found in vitro during ischemia that the rapidly formed adenosine, resulting from the intracellular breakdown of ATP, may inhibit synaptic transmission via the A(1......) receptor subtype. The link between endogenous A(1) receptor activation during ischemia and the suppression of spontaneous electrocortical activity has not yet been established in the intact brain. The aim of this study was to investigate in vivo the effects of A(1) receptor antagonism by 8-cyclopentyl-1...

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.

Sensory memory for odors is encoded in spontaneous correlated activity between olfactory glomeruli.

Science.gov (United States)

Galán, Roberto F; Weidert, Marcel; Menzel, Randolf; Herz, Andreas V M; Galizia, C Giovanni

2006-01-01

Sensory memory is a short-lived persistence of a sensory stimulus in the nervous system, such as iconic memory in the visual system. However, little is known about the mechanisms underlying olfactory sensory memory. We have therefore analyzed the effect of odor stimuli on the first odor-processing network in the honeybee brain, the antennal lobe, which corresponds to the vertebrate olfactory bulb. We stained output neurons with a calcium-sensitive dye and measured across-glomerular patterns of spontaneous activity before and after a stimulus. Such a single-odor presentation changed the relative timing of spontaneous activity across glomeruli in accordance with Hebb's theory of learning. Moreover, during the first few minutes after odor presentation, correlations between the spontaneous activity fluctuations suffice to reconstruct the stimulus. As spontaneous activity is ubiquitous in the brain, modifiable fluctuations could provide an ideal substrate for Hebbian reverberations and sensory memory in other neural systems.

Spontaneous Electrical Activity in the Nervous System and its ...

African Journals Online (AJOL)

The present study was carried out to examine the effects of biogenic amines on the spontaneous electrical activity of the nervous system in the silkworm Bombyx mori. The activity recorded from different segments of the ventral nerve cord differed in the frequency and number of spike categories firing. The activity was highest ...

Patchwork-Type Spontaneous Activity in Neonatal Barrel Cortex Layer 4 Transmitted via Thalamocortical Projections

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Hidenobu Mizuno

2018-01-01

Full Text Available Summary: Establishment of precise neuronal connectivity in the neocortex relies on activity-dependent circuit reorganization during postnatal development; however, the nature of cortical activity during this period remains largely unknown. Using two-photon calcium imaging of the barrel cortex in vivo during the first postnatal week, we reveal that layer 4 (L4 neurons within the same barrel fire synchronously in the absence of peripheral stimulation, creating a “patchwork” pattern of spontaneous activity corresponding to the barrel map. By generating transgenic mice expressing GCaMP6s in thalamocortical axons, we show that thalamocortical axons also demonstrate the spontaneous patchwork activity pattern. Patchwork activity is diminished by peripheral anesthesia but is mostly independent of self-generated whisker movements. The patchwork activity pattern largely disappeared during postnatal week 2, as even L4 neurons within the same barrel tended to fire asynchronously. This spontaneous L4 activity pattern has features suitable for thalamocortical (TC circuit refinement in the neonatal barrel cortex. : By two-photon calcium imaging of layer 4 neurons and thalamocortical axon terminals in neonatal mouse barrel cortex, Mizuno et al. find a patchwork-like spontaneous activity pattern corresponding to the barrel map, which may be important for thalamocortical circuit maturation. Keywords: activity-dependent development, spontaneous activity, synchronized activity, barrel cortex, thalamocortical axons, neonates, in vivo calcium imaging, awake, single-cell labeling, whisker monitoring

Cardiac contractility structure-activity relationship and ligand-receptor interactions; the discovery of unique and novel molecular switches in myosuppressin signaling.

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Megan Leander

Full Text Available Peptidergic signaling regulates cardiac contractility; thus, identifying molecular switches, ligand-receptor contacts, and antagonists aids in exploring the underlying mechanisms to influence health. Myosuppressin (MS, a decapeptide, diminishes cardiac contractility and gut motility. Myosuppressin binds to G protein-coupled receptor (GPCR proteins. Two Drosophila melanogaster myosuppressin receptors (DrmMS-Rs exist; however, no mechanism underlying MS-R activation is reported. We predicted DrmMS-Rs contained molecular switches that resembled those of Rhodopsin. Additionally, we believed DrmMS-DrmMS-R1 and DrmMS-DrmMS-R2 interactions would reflect our structure-activity relationship (SAR data. We hypothesized agonist- and antagonist-receptor contacts would differ from one another depending on activity. Lastly, we expected our study to apply to other species; we tested this hypothesis in Rhodnius prolixus, the Chagas disease vector. Searching DrmMS-Rs for molecular switches led to the discovery of a unique ionic lock and a novel 3-6 lock, as well as transmission and tyrosine toggle switches. The DrmMS-DrmMS-R1 and DrmMS-DrmMS-R2 contacts suggested tissue-specific signaling existed, which was in line with our SAR data. We identified R. prolixus (RhpMS-R and discovered it, too, contained the unique myosuppressin ionic lock and novel 3-6 lock found in DrmMS-Rs as well as transmission and tyrosine toggle switches. Further, these motifs were present in red flour beetle, common water flea, honey bee, domestic silkworm, and termite MS-Rs. RhpMS and DrmMS decreased R. prolixus cardiac contractility dose dependently with EC50 values of 140 nM and 50 nM. Based on ligand-receptor contacts, we designed RhpMS analogs believed to be an active core and antagonist; testing on heart confirmed these predictions. The active core docking mimicked RhpMS, however, the antagonist did not. Together, these data were consistent with the unique ionic lock, novel 3-6 lock

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

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.

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.

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.

Voluntary breath holding affects spontaneous brain activity measured by magnetoencephalography

NARCIS (Netherlands)

Schellart, N. A.; Reits, D.

1999-01-01

Spontaneous brain activity was measured by multichannel magnetoencephalography (MEG) during voluntary breath holds. Significant changes in the activity are limited to the alpha rhythm: 0.25 Hz frequency increase and narrowing of the peak. The area of alpha activity shifts slightly toward (fronto-)

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.

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

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 ...

Recurrently connected and localized neuronal communities initiate coordinated spontaneous activity in neuronal networks

Science.gov (United States)

Amin, Hayder; Maccione, Alessandro; Nieus, Thierry

2017-01-01

Developing neuronal systems intrinsically generate coordinated spontaneous activity that propagates by involving a large number of synchronously firing neurons. In vivo, waves of spikes transiently characterize the activity of developing brain circuits and are fundamental for activity-dependent circuit formation. In vitro, coordinated spontaneous spiking activity, or network bursts (NBs), interleaved within periods of asynchronous spikes emerge during the development of 2D and 3D neuronal cultures. Several studies have investigated this type of activity and its dynamics, but how a neuronal system generates these coordinated events remains unclear. Here, we investigate at a cellular level the generation of network bursts in spontaneously active neuronal cultures by exploiting high-resolution multielectrode array recordings and computational network modelling. Our analysis reveals that NBs are generated in specialized regions of the network (functional neuronal communities) that feature neuronal links with high cross-correlation peak values, sub-millisecond lags and that share very similar structural connectivity motifs providing recurrent interactions. We show that the particular properties of these local structures enable locally amplifying spontaneous asynchronous spikes and that this mechanism can lead to the initiation of NBs. Through the analysis of simulated and experimental data, we also show that AMPA currents drive the coordinated activity, while NMDA and GABA currents are only involved in shaping the dynamics of NBs. Overall, our results suggest that the presence of functional neuronal communities with recurrent local connections allows a neuronal system to generate spontaneous coordinated spiking activity events. As suggested by the rules used for implementing our computational model, such functional communities might naturally emerge during network development by following simple constraints on distance-based connectivity. PMID:28749937

Recurrently connected and localized neuronal communities initiate coordinated spontaneous activity in neuronal networks.

Directory of Open Access Journals (Sweden)

Davide Lonardoni

2017-07-01

Full Text Available Developing neuronal systems intrinsically generate coordinated spontaneous activity that propagates by involving a large number of synchronously firing neurons. In vivo, waves of spikes transiently characterize the activity of developing brain circuits and are fundamental for activity-dependent circuit formation. In vitro, coordinated spontaneous spiking activity, or network bursts (NBs, interleaved within periods of asynchronous spikes emerge during the development of 2D and 3D neuronal cultures. Several studies have investigated this type of activity and its dynamics, but how a neuronal system generates these coordinated events remains unclear. Here, we investigate at a cellular level the generation of network bursts in spontaneously active neuronal cultures by exploiting high-resolution multielectrode array recordings and computational network modelling. Our analysis reveals that NBs are generated in specialized regions of the network (functional neuronal communities that feature neuronal links with high cross-correlation peak values, sub-millisecond lags and that share very similar structural connectivity motifs providing recurrent interactions. We show that the particular properties of these local structures enable locally amplifying spontaneous asynchronous spikes and that this mechanism can lead to the initiation of NBs. Through the analysis of simulated and experimental data, we also show that AMPA currents drive the coordinated activity, while NMDA and GABA currents are only involved in shaping the dynamics of NBs. Overall, our results suggest that the presence of functional neuronal communities with recurrent local connections allows a neuronal system to generate spontaneous coordinated spiking activity events. As suggested by the rules used for implementing our computational model, such functional communities might naturally emerge during network development by following simple constraints on distance-based connectivity.

Altered spontaneous activity in anisometropic amblyopia subjects: revealed by resting-state FMRI.

Directory of Open Access Journals (Sweden)

Xiaoming Lin

Full Text Available Amblyopia, also known as lazy eye, usually occurs during early childhood and results in poor or blurred vision. Recent neuroimaging studies have found cortical structural/functional abnormalities in amblyopia. However, until now, it was still not known whether the spontaneous activity of the brain changes in amblyopia subjects. In the present study, regional homogeneity (ReHo, a measure of the homogeneity of functional magnetic resonance imaging signals, was used for the first time to investigate changes in resting-state local spontaneous brain activity in individuals with anisometropic amblyopia. Compared with age- and gender-matched subjects with normal vision, the anisometropic amblyopia subjects showed decreased ReHo of spontaneous brain activity in the right precuneus, the left medial prefrontal cortex, the left inferior frontal gyrus, and the left cerebellum, and increased ReHo of spontaneous brain activity was found in the bilateral conjunction area of the postcentral and precentral gyri, the left paracentral lobule, the left superior temporal gyrus, the left fusiform gyrus, the conjunction area of the right insula, putamen and the right middle occipital gyrus. The observed decreases in ReHo may reflect decreased visuo-motor processing ability, and the increases in ReHo in the somatosensory cortices, the motor areas and the auditory area may indicate compensatory plasticity in amblyopia.

KChIP2 regulates the cardiac Ca2+ transient and myocyte contractility by targeting ryanodine receptor activity.

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Drew M Nassal

Full Text Available Pathologic electrical remodeling and attenuated cardiac contractility are featured characteristics of heart failure. Coinciding with these remodeling events is a loss of the K+ channel interacting protein, KChIP2. While, KChIP2 enhances the expression and stability of the Kv4 family of potassium channels, leading to a more pronounced transient outward K+ current, Ito,f, the guinea pig myocardium is unique in that Kv4 expression is absent, while KChIP2 expression is preserved, suggesting alternative consequences to KChIP2 loss. Therefore, KChIP2 was acutely silenced in isolated guinea pig myocytes, which led to significant reductions in the Ca2+ transient amplitude and prolongation of the transient duration. This change was reinforced by a decline in sarcomeric shortening. Notably, these results were unexpected when considering previous observations showing enhanced ICa,L and prolonged action potential duration following KChIP2 loss, suggesting a disruption of fundamental Ca2+ handling proteins. Evaluation of SERCA2a, phospholamban, RyR, and sodium calcium exchanger identified no change in protein expression. However, assessment of Ca2+ spark activity showed reduced spark frequency and prolonged Ca2+ decay following KChIP2 loss, suggesting an altered state of RyR activity. These changes were associated with a delocalization of the ryanodine receptor activator, presenilin, away from sarcomeric banding to more diffuse distribution, suggesting that RyR open probability are a target of KChIP2 loss mediated by a dissociation of presenilin. Typically, prolonged action potential duration and enhanced Ca2+ entry would augment cardiac contractility, but here we see KChIP2 fundamentally disrupts Ca2+ release events and compromises myocyte contraction. This novel role targeting presenilin localization and RyR activity reveals a significance for KChIP2 loss that reflects adverse remodeling observed in cardiac disease settings.

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.

Computational Account of Spontaneous Activity as a Signature of Predictive Coding.

Directory of Open Access Journals (Sweden)

Veronika Koren

2017-01-01

Full Text Available Spontaneous activity is commonly observed in a variety of cortical states. Experimental evidence suggested that neural assemblies undergo slow oscillations with Up ad Down states even when the network is isolated from the rest of the brain. Here we show that these spontaneous events can be generated by the recurrent connections within the network and understood as signatures of neural circuits that are correcting their internal representation. A noiseless spiking neural network can represent its input signals most accurately when excitatory and inhibitory currents are as strong and as tightly balanced as possible. However, in the presence of realistic neural noise and synaptic delays, this may result in prohibitively large spike counts. An optimal working regime can be found by considering terms that control firing rates in the objective function from which the network is derived and then minimizing simultaneously the coding error and the cost of neural activity. In biological terms, this is equivalent to tuning neural thresholds and after-spike hyperpolarization. In suboptimal working regimes, we observe spontaneous activity even in the absence of feed-forward inputs. In an all-to-all randomly connected network, the entire population is involved in Up states. In spatially organized networks with local connectivity, Up states spread through local connections between neurons of similar selectivity and take the form of a traveling wave. Up states are observed for a wide range of parameters and have similar statistical properties in both active and quiescent state. In the optimal working regime, Up states are vanishing, leaving place to asynchronous activity, suggesting that this working regime is a signature of maximally efficient coding. Although they result in a massive increase in the firing activity, the read-out of spontaneous Up states is in fact orthogonal to the stimulus representation, therefore interfering minimally with the network

Myocardial mitochondrial and contractile function are preserved in mice lacking adiponectin.

Directory of Open Access Journals (Sweden)

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.

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.

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

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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.

TREK-1 Channel Expression in Smooth Muscle as a Target for Regulating Murine Intestinal Contractility: Therapeutic Implications for Motility Disorders

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Ruolin Ma

2018-03-01

Full Text Available Gastrointestinal (GI motility disorders such as irritable bowel syndrome (IBS can occur when coordinated smooth muscle contractility is disrupted. Potassium (K+ channels regulate GI smooth muscle tone and are key to GI tract relaxation, but their molecular and functional phenotypes are poorly described. Here we define the expression and functional roles of mechano-gated K2P channels in mouse ileum and colon. Expression and distribution of the K2P channel family were investigated using quantitative RT-PCR (qPCR, immunohistochemistry and confocal microscopy. The contribution of mechano-gated K2P channels to mouse intestinal muscle tension was studied pharmacologically using organ bath. Multiple K2P gene transcripts were detected in mouse ileum and colon whole tissue preparations. Immunohistochemistry confirmed TREK-1 expression was smooth muscle specific in both ileum and colon, whereas TREK-2 and TRAAK channels were detected in enteric neurons but not smooth muscle. In organ bath, mechano-gated K2P channel activators (Riluzole, BL-1249, flufenamic acid, and cinnamyl 1-3,4-dihydroxy-alpha-cyanocinnamate induced relaxation of KCl and CCh pre-contracted ileum and colon tissues and reduced the amplitude of spontaneous contractions. These data reveal the specific expression of mechano-gated K2P channels in mouse ileum and colon tissues and highlight TREK-1, a smooth muscle specific K2P channel in GI tract, as a potential therapeutic target for combating motility pathologies arising from hyper-contractility.

Protein kinase Cα deletion causes hypotension and decreased vascular contractility.

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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.

Stochastic Ratcheting on a Funneled Energy Landscape Is Necessary for Highly Efficient Contractility of Actomyosin Force Dipoles

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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.

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.

Different responses of spontaneous and stimulus-related alpha activity to ambient luminance changes.

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Benedetto, Alessandro; Lozano-Soldevilla, Diego; VanRullen, Rufin

2017-12-04

Alpha oscillations are particularly important in determining our percepts and have been implicated in fundamental brain functions. Oscillatory activity can be spontaneous or stimulus-related. Furthermore, stimulus-related responses can be phase- or non-phase-locked to the stimulus. Non-phase-locked (induced) activity can be identified as the average amplitude changes in response to a stimulation, while phase-locked activity can be measured via reverse-correlation techniques (echo function). However, the mechanisms and the functional roles of these oscillations are far from clear. Here, we investigated the effect of ambient luminance changes, known to dramatically modulate neural oscillations, on spontaneous and stimulus-related alpha. We investigated the effect of ambient luminance on EEG alpha during spontaneous human brain activity at rest (experiment 1) and during visual stimulation (experiment 2). Results show that spontaneous alpha amplitude increased by decreasing ambient luminance, while alpha frequency remained unaffected. In the second experiment, we found that under low-luminance viewing, the stimulus-related alpha amplitude was lower, and its frequency was slightly faster. These effects were evident in the phase-locked part of the alpha response (echo function), but weaker or absent in the induced (non-phase-locked) alpha responses. Finally, we explored the possible behavioural correlates of these modulations in a monocular critical flicker frequency task (experiment 3), finding that dark adaptation in the left eye decreased the temporal threshold of the right eye. Overall, we found that ambient luminance changes impact differently on spontaneous and stimulus-related alpha expression. We suggest that stimulus-related alpha activity is crucial in determining human temporal segmentation abilities. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Oscillatory brain activity in spontaneous and induced sleep stages in flies.

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Yap, Melvyn H W; Grabowska, Martyna J; Rohrscheib, Chelsie; Jeans, Rhiannon; Troup, Michael; Paulk, Angelique C; van Alphen, Bart; Shaw, Paul J; van Swinderen, Bruno

2017-11-28

Sleep is a dynamic process comprising multiple stages, each associated with distinct electrophysiological properties and potentially serving different functions. While these phenomena are well described in vertebrates, it is unclear if invertebrates have distinct sleep stages. We perform local field potential (LFP) recordings on flies spontaneously sleeping, and compare their brain activity to flies induced to sleep using either genetic activation of sleep-promoting circuitry or the GABA A agonist Gaboxadol. We find a transitional sleep stage associated with a 7-10 Hz oscillation in the central brain during spontaneous sleep. Oscillatory activity is also evident when we acutely activate sleep-promoting neurons in the dorsal fan-shaped body (dFB) of Drosophila. In contrast, sleep following Gaboxadol exposure is characterized by low-amplitude LFPs, during which dFB-induced effects are suppressed. Sleep in flies thus appears to involve at least two distinct stages: increased oscillatory activity, particularly during sleep induction, followed by desynchronized or decreased brain activity.

A gravimetric method for the measurement of total spontaneous activity in rats.

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Biesiadecki, B J; Brand, P H; Koch, L G; Britton, S L

1999-10-01

Currently available methods for the measurement of spontaneous activity of laboratory animals require expensive, specialized equipment and may not be suitable for use in low light conditions with nocturnal species. We developed a gravimetric method that uses common laboratory equipment to quantify the total spontaneous activity of rats and is suitable for use in the dark. The rat in its home cage is placed on a top-loading electronic balance interfaced to a computer. Movements are recorded by the balance as changes in weight and transmitted to the computer at 10 Hz. Data are analyzed on-line to derive the absolute value of the difference in weight between consecutive samples, and the one-second average of the absolute values is calculated. The averages are written to file for off-line analysis and summed over the desired observation period to provide a measure of total spontaneous activity. The results of in vitro experiments demonstrated that: 1) recorded weight changes were not influenced by position of the weight on the bottom of the cage, 2) values recorded from a series of weight changes were not significantly different from the calculated values, 3) the constantly decreasing force exerted by a swinging pendulum placed on the balance was accurately recorded, 4) the measurement of activity was not influenced by the evaporation of a fluid such as urine, and 5) the method can detect differences in the activity of sleeping and waking rats over a 10-min period, as well as during 4-hr intervals recorded during active (night-time) and inactive (daytime) periods. These results demonstrate that this method provides an inexpensive, accurate, and noninvasive method to quantitate the spontaneous activity of small animals.

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

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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.

Effect of Propafenone on the Contractile Activity of Latissimus Dorsi Muscle Isolated in an Organ Chamber: Experimental Study in Rats

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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.

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

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

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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

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

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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.

Spontaneous high-gamma band activity reflects functional organization of auditory cortex in the awake macaque.

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Fukushima, Makoto; Saunders, Richard C; Leopold, David A; Mishkin, Mortimer; Averbeck, Bruno B

2012-06-07

In the absence of sensory stimuli, spontaneous activity in the brain has been shown to exhibit organization at multiple spatiotemporal scales. In the macaque auditory cortex, responses to acoustic stimuli are tonotopically organized within multiple, adjacent frequency maps aligned in a caudorostral direction on the supratemporal plane (STP) of the lateral sulcus. Here, we used chronic microelectrocorticography to investigate the correspondence between sensory maps and spontaneous neural fluctuations in the auditory cortex. We first mapped tonotopic organization across 96 electrodes spanning approximately two centimeters along the primary and higher auditory cortex. In separate sessions, we then observed that spontaneous activity at the same sites exhibited spatial covariation that reflected the tonotopic map of the STP. This observation demonstrates a close relationship between functional organization and spontaneous neural activity in the sensory cortex of the awake monkey. Copyright © 2012 Elsevier Inc. All rights reserved.

Reduced Contractility and Motility of Prostatic Cancer-Associated Fibroblasts after Inhibition of Heat Shock Protein 90

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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.

[Cellular mechanism of the generation of spontaneous activity in gastric muscle].

Science.gov (United States)

Nakamura, Eri; Kito, Yoshihiko; Fukuta, Hiroyasu; Yanai, Yoshimasa; Hashitani, Hikaru; Yamamoto, Yoshimichi; Suzuki, Hikaru

2004-03-01

In gastric smooth muscles, interstitial cells of Cajal (ICC) might be the pacemaker cells of spontaneous activities since ICC are rich in mitochondria and are connected with smooth muscle cells via gap junctions. Several types of ICC are distributed widely in the stomach wall. A group of ICC distributed in the myenteric layer (ICC-MY) were the pacemaker cells of gastrointestinal smooth muscles. Pacemaker potentials were generated in ICC-MY, and the potentials were conducted to circular smooth muscles to trigger slow waves and also conducted to longitudinal muscles to form follower potentials. In circular muscle preparations, interstitial cells distributed within muscle bundles (ICC-IM) produced unitary potentials, which were conducted to circular muscles to form slow potentials by summation. In mutant mice lacking inositol trisphosphate (IP(3)) receptor, slow waves were absent in gastric smooth muscles. The generation of spontaneous activity was impaired by the inhibition of Ca(2+)-release from internal stores through IP(3) receptors, inhibition of mitochondrial Ca(2+)-handling with proton pump inhibitors, and inhibition of ATP-sensitive K(+)-channels at the mitochondrial inner membrane. These results suggested that mitochondrial Ca(2+)-handling causes the generation of spontaneous activity in pacemaker cells. Possible involvement of protein kinase C (PKC) in the Ca(2+) signaling system was also suggested.

Efffects of vigabatrin on spontaneous locomotor activity of rats

NARCIS (Netherlands)

Bouwman, B.M.; Rijn, C.M. van; Willems-van Bree, P.C.M.; Coenen, A.M.L.

2003-01-01

Effects of vigibatrin (saline, 125, 250, or 500 mg/kg i.p.) on spontaneous locomotor activity in Wistar rats were investigated. There was a dose dependent decrease in amount of locomotion for doses up to 250 mg/kg. This decrease was measurable 2-4 hours after injection and still became more

Endosulfan induces changes in spontaneous swimming activity and acetylcholinesterase activity of Jenynsia multidentata (Anablepidae, Cyprinodontiformes)

International Nuclear Information System (INIS)

Ballesteros, M.L.; Durando, P.E.; Nores, M.L.; Diaz, M.P.; Bistoni, M.A.; Wunderlin, D.A.

2009-01-01

We assessed changes in spontaneous swimming activity and acetylcholinesterase (AchE) activity of Jenynsia multidentata exposed to Endosulfan (EDS). Females of J. multidentata were exposed to 0.072 and 1.4 μg L -1 EDS. Average speed and movement percentage were recorded during 48 h. We also exposed females to EDS at five concentrations between 0.072 and 1.4 μg L -1 during 24 h, and measured the AchE activity in brain and muscle. At 0.072 μg L -1 EDS swimming motility decreased relative to the control group after 45 h, while at 1.4 μg L -1 EDS swimming motility decreased after 24 h. AchE activity significantly decreased in muscle when J. multidentata were exposed to EDS above 0.072 μg L -1 , while no significant changes were observed in brain. Thus, changes in swimming activity and AchE activity in muscle are good biomarkers of exposure to EDS in J. multidentata. - This work reports changes observed in spontaneous swimming activity and AchE activity of Jenynsia multidentata exposed to sublethal concentrations of Endosulfan.

Endosulfan induces changes in spontaneous swimming activity and acetylcholinesterase activity of Jenynsia multidentata (Anablepidae, Cyprinodontiformes)

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Ballesteros, M.L. [Facultad de Ciencias Exactas, Fisicas y Naturales, Catedra Diversidad Animal II, Universidad Nacional de Cordoba, Av. Velez Sarsfield 299, 5000 Cordoba (Argentina); Durando, P.E. [Facultad de Ciencias Exactas, Fisicas y Naturales, Departamento de Biologia, Catedra de Fisiologia Animal, Universidad Nacional de San Juan, Complejo ' Islas Malvinas' , Av. Jose I. de la Roza y Meglioli, Rivadavia, San Juan (Argentina); Nores, M.L. [Facultad de Ciencias Medicas, Universidad Nacional de Cordoba-CONICET, Ciudad Universitaria, Cordoba (Argentina); Diaz, M.P. [Facultad de Ciencias Medicas, Catedra de Estadistica y Bioestadistica, Escuela de Nutricion, Universidad Nacional de Cordoba, Pabellon Chile, Ciudad Universitaria, 5000 Cordoba (Argentina); Bistoni, M.A., E-mail: mbistoni@com.uncor.ed [Facultad de Ciencias Exactas, Fisicas y Naturales, Catedra Diversidad Animal II, Universidad Nacional de Cordoba, Av. Velez Sarsfield 299, 5000 Cordoba (Argentina); Wunderlin, D.A. [Facultad de Ciencias Quimicas, Dto. Bioquimica Clinica-CIBICI, Universidad Nacional de Cordoba-CONICET, Haya de la Torre esq. Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina)

2009-05-15

We assessed changes in spontaneous swimming activity and acetylcholinesterase (AchE) activity of Jenynsia multidentata exposed to Endosulfan (EDS). Females of J. multidentata were exposed to 0.072 and 1.4 mug L{sup -1} EDS. Average speed and movement percentage were recorded during 48 h. We also exposed females to EDS at five concentrations between 0.072 and 1.4 mug L{sup -1} during 24 h, and measured the AchE activity in brain and muscle. At 0.072 mug L{sup -1} EDS swimming motility decreased relative to the control group after 45 h, while at 1.4 mug L{sup -1} EDS swimming motility decreased after 24 h. AchE activity significantly decreased in muscle when J. multidentata were exposed to EDS above 0.072 mug L{sup -1}, while no significant changes were observed in brain. Thus, changes in swimming activity and AchE activity in muscle are good biomarkers of exposure to EDS in J. multidentata. - This work reports changes observed in spontaneous swimming activity and AchE activity of Jenynsia multidentata exposed to sublethal concentrations of Endosulfan.

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.

Acute exposure to lead increases myocardial contractility independent of hypertension development

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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.

Acute exposure to lead increases myocardial contractility independent of hypertension development

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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

SPASMOLYTIC ACTIVITY OF THE AQUEOUS AND ETHANOL CELERY LEAVES (APIUM GRAVEOLENS L. EXTRACTS ON THE CONTRACTION OF ISOLATED RAT ILEUM

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Suzana Branković

2015-06-01

Full Text Available Celery (Apium graveolens L. is a plant species in the family Apiaceae, which has been used in traditional medicine for the treatment of gastrointestinal diseases. This study investigated the effects of aqueous and ethanol extracts from celery leaves on intestinal contractility. Air-dried and powdered leaves were extracted with distilled water and 96% ethanol, respectively. The activities of the extracts on the smooth muscle contractions were evaluated using isolated rat ileum model. The isolated rat ileum was mounted in a 10ml tissue bath. The results suggest that the cumulative concentrations of the extracts of celery statistically significantly inhibited spontaneous rat ileum contractions (p<0.01. The extracts dose-dependently reduced the contractile effects of acetylcholine on the isolated ileum (p<0.05. Ethanol extract exhibited significantly greater relaxant activity than the aqueous extract (p<0.05. These results suggest that the aqueous and ethanol extracts of celery leaves can produce the inhibition of the spontaneous rat ileum contractions and contractions induced by acetylcholine. These data indicate that celery extracts act as intestinal smooth muscle relaxants, which justifies their use in gastrointestinal disorders.

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

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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.

Changes in spontaneous brain activity in early Parkinson's disease.

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Yang, Hong; Zhou, Xiaohong Joe; Zhang, Min-Ming; Zheng, Xu-Ning; Zhao, Yi-Lei; Wang, Jue

2013-08-09

Resting state brain activity can provide valuable insights into the pathophysiology of Parkinson's disease (PD). The purpose of the present study was (a) to investigate abnormal spontaneous neuronal activity in early PD patients using resting-state functional MRI (fMRI) with a regional homogeneity (ReHo) method and (b) to demonstrate the potential of using changes in abnormal spontaneous neuronal activity for monitoring the progression of PD during its early stages. Seventeen early PD patients were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr disability scale and the Mini-mental State Examination (MMSE) were compared with seventeen gender- and age-matched healthy controls. All subjects underwent MRI scans using a 1.5T General Electric Signa Excite II scanner. The MRI scan protocol included whole-brain volumetric imaging using a 3D inversion recovery prepared (IR-Prep) fast spoiled gradient-echo pulse sequence and 2D multi-slice (22 axial slices covering the whole brain) resting-state fMRI using an echo planar imaging (EPI) sequence. Images were analyzed in SPM5 together with a ReHo algorithm using the in-house software program REST. A corrected threshold of pbrain regions, including the left cerebellum, left parietal lobe, right middle temporal lobe, right sub-thalamic nucleus areas, right superior frontal gyrus, middle frontal gyrus (MFG), right inferior parietal lobe (IPL), right precuneus lobe, left MFG and left IPL. Additionally, significantly reduced ReHo was also observed in the early PD patients in the following brain regions: the left putamen, left inferior frontal gyrus, right hippocampus, right anterior cingulum, and bilateral lingual gyrus. Moreover, in PD patients, ReHo in the left putamen was negatively correlated with the UPDRS scores (r=-0.69). These results indicate that the abnormal resting state spontaneous brain activity associated with patients with early PD can be revealed by Reho analysis. Copyright �

Validation of an in vitro contractility assay using canine ventricular myocytes

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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.

Dopamine Attenuates Ketamine-Induced Neuronal Apoptosis in the Developing Rat Retina Independent of Early Synchronized Spontaneous Network Activity.

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Dong, Jing; Gao, Lingqi; Han, Junde; Zhang, Junjie; Zheng, Jijian

2017-07-01

Deprivation of spontaneous rhythmic electrical activity in early development by anesthesia administration, among other interventions, induces neuronal apoptosis. However, it is unclear whether enhancement of neuronal electrical activity attenuates neuronal apoptosis in either normal development or after anesthesia exposure. The present study investigated the effects of dopamine, an enhancer of spontaneous rhythmic electrical activity, on ketamine-induced neuronal apoptosis in the developing rat retina. TUNEL and immunohistochemical assays indicated that ketamine time- and dose-dependently aggravated physiological and ketamine-induced apoptosis and inhibited early-synchronized spontaneous network activity. Dopamine administration reversed ketamine-induced neuronal apoptosis, but did not reverse the inhibitory effects of ketamine on early synchronized spontaneous network activity despite enhancing it in controls. Blockade of D1, D2, and A2A receptors and inhibition of cAMP/PKA signaling partially antagonized the protective effect of dopamine against ketamine-induced apoptosis. Together, these data indicate that dopamine attenuates ketamine-induced neuronal apoptosis in the developing rat retina by activating the D1, D2, and A2A receptors, and upregulating cAMP/PKA signaling, rather than through modulation of early synchronized spontaneous network activity.

Effects of hypoxia and hypercapnia on geniohyoid contractility and endurance.

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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.

Perfusion-induced changes in cardiac contractility depend on capillary perfusion.

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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.

Spontaneous and Evoked Activity from Murine Ventral Horn Cultures on Microelectrode Arrays

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Bryan J. Black

2017-09-01

Full Text Available Motor neurons are the site of action for several neurological disorders and paralytic toxins, with cell bodies located in the ventral horn (VH of the spinal cord along with interneurons and support cells. Microelectrode arrays (MEAs have emerged as a high content assay platform for mechanistic studies and drug discovery. Here, we explored the spontaneous and evoked electrical activity of VH cultures derived from embryonic mouse spinal cord on multi-well plates of MEAs. Primary VH cultures from embryonic day 15–16 mice were characterized by expression of choline acetyltransferase (ChAT by immunocytochemistry. Well resolved, all-or-nothing spontaneous spikes with profiles consistent with extracellular action potentials were observed after 3 days in vitro, persisting with consistent firing rates until at least day in vitro 19. The majority of the spontaneous activity consisted of tonic firing interspersed with coordinated bursting across the network. After 5 days in vitro, spike activity was readily evoked by voltage pulses where a minimum amplitude and duration required for excitation was 300 mV and 100 μs/phase, respectively. We characterized the sensitivity of spontaneous and evoked activity to a host of pharmacological agents including AP5, CNQX, strychnine, ω-agatoxin IVA, and botulinum neurotoxin serotype A (BoNT/A. These experiments revealed sensitivity of the cultured VH to both agonist and antagonist compounds in a manner consistent with mature tissue derived from slices. In the case of BoNT/A, we also demonstrated intoxication persistence over an 18-day period, followed by partial intoxication recovery induced by N- and P/Q-type calcium channel agonist GV-58. In total, our findings suggest that VH cultures on multi-well MEA plates may represent a moderate throughput, high content assay for performing mechanistic studies and for screening potential therapeutics pertaining to paralytic toxins and neurological disorders.

Comparison of contractile and extensile pneumatic artificial muscles

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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.

Modifications of spontaneous oculomotor activity in microgravitational conditions

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Kornilova, L. N.; Goncharenko, A. M.; Polyakov, V. V.; Grigorova, V.; Manev, A.

Investigations on spontaneous oculomotor activity were carried out prior to and after (five cosmonauts) and during space flight (two cosmonauts) on the 3rd, 5th and 164th days of the space flight. Recording of oculomotor activity was carried out by electrooculography on automated data acquisition and processing system "Zora" based on personal computers. During the space flight and after it all the cosmonauts with the eyes closed or open and dark-goggled showed an essential increase of the movements' amplitude when removing the eyes into the extreme positions especially in a vertical direction, occurrence of correcting saccadic movements (or nystagmus), an increase in time of fixing reactions.

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

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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

Tinnitus perception and distress is related to abnormal spontaneous brain activity as measured by magnetoencephalography.

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2005-06-01

Full Text Available BACKGROUND: The neurophysiological mechanisms underlying tinnitus perception are not well understood. Surprisingly, there have been no group studies comparing abnormalities in ongoing, spontaneous neuronal activity in individuals with and without tinnitus perception. METHODS AND FINDINGS: Here, we show that the spontaneous neuronal activity of a group of individuals with tinnitus (n = 17 is characterised by a marked reduction in alpha (8-12 Hz power together with an enhancement in delta (1.5-4 Hz as compared to a normal hearing control group (n = 16. This pattern was especially pronounced for temporal regions. Moreover, correlations with tinnitus-related distress revealed strong associations with this abnormal spontaneous activity pattern, particularly in right temporal and left frontal areas. Overall, effects were stronger for the alpha than for the delta frequency band. A data stream of 5 min, recorded with a whole-head neuromagnetometer under a resting condition, was sufficient to extract the marked differences. CONCLUSIONS: Despite some limitations, there are arguments that the regional pattern of abnormal spontaneous activity we found could reflect a tinnitus-related cortical network. This finding, which suggests that a neurofeedback approach could reduce the adverse effects of this disturbing condition, could have important implications for the treatment of tinnitus.

Recruitment of Perisomatic Inhibition during Spontaneous Hippocampal Activity In Vitro.

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Anna Beyeler

Full Text Available It was recently shown that perisomatic GABAergic inhibitory postsynaptic potentials (IPSPs originating from basket and chandelier cells can be recorded as population IPSPs from the hippocampal pyramidal layer using extracellular electrodes (eIPSPs. Taking advantage of this approach, we have investigated the recruitment of perisomatic inhibition during spontaneous hippocampal activity in vitro. Combining intracellular and extracellular recordings from pyramidal cells and interneurons, we confirm that inhibitory signals generated by basket cells can be recorded extracellularly, but our results suggest that, during spontaneous activity, eIPSPs are mostly confined to the CA3 rather than CA1 region. CA3 eIPSPs produced the powerful time-locked inhibition of multi-unit activity expected from perisomatic inhibition. Analysis of the temporal dynamics of spike discharges relative to eIPSPs suggests significant but moderate recruitment of excitatory and inhibitory neurons within the CA3 network on a 10 ms time scale, within which neurons recruit each other through recurrent collaterals and trigger powerful feedback inhibition. Such quantified parameters of neuronal interactions in the hippocampal network may serve as a basis for future characterisation of pathological conditions potentially affecting the interactions between excitation and inhibition in this circuit.

Stalk-length-dependence of the contractility of Vorticella convallaria

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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.

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

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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.

[Effects of vitamin K3 on the contractile activity of the colonic smooth muscles of guinea pig through the calcium activated potassium channel].

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Li, Jun; Luo, He-sheng; He, Xiao-gu

2006-07-25

To study the mechanism of relaxation of gastrointestinal smooth muscles by vitamin K(3). Stripes of proximal colon were collected from guinea pigs. Suspension of single cells was created from these stripes. TD-112S transducer was used to measure the contraction of the stripes stimulated by vitamin K(3) of the concentrations of 40, 100, 400, and 800 micromol/L respectively. The Ca(2+)-activated K(+) current [IK(Ca)] of the cytomembrane of the colon smooth muscle was recorded with an EPC 10 amplifier under conventional whole cell patterns. The contraction frequencies of the muscle stripes stimulated by vitamin K(3) of the concentrations of 40, 100, 400, and 800 micromol/L were 79% +/- 4%, 58% +/- 5%, 33% +/- 4%, and 12% +/- 3% respectively of that of the control group (all P Vitamin K(3) inhibits the contractile activity of the colonic muscle stripes and increases the IK(Ca) of single myocytes concentration-dependently. The mechanism is activation of the Ca(2+)-activated K(+) channel, thus promoting the potassium efflux.

Where's the Noise? Key Features of Spontaneous Activity and Neural Variability Arise through Learning in a Deterministic Network.

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Christoph Hartmann

2015-12-01

Full Text Available Even in the absence of sensory stimulation the brain is spontaneously active. This background "noise" seems to be the dominant cause of the notoriously high trial-to-trial variability of neural recordings. Recent experimental observations have extended our knowledge of trial-to-trial variability and spontaneous activity in several directions: 1. Trial-to-trial variability systematically decreases following the onset of a sensory stimulus or the start of a motor act. 2. Spontaneous activity states in sensory cortex outline the region of evoked sensory responses. 3. Across development, spontaneous activity aligns itself with typical evoked activity patterns. 4. The spontaneous brain activity prior to the presentation of an ambiguous stimulus predicts how the stimulus will be interpreted. At present it is unclear how these observations relate to each other and how they arise in cortical circuits. Here we demonstrate that all of these phenomena can be accounted for by a deterministic self-organizing recurrent neural network model (SORN, which learns a predictive model of its sensory environment. The SORN comprises recurrently coupled populations of excitatory and inhibitory threshold units and learns via a combination of spike-timing dependent plasticity (STDP and homeostatic plasticity mechanisms. Similar to balanced network architectures, units in the network show irregular activity and variable responses to inputs. Additionally, however, the SORN exhibits sequence learning abilities matching recent findings from visual cortex and the network's spontaneous activity reproduces the experimental findings mentioned above. Intriguingly, the network's behaviour is reminiscent of sampling-based probabilistic inference, suggesting that correlates of sampling-based inference can develop from the interaction of STDP and homeostasis in deterministic networks. We conclude that key observations on spontaneous brain activity and the variability of neural

The wiring of developing sensory circuits - from patterned spontaneous activity to mechanisms of synaptic plasticity

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Alexandra Helen Leighton

2016-09-01

Full Text Available In order to accurately process incoming sensory stimuli, neurons must be organized into functional networks, with both genetic and environmental factors influencing the precise arrangement of connections between cells. Teasing apart the relative contributions of molecular guidance cues, spontaneous activity and visual experience during this maturation is on-going. During development of the sensory system, the first, rough organization of connections is created by molecular factors. These connections are then modulated by the intrinsically generated activity of neurons, even before the senses have become operational. Spontaneous waves of depolarisations sweep across the nervous system, placing them in a prime position to strengthen correct connections and weaken others, shaping synapses into a useful network. A large body of work now supports the idea that, rather than being a mere side-effect of the system, spontaneous activity actually contains information which readies the nervous system so that, as soon as the senses become active, sensory information can be utilized by the animal. An example is the neonatal mouse. As soon as the eyelids first open, neurons in the cortex respond to visual information without the animal having previously encountered structured sensory input (Cang et al., 2005a; Ko et al., 2013; Rochefort et al., 2011; Zhang et al., 2012. In vivo imaging techniques have advanced considerably, allowing observation of the natural activity in the brain of living animals down to the level of the individual synapse. New (optogenetic methods make it possible to subtly modulate the spatio-temporal properties of activity, aiding our understanding of how these characteristics relate to the function of spontaneous activity. Such experiments have had a huge impact on our knowledge by permitting direct testing of ideas about the plasticity mechanisms at play in the intact system, opening up a provocative range of fresh questions. Here, we

Copper is an endogenous modulator of neural circuit spontaneous activity.

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Dodani, Sheel C; Firl, Alana; Chan, Jefferson; Nam, Christine I; Aron, Allegra T; Onak, Carl S; Ramos-Torres, Karla M; Paek, Jaeho; Webster, Corey M; Feller, Marla B; Chang, Christopher J

2014-11-18

For reasons that remain insufficiently understood, the brain requires among the highest levels of metals in the body for normal function. The traditional paradigm for this organ and others is that fluxes of alkali and alkaline earth metals are required for signaling, but transition metals are maintained in static, tightly bound reservoirs for metabolism and protection against oxidative stress. Here we show that copper is an endogenous modulator of spontaneous activity, a property of functional neural circuitry. Using Copper Fluor-3 (CF3), a new fluorescent Cu(+) sensor for one- and two-photon imaging, we show that neurons and neural tissue maintain basal stores of loosely bound copper that can be attenuated by chelation, which define a labile copper pool. Targeted disruption of these labile copper stores by acute chelation or genetic knockdown of the CTR1 (copper transporter 1) copper channel alters the spatiotemporal properties of spontaneous activity in developing hippocampal and retinal circuits. The data identify an essential role for copper neuronal function and suggest broader contributions of this transition metal to cell signaling.

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

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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.

Altered spontaneous brain activity in patients with hemifacial spasm: a resting-state functional MRI study.

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Ye Tu

Full Text Available Resting-state functional magnetic resonance imaging (fMRI has been used to detect the alterations of spontaneous neuronal activity in various neurological and neuropsychiatric diseases, but rarely in hemifacial spasm (HFS, a nervous system disorder. We used resting-state fMRI with regional homogeneity (ReHo analysis to investigate changes in spontaneous brain activity of patients with HFS and to determine the relationship of these functional changes with clinical features. Thirty patients with HFS and 33 age-, sex-, and education-matched healthy controls were included in this study. Compared with controls, HFS patients had significantly decreased ReHo values in left middle frontal gyrus (MFG, left medial cingulate cortex (MCC, left lingual gyrus, right superior temporal gyrus (STG and right precuneus; and increased ReHo values in left precentral gyrus, anterior cingulate cortex (ACC, right brainstem, and right cerebellum. Furthermore, the mean ReHo value in brainstem showed a positive correlation with the spasm severity (r = 0.404, p = 0.027, and the mean ReHo value in MFG was inversely related with spasm severity in HFS group (r = -0.398, p = 0.028. This study reveals that HFS is associated with abnormal spontaneous brain activity in brain regions most involved in motor control and blinking movement. The disturbances of spontaneous brain activity reflected by ReHo measurements may provide insights into the neurological pathophysiology of HFS.

Spontaneous cortical activity reveals hallmarks of an optimal internal model of the environment.

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Berkes, Pietro; Orbán, Gergo; Lengyel, Máté; Fiser, József

2011-01-07

The brain maintains internal models of its environment to interpret sensory inputs and to prepare actions. Although behavioral studies have demonstrated that these internal models are optimally adapted to the statistics of the environment, the neural underpinning of this adaptation is unknown. Using a Bayesian model of sensory cortical processing, we related stimulus-evoked and spontaneous neural activities to inferences and prior expectations in an internal model and predicted that they should match if the model is statistically optimal. To test this prediction, we analyzed visual cortical activity of awake ferrets during development. Similarity between spontaneous and evoked activities increased with age and was specific to responses evoked by natural scenes. This demonstrates the progressive adaptation of internal models to the statistics of natural stimuli at the neural level.

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

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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.

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

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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.

Spatiotemporal stability of neonatal rat cardiomyocyte monolayers spontaneous activity is dependent on the culture substrate.

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Jonathan Boudreau-Béland

Full Text Available In native conditions, cardiac cells must continuously comply with diverse stimuli necessitating a perpetual adaptation. Polydimethylsiloxane (PDMS is commonly used in cell culture to study cellular response to changes in the mechanical environment. The aim of this study was to evaluate the impact of using PDMS substrates on the properties of spontaneous activity of cardiomyocyte monolayer cultures. We compared PDMS to the gold standard normally used in culture: a glass substrate. Although mean frequency of spontaneous activity remained unaltered, incidence of reentrant activity was significantly higher in samples cultured on glass compared to PDMS substrates. Higher spatial and temporal instability of the spontaneous rate activation was found when cardiomyocytes were cultured on PDMS, and correlated with decreased connexin-43 and increased CaV3.1 and HCN2 mRNA levels. Compared to cultures on glass, cultures on PDMS were associated with the strongest response to isoproterenol and acetylcholine. These results reveal the importance of carefully selecting the culture substrate for studies involving mechanical stimulation, especially for tissue engineering or pharmacological high-throughput screening of cardiac tissue analog.

Search for spontaneous fission activity in Salton Sea and Atlantis II hot brines

International Nuclear Information System (INIS)

Ter-Akopian, G.M.; Sokol, E.A.; Fam Ngoc Chuong; Ivanov, M.P.; Popeko, G.S.; Molzahn, D.; Lund, T.; Feige, G.; Brandt, R.

1984-01-01

A search for an unknown spontaneously fissioning activity, possibly due to SHE, was carried out with the Dubna 3 He-counter system. In the investigation of Salton Sea samples and Atlantis II samples no such activity could be detected with limits -12 g/g. (orig.)

Reproduction of overall spontaneous pain pattern by manual stimulation of active myofascial trigger points in fibromyalgia patients

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Ge, Hong-You; Wang, Ying; Fernandez-de-las-Penas, Cesar

2011-01-01

It has previously been reported that local and referred pain from active myofascial trigger points (MTPs) in the neck and shoulder region contribute to fibromyalgia (FM) pain and that the pain pattern induced from active MTPs can reproduce parts of the spontaneous clinical FM pain pattern....... The current study investigated whether the overall spontaneous FM pain pattern can be reproduced by local and referred pain from active MTPs located in different muscles....

Oscillatory brain activity in spontaneous and induced sleep stages in flies

OpenAIRE

Yap, Melvyn H. W.; Grabowska, Martyna J.; Rohrscheib, Chelsie; Jeans, Rhiannon; Troup, Michael; Paulk, Angelique C.; van Alphen, Bart; Shaw, Paul J.; van Swinderen, Bruno

2017-01-01

Sleep is a dynamic process comprising multiple stages, each associated with distinct electrophysiological properties and potentially serving different functions. While these phenomena are well described in vertebrates, it is unclear if invertebrates have distinct sleep stages. We perform local field potential (LFP) recordings on flies spontaneously sleeping, and compare their brain activity to flies induced to sleep using either genetic activation of sleep-promoting circuitry or the GABAA ago...

Transcellular tunnel dynamics: Control of cellular dewetting by actomyosin contractility and I-BAR proteins.

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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.

[A basis for application of cardiac contractility variability in the Evaluation and assessment of exercise and fitness].

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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.

Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy.

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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.

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

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.

Endo- and exocytic rate constants for spontaneous and protein kinase C-activated T cell receptor cycling

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Menné, Charlotte; Møller Sørensen, Tine; Siersma, Volkert

2002-01-01

To determine the rate constants of spontaneous and activated TCR cycling, we examined TCR endo- and exocytosis in the human T cell line Jurkat by three different methods. Using a simple kinetic model for TCR cycling and non-linear regression analyses, we found that the spontaneous endocytic rate...... constant of the TCR was low (approximately 0.012 min(-1)) whereas the spontaneous exocytic rate constant was similar to that of other cycling receptors (approximately 0.055 min(-1)). Following protein kinase C activation (PKC) the endocytic rate constant was increased tenfold (to approximately 0.128 min(-1......)) whereas the exocytic rate constant was unaffected. Thus, the TCR becomes a rapidly cycling receptor with kinetics similar to classical cycling receptors subsequent to PKC activation. This results in a reduction of the half-life of cell surface expressed TCR from approximately 58 to 6 min and allows rapid...

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

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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.

Moderate ethanol administration accentuates cardiomyocyte contractile dysfunction and mitochondrial injury in high fat diet-induced obesity.

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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 �

Neurofeedback Tunes Scale-Free Dynamics in Spontaneous Brain Activity.

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Ros, T; Frewen, P; Théberge, J; Michela, A; Kluetsch, R; Mueller, A; Candrian, G; Jetly, R; Vuilleumier, P; Lanius, R A

2017-10-01

Brain oscillations exhibit long-range temporal correlations (LRTCs), which reflect the regularity of their fluctuations: low values representing more random (decorrelated) while high values more persistent (correlated) dynamics. LRTCs constitute supporting evidence that the brain operates near criticality, a state where neuronal activities are balanced between order and randomness. Here, healthy adults used closed-loop brain training (neurofeedback, NFB) to reduce the amplitude of alpha oscillations, producing a significant increase in spontaneous LRTCs post-training. This effect was reproduced in patients with post-traumatic stress disorder, where abnormally random dynamics were reversed by NFB, correlating with significant improvements in hyperarousal. Notably, regions manifesting abnormally low LRTCs (i.e., excessive randomness) normalized toward healthy population levels, consistent with theoretical predictions about self-organized criticality. Hence, when exposed to appropriate training, spontaneous cortical activity reveals a residual capacity for "self-tuning" its own temporal complexity, despite manifesting the abnormal dynamics seen in individuals with psychiatric disorder. Lastly, we observed an inverse-U relationship between strength of LRTC and oscillation amplitude, suggesting a breakdown of long-range dependence at high/low synchronization extremes, in line with recent computational models. Together, our findings offer a broader mechanistic framework for motivating research and clinical applications of NFB, encompassing disorders with perturbed LRTCs. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Spontaneous brain activity predicts learning ability of foreign sounds.

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Ventura-Campos, Noelia; Sanjuán, Ana; González, Julio; Palomar-García, María-Ángeles; Rodríguez-Pujadas, Aina; Sebastián-Gallés, Núria; Deco, Gustavo; Ávila, César

2013-05-29

Can learning capacity of the human brain be predicted from initial spontaneous functional connectivity (FC) between brain areas involved in a task? We combined task-related functional magnetic resonance imaging (fMRI) and resting-state fMRI (rs-fMRI) before and after training with a Hindi dental-retroflex nonnative contrast. Previous fMRI results were replicated, demonstrating that this learning recruited the left insula/frontal operculum and the left superior parietal lobe, among other areas of the brain. Crucially, resting-state FC (rs-FC) between these two areas at pretraining predicted individual differences in learning outcomes after distributed (Experiment 1) and intensive training (Experiment 2). Furthermore, this rs-FC was reduced at posttraining, a change that may also account for learning. Finally, resting-state network analyses showed that the mechanism underlying this reduction of rs-FC was mainly a transfer in intrinsic activity of the left frontal operculum/anterior insula from the left frontoparietal network to the salience network. Thus, rs-FC may contribute to predict learning ability and to understand how learning modifies the functioning of the brain. The discovery of this correspondence between initial spontaneous brain activity in task-related areas and posttraining performance opens new avenues to find predictors of learning capacities in the brain using task-related fMRI and rs-fMRI combined.

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

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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.

Bidirectional global spontaneous network activity precedes the canonical unidirectional circuit organization in the developing hippocampus.

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Shi, Yulin; Ikrar, Taruna; Olivas, Nicholas D; Xu, Xiangmin

2014-06-15

Spontaneous network activity is believed to sculpt developing neural circuits. Spontaneous giant depolarizing potentials (GDPs) were first identified with single-cell recordings from rat CA3 pyramidal neurons, but here we identify and characterize a large-scale spontaneous network activity we term global network activation (GNA) in the developing mouse hippocampal slices, which is measured macroscopically by fast voltage-sensitive dye imaging. The initiation and propagation of GNA in the mouse is largely GABA-independent and dominated by glutamatergic transmission via AMPA receptors. Despite the fact that signal propagation in the adult hippocampus is strongly unidirectional through the canonical trisynaptic circuit (dentate gyrus [DG] to CA3 to CA1), spontaneous GNA in the developing hippocampus originates in distal CA3 and propagates both forward to CA1 and backward to DG. Photostimulation-evoked GNA also shows prominent backward propagation in the developing hippocampus from CA3 to DG. Mouse GNA is strongly correlated to electrophysiological recordings of highly localized single-cell and local field potential events. Photostimulation mapping of neural circuitry demonstrates that the enhancement of local circuit connections to excitatory pyramidal neurons occurs over the same time course as GNA and reveals the underlying pathways accounting for GNA backward propagation from CA3 to DG. The disappearance of GNA coincides with a transition to the adult-like unidirectional circuit organization at about 2 weeks of age. Taken together, our findings strongly suggest a critical link between GNA activity and maturation of functional circuit connections in the developing hippocampus. Copyright © 2013 Wiley Periodicals, Inc.

Outcomes of Nulliparous Women with Spontaneous Labor Onset Admitted to Hospitals in Pre-active versus Active Labor

Science.gov (United States)

NEAL, Jeremy L.; LAMP, Jane M.; BUCK, Jacalyn S.; LOWE, Nancy K.; GILLESPIE, Shannon L.; RYAN, Sharon L.

2014-01-01

Introduction The timing of when a woman is admitted to the hospital for labor care following spontaneous contraction onset may be among the most important decisions that labor attendants make as it can influence care patterns and birth outcomes. The aims of this study were to estimate the percentage of low-risk, nulliparous women at term who are admitted to labor units prior to active labor and to evaluate the effects of the timing of admission (i.e., pre-active versus active labor) on labor interventions and mode of birth. Methods Obstetrics data from low-risk, nulliparous women with spontaneous labor onset at term gestation (N = 216) were merged from two prospective studies conducted at three large, Midwestern hospitals. Baseline characteristics, labor interventions, and outcomes were compared between groups using Fisher’s exact and Mann-Whitney U tests, as appropriate. Likelihoods for oxytocin augmentation, amniotomy, and cesarean delivery were assessed by logistic regression. Results Of the sample of 216 low-risk nulliparous women, 114 (52.8%) were admitted in pre-active labor and 102 (47.2%) were admitted in active labor. Women admitted in pre-active labor were more likely to undergo oxytocin augmentation (84.2% and 45.1%, respectively; odds ratio (OR) 6.5, 95% confidence interval (CI) 3.43–12.27) but not amniotomy (55.3% and 61.8%, respectively; OR 0.8, 95% CI 0.44–1.32) when compared to women admitted in active labor. The likelihood of cesarean delivery was higher for women admitted before active labor onset (15.8% and 6.9%, respectively; OR 2.6, 95% CI 1.02–6.37). Discussion Many low-risk nulliparous women with regular, spontaneous uterine contractions are admitted to labor units before active labor onset, which increases their likelihood of receiving oxytocin and being delivered via cesarean section. An evidence-based, standardized approach for labor admission decision-making is recommended to decrease inadvertent admissions of women in pre-active

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.

Altered spontaneous brain activity in patients with acute spinal cord injury revealed by resting-state functional MRI.

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Ling Zhu

Full Text Available Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI. However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo analysis based on resting-state functional magnetic resonance imaging.A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity.Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores.Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as potential biomarkers for

Effects of DISC1 Polymorphisms on Resting-State Spontaneous Neuronal Activity in the Early-Stage of Schizophrenia

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Ningzhi Gou

2018-05-01

Full Text Available Background: Localized abnormalities in the synchrony of spontaneous neuronal activity, measured with regional homogeneity (ReHo, has been consistently reported in patients with schizophrenia (SCZ and their unaffected siblings. To date, little is known about the genetic influences affecting the spontaneous neuronal activity in SCZ. DISC1, a strong susceptible gene for SCZ, has been implicated in neuronal excitability and synaptic function possibly associated with regional spontaneous neuronal activity. This study aimed to examine the effects of DISC1 variations on the regional spontaneous neuronal activity in SCZ.Methods: Resting-state fMRI data were obtained from 28 SCZ patients and 21 healthy controls (HC for ReHo analysis. Six single nucleotide polymorphisms (SNPs of DISC1 gene were genotyped using the PCR and direct sequencing.Results: Significant diagnosis × genotype interactions were noted for three SNPs (rs821616, rs821617, and rs2738880. For rs821617, the interactions were localized to the precuneus, basal ganglia and pre-/post-central regions. Significant interactive effects were identified at the temporal and post-central gyri for rs821616 (Ser704Cys and the inferior temporal gyrus for rs2738880. Furthermore, post-hoc analysis revealed that the DISC1 variations on these SNPs exerted different influences on ReHo between SCZ patients and HC.Conclusion: To our knowledge this is the first study to unpick the influence of DISC1 variations on spontaneous neuronal activity in SCZ; Given the emerging evidence that ReHo is a stable inheritable phenotype for schizophrenia, our findings suggest the DISC1 variations are possibly an inheritable source for the altered ReHo in this disorder.

Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

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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.

Steady-state hydrodynamic instabilities of active liquid crystals: hybrid lattice Boltzmann simulations.

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Marenduzzo, D; Orlandini, E; Cates, M E; Yeomans, J M

2007-09-01

We report hybrid lattice Boltzmann (HLB) simulations of the hydrodynamics of an active nematic liquid crystal sandwiched between confining walls with various anchoring conditions. We confirm the existence of a transition between a passive phase and an active phase, in which there is spontaneous flow in the steady state. This transition is attained for sufficiently "extensile" rods, in the case of flow-aligning liquid crystals, and for sufficiently "contractile" ones for flow-tumbling materials. In a quasi-one-dimensional geometry, deep in the active phase of flow-aligning materials, our simulations give evidence of hysteresis and history-dependent steady states, as well as of spontaneous banded flow. Flow-tumbling materials, in contrast, rearrange themselves so that only the two boundary layers flow in steady state. Two-dimensional simulations, with periodic boundary conditions, show additional instabilities, with the spontaneous flow appearing as patterns made up of "convection rolls." These results demonstrate a remarkable richness (including dependence on anchoring conditions) in the steady-state phase behavior of active materials, even in the absence of external forcing; they have no counterpart for passive nematics. Our HLB methodology, which combines lattice Boltzmann for momentum transport with a finite difference scheme for the order parameter dynamics, offers a robust and efficient method for probing the complex hydrodynamic behavior of active nematics.

Effects of dihydropyridines on tension and calcium-45 influx in isolated mesenteric resistance vessels from spontaneously hypertensive and normotensive rats

International Nuclear Information System (INIS)

Cauvin, C.; Hwang, O.; Yamamoto, M.; van Breemen, C.

1987-01-01

Contractile tension responses to norepinephrine and depolarizing potassium (80 mM K+), as well as calcium-45 influx stimulated by these agents, were studied in isolated mesenteric resistance vessels (each 100 microM internal diameter) from spontaneously hypertensive rats (SHRs) and from normotensive Wistar Kyoto rats (WKYs). Inhibitory effects of 2 dihydropyridine Ca++ antagonists, PN 200-110 (isradipine) and nisoldipine, on these parameters were also determined. Contractile responses to 80 mM K+ were inhibited by both Ca++ antagonists with the same potency and efficacy in SHR compared with WKY vessels (PN 200-110 IC50 = 2.8 +/- 1.3 X 10(-8) M in SHRs and 2.5 +/- 1.5 X 10(-8) M in WKYs; nisoldipine IC50 = 1.1 +/- 0.4 X 10(-8) M in SHRs and 1.2 +/- 0.9 X 10(-8) M in WKYs). However, contractile responses to norepinephrine (10(-4) M) were inhibited less potently by nisoldipine in SHR vessels (IC50 = 2.2 +/- 0.3 X 10(-9) M) compared with WKY vessels (IC50 = 1.6 +/- 0.6 X 10(-10) M). Similarly, PN 200-110 tended to be less (but not significantly less) potent in SHR vessels (IC50 = 3.3 +/- 1.8 X 10(-8) M) than in WKY vessels (IC50 = 3.4 +/- 0.9 X 10(-9) M); its efficacy was significantly depressed in the SHR vessels (by approximately 20%). When norepinephrine-stimulated calcium-45 influx was determined in the presence of these Ca++ antagonists, a similar profile emerged with respect to a comparison of SHR and WKY vessels. These results support a previously hypothesized alteration in receptor-activated Ca++ influx pathways in SHR mesenteric resistance vessels

Dorsomedial prefontal cortex supports spontaneous thinking per se.

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Raij, T T; Riekki, T J J

2017-06-01

Spontaneous thinking, an action to produce, consider, integrate, and reason through mental representations, is central to our daily experience and has been suggested to serve crucial adaptive purposes. Such thinking occurs among other experiences during mind wandering that is associated with activation of the default mode network among other brain circuitries. Whether and how such brain activation is linked to the experience of spontaneous thinking per se remains poorly known. We studied 51 healthy subjects using a comprehensive experience-sampling paradigm during 3T functional magnetic resonance imaging. In comparison with fixation, the experiences of spontaneous thinking and spontaneous perception were related to activation of wide-spread brain circuitries, including the cortical midline structures, the anterior cingulate cortex and the visual cortex. In direct comparison of the spontaneous thinking versus spontaneous perception, activation was observed in the anterior dorsomedial prefrontal cortex. Modality congruence of spontaneous-experience-related brain activation was suggested by several findings, including association of the lingual gyrus with visual in comparison with non-verbal-non-visual thinking. In the context of current literature, these findings suggest that the cortical midline structures are involved in the integrative core substrate of spontaneous thinking that is coupled with other brain systems depending on the characteristics of thinking. Furthermore, involvement of the anterior dorsomedial prefrontal cortex suggests the control of high-order abstract functions to characterize spontaneous thinking per se. Hum Brain Mapp 38:3277-3288, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

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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.

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...

Spontaneous Brain Activity Did Not Show the Effect of Violent Video Games on Aggression: A Resting-State fMRI Study

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Pan, Wei; Gao, Xuemei; Shi, Shuo; Liu, Fuqu; Li, Chao

2018-01-01

A great many of empirical researches have proved that longtime exposure to violent video game can lead to a series of negative effects. Although research has focused on the neural basis of the correlation between violent video game and aggression, little is known whether the spontaneous brain activity is associated with violent video game exposure. To address this question, we measured the spontaneous brain activity using resting-state functional magnetic resonance imaging (fMRI). We used the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) to quantify spontaneous brain activity. The results showed there is no significant difference in ALFF, or fALFF, between violent video game group and the control part, indicating that long time exposure to violent video games won’t significantly influence spontaneous brain activity, especially the core brain regions such as execution control, moral judgment and short-term memory. This implies the adverse impact of violent video games is exaggerated. PMID:29375416

Spontaneous Brain Activity Did Not Show the Effect of Violent Video Games on Aggression: A Resting-State fMRI Study.

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Pan, Wei; Gao, Xuemei; Shi, Shuo; Liu, Fuqu; Li, Chao

2017-01-01

A great many of empirical researches have proved that longtime exposure to violent video game can lead to a series of negative effects. Although research has focused on the neural basis of the correlation between violent video game and aggression, little is known whether the spontaneous brain activity is associated with violent video game exposure. To address this question, we measured the spontaneous brain activity using resting-state functional magnetic resonance imaging (fMRI). We used the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) to quantify spontaneous brain activity. The results showed there is no significant difference in ALFF, or fALFF, between violent video game group and the control part, indicating that long time exposure to violent video games won't significantly influence spontaneous brain activity, especially the core brain regions such as execution control, moral judgment and short-term memory. This implies the adverse impact of violent video games is exaggerated.

Spontaneous Brain Activity Did Not Show the Effect of Violent Video Games on Aggression: A Resting-State fMRI Study

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Wei Pan

2018-01-01

Full Text Available A great many of empirical researches have proved that longtime exposure to violent video game can lead to a series of negative effects. Although research has focused on the neural basis of the correlation between violent video game and aggression, little is known whether the spontaneous brain activity is associated with violent video game exposure. To address this question, we measured the spontaneous brain activity using resting-state functional magnetic resonance imaging (fMRI. We used the amplitude of low-frequency fluctuations (ALFF and fractional ALFF (fALFF to quantify spontaneous brain activity. The results showed there is no significant difference in ALFF, or fALFF, between violent video game group and the control part, indicating that long time exposure to violent video games won’t significantly influence spontaneous brain activity, especially the core brain regions such as execution control, moral judgment and short-term memory. This implies the adverse impact of violent video games is exaggerated.

Slow-light enhancement of spontaneous emission in active photonic crystal waveguides

DEFF Research Database (Denmark)

Ek, Sara; Chen, Yaohui; Semenova, Elizaveta

2012-01-01

Photonic crystal defect waveguides with embedded active layers containing single or multiple quantum wells or quantum dots have been fabricated. Spontaneous emission spectra are enhanced close to the bandedge, consistently with the enhancement of gain by slow light effects. These are promising...... results for future compact devices for terabit/s communication, such as miniaturised semiconductor optical amplifiers and mode-locked lasers....

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

Prophage spontaneous activation promotes DNA release enhancing biofilm formation in Streptococcus pneumoniae.

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Margarida Carrolo

Full Text Available Streptococcus pneumoniae (pneumococcus is able to form biofilms in vivo and previous studies propose that pneumococcal biofilms play a relevant role both in colonization and infection. Additionally, pneumococci recovered from human infections are characterized by a high prevalence of lysogenic bacteriophages (phages residing quiescently in their host chromosome. We investigated a possible link between lysogeny and biofilm formation. Considering that extracellular DNA (eDNA is a key factor in the biofilm matrix, we reasoned that prophage spontaneous activation with the consequent bacterial host lysis could provide a source of eDNA, enhancing pneumococcal biofilm development. Monitoring biofilm growth of lysogenic and non-lysogenic pneumococcal strains indicated that phage-infected bacteria are more proficient at forming biofilms, that is their biofilms are characterized by a higher biomass and cell viability. The presence of phage particles throughout the lysogenic strains biofilm development implicated prophage spontaneous induction in this effect. Analysis of lysogens deficient for phage lysin and the bacterial major autolysin revealed that the absence of either lytic activity impaired biofilm development and the addition of DNA restored the ability of mutant strains to form robust biofilms. These findings establish that limited phage-mediated host lysis of a fraction of the bacterial population, due to spontaneous phage induction, constitutes an important source of eDNA for the S. pneumoniae biofilm matrix and that this localized release of eDNA favors biofilm formation by the remaining bacterial population.

Brain modularity controls the critical behavior of spontaneous activity.

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Russo, R; Herrmann, H J; de Arcangelis, L

2014-03-13

The human brain exhibits a complex structure made of scale-free highly connected modules loosely interconnected by weaker links to form a small-world network. These features appear in healthy patients whereas neurological diseases often modify this structure. An important open question concerns the role of brain modularity in sustaining the critical behaviour of spontaneous activity. Here we analyse the neuronal activity of a model, successful in reproducing on non-modular networks the scaling behaviour observed in experimental data, on a modular network implementing the main statistical features measured in human brain. We show that on a modular network, regardless the strength of the synaptic connections or the modular size and number, activity is never fully scale-free. Neuronal avalanches can invade different modules which results in an activity depression, hindering further avalanche propagation. Critical behaviour is solely recovered if inter-module connections are added, modifying the modular into a more random structure.

Spontaneous recombinase activity of Cre-ERT2 in vivo.

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Kristianto, Jasmin; Johnson, Michael G; Zastrow, Ryley K; Radcliff, Abigail B; Blank, Robert D

2017-06-01

Inducible Cre-ERT recombinase technology is widely used for gene targeting studies. The second generation of inducible Cre-ERT recombinase, hemizygous B6.129S-Tg(UBC-cre/ERT2)1Ejb/J (hereafter abbreviated as Cre-ERT2), a fusion of a mutated estrogen receptor and Cre recombinase, was engineered to be more efficient and specific than the original Cre-ERT. The putative mechanism of selective Cre-mediated recombination is Cre sequestration in the cytoplasm in the basal state with translocation to the nucleus only in the presence of tamoxifen. We utilized both a reporter mouse (B6.129 (Cg)-Gt(ROSA)26Sor tm4(ACTB-tdTomato,-EGFP)Luo /J) and endothelin converting enzyme-1 floxed transgenic mouse line to evaluate Cre-ERT2 activity. We observed spontaneous Cre activity in both settings. Unintended Cre activity is a confounding factor that has a potentially large impact on data interpretation. Thus, it is important to consider background Cre activity in experimental design.

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

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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.

Neural activation and memory for natural scenes: Explicit and spontaneous retrieval.

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Weymar, Mathias; Bradley, Margaret M; Sege, Christopher T; Lang, Peter J

2018-05-06

Stimulus repetition elicits either enhancement or suppression in neural activity, and a recent fMRI meta-analysis of repetition effects for visual stimuli (Kim, 2017) reported cross-stimulus repetition enhancement in medial and lateral parietal cortex, as well as regions of prefrontal, temporal, and posterior cingulate cortex. Repetition enhancement was assessed here for repeated and novel scenes presented in the context of either an explicit episodic recognition task or an implicit judgment task, in order to study the role of spontaneous retrieval of episodic memories. Regardless of whether episodic memory was explicitly probed or not, repetition enhancement was found in medial posterior parietal (precuneus/cuneus), lateral parietal cortex (angular gyrus), as well as in medial prefrontal cortex (frontopolar), which did not differ by task. Enhancement effects in the posterior cingulate cortex were significantly larger during explicit compared to implicit task, primarily due to a lack of functional activity for new scenes. Taken together, the data are consistent with an interpretation that medial and (ventral) lateral parietal cortex are associated with spontaneous episodic retrieval, whereas posterior cingulate cortical regions may reflect task or decision processes. © 2018 Society for Psychophysiological Research.

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

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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

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

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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

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

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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

On nature of spontaneous elongation of polymers preliminarily stretched in adsorption-active media under irradiation

International Nuclear Information System (INIS)

Sinevich, E.A.; Prazdnichnyj, A.M.; Tikhomirov, V.S.; Bakeev, N.F.

1989-01-01

The nature of the spontaneous elongation under irradiation with fast electrons of polymers preliminary stretched in adsorption-active media has been studied. This effect is related with radiation-induced heating of microporous polymer samples. Its manifestation in amorphous PETP requires the presence of crazes having well developed microfibrillar structure. The spontaneous elongation effect is shown to be a result of crystallization of partially oriented material in transitional regions relating the oriented material of microfibrils inside crazes with nonstrained polymer between them

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

The effects of space flight on the contractile apparatus of antigravity muscles: implications for aging and deconditioning

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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.

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.

To Take the Stairs or Not to Take the Stairs? Employing the Reflective–Impulsive Model to Predict Spontaneous Physical Activity

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Marcos Daou

2017-09-01

Full Text Available The reflective–impulsive model (RIM has been employed to explain various health behaviors. The present study used RIM to predict a spontaneous physical activity behavior. Specifically, 107 participants (75 females; Mage = 20.6 years, SD = 1.92 years completed measures of (1 reflections about spontaneous physical activity, as indexed by self-report questionnaire; (2 impulse toward physical activity, as indexed by the manikin task; and (3 (state self-control, as indexed by the Stroop task. The dependent variable was whether participants took the stairs or the elevator to the study laboratory. Results revealed reflections toward spontaneous physical activity positively predicted stair-taking. Further, a significant impulse toward physical activity × self-control interaction was observed. This interaction revealed that participants with high self-control who had a high impulse toward PA were more likely to take the stairs than their counterparts with a low impulse toward PA, whereas the opposite was the case for participants with low self-control. However, the impulse × self-control interaction was not significant when employing a self-report measure of trait self-control. Thus, RIM may be a good framework with which to consider spontaneous physical activity, but careful consideration must be given when examining variables within RIM (e.g., the boundary condition of self-control.

Role of contractile prostaglandins and Rho-kinase in growth factor-induced airway smooth muscle contraction

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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

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

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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.

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

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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.

EFFECT OF HYDROGEN SULFIDE ON ATRIUM CONTRACTILITY IN CONTROL AND DIABETHIC MICE

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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.

[Effects of reversing the feeding cycle and the light period on the spontaneous activity of the rat (author's transl)].

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Ticca, M

1976-01-01

The amount and the circadian distribution of spontaneous activity in the rat are influenced by a number of factors, whose importance and interrelationships are still deeply discussed. In order to check the reliability of previous studies about the effects of meal-eating on the spontaneous activity (wheel running) of rats of our Sprague-Dawley strain, the adjustment to the modifications of the normal day-night cycle and of the normal nocturnal feeding rhythm have been controlled. Reversing the normal light and dark periods caused the rats, after a 24 hours period, to lower and to irregularly distribute their spontaneous activity. Rats shifted their pattern of maximal activity by 12 hours in the new period of darkness in about five days, and showed to have completely fixed the new reversed running habit. Also feeding habits changed in a similar way, but more slowly. The levels of mean daily activity did not change. In a second experiment, rats, received food during light hours, and were deprived during dark hours. Their activity increased considerably and irregularly during dark hours, while a very slight rise of wheel running was shown during light hours. Body weight gain and food consumption were similar to those of the control group. These results slightly differ from those obtained using other rat strains, and are an interesting example of reinforcement of a spontaneous behavior resulting more from the light-dark cycle than from cues provided by food deprivation.

L-arginine fails to prevent ventricular remodeling and heart failure in the spontaneously hypertensive rat.

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Brooks, Wesley W; Conrad, Chester H; Robinson, Kathleen G; Colucci, Wilson S; Bing, Oscar H L

2009-02-01

The effects of long-term oral administration of L-arginine, a substrate for nitric oxide (NO) production, on left ventricular (LV) remodeling, myocardial function and the prevention of heart failure (HF) was compared to the angiotensin-converting enzyme (ACE) inhibitor captopril in a rat model of hypertensive HF (aged spontaneously hypertensive rat (SHR)). SHRs and age-matched normotensive Wistar-Kyoto (WKY) rats were assigned to either no treatment, treatment with L-arginine (7.5 g/l in drinking water) or captopril (1 g/l in drinking water) beginning at 14 months of age, a time when SHRs exhibit stable compensated hypertrophy with no hemodynamic impairment; animals were studied at 23 months of age or at the time of HF. In untreated SHR, relative to WKY, there was significant LV hypertrophy, myocardial fibrosis, and isolated LV muscle performance and response to isoproterenol (ISO) were depressed; and, 7 of 10 SHRs developed HF. Captopril administration to six SHRs attenuated hypertrophy and prevented impaired inotropic responsiveness to ISO, contractile dysfunction, fibrosis, increased passive stiffness, and HF. In contrast, L-arginine administration to SHR increased LV hypertrophy and myocardial fibrosis while cardiac performance was depressed; and 7 of 9 SHRs developed HF. In WKY, L-arginine treatment but not captopril resulted in increased LV weight and the contractile response to ISO was blunted. Neither L-arginine nor captopril treatment of WKY changed fibrosis and HF did not occur. These data demonstrate that in contrast to captopril, long-term treatment with L-arginine exacerbates age-related cardiac hypertrophy, fibrosis, and did not prevent contractile dysfunction or the development of HF in aging SHR.

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

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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

Spontaneous membrane formation and self-encapsulation of active rods in an inhomogeneous motility field

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Grauer, J.; Löwen, H.; Janssen, L.M.C.

2018-01-01

We study the collective dynamics of self-propelled rods in an inhomogeneous motility field. At the interface between two regions of constant but different motility, a smectic rod layer is spontaneously created through aligning interactions between the active rods, reminiscent of an artificial,

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

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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.

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.

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

Contractility Dispersion in Long QT Syndrome

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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.

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

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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.

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

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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.

Pharmacological characterization and chemical fractionation of a liposterolic extract of saw palmetto (Serenoa repens): effects on rat prostate contractility.

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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.

General theory for spontaneous emission in active dielectric microstructures: Example of a fiber amplifier

DEFF Research Database (Denmark)

Søndergaard, Thomas; Tromborg, Bjarne

2001-01-01

A model for spontaneous emission in active dielectric microstructures is given in terms of the classical electric field Green's tensor and the quantum-mechanical operators for the generating currents. A formalism is given for calculating the Green's tensor, which does not rely on the existence...

Inhibition of CYP2E1 attenuates chronic alcohol intake-induced myocardial contractile dysfunction and apoptosis.

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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.

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

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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.

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

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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

Regional gastrointestinal contractility parameters using the wireless motility capsule

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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...

Brain activity for spontaneous and explicit mentalizing in adults with autism spectrum disorder: An fMRI study

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Annabel D. Nijhof

Full Text Available The socio-communicative difficulties of individuals with autism spectrum disorder (ASD are hypothesized to be caused by a specific deficit in the ability to represent one's own and others' mental states, referred to as Theory of Mind or mentalizing. However, many individuals with ASD show successful performance on explicit measures of mentalizing, and for this reason, the deficit is thought to be better captured by measures of spontaneous mentalizing. While there is initial behavioral support for this hypothesis, spontaneous mentalizing in ASD has not yet been studied at the neural level. Recent findings indicate involvement of the right temporoparietal junction (rTPJ in both explicit and spontaneous mentalizing (Bardi et al., 2016. In the current study, we investigated brain activation during explicit and spontaneous mentalizing in adults with ASD by means of fMRI. Based on our hypothesis of a core mentalizing deficit in ASD, decreased rTPJ activity was expected for both forms of mentalizing. A group of 24 adults with ASD and 21 neurotypical controls carried out a spontaneous and an explicit version of the same mentalizing task. They watched videos in which both they themselves and another agent formed a belief about the location of an object (belief formation phase. Only in the explicit task version participants were instructed to report the agent's belief on some trials. At the behavioral level, no group differences were revealed in either of the task versions. A planned region-of-interest analysis of the rTPJ showed that this region was more active for false- than for true-belief formation, independent of task version, especially when the agent's belief had a positive content (when the agent was expecting the object. This effect of belief was absent in adults with ASD. A whole-brain analysis revealed reduced activation in the anterior middle temporal pole in ASD for false - versus true-belief trials, independent of task version. Our findings

Spontaneous Activity Associated with Delusions of Schizophrenia in the Left Medial Superior Frontal Gyrus: A Resting-State fMRI Study.

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Bin Gao

Full Text Available Delusions of schizophrenia have been found to be associated with alterations of some brain regions in structure and task-induced activation. However, the relationship between spontaneously occurring symptoms and spontaneous brain activity remains unclear. In the current study, 14 schizophrenic patients with delusions and 14 healthy controls underwent a resting-state functional magnetic resonance imaging (RS-fMRI scan. Patients with delusions of schizophrenia patients were rated with Positive and Negative Syndrome Scale (PANSS and Characteristics of Delusional Rating Scale (CDRS. Regional homogeneity (ReHo was calculated to measure the local synchronization of the spontaneous activity in a voxel-wise way. A two-sample t-test showed that ReHo of the right anterior cingulate gyrus and left medial superior frontal gyrus were higher in patients, and ReHo of the left superior occipital gyrus was lower, compared to healthy controls. Further, among patients, correlation analysis showed a significant difference between delusion scores of CRDS and ReHo of brain regions. ReHo of the left medial superior frontal gyrus was negatively correlated with patients' CDRS scores but not with delusional PANSS scores. These results suggested that altered local synchronization of spontaneous brain activity may be related to the pathophysiology of delusion in schizophrenia.

Spontaneous Activity Associated with Delusions of Schizophrenia in the Left Medial Superior Frontal Gyrus: A Resting-State fMRI Study.

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Gao, Bin; Wang, Yiquan; Liu, Weibo; Chen, Zhiyu; Zhou, Heshan; Yang, Jinyu; Cohen, Zachary; Zhu, Yihong; Zang, Yufeng

2015-01-01

Delusions of schizophrenia have been found to be associated with alterations of some brain regions in structure and task-induced activation. However, the relationship between spontaneously occurring symptoms and spontaneous brain activity remains unclear. In the current study, 14 schizophrenic patients with delusions and 14 healthy controls underwent a resting-state functional magnetic resonance imaging (RS-fMRI) scan. Patients with delusions of schizophrenia patients were rated with Positive and Negative Syndrome Scale (PANSS) and Characteristics of Delusional Rating Scale (CDRS). Regional homogeneity (ReHo) was calculated to measure the local synchronization of the spontaneous activity in a voxel-wise way. A two-sample t-test showed that ReHo of the right anterior cingulate gyrus and left medial superior frontal gyrus were higher in patients, and ReHo of the left superior occipital gyrus was lower, compared to healthy controls. Further, among patients, correlation analysis showed a significant difference between delusion scores of CRDS and ReHo of brain regions. ReHo of the left medial superior frontal gyrus was negatively correlated with patients' CDRS scores but not with delusional PANSS scores. These results suggested that altered local synchronization of spontaneous brain activity may be related to the pathophysiology of delusion in schizophrenia.

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

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

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.

Auditory Tones and Foot-Shock Recapitulate Spontaneous Sub-Threshold Activity in Basolateral Amygdala Principal Neurons and Interneurons.

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François Windels

Full Text Available In quiescent states such as anesthesia and slow wave sleep, cortical networks show slow rhythmic synchronized activity. In sensory cortices this rhythmic activity shows a stereotypical pattern that is recapitulated by stimulation of the appropriate sensory modality. The amygdala receives sensory input from a variety of sources, and in anesthetized animals, neurons in the basolateral amygdala (BLA show slow rhythmic synchronized activity. Extracellular field potential recordings show that these oscillations are synchronized with sensory cortex and the thalamus, with both the thalamus and cortex leading the BLA. Using whole-cell recording in vivo we show that the membrane potential of principal neurons spontaneously oscillates between up- and down-states. Footshock and auditory stimulation delivered during down-states evokes an up-state that fully recapitulates those occurring spontaneously. These results suggest that neurons in the BLA receive convergent input from networks of cortical neurons with slow oscillatory activity and that somatosensory and auditory stimulation can trigger activity in these same networks.

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

Science.gov (United States)

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

2015-01-01

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

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.

Spontaneous Brain Activity Did Not Show the Effect of Violent Video Games on Aggression: A Resting-State fMRI Study

OpenAIRE

Wei Pan; Wei Pan; Wei Pan; Xuemei Gao; Shuo Shi; Fuqu Liu; Chao Li

2018-01-01

A great many of empirical researches have proved that longtime exposure to violent video game can lead to a series of negative effects. Although research has focused on the neural basis of the correlation between violent video game and aggression, little is known whether the spontaneous brain activity is associated with violent video game exposure. To address this question, we measured the spontaneous brain activity using resting-state functional magnetic resonance imaging (fMRI). We used the...

Effect of a non lethal whole-body gamma irradiation on the spontaneous and evoked electroencephalographic activities of the adult rabbit

International Nuclear Information System (INIS)

Court, L.

1969-01-01

The whole of the experimental methods described (animal preparation, achievement of a precise physiological technique, dosimetry, biological information processing) allowed us to follow the changes for 15 days in the spontaneous and evoked electroencephalogram activities of rabbits submitted to a non-lethal 400 rads whole-body gamma-irradiation. Behavioural troubles, changes in the arousal state and the spontaneous electrical activity of the neo-cortex and hippocampus were noticed constantly together with an enhanced cortical excitability, and the appearance of elements of the paroxystic series sometimes in contrast with a general decrease in amplitude. After a visual stimulus the general morphology of evoked activities at the level of the primary visual areas and hippocampus was unchanged, but enhanced latencies and delays, less systematic modifications in amplitudes seemed to show out a direct effect of radiations on the nervous system and sensorial activities; these troubles seemed to occur independently from the basic electrical activity. As a whole, the changes observed were usually transitory and varied with each individual. Finally an assumption is made to explain the mechanism of arousal troubles and the general evolution of spontaneous electrical activity in the brain. (author) [fr

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

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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

Reconstruction of human brain spontaneous activity based on frequency-pattern analysis of magnetoencephalography data

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Rodolfo R Llinas

2015-10-01

Full Text Available A new method for the analysis and localization of brain activity has been developed, based on multichannel magnetic field recordings, over minutes, superimposed on the MRI of the individual. Here, a high resolution Fourier Transform is obtained over the entire recording period, leading to a detailed multi-frequency spectrum. Further analysis implements a total decomposition of the frequency components into functionally invariant entities, each having an invariant field pattern localizable in recording space. The method, addressed as functional tomography, makes it possible to find the distribution of magnetic field sources in space. Here, the method is applied to the analysis of simulated data, to oscillating signals activating a physical current dipoles phantom, and to recordings of spontaneous brain activity in ten healthy adults. In the analysis of simulated data, 61 dipoles are localized with 0.7 mm precision. Concerning the physical phantom the method is able to localize three simultaneously activated current dipoles with 1 mm precision. Spatial resolution 3 mm was attained when localizing spontaneous alpha rhythm activity in ten healthy adults, where the alpha peak was specified for each subject individually. Co-registration of the functional tomograms with each subject’s head MRI localized alpha range activity to the occipital and/or posterior parietal brain region. This is the first application of this new functional tomography to human brain activity. The method successfully provides an overall view of brain electrical activity, a detailed spectral description and, combined with MRI, the localization of sources in anatomical brain space.

Reconstruction of human brain spontaneous activity based on frequency-pattern analysis of magnetoencephalography data

Science.gov (United States)

Llinás, Rodolfo R.; Ustinin, Mikhail N.; Rykunov, Stanislav D.; Boyko, Anna I.; Sychev, Vyacheslav V.; Walton, Kerry D.; Rabello, Guilherme M.; Garcia, John

2015-01-01

A new method for the analysis and localization of brain activity has been developed, based on multichannel magnetic field recordings, over minutes, superimposed on the MRI of the individual. Here, a high resolution Fourier Transform is obtained over the entire recording period, leading to a detailed multi-frequency spectrum. Further analysis implements a total decomposition of the frequency components into functionally invariant entities, each having an invariant field pattern localizable in recording space. The method, addressed as functional tomography, makes it possible to find the distribution of magnetic field sources in space. Here, the method is applied to the analysis of simulated data, to oscillating signals activating a physical current dipoles phantom, and to recordings of spontaneous brain activity in 10 healthy adults. In the analysis of simulated data, 61 dipoles are localized with 0.7 mm precision. Concerning the physical phantom the method is able to localize three simultaneously activated current dipoles with 1 mm precision. Spatial resolution 3 mm was attained when localizing spontaneous alpha rhythm activity in 10 healthy adults, where the alpha peak was specified for each subject individually. Co-registration of the functional tomograms with each subject's head MRI localized alpha range activity to the occipital and/or posterior parietal brain region. This is the first application of this new functional tomography to human brain activity. The method successfully provides an overall view of brain electrical activity, a detailed spectral description and, combined with MRI, the localization of sources in anatomical brain space. PMID:26528119

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.

Inhibition of PKC-dependent extracellular Ca{sup 2+} entry contributes to the depression of contractile activity in long-term pressure-overloaded endothelium-denuded rat aortas

Energy Technology Data Exchange (ETDEWEB)

Padilla, J.; López, R.M.; López, P.; Castillo, M.C.; Querejeta, E.; Ruiz, A.; Castillo, E.F. [Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, DF (Mexico)

2014-08-01

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{sub 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{sub 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{sup 2+}-free medium or the subsequent tonic constrictions induced by the addition of Ca{sup 2+} in the absence of agonists. Thus, the contractions induced by Ca{sup 2+} release from intracellular stores and Ca{sup 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{sup 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{sup 2+}. Neither levels of angiotensins nor of AT{sub 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{sup 2+} entry.

Generation of Functional Cardiomyocytes from Efficiently Generated Human iPSCs and a Novel Method of Measuring Contractility.

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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.

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.

The activity of spontaneous action potentials in developing hair cells is regulated by Ca(2+-dependence of a transient K+ current.

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Snezana Levic

Full Text Available Spontaneous action potentials have been described in developing sensory systems. These rhythmic activities may have instructional roles for the functional development of synaptic connections. The importance of spontaneous action potentials in the developing auditory system is underpinned by the stark correlation between the time of auditory system functional maturity, and the cessation of spontaneous action potentials. A prominent K(+ current that regulates patterning of action potentials is I(A. This current undergoes marked changes in expression during chicken hair cell development. Although the properties of I(A are not normally classified as Ca(2+-dependent, we demonstrate that throughout the development of chicken hair cells, I(A is greatly reduced by acute alterations of intracellular Ca(2+. As determinants of spike timing and firing frequency, intracellular Ca(2+ buffers shift the activation and inactivation properties of the current to more positive potentials. Our findings provide evidence to demonstrate that the kinetics and functional expression of I(A are tightly regulated by intracellular Ca(2+. Such feedback mechanism between the functional expression of I(A and intracellular Ca(2+ may shape the activity of spontaneous action potentials, thus potentially sculpting synaptic connections in an activity-dependent manner in the developing cochlea.

Urokinase vs Tissue-Type Plasminogen Activator for Thrombolytic Evacuation of Spontaneous Intracerebral Hemorrhage in Basal Ganglia

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Yuqian Li

2017-08-01

Full Text Available Spontaneous intracerebral hemorrhage (ICH is a devastating form of stroke, which leads to a high rate of mortality and poor neurological outcomes worldwide. Thrombolytic evacuation with urokinase-type plasminogen activator (uPA or tissue-type plasminogen activator (tPA has been showed to be a hopeful treatment for ICH. However, to the best of our knowledge, no clinical trials were reported to compare the efficacy and safety of these two fibrinolytics administrated following minimally invasive stereotactic puncture (MISP in patients with spontaneous basal ganglia ICH. Therefore, the authors intended here to evaluate the differential impact of uPA and tPA in a retrospective study. In the present study, a total of 86 patients with spontaneous ICH in basal ganglia using MISP received either uPA (uPA group, n = 45 or tPA (tPA group, n = 41, respectively. The clinical baseline characteristics prior to the operation were collected. In addition, therapeutic responses were assessed by the short-term outcomes within 30 days postoperation, as well as long-term outcomes at 1 year postoperation. Our findings showed that, in comparison with tPA, uPA was able to better promote hematoma evacuation and ameliorate perihematomal edema, but the differences were not statistically significant. Moreover, the long-term functional outcomes of both groups were similar, with no statistical difference. In conclusion, these results provide evidence supporting that uPA and tPA are similar in the efficacy and safety for thrombolytic evacuation in combination with MISP in patients with spontaneous basal ganglia ICH.

Circadian and individual variations in duration of spontaneous activity among ankle muscles of the cat

NARCIS (Netherlands)

Hensbergen, E; Kernell, D

This article concerns the spontaneous motor behavior of cat hindlimb muscles and muscle regions using 24-h electromyographic (EMG) recordings. Previously, we found marked differences in average daily "duty time" (i.e., the percentage of total sampling time filled with EMG activity) between different

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.

Alpha-Band Activity Reveals Spontaneous Representations of Spatial Position in Visual Working Memory.

Science.gov (United States)

Foster, Joshua J; Bsales, Emma M; Jaffe, Russell J; Awh, Edward

2017-10-23

An emerging view suggests that spatial position is an integral component of working memory (WM), such that non-spatial features are bound to locations regardless of whether space is relevant [1, 2]. For instance, past work has shown that stimulus position is spontaneously remembered when non-spatial features are stored. Item recognition is enhanced when memoranda appear at the same location where they were encoded [3-5], and accessing non-spatial information elicits shifts of spatial attention to the original position of the stimulus [6, 7]. However, these findings do not establish that a persistent, active representation of stimulus position is maintained in WM because similar effects have also been documented following storage in long-term memory [8, 9]. Here we show that the spatial position of the memorandum is actively coded by persistent neural activity during a non-spatial WM task. We used a spatial encoding model in conjunction with electroencephalogram (EEG) measurements of oscillatory alpha-band (8-12 Hz) activity to track active representations of spatial position. The position of the stimulus varied trial to trial but was wholly irrelevant to the tasks. We nevertheless observed active neural representations of the original stimulus position that persisted throughout the retention interval. Further experiments established that these spatial representations are dependent on the volitional storage of non-spatial features rather than being a lingering effect of sensory energy or initial encoding demands. These findings provide strong evidence that online spatial representations are spontaneously maintained in WM-regardless of task relevance-during the storage of non-spatial features. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

The actions of isoprenaline and mirabegron in the isolated whole rat and guinea pig bladder.

Science.gov (United States)

Persyn, Sara; De Wachter, Stefan; Wyndaele, Jean-Jacques; Eastham, Jane; Gillespie, James

2016-07-01

β3-adrenoceptor agonists influence overactive bladder in humans and animal models. However, data is emerging that the mode of action of these drugs is complex. The present study explored the actions of the β3-adrenergic agonist mirabegron and the non-selective agonist isoprenaline on the contractile systems in the rat and guinea pig bladder. Intravesical pressure was measured in isolated whole bladders from female adult animals. In both species spontaneous contractile activity was observed. The muscarinic agonist arecaidine produced complex responses consisting of an initial transient pressure rise followed by complex phasic activity. Three contractile elements were identified: intrinsic micro-contractile activity, initial transient response and steady state phasic activity. The intrinsic and steady state activity could be further divided into a baseline pressure with superimposed phasic activity. The effects of isoprenaline and mirabegron were investigated on these elements. In the rat, the micro-contractile activity could be completely inhibited by isoprenaline (full agonist). The arecaidine-induced initial and steady state baseline pressures were partially reduced, while the phasic activity was little affected. In the guinea pig, both the arecaidine-induced baseline pressure and the phasic activity were affected by isoprenaline. Mirabegron didn't produce significant inhibitory effects in any of the contractile elements in either species. These results show that complex contractile systems operate in the rat and guinea pig bladder that can be modulated by β1/β2-adrenoceptor mechanisms. No evidence was obtained for any β3-dependent regulation of contraction. These data support similar data in humans. Therefore the primary site of therapeutic action of β3-adrenergic agonists remains unknown. Copyright © 2016 Elsevier B.V. All rights reserved.

Reproduction of overall spontaneous pain pattern by manual stimulation of active myofascial trigger points in fibromyalgia patients

DEFF Research Database (Denmark)

Ge, Hong-You; Wang, Ying; Fernández-de-las-Peñas, César

2011-01-01

It has previously been reported that local and referred pain from active myofascial trigger points (MTPs) in the neck and shoulder region contribute to fibromyalgia (FM) pain and that the pain pattern induced from active MTPs can reproduce parts of the spontaneous clinical FM pain pattern. The cu...

Bilateral Changes of Spontaneous Activity Within the Central Auditory Pathway Upon Chronic Unilateral Intracochlear Electrical Stimulation.

Science.gov (United States)

Basta, Dietmar; Götze, Romy; Gröschel, Moritz; Jansen, Sebastian; Janke, Oliver; Tzschentke, Barbara; Boyle, Patrick; Ernst, Arne

2015-12-01

In recent years, cochlear implants have been applied successfully for the treatment of unilateral hearing loss with quite surprising benefit. One reason for this successful treatment, including the relief from tinnitus, could be the normalization of spontaneous activity in the central auditory pathway because of the electrical stimulation. The present study, therefore, investigated at a cellular level, the effect of a unilateral chronic intracochlear stimulation on key structures of the central auditory pathway. Normal-hearing guinea pigs were mechanically single-sided deafened through a standard HiFocus1j electrode array (on a HiRes 90k cochlear implant) being inserted into the first turn of the cochlea. Four to five electrode contacts could be used for the stimulation. Six weeks after surgery, the speech processor (Auria) was fitted, based on tNRI values and mounted on the animal's back. The two experimental groups were stimulated 16 hours per day for 90 days, using a HiRes strategy based on different stimulation rates (low rate (275 pps/ch), high rate (5000 pps/ch)). The results were compared with those of unilateral deafened controls (implanted but not stimulated), as well as between the treatment groups. All animals experienced a standardized free field auditory environment. The low-rate group showed a significantly lower average spontaneous activity bilaterally in the dorsal cochlear nucleus and the medial geniculate body than the controls. However, there was no difference in the inferior colliculus and the primary auditory cortex. Spontaneous activity of the high-rate group was also reduced bilaterally in the dorsal cochlear nucleus and in the primary auditory cortex. No differences could be observed between the high-rate group and the controls in the contra-lateral inferior colliculus and medial geniculate body. The high-rate group showed bilaterally a higher activity in the CN and the MGB compared with the low-rate group, whereas in the IC and in the

Spontaneously emerging cortical representations of visual attributes

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Kenet, Tal; Bibitchkov, Dmitri; Tsodyks, Misha; Grinvald, Amiram; Arieli, Amos

2003-10-01

Spontaneous cortical activity-ongoing activity in the absence of intentional sensory input-has been studied extensively, using methods ranging from EEG (electroencephalography), through voltage sensitive dye imaging, down to recordings from single neurons. Ongoing cortical activity has been shown to play a critical role in development, and must also be essential for processing sensory perception, because it modulates stimulus-evoked activity, and is correlated with behaviour. Yet its role in the processing of external information and its relationship to internal representations of sensory attributes remains unknown. Using voltage sensitive dye imaging, we previously established a close link between ongoing activity in the visual cortex of anaesthetized cats and the spontaneous firing of a single neuron. Here we report that such activity encompasses a set of dynamically switching cortical states, many of which correspond closely to orientation maps. When such an orientation state emerged spontaneously, it spanned several hypercolumns and was often followed by a state corresponding to a proximal orientation. We suggest that dynamically switching cortical states could represent the brain's internal context, and therefore reflect or influence memory, perception and behaviour.

Abnormal regional spontaneous neuronal activity associated with symptom severity in treatment-naive patients with obsessive-compulsive disorder revealed by resting-state functional MRI.

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Qiu, Linlin; Fu, Xiangshuai; Wang, Shuai; Tang, Qunfeng; Chen, Xingui; Cheng, Lin; Zhang, Fuquan; Zhou, Zhenhe; Tian, Lin

2017-02-15

A large number of neuroimaging studies have revealed the dysfunction of brain activities in obsessive-compulsive disorder (OCD) during various tasks. However, regional spontaneous activity abnormalities in OCD are gradually being revealed. In this current study, we aimed to investigate cerebral regions with abnormal spontaneous activity using resting-state functional magnetic resonance imaging (fMRI) and further explored the relationship between the spontaneous neuronal activity and symptom severity of patients with OCD. Thirty-one patients with OCD and 32 age-and sex-matched normal controls received the fMRI scans and fractional amplitude of low-frequency fluctuation (fALFF) approach was applied to identify the abnormal brain activity. We found that patients with OCD showed decreased fALFF not only in the cortical-striato-thalamo-cortical (CSTC) circuits like the thalamus, but also in other cerebral systems like the cerebellum, the parietal cortex and the temporal cortex. Additionally, OCD patients demonstrated significant associations between decreased fALFF and obsessive-compulsive symptom severity in the thalamus, the paracentral lobule and the cerebellum. Our results provide evidence for abnormal spontaneous neuronal activity in distributed cerebral areas and support the notion that brain areas outside the CSTC circuits may also play an important role in the pathophysiology of OCD. Copyright © 2017 Elsevier B.V. All rights reserved.

Biologically active polymers from spontaneous carotenoid oxidation: a new frontier in carotenoid activity.

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James B Johnston

Full Text Available In animals carotenoids show biological activity unrelated to vitamin A that has been considered to arise directly from the behavior of the parent compound, particularly as an antioxidant. However, the very property that confers antioxidant activity on some carotenoids in plants also confers susceptibility to oxidative transformation. As an alternative, it has been suggested that carotenoid oxidative breakdown or metabolic products could be the actual agents of activity in animals. However, an important and neglected aspect of the behavior of the highly unsaturated carotenoids is their potential to undergo addition of oxygen to form copolymers. Recently we reported that spontaneous oxidation of ß-carotene transforms it into a product dominated by ß-carotene-oxygen copolymers. We now report that the polymeric product is biologically active. Results suggest an overall ability to prime innate immune function to more rapidly respond to subsequent microbial challenges. An underlying structural resemblance to sporopollenin, found in the outer shell of spores and pollen, may allow the polymer to modulate innate immune responses through interactions with the pattern recognition receptor system. Oxygen copolymer formation appears common to all carotenoids, is anticipated to be widespread, and the products may contribute to the health benefits of carotenoid-rich fruits and vegetables.

Novel insights on the relationship between T-tubular defects and contractile dysfunction in a mouse model of hypertrophic cardiomyopathy.

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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

Measuring the Contractile Response of Isolated Tissue Using an Image Sensor

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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.

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

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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.

Effects of epidermal growth factor, interleukin 1 and nitric oxide on prostaglandin production by guinea-pig uterus.

Science.gov (United States)

Keeble, J E; Poyser, N L

2002-08-01

Initial experiments in the present study investigated the effects of epidermal growth factor (EGF), interleukin 1beta (IL-1beta) and sodium nitroprusside (a nitric oxide donor) on the output of prostaglandins from guinea-pig uterus on day 7 of the oestrous cycle. Superfusion of day 7 guinea-pig uterus in vitro with either EGF or sodium nitroprusside increased the output of PGF(2alpha) and 6-keto-PGF(1alpha), but not of PGE(2). IL-1beta had no effect on the output of these three prostaglandins. EGF still increased the output of PGF(2alpha), but did not increase the output of 6-keto-PGF(1alpha) in a calcium-depleted superfusate. Subsequent experiments investigated the effect of sodium nitroprusside on contractile activity of day 7 guinea-pig uterus. Basal spontaneous activity of both the intact uterus and isolated myometrium superfused in vitro was low. Sodium nitroprusside increased the contractile activity of these tissues two- to fourfold. EGF did not affect the contractile activity of the uterus, indicating that sodium nitroprusside-induced contractions are not due to increased prostaglandin production. Overall, the findings indicate that EGF and nitric oxide may act as mediators in the mechanism by which oestradiol acting on a progesterone-primed uterus stimulates the increase in PGF(2alpha) production by the guinea-pig uterus necessary for luteolysis. Nitric oxide may increase the spontaneous activity of the uterus when this activity is low.

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

Combining task-evoked and spontaneous activity to improve pre-operative brain mapping with fMRI

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Fox, Michael D.; Qian, Tianyi; Madsen, Joseph R.; Wang, Danhong; Li, Meiling; Ge, Manling; Zuo, Huan-cong; Groppe, David M.; Mehta, Ashesh D.; Hong, Bo; Liu, Hesheng

2016-01-01

Noninvasive localization of brain function is used to understand and treat neurological disease, exemplified by pre-operative fMRI mapping prior to neurosurgical intervention. The principal approach for generating these maps relies on brain responses evoked by a task and, despite known limitations, has dominated clinical practice for over 20 years. Recently, pre-operative fMRI mapping based on correlations in spontaneous brain activity has been demonstrated, however this approach has its own limitations and has not seen widespread clinical use. Here we show that spontaneous and task-based mapping can be performed together using the same pre-operative fMRI data, provide complimentary information relevant for functional localization, and can be combined to improve identification of eloquent motor cortex. Accuracy, sensitivity, and specificity of our approach are quantified through comparison with electrical cortical stimulation mapping in eight patients with intractable epilepsy. Broad applicability and reproducibility of our approach is demonstrated through prospective replication in an independent dataset of six patients from a different center. In both cohorts and every individual patient, we see a significant improvement in signal to noise and mapping accuracy independent of threshold, quantified using receiver operating characteristic curves. Collectively, our results suggest that modifying the processing of fMRI data to incorporate both task-based and spontaneous activity significantly improves functional localization in pre-operative patients. Because this method requires no additional scan time or modification to conventional pre-operative data acquisition protocols it could have widespread utility. PMID:26408860

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...

On-off intermittency in time series of spontaneous paroxysmal activity in rats with genetic absence epilepsy

International Nuclear Information System (INIS)

Hramov, Alexander; Koronovskii, Alexey A.; Midzyanovskaya, I.S.; Sitnikova, E.; Rijn, C.M. van

2006-01-01

In the present paper we consider the on-off intermittency phenomena observed in time series of spontaneous paroxysmal activity in rats with genetic absence epilepsy. The method to register and analyze the electroencephalogram with the help of continuous wavelet transform is also suggested

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.

Sources of variation and genetic profile of spontaneous, out-of-season ovulatory activity in the Chios sheep

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Kouttos Athanasios

2003-01-01

Full Text Available Abstract Organising the breeding plan of a seasonally breeding species, such as sheep, presents a challenge to farmers and the industry as a whole, since both economical and biological considerations need to be carefully balanced. Understanding the breeding activity of individual animals becomes a prerequisite for a successful breeding program. This study set out to investigate the sources of variation and the genetic profile of the spontaneous, out-of-season ovulatory activity of ewes of the Chios dairy sheep breed in Greece. The definition of the trait was based on blood progesterone levels, measured before exposing the ewes to rams, which marks the onset of the usual breeding season. Data were 707 records, taken over two consecutive years, of 435 ewes kept at the Agricultural Research Station of Chalkidiki in northern Greece. When all available pedigree was included, the total number of animals involved was 1068. On average, 29% of all ewes exhibited spontaneous, out-of-season ovulatory activity, with no substantial variation between the years. Significant sources of systematic variation were the ewe age and live weight, and the month of previous lambing. Older, heavier ewes, that had lambed early the previous autumn, exhibited more frequent activity. Heritability estimates were 0.216 (± 0.084 with a linear and 0.291 with a threshold model. The latter better accounts for the categorical nature of the trait. The linear model repeatability was 0.230 (± 0.095. The results obtained in this study support the notion that spontaneous out-of-season ovulatory activity can be considered in the development of a breeding plan for the Chios sheep breed.

Glucuronidated quercetin lowers blood pressure in spontaneously hypertensive rats via deconjugation.

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Pilar Galindo

Full Text Available BACKGROUND: Chronic oral quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone is usually not present in plasma, because it is rapidly metabolized into conjugated, mostly inactive, metabolites. The aim of the study is to analyze whether deconjugation of these metabolites is involved in the blood pressure lowering effect of quercetin. METHODOLOGY/PRINCIPAL FINDINGS: We have analyzed the effects on blood pressure and vascular function in vitro of the conjugated metabolites of quercetin (quercetin-3-glucuronide, Q3GA; isorhamnetin-3-glucuronide, I3GA; and quercetin-3'-sulfate, Q3'S in spontaneously hypertensive rats (SHR. Q3GA and I3GA (1 mg/kg i.v., but not Q3'S, progressively reduced mean blood pressure (MBP, measured in conscious SHR. The hypotensive effect of Q3GA was abolished in SHR treated with the specific inhibitor of β-glucuronidase, saccharic acid 1,4-lactone (SAL, 10 mg/ml. In mesenteric arteries, unlike quercetin, Q3GA had no inhibitory effect in the contractile response to phenylephrine after 30 min of incubation. However, after 1 hour of incubation Q3GA strongly reduced this contractile response and this effect was prevented by SAL. Oral administration of quercetin (10 mg/Kg induced a progressive decrease in MBP, which was also suppressed by SAL. CONCLUSIONS: Conjugated metabolites are involved in the in vivo antihypertensive effect of quercetin, acting as molecules for the plasmatic transport of quercetin to the target tissues. Quercetin released from its glucuronidated metabolites could be responsible for its vasorelaxant and hypotensive effect.

Pharmacological action of DA-9701 on the motility of feline stomach circular smooth muscle.

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Nguyen, Thanh Thao; Song, Hyun Ju; Ko, Sung Kwon; Sohn, Uy Dong

2015-03-01

DA-9701, a new prokinetic agent for the treatment of functional dyspepsia, is formulated with Pharbitis semen and Corydalis tuber. This study wasconducted to determine the pharmacological action of DA-9701 and to identify the receptors involved in DA-9701 -induced contractile responsesin the feline gastric corporal, fundic and antral circular smooth muscle. Concentration-response curve to DA-9701 was established. The tissue trips were exposed to methylsergide, ketanserin, ondansetron, GR 113808, atropine and dopamine before administration of DA-9701. The contractile force was determined before and after administration of drugs by a polygraph.DA-9701 enhanced the spontaneous contractile amplitude of antrum, corpus and fundus. However, it did not change the spontaneous contractile frequency of antrum and corpus, but concentration-dependently reduced that of fundus. In the fundus, DA-9701 -induced tonic contractions were inhibited by dopamine, methylsergide, ketanserine, ondansetron or GR 113808 respectively, but not by atropine, indicating that the contractile responses are mediated by multiple receptors: 5-HT2, 5-HT3, 5-HT4, and dopamine receptors. In the corpus, DA-9701-induced contractions were blocked by atropine, dopamine or GR 113808, but not by methysergide, ketanserin or ondansetron, indicating that they are involved in receptors on both, smooth muscles and neurons: 5-HT4 and dopamine receptors. However, contractile responses to DA-9701 are mainly mediated by dopamine receptors in the antrum. These results suggest that DA-9701 has important roles in gastric accommodation by enhancing tonic activity of fundus, and in gastric emptying and gastrointestinal transit by phasic contractions of corpus and antrum mediated by multiple receptors.

Two types of mental fatigue affect spontaneous oscillatory brain activities in different ways

OpenAIRE

Shigihara, Yoshihito; Tanaka, Masaaki; Ishii, Akira; Kanai, Etsuko; Funakura, Masami; Watanabe, Yasuyoshi

2013-01-01

Abstract Background Fatigue has a multi-factorial nature. We examined the effects of two types of mental fatigue on spontaneous oscillatory brain activity using magnetoencephalography (MEG). Methods Participants were randomly assigned to two groups in a single-blinded, crossover fashion to perform two types of mental fatigue-inducing experiments. Each experiment consisted of a 30-min fatigue-inducing 0- or 2-back test session and two evaluation sessions performed just before and after the fat...

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.

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.

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

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.

Research on spontaneous activity in adult anisometropic amblyopia with regional homogeneity

Science.gov (United States)

Huang, Yufeng; Zhou, Yifeng

2017-06-01

Amblyopia usually occurs in early childhood and results in monocular visual impairment. The functional magnetic resonance imaging (fMRI) studies have reflected functional anomaly in amblyopia. In resting-state fMRI study, spontaneous activity changes abnormally in anisometropic amblyopia could be revealed by the regional homogeneity (ReHo). Twenty two adult anisometropic amblyopes and Twenty one normal controls participated in this fMRI study. Two sample T test was carried out to analysis ReHo within the whole brain for the inter groups. Compare with normal group, our study found that the amblyopia’s ReHo mainly increased in the left frontal lobe, while decreased in the left cerebellum, the temporal lobe (left and right), and the left parietal lobe. And the ReHo values in middle and inferior temporal lobe, the prefrontal lobe, frontal lobe (positive) and parietal lobe and medial frontal gyrus (negative) could be correlated with the acuity deficit of amblyopia. The results increased in ReHo may indicate compensatory plasticity in higher vision information process, while the decreased in ReHo may reflect decreased ability in eye movement, spatial sense and visuo-motor coordination. The correlation revealed that the vision deficit may correspond to the spontaneous in certain brain area.

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.

Spaced sessions of avoidance extinction reduce spontaneous recovery and promote infralimbic cortex activation.

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Tapias-Espinosa, Carles; Kádár, Elisabet; Segura-Torres, Pilar

2018-01-15

Extinction-based therapies (EBT) are the psychological treatments of choice for certain anxiety disorders, such as post-traumatic stress disorder. However, some patients relapse and suffer spontaneous recovery (SR) of anxiety symptoms and persistence of avoidance behaviour, which underlines the need for improving EBT. In rats, recent evidence has highlighted the relevance of the temporal distribution of extinction sessions in reducing SR of auditory fear conditioning, although it has seldom been studied in procedures involving proactive avoidance responses, such as two-way active avoidance conditioning (TWAA). We examined whether the temporal distribution of two extinction sessions separated by 24h or 7days (contiguous versus spaced extinction paradigms, respectively), influences SR after 28days of a TWAA task. c-Fos expression, as a marker of neuronal activation, was also measured by immunohistochemistry 90min after the SR test in the amygdala and the medial prefrontal cortex. The temporal distribution of extinction sessions did not affect the degree of extinction learning. However, only the rats that underwent the 7-day spaced extinction paradigm maintained the level of extinction in the long term, showing no SR in TWAA. This behavioural finding was consistent with a greater number of c-Fos-labelled neurons in the infralimbic cortex in the 7-day group, and in the Lateral and Central nuclei of the amygdala in the 24-hour group. These findings show that a time-spaced extinction paradigm reduces the spontaneous recovery of active avoidance behaviour, and that this behavioural advantage appears to be related to the activation of the infralimbic cortex. Copyright © 2017 Elsevier B.V. All rights reserved.

Resolving the role of actoymyosin contractility in cell microrheology.

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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.

Investigating Cardiac MRI Based Right Ventricular Contractility As A Novel Non-Invasive Metric of Pulmonary Arterial Pressure

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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

Accuracy of rate coding: When shorter time window and higher spontaneous activity help

Czech Academy of Sciences Publication Activity Database

Leváková, Marie; Tamborrino, M.; Košťál, Lubomír; Lánský, Petr

2017-01-01

Roč. 95, č. 2 (2017), č. článku 022310. ISSN 2470-0045 R&D Projects: GA ČR(CZ) GA15-08066S; GA MŠk(CZ) 7AMB17AT048 Institutional support: RVO:67985823 Keywords : rate coding * observation window * spontaneous activity * Fisher information * perfect integrate- and -fire model * Wiener process Subject RIV: BB - Applied Statistics, Operational Research OBOR OECD: Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology Impact factor: 2.366, year: 2016

Force percolation of contractile active gels

NARCIS (Netherlands)

Alvarado, José; Sheinman, Michael; Sharma, Abhinav; MacKintosh, Fred C.; Koenderink, Gijsje H.

2017-01-01

Living systems provide a paradigmatic example of active soft matter. Cells and tissues comprise viscoelastic materials that exert forces and can actively change shape. This strikingly autonomous behavior is powered by the cytoskeleton, an active gel of semiflexible filaments, crosslinks, and

Combining task-evoked and spontaneous activity to improve pre-operative brain mapping with fMRI.

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Fox, Michael D; Qian, Tianyi; Madsen, Joseph R; Wang, Danhong; Li, Meiling; Ge, Manling; Zuo, Huan-Cong; Groppe, David M; Mehta, Ashesh D; Hong, Bo; Liu, Hesheng

2016-01-01

Noninvasive localization of brain function is used to understand and treat neurological disease, exemplified by pre-operative fMRI mapping prior to neurosurgical intervention. The principal approach for generating these maps relies on brain responses evoked by a task and, despite known limitations, has dominated clinical practice for over 20years. Recently, pre-operative fMRI mapping based on correlations in spontaneous brain activity has been demonstrated, however this approach has its own limitations and has not seen widespread clinical use. Here we show that spontaneous and task-based mapping can be performed together using the same pre-operative fMRI data, provide complimentary information relevant for functional localization, and can be combined to improve identification of eloquent motor cortex. Accuracy, sensitivity, and specificity of our approach are quantified through comparison with electrical cortical stimulation mapping in eight patients with intractable epilepsy. Broad applicability and reproducibility of our approach are demonstrated through prospective replication in an independent dataset of six patients from a different center. In both cohorts and every individual patient, we see a significant improvement in signal to noise and mapping accuracy independent of threshold, quantified using receiver operating characteristic curves. Collectively, our results suggest that modifying the processing of fMRI data to incorporate both task-based and spontaneous activity significantly improves functional localization in pre-operative patients. Because this method requires no additional scan time or modification to conventional pre-operative data acquisition protocols it could have widespread utility. Copyright © 2015. Published by Elsevier Inc.

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

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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.

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

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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.

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)

A Conserved RhoGAP Limits M-phase Contractility and Coordinates with Microtubule Asters to Restrict Active RhoA to the Cell Equator During Cytokinesis

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Zanin, Esther; Desai, Arshad; Poser, Ina; Toyoda, Yusuke; Andree, Cordula; Moebius, Claudia; Bickle, Marc; Conradt, Barbara; Piekny, Alisa; Oegema, Karen

2014-01-01

SUMMARY During animal cell cytokinesis, the spindle directs contractile ring assembly by activating RhoA in a narrow equatorial zone. Rapid GTPase activating protein (GAP)-mediated inactivation (RhoA flux) is proposed to limit RhoA zone dimensions. Testing the significance of RhoA flux has been hampered by the fact that the GAP targeting RhoA is not known. Here, we identify M-phase GAP (MP-GAP) as the primary GAP targeting RhoA during mitosis/cytokinesis. MP-GAP inhibition caused excessive RhoA activation in M-phase leading to the uncontrolled formation of large cortical protrusions and late cytokinesis failure. RhoA zone width was broadened by attenuation of the centrosomal asters but was not affected by MP-GAP inhibition alone. Simultaneous aster attenuation and MP-GAP inhibition led to RhoA accumulation around the entire cell periphery. These results identify the major GAP restraining RhoA during cell division and delineate the relative contributions of RhoA flux and centrosomal asters in controlling RhoA zone dimensions. PMID:24012485

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

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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.

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

Spontaneous mutation by mutagenic repair of spontaneous lesions in DNA

International Nuclear Information System (INIS)

Hastings, P.J.; Quah, S.-K.; Borstel, R.C. von

1976-01-01

It is stated that strains of yeast carrying mutations in many of the steps in pathways repairing radiation-induced damage to DNA have enhanced spontaneous mutation rates. Most strains isolated because they have enhanced spontaneous mutation carry mutations in DNA repair systems. This suggests that much spontaneous mutation arises by mutagenic repair of spontaneous lesions. (author)

Salicylate-induced changes in spontaneous activity of single units in the inferior colliculus of the guinea pig.

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Jastreboff, P J; Sasaki, C T

1986-11-01

Changes in spontaneous neuronal activity of the inferior colliculus in albino guinea pigs before and after administration of sodium salicylate were analyzed. Animals were anesthetized with pentobarbital, and two microelectrodes separated by a few hundred microns were driven through the inferior colliculus. After collecting a sufficiently large sample of cells, sodium salicylate (450 mg/kg) was injected i.p. and recordings again made 2 h after the injection. Comparison of spontaneous activity recorded before and after salicylate administration revealed highly statistically significant differences (p less than 0.001). After salicylate, the mean rate of the cell population increased from 29 to 83 Hz and the median from 26 to 74 Hz. Control experiments in which sodium salicylate was replaced by saline injection revealed no statistically significant differences in cell discharges. Recordings made during the same experiments from lobulus V of the cerebellar vermis revealed no changes in response to salicylate. The observed changes in single-unit activity due to salicylate administration may represent the first systematic evidence of a tinnituslike phenomenon in animals.

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

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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

Distinct Temporal Coordination of Spontaneous Population Activity between Basal Forebrain and Auditory Cortex

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Josue G. Yague

2017-09-01

Full Text Available The basal forebrain (BF has long been implicated in attention, learning and memory, and recent studies have established a causal relationship between artificial BF activation and arousal. However, neural ensemble dynamics in the BF still remains unclear. Here, recording neural population activity in the BF and comparing it with simultaneously recorded cortical population under both anesthetized and unanesthetized conditions, we investigate the difference in the structure of spontaneous population activity between the BF and the auditory cortex (AC in mice. The AC neuronal population show a skewed spike rate distribution, a higher proportion of short (≤80 ms inter-spike intervals (ISIs and a rich repertoire of rhythmic firing across frequencies. Although the distribution of spontaneous firing rate in the BF is also skewed, a proportion of short ISIs can be explained by a Poisson model at short time scales (≤20 ms and spike count correlations are lower compared to AC cells, with optogenetically identified cholinergic cell pairs showing exceptionally higher correlations. Furthermore, a smaller fraction of BF neurons shows spike-field entrainment across frequencies: a subset of BF neurons fire rhythmically at slow (≤6 Hz frequencies, with varied phase preferences to ongoing field potentials, in contrast to a consistent phase preference of AC populations. Firing of these slow rhythmic BF cells is correlated to a greater degree than other rhythmic BF cell pairs. Overall, the fundamental difference in the structure of population activity between the AC and BF is their temporal coordination, in particular their operational timescales. These results suggest that BF neurons slowly modulate downstream populations whereas cortical circuits transmit signals on multiple timescales. Thus, the characterization of the neural ensemble dynamics in the BF provides further insight into the neural mechanisms, by which brain states are regulated.

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.

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.

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

Hydrodynamic interaction induced spontaneous rotation of coupled active filaments.

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Jiang, Huijun; Hou, Zhonghuai

2014-12-14

We investigate the coupled dynamics of active filaments with long range hydrodynamic interactions (HI). Remarkably, we find that filaments can rotate spontaneously under the same conditions in which a single filament alone can only move in translation. Detailed analysis reveals that the emergence of coupled rotation originates from an asymmetric flow field associated with HI which breaks the symmetry of translational motion when filaments approach. The breaking is then further stabilized by HI to form self-sustained coupled rotation. Intensive simulations show that coupled rotation forms easily when one filament tends to collide with the front-half of the other. For head-to-tail approaching, we observe another interesting HI-induced coupled motion, where filaments move together in the form of one following the other. Moreover, the radius of coupled rotation increases exponentially as the rigidity of the filament increases, which suggests that HI are also important for the alignment of rigid-rod-like filaments which has been assumed to be solely a consequence of direct collisions.

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....

THE ROLE OF CARBON MONOXIDE IN THE REGULATION OF ELECTRICAL AND CONTRACTILE PROPERTIES OF SMOOTH MUSCLE CELLS OF THE GUINEA PIG URETER

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I. V. Kovalyov

2014-01-01

Full Text Available Carbon monoxide CO, as well as nitric oxide and hydrogen sulfide, make up the family of labile biological mediators termed gasotransmitters. We hypothesized that CO may be involved in the mechanisms of regulation electrical and contractile properties of smooth muscles.The effects of carbon monoxide donor CORM II (tricarbonyldichlororuthenium(II-dimer on the electrical and contractile activities of smooth muscles of the guinea pig ureter were studied by the method of the double sucrose bridge. This method allows to register simultaneously the parameters of the action potential (AP and the contraction of smooth muscle cells (SMCs, caused by an electrical stimulus.CORM II in a concentration of 10 mmol has reduced the amplitude of contractions SMCs to (86.5 ± 9.7% (n = 6, p < 0.05, the amplitude of the AP to (88.9 ± 4.2% (n = 6, p < 0.05 and the duration of the plateau of the AP to (91.7 ± 6.0% (n = 6, p < 0.05. On the background of the action of biologically active substances (phenylephrine, 10 µmol or histamine, 10 µmol, these effects of CORM II amplified. The inhibitory action of СORM II on the parameters of the contractile and electrical activities of the smooth muscles of guinea pig ureter has been decreased by blocking potassium channels in membrane of SMCs by tetraethylammonium chloride (TEA оr inhibition of soluble guanylate cyclase (ODQ [1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-l-one]. On the background of TEA (5 mmol, a donor of CO (10 mmol caused a reduction the amplitude of contraction SMCs to (87.0 ± 10.8% (n = 6, p < 0.05, the amplitude of the AP to (91.7 ± 6.4% (n = 6, p < 0.05 and the duration of the plateau of the AP to (93.4 ± 7.5% (n = 6, p < 0.05. After the pretreatment of ODQ (1 µmol adding CORM II (10 mmol in solution has resulted to augment of the amplitude of contraction ureteral smooth muscle strips to (90.9 ± 4.2% (n = 6, p < 0.05, the amplitude of the AP to (97.2 ± 10.3% (n = 6, p < 0.05 and the duration of the

Neuronal activity in the isolated mouse spinal cord during spontaneous deletions in fictive locomotion: insights into locomotor central pattern generator organization

Science.gov (United States)

Zhong, Guisheng; Shevtsova, Natalia A; Rybak, Ilya A; Harris-Warrick, Ronald M

2012-01-01

We explored the organization of the spinal central pattern generator (CPG) for locomotion by analysing the activity of spinal interneurons and motoneurons during spontaneous deletions occurring during fictive locomotion in the isolated neonatal mouse spinal cord, following earlier work on locomotor deletions in the cat. In the isolated mouse spinal cord, most spontaneous deletions were non-resetting, with rhythmic activity resuming after an integer number of cycles. Flexor and extensor deletions showed marked asymmetry: flexor deletions were accompanied by sustained ipsilateral extensor activity, whereas rhythmic flexor bursting was not perturbed during extensor deletions. Rhythmic activity on one side of the cord was not perturbed during non-resetting spontaneous deletions on the other side, and these deletions could occur with no input from the other side of the cord. These results suggest that the locomotor CPG has a two-level organization with rhythm-generating (RG) and pattern-forming (PF) networks, in which only the flexor RG network is intrinsically rhythmic. To further explore the neuronal organization of the CPG, we monitored activity of motoneurons and selected identified interneurons during spontaneous non-resetting deletions. Motoneurons lost rhythmic synaptic drive during ipsilateral deletions. Flexor-related commissural interneurons continued to fire rhythmically during non-resetting ipsilateral flexor deletions. Deletion analysis revealed two classes of rhythmic V2a interneurons. Type I V2a interneurons retained rhythmic synaptic drive and firing during ipsilateral motor deletions, while type II V2a interneurons lost rhythmic synaptic input and fell silent during deletions. This suggests that the type I neurons are components of the RG, whereas the type II neurons are components of the PF network. We propose a computational model of the spinal locomotor CPG that reproduces our experimental results. The results may provide novel insights into the

Multichannel detrended fluctuation analysis reveals synchronized patterns of spontaneous spinal activity in anesthetized cats.

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Erika E Rodríguez

Full Text Available The analysis of the interaction and synchronization of relatively large ensembles of neurons is fundamental for the understanding of complex functions of the nervous system. It is known that the temporal synchronization of neural ensembles is involved in the generation of specific motor, sensory or cognitive processes. Also, the intersegmental coherence of spinal spontaneous activity may indicate the existence of synaptic neural pathways between different pairs of lumbar segments. In this study we present a multichannel version of the detrended fluctuation analysis method (mDFA to analyze the correlation dynamics of spontaneous spinal activity (SSA from time series analysis. This method together with the classical detrended fluctuation analysis (DFA were used to find out whether the SSA recorded in one or several segments in the spinal cord of the anesthetized cat occurs either in a random or in an organized manner. Our results are consistent with a non-random organization of the sets of neurons involved in the generation of spontaneous cord dorsum potentials (CDPs recorded either from one lumbar segment (DFA-α mean = 1.04[Formula: see text]0.09 or simultaneously from several lumbar segments (mDFA-α mean = 1.01[Formula: see text]0.06, where α = 0.5 indicates randomness while α = 0.5 indicates long-term correlations. To test the sensitivity of the mDFA method we also examined the effects of small spinal lesions aimed to partially interrupt connectivity between neighboring lumbosacral segments. We found that the synchronization and correlation between the CDPs recorded from the L5 and L6 segments in both sides of the spinal cord were reduced when a lesion comprising the left dorsal quadrant was performed between the segments L5 and L6 (mDFA-[Formula: see text] = 0.992 as compared to initial conditions mDFA-α = 1.186. The synchronization and correlation were reduced even further after a similar additional right spinal lesion (mDFA-α = 0

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

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

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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.

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

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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.

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.

Preictal activity of subicular, CA1, and dentate gyrus principal neurons in the dorsal hippocampus before spontaneous seizures in a rat model of temporal lobe epilepsy.

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Fujita, Satoshi; Toyoda, Izumi; Thamattoor, Ajoy K; Buckmaster, Paul S

2014-12-10

Previous studies suggest that spontaneous seizures in patients with temporal lobe epilepsy might be preceded by increased action potential firing of hippocampal neurons. Preictal activity is potentially important because it might provide new opportunities for predicting when a seizure is about to occur and insight into how spontaneous seizures are generated. We evaluated local field potentials and unit activity of single, putative excitatory neurons in the subiculum, CA1, CA3, and dentate gyrus of the dorsal hippocampus in epileptic pilocarpine-treated rats as they experienced spontaneous seizures. Average action potential firing rates of neurons in the subiculum, CA1, and dentate gyrus, but not CA3, increased significantly and progressively beginning 2-4 min before locally recorded spontaneous seizures. In the subiculum, CA1, and dentate gyrus, but not CA3, 41-57% of neurons displayed increased preictal activity with significant consistency across multiple seizures. Much of the increased preictal firing of neurons in the subiculum and CA1 correlated with preictal theta activity, whereas preictal firing of neurons in the dentate gyrus was independent of theta. In addition, some CA1 and dentate gyrus neurons displayed reduced firing rates preictally. These results reveal that different hippocampal subregions exhibit differences in the extent and potential underlying mechanisms of preictal activity. The finding of robust and significantly consistent preictal activity of subicular, CA1, and dentate neurons in the dorsal hippocampus, despite the likelihood that many seizures initiated in other brain regions, suggests the existence of a broader neuronal network whose activity changes minutes before spontaneous seizures initiate. Copyright © 2014 the authors 0270-6474/14/3416671-17$15.00/0.

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

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...

Studies on the ovarian motility of small laboratory rodents.

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Gimeno, M F; Gimeno, A L

1975-01-01

Guinea pig ovaries were isolated and immersed in Krebs-Ringer bicarbonate solution, gassed with carbogen and added with glucose as the substrate. The experiments were carried out at 37 degrees C and the preparations were subjected to a basal tension of 500 mg. The spontaneous motility (contractile tension and frequency) of guinea pig ovaries obtained in late proestrus was significantly greater than that of the estrus or early proestrus. The influence of oxytocin on ovarian motility was significantly more marked in late proestrus than in estrus or early proestrus. Both the spontaneous and induced mortility of guinea pig ovaries are augmented in the immediate prevoulatory moment. In isolated rat ovaries, the isometric contractile tension and the frequency of contractions increased as the estral cycle progressed. During late proestrus, left ovaries had a contractile activity of greater intensity and frequency than the right ones, whereas during early proestrus the magnitudes were comparable. Oxytocin elicited greater responses in left than right ovaries of the late proestrus, the effect becoming similar in estrus and early proestrus. Rat ovaries obtained immediately before ovulation are specifically sensitized to the influence of oxytocin and not to other smooth muscle stimulants.

[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.

Vitamin K3 inhibits mouse uterine contraction in vitro via interference with the calcium transfer and the potassium channels.

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Zhang, Xian-Xia; Lu, Li-Min; Wang, Li

2016-08-05

Previous studies have demonstrated vitamin K3 had a great relief to smooth muscle spastic disorders, but no researches have yet pinpointed its possible anti-contractile activity in the uterus. Here, we evaluated the effect of vitamin K3 on myometrial contractility and explored the possible mechanisms of vitamin K3 action. Myograph apparatus were used to record the changes in contractility of isolated mouse uterine strips in a tissue bath. Uterine strips were exposed to vitamin K3 or vehicle. Vitamin K3 suppressed spontaneous contractions in a concentration dependent manner. It significantly decreased the contractile frequency induced by PGF2ɑ but not their amplitude (expect 58.0 μM). Prior incubation with vitamin K3 reduced the effectiveness of PGF2ɑ-induced contraction. The antispasmodic effect of vitamin K3 was also sensitive to potassium channel blockers, such as tetraethylammonium, 4-aminopyridine, iberiotoxin) but not to the nitric oxide related pathway blockers. High concentrations (29.0, 58.0 μM) of vitamin K3 weakened the Ca(2+) dose response and inhibited phase 1 contraction (intracellular stored calcium release). These dates suggest that vitamin K3 specifically suppresses myometrial contractility by affecting calcium and potassium channels; thus, this approach has potential therapy for uterine contractile activity related disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Mucuna pruriens Seed Extract Pretreatment on the Responses of Spontaneously Beating Rat Atria and Aortic Ring to Naja sputatrix (Javan Spitting Cobra) Venom

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Fung, Shin Yee; Tan, Nget Hong; Sim, Si Mui; Aguiyi, John C.

2012-01-01

Mucuna pruriens Linn. (velvet bean) has been used by native Nigerians as a prophylactic for snakebite. Rats pretreated with M. pruriens seed extract (MPE) have been shown to protect against the lethal and cardiovascular depressant effects of Naja sputatrix (Javan spitting cobra) venoms, and the protective effect involved immunological neutralization of the venom toxins. To investigate further the mechanism of the protective effect of MPE pretreatment against cobra venom toxicity, the actions of Naja sputatrix venom on spontaneously beating rat atria and aortic rings isolated from both MPE pretreated and untreated rats were studied. Our results showed that the MPE pretreatment conferred protection against cobra venom-induced depression of atrial contractility and atrial rate in the isolated atrial preparations, but it had no effect on the venom-induced contractile response of aortic ring preparation. These observations suggested that the protective effect of MPE pretreatment against cobra venom toxicity involves a direct protective action of MPE on the heart function, in addition to the known immunological neutralization mechanism, and that the protective effect does not involve action on blood vessel contraction. The results also suggest that M. pruriens seed may contain novel cardioprotective agent with potential therapeutic value. PMID:21785646

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)

Active caspase-3 and ultrastructural evidence of apoptosis in spontaneous and induced cell death in bovine in vitro produced pre-implantation embryos

DEFF Research Database (Denmark)

Gjørret, Jakob O.; Fabian, Dusan; Avery, Birthe

2007-01-01

In this study we investigated chronological onset and involvement of active caspase-3, apoptotic nuclear morphology, and TUNEL-labeling, as well as ultrastructural evidence of apoptosis, in both spontaneous and induced cell death during pre-implantation development of bovine in vitro produced...... microscopy in both treated and untreated blastocysts. Activation of caspase-3 is likely involved in both spontaneous and induced apoptosis in bovine pre-implantation embryos, and immunohistochemical staining of active caspase-3 may be used in combination with other markers to identify apoptosis in pre...... embryos. Pre-implantation embryos (2-cell to Day 8 blastocysts) were cultured with either no supplementation (untreated) or with 10 µM staurosporine for 24 hr (treated). Embryos were subjected to immunohistochemical staining of active caspase-3, TUNEL-reaction for detection of DNA degradation and DAPI...

Chronic levothyroxine and acute T3 treatments enhance the amplitude and time course of uterine contractions in human.

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Corriveau, Stéphanie; Pasquier, Jean-Charles; Blouin, Simon; Bellabarba, Diego; Rousseau, Éric

2013-03-01

This study compares the functional consequences of levothyroxine (T4) treatment during pregnancy as well as the acute affects of triiodothyronine (T3) on spontaneous uterine contractile activities observed in vitro. Uterine biopsies were obtained from consenting women undergoing elective caesarean at term (n = 28). Spontaneous contractile activities from T4-treated pregnant women (n = 8) were compared with control patients (n = 20) by isometric tension measurements. Effects of acute T3 and T4 on control tissues were also monitored. Area under the curve, amplitude, time to peak, duration, and frequency were quantified. In uterine strips from women treated for hypothyroidism, phasic uterine contractions of larger amplitude (+77%) were observed, with a prolonged duration at 90% relaxation (+138%) and reduced frequency (-55%) compared with values of the control group. The addition of exogenous T3 in vitro on control strips induced a significant increase in the duration of the contractions and a significant decrease in frequency (P women. Significant modifications of contractile properties were observed in strips from pregnant women treated with levothyroxine, consistent with those observed with the addition of exogenous T3. Clinical practices of modern obstetrics should take into account the effect of thyroid hormones on uterine contractions' time course to ensure a tighter followup at the end of pregnancy to achieve safer delivery.

Modulation by endothelin-1 of spontaneous activity and membrane currents of atrioventricular node myocytes from the rabbit heart.

Directory of Open Access Journals (Sweden)

Stéphanie C Choisy

Full Text Available The atrioventricular node (AVN is a key component of the cardiac pacemaker-conduction system. Although it is known that receptors for the peptide hormone endothelin-1 (ET-1 are expressed in the AVN, there is very little information available on the modulatory effects of ET-1 on AVN electrophysiology. This study characterises for the first time acute modulatory effects of ET-1 on AVN cellular electrophysiology.Electrophysiological experiments were conducted in which recordings were made from rabbit isolated AVN cells at 35-37°C using the whole-cell patch clamp recording technique.Application of ET-1 (10 nM to spontaneously active AVN cells led rapidly (within ~13 s to membrane potential hyperpolarisation and cessation of spontaneous action potentials (APs. This effect was prevented by pre-application of the ET(A receptor inhibitor BQ-123 (1 µM and was not mimicked by the ET(B receptor agonist IRL-1620 (300 nM. In whole-cell voltage-clamp experiments, ET-1 partially inhibited L-type calcium current (I(Ca,L and rapid delayed rectifier K(+ current (I(Kr, whilst it transiently activated the hyperpolarisation-activated current (I(f at voltages negative to the pacemaking range, and activated an inwardly rectifying current that was inhibited by both tertiapin-Q (300 nM and Ba(2+ ions (2 mM; each of these effects was sensitive to ET(A receptor inhibition. In cells exposed to tertiapin-Q, ET-1 application did not produce membrane potential hyperpolarisation or immediate cessation of spontaneous activity; instead, there was a progressive decline in AP amplitude and depolarisation of maximum diastolic potential.Acutely applied ET-1 exerts a direct modulatory effect on AVN cell electrophysiology. The dominant effect of ET-1 in this study was activation of a tertiapin-Q sensitive inwardly rectifying K(+ current via ET(A receptors, which led rapidly to cell quiescence.

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.

Activation of KCNQ Channels Suppresses Spontaneous Activity in Dorsal Root Ganglion Neurons and Reduces Chronic Pain after Spinal Cord Injury.

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Wu, Zizhen; Li, Lin; Xie, Fuhua; Du, Junhui; Zuo, Yan; Frost, Jeffrey A; Carlton, Susan M; Walters, Edgar T; Yang, Qing

2017-03-15

A majority of people who have sustained spinal cord injury (SCI) experience chronic pain after injury, and this pain is highly resistant to available treatments. Contusive SCI in rats at T10 results in hyperexcitability of primary sensory neurons, which contributes to chronic pain. KCNQ channels are widely expressed in nociceptive dorsal root ganglion (DRG) neurons, are important for controlling their excitability, and their activation has proven effective in reducing pain in peripheral nerve injury and inflammation models. The possibility that activators of KCNQ channels could be useful for treating SCI-induced chronic pain is strongly supported by the following findings. First, SCI, unlike peripheral nerve injury, failed to decrease the functional or biochemical expression of KCNQ channels in DRG as revealed by electrophysiology, real-time quantitative polymerase chain reaction, and Western blot; therefore, these channels remain available for pharmacological targeting of SCI pain. Second, treatment with retigabine, a specific KCNQ channel opener, profoundly decreased spontaneous activity in primary sensory neurons of SCI animals both in vitro and in vivo without changing the peripheral mechanical threshold. Third, retigabine reversed SCI-induced reflex hypersensitivity, adding to our previous demonstration that retigabine supports the conditioning of place preference after SCI (an operant measure of spontaneous pain). In contrast to SCI animals, naïve animals showed no effects of retigabine on reflex sensitivity or conditioned place preference by pairing with retigabine, indicating that a dose that blocks chronic pain-related behavior has no effect on normal pain sensitivity or motivational state. These results encourage the further exploration of U.S. Food and Drug Administration-approved KCNQ activators for treating SCI pain, as well as efforts to develop a new generation of KCNQ activators that lack central side effects.

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.

Cavity enhanced rephased amplified spontaneous emission

International Nuclear Information System (INIS)

A Williamson, Lewis; J Longdell, Jevon

2014-01-01

Amplified spontaneous emission is usually treated as an incoherent noise process. Recent theoretical and experimental work using rephasing optical pulses has shown that rephased amplified spontaneous emission (RASE) is a potential source of wide bandwidth time-delayed entanglement. Due to poor echo efficiency the plain RASE protocol does not in theory achieve perfect entanglement. Experiments done to date show a very small amount of entanglement at best. Here we show that RASE can, in principle, produce perfect multimode time-delayed two mode squeezing when the active medium is placed inside a Q-switched cavity. (paper)

Spontaneous and evoked cerebral activity modifications on whole-body γ irradiated adult rabbit

International Nuclear Information System (INIS)

Court, L.; Dufour, R.; Bassant, M.H.; Fatome, M.

1976-01-01

Whole-body γ-exposure from 150 to 850 rads (dose-rate: 14 rads.min -1 ) delivered to adult rabbits chronically implanted with electrodes resulted in prompt and delayed changes of behavior, arousal and spontaneous and evoked electrical activities. Electrophysiological techniques of polygraphic recording and signal processing showed that the alterations were related to the absorbed dose. The threshold dose accompanied with transient changes of arousal should be in the range of 50-100 rads; below this range, to the exclusion of some possible behavior changes, exposure should act as a stimulation that would become nociceptive at higher doses only [fr

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.

Early spontaneous intermittent myocardial reperfusion during acute myocardial infarction is associated with augmented thrombogenic activity and less myocardial damage

NARCIS (Netherlands)

Haider, A.W.; Andreotti, F.; Hackett, D.R.; Tousoulis, D.; Kluft, C.; Maseri, A.; Davies, G.J.

1995-01-01

Objectives. This study investigated the influence of early spontaneous intermittent reperfusion on the extent of myocardial damage and its relation to endogenous hemostatic activity, Background. In the early phase of acute myocardial infarction coronary occlusion is often intermittent, even before

Does Spontaneous Favorability to Power (vs. Universalism) Values Predict Spontaneous Prejudice and Discrimination?

Science.gov (United States)

Souchon, Nicolas; Maio, Gregory R; Hanel, Paul H P; Bardin, Brigitte

2017-10-01

We conducted five studies testing whether an implicit measure of favorability toward power over universalism values predicts spontaneous prejudice and discrimination. Studies 1 (N = 192) and 2 (N = 86) examined correlations between spontaneous favorability toward power (vs. universalism) values, achievement (vs. benevolence) values, and a spontaneous measure of prejudice toward ethnic minorities. Study 3 (N = 159) tested whether conditioning participants to associate power values with positive adjectives and universalism values with negative adjectives (or inversely) affects spontaneous prejudice. Study 4 (N = 95) tested whether decision bias toward female handball players could be predicted by spontaneous attitude toward power (vs. universalism) values. Study 5 (N = 123) examined correlations between spontaneous attitude toward power (vs. universalism) values, spontaneous importance toward power (vs. universalism) values, and spontaneous prejudice toward Black African people. Spontaneous positivity toward power (vs. universalism) values was associated with spontaneous negativity toward minorities and predicted gender bias in a decision task, whereas the explicit measures did not. These results indicate that the implicit assessment of evaluative responses attached to human values helps to model value-attitude-behavior relations. © 2016 The Authors. Journal of Personality Published by Wiley Periodicals, Inc.

Increased O-GlcNAcylation of Endothelial Nitric Oxide Synthase Compromises the Anti-contractile Properties of Perivascular Adipose Tissue in Metabolic Syndrome.

Science.gov (United States)

da Costa, Rafael M; da Silva, Josiane F; Alves, Juliano V; Dias, Thiago B; Rassi, Diane M; Garcia, Luis V; Lobato, Núbia de Souza; Tostes, Rita C

2018-01-01

Under physiological conditions, the perivascular adipose tissue (PVAT) negatively modulates vascular contractility. This property is lost in experimental and human obesity and in the metabolic syndrome, indicating that changes in PVAT function may contribute to vascular dysfunction associated with increased body weight and hyperglycemia. The O -linked β-N-acetylglucosamine ( O -GlcNAc) modification of proteins ( O -GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity. Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O -GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions. We hypothesized that chronic consumption of glucose, a condition that progresses to metabolic syndrome, leads to increased O -GlcNAc modification of proteins in the PVAT, decreasing its anti-contractile effects. Therefore, the current study was devised to determine whether a high-sugar diet increases O -GlcNAcylation in the PVAT and how increased O -GlcNAc interferes with PVAT vasorelaxant function. To assess molecular mechanisms by which O -GlcNAc contributes to PVAT dysfunction, thoracic aortas surrounded by PVAT were isolated from Wistar rats fed either a control or high sugar diet, for 10 and 12 weeks. Rats chronically fed a high sugar diet exhibited metabolic syndrome features, increased O -GlcNAcylated-proteins in the PVAT and loss of PVAT anti-contractile effect. PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O -GlcNAcylation of eNOS. High sugar diet also decreased OGA activity and increased superoxide anion generation in the PVAT. Visceral adipose tissue samples from hyperglycemic patients showed increased levels of O -GlcNAc-modified proteins, increased ROS

Arginine vasopressin antagonizes the effects of prostaglandin E2 on the spontaneous activity of warm-sensitive and temperature-insensitive neurons in the medial preoptic area in rats.

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Xu, Jian-Hui; Hou, Xiao-Yu; Tang, Yu; Luo, Rong; Zhang, Jie; Liu, Chang; Yang, Yong-Lu

2018-01-01

Arginine vasopressin (AVP) plays an important role in thermoregulation and antipyresis. We have demonstrated that AVP could change the spontaneous activity of thermosensitive and temperature insensitive neurons in the preoptic area. However, whether AVP influences the effects of prostaglandin E 2 (PGE 2 ) on the spontaneous activity of neurons in the medial preoptic area (MPO) remains unclear. Our experiment showed that PGE 2 decreased the spontaneous activity of warm-sensitive neurons, and increased that of low-slope temperature-insensitive neurons in the MPO. AVP attenuated the inhibitory effect of PGE 2 on warm-sensitive neurons, and reversed the excitatory effect of PGE 2 on low-slope temperature-insensitive neurons, demonstrating that AVP antagonized the effects of PGE 2 on the spontaneous activity of these neurons. The effect of AVP was suppressed by an AVP V 1a receptor antagonist, suggesting that V 1a receptor mediated the action of AVP. We also demonstrated that AVP attenuated the PGE 2 -induced decrease in the prepotential's rate of rise in warm-sensitive neurons and the PGE 2 -induced increase in that in low-slope temperature-insensitive neurons through the V 1a receptor. Together, these data indicated that AVP antagonized the PGE 2 -induced change in the spontaneous activity of warm-sensitive and low-slope temperature-insensitive neurons in the MPO partly by reducing the PGE 2 -induced change in the prepotential of these neurons in a V 1a receptor-dependent manner. Copyright © 2017 Elsevier B.V. All rights reserved.

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...

Contractile Defect Caused by Mutation in MYBPC3 Revealed under Conditions Optimized for Human PSC-Cardiomyocyte Function

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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.

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...

Altered regional homogeneity of spontaneous brain activity in idiopathic trigeminal neuralgia.

Science.gov (United States)

Wang, Yanping; Zhang, Xiaoling; Guan, Qiaobing; Wan, Lihong; Yi, Yahui; Liu, Chun-Feng

2015-01-01

The pathophysiology of idiopathic trigeminal neuralgia (ITN) has conventionally been thought to be induced by neurovascular compression theory. Recent structural brain imaging evidence has suggested an additional central component for ITN pathophysiology. However, far less attention has been given to investigations of the basis of abnormal resting-state brain activity in these patients. The objective of this study was to investigate local brain activity in patients with ITN and its correlation with clinical variables of pain. Resting-state functional magnetic resonance imaging data from 17 patients with ITN and 19 age- and sex-matched healthy controls were analyzed using regional homogeneity (ReHo) analysis, which is a data-driven approach used to measure the regional synchronization of spontaneous brain activity. Patients with ITN had decreased ReHo in the left amygdala, right parahippocampal gyrus, and left cerebellum and increased ReHo in the right inferior temporal gyrus, right thalamus, right inferior parietal lobule, and left postcentral gyrus (corrected). Furthermore, the increase in ReHo in the left precentral gyrus was positively correlated with visual analog scale (r=0.54; P=0.002). Our study found abnormal functional homogeneity of intrinsic brain activity in several regions in ITN, suggesting the maladaptivity of the process of daily pain attacks and a central role for the pathophysiology of ITN.

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

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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.

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

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

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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.

Spontaneous food allergy in Was-/- mice occurs independent of FcεRI-mediated mast cell activation.

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Lexmond, W S; Goettel, J A; Sallis, B F; McCann, K; Rings, E H H M; Jensen-Jarolim, E; Nurko, S; Snapper, S B; Fiebiger, E

2017-12-01

Food allergies are a growing health problem, and the development of therapies that prevent disease onset is limited by the lack of adjuvant-free experimental animal models. We compared allergic sensitization in patients with food allergy or Wiskott-Aldrich syndrome (WAS) and defined whether spontaneous disease in Was -/- mice recapitulates the pathology of a conventional disease model and/or human food allergy. Comparative ImmunoCAP ISAC microarray was performed in patients with food allergy or WAS. Spontaneous food allergy in Was -/- mice was compared to an adjuvant-based model in wild-type mice (WT-OVA/alum). Intestinal and systemic anaphylaxis was assessed, and the role of the high-affinity IgE Fc receptor (FcεRI) in allergic sensitization was evaluated using Was -/- Fcer1a -/- mice. Polysensitization to food was detected in both WAS and food-allergic patients which was recapitulated in the Was -/- model. Oral administration of ovalbumin (OVA) in Was -/- mice induced low titers of OVA-specific IgE compared to the WT-OVA/alum model. Irrespectively, 79% of Was -/- mice developed allergic diarrhea following oral OVA challenge. Systemic anaphylaxis occurred in Was -/- mice (95%) with a mortality rate >50%. Spontaneous sensitization and intestinal allergy occurred independent of FcεRI expression on mast cells (MCs) and basophils. Was -/- mice provide a model of food allergy with the advantage of mimicking polysensitization and low food-antigen IgE titers as observed in humans with clinical food allergy. This model will facilitate studies on aberrant immune responses during spontaneous disease development. Our results imply that therapeutic targeting of the IgE/FcεRI activation cascade will not affect sensitization to food. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

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

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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).

Altered spontaneous activity of posterior cingulate cortex and superior temporal gyrus are associated with a smoking cessation treatment outcome using varenicline revealed by regional homogeneity.

Science.gov (United States)

Wang, Chao; Shen, Zhujing; Huang, Peiyu; Qian, Wei; Yu, Xinfeng; Sun, Jianzhong; Yu, Hualiang; Yang, Yihong; Zhang, Minming

2017-06-01

Compared to nonsmokers, smokers exhibit a number of potentially important differences in regional brain function. However, little is known about the associations between the local spontaneous brain activity and smoking cessation treatment outcomes. In the present analysis, we aimed to evaluate whether the local features of spontaneous brain activity prior to the target quit date was associated with the smoking cessation outcomes. All the participants underwent magnetic resonance imaging scans and smoking-related behavioral assessments. After a 12-week treatment with varenicline, 23 smokers succeeded in quitting smoking and 32 failed. Smokers underwent functional magnetic resonance imaging (fMRI) scanning prior to an open label smoking cessation treatment trial. Regional homogeneity (ReHo) was used to measure spontaneous brain activity, and whole-brain voxel-wise comparisons of ReHo were performed to detect brain regions with altered spontaneous brain activity between relapser and quitter groups. After controlling for potentially confounding factors including years of education, years smoked, cigarettes smoked per day and FTND score as covariates, compared to quitters, relapsers displayed significantly decreased ReHo in bilateral posterior cingulate cortex (PCC), as well as increased ReHo in left superior temporal gyrus (STG). These preliminary results suggest that regional brain function variables may be promising predictors of smoking relapse. This study provided novel insights into the neurobiological mechanisms underlying smoking relapse. A deeper understanding of the neurobiological mechanisms associated with relapse may result in novel pharmacological and behavioral interventions.

Spontaneous distal rupture of the plantar fascia.

Science.gov (United States)

Gitto, Salvatore; Draghi, Ferdinando

2018-07-01

Spontaneous ruptures of the plantar fascia are uncommon injuries. They typically occur at its calcaneal insertion and usually represent a complication of plantar fasciitis and local treatment with steroid injections. In contrast, distal ruptures commonly result from traumatic injuries. We describe the case of a spontaneous distal rupture of the plantar fascia in a 48-year-old woman with a low level of physical activity and no history of direct injury to the foot, plantar fasciitis, or steroid injections. © 2017 Wiley Periodicals, Inc.

Effects of testosterone on contractile properties of sexually dimorphic forelimb muscles in male bullfrogs (Rana catesbeiana, Shaw 1802

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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.

Comparative Analysis of Human and Rodent Brain Primary Neuronal Culture Spontaneous Activity Using Micro-Electrode Array Technology.

Science.gov (United States)

Napoli, Alessandro; Obeid, Iyad

2016-03-01

Electrical activity in embryonic brain tissue has typically been studied using Micro Electrode Array (MEA) technology to make dozens of simultaneous recordings from dissociated neuronal cultures, brain stem cell progenitors, or brain slices from fetal rodents. Although these rodent neuronal primary culture electrical properties are mostly investigated, it has not been yet established to what extent the electrical characteristics of rodent brain neuronal cultures can be generalized to those of humans. A direct comparison of spontaneous spiking activity between rodent and human primary neurons grown under the same in vitro conditions using MEA technology has never been carried out before and will be described in the present study. Human and rodent dissociated fetal brain neuronal cultures were established in-vitro by culturing on a glass grid of 60 planar microelectrodes neurons under identical conditions. Three different cultures of human neurons were produced from tissue sourced from a single aborted fetus (at 16-18 gestational weeks) and these were compared with seven different cultures of embryonic rat neurons (at 18 gestational days) originally isolated from a single rat. The results show that the human and rodent cultures behaved significantly differently. Whereas the rodent cultures demonstrated robust spontaneous activation and network activity after only 10 days, the human cultures required nearly 40 days to achieve a substantially weaker level of electrical function. These results suggest that rat neuron preparations may yield inferences that do not necessarily transfer to humans. © 2015 Wiley Periodicals, Inc.

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.

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

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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

Are interstitial cells of Cajal involved in mechanical stress-induced gene expression and impairment of smooth muscle contractility in bowel obstruction?

Directory of Open Access Journals (Sweden)

Chester C Wu

Full Text Available The network of interstitial cells of Cajal (ICC is altered in obstructive bowel disorders (OBD. However, whether alteration in ICC network is a cause or consequence of OBD remains unknown. This study tested the hypothesis that mechanical dilation in obstruction disrupts the ICC network and that ICC do not mediate mechanotranscription of COX-2 and impairment of smooth muscle contractility in obstruction.Medical-grade silicon bands were wrapped around the distal colon to induce partial obstruction in wild-type and ICC deficient (W/W(v mice.In wild-type mice, colon obstruction led to time-dependent alterations of the ICC network in the proximal colon segment. Although unaffected on days 1 and 3, the ICC density decreased markedly and the network was disrupted on day 7 of obstruction. COX-2 expression increased, and circular muscle contractility decreased significantly in the segment proximal to obstruction. In W/W(v control mice, COX-2 mRNA level was 4.0 (±1.1-fold higher (n=4 and circular muscle contractility was lower than in wild-type control mice. Obstruction further increased COX-2 mRNA level in W/W(v mice to 7.2 (±1.0-fold vs. W/W(v controls [28.8 (±4.1-fold vs. wild-type controls] on day 3. Obstruction further suppressed smooth muscle contractility in W/W(v mice. However, daily administration of COX-2 inhibitor NS-398 significantly improved muscle contractility in both W/W(v sham and obstruction mice.Lumen dilation disrupts the ICC network. ICC deficiency has limited effect on stretch-induced expression of COX-2 and suppression of smooth muscle contractility in obstruction. Rather, stretch-induced COX-2 plays a critical role in motility dysfunction in partial colon obstruction.

Effect of Mucuna pruriens Seed Extract Pretreatment on the Responses of Spontaneously Beating Rat Atria and Aortic Ring to Naja sputatrix (Javan Spitting Cobra Venom

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Shin Yee Fung

2012-01-01

Full Text Available Mucuna pruriens Linn. (velvet bean has been used by native Nigerians as a prophylactic for snakebite. Rats pretreated with M. pruriens seed extract (MPE have been shown to protect against the lethal and cardiovascular depressant effects of Naja sputatrix (Javan spitting cobra venoms, and the protective effect involved immunological neutralization of the venom toxins. To investigate further the mechanism of the protective effect of MPE pretreatment against cobra venom toxicity, the actions of Naja sputatrix venom on spontaneously beating rat atria and aortic rings isolated from both MPE pretreated and untreated rats were studied. Our results showed that the MPE pretreatment conferred protection against cobra venom-induced depression of atrial contractility and atrial rate in the isolated atrial preparations, but it had no effect on the venom-induced contractile response of aortic ring preparation. These observations suggested that the protective effect of MPE pretreatment against cobra venom toxicity involves a direct protective action of MPE on the heart function, in addition to the known immunological neutralization mechanism, and that the protective effect does not involve action on blood vessel contraction. The results also suggest that M. pruriens seed may contain novel cardioprotective agent with potential therapeutic value.

Spontaneous Generation of Chirality in Simple Diaryl Ethers.

Science.gov (United States)

Lennartson, Anders; Hedström, Anna; Håkansson, Mikael

2015-07-01

We studied the spontaneous formation of chiral crystals of four diaryl ethers, 3-phenoxybenzaldehyde, 1; 1,3-dimethyl-2-phenoxybenzene, 2; di(4-aminophenyl) ether, 3; and di(p-tolyl) ether, 4. Compounds 1, 3, and 4 form conformationally chiral molecules in the solid state, while the chirality of 2 arises from the formation of supramolecular helices. Compound 1 is a liquid at ambient temperature, but 2-4 are crystalline, and solid-state CD-spectroscopy showed that they could be obtained as optically active bulk samples. It should be noted that the optical activity arise upon crystallization, and no optically active precursors were used. Indeed, even commercial samples of 3 and 4 were found to be optically active, giving evidence for the ease at which total spontaneous resolution may occur in certain systems. © 2015 Wiley Periodicals, Inc.

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.

Evidence of direct smooth muscle relaxant effects of the fibrate gemfibrozil.

Science.gov (United States)

Phelps, Laura E; Peuler, Jacob D

2010-01-01

Fibrates are commonly employed to treat abnormal lipid metabolism via their unique ability to stimulate peroxisome proliferator-activated receptor alpha (PPARalpha). Interestingly, they also decrease systemic arterial pressure, despite recent evidence that PPAR alpha may contribute to expression of renin and related hypertension. Yet, mechanisms responsible for their potential antihypertensive activity remain unresolved. Rapid decreases in arterial pressure following bolus intravenous injections of bezafibrate strongly suggest they may relax arterial smooth muscle directly. But since bezafibrate is highly susceptible to photodegradation in aqueous media, it has never been critically tested for this possibility in vitro with isolated arterial smooth muscle preparations. Accordingly, we tested gemfibrozil which is resistant to photodegradation. We examined it over a therapeutically-relevant range (50-400 microM) for both acute and delayed relaxant effects on contractions of the isolated rat tail artery; contractions induced by either depolarizing its smooth muscle cell membranes with high potassium or stimulating its membrane-bound receptors with norepinephrine and arginine-vasopressin. We also examined these same gemfibrozil levels for effects on spontaneously-occurring phasic rhythmic contractile activity, typically not seen in arteries under in vitro conditions but commonly exhibited by smooth muscle of uterus, duodenum and bladder. We found that gemfibrozil significantly relaxed all induced forms of contraction in the rat tail artery, acutely at the higher test levels and after a delay of a few hours at the lower test levels. The highest test level of gemfibrozil (400 microM) also completely abolished spontaneously-occurring contractile activity of the isolated uterus and duodenum and markedly suppressed it in the bladder. This is the first evidence that a fibrate drug can directly relax smooth muscle contractions, either induced by various contractile agents or

Loss of functional K+ channels encoded by ether-à-go-go-related genes in mouse myometrium prior to labour onset

Science.gov (United States)

Greenwood, I A; Yeung, S Y; Tribe, R M; Ohya, S

2009-01-01

There is a growing appreciation that ion channels encoded by the ether-à-go-go-related gene family have a functional impact in smooth muscle in addition to their accepted role in cardiac myocytes and neurones. This study aimed to assess the expression of ERG1–3 (KCNH1–3) genes in the murine myometrium (smooth muscle layer of the uterus) and determine the functional impact of the ion channels encoded by these genes in pregnant and non-pregnant animals. Quantitative RT-PCR did not detect message for ERG2 and 3 in whole myometrial tissue extracts. In contrast, message for two isoforms of mERG1 were readily detected with mERG1a more abundant than mERG1b. In isometric tension studies of non-pregnant myometrium, the ERG channel blockers dofetilide (1 μm), E4031 (1 μm) and Be-KM1 (100 nm) increased spontaneous contractility and ERG activators (PD118057 and NS1643) inhibited spontaneous contractility. In contrast, neither ERG blockade nor activation had any effect on the inherent contractility in myometrium from late pregnant (19 days gestation) animals. Moreover, dofetilide-sensitive K+ currents with distinctive ‘hooked’ kinetics were considerably smaller in uterine myocytes from late pregnant compared to non-pregnant animals. Expression of mERG1 isoforms did not alter throughout gestation or upon delivery, but the expression of genes encoding auxillary subunits (KCNE) were up-regulated considerably. This study provides the first evidence for a regulation of ERG-encoded K+ channels as a precursor to late pregnancy physiological activity. PMID:19332483

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

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.

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

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.

Structure of the Elastin-Contractile Units in the Thoracic Aorta and How Genes That Cause Thoracic Aortic Aneurysms and Dissections Disrupt This Structure.

Science.gov (United States)

Karimi, Ashkan; Milewicz, Dianna M

2016-01-01

The medial layer of the aorta confers elasticity and strength to the aortic wall and is composed of alternating layers of smooth muscle cells (SMCs) and elastic fibres. The SMC elastin-contractile unit is a structural unit that links the elastin fibres to the SMCs and is characterized by the following: (1) layers of elastin fibres that are surrounded by microfibrils; (2) microfibrils that bind to the integrin receptors in focal adhesions on the cell surface of the SMCs; and (3) SMC contractile filaments that are linked to the focal adhesions on the inner side of the membrane. The genes that are altered to cause thoracic aortic aneurysms and aortic dissections encode proteins involved in the structure or function of the SMC elastin-contractile unit. Included in this gene list are the genes encoding protein that are structural components of elastin fibres and microfibrils, FBN1, MFAP5, ELN, and FBLN4. Also included are genes that encode structural proteins in the SMC contractile unit, including ACTA2, which encodes SMC-specific α-actin and MYH11, which encodes SMC-specific myosin heavy chain, along with MYLK and PRKG1, which encode kinases that control SMC contraction. Finally, mutations in the gene encoding the protein linking integrin receptors to the contractile filaments, FLNA, also predispose to thoracic aortic disease. Thus, these data suggest that functional SMC elastin-contractile units are important for maintaining the structural integrity of the aorta. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Electrophysiological study in the infraorbital nerve of the rat: Spontaneous and evoked activity

Energy Technology Data Exchange (ETDEWEB)

AlbarracIn, A L [Catedra de Neurociencias, Facultad de Medicina, Universidad Nacional de Tucuman, Av. Roca 2200, PC 4000 (Argentina); Farfan, F D [Departamento de BioingenierIa, FACET, Universidad Nacional de Tucuman, INSIBIO - CONICET, CC 327, PC 4000 (Argentina); Felice, C J [Departamento de BioingenierIa, FACET, Universidad Nacional de Tucuman, INSIBIO - CONICET, CC 327, PC 4000 (Argentina)

2007-11-15

In this work we present some studies in the afferent nerve of the rat vibrissae. Studies on spontaneous activity (SA) in this sensorial system are of long data. Nevertheless, SA recordings in the nerve of a single vibrissa have not been made until present. In this work, we use an algorithm based on signal decomposition with Continuous Wavelet Transform (CWT) to analyse the discharges of two nerves. The action potentials of both nerves were detected and the firing rates were calculated. These results suggest that the firing rate of one vibrissa innervation is low considering that this nerve contains hundred of fibers. In addition, we present preliminary studies suggesting important effects of the hair shaft length in the afferent discharge during the vibrissae movements. The experiments consisted in recording the nerve activity after the vibrissae were sectioned at two different levels. The results showed important differences in the signal energy contents. It suggests that the hair shaft length would produce a differential activation of the mechanoreceptors located in the vibrissae follicle.

Electrophysiological study in the infraorbital nerve of the rat: Spontaneous and evoked activity

International Nuclear Information System (INIS)

AlbarracIn, A L; Farfan, F D; Felice, C J

2007-01-01

In this work we present some studies in the afferent nerve of the rat vibrissae. Studies on spontaneous activity (SA) in this sensorial system are of long data. Nevertheless, SA recordings in the nerve of a single vibrissa have not been made until present. In this work, we use an algorithm based on signal decomposition with Continuous Wavelet Transform (CWT) to analyse the discharges of two nerves. The action potentials of both nerves were detected and the firing rates were calculated. These results suggest that the firing rate of one vibrissa innervation is low considering that this nerve contains hundred of fibers. In addition, we present preliminary studies suggesting important effects of the hair shaft length in the afferent discharge during the vibrissae movements. The experiments consisted in recording the nerve activity after the vibrissae were sectioned at two different levels. The results showed important differences in the signal energy contents. It suggests that the hair shaft length would produce a differential activation of the mechanoreceptors located in the vibrissae follicle

Factors affecting the spontaneous mutational spectra in somatic mammalian cells

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О.А. Ковальова

2006-04-01

Full Text Available  In our survey of references we are discussed the influence of factors biological origin on the spontaneous mutation specters in mammalian. Seasonal and age components influence on the frequence of cytogenetic anomalies. The immune and endocrinous systems are take part in control of the alteration of the spontaneous mutation specters. Genetical difference of sensibility in animal and human at the alteration of factors enviroment as and  genetical differences of repair systems activity are may influence on individual variation of spontaneous destabilization characters of chromosomal apparatus.

Contractile Force of Human Extraocular Muscle: A Theoretical Analysis

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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.

Ca2+ sparks act as potent regulators of excitation-contraction coupling in airway smooth muscle.

Science.gov (United States)

Zhuge, Ronghua; Bao, Rongfeng; Fogarty, Kevin E; Lifshitz, Lawrence M

2010-01-15

Ca2+ sparks are short lived and localized Ca2+ transients resulting from the opening of ryanodine receptors in sarcoplasmic reticulum. These events relax certain types of smooth muscle by activating big conductance Ca2+-activated K+ channels to produce spontaneous transient outward currents (STOCs) and the resultant closure of voltage-dependent Ca2+ channels. But in many smooth muscles from a variety of organs, Ca2+ sparks can additionally activate Ca2+-activated Cl(-) channels to generate spontaneous transient inward current (STICs). To date, the physiological roles of Ca2+ sparks in this latter group of smooth muscle remain elusive. Here, we show that in airway smooth muscle, Ca2+ sparks under physiological conditions, activating STOCs and STICs, induce biphasic membrane potential transients (BiMPTs), leading to membrane potential oscillations. Paradoxically, BiMPTs stabilize the membrane potential by clamping it within a negative range and prevent the generation of action potentials. Moreover, blocking either Ca2+ sparks or hyperpolarization components of BiMPTs activates voltage-dependent Ca2+ channels, resulting in an increase in global [Ca2+](i) and cell contraction. Therefore, Ca2+ sparks in smooth muscle presenting both STICs and STOCs act as a stabilizer of membrane potential, and altering the balance can profoundly alter the status of excitability and contractility. These results reveal a novel mechanism underlying the control of excitability and contractility in smooth muscle.

Opportunities to Target Specific Contractile Abnormalities with Smooth Muscle Protein Kinase Inhibitors

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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.

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.

The retardation of myometrial infiltration, reduction of uterine contractility, and alleviation of generalized hyperalgesia in mice with induced adenomyosis by levo-tetrahydropalmatine (l-THP) and andrographolide.

Science.gov (United States)

Mao, Xiaoyan; Wang, Yuedong; Carter, Andrew V; Zhen, Xuechu; Guo, Sun-Wei

2011-10-01

Adenomyosis is a tough disease to manage nonsurgically. Levo-tetrahydropalmatine (l-THP), a known analgesic, and andrographolide, a nuclear factor kappa B (NF-κB) inhibitor, are both active ingredients extracted from Chinese medicinal herbs. We sought to determine whether treatment of l-THP, andrographolide, and valproic acid (VPA) would suppress the myometrial infiltration, improve pain behavior, and reduce uterine contractility in a mice model of adenomyosis. Adenomyosis was induced in 55 female ICR mice neonatally dosed with tamoxifen, while another 8 (group C) were dosed with solvent only. Starting from 4 weeks after birth, hotplate test was administrated to all mice every 4 weeks. At the 16th week, all mice with induced adenomyosis were randomly divided into 6 groups, each receiving different treatment for 3 weeks: low- or high-dose l-THP, andrographolide, low-dose l-THP and andrographolide jointly, VPA, and untreated. Group C received no treatment. After treatment, the hotplate test was administered and all mice were killed. The depth of myometrial infiltration of ectopic endometrium and uterine contractility were measured and compared across groups. We found that induction of adenomyosis resulted in progressive generalized hyperalgesia, along with elevated amplitude and irregularity of uterine contractions. Treatment with either l-THP, andrographolide, VPA, or l-THP and andrographolide jointly suppressed myometrial infiltration, improved generalized hyperalgesia, and reduced the amplitude and irregularity of uterine contractions. These results suggest that increased uterine contractility, in the form of increased contractile amplitude and irregularity, may contribute to dysmenorrhea in women with adenomyosis. More importantly, l-THP, andrographolide, and VPA all seem to be promising compounds for treating adenomyosis.

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

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

Spontaneous acute spinal subdural hematoma: spontaneous recovery from severe paraparesis--case report and review.

Science.gov (United States)

Payer, Michael; Agosti, Reto

2010-11-01

Spontaneous idiopathic acute spinal subdural hematomas are highly exceptional. Neurological symptoms are usually severe, and rapid diagnosis with MRI is mandatory. Surgical evacuation has frequently been used therapeutically; however, spontaneous recovery in mild cases has also been reported. We present a case of spontaneous recovery from severe paraparesis after spontaneous acute SSDH, and review the English-speaking literature.

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...

Functional structure of spontaneous sleep slow oscillation activity in humans.

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Danilo Menicucci

Full Text Available BACKGROUND: During non-rapid eye movement (NREM sleep synchronous neural oscillations between neural silence (down state and neural activity (up state occur. Sleep Slow Oscillations (SSOs events are their EEG correlates. Each event has an origin site and propagates sweeping the scalp. While recent findings suggest a SSO key role in memory consolidation processes, the structure and the propagation of individual SSO events, as well as their modulation by sleep stages and cortical areas have not been well characterized so far. METHODOLOGY/PRINCIPAL FINDINGS: We detected SSO events in EEG recordings and we defined and measured a set of features corresponding to both wave shapes and event propagations. We found that a typical SSO shape has a transition to down state, which is steeper than the following transition from down to up state. We show that during SWS SSOs are larger and more locally synchronized, but less likely to propagate across the cortex, compared to NREM stage 2. Also, the detection number of SSOs as well as their amplitudes and slopes, are greatest in the frontal regions. Although derived from a small sample, this characterization provides a preliminary reference about SSO activity in healthy subjects for 32-channel sleep recordings. CONCLUSIONS/SIGNIFICANCE: This work gives a quantitative picture of spontaneous SSO activity during NREM sleep: we unveil how SSO features are modulated by sleep stage, site of origin and detection location of the waves. Our measures on SSOs shape indicate that, as in animal models, onsets of silent states are more synchronized than those of neural firing. The differences between sleep stages could be related to the reduction of arousal system activity and to the breakdown of functional connectivity. The frontal SSO prevalence could be related to a greater homeostatic need of the heteromodal association cortices.

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...

Interprofessional learning, impression management, and spontaneity in the acute healthcare setting.

Science.gov (United States)

Bell, Elaine; McAllister, Sue; Ward, Paul R; Russell, Alison

2016-09-01

Spontaneous learning is integral to definitions of interprofessional learning (IPL) because it has been suggested that spontaneous learning can be deeply connected with the work that people do in collaboration with colleagues via their professional networks. However, its nature and the processes involved are not well understood. Goffman's theory of impression management offers a useful theoretical framework to consider the way in which interaction in the workplace connects to spontaneous learning. This article explores the current literature to investigate the usefulness of this framework to better understand and identify spontaneous learning in the workplace. Aspects such as the connections between spontaneous learning occurring in formal and informal work activities, the spaces in which it occurs, and the influence of professional networking are considered. It is proposed that research directed to developing a better understanding of the nature of spontaneous learning in IPL will assist in connecting this learning to formal IPL curricula, enhancing IPL and patient outcomes.

Ultrafast table-top dynamic radiography of spontaneous or stimulated events

Science.gov (United States)

Smilowitz, Laura; Henson, Bryan

2018-01-16

Disclosed herein are representative embodiments of methods, apparatus, and systems for performing radiography. For example, certain embodiments concern X-ray radiography of spontaneous events. Particular embodiments of the disclosed technology provide continuous high-speed x-ray imaging of spontaneous dynamic events, such as explosions, reaction-front propagation, and even material failure. Further, in certain embodiments, x-ray activation and data collection activation are triggered by the object itself that is under observation (e.g., triggered by a change of state detected by one or more sensors monitoring the object itself).

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.

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)

Electrical responses and spontaneous activity of human iPS-derived neuronal networks characterized for three-month culture with 4096-electrode arrays

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Hayder eAmin

2016-03-01

Full Text Available The recent availability of human induced pluripotent stem cells (hiPSCs holds great promise as a novel source of human-derived neurons for cell and tissue therapies as well as for in vitro drug screenings that might replace the use of animal models. However, there is still a considerable lack of knowledge on the functional properties of hiPSC-derived neuronal networks, thus limiting their application. Here, upon optimization of cell culture protocols, we demonstrate that both spontaneous and evoked electrical spiking activities of these networks can be characterized on-chip by taking advantage of the resolution provided by CMOS multielectrode arrays (CMOS-MEAs. These devices feature a large and closely-spaced array of 4096 simultaneously recording electrodes and multi-site on-chip electrical stimulation. Our results show that networks of human-derived neurons can respond to electrical stimulation with a physiological repertoire of spike waveforms after three months of cell culture, a period of time during which the network undergoes the expression of developing patterns of spontaneous spiking activity. To achieve this, we have investigated the impact on the network formation and on the emerging network-wide functional properties induced by different biochemical substrates, i.e. poly-dl-ornithine (PDLO, poly-l-ornithine (PLO, and polyethylenimine (PEI, that were used as adhesion promoters for the cell culture. Interestingly, we found that neuronal networks grown on PDLO coated substrates show significantly higher spontaneous firing activity, reliable responses to low-frequency electrical stimuli, and an appropriate level of PSD-95 that may denote a physiological neuronal maturation profile and synapse stabilization. However, our results also suggest that even three-month culture might not be sufficient for human-derived neuronal network maturation. Taken together, our results highlight the tight relationship existing between substrate coatings

Dietary fat influences the expression of contractile and metabolic genes in rat skeletal muscle.

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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.

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(-/-)

Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen.

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Mathiesen, Claus; Brazhe, Alexey; Thomsen, Kirsten; Lauritzen, Martin

2013-02-01

Glial calcium (Ca(2+)) waves constitute a means to spread signals between glial cells and to neighboring neurons and blood vessels. These waves occur spontaneously in Bergmann glia (BG) of the mouse cerebellar cortex in vivo. Here, we tested three hypotheses: (1) aging and reduced blood oxygen saturation alters wave activity; (2) glial Ca(2+) waves change cerebral oxygen metabolism; and (3) neuronal and glial wave activity is correlated. We used two-photon microscopy in the cerebellar cortexes of adult (8- to 15-week-old) and aging (48- to 80-week-old) ketamine-anesthetized mice after bolus loading with OGB-1/AM and SR101. We report that the occurrence of spontaneous waves is 20 times more frequent in the cerebellar cortex of aging as compared with adult mice, which correlated with a reduction in resting brain oxygen tension. In adult mice, spontaneous glial wave activity increased on reducing resting brain oxygen tension, and ATP-evoked glial waves reduced the tissue O(2) tension. Finally, although spontaneous Purkinje cell (PC) activity was not associated with increased glia wave activity, spontaneous glial waves did affect intracellular Ca(2+) activity in PCs. The increased wave activity during aging, as well as low resting brain oxygen tension, suggests a relationship between glial waves, brain energy homeostasis, and pathology.

Starting and Stopping Spontaneous Family Conflicts.

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Vuchinich, Samuel

1987-01-01

Examined how 52 nondistressed families managed spontaneous verbal conflicts during family dinners. Found conflict initiation to be evenly distributed across family roles. Extension of conflict was constrained by constant probability of a next conflict move occurring. Most conflicts ended with no resolution. Mothers were most active in closing…

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

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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

Bistable front dynamics in a contractile medium: Travelling wave fronts and cortical advection define stable zones of RhoA signaling at epithelial adherens junctions

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Budnar, Srikanth; Yap, Alpha S.

2017-01-01

Mechanical coherence of cell layers is essential for epithelia to function as tissue barriers and to control active tissue dynamics during morphogenesis. RhoA signaling at adherens junctions plays a key role in this process by coupling cadherin-based cell-cell adhesion together with actomyosin contractility. Here we propose and analyze a mathematical model representing core interactions involved in the spatial localization of junctional RhoA signaling. We demonstrate how the interplay between biochemical signaling through positive feedback, combined with diffusion on the cell membrane and mechanical forces generated in the cortex, can determine the spatial distribution of RhoA signaling at cell-cell junctions. This dynamical mechanism relies on the balance between a propagating bistable signal that is opposed by an advective flow generated by an actomyosin stress gradient. Experimental observations on the behavior of the system when contractility is inhibited are in qualitative agreement with the predictions of the model. PMID:28273072

Bistable front dynamics in a contractile medium: Travelling wave fronts and cortical advection define stable zones of RhoA signaling at epithelial adherens junctions.

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Rashmi Priya

2017-03-01

Full Text Available Mechanical coherence of cell layers is essential for epithelia to function as tissue barriers and to control active tissue dynamics during morphogenesis. RhoA signaling at adherens junctions plays a key role in this process by coupling cadherin-based cell-cell adhesion together with actomyosin contractility. Here we propose and analyze a mathematical model representing core interactions involved in the spatial localization of junctional RhoA signaling. We demonstrate how the interplay between biochemical signaling through positive feedback, combined with diffusion on the cell membrane and mechanical forces generated in the cortex, can determine the spatial distribution of RhoA signaling at cell-cell junctions. This dynamical mechanism relies on the balance between a propagating bistable signal that is opposed by an advective flow generated by an actomyosin stress gradient. Experimental observations on the behavior of the system when contractility is inhibited are in qualitative agreement with the predictions of the model.

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

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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.

Radionuclide cisternographic findings in patients with spontaneous intracranial hypotension

International Nuclear Information System (INIS)

Jung, Dong Jin; Kim, Jae Seung; Ryu, Jin Sook; Shin, Jung Woo; Im, Joo Hyuk; Lee, Myoung Chong; Jung, Sung Joo; Moon, Dae Hyuk; Lee, Hee Kyung

1998-01-01

Radionuclide cisternography may be helpful in understanding pathophysiology of postural headache and low CSF pressure in patients with spontaneous intracranial hypotension. The purpose of this study was to characterize radionuclide cisternogrpahic findings of spontaneous intracranial hypotension. The study population consists of 15 patients with spontaneous intracranial hypotension. Diagnosis was based on their clinical symptoms and results of lumbar puncture. All patients underwent radionuclide cisternography following injection of 111 to 222 MBq of Tc-99m DTPA into the lumbar subarachnoid space. Sequential images were obtained between 1/2 hour and 24 hour after the injection of Tc-99m DTPA. Radioactivity of the bladder, soft tissue uptake, migration of radionuclide in the subarachnoid space, and extradural leakage of radionuclide were evaluated according to the scan time. Radionuclide cisternogram showed delayed migration of radionuclide into the cerebral convexity (14/15), increased soft tissue uptake (11/15), and early visualization of bladder activity at 30 min (6/10) and 2 hr (13/13). Cisternography also demonstrated leakage site of CSF in 4 cases and 2 of these were depicted at 30min. Epidural blood patch was done in 11 patients and headache was improved in all cases. The characteristics findings of spontaneous intracranial hypotension were delayed migration of radionuclide and early visualization of the soft tissue and bladder activity. These scintigraphic findings suggest that CSF leakage rather than increased CSF absorption or decreased production may be the main pathophysiology of spontaneous intracranial hypotension. Early and multiple imaging including the bladder and soft tissue is required to observe the entire dynamics of radionuclide migration

Experimental investigation on spontaneously active hippocampal cultures recorded by means of high-density MEAs: analysis of the spatial resolution effects

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Alessandro Maccione

2010-05-01

Full Text Available Based on experiments performed with high-resolution Active Pixel Sensor microelectrode arrays (APS-MEAs coupled with spontaneously active hippocampal cultures, this work investigates the spatial resolution effects of the neuroelectronic interface on the analysis of the recorded electrophysiological signals. The adopted methodology consists, first, in recording the spontaneous activity at the highest spatial resolution (inter-electrode separation of 21 µm from the whole array of 4096 microelectrodes. Then, the full resolution dataset is spatially down sampled in order to evaluate the effects on raster plot representation, array-wide spike rate (AWSR, mean firing rate (MFR and mean bursting rate (MBR. Furthermore, the effects of the array-to-network relative position are evaluated by shifting a subset of equally spaced electrodes on the entire recorded area. Results highlight that MFR and MBR are particularly influenced by the spatial resolution provided by the neuroelectronic interface. On high-resolution large MEAs, such analysis better represent the time-based parameterization of the network dynamics. Finally, this work suggest interesting capabilities of high-resolution MEAs for spatial-based analysis in dense and low-dense neuronal preparation for investigating signalling at both local and global neuronal circuitries.

Passive heating following the prematch warm-up in soccer: examining the time-course of changes in muscle temperature and contractile function.

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Marshall, Paul W M; Cross, Rebecca; Lovell, Ric

2015-12-01

This study examined changes in muscle temperature, electrically evoked muscle contractile properties, and voluntary power before and after a soccer specific active warm-up and subsequent rest period. Ten amateur soccer players performed two experimental sessions that involved performance of a modified FIFA 11+ soccer specific warm-up, followed by a 12.5-min rest period where participants were required to wear either normal clothing or a passive electrical heating garment was applied to the upper thigh muscles. Assessments around the warm-up and cool-down included measures of maximal torque, rate of torque development, muscle temperature (Tm), and electrically evoked measures of quadriceps contractile function. Tm was increased after the warm-up by 3.2 ± 0.7°C (P warm-up between 20% and 30% (P warm-up did not effect variables measured. While Tm was reduced by 1.4 ± 0.4°C after the rest period (P warm-up levels. Voluntary and evoked rate of torque development remained elevated from pre warm-up levels at the end of the cool-down (P warm-up elevated muscle temperature by 3.2°C and was associated with concomitant increases of between 20% and 30% in voluntary rate of torque development, which seems explained by elevations in rate-dependent measures of intrinsic muscle contractile function. Application of a passive heating garment did not attenuate declines in muscle temperature during a 12.5-min rest period. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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.

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

Changes in Brain Activation Associated with Spontaneous Improvization and Figural Creativity After Design-Thinking-Based Training: A Longitudinal fMRI Study.

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Saggar, Manish; Quintin, Eve-Marie; Bott, Nicholas T; Kienitz, Eliza; Chien, Yin-Hsuan; Hong, Daniel W-C; Liu, Ning; Royalty, Adam; Hawthorne, Grace; Reiss, Allan L

2017-07-01

Creativity is widely recognized as an essential skill for entrepreneurial success and adaptation to daily-life demands. However, we know little about the neural changes associated with creative capacity enhancement. For the first time, using a prospective, randomized control design, we examined longitudinal changes in brain activity associated with participating in a five-week design-thinking-based Creative Capacity Building Program (CCBP), when compared with Language Capacity Building Program (LCBP). Creativity, an elusive and multifaceted construct, is loosely defined as an ability to produce useful/appropriate and novel outcomes. Here, we focus on one of the facets of creative thinking-spontaneous improvization. Participants were assessed pre- and post-intervention for spontaneous improvization skills using a game-like figural Pictionary-based fMRI task. Whole-brain group-by-time interaction revealed reduced task-related activity in CCBP participants (compared with LCBP participants) after training in the right dorsolateral prefrontal cortex, anterior/paracingulate gyrus, supplementary motor area, and parietal regions. Further, greater cerebellar-cerebral connectivity was observed in CCBP participants at post-intervention when compared with LCBP participants. In sum, our results suggest that improvization-based creative capacity enhancement is associated with reduced engagement of executive functioning regions and increased involvement of spontaneous implicit processing. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Defect Proliferation in Active Nematic Suspensions

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Mishra, Prashant; Bowick, Mark J.; Giomi, Luca; Marchetti, M. Cristina

2014-03-01

The rich structure of equilibrium nematic suspensions, with their characteristic disclination defects, is modified when active forces come into play. The uniform nematic state is known to be unstable to splay (extensile) or bend (contractile) deformations above a critical activity. At even higher activity the flow becomes oscillatory and eventually turbulent. Using hydrodynamics, we classify the active flow regimes as functions of activity and order parameter friction for both contractile and extensile systems. The turbulent regime is marked by a non-zero steady state density of mobile defect pairs. The defect density itself scales with an ``active Ericksen number,'' defined as the ratio of the rate at which activity is injected into the system to the relaxation rate of orientational deformations. The work at Syracuse University was supported by the NSF on grant DMR-1004789 and by the Syracuse Soft Matter Program.

Insulin-Like Growth Factor I (IGF-1) Deficiency Ameliorates Sex Difference in Cardiac Contractile Function and Intracellular Ca2+ Homeostasis

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Ceylan-Isik, Asli F.; Li, Qun; Ren, Jun

2011-01-01

Sex difference in cardiac contractile function exists which may contribute to the different prevalence in cardiovascular diseases between genders. However, the precise mechanisms of action behind sex difference in cardiac function are still elusive. Given that sex difference exists in insulin-like growth factor I (IGF-1) cascade, this study is designed to evaluate the impact of severe liver IGF-1 deficiency (LID) on sex difference in cardiac function. Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ properties were evaluated including ventricular geometry, fractional shortening, peak shortening, maximal velocity of shortening/relengthening (± dL/dt), time-to-peak shortening (TPS), time-to-90% relengthening (TR90), fura-fluorescence intensity (FFI) and intracellular Ca2+ clearance. Female C57 mice exhibited significantly higher plasma IGF-1 levels than their male counterpart. LID mice possessed comparably low IGF-1 levels in both sexes. Female C57 and LID mice displayed lower body, heart and liver weights compared to male counterparts. Echocardiographic analysis revealed larger LV mass in female C57 but not LID mice without sex difference in other cardiac geometric indices. Myocytes from female C57 mice exhibited reduced peak shortening, ± dL/dt, longer TPS, TR90 and intracellular Ca2+ clearance compared with males. Interestingly, this sex difference was greatly attenuated or abolished by IGF-1 deficiency. Female C57 mice displayed significantly decreased mRNA and protein levels of Na+-Ca2+ exchanger, SERCA2a and phosphorylated phospholamban as well as SERCA activity compared with male C57 mice. These sex differences in Ca2+ regulatory proteins were abolished or overtly attenuated by IGF-1 deficiency. In summary, our data suggested that IGF-1 deficiency may significantly attenuated or mitigate the sex difference in cardiomyocyte contractile function associated with intracellular Ca2+ regulation. PMID:21763763

Insulin-like growth factor I (IGF-1) deficiency ameliorates sex difference in cardiac contractile function and intracellular Ca(2+) homeostasis.

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Ceylan-Isik, Asli F; Li, Qun; Ren, Jun

2011-10-10

Sex difference in cardiac contractile function exists which may contribute to the different prevalence in cardiovascular diseases between genders. However, the precise mechanisms of action behind sex difference in cardiac function are still elusive. Given that sex difference exists in insulin-like growth factor I (IGF-1) cascade, this study is designed to evaluate the impact of severe liver IGF-1 deficiency (LID) on sex difference in cardiac function. Echocardiographic, cardiomyocyte contractile and intracellular Ca(2+) properties were evaluated including ventricular geometry, fractional shortening, peak shortening, maximal velocity of shortening/relengthening (±dL/dt), time-to-peak shortening (TPS), time-to-90% relengthening (TR(90)), fura-fluorescence intensity (FFI) and intracellular Ca(2+) clearance. Female C57 mice exhibited significantly higher plasma IGF-1 levels than their male counterpart. LID mice possessed comparably low IGF-1 levels in both sexes. Female C57 and LID mice displayed lower body, heart and liver weights compared to male counterparts. Echocardiographic analysis revealed larger LV mass in female C57 but not LID mice without sex difference in other cardiac geometric indices. Myocytes from female C57 mice exhibited reduced peak shortening, ±dL/dt, longer TPS, TR(90) and intracellular Ca(2+) clearance compared with males. Interestingly, this sex difference was greatly attenuated or abolished by IGF-1 deficiency. Female C57 mice displayed significantly decreased mRNA and protein levels of Na(+)-Ca(2+) exchanger, SERCA2a and phosphorylated phospholamban as well as SERCA activity compared with male C57 mice. These sex differences in Ca(2+) regulatory proteins were abolished or overtly attenuated by IGF-1 deficiency. In summary, our data suggested that IGF-1 deficiency may significantly attenuated or mitigate the sex difference in cardiomyocyte contractile function associated with intracellular Ca(2+) regulation. Copyright © 2011 Elsevier Ireland

Neural substrates of spontaneous musical performance: an FMRI study of jazz improvisation.

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Limb, Charles J; Braun, Allen R

2008-02-27

To investigate the neural substrates that underlie spontaneous musical performance, we examined improvisation in professional jazz pianists using functional MRI. By employing two paradigms that differed widely in musical complexity, we found that improvisation (compared to production of over-learned musical sequences) was consistently characterized by a dissociated pattern of activity in the prefrontal cortex: extensive deactivation of dorsolateral prefrontal and lateral orbital regions with focal activation of the medial prefrontal (frontal polar) cortex. Such a pattern may reflect a combination of psychological processes required for spontaneous improvisation, in which internally motivated, stimulus-independent behaviors unfold in the absence of central processes that typically mediate self-monitoring and conscious volitional control of ongoing performance. Changes in prefrontal activity during improvisation were accompanied by widespread activation of neocortical sensorimotor areas (that mediate the organization and execution of musical performance) as well as deactivation of limbic structures (that regulate motivation and emotional tone). This distributed neural pattern may provide a cognitive context that enables the emergence of spontaneous creative activity.

Neural substrates of spontaneous musical performance: an FMRI study of jazz improvisation.

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Charles J Limb

Full Text Available To investigate the neural substrates that underlie spontaneous musical performance, we examined improvisation in professional jazz pianists using functional MRI. By employing two paradigms that differed widely in musical complexity, we found that improvisation (compared to production of over-learned musical sequences was consistently characterized by a dissociated pattern of activity in the prefrontal cortex: extensive deactivation of dorsolateral prefrontal and lateral orbital regions with focal activation of the medial prefrontal (frontal polar cortex. Such a pattern may reflect a combination of psychological processes required for spontaneous improvisation, in which internally motivated, stimulus-independent behaviors unfold in the absence of central processes that typically mediate self-monitoring and conscious volitional control of ongoing performance. Changes in prefrontal activity during improvisation were accompanied by widespread activation of neocortical sensorimotor areas (that mediate the organization and execution of musical performance as well as deactivation of limbic structures (that regulate motivation and emotional tone. This distributed neural pattern may provide a cognitive context that enables the emergence of spontaneous creative activity.

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

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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.

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

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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.

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

Neurogenic detrusor overactivity is associated with decreased expression and function of the large conductance voltage- and Ca(2+-activated K(+ channels.

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Kiril L Hristov

Full Text Available Patients suffering from a variety of neurological diseases such as spinal cord injury, Parkinson's disease, and multiple sclerosis often develop neurogenic detrusor overactivity (NDO, which currently lacks a universally effective therapy. Here, we tested the hypothesis that NDO is associated with changes in detrusor smooth muscle (DSM large conductance Ca(2+-activated K(+ (BK channel expression and function. DSM tissue samples from 33 patients were obtained during open bladder surgeries. NDO patients were clinically characterized preoperatively with pressure-flow urodynamics demonstrating detrusor overactivity, in the setting of a clinically relevant neurological condition. Control patients did not have overactive bladder and did not have a clinically relevant neurological disease. We conducted quantitative polymerase chain reactions (qPCR, perforated patch-clamp electrophysiology on freshly-isolated DSM cells, and functional studies on DSM contractility. qPCR experiments revealed that DSM samples from NDO patients showed decreased BK channel mRNA expression in comparison to controls. Patch-clamp experiments demonstrated reduced whole cell and transient BK currents (TBKCs in freshly-isolated DSM cells from NDO patients. Functional studies on DSM contractility showed that spontaneous phasic contractions had a decreased sensitivity to iberiotoxin, a selective BK channel inhibitor, in DSM strips isolated from NDO patients. These results reveal the novel finding that NDO is associated with decreased DSM BK channel expression and function leading to increased DSM excitability and contractility. BK channel openers or BK channel gene transfer could be an alternative strategy to control NDO. Future clinical trials are needed to evaluate the value of BK channel opening drugs or gene therapies for NDO treatment and to identify any possible adverse effects.

Hibiscus Sabdariffa L. Flowers and Olea Europea L. Leaves Extract-Based Formulation for Hypertension Care: In Vitro Efficacy and Toxicological Profile.

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Micucci, Matteo; Angeletti, Andrea; Cont, Massimiliano; Corazza, Ivan; Aldini, Rita; Donadio, Elisa; Chiarini, Alberto; Budriesi, Roberta

2016-05-01

Olea europaea L. leaves extract (Oe) and Hybiscus sabdariffa L. flowers extract (Hs) have calcium antagonistic properties. Aim of this work was to study the cardiovascular effects of Pres Phytum(®), a nutraceutical formulation containing a mixture of the two extracts and the excipients, and investigate its possible off-target effects, using in vitro biological assays on guinea pig isolated organs. Cardiovascular effects were assessed using guinea pig atria and aorta. The effects of Pres Phytum on spontaneous gastrointestinal, urinary, and respiratory tracts smooth muscle contractility were evaluated. Pres Phytum exerted a vasorelaxant effect (IC50 = 2.38 mg/mL) and a negative chronotropic effect (IC50 = 1.04 mg/mL) at concentrations lower than those producing smooth muscle spontaneous contractility alterations in the other organs. Compared to Pres Phytum, the mixture did not exert negative inotropic activity, while it maintained a negative chronotropic efficacy (IC50 = 1.04 mg/mL). These experimental data suggest a possible nutraceutical use of this food supplement for the management of preclinical hypertension.

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

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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

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

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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.

Transformation quantum optics: designing spontaneous emission using coordinate transformations

DEFF Research Database (Denmark)

Zhang, Jingjing; Wubs, Martijn; Ginzburg, Pavel

2016-01-01

Spontaneous decay is a fundamental quantum property of emitters that can be controlled in a material environment via modification of the local density of optical states (LDOS). Here we use transformation optics methods in order to design required density of states and thus spontaneous emission (S......, affect the LDOS in complex materials. Tailoring SE properties using transformation optics approach provides an innovative way for designing emission properties in a complex material environment needed for the development of active nanophotonic devices....

Drug-induced modification of the system properties associated with spontaneous human electroencephalographic activity

Science.gov (United States)

Liley, David T.; Cadusch, Peter J.; Gray, Marcus; Nathan, Pradeep J.

2003-11-01

The benzodiazepine (BZ) class of minor tranquilizers are important modulators of the γ-amino butyric acid (GABAA)/BZ receptor complex that are well known to affect the spectral properties of spontaneous electroencephalographic activity. While it is experimentally well established that the BZs reduce total alpha band (8 13 Hz) power and increase total beta band (13 30 Hz) power, it is unclear what the physiological basis for this effect is. Based on a detailed theory of cortical electrorhythmogenesis it is conjectured that such an effect is explicable in terms of the modulation of GABAergic neurotransmission within locally connected populations of excitatory and inhibitory cortical neurons. Motivated by this theory, fixed order autoregressive moving average (ARMA) models were fitted to spontaneous eyes-closed electroencephalograms recorded from subjects before and approximately 2 h after the oral administration of a single 1 mg dose of the BZ alprazolam. Subsequent pole-zero analysis revealed that BZs significantly transform the dominant system pole such that its frequency and damping increase. Comparisons of ARMA derived power spectra with fast Fourier transform derived spectra indicate an enhanced ability to identify benzodiazepine induced electroencephalographic changes. This experimental result is in accord with the theoretical predictions implying that alprazolam enhances inhibition acting on inhibitory neurons more than inhibition acting on excitatory neurons. Further such a result is consistent with reported cortical neuronal distributions of the various GABAA receptor pharmacological subtypes. Therefore physiologically specified fixed order ARMA modeling is expected to become an important tool for the systematic investigation and modeling of a wide range of cortically acting compounds.

ANTIMICROBIAL ACTIVITY OF EXTRACTS OF WILD GARLIC (Allium ursinum FROM ROMANIAN SPONTANEOUS FLORA

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MARIANA LUPOAE

2014-05-01

Full Text Available Wild Romanian spontaneous garlic’s (Allium ursinum antimicrobial activity was tested in order to establish the inhibition potential of growth of some microorganisms. As test microorganisms were used pure cultures of fungs (Aspergillus glaucus, Geotrichum candidum, Mucor mucedo, Saccharomyces cerevisiae and bacteria (Bacillus subtilis isolated from food microbiota. There were also, used microbial strains isolated from different pathological products: wound secretions (Staphylococcus aureus, throat swab (Streptococcus pyogenes, urine (Escherichia coli and oral mucosa (Candida albicans. The antimicrobial potential of used extracts is highlighted depending on the type of the vegetal tissue (leaves, roots, bulbs and the nature of the solvent used for extraction. Extracts used in these experiments are recommended to use in food industry to preserve the stability and to improve the organoleptic quality of products.

Spontaneous external gallbladder perforation

International Nuclear Information System (INIS)

Noeldge, G.; Wimmer, B.; Kirchner, R.

1981-01-01

Spontaneous perforation of the gallbladder is one complication of cholelithiasis. There is a greater occurence of free perforation in the peritoneal cavity with bilary pertonitis, followed by the perforation into the stomach, small intestine and colon. A single case of the nowadays rare spontaneous perforation in and through the abdominal wall will be reported. Spontaneous gallbladder perforation appears nearly asymptomatic in its clinical course because of absent biliary peritonitis. (orig.) [de

Use of scripts and script-fading procedures and activity schedules to develop spontaneous social interaction in a three-year-old girl with autism

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Anna Budzińska

2014-05-01

Full Text Available Autism entails serious deficiencies in communication and social behaviors. Individuals with autism, even those who have received intensive language intervention, are often viewed as lacking spontaneous language. In addition, some children with autism lack the ability of spontaneously seeking to share enjoyment, interests, or achievements with other people (e.g., a lack of showing, bringing, or pointing out objects of interest to other people. The aim of the study was to use ABA teaching techniques such as script and script fading procedure and activity schedule to teach three-year-old girl with autism spontaneous social interaction and shape joint attention skills. The result shows that ABA techniques were very effective in teaching many verbal skills such as answering questions, making requests, initiating conversation and asking question. Comparison made after implemented teaching procedure shows her initiating of joint attention skill (IJA is at the appropriate level for her age.

High Intensity Exercise in Multiple Sclerosis: Effects on Muscle Contractile Characteristics and Exercise Capacity, a Randomised Controlled Trial.

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Inez Wens

Full Text Available Low-to-moderate intensity exercise improves muscle contractile properties and endurance capacity in multiple sclerosis (MS. The impact of high intensity exercise remains unknown.Thirty-four MS patients were randomized into a sedentary control group (SED, n = 11 and 2 exercise groups that performed 12 weeks of a high intensity interval (HITR, n = 12 or high intensity continuous cardiovascular training (HCTR, n = 11, both in combination with resistance training. M.vastus lateralis fiber cross sectional area (CSA and proportion, knee-flexor/extensor strength, body composition, maximal endurance capacity and self-reported physical activity levels were assessed before and after 12 weeks.Compared to SED, 12 weeks of high intensity exercise increased mean fiber CSA (HITR: +21 ± 7%, HCTR: +23 ± 5%. Furthermore, fiber type I CSA increased in HCTR (+29 ± 6%, whereas type II (+23 ± 7% and IIa (+23 ± 6%, CSA increased in HITR. Muscle strength improved in HITR and HCTR (between +13 ± 7% and +45 ± 20% and body fat percentage tended to decrease (HITR: -3.9 ± 2.0% and HCTR: -2.5 ± 1.2%. Furthermore, endurance capacity (Wmax +21 ± 4%, time to exhaustion +24 ± 5%, VO2max +17 ± 5% and lean tissue mass (+1.4 ± 0.5% only increased in HITR. Finally self-reported physical activity levels increased 73 ± 19% and 86 ± 27% in HCTR and HITR, respectively.High intensity cardiovascular exercise combined with resistance training was safe, well tolerated and improved muscle contractile characteristics and endurance capacity in MS.ClinicalTrials.gov NCT01845896.

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.

Spontaneous and posed facial expression in Parkinson's disease.

Science.gov (United States)

Smith, M C; Smith, M K; Ellgring, H

1996-09-01

Spontaneous and posed emotional facial expressions in individuals with Parkinson's disease (PD, n = 12) were compared with those of healthy age-matched controls (n = 12). The intensity and amount of facial expression in PD patients were expected to be reduced for spontaneous but not posed expressions. Emotional stimuli were video clips selected from films, 2-5 min in duration, designed to elicit feelings of happiness, sadness, fear, disgust, or anger. Facial movements were coded using Ekman and Friesen's (1978) Facial Action Coding System (FACS). In addition, participants rated their emotional experience on 9-point Likert scales. The PD group showed significantly less overall facial reactivity than did controls when viewing the films. The predicted Group X Condition (spontaneous vs. posed) interaction effect on smile intensity was found when PD participants with more severe disease were compared with those with milder disease and with controls. In contrast, ratings of emotional experience were similar for both groups. Depression was positively associated with emotion rating but not with measures of facial activity. Spontaneous facial expression appears to be selectively affected in PD, whereas posed expression and emotional experience remain relatively intact.

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

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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

Definition of spontaneous reconnection

International Nuclear Information System (INIS)

Schindler, K.

1984-01-01

The author discusses his view of driven versus spontaneous. There is a close link between ''spontaneous'' and ''instability.'' One of the prominent examples for instability is the thermal convection instability. Just to remind you, if you heat a fluid layer from below, it takes a certain Rayleigh number to make it unstable. Beyond the onset point you find qualitatively new features. That is called ''spontaneous,'' and this is a bit more than semantics. It's a new qualitative property that appears and it is spontaneous although we have an energy flux through the system. It's a misconception, to call this ''driven'' pointing at the energy flux through it. Of course, the convection would not exist without this energy flux. But what makes it ''spontaneous'' is that without any particular external signal, a new qualitative feature appears. And this is what is called an ''instability'' and ''spontaneous.'' From these considerations the author got a little reassured of what distinction should be made in the field of the magnetosphere. If we have a smooth energy transport into the magnetosphere and suddenly we have this qualitatively new feature (change of B-topology) coming up; then, using this terminology we don't have a choice other than calling this spontaneous or unstable, if you like. If we ''tell'' the system where it should make its neutral line and where it should make its plasmoids, then, it is driven. And this provides a very clear-cut observational distinction. The author emphasizes the difference he sees is a qualitative difference, not only a quantitative one

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.

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

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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.

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.

Central hemodynamics and left-ventricural contractility in patients with chronic obstructive pulmonary diseases and stable pulmonary hypertension: a radionuclide study

International Nuclear Information System (INIS)

Paleev, N.R.; Malov, G.A.; Cherejskaya, N.K.; Oblovatskaya, O.G.; Tsar'kova, L.N.; Zil'berman, E.Eh.; Akademiya Meditsinskikh Nauk SSSR, Moscow. Inst. Serdechno-Sosudistoj Khirurgii)

1987-01-01

Systemic, central and intracardiac hemodynamics and left-ventricular contractility were studied radiocardiographically and radioventriculographically in 22 patients with stable pulmanory hypertension, developing in the presence of chronic obstructive pulmanory diseases. A tendency to increased circulating blood volume, significantly elevated end diastolic and end systolic indices, reduced total ejection fraction, and a tendency to decreased segmental ejection fractions were demonstrated. A significant reduction of the speed and percetage of left-ventricular myocardial circular fibre contraction is another evedence of incompetent left-ventricular contractility, in addition to the reduced ejection fraction

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...

Spontaneous ad hoc mobile cloud computing network.

Science.gov (United States)

Lacuesta, Raquel; Lloret, Jaime; Sendra, Sandra; Peñalver, Lourdes

2014-01-01

Cloud computing helps users and companies to share computing resources instead of having local servers or personal devices to handle the applications. Smart devices are becoming one of the main information processing devices. Their computing features are reaching levels that let them create a mobile cloud computing network. But sometimes they are not able to create it and collaborate actively in the cloud because it is difficult for them to build easily a spontaneous network and configure its parameters. For this reason, in this paper, we are going to present the design and deployment of a spontaneous ad hoc mobile cloud computing network. In order to perform it, we have developed a trusted algorithm that is able to manage the activity of the nodes when they join and leave the network. The paper shows the network procedures and classes that have been designed. Our simulation results using Castalia show that our proposal presents a good efficiency and network performance even by using high number of nodes.

Electromyographic activity associated with spontaneous functional recovery after spinal cord injury in rats.

Science.gov (United States)

Kaegi, Sibille; Schwab, Martin E; Dietz, Volker; Fouad, Karim

2002-07-01

This investigation was designed to study the spontaneous functional recovery of adult rats with incomplete spinal cord injury (SCI) at thoracic level during a time course of 2 weeks. Daily testing sessions included open field locomotor examination and electromyographic (EMG) recordings from a knee extensor (vastus lateralis, VL) and an ankle flexor muscle (tibialis anterior, TA) in the hindlimbs of treadmill walking rats. The BBB score (a locomotor score named after Basso et al., 1995, J. Neurotrauma, 12, 1-21) and various measures from EMG recordings were analysed (i.e. step cycle duration, rhythmicity of limb movements, flexor and extensor burst duration, EMG amplitude, root-mean-square, activity overlap between flexor and extensor muscles and hindlimb coupling). Directly after SCI, a marked drop in locomotor ability occurred in all rats with subsequent partial recovery over 14 days. The recovery was most pronounced during the first week. Significant changes were noted in the recovery of almost all analysed EMG measures. Within the 14 days of recovery, many of these measures approached control levels. Persistent abnormalities included a prolonged flexor burst and increased activity overlap between flexor and extensor muscles. Activity overlap between flexor and extensor muscles might be directly caused by altered descending input or by maladaptation of central pattern generating networks and/or sensory feedback.

Altered regional homogeneity of spontaneous brain activity in idiopathic trigeminal neuralgia

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Wang Y

2015-10-01

Full Text Available Yanping Wang,1,2 Xiaoling Zhang,2 Qiaobing Guan,2 Lihong Wan,2 Yahui Yi,2 Chun-Feng Liu1 1Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 2Department of Neurology, The Second Hospital of Jiaxing City, Jiaxing, Zhejiang Province, People’s Republic of China Abstract: The pathophysiology of idiopathic trigeminal neuralgia (ITN has conventionally been thought to be induced by neurovascular compression theory. Recent structural brain imaging evidence has suggested an additional central component for ITN pathophysiology. However, far less attention has been given to investigations of the basis of abnormal resting-state brain activity in these patients. The objective of this study was to investigate local brain activity in patients with ITN and its correlation with clinical variables of pain. Resting-state functional magnetic resonance imaging data from 17 patients with ITN and 19 age- and sex-matched healthy controls were analyzed using regional homogeneity (ReHo analysis, which is a data-driven approach used to measure the regional synchronization of spontaneous brain activity. Patients with ITN had decreased ReHo in the left amygdala, right parahippocampal gyrus, and left cerebellum and increased ReHo in the right inferior temporal gyrus, right thalamus, right inferior parietal lobule, and left postcentral gyrus (corrected. Furthermore, the increase in ReHo in the left precentral gyrus was positively correlated with visual analog scale (r=0.54; P=0.002. Our study found abnormal functional homogeneity of intrinsic brain activity in several regions in ITN, suggesting the maladaptivity of the process of daily pain attacks and a central role for the pathophysiology of ITN. Keywords: trigeminal neuralgia, resting fMRI, brain, chronic pain, local connectivity

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.

Intestinal myoelectric activity and contractile motility in dogs with a reversed jejunal segment after extensive small bowel resection.

Science.gov (United States)

Uchiyama, M; Iwafuchi, M; Ohsawa, Y; Yagi, M; Iinuma, Y; Ohtani, S

1992-06-01

To evaluate the functioning and effectiveness of a reversed jejunal segment after extensive small bowel resection, we continuously measured the postoperative bowel motility (using bipolar electrodes and/or contractile strain gage force transducers) in interdigestive and postprandial conscious dogs at 2 to 5 weeks after surgery. The fasting duodenal migrating myoelectric (or motor) complex (MMC) occurred at markedly longer intervals in dogs with a 20-cm reversed jejunal segment created after 75% to 80% extensive small bowel resection (group 3) than in dogs that received extensive resection alone (group 2) or dogs that underwent construction of a reversed jejunal segment without bowel resection (group 1). The MMC arising from the duodenum was often interrupted at the jejunum above the proximal anastomosis and did not migrate smoothly to the reversed segment or terminal ileum in group 3. In addition, brief small discordant contractions were frequent in the reversed segment and the jejunum above the proximal anastomosis in group 3. The duration of the postprandial period without duodenal MMC activity was significantly prolonged in groups 2 and 3. These results suggest that the transit time and passage of intestinal contents were delayed and that the periodical MMC was disturbed in group 3. The delay of transit time was due to prolongation of the interval between duodenal MMCs, the interruption of MMC propagation at the jejunum above the proximal anastomosis, the dominance of MMCs that followed the inherent anatomical continuity of the bowel, and discordant movements across the proximal anastomosis. Functional obstruction could be a potential problem in a 20-cm reversed jejunal segment inserted after extensive small bowel resection.

Effect of aqueous extract of mango kernel (Mangifera Indica on basal activity of virgin rat uterine smooth muscle: role of muscarinic receptors

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Mehdi Noureddini

2017-04-01

Full Text Available Background: Mango belongs to the Anacardiaceae and the extracts from its stems, leaves, fruit and kernel are reported to affect smooth muscle contractility. We studied the role of cholinergic muscarinic receptors for the effects of aqueous extract of mango kernel (Mangifera indica on the basal activity of virgin rat uterine smooth muscle. Materials and Methods: In this experimental study, mid-sections (n=24 of the uterine of healthy virgin rats were placed in an organ bath containing carbonated Tyrode’s solution under 1 g tension. The cumulative effects of the aqueous extracts of mango kernel (0.002, 0.02, 0.2, 2, 20, 200, and 2000 μg/mL or extract vehicle (Tyrode’s solution in the presence or absence of atropine were examined by isometric method using the strength, frequency and contractile activity of uterine smooth muscle. Results: The cumulative concentrations (0.002-20 µg/ml of mango kernel aqueous extract was significantly decreased the strength, frequency and contractile activity of uterine smooth muscle, but the contractile activity was returned to the basal level at the concentrations of 200 and 2000 µg/ml. Atropine (1 µM could not significantly change the effects of cumulative use of extract on the strength and contractile activity of uterine smooth muscle, but it significantly enhanced the contractile frequency at low concentrations. Conclusion: The effects of aqueous extract of mango kernel on the activity of the uterine smooth muscle might not be through cholinergic muscarinic receptors and atropine could enhance the effects of the extract on frequency through other receptors.

Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation.

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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.

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.

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

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

Analysis of SOS-Induced Spontaneous Prophage Induction in Corynebacterium glutamicum at the Single-Cell Level

Science.gov (United States)

Nanda, Arun M.; Heyer, Antonia; Krämer, Christina; Grünberger, Alexander; Kohlheyer, Dietrich

2014-01-01

The genome of the Gram-positive soil bacterium Corynebacterium glutamicum ATCC 13032 contains three integrated prophage elements (CGP1 to -3). Recently, it was shown that the large lysogenic prophage CGP3 (∼187 kbp) is excised spontaneously in a small number of cells. In this study, we provide evidence that a spontaneously induced SOS response is partly responsible for the observed spontaneous CGP3 induction. Whereas previous studies focused mainly on the induction of prophages at the population level, we analyzed the spontaneous CGP3 induction at the single-cell level using promoters of phage genes (Pint2 and Plysin) fused to reporter genes encoding fluorescent proteins. Flow-cytometric analysis revealed a spontaneous CGP3 activity in about 0.01 to 0.08% of the cells grown in standard minimal medium, which displayed a significantly reduced viability. A PrecA-eyfp promoter fusion revealed that a small fraction of C. glutamicum cells (∼0.2%) exhibited a spontaneous induction of the SOS response. Correlation of PrecA to the activity of downstream SOS genes (PdivS and PrecN) confirmed a bona fide induction of this stress response rather than stochastic gene expression. Interestingly, the reporter output of PrecA and CGP3 promoter fusions displayed a positive correlation at the single-cell level (ρ = 0.44 to 0.77). Furthermore, analysis of the PrecA-eyfp/Pint2-e2-crimson strain during growth revealed the highest percentage of spontaneous PrecA and Pint2 activity in the early exponential phase, when fast replication occurs. Based on these studies, we postulate that spontaneously occurring DNA damage induces the SOS response, which in turn triggers the induction of lysogenic prophages. PMID:24163339

Spontaneous intracranial hypotension.

LENUS (Irish Health Repository)

Fullam, L

2012-01-31

INTRODUCTION: Spontaneous\\/primary intracranial hypotension is characterised by orthostatic headache and is associated with characteristic magnetic resonance imaging findings. CASE REPORT: We present a case report of a patient with typical symptoms and classical radiological images. DISCUSSION: Spontaneous intracranial hypotension is an under-recognised cause of headache and can be diagnosed by history of typical orthostatic headache and findings on MRI brain.

Observation of new spontaneous fission activities from elements 100 to 105

International Nuclear Information System (INIS)

Somerville, L.P.

1982-03-01

Several new Spontaneous Fission (SF) activities have been found. No definite identification could be made for any of the new SF activities; however, half-lives and possible assignments to element-104 isotopes consistent with several cross bombardments include 257 Rf(3.8 s, 14% SF), 258 Rf(13 ms), 259 Rf(approx. 3 s, 8% SF), 260 Rf(approx. 20 ms), and 262 Rf(approx. 50 ms). The 80-ms SF activity claimed by the Dubna group for the discovery of element 104 ( 260 104) was not observed. A difficulty exists in the interpretation that 260 Rf is a approx. 20-ms SF activity: in order to be correct, for example, the SF activities with half-lives between 14 and 24 ms produced in the reactions 109- to 119-MeV 18 O + 248 Cm, 88- to 100-MeV 15 N + 249 Bk, and 96-MeV 18 O + 249 Cf must be other nuclides due to their large production cross sections, or the cross sections for production of 260 Rf must be enhanced by unknown mechanisms. Based on calculated total production cross sections a possible approx. 1% electron-capture branch in 258 Lr(4.5 s) to the SF emitter 258 No(1.2 ms) and an upper limit of 0.05% for SF branching in 254 No(55 s) were determined. Other measured half-lives from unknown nuclides produced in respective reactions include approx. 1.6 s ( 18 O + 248 CM), indications of a approx. 47-s SF activity (75-MeV 12 C + 249 Cf), and two or more SF activities with 3 s less than or equal to T/sub 1/2/ less than or equal to 60 s ( 18 O + 249 Bk). The most exciting conclusion of this work is that if the tentative assignments to even-even element 104 isotopes are correct, there would be a sudden change in the SF half-life systematics at element 104 which has been predicted theoretically and attributed to the disappearance of the second hump of the double-humped fission barrier

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.

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...

The perception of musical spontaneity in improvised and imitated jazz performances

Directory of Open Access Journals (Sweden)

Annerose eEngel

2011-05-01

Full Text Available The ability to evaluate spontaneity in human behavior is called upon in the aesthetic appreciation of dramatic arts and music. The current study addresses the behavioral and brain mechanisms that mediate the perception of spontaneity in music performance. In a functional Magnetic Resonance Imaging experiment, 22 jazz musicians listened to piano melodies and judged whether they were improvised or imitated. Judgment accuracy (mean 55%; range 44-65%, which was low but above chance, was positively correlated with musical experience and empathy. Analysis of listeners’ hemodynamic responses revealed that amygdala activation was stronger for improvisations than imitations. This activation correlated with the variability of performance timing and intensity (loudness in the melodies, suggesting that the amygdala is involved in the detection of behavioral uncertainty. An analysis based on the subjective classification of melodies according to listeners’ judgments revealed that a network including the pre-supplementary motor area, frontal operculum, and anterior insula was most strongly activated for melodies judged to be improvised. This may reflect the increased engagement of an action simulation network when melodic predictions are rendered challenging due to perceived instability in the performer’s actions. Taken together, our results suggest that, while certain brain regions in skilled individuals may be generally sensitive to objective cues to spontaneity in human behavior, the ability to evaluate spontaneity accurately depends upon whether an individual’s action-related experience and perspective taking skills enable faithful internal simulation of the given behavior.

The perception of musical spontaneity in improvised and imitated jazz performances.

Science.gov (United States)

Engel, Annerose; Keller, Peter E

2011-01-01

The ability to evaluate spontaneity in human behavior is called upon in the esthetic appreciation of dramatic arts and music. The current study addresses the behavioral and brain mechanisms that mediate the perception of spontaneity in music performance. In a functional magnetic resonance imaging experiment, 22 jazz musicians listened to piano melodies and judged whether they were improvised or imitated. Judgment accuracy (mean 55%; range 44-65%), which was low but above chance, was positively correlated with musical experience and empathy. Analysis of listeners' hemodynamic responses revealed that amygdala activation was stronger for improvisations than imitations. This activation correlated with the variability of performance timing and intensity (loudness) in the melodies, suggesting that the amygdala is involved in the detection of behavioral uncertainty. An analysis based on the subjective classification of melodies according to listeners' judgments revealed that a network including the pre-supplementary motor area, frontal operculum, and anterior insula was most strongly activated for melodies judged to be improvised. This may reflect the increased engagement of an action simulation network when melodic predictions are rendered challenging due to perceived instability in the performer's actions. Taken together, our results suggest that, while certain brain regions in skilled individuals may be generally sensitive to objective cues to spontaneity in human behavior, the ability to evaluate spontaneity accurately depends upon whether an individual's action-related experience and perspective taking skills enable faithful internal simulation of the given behavior.

Shh mediates PDGF-induced contractile-to-synthetic phenotypic modulation in vascular smooth muscle cells through regulation of KLF4

Energy Technology Data Exchange (ETDEWEB)

Zeng, Qiu [Department of Vascular Surgery, 1st Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Wei, Bin [Department of Dermatology, 1st Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Zhao, Yu; Wang, Xuehu; Fu, Qining; Liu, Hong [Department of Vascular Surgery, 1st Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Li, Fenghe, E-mail: lfh_cmu@126.com [Department of Vascular Surgery, 1st Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China)

2016-07-01

Platelet-derived growth factor (PDGF) is known to induce phenotypic switching of vascular smooth muscle cells (VSMCs) from contractile to a pathological synthetic state, which played an essential role in proliferation of VSMCs. Sonic hedgehog (Shh) contributes to the proliferation of VSMCs when induced by PDGF. Here, we investigated the probable role of Shh in PDGF-induced VSMC dedifferentiation and its underlying mechanisms. We found that PDGF stimulated Shh expression in VSMCs, which was mediated by activation of PDGFRβ/ERK1/2 cell signaling pathway. Further, we found PDGF-induced VSMC phenotypic modulation was accompanied by up-regulation of Shh/Gli family zinc finger 2 (Gli2) signaling and Krüppel-like factor 4 (KLF4). When inhibited Shh in the presence of PDGF, the expressions of KLF4 and VSMC dedifferentiation markers were down-regulated and the effect of PDGF in inducing VSMC dedifferentiation was blocked. In the absence of PDGF, Shh signaling activation increased the expression of KLF4 and promoted VSMC dedifferentiation. The results indicate Shh participated in the regulation of PDGF-induced VSMC dedifferentiation. Finally, we found that KLF4 was closely involved in this process. On inhibition of KLF4, PDGF induced VSMC dedifferentiation was abrogated, even in the presence of Shh. Taken together, the results provide critical insights into the newly discovered role of Shh in phenotypic modulation of VSMCs which depends on KLF4. - Highlights: • Shh as a downstream effector of PDGF participates in PDGF-induced VSMC phenotypic modulation. • Shh can promote VSMC phenotypic switching from contractile to synthetic state. • Shh mediates VSMC phenotypic modulation through regulation of KLF4.

Shh mediates PDGF-induced contractile-to-synthetic phenotypic modulation in vascular smooth muscle cells through regulation of KLF4

International Nuclear Information System (INIS)

Zeng, Qiu; Wei, Bin; Zhao, Yu; Wang, Xuehu; Fu, Qining; Liu, Hong; Li, Fenghe

2016-01-01

Platelet-derived growth factor (PDGF) is known to induce phenotypic switching of vascular smooth muscle cells (VSMCs) from contractile to a pathological synthetic state, which played an essential role in proliferation of VSMCs. Sonic hedgehog (Shh) contributes to the proliferation of VSMCs when induced by PDGF. Here, we investigated the probable role of Shh in PDGF-induced VSMC dedifferentiation and its underlying mechanisms. We found that PDGF stimulated Shh expression in VSMCs, which was mediated by activation of PDGFRβ/ERK1/2 cell signaling pathway. Further, we found PDGF-induced VSMC phenotypic modulation was accompanied by up-regulation of Shh/Gli family zinc finger 2 (Gli2) signaling and Krüppel-like factor 4 (KLF4). When inhibited Shh in the presence of PDGF, the expressions of KLF4 and VSMC dedifferentiation markers were down-regulated and the effect of PDGF in inducing VSMC dedifferentiation was blocked. In the absence of PDGF, Shh signaling activation increased the expression of KLF4 and promoted VSMC dedifferentiation. The results indicate Shh participated in the regulation of PDGF-induced VSMC dedifferentiation. Finally, we found that KLF4 was closely involved in this process. On inhibition of KLF4, PDGF induced VSMC dedifferentiation was abrogated, even in the presence of Shh. Taken together, the results provide critical insights into the newly discovered role of Shh in phenotypic modulation of VSMCs which depends on KLF4. - Highlights: • Shh as a downstream effector of PDGF participates in PDGF-induced VSMC phenotypic modulation. • Shh can promote VSMC phenotypic switching from contractile to synthetic state. • Shh mediates VSMC phenotypic modulation through regulation of KLF4.

Stretch activates human myometrium via ERK, caldesmon and focal adhesion signaling.

Directory of Open Access Journals (Sweden)

Yunping Li

2009-10-01

Full Text Available An incomplete understanding of the molecular mechanisms responsible for myometrial activation from the quiescent pregnant state to the active contractile state during labor has hindered the development of effective therapies for preterm labor. Myometrial stretch has been implicated clinically in the initiation of labor and the etiology of preterm labor, but the molecular mechanisms involved in the human have not been determined. We investigated the mechanisms by which gestation-dependent stretch contributes to myometrial activation, by using human uterine samples from gynecologic hysterectomies and Cesarean sections. Here we demonstrate that the Ca requirement for activation of the contractile filaments in human myometrium increases with caldesmon protein content during gestation and that an increase in caldesmon phosphorylation can reverse this inhibitory effect during labor. By using phosphotyrosine screening and mass spectrometry of stretched human myometrial samples, we identify 3 stretch-activated focal adhesion proteins, FAK, p130Cas, and alpha actinin. FAK-Y397, which signals integrin engagement, is constitutively phosphorylated in term human myometrium whereas FAK-Y925, which signals downstream ERK activation, is phosphorylated during stretch. We have recently identified smooth muscle Archvillin (SmAV as an ERK regulator. A newly produced SmAV-specific antibody demonstrates gestation-specific increases in SmAV protein levels and stretch-specific increases in SmAV association with focal adhesion proteins. Thus, whereas increases in caldesmon levels suppress human myometrium contractility during pregnancy, stretch-dependent focal adhesion signaling, facilitated by the ERK activator SmAV, can contribute to myometrial activation. These results suggest that focal adhesion proteins may present new targets for drug discovery programs aimed at regulation of uterine contractility.

Optimization of an NLEO-based algorithm for automated detection of spontaneous activity transients in early preterm EEG

International Nuclear Information System (INIS)

Palmu, Kirsi; Vanhatalo, Sampsa; Stevenson, Nathan; Wikström, Sverre; Hellström-Westas, Lena; Palva, J Matias

2010-01-01

We propose here a simple algorithm for automated detection of spontaneous activity transients (SATs) in early preterm electroencephalography (EEG). The parameters of the algorithm were optimized by supervised learning using a gold standard created from visual classification data obtained from three human raters. The generalization performance of the algorithm was estimated by leave-one-out cross-validation. The mean sensitivity of the optimized algorithm was 97% (range 91–100%) and specificity 95% (76–100%). The optimized algorithm makes it possible to systematically study brain state fluctuations of preterm infants. (note)

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.

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.

[Spontaneous bacterial peritonitis].

Science.gov (United States)

Velkey, Bálint; Vitális, Eszter; Vitális, Zsuzsanna

2017-01-01

Spontaneous bacterial peritonitis occurs most commonly in cirrhotic patients with ascites. Pathogens get into the circulation by intestinal translocation and colonize in peritoneal fluid. Diagnosis of spontaneous bacterial peritonitis is based on elevated polymorphonuclear leukocyte count in the ascites (>0,25 G/L). Ascites culture is often negative but aids to get information about antibiotic sensitivity in positive cases. Treatment in stable patient can be intravenous then orally administrated ciprofloxacin or amoxicillin/clavulanic acid, while in severe cases intravenous III. generation cephalosporin. Nosocomial spontaneous bacterial peritonitis often caused by Gram-positive bacteria and multi-resistant pathogens can also be expected thus carbapenem should be the choice of the empiric treatment. Antibiotic prophylaxis should be considered. Norfloxacin is used most commonly, but changes are expected due to increase in quinolone resistance. As a primary prophylaxis, a short-term antibiotic treatment is recommended after gastrointestinal bleeding for 5 days, while long-term prophylaxis is for patients with low ascites protein, and advanced disease (400 mg/day). Secondary prophylaxis is recommended for all patients recovered from spontaneous bacterial peritonitis. Due to increasing antibiotic use of antibiotics prophylaxis is debated to some degree. Orv. Hetil., 2017, 158(2), 50-57.

High-efficiency electroluminescence and amplified spontaneous emission from a thermally activated delayed fluorescent near-infrared emitter

Science.gov (United States)

Kim, Dae-Hyeon; D'Aléo, Anthony; Chen, Xian-Kai; Sandanayaka, Atula D. S.; Yao, Dandan; Zhao, Li; Komino, Takeshi; Zaborova, Elena; Canard, Gabriel; Tsuchiya, Youichi; Choi, Eunyoung; Wu, Jeong Weon; Fages, Frédéric; Brédas, Jean-Luc; Ribierre, Jean-Charles; Adachi, Chihaya

2018-02-01

Near-infrared organic light-emitting diodes and semiconductor lasers could benefit a variety of applications including night-vision displays, sensors and information-secured displays. Organic dyes can generate electroluminescence efficiently at visible wavelengths, but organic light-emitting diodes are still underperforming in the near-infrared region. Here, we report thermally activated delayed fluorescent organic light-emitting diodes that operate at near-infrared wavelengths with a maximum external quantum efficiency of nearly 10% using a boron difluoride curcuminoid derivative. As well as an effective upconversion from triplet to singlet excited states due to the non-adiabatic coupling effect, this donor-acceptor-donor compound also exhibits efficient amplified spontaneous emission. By controlling the polarity of the active medium, the maximum emission wavelength of the electroluminescence spectrum can be tuned from 700 to 780 nm. This study represents an important advance in near-infrared organic light-emitting diodes and the design of alternative molecular architectures for photonic applications based on thermally activated delayed fluorescence.

Kv1.1 knock-in ataxic mice exhibit spontaneous myokymic activity exacerbated by fatigue, ischemia and low temperature.

Science.gov (United States)

Brunetti, Orazio; Imbrici, Paola; Botti, Fabio Massimo; Pettorossi, Vito Enrico; D'Adamo, Maria Cristina; Valentino, Mario; Zammit, Christian; Mora, Marina; Gibertini, Sara; Di Giovanni, Giuseppe; Muscat, Richard; Pessia, Mauro

2012-09-01

Episodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder characterized by myokymia and attacks of ataxic gait often precipitated by stress. Several genetic mutations have been identified in the Shaker-like K(+) channel Kv1.1 (KCNA1) of EA1 individuals, including V408A, which result in remarkable channel dysfunction. By inserting the heterozygous V408A, mutation in one Kv1.1 allele, a mouse model of EA1 has been generated (Kv1.1(V408A/+)). Here, we investigated the neuromuscular transmission of Kv1.1(V408A/+) ataxic mice and their susceptibility to physiologically relevant stressors. By using in vivo preparations of lateral gastrocnemius (LG) nerve-muscle from Kv1.1(+/+) and Kv1.1(V408A/+) mice, we show that the mutant animals exhibit spontaneous myokymic discharges consisting of repeated singlets, duplets or multiplets, despite motor nerve axotomy. Two-photon laser scanning microscopy from the motor nerve, ex vivo, revealed spontaneous Ca(2+) signals that occurred abnormally only in preparations dissected from Kv1.1(V408A/+) mice. Spontaneous bursting activity, as well as that evoked by sciatic nerve stimulation, was exacerbated by muscle fatigue, ischemia and low temperatures. These stressors also increased the amplitude of compound muscle action potential. Such abnormal neuromuscular transmission did not alter fiber type composition, neuromuscular junction and vascularization of LG muscle, analyzed by light and electron microscopy. Taken together these findings provide direct evidence that identifies the motor nerve as an important generator of myokymic activity, that dysfunction of Kv1.1 channels alters Ca(2+) homeostasis in motor axons, and also strongly suggest that muscle fatigue contributes more than PNS fatigue to exacerbate the myokymia/neuromyotonia phenotype. More broadly, this study points out that juxtaparanodal K(+) channels composed of Kv1.1 subunits exert an important role in dampening the excitability of motor nerve axons during

Genetics Home Reference: primary spontaneous pneumothorax

Science.gov (United States)

... Home Health Conditions Primary spontaneous pneumothorax Primary spontaneous pneumothorax Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Primary spontaneous pneumothorax is an abnormal accumulation of air in the ...

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

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

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.

Adenylate cyclase regulation in intact cultured myocardial cells

International Nuclear Information System (INIS)

Marsh, J.D.; Roberts, D.J.

1987-01-01

To examine the coupling of cardiac cell-surface β-adrenergic receptors to adenylate cyclase activation and contractile response, the authors studied this receptor-effector response system in monolayers of spontaneously contracting chick embryo ventricular cells under physiological conditions. The hydrophilic ligand 3 H-CGP12177 identified uniformly high-agonist affinity β-adrenergic receptors. Isoproterenol-stimulated cyclic AMP (cAMP) accumulation with 50% effective concentration at (EC 50 ) = 12.1 nM and augmented contractile response with EC 50 = 6 nM under identical conditions. One micromolar isoproterenol induced receptor loss from the cell surface with t/sub 1/2/ = 13.2 min; under identical conditions cAMP content declined with t/sub 1/2/ = 13.5 min and contractile response with t/sub 1/2/ = 20.7 min. After agonist removal cAMP response recovered with t/sub 1/2/ = 15.7 min and receptors with t/sub 1/2/ = 24.7 min. Sixty minutes after agonist removal there was recovery of 52% of maximal cAMP responsiveness and 82% of the initial number of receptors; receptor occupancy was associated with 78% of initial contractile response. Agonist affinity for cell-surface receptors was changed only modestly by agonist exposure. They conclude that for this system there is relatively close coupling between high-affinity receptors, adenylate cyclase stimulation, and contractile response

Reduced spontaneous neuronal activity in the insular cortex and thalamus in healthy adults with insomnia symptoms.

Science.gov (United States)

Liu, Chun-Hong; Liu, Cun-Zhi; Zhang, Jihui; Yuan, Zhen; Tang, Li-Rong; Tie, Chang-Le; Fan, Jin; Liu, Qing-Quan

2016-10-01

Poor sleep and insomnia have been recognized to be strongly correlated with the development of depression. The exploration of the basic mechanism of sleep disturbance could provide the basis for improved understanding and treatment of insomnia and prevention of depression. In this study, 31 subjects with insomnia symptoms as measured by the Hamilton Rating Scale for Depression (HAMD-17) and 71 age- and gender-matched subjects without insomnia symptoms were recruited to participate in a clinical trial. Using resting-state functional magnetic resonance imaging (rs-fMRI), we examined the alterations in spontaneous brain activity between the two groups. Correlations between the fractional amplitude of low frequency fluctuations (fALFF) and clinical measurements (e.g., insomnia severity and Hamilton Depression Rating Scale [HAMD] scores) were also tested in all subjects. Compared to healthy participants without insomnia symptoms, participants with insomnia symptoms showed a decreased fALFF in the left ventral anterior insula, bilateral posterior insula, left thalamus, and pons but an increased fALFF in the bilateral middle occipital gyrus and right precentral gyrus. More specifically, a significant, negative correlation of fALFF in the left thalamus with early morning awakening scores and HAMD scores in the overall sample was identified. These results suggest that insomnia symptoms are associated with altered spontaneous activity in the brain regions of several important functional networks, including the insular cortex of the salience and the thalamus of the hyperarousal network. The altered fALFF in the left thalamus supports the "hyperarousal theory" of insomnia symptoms, which could serve as a biomarker for insomnia. Copyright © 2016 Elsevier B.V. All rights reserved.

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...

Ziprasidone-induced spontaneous orgasm.

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Boora, K; Chiappone, K; Dubovsky, S; Xu, J

2010-06-01

Neuroleptic treatment in schizophrenic patients has been associated with sexual dysfunction, including impotence and decreased libido. Spontaneous ejaculation without sexual arousal during typical antipsychotic treatment is a rare condition that has been described with zuclopentixol, trifluoperazine, and thiothixene. Here, we are reporting a case of spontaneous orgasm with ziprasidone in a bipolar patient. This patient began to repeatedly experience spontaneous sexual arousal and orgasm, which she had never experienced in the past. Ziprasidone might be causing an increase in sexual orgasm by 5-HT2 receptor antagonism, which preclinical evidence suggests that it facilitates dopamine release in the cortex.

Improved sphincter contractility after allogenic muscle-derived progenitor cell injection into the denervated rat urethra.

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