Post-activation depression of soleus stretch reflexes in healthy and spastic humans

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Grey, Michael James; Klinge, Klaus; Crone, Clarissa

2007-01-01

Reduced depression of transmitter release from Ia afferents following previous activation (post-activation depression) has been suggested to be involved in the pathophysiology of spasticity. However, the effect of this mechanism on the myotatic reflex and its possible contribution to increased...... reflex excitability in spastic participants has not been tested. To investigate these effects, we examined post-activation depression in Soleus H-reflex responses and in mechanically evoked Soleus stretch reflex responses. Stretch reflex responses were evoked with consecutive dorsiflexion perturbations...... of the soleus stretch reflex and H-reflex decreased as the interval between the stimulus/perturbation was decreased. Similarly, the stretch-evoked torque decreased. In the spastic participants, the post-activation depression of both reflexes and the stretch-evoked torque was significantly smaller than...

Cyclic Stretch Alters Vascular Reactivity of Mouse Aortic Segments

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Arthur Leloup

2017-10-01

Full Text Available Large, elastic arteries buffer the pressure wave originating in the left ventricle and are constantly exposed to higher amplitudes of cyclic stretch (10% than muscular arteries (2%. As a crucial factor for endothelial and smooth muscle cell function, cyclic stretch has, however, never been studied in ex vivo aortic segments of mice. To investigate the effects of cyclic stretch on vaso-reactivity of mouse aortic segments, we used the Rodent Oscillatory Tension Set-up to study Arterial Compliance (ROTSAC. The aortic segments were clamped at frequencies of 6–600 bpm between two variable preloads, thereby mimicking dilation as upon left ventricular systole and recoiling as during diastole. The preloads corresponding to different transmural pressures were chosen to correspond to a low, normal or high amplitude of cyclic stretch. At different time intervals, cyclic stretch was interrupted, the segments were afterloaded and isometric contractions by α1-adrenergic stimulation with 2 μM phenylephrine in the absence and presence of 300 μM L-NAME (eNOS inhibitor and/or 35 μM diltiazem (blocker of voltage-gated Ca2+ channels were measured. As compared with static or cyclic stretch at low amplitude (<10 mN or low frequency (0.1 Hz, cyclic stretch at physiological amplitude (>10 mN and frequency (1–10 Hz caused better ex vivo conservation of basal NO release with time after mounting. The relaxation of PE-precontracted segments by addition of ACh to stimulate NO release was unaffected by cyclic stretch. In the absence of basal NO release (hence, presence of L-NAME, physiological in comparison with aberrant cyclic stretch decreased the baseline tension, attenuated the phasic contraction by phenylephrine in the absence of extracellular Ca2+ and shifted the smaller tonic contraction more from a voltage-gated Ca2+ channel-mediated to a non-selective cation channel-mediated. Data highlight the need of sufficient mechanical activation of endothelial and

Local calcium signalling is mediated by mechanosensitive ion channels in mesenchymal stem cells

International Nuclear Information System (INIS)

Chubinskiy-Nadezhdin, Vladislav I.; Vasileva, Valeria Y.; Pugovkina, Natalia A.; Vassilieva, Irina O.; Morachevskaya, Elena A.; Nikolsky, Nikolay N.; Negulyaev, Yuri A.

2017-01-01

Mechanical forces are implicated in key physiological processes in stem cells, including proliferation, differentiation and lineage switching. To date, there is an evident lack of understanding of how external mechanical cues are coupled with calcium signalling in stem cells. Mechanical reactions are of particular interest in adult mesenchymal stem cells because of their promising potential for use in tissue remodelling and clinical therapy. Here, single channel patch-clamp technique was employed to search for cation channels involved in mechanosensitivity in mesenchymal endometrial-derived stem cells (hMESCs). Functional expression of native mechanosensitive stretch-activated channels (SACs) and calcium-sensitive potassium channels of different conductances in hMESCs was shown. Single current analysis of stretch-induced channel activity revealed functional coupling of SACs and BK channels in plasma membrane. The combination of cell-attached and inside-out experiments have indicated that highly localized Ca 2+ entry via SACs triggers BK channel activity. At the same time, SK channels are not coupled with SACs despite of high calcium sensitivity as compared to BK. Our data demonstrate novel mechanism controlling BK channel activity in native cells. We conclude that SACs and BK channels are clusterized in functional mechanosensitive domains in the plasma membrane of hMESCs. Co-clustering of ion channels may significantly contribute to mechano-dependent calcium signalling in stem cells. - Highlights: • Stretch-induced channel activity in human mesenchymal stem cells was analyzed. • Functional expression of SACs and Ca 2+ -sensitive BK and SK channels was shown. • Local Ca 2+ influx via stretch-activated channels triggers BK channel activity. • SK channels are not coupled with SACs despite higher sensitivity to [Ca 2+ ] i . • Functional clustering of SACs and BK channels in stem cell membrane is proposed.

Cloning, functional expression, and characterization of a PKA-activated gastric Cl- channel.

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Malinowska, D H; Kupert, E Y; Bahinski, A; Sherry, A M; Cuppoletti, J

1995-01-01

cDNA encoding a Cl- channel was isolated from a rabbit gastric library, sequenced, and expressed in Xenopus oocytes. The predicted protein (898 amino acids, relative molecular mass 98,433 Da) was overall 93% similar to the rat brain ClC-2 Cl- channel. However, a 151-amino acid stretch toward the COOH-terminus was 74% similar to ClC-2 with six amino acids deleted. Two new potential protein kinase A (PKA) phosphorylation sites (also protein kinase C phosphorylation sites) were introduced. cRNA-injected Xenopus oocytes expressed a Cl- channel that was active at pHtrans 3 and had a linear current-voltage (I-V) curve and a slope conductance of 29 +/- 1 pS at 800 mM CsCl. A fivefold Cl- gradient caused a rightward shift in the I-V curve with a reversal potential of +30 +/- 3 mV, indicating anion selectivity. The selectivity was I- > Cl- > NO3-. The native and recombinant Cl- channel were both activated in vitro by PKA catalytic subunit and ATP. The electrophysiological and regulatory properties of the cloned and the native channel were similar. The cloned protein may be the Cl- channel involved in gastric HCl secretion.

Mechanical stretch induces MMP-2 release and activation in lung endothelium: role of EMMPRIN.

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Haseneen, Nadia A; Vaday, Gayle G; Zucker, Stanley; Foda, Hussein D

2003-03-01

High-volume mechanical ventilation leads to ventilator-induced lung injury. This type of lung injury is accompanied by an increased release and activation of matrix metalloproteinases (MMPs). To investigate the mechanism leading to the increased MMP release, we systematically studied the effect of mechanical stretch on human microvascular endothelial cells isolated from the lung. We exposed cells grown on collagen 1 BioFlex plates to sinusoidal cyclic stretch at 0.5 Hz using the Flexercell system with 17-18% elongation of cells. After 4 days of cell stretching, conditioned media and cell lysate were collected and analyzed by gelatin, casein, and reverse zymograms as well as Western blotting. RT-PCR of mRNA extracted from stretched cells was performed. Our results show that 1) cyclic stretch led to increased release and activation of MMP-2 and MMP-1; 2) the activation of MMP-2 was accompanied by an increase in membrane type-1 MMP (MT1-MMP) and inhibited by a hydroxamic acid-derived inhibitor of MMPs (Prinomastat, AG3340); and 3) the MMP-2 release and activation were preceded by an increase in production of extracellular MMP inducer (EMMPRIN). These results suggest that cyclic mechanical stretch leads to MMP-2 activation through an MT1-MMP mechanism. EMMPRIN may play an important role in the release and activation of MMPs during lung injury.

Effect of acute stretch injury on action potential and network activity of rat neocortical neurons in culture.

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Magou, George C; Pfister, Bryan J; Berlin, Joshua R

2015-10-22

The basis for acute seizures following traumatic brain injury (TBI) remains unclear. Animal models of TBI have revealed acute hyperexcitablility in cortical neurons that could underlie seizure activity, but studying initiating events causing hyperexcitability is difficult in these models. In vitro models of stretch injury with cultured cortical neurons, a surrogate for TBI, allow facile investigation of cellular changes after injury but they have only demonstrated post-injury hypoexcitability. The goal of this study was to determine if neuronal hyperexcitability could be triggered by in vitro stretch injury. Controlled uniaxial stretch injury was delivered to a spatially delimited region of a spontaneously active network of cultured rat cortical neurons, yielding a region of stretch-injured neurons and adjacent regions of non-stretched neurons that did not directly experience stretch injury. Spontaneous electrical activity was measured in non-stretched and stretch-injured neurons, and in control neuronal networks not subjected to stretch injury. Non-stretched neurons in stretch-injured cultures displayed a three-fold increase in action potential firing rate and bursting activity 30-60 min post-injury. Stretch-injured neurons, however, displayed dramatically lower rates of action potential firing and bursting. These results demonstrate that acute hyperexcitability can be observed in non-stretched neurons located in regions adjacent to the site of stretch injury, consistent with reports that seizure activity can arise from regions surrounding the site of localized brain injury. Thus, this in vitro procedure for localized neuronal stretch injury may provide a model to study the earliest cellular changes in neuronal function associated with acute post-traumatic seizures. Copyright © 2015. Published by Elsevier B.V.

EFFECTS OF DYNAMIC AND STATIC STRETCHING WITHIN GENERAL AND ACTIVITY SPECIFIC WARM-UP PROTOCOLS

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Michael Samson

2012-06-01

Full Text Available The purpose of the study was to determine the effects of static and dynamic stretching protocols within general and activity specific warm-ups. Nine male and ten female subjects were tested under four warm-up conditions including a 1 general aerobic warm-up with static stretching, 2 general aerobic warm-up with dynamic stretching, 3 general and specific warm-up with static stretching and 4 general and specific warm-up with dynamic stretching. Following all conditions, subjects were tested for movement time (kicking movement of leg over 0.5 m distance, countermovement jump height, sit and reach flexibility and 6 repetitions of 20 metre sprints. Results indicated that when a sport specific warm-up was included, there was an 0.94% improvement (p = 0.0013 in 20 meter sprint time with both the dynamic and static stretch groups. No such difference in sprint performance between dynamic and static stretch groups existed in the absence of the sport specific warm-up. The static stretch condition increased sit and reach range of motion (ROM by 2.8% more (p = 0.0083 than the dynamic condition. These results would support the use of static stretching within an activity specific warm-up to ensure maximal ROM along with an enhancement in sprint performance

Mechanical stretch endows mesenchymal stem cells stronger angiogenic and anti-apoptotic capacities via NFκB activation

International Nuclear Information System (INIS)

Zhu, Zhuoli; Gan, Xueqi; Fan, Hongyi; Yu, Haiyang

2015-01-01

Mesenchymal stem cells (MSCs) have been broadly used for tissue regeneration and repair due to their broad differentiation potential and potent paracrine properties such as angiogenic capacity. Strategies to increase their survival rate after transplantation and the angiogenic ability are of priority for the utility of MSCs. In this study, we found that mechanical stretch (10% extension, 30 cycles/min cyclic stretch) preconditioning increase the angiogenic capacity via VEGFA induction. In addition, mechanical stretch also increases the survival rate of mesenchymal stem cells under nutrients deprivation. Consistent with the increase VEGFA expression and resistance to apoptosis, nuclear localization of NFκB activity p65 increased upon mechanical stretch. Inhibition of NFκB activity by BAY 11-708 blocks the pro-angiogenesis and anti-apoptosis function of mechanical stretch. Taken together, our findings here raise the possibility that mechanical stretch preconditioning might enhance the therapeutic efficacy of mesenchymal stem cells. - Highlights: • Mechanical stretch increases the angiogenic capacity via VEGFA induction in MSCs. • Mechanical stretch increases the survival rate of MSCs under nutrients deprivation. • Mechanical stretch manipulates MSCs via the activation of NFκB.

Mechanical stretch endows mesenchymal stem cells stronger angiogenic and anti-apoptotic capacities via NFκB activation

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Zhu, Zhuoli; Gan, Xueqi [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Fan, Hongyi [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Department of Applied Mechanics, College of Architecture and Environment, Sichuan University, Chengdu 610065 (China); Yu, Haiyang, E-mail: yhyang6812@foxmail.com [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China)

2015-12-25

Mesenchymal stem cells (MSCs) have been broadly used for tissue regeneration and repair due to their broad differentiation potential and potent paracrine properties such as angiogenic capacity. Strategies to increase their survival rate after transplantation and the angiogenic ability are of priority for the utility of MSCs. In this study, we found that mechanical stretch (10% extension, 30 cycles/min cyclic stretch) preconditioning increase the angiogenic capacity via VEGFA induction. In addition, mechanical stretch also increases the survival rate of mesenchymal stem cells under nutrients deprivation. Consistent with the increase VEGFA expression and resistance to apoptosis, nuclear localization of NFκB activity p65 increased upon mechanical stretch. Inhibition of NFκB activity by BAY 11-708 blocks the pro-angiogenesis and anti-apoptosis function of mechanical stretch. Taken together, our findings here raise the possibility that mechanical stretch preconditioning might enhance the therapeutic efficacy of mesenchymal stem cells. - Highlights: • Mechanical stretch increases the angiogenic capacity via VEGFA induction in MSCs. • Mechanical stretch increases the survival rate of MSCs under nutrients deprivation. • Mechanical stretch manipulates MSCs via the activation of NFκB.

Acute effects of active isolated stretching on vertical jump ...

African Journals Online (AJOL)

The purpose of the study was to determine the acute effects of active isolated stretching on muscular peak power production. Sixty healthy, physically active volunteers (aged 18-28) participated as subjects in this study. Subjects were randomly assigned to two groups; the control group and the experimental group. Subjects ...

Stretch-dependent slow force response in isolated rabbit myocardium is Na+ dependent.

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von Lewinski, Dirk; Stumme, Burkhard; Maier, Lars S; Luers, Claus; Bers, Donald M; Pieske, Burkert

2003-03-15

Stretch induces functional and trophic effects in mammalian myocardium via various signal transduction pathways. We tested stretch signal transduction on immediate and slow force response (SFR) in rabbit myocardium. Experiments were performed in isolated right ventricular muscles from adult rabbit hearts (37 degrees C, 1 Hz stimulation rate, bicarbonate-buffer). Muscles were rapidly stretched from 88% of optimal length (L88) to near optimal length (L98) for functional analysis. The resulting immediate and slow increases in twitch force (first phase and SFR, respectively) were assessed at reduced [Na+]o or without and with blockade of stretch activated ion channels (SACs), angiotensin-II (AT1) receptors, endothelin-A (ET(A)) receptors, Na+/H+-exchange (NHE1), reverse mode Na+/Ca2+-exchange (NCX), or Na+/K+-ATPase. The effects of stretch on sarcoplasmic reticulum Ca2+-load were characterized using rapid cooling contractures (RCCs). Intracellular pH was measured in BCECF-AM loaded muscles, and action potential duration (APD) was assessed using floating electrodes. On average, force increased to 216+/-8% of the pre-stretch value during the immediate phase, followed by a further increase to 273+/-10% during the SFR (n=81). RCCs significantly increased during SFR, whereas pH and APD did not change. Neither inhibition of SACs, AT1, or ET(A) receptors affected the stretch-dependent immediate phase nor SFR. In contrast, SFR was reduced by NHE inhibition and almost completely abolished by reduced [Na+]o or inhibition of reverse-mode NCX, whereas increased SFR was seen after raising [Na+]i by Na+/K+-ATPase inhibition. The data demonstrate the existence of a delayed, Na+- and Ca2+-dependent but pH and APD independent SFR to stretch in rabbit myocardium. This inotropic response appears to be independent of autocrine/paracrine AT1 or ET(A) receptor activation, but mediated through stretch-induced activation of NHE and reverse mode NCX.

p38 mitogen-activated protein kinase up-regulates NF-κB transcriptional activation through RelA phosphorylation during stretch-induced myogenesis

International Nuclear Information System (INIS)

Ji, Guoping; Liu, Dongxu; Liu, Jing; Gao, Hui; Yuan, Xiao; Shen, Gang

2010-01-01

p38 MAPK and nuclear factor-B (NF-B) signaling pathways play an indispensable role in the control of skeletal myogenesis. The specific contribution of these signaling pathways to the response of myoblast to the mechanical stimulation and the molecular mechanisms underlying this response remain unresolved. Using an established in vitro model, we now show that p38 MAP kinase activity regulates the transcriptional activation of NF-κB in response to mechanical stimulation of myoblasts. Furthermore, SB203580 blocked stretch-induced NF-κB activation during myogenesis, not through down-regulation of degradation of IκB-α, and consequent translocation of the p65 subunit of NF-κB to the nucleus. It is likely that stretch-induced NF-κB activation by phosphorylation of p65 NF-κB. Moreover, depletion of p38α using siRNA significantly reduces stretch-induced phosphorylation of RelA and NF-κB activity. These results provides the first evidence of a cross-talk between p38 MAPK and NF-κB signaling pathways during stretch-induced myogenesis, with phosphorylation of RelA being one of the effectors of this promyogenic mechanism. The α isoform of p38MAP kinase regulates the transcriptional activation of NF-κB following stimulation with cyclic stretch.

p38 mitogen-activated protein kinase up-regulates NF-{kappa}B transcriptional activation through RelA phosphorylation during stretch-induced myogenesis

Energy Technology Data Exchange (ETDEWEB)

Ji, Guoping [Department of Orthodontics, College of Stomatology, Ninth People' s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai 200011 (China); Liu, Dongxu [Department of Orthodontics, College of Stomatology, Shandong University, Jinan, Shandong Province 250012 (China); Liu, Jing [Department of Orthodontics, The Affiliated Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Province 266075 (China); Gao, Hui [Department of Orthodontics, Tianjin Stomatological Hospital, Tianjin 300041 (China); Yuan, Xiao, E-mail: yuanxiaoqd@163.com [Department of Orthodontics, The Affiliated Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Province 266075 (China); Shen, Gang, E-mail: ganshen2007@163.com [Department of Orthodontics, College of Stomatology, Ninth People' s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai 200011 (China)

2010-01-01

p38 MAPK and nuclear factor-B (NF-B) signaling pathways play an indispensable role in the control of skeletal myogenesis. The specific contribution of these signaling pathways to the response of myoblast to the mechanical stimulation and the molecular mechanisms underlying this response remain unresolved. Using an established in vitro model, we now show that p38 MAP kinase activity regulates the transcriptional activation of NF-{kappa}B in response to mechanical stimulation of myoblasts. Furthermore, SB203580 blocked stretch-induced NF-{kappa}B activation during myogenesis, not through down-regulation of degradation of I{kappa}B-{alpha}, and consequent translocation of the p65 subunit of NF-{kappa}B to the nucleus. It is likely that stretch-induced NF-{kappa}B activation by phosphorylation of p65 NF-{kappa}B. Moreover, depletion of p38{alpha} using siRNA significantly reduces stretch-induced phosphorylation of RelA and NF-{kappa}B activity. These results provides the first evidence of a cross-talk between p38 MAPK and NF-{kappa}B signaling pathways during stretch-induced myogenesis, with phosphorylation of RelA being one of the effectors of this promyogenic mechanism. The {alpha} isoform of p38MAP kinase regulates the transcriptional activation of NF-{kappa}B following stimulation with cyclic stretch.

Effect of Active-Assisted Stretching of 30 Seconds and 60 Seconds in Muscle Force

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Mirian dos Santos Monteiro

2018-01-01

Full Text Available This study aims to analyze the interference of the active-assisted stretching technique in muscle strength. Participating in this study were 39 healthy and physically active individuals subdivided into three groups of active-assisted stretching G30 - 30 seconds, G60 - 60 seconds and CG - control. The muscular strength was evaluated using the isokinetic dynamometer, obtaining the analyzed conditions of torque peak, total work and agonist and antagonist relationship of the dorsiflexor and flexor muscles ankle. The values obtained were statistically analyzed by the SPSS from the “t-test for paired sample” (p ≤ 0.05. When analyzing the effect produced by the stretching, it was observed that the 30-second elongation showed a reduction of the average of the muscular torque in all conditions analyzed, with the exception of the relation between the agonist and the left antagonist and the total work of the right plantar flexors, the G60 - 60 seconds group had a reduction in average muscle torque in all conditions analyzed, except for the relation between agonist and left antagonist that obtained an increase in muscle torque and the CG - control group, there was a reduction in the average of the muscular torque in all the analyzed conditions, except for the torque and total work of the left plantar flexor muscles that presented increase. Thus, it can be concluded that there were differences between the groups of active-assisted stretching of 30 and 60 and that the effect produced by stretching did not present a significant reduction of muscle strength.

OH vibrational activation and decay dynamics of CH4-OH entrance channel complexes

International Nuclear Information System (INIS)

Wheeler, Martyn D.; Tsiouris, Maria; Lester, Marsha I.; Lendvay, Gyoergy

2000-01-01

Infrared spectroscopy has been utilized to examine the structure and vibrational decay dynamics of CH 4 -OH complexes that have been stabilized in the entrance channel to the CH 4 +OH hydrogen abstraction reaction. Rotationally resolved infrared spectra of the CH 4 -OH complexes have been obtained in the OH fundamental and overtone regions using an IR-UV (infrared-ultraviolet) double-resonance technique. Pure OH stretching bands have been identified at 3563.45(5) and 6961.98(4) cm-1 (origins), along with combination bands involving the simultaneous excitation of OH stretching and intermolecular bending motions. The infrared spectra exhibit extensive homogeneous broadening arising from the rapid decay of vibrationally activated CH 4 -OH complexes due to vibrational relaxation and/or reaction. Lifetimes of 38(5) and 25(3) ps for CH 4 -OH prepared with one and two quanta of OH excitation, respectively, have been extracted from the infrared spectra. The nascent distribution of the OH products from vibrational predissociation has been evaluated by ultraviolet probe laser-induced fluorescence measurements. The dominant inelastic decay channel involves the transfer of one quantum of OH stretch to the pentad of CH 4 vibrational states with energies near 3000 cm-1. The experimental findings are compared with full collision studies of vibrationally excited OH with CH 4 . In addition, ab initio electronic structure calculations have been carried out to elucidate the minimum energy configuration of the CH 4 -OH complex. The calculations predict a C 3v geometry with the hydrogen of OH pointing toward one of four equivalent faces of the CH 4 tetrahedron, consistent with the analysis of the experimental infrared spectra. (c) 2000 American Institute of Physics

Muscle activation patterns when passively stretching spastic lower limb muscles of children with cerebral palsy.

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Lynn Bar-On

Full Text Available The definition of spasticity as a velocity-dependent activation of the tonic stretch reflex during a stretch to a passive muscle is the most widely accepted. However, other mechanisms are also thought to contribute to pathological muscle activity and, in patients post-stroke and spinal cord injury can result in different activation patterns. In the lower-limbs of children with spastic cerebral palsy (CP these distinct activation patterns have not yet been thoroughly explored. The aim of the study was to apply an instrumented assessment to quantify different muscle activation patterns in four lower-limb muscles of children with CP. Fifty-four children with CP were included (males/females n = 35/19; 10.8 ± 3.8 yrs; bilateral/unilateral involvement n =  32/22; Gross Motor Functional Classification Score I-IV of whom ten were retested to evaluate intra-rater reliability. With the subject relaxed, single-joint, sagittal-plane movements of the hip, knee, and ankle were performed to stretch the lower-limb muscles at three increasing velocities. Muscle activity and joint motion were synchronously recorded using inertial sensors and electromyography (EMG from the adductors, medial hamstrings, rectus femoris, and gastrocnemius. Muscles were visually categorised into activation patterns using average, normalized root mean square EMG (RMS-EMG compared across increasing position zones and velocities. Based on the visual categorisation, quantitative parameters were defined using stretch-reflex thresholds and normalized RMS-EMG. These parameters were compared between muscles with different activation patterns. All patterns were dominated by high velocity-dependent muscle activation, but in more than half, low velocity-dependent activation was also observed. Muscle activation patterns were found to be both muscle- and subject-specific (p<0.01. The intra-rater reliability of all quantitative parameters was moderate to good. Comparing RMS-EMG between

Stretching of Active Muscle Elicits Chronic Changes in Multiple Strain Risk Factors.

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Kay, Anthony David; Richmond, Dominic; Talbot, Chris; Mina, Minas; Baross, Anthony William; Blazevich, Anthony John

2016-07-01

The muscle stretch intensity imposed during "flexibility" training influences the magnitude of joint range of motion (ROM) adaptation. Thus, stretching while the muscle is voluntarily activated was hypothesized to provide a greater stimulus than passive stretching. The effect of a 6-wk program of stretch imposed on an isometrically contracting muscle (i.e., qualitatively similar to isokinetic eccentric training) on muscle-tendon mechanics was therefore studied in 13 healthy human volunteers. Before and after the training program, dorsiflexion ROM, passive joint moment, and maximal isometric plantarflexor moment were recorded on an isokinetic dynamometer. Simultaneous real-time motion analysis and ultrasound imaging recorded gastrocnemius medialis muscle and Achilles tendon elongation. Training was performed twice weekly and consisted of five sets of 12 maximal isokinetic eccentric contractions at 10°·s. Significant increases (P tendon stiffness) was detected (-1.5%, P > 0.05), a significant increase in tendon stiffness (31.2%, P tendon stiffness simultaneous with significant increases in tendon stiffness and decreases in passive muscle stiffness indicates that tissue-specific effects were elicited.

The effect of streptomycin on stretch-induced electrophysiological changes of isolated acute myocardial infarcted hearts in rats.

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Fu, Lu; Cao, Jun-xian; Xie, Rong-sheng; Li, Jia; Han, Ying; Zhu, Li-qun; Dai, Ying-nan

2007-08-01

To explore whether the stretch of ischaemic myocardium could modulate the electrophysiological characteristics, especially repolarization via mechanoelectric feedback (MEF), as well as the effect of streptomycin (SM) on these changes. Methods Thirty-six wistar rats were randomly divided into four groups: control group (n = 9), SM group (n = 9), myocardial infarction (MI) group (n = 9), and MI + SM group (n = 9). After perfused on Langendorff, the isolated hearts were stretched for 5s by a ballon inflation of 0.2mL. After being stretched, the effect of the stretch was observed for 30s, including the 20, 20-70, 70, and 90% monophasic action potential duration (MAPD), i.e. MAPD(20), MAPD(20-70), MAPD(70), and MAPD(90), respectively, premature ventricular beats (PVB), and ventricular tachycardia (VT). Results The stretch caused a decrease in MAPD(20-70) (both P 0.05, except MAPD(20-70) between the control and SM groups, P maintenance of malignant arrhythmias. SM could significantly inhibit the occurrence of arrhythmias, which may correlate with the effect on blocking stretch-activated ion channels.

Transmembrane proteoglycans control stretch-activated channels to set cytosolic calcium levels

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Gopal, Sandeep; Søgaard, Pernille; Multhaupt, Hinke A B

2015-01-01

show that syndecans regulate transient receptor potential canonical (TRPCs) channels to control cytosolic calcium equilibria and consequent cell behavior. In fibroblasts, ligand interactions with heparan sulfate of syndecan-4 recruit cytoplasmic protein kinase C to target serine714 of TRPC7...... with subsequent control of the cytoskeleton and the myofibroblast phenotype. In epidermal keratinocytes a syndecan-TRPC4 complex controls adhesion, adherens junction composition, and early differentiation in vivo and in vitro. In Caenorhabditis elegans, the TRPC orthologues TRP-1 and -2 genetically complement...

Detection of TRPV4 channel current-like activity in Fawn Hooded hypertensive (FHH rat cerebral arterial muscle cells.

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Debebe Gebremedhin

Full Text Available The transient receptor potential vallinoid type 4 (TRPV4 is a calcium entry channel known to modulate vascular function by mediating endothelium-dependent vasodilation. The present study investigated if isolated cerebral arterial myocytes of the Fawn Hooded hypertensive (FHH rat, known to display exaggerated KCa channel current activity and impaired myogenic tone, express TRPV4 channels at the transcript and protein level and exhibit TRPV4-like single-channel cationic current activity. Reverse transcription polymerase chain reaction (RT-PCR, Western blot, and immunostaining analysis detected the expression of mRNA transcript and translated protein of TRPV4 channel in FHH rat cerebral arterial myocytes. Patch clamp recording of single-channel current activity identified the presence of a single-channel cationic current with unitary conductance of ~85 pS and ~96 pS at hyperpolarizing and depolarizing potentials, respectively, that was inhibited by the TRPV4 channel antagonist RN 1734 or HC 067074 and activated by the potent TRPV4 channel agonist GSK1016790A. Application of negative pressure via the interior of the patch pipette increased the NPo of the TRPV4-like single-channel cationic current recorded in cell-attached patches at a patch potential of 60 mV that was inhibited by prior application of the TRPV4 channel antagonist RN 1734 or HC 067047. Treatment with the TRPV4 channel agonist GSK1016790A caused concentration-dependent increase in the NPo of KCa single-channel current recorded in cell-attached patches of cerebral arterial myocytes at a patch potential of 40 mV, which was not influenced by pretreatment with the voltage-gated L-type Ca2+ channel blocker nifedipine or the T-type Ca2+ channel blocker Ni2+. These findings demonstrate that FHH rat cerebral arterial myocytes express mRNA transcript and translated protein for TRPV4 channel and display TRPV4-like single-channel cationic current activity that was stretch-sensitive and

Activation of TRPV1 channels inhibits mechanosensitive Piezo channel activity by depleting membrane phosphoinositides

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Borbiro, Istvan; Badheka, Doreen; Rohacs, Tibor

2015-01-01

Capsaicin is an activator of the heat-sensitive TRPV1 (transient receptor potential vanilloid 1) ion channels and has been used as a local analgesic. We found that activation of TRPV1 channels with capsaicin either in dorsal root ganglion neurons or in a heterologous expression system inhibited the mechanosensitive Piezo1 and Piezo2 channels by depleting phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and its precursor PI(4)P from the plasma membrane through Ca2+-induced phospholipase Cδ (PLCδ) activation. Experiments with chemically inducible phosphoinositide phosphatases and receptor-induced activation of PLCβ indicated that inhibition of Piezo channels required depletion of both PI(4)P and PI(4,5)P2. The mechanically activated current amplitudes decreased substantially in the excised inside-out configuration, where the membrane patch containing Piezo1 channels is removed from the cell. PI(4,5)P2 and PI(4)P applied to these excised patches inhibited this decrease. Thus, we concluded that Piezo channel activity requires the presence of phosphoinositides, and the combined depletion of PI(4,5)P2 or PI(4)P reduces channel activity. In addition to revealing a role for distinct membrane lipids in mechanosensitive ion channel regulation, these data suggest that inhibition of Piezo2 channels may contribute to the analgesic effect of capsaicin. PMID:25670203

EFFICACY OF MODIFIED PROPRIOCEPTIVE NEUROMUSCULAR FACILITATION STRETCHING WITH CRYOTHERAPY OVER MANUAL PASSIVE STRETCHING WITH CRYOTHERAPY ON HAMSTRING FLEXIBILITY

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Shamik Bhattacharjee

2016-04-01

Full Text Available Background: Healthy individuals, to ease and accomplish their activities of daily living they need flexible body without any tightness in the muscles, particularly those used for a definite function. Cooling soft tissues in a lengthened position after stretching has been shown to promote more lasting increases in soft tissue length and minimize post stretch muscle soreness. There are less documented studies which compared modified proprioceptive neuromuscular facilitation (PNF stretch over passive manual stretch with cold application commonly after the interventions. Methods: Thirty high school going healthy students were divided into two groups- Group I received Passive Manual stretching (n=15 and Group II received modified PNF stretching (n=15 and both groups received cold application after the interventions for 10 minutes commonly for 5 days. ROM was taken on day 1, day 5 and day 7. Results: After day 7, Group II with Modified PNF stretching along with cold application showed a significant increase in range of motion tested with active knee extension test (AKET. Conclusion: Modified PNF stretching is considered to be the effective intervention in increasing and maintaining ROM in AKET over passive manual stretching with cold applications commonly after the interventions.

Ballistic stretching increases flexibility and acute vertical jump height when combined with basketball activity.

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Woolstenhulme, Mandy T; Griffiths, Christine M; Woolstenhulme, Emily M; Parcell, Allen C

2006-11-01

Stretching is often included as part of a warm-up procedure for basketball activity. However, the efficacy of stretching with respect to sport performance has come into question. We determined the effects of 4 different warm-up protocols followed by 20 minutes of basketball activity on flexibility and vertical jump height. Subjects participated in 6 weeks (2 times per week) of warm-up and basketball activity. The warm-up groups participated in ballistic stretching, static stretching, sprinting, or basketball shooting (control group). We asked 3 questions. First, what effect does 6 weeks of warm-up exercise and basketball play have on both flexibility and vertical jump height? We measured sit and reach and vertical jump height before (week -1) and after (week 7) the 6 weeks. Flexibility increased for the ballistic, static, and sprint groups compared to the control group (p vertical jump height did not change for any of the groups. Our second question was what is the acute effect of each warm-up on vertical jump height? We measured vertical jump immediately after the warm-up on 4 separate occasions during the 6 weeks (at weeks 0, 2, 4, and 6). Vertical jump height was not different for any group. Finally, our third question was what is the acute effect of each warm-up on vertical jump height following 20 minutes of basketball play? We measured vertical jump height immediately following 20 minutes of basketball play at weeks 0, 2, 4, and 6. Only the ballistic stretching group demonstrated an acute increase in vertical jump 20 minutes after basketball play (p basketball play, as it is beneficial to vertical jump performance.

Active stretching for lower extremity muscle tightness in pediatric patients with lumbar spondylolysis.

Science.gov (United States)

Sato, Masahiro; Mase, Yasuyoshi; Sairyo, Koichi

2017-01-01

It was reported that hamstring muscle tightness may increase mechanical loading on the lumbar spine. Therefore, we attempt to decrease tightness in the leg muscles in pediatric patients. Forty-six pediatric patients with spondylolysis underwent rehabilitation. We applied active stretching to the hamstrings, quadriceps, and triceps surae. Tightness in each muscle was graded as good, fair, or poor. We educated each patient on how to perform active stretching at home. They were re-evaluated for muscle tightness 2 months later. Tightness at baseline and after 2 months was as follows: for the hamstrings, good in 3 patients, fair in 9, and poor in 34 and significant improved after 2 months (p<0.05), with improvement by least 1 grade seen in 86% of patients with fair or poor at baseline; for the quadriceps, 7, 3, and 30 patients had good, fair and poor, with significant improvements in 72% (p<0.05). For the triceps surae, 6, 3 and 10 patients had good, fair and poor, which improved significantly (p<0.05). Home-based active stretching was effective for relieving muscle tightness in the leg in a pediatric population. Adolescent athletes should perform such exercise to maintain flexibility and prevent lumbar disorders. J. Med. Invest. 64: 136-139, February, 2017.

Studying Mechanosensitivity of Two-Pore Domain K+ Channels in Cellular and Reconstituted Proteoliposome Membranes.

Science.gov (United States)

Del Mármol, Josefina; Rietmeijer, Robert A; Brohawn, Stephen G

2018-01-01

Mechanical force sensation is fundamental to a wide breadth of biology from the classic senses of touch, pain, hearing, and balance to less conspicuous sensations of proprioception, blood pressure, and osmolarity and basic aspects of cell growth, differentiation, and development. These diverse and essential systems use force-gated (or mechanosensitive) ion channels that convert mechanical stimuli into cellular electrical signals. TRAAK, TREK1, and TREK2 are K + -selective ion channels of the two-pore domain K + (K2P) family that are mechanosensitive: they are gated open by increasing membrane tension. TRAAK and TREK channels are thought to play roles in somatosensory and other mechanosensory processes in neuronal and non-neuronal tissues. Here, we present protocols for three assays to study mechanical activation of these channels in cell membranes: (1) cell swelling, (2) cell poking, and (3) patched membrane stretching. Patched membrane stretching is also applicable to the study of mechanosensitive K2P channel activity in a cell-free system and a procedure for proteoliposome reconstitution and patching is also presented. These approaches are also readily applicable to the study of other mechanosensitive ion channels.

Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin–Darby canine kidney cells

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Sheng-Nan Wu

2015-01-01

Full Text Available The nitrogen-containing bisphosphonates used for management of the patients with osteoporosis were reported to influence the function of renal tubular cells. However, how nitrogen-containing bisphosphates exert any effects on ion currents remains controversial. The effects of ibandronate (Iban, a nitrogen-containing bisphosphonate, on ionic channels, including two types of Ca2+-activated K+ (KCa channels, namely, large-conductance KCa (BKCa and intermediate-conductance KCa (IKCa channels, were investigated in Madin–Darby canine kidney (MDCK cells. In whole-cell current recordings, Iban suppressed the amplitude of voltage-gated K+ current elicited by long ramp pulse. Addition of Iban caused a reduction of BKCa channels accompanied by a right shift in the activation curve of BKCa channels, despite no change in single-channel conductance. Ca2+ sensitivity of these channels was modified in the presence of this compound; however, the magnitude of Iban-mediated decrease in BKCa-channel activity under membrane stretch with different negative pressure remained unchanged. Iban suppressed the probability of BKCa-channel openings linked primarily to a shortening in the slow component of mean open time in these channels. The dissociation constant needed for Iban-mediated suppression of mean open time in MDCK cells was 12.2 μM. Additionally, cell exposure to Iban suppressed the activity of IKCa channels, and DC-EBIO or 9-phenanthrol effectively reversed its suppression. Under current-clamp configuration, Iban depolarized the cells and DC-EBIO or PF573228 reversed its depolarizing effect. Taken together, the inhibitory action of Iban on KCa-channel activity may contribute to the underlying mechanism of pharmacological or toxicological actions of Iban and its structurally similar bisphosphonates on renal tubular cells occurring in vivo.

Stretch activates myosin light chain kinase in arterial smooth muscle

International Nuclear Information System (INIS)

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

1990-01-01

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

Reduced Mechanical Stretch Induces Enhanced Endothelin B Receptor-mediated Contractility via Activation of Focal Adhesion Kinase and Extra Cellular-regulated Kinase 1/2 in Cerebral Arteries from Rat

DEFF Research Database (Denmark)

Spray, Stine; Rasmussen, Marianne N P; Skovsted, Gry F

2016-01-01

that rapid and sustained reduction in wall tension/stretch is a possible trigger mechanism for this vascular remodelling. Isolated rat middle cerebral artery (MCA) segments were incubated in a wire-myograph with or without mechanical stretch, prior to assessment of their contractile response to the selective...... expression to SMC expression and 2) an increased calcium sensitivity of the SMCs due to an increased expression of the calcium channel transient receptor potential canonical 1. Collectively, our results present a possible mechanism linking lack of vessel wall stretch/tension to changes in ETB receptor...

Pre-Activity and Post-Activity Stretching Perceptions and Practices in NCAA Division I Volleyball Programs

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Judge, Lawrence W.; Bodey, Kimberly J.; Bellar, David; Bottone, Adam; Wanless, Elizabeth

2010-01-01

The purpose of this study was to determine if NCAA Division I women's volleyball programs were in compliance with suggested current pre- and post-activity stretching protocols. Questionnaires were sent to NCAA division I women's volleyball programs in the United States. Fifty six coaches (23 males & 33 females) participated in the study. Some…

Developmental axon stretch stimulates neuron growth while maintaining normal electrical activity, intracellular calcium flux, and somatic morphology.

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Loverde, Joseph R; Pfister, Bryan J

2015-01-01

Elongation of nerve fibers intuitively occurs throughout mammalian development, and is synchronized with expansion of the growing body. While most tissue systems enlarge through mitosis and differentiation, elongation of nerve fibers is remarkably unique. The emerging paradigm suggests that axons undergo stretch as contiguous tissues enlarge between the proximal and distal segments of spanning nerve fibers. While stretch is distinct from growth, tension is a known stimulus which regulates the growth of axons. Here, we hypothesized that the axon stretch-growth process may be a natural form of injury, whereby regenerative processes fortify elongating axons in order to prevent disconnection. Harnessing the live imaging capability of our axon stretch-growth bioreactors, we assessed neurons both during and following stretch for biomarkers associated with injury. Utilizing whole-cell patch clamp recording, we found no evidence of changes in spontaneous action potential activity or degradation of elicited action potentials during real-time axon stretch at strains of up to 18% applied over 5 min. Unlike traumatic axonal injury, functional calcium imaging of the soma revealed no shifts in free intracellular calcium during axon stretch. Finally, the cross-sectional areas of nuclei and cytoplasms were normal, with no evidence of chromatolysis following week-long stretch-growth limited to the lower of 25% strain or 3 mm total daily stretch. The neuronal growth cascade coupled to stretch was concluded to be independent of the changes in membrane potential, action potential generation, or calcium flux associated with traumatic injury. While axon stretch-growth is likely to share overlap with regenerative processes, we conclude that developmental stretch is a distinct stimulus from traumatic axon injury.

Developmental Axon Stretch Stimulates Neuron Growth While Maintaining Normal Electrical Activity, Intracellular Calcium Flux, and Somatic Morphology

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Joseph R Loverde

2015-08-01

Full Text Available Elongation of nerve fibers intuitively occurs throughout mammalian development, and is synchronized with expansion of the growing body. While most tissue systems enlarge through mitosis and differentiation, elongation of nerve fibers is remarkably unique. The emerging paradigm suggests that axons undergo stretch as contiguous tissues enlarge between the proximal and distal segments of spanning nerve fibers. While stretch is distinct from growth, tension is a known stimulus which regulates the growth of axons. Here, we hypothesized that the axon stretch-growth process may be a natural form of injury, whereby regenerative processes fortify elongating axons in order to prevent disconnection. Harnessing the live imaging capability of our axon stretch-growth bioreactors, we assessed neurons both during and following stretch for biomarkers associated with injury. Utilizing whole-cell patch clamp recording, we found no evidence of changes in spontaneous action potential activity or degradation of elicited action potentials during real-time axon stretch at strains of up to 18 % applied over 5 minutes. Unlike traumatic axonal injury, functional calcium imaging of the soma revealed no shifts in free intracellular calcium during axon stretch. Finally, the cross-sectional areas of nuclei and cytoplasms were normal, with no evidence of chromatolysis following week-long stretch-growth limited to the lower of 25 % strain or 3 mm total daily stretch. The neuronal growth cascade coupled to stretch was concluded to be independent of the changes in membrane potential, action potential generation, or calcium flux associated with traumatic injury. While axon stretch-growth is likely to share overlap with regenerative processes, we conclude that developmental stretch is a distinct stimulus from traumatic axon injury.

EFFECTIVENESS OF PNF STRETCHING VERSUS STATIC STRETCHING ON PAIN AND HAMSTRING FLEXIBILITY FOLLOWING MOIST HEAT IN INDIVIDUALS WITH KNEE OSTEOARTHRITIS

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Meena .V

2016-10-01

Full Text Available Background: Osteoarthritis (OA is a degenerative joint disease and one of the major public health problem that causesfunctional impairment and reduced quality of life. To compare the effectiveness of PNF Hold relax stretching versus Static stretching on pain and flexibility of hamstring following moist heat in individuals with knee osteoarthritis. Hamstring tightness is the major problem in knee osteoarthritis individuals. Therefore the need of study is comparing the effectiveness of PNF Hold relax stretching versus static stretching on pain and flexibility of hamstrings following moist heat in knee osteoarthritis participants. Determining the effects of PNF Hold relax stretching versus Static stretching along with moist heat on pain and hamstring flexibility by VAS and Active knee extension range of motion in knee osteoarthritis individuals. Methods: 30 subjects with symptoms of knee osteoarthritis were randomly distributed into 2 groups 15 in each group. PNF Hold relax stretching along with moist heat is compared to Static stretching along with moist heat. Pain was measured by Visual Analogue Scale (VAS and hamstring flexibility by Active knee Extension Range of Motion (AKEROM by universal goniometer. Measurements are taken pre and post intervention. Results: The results indicated PNF Hold relax stretching along with moist heat showed a statistically significant improvement in pain (p<0.05 and improvement in hamstring flexibility (p<0.05 when compared to Static stretching along with moist heat. Conclusion: Subjects with PNF Hold relax stretching along with moist heat showed significant improvement in pain reduction and improving hamstring flexibility than Static stretching along with moist heat.

Localization and stretch-dependence of lung elastase activity in development and compensatory growth.

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Young, Sarah Marie; Liu, Sheng; Joshi, Rashika; Batie, Matthew R; Kofron, Matthew; Guo, Jinbang; Woods, Jason C; Varisco, Brian Michael

2015-04-01

Synthesis and remodeling of the lung matrix is necessary for primary and compensatory lung growth. Because cyclic negative force is applied to developing lung tissue during the respiratory cycle, we hypothesized that stretch is a critical regulator of lung matrix remodeling. By using quantitative image analysis of whole-lung and whole-lobe elastin in situ zymography images, we demonstrated that elastase activity increased twofold during the alveolar stage of postnatal lung morphogenesis in the mouse. Remodeling was restricted to alveolar walls and ducts and was nearly absent in dense elastin band structures. In the mouse pneumonectomy model of compensatory lung growth, elastase activity increased threefold, peaking at 14 days postpneumonectomy and was higher in the accessory lobe compared with other lobes. Remodeling during normal development and during compensatory lung growth was different with increased major airway and pulmonary arterial remodeling during development but not regeneration, and with homogenous remodeling throughout the parenchyma during development, but increased remodeling only in subpleural regions during compensatory lung growth. Left lung wax plombage prevented increased lung elastin during compensatory lung growth. To test whether the adult lung retains an innate capacity to remodel elastin, we developed a confocal microscope-compatible stretching device. In ex vivo adult mouse lung sections, lung elastase activity increased exponentially with strain and in peripheral regions of lung more than in central regions. Our study demonstrates that lung elastase activity is stretch-dependent and supports a model in which externally applied forces influence the composition, structure, and function of the matrix during periods of alveolar septation. Copyright © 2015 the American Physiological Society.

DNA analysis by single molecule stretching in nanofluidic biochips

DEFF Research Database (Denmark)

Abad, E.; Juarros, A.; Retolaza, A.

2011-01-01

Imprint Lithography (NIL) technology combined with a conventional anodic bonding of the silicon base and Pyrex cover. Using this chip, we have performed single molecule imaging on a bench-top fluorescent microscope system. Lambda phage DNA was used as a model sample to characterize the chip. Single molecules of λ-DNA......Stretching single DNA molecules by confinement in nanofluidic channels has attracted a great interest during the last few years as a DNA analysis tool. We have designed and fabricated a sealed micro/nanofluidic device for DNA stretching applications, based on the use of the high throughput Nano...... stained with the fluorescent dye YOYO-1 were stretched in the nanochannel array and the experimental results were analysed to determine the extension factor of the DNA in the chip and the geometrical average of the nanochannel inner diameter. The determination of the extension ratio of the chip provides...

Stretch Sensor Device

DEFF Research Database (Denmark)

2013-01-01

The invention relates to a method for determining stretch values and movement of body parts, e.g. a foot, by analysing stretch data from a stretch sensor. By analysing data from the stretch sensor it is possible to determine stretch samples which are associated with particular motion phases...

METODE ACTIVE ISOLATED STRETCHING (AIS DAN METODE HOLD RELAX STRETCHING (HRS SAMA EFEKTIF DALAM MENINGKATKAN FLEKSIBILITAS OTOT HAMSTRING PADA MAHASISWA AKADEMI FISIOTERAPI WIDYA HUSADA SEMARANG YANG MENGALAMI HAMSTRING MUSCLE TIGHTNESS (HMTs

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Akhmad alfajri

2015-08-01

Full Text Available Students with Hamstring Muscle Tightness (HMTs will be at risk of Anterior Crusiatum Ligament (ACL, Low Back Pain (LBP and also Plantar Faciitis. One of the efforts to reduce tightness and improve hamstring muscle flexibility is stretching. Active Isolated Stretching (AIS and Hold Relax Stretching (HRS are the methods of influential stretching to improve muscle flexibility. The goal of the research is to prove that AIS method is equally effective with the HRS method to improve hamstring muscle flexibility to the HMTs patients. The research method was true experimental with pre and post test group design. The research was conducted for 3 weeks and the samples are 23 students in range of 18-25 years old students of physical therapy in Physical Therapy Academy of Widya Husada Semarang which divided into 2 groups; AIS group (n= 12 and HRS group (n= 11. The research used Sit and Reach Test (SRT as the measurement instrument. The result of the research was the average result of AIS group used SRT before treatment was 1.75 cm, SB= 4.309 and after treatment was 10. 58 cm, SB = 8. 005 within p= 0.000 (p 0.05. Those explain that the improvement of hamstring muscle flexibility to the two groups does not show any significant difference. Conclusion from this study was active isolated stretching method and hold relax stretching method are equally effective to improving muscle flexibility of hamstring muscle tightness students of physical therapy in Physical Therapy Academy of Widya Husada Semarang.

Bruxism: Is There an Indication for Muscle-Stretching Exercises?

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Gouw, Simone; de Wijer, Anton; Creugers, Nico Hj; Kalaykova, Stanimira I

Bruxism is a common phenomenon involving repetitive activation of the masticatory muscles. Muscle-stretching exercises are a recommended part of several international guidelines for musculoskeletal disorders and may be effective in management of the jaw muscle activity that gives rise to bruxism. However, most studies of muscle-stretching exercises have mainly focused on their influence on performance (eg, range of motion, coordination, and muscle strength) of the limb or trunk muscles of healthy individuals or individuals with sports-related injuries. Very few have investigated stretching of the human masticatory muscles and none muscle-stretching exercises in the management of (sleep) bruxism. This article reviews the literature on muscle-stretching exercises and their potential role in the management of sleep bruxism or its consequences in the musculoskeletal system.

Stretching & Flexibility: An Interactive Encyclopedia of Stretching. [CD-ROM].

Science.gov (United States)

2002

This CD-ROM offers 140 different stretches in full-motion video sequences. It focuses on the proper techniques for overall physical fitness, injury prevention and rehabilitation, and 23 different sports (e.g., golf, running, soccer, skiing, climbing, football, and baseball). Topics include stretching for sports; stretching awareness and education…

The effects of ramp stretches on active contractions in intact mammalian fast and slow muscle fibres.

Science.gov (United States)

Mutungi, G; Ranatunga, K W

2001-01-01

The effects of a ramp stretch (amplitude muscle fibre length (L0), speed twitch tension and twitch tension re-development were examined in intact mammalian (rat) fast and slow muscle fibre bundles. The experiments were done in vitro at 20 degrees C and at an initial sarcomere length of 2.68 microm. In both fibre types, a stretch applied during the rising phase of the twitch response (including the time of stimulation) increased the re-developed twitch tension (15-35%). A stretch applied before the stimulus had little or no effect on the twitch myogram in fast muscle fibres, but it increased the twitch tension (approximately 5%) in slow muscle fibres. A similar stretch had little or no effect on tetanic tension in either muscle fibre type. In general, the results indicate that the contractile-activation mechanism may be stretch sensitive and this is particularly pronounced in slow muscle fibres. Recorded at a high sampling rate and examined at an appropriate time scale, the transitory tension response to a stretch rose in at least two phases; an initial rapid tension rise to a break (break point tension, P1a) followed by a slower tension rise (apparent P2a) to a peak reached at the end of the stretch. Plotted against stretch velocity, P1a tension increased in direct proportion to stretch velocity (viscous-like) whereas, P2a tension (calculated as peak tension minus P1a tension) increased with stretch velocity to a plateau (visco-elastic). Examined at the peak of a twitch, P1a tension had a slope (viscosity coefficient) of 1.8 kN m(-2) per L0 s(-1) in fast fibres and 4.7 kN m(-2) per L0 s(-1) in slow muscle fibres. In the same preparations, P2a tension had a relaxation time of 8 ms in the fast muscle fibres and 25 ms in the slow muscle fibres. The amplitudes of both tension components scaled with the instantaneous twitch tension in qualitatively the same way as the instantaneous fibre stiffness. These fast/slow fibre type differences probably reflect differences in

Channel and island change in the lower Platte River, Eastern Nebraska, USA: 1855 2005

Science.gov (United States)

Joeckel, R. M.; Henebry, G. M.

2008-12-01

The lower Platte River has undergone considerable change in channel and bar characteristics since the mid-1850s in four 20-25 km-long study stretches. The same net effect of historical channel shrinkage that was detected upstream from Grand Island, Nebraska, can also be detected in the lower river but differences in the behaviors of study stretches upstream and downstream from major tributaries are striking. The least relative decrease occurred downstream from the Loup River confluence, and the stretch downstream from the Elkhorn River confluence actually showed an increase in channel area during the 1940s. Bank erosion was also greater downstream of the tributaries between ca. 1860 and 1938/1941, particularly in stretch RG, which showed more lateral migration. The cumulative island area and the ratio of island area to channel area relative to the 1938/1941 baseline data showed comparatively great fluctuations in median island size in both downstream stretches. The erratic behavior of island size distributions over time indicates that large islands were accreted to the banks at different times, and that some small, newly-stabilized islands were episodically "flushed" out of the system. In the upstream stretches the stabilization of mobile bars to create new, small islands had a more consistent impact over time. Channel decrease by the abandonment of large, long-lived anabranches and by the in-place narrowing resulting from island accretion were more prominent in these upstream stretches. Across all of the study area, channel area appears to be stabilizing gradually as the rate of decrease lessens. This trend began earliest in stretch RG in the late 1950s and was accompanied by shifts in the size distributions of stabilized islands in that stretch into the 1960s. Elsewhere, even in the easternmost study stretch, stabilizing was occurring by the late 1960s, the same time frame documented by investigations of the Platte system upstream of the study area. Comprehensive

Metaflumizone is a novel sodium channel blocker insecticide.

Science.gov (United States)

Salgado, V L; Hayashi, J H

2007-12-15

Metaflumizone is a novel semicarbazone insecticide, derived chemically from the pyrazoline sodium channel blocker insecticides (SCBIs) discovered at Philips-Duphar in the early 1970s, but with greatly improved mammalian safety. This paper describes studies confirming that the insecticidal action of metaflumizone is due to the state-dependent blockage of sodium channels. Larvae of the moth Spodoptera eridania injected with metaflumizone became paralyzed, concomitant with blockage of all nerve activity. Furthermore, tonic firing of abdominal stretch receptor organs from Spodoptera frugiperda was blocked by metaflumizone applied in the bath, consistent with the block of voltage-dependent sodium channels. Studies on native sodium channels, in primary-cultured neurons isolated from the CNS of the larvae of the moth Manduca sexta and on Para/TipE sodium channels heterologously expressed in Xenopus (African clawed frog) oocytes, confirmed that metaflumizone blocks sodium channels by binding selectively to the slow-inactivated state, which is characteristic of the SCBIs. The results confirm that metaflumizone is a novel sodium channel blocker insecticide.

Lewis lung carcinoma regulation of mechanical stretch-induced protein synthesis in cultured myotubes.

Science.gov (United States)

Gao, Song; Carson, James A

2016-01-01

Mechanical stretch can activate muscle and myotube protein synthesis through mammalian target of rapamycin complex 1 (mTORC1) signaling. While it has been established that tumor-derived cachectic factors can induce myotube wasting, the effect of this catabolic environment on myotube mechanical signaling has not been determined. We investigated whether media containing cachectic factors derived from Lewis lung carcinoma (LLC) can regulate the stretch induction of myotube protein synthesis. C2C12 myotubes preincubated in control or LLC-derived media were chronically stretched. Protein synthesis regulation by anabolic and catabolic signaling was then examined. In the control condition, stretch increased mTORC1 activity and protein synthesis. The LLC treatment decreased basal mTORC1 activity and protein synthesis and attenuated the stretch induction of protein synthesis. LLC media increased STAT3 and AMP-activated protein kinase phosphorylation in myotubes, independent of stretch. Both stretch and LLC independently increased ERK1/2, p38, and NF-κB phosphorylation. In LLC-treated myotubes, the inhibition of ERK1/2 and p38 rescued the stretch induction of protein synthesis. Interestingly, either leukemia inhibitory factor or glycoprotein 130 antibody administration caused further inhibition of mTORC1 signaling and protein synthesis in stretched myotubes. AMP-activated protein kinase inhibition increased basal mTORC1 signaling activity and protein synthesis in LLC-treated myotubes, but did not restore the stretch induction of protein synthesis. These results demonstrate that LLC-derived cachectic factors can dissociate stretch-induced signaling from protein synthesis through ERK1/2 and p38 signaling, and that glycoprotein 130 signaling is associated with the basal stretch response in myotubes. Copyright © 2016 the American Physiological Society.

Micropatterning stretched and aligned DNA for sequence-specific nanolithography

Science.gov (United States)

Petit, Cecilia Anna Paulette

Techniques for fabricating nanostructured materials can be categorized as either "top-down" or "bottom-up". Top-down techniques use lithography and contact printing to create patterned surfaces and microfluidic channels that can corral and organize nanoscale structures, such as molecules and nanorods in contrast; bottom-up techniques use self-assembly or molecular recognition to direct the organization of materials. A central goal in nanotechnology is the integration of bottom-up and top-down assembly strategies for materials development, device design; and process integration. With this goal in mind, we have developed strategies that will allow this integration by using DNA as a template for nanofabrication; two top-down approaches allow the placement of these templates, while the bottom-up technique uses the specific sequence of bases to pattern materials along each strand of DNA. Our first top-down approach, termed combing of molecules in microchannels (COMMIC), produces microscopic patterns of stretched and aligned molecules of DNA on surfaces. This process consists of passing an air-water interface over end adsorbed molecules inside microfabricated channels. The geometry of the microchannel directs the placement of the DNA molecules, while the geometry of the airwater interface directs the local orientation and curvature of the molecules. We developed another top-down strategy for creating micropatterns of stretched and aligned DNA using surface chemistry. Because DNA stretching occurs on hydrophobic surfaces, this technique uses photolithography to pattern vinyl-terminated silanes on glass When these surface-, are immersed in DNA solution, molecules adhere preferentially to the silanized areas. This approach has also proven useful in patterning protein for cell adhesion studies. Finally, we describe the use of these stretched and aligned molecules of DNA as templates for the subsequent bottom-up construction of hetero-structures through hybridization

EFFECTIVENESS OF PNF STRETCHING AND CYCLIC STRETCHING OF CALF TIGHTNESS ON COLLEGE GOING GIRLS

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Ashlesha Sirari

2015-06-01

Full Text Available Background: Flexibility helps with injury prevention, the reduction of soreness following a workout, and a general sense of well-being. There are different stretching techniques and protocols for improvements in calf extensibility and flexibility. The purpose of the study was to investigate the effectiveness of two techniques i.e. CYCLIC and PNF stretching which improves calf flexibility. This study was done to find the effectiveness of calf Cyclic and PNF stretching technique to improve calf flexibility. Methods: 30 subjects with age group 21-22 years were randomly allocated to 2 groups equally. Group 1(n=15 were given CYCLIC and group 2(n=15 were given PNF stretching technique. Plantar flexion was used to measure the calf tightness which was done before and after the treatment. Treatment was given for 7 days and on the 7th day the calf tightness was again measured. Results: The mean difference of the CYCLIC is 4.6 and mean difference of PNF is 4.7 which indicate that CYCLIC and PNF both are effective to improve calf flexibility but PNF is more effective than CYCLIC to improve calf flexibility. Conclusion: The neurophysiological basis of PNF, stating that the excitatory efficient of the neuromuscular spindle or the inhibitory afferent of the Golgi tendon organ (GTO or both are responsible for the effects. During PNF stretch and isometric contraction of stretched agonists for extended period may cause activation of its neuromuscular spindle. The increase in tension created during the isometric contraction of the pre – lengthened agonist contracts concentrically. Both the fascia & the spindle of the agonist adjust to the nearly lengthened position. These impulses travel via causing post synaptic inhibition of the motor neuron to agonist increasing the tension from the GTO. These impulses can override the impulses coming from the neuromuscular spindles arousing the muscle to reflexly resist to the change in length, thus helping in lengthening

Slack, Slick, and Sodium-Activated Potassium Channels

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Kaczmarek, Leonard K.

2013-01-01

The Slack and Slick genes encode potassium channels that are very widely expressed in the central nervous system. These channels are activated by elevations in intracellular sodium, such as those that occur during trains of one or more action potentials, or following activation of nonselective cationic neurotransmitter receptors such as AMPA receptors. This review covers the cellular and molecular properties of Slack and Slick channels and compares them with findings on the properties of sodium-activated potassium currents (termed KNa currents) in native neurons. Human mutations in Slack channels produce extremely severe defects in learning and development, suggesting that KNa channels play a central role in neuronal plasticity and intellectual function. PMID:24319675

A quantized mechanism for activation of pannexin channels

Science.gov (United States)

Chiu, Yu-Hsin; Jin, Xueyao; Medina, Christopher B.; Leonhardt, Susan A.; Kiessling, Volker; Bennett, Brad C.; Shu, Shaofang; Tamm, Lukas K.; Yeager, Mark; Ravichandran, Kodi S.; Bayliss, Douglas A.

2017-01-01

Pannexin 1 (PANX1) subunits form oligomeric plasma membrane channels that mediate nucleotide release for purinergic signalling, which is involved in diverse physiological processes such as apoptosis, inflammation, blood pressure regulation, and cancer progression and metastasis. Here we explore the mechanistic basis for PANX1 activation by using wild type and engineered concatemeric channels. We find that PANX1 activation involves sequential stepwise sojourns through multiple discrete open states, each with unique channel gating and conductance properties that reflect contributions of the individual subunits of the hexamer. Progressive PANX1 channel opening is directly linked to permeation of ions and large molecules (ATP and fluorescent dyes) and occurs during both irreversible (caspase cleavage-mediated) and reversible (α1 adrenoceptor-mediated) forms of channel activation. This unique, quantized activation process enables fine tuning of PANX1 channel activity and may be a generalized regulatory mechanism for other related multimeric channels. PMID:28134257

Channel sialic acids limit hERG channel activity during the ventricular action potential.

Science.gov (United States)

Norring, Sarah A; Ednie, Andrew R; Schwetz, Tara A; Du, Dongping; Yang, Hui; Bennett, Eric S

2013-02-01

Activity of human ether-a-go-go-related gene (hERG) 1 voltage-gated K(+) channels is responsible for portions of phase 2 and phase 3 repolarization of the human ventricular action potential. Here, we questioned whether and how physiologically and pathophysiologically relevant changes in surface N-glycosylation modified hERG channel function. Voltage-dependent hERG channel gating and activity were evaluated as expressed in a set of Chinese hamster ovary (CHO) cell lines under conditions of full glycosylation, no sialylation, no complex N-glycans, and following enzymatic deglycosylation of surface N-glycans. For each condition of reduced glycosylation, hERG channel steady-state activation and inactivation relationships were shifted linearly by significant depolarizing ∼9 and ∼18 mV, respectively. The hERG window current increased significantly by 50-150%, and the peak shifted by a depolarizing ∼10 mV. There was no significant change in maximum hERG current density. Deglycosylated channels were significantly more active (20-80%) than glycosylated controls during phases 2 and 3 of action potential clamp protocols. Simulations of hERG current and ventricular action potentials corroborated experimental data and predicted reduced sialylation leads to a 50-70-ms decrease in action potential duration. The data describe a novel mechanism by which hERG channel gating is modulated through physiologically and pathophysiologically relevant changes in N-glycosylation; reduced channel sialylation increases hERG channel activity during the action potential, thereby increasing the rate of action potential repolarization.

The core domain as the force sensor of the yeast mechanosensitive TRP channel.

Science.gov (United States)

Su, Zhenwei; Anishkin, Andriy; Kung, Ching; Saimi, Yoshiro

2011-12-01

Stretch-activated conductances are commonly encountered in careful electric recordings. Those of known proteins (TRP, MscL, MscS, K(2p), Kv, etc.) all share a core, which houses the ion pathway and the gate, but no recognizable force-sensing domain. Like animal TRPs, the yeast TRPY1 is polymodal, activated by stretch force, Ca(2+), etc. To test whether its S5-S6 core senses the stretch force, we tried to uncouple it from the peripheral domains by strategic peptide insertions to block the covalent core-periphery interactions. Insertion of long unstructured peptides should distort, if not disrupt, protein structures that transmit force. Such insertions between S6 and the C-terminal tail largely removed Ca(2+) activation, showing their effectiveness. However, such insertions as well as those between S5 and the N-terminal region, which includes S1-S4, did not significantly alter mechanosensitivity. Even insertions at both locations flanking the S5-S6 core did not much alter mechanosensitivity. Tryptophan scanning mutations in S5 were also constructed to perturb possible noncovalent core-periphery contacts. The testable tryptophan mutations also have little or no effects on mechanosensitivity. Boltzmann fits of the wild-type force-response curves agree with a structural homology model for a stretch-induced core expansion of ~2 nm(2) upon opening. We hypothesize that membrane tension pulls on S5-S6, expanding the core and opening the TRPY1 gate. The core being the major force sensor offers the simplest, though not the only, explanation of why so many channels of disparate designs are mechanically sensitive. Compared with the bacterial MscL, TRPY1 is much less sensitive to force, befitting a polymodal channel that relies on multiple stimuli.

Stretch-minimising stream surfaces

KAUST Repository

Barton, Michael; Kosinka, Jin; Calo, Victor M.

2015-01-01

We study the problem of finding stretch-minimising stream surfaces in a divergence-free vector field. These surfaces are generated by motions of seed curves that propagate through the field in a stretch minimising manner, i.e., they move without stretching or shrinking, preserving the length of their arbitrary arc. In general fields, such curves may not exist. How-ever, the divergence-free constraint gives rise to these 'stretch-free' curves that are locally arc-length preserving when infinitesimally propagated. Several families of stretch-free curves are identified and used as initial guesses for stream surface generation. These surfaces are subsequently globally optimised to obtain the best stretch-minimising stream surfaces in a given divergence-free vector field. Our algorithm was tested on benchmark datasets, proving its applicability to incompressible fluid flow simulations, where our stretch-minimising stream surfaces realistically reflect the flow of a flexible univariate object. © 2015 Elsevier Inc. All rights reserved.

Stretch-minimising stream surfaces

KAUST Repository

Barton, Michael

2015-05-01

We study the problem of finding stretch-minimising stream surfaces in a divergence-free vector field. These surfaces are generated by motions of seed curves that propagate through the field in a stretch minimising manner, i.e., they move without stretching or shrinking, preserving the length of their arbitrary arc. In general fields, such curves may not exist. How-ever, the divergence-free constraint gives rise to these \\'stretch-free\\' curves that are locally arc-length preserving when infinitesimally propagated. Several families of stretch-free curves are identified and used as initial guesses for stream surface generation. These surfaces are subsequently globally optimised to obtain the best stretch-minimising stream surfaces in a given divergence-free vector field. Our algorithm was tested on benchmark datasets, proving its applicability to incompressible fluid flow simulations, where our stretch-minimising stream surfaces realistically reflect the flow of a flexible univariate object. © 2015 Elsevier Inc. All rights reserved.

Stretching Safely and Effectively

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... shown that stretching immediately before an event weakens hamstring strength. Instead of static stretching, try performing a " ... If you play soccer, for instance, stretch your hamstrings as you're more vulnerable to hamstring strains. ...

The Relation Between Stretching Typology and Stretching Duration: The Effects on Range of Motion.

Science.gov (United States)

Thomas, Ewan; Bianco, Antonino; Paoli, Antonio; Palma, Antonio

2018-04-01

Different stretching strategies and protocols are widely used to improve flexibility or maintain health, acting on the muscle tendon-unit, in order to improve the range of motion (ROM) of the joints. This review aims to evaluate the current body of literature in order to understand the relation between stretching typology and ROM, and secondly to evaluate if a relation exists between stretching volume (either as a single training session, weekly training and weekly frequency) and ROM, after long-term stretching. Twenty-three articles were considered eligible and included in the quantitative synthesis. All stretching typologies showed ROM improvements over a long-term period, however the static protocols showed significant gains (p<0.05) when compared to the ballistic or PNF protocols. Time spent stretching per week seems fundamental to elicit range of movement improvements when stretches are applied for at least or more than 5 min, whereas the time spent stretching within a single session does not seem to have significant effects for ROM gains. Weekly frequency is positively associated to ROM. Evaluated data indicates that performing stretching at least 5 days a week for at least 5 min per week using static stretching may be beneficial to promote ROM improvements. © Georg Thieme Verlag KG Stuttgart · New York.

Modulation of ASIC channels in rat cerebellar purkinje neurons by ischaemia-related signals

Science.gov (United States)

Allen, Nicola J; Attwell, David

2002-01-01

Acid-sensing ion channels (ASICs), activated by a decrease of extracellular pH, are found in neurons throughout the nervous system. They have an amino acid sequence similar to that of ion channels activated by membrane stretch, and have been implicated in touch sensation. Here we characterize the pH-dependent activation of ASICs in cerebellar Purkinje cells and investigate how they are modulated by factors released in ischaemia. Lowering the external pH from 7.4 activated an inward current at −66 mV, carried largely by Na+ ions, which was half-maximal for a step to pH 6.4 and was blocked by amiloride and gadolinium. The H+-gated current desensitized within a few seconds, but approximately 30% of cells showed a sustained inward current (11% of the peak current) in response to the maintained presence of pH 6 solution. The peak H+-evoked current was potentiated by membrane stretch (which occurs in ischaemia when [K+]o rises) and by arachidonic acid (which is released when [Ca2+]i rises in ischaemia). Arachidonic acid increased to 77% the fraction of cells showing a sustained current evoked by acid pH. The ASIC currents were also potentiated by lactate (which is released when metabolism becomes anaerobic in ischaemia) and by FMRFamide (which may mimic the action of related mammalian RFamide transmitters). These data reinforce suggestions of a mechanosensory aspect to ASIC channel function, and show that the activation of ASICs reflects the integration of multiple signals which are present during ischaemia. PMID:12205186

Prolonged passive static stretching-induced innervation zone shift in biceps brachii.

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Ye, Xin; Beck, Travis W; Wages, Nathan P

2015-05-01

The purpose of this study was to examine the influence of a bout of repeated and prolonged passive static stretching on the innervation zone (IZ) location of the human biceps brachii muscle. Eleven men performed 12 sets of 100-s passive stretches on their biceps brachii. Before (Pre) and immediately after (Post) the stretching intervention, isometric strength was tested during the maximal voluntary contractions (MVCs) of the forearm flexors. The subjects also performed several separate isometric forearm flexion muscle actions at 30%, 50%, and 70% of their predetermined MVCs for examining the locations of the IZ at different contraction intensities. The IZ was identified through multi-channel surface electromyographic (EMG) recordings from a linear electrode array. The stretching intervention induced an average of 10% isometric strength loss for the forearm flexors (mean±SD: Pre-MVC vs. Post-MVC=332.12±59.40 N vs. 299.53±70.51 N; p<0.001). In addition, the average IZ shift was nearly 4.5 mm in average in the proximal direction. However, this shift was not specific to the contraction intensity. We believe that the IZ shift was caused by the elongation of the entire muscle-tendon unit in the proximal direction. Therefore, caution should be taken when using surface EMG technique to examine possible changes in the EMG variables after a stretching protocol, as these variables can be contaminated by the shift of the IZ.

Knotting in stretched polygons

International Nuclear Information System (INIS)

Rensburg, E J Janse van; Orlandini, E; Tesi, M C; Whittington, S G

2008-01-01

The knotting in a lattice polygon model of ring polymers is examined when a stretching force is applied to the polygon. By examining the incidence of cut-planes in the polygon, we prove a pattern theorem in the stretching regime for large applied forces. This theorem can be used to examine the incidence of entanglements such as knotting and writhing. In particular, we prove that for arbitrarily large positive, but finite, values of the stretching force, the probability that a stretched polygon is knotted approaches 1 as the length of the polygon increases. In the case of writhing, we prove that for stretched polygons of length n, and for every function f(n)=o(√n), the probability that the absolute value of the mean writhe is less than f(n) approaches 0 as n → ∞, for sufficiently large values of the applied stretching force

ACUTE EFFECTS OF DIFFERENT STATIC STRETCHING PROTOCOLS ON PEAK TORQUE, CONVENTIONAL AND FUNCTIONAL HAMSTRINGS-TO-QUADRICEPS RATIOS IN ACTIVE WOMEN

Directory of Open Access Journals (Sweden)

Ghada M. ALQaslah

2016-10-01

Full Text Available Background: This study might have been directed to some degree because of clashing results in the past studies regarding the impacts for different SS protocols on muscle strength and possibility for injury. The objective of the study was to investigate the acute effects of different static stretching (SS durations (20, 30, and 60s on isokinetic concentric quadriceps (Q and hamstrings (H peak torque (PT, eccentric H PT and conventional and functional H:Q ratios under different stretching conditions and angular velocities (60°and180°/s in active women. Methods: Isokinetic tests were performed on 108 active women. A HUMAC system was used to measure unilateral concentric Q and H PT, and eccentric H PT at 60 and 180º/s at baseline and after a bout of H-only, Q-only, and combined H and Q muscles SS. The data were statistically treated using five separate three-way (time x conditions x velocity ANOVA. Results: There were no significant differences among groups at baseline (P > 0.05. Significant reductions of all outcome measures have been shown to occur after 30 and 60s of SS (P 0.05. Conclusion: Short-lasting stretching can be done before exercises that require strength. However, since 30s or 60s stretching protocols adversely affect the muscle strength, performance and lower H:Q ratios they are not recommended prior to activities demanding the production of high forces.

Wall to membrane linkers, stretch activated channels, and the detection of tension, voltage, temperature, auxin, and pH

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Pickard, B. G.

1992-01-01

Introduction. The higher plant is a heterogeneous, mechanically prestressed structure continually subject to shifting forces. When a cell grows in a plant at gravitropic equilibrium, it must create localized maxima of shear in walls of neighboring cells. Such mechanical stress and strain are likely detected in a variety of ways. However, tension-sensitive ion channels are of particular interest because it appears that they are elaborately evolved for sensory function. We hypothesize that 1) the patchy patterns of high shear are focused via wall-to-membrane linkers onto the plasma membrane, where 2) they are translated by mechanosensory cation channels into corresponding patterns of high cytosolic Ca2+, which 3) initiate local enhancement of wall expansion. Further, we hypothesize that the local promotion of enhancement is achieved at least in part by local intensification of auxin transport across the plasma membrane. By implication, when an organ is asymmetrically pressed, rubbed, or bent or when it is displaced in the gravitational field, the net asymmetry of shear stress occurring across the organ would lead to asymmetric redistribution of auxin and corrective asymmetric growth. We shall describe a representative mechanosensitive Ca(2+) -selective cation channel (MCaC) with susceptibilities to xenobiotics implicating it as a force transducer in thigmo- and gravitropism. Then, we shall consider whether a putative wall-to-membrane linker (WML) could be a key feature of the molecular architecture permitting the stress distributed in the wall system to be focused on the channels.

Stretch-sensitive paresis and effort perception in hemiparesis.

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Vinti, Maria; Bayle, Nicolas; Hutin, Emilie; Burke, David; Gracies, Jean-Michel

2015-08-01

In spastic paresis, stretch applied to the antagonist increases its inappropriate recruitment during agonist command (spastic co-contraction). It is unknown whether antagonist stretch: (1) also affects agonist recruitment; (2) alters effort perception. We quantified voluntary activation of ankle dorsiflexors, effort perception, and plantar flexor co-contraction during graded dorsiflexion efforts at two gastrocnemius lengths. Eighteen healthy (age 41 ± 13) and 18 hemiparetic (age 54 ± 12) subjects performed light, medium and maximal isometric dorsiflexion efforts with the knee flexed or extended. We determined dorsiflexor torque, Root Mean Square EMG and Agonist Recruitment/Co-contraction Indices (ARI/CCI) from the 500 ms peak voluntary agonist recruitment in a 5-s maximal isometric effort in tibialis anterior, soleus and medial gastrocnemius. Subjects retrospectively reported effort perception on a 10-point visual analog scale. During gastrocnemius stretch in hemiparetic subjects, we observed: (1) a 25 ± 7 % reduction of tibialis anterior voluntary activation (maximum reduction 98 %; knee extended vs knee flexed; p = 0.007, ANOVA); (2) an increase in dorsiflexion effort perception (p = 0.03, ANCOVA). Such changes did not occur in healthy subjects. Effort perception depended on tibialis anterior recruitment only (βARI(TA) = 0.61, p hemiparesis, voluntary ability to recruit agonist motoneurones is impaired--sometimes abolished--by antagonist stretch, a phenomenon defined here as stretch-sensitive paresis. In addition, spastic co-contraction increases effort perception, an additional incentive to evaluate and treat this phenomenon.

Effects of Static Stretching and Playing Soccer on Knee Laxity.

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Baumgart, Christian; Gokeler, Alli; Donath, Lars; Hoppe, Matthias W; Freiwald, Jürgen

2015-11-01

This study investigated exercise-induced effects of static stretching and playing soccer on anterior tibial translation (ATT) of the knee joint. Randomized controlled trial. University biomechanics laboratory. Thirty-one athletes were randomly assigned into a stretching (26.9 ± 6.2 years, 1.77 ± 0.09 m, 67.9 ± 10.7 kg) and a control group (27.9 ± 7.4 years, 1.75 ± 0.08 m, 72.0 ± 14.9 kg). Thirty-one amateur soccer players in an additional soccer group (25.1 ± 5.6 years, 1.74 ± 0.10 m, 71.8 ± 14.8 kg). All participants had no history of knee injury requiring surgery and any previous knee ligament or cartilage injury. The stretching group performed 4 different static stretching exercises with a duration of 2 × 20 seconds interspersed with breaks of 10 seconds. The soccer group completed a 90-minute soccer-specific training program. The control group did not perform any physical activity for approximately 30 minutes. Anterior tibial translation was measured with the KT-1000 knee arthrometer at forces of 67 N, 89 N, and maximal manual force (Max) before and after the intervention. There was a significant increase in ATT after static stretching and playing soccer at all applied forces. Maximal manual testing revealed a mean increase of ATT after static stretching of 2.1 ± 1.6 mm (P soccer of 1.0 ± 1.5 mm (P = 0.001). The ATT increase after static stretching at 67 and 89 N is significantly higher than in controls. At maximum manual testing, significant differences were evident between all groups. Static stretching and playing soccer increase ATT and may consequently influence mechanical factors of the anterior cruciate ligament. The ATT increase after static stretching was greater than after playing soccer. The observed increase in ATT after static stretching and playing soccer may be associated with changes in kinesthetic perception and sensorimotor control, activation of muscles, joint stability, overall performance, and higher injury risk.

Stretch-induced Ca2+ independent ATP release in hippocampal astrocytes.

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Xiong, Yingfei; Teng, Sasa; Zheng, Lianghong; Sun, Suhua; Li, Jie; Guo, Ning; Li, Mingli; Wang, Li; Zhu, Feipeng; Wang, Changhe; Rao, Zhiren; Zhou, Zhuan

2018-02-28

Similar to neurons, astrocytes actively participate in synaptic transmission via releasing gliotransmitters. The Ca 2+ -dependent release of gliotransmitters includes glutamate and ATP. Following an 'on-cell-like' mechanical stimulus to a single astrocyte, Ca 2+ independent single, large, non-quantal, ATP release occurs. Astrocytic ATP release is inhibited by either selective antagonist treatment or genetic knockdown of P2X7 receptor channels. Our work suggests that ATP can be released from astrocytes via two independent pathways in hippocampal astrocytes; in addition to the known Ca 2+ -dependent vesicular release, larger non-quantal ATP release depends on P2X7 channels following mechanical stretch. Astrocytic ATP release is essential for brain functions such as synaptic long-term potentiation for learning and memory. However, whether and how ATP is released via exocytosis remains hotly debated. All previous studies of non-vesicular ATP release have used indirect assays. By contrast, two recent studies report vesicular ATP release using more direct assays. In the present study, using patch clamped 'ATP-sniffer cells', we re-investigated astrocytic ATP release at single-vesicle resolution in hippocampal astrocytes. Following an 'on-cell-like' mechanical stimulus of a single astrocyte, a Ca 2+ independent single large non-quantal ATP release occurred, in contrast to the Ca 2+ -dependent multiple small quantal ATP release in a chromaffin cell. The mechanical stimulation-induced ATP release from an astrocyte was inhibited by either exposure to a selective antagonist or genetic knockdown of P2X7 receptor channels. Functional P2X7 channels were expressed in astrocytes in hippocampal brain slices. Thus, in addition to small quantal ATP release, larger non-quantal ATP release depends on P2X7 channels in astrocytes. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Immediate effects of hamstring stretching alone or combined with ischemic compression of the masseter muscle on hamstrings extensibility, active mouth opening and pain in athletes with temporomandibular dysfunction.

Science.gov (United States)

Espejo-Antúnez, Luis; Castro-Valenzuela, Elisa; Ribeiro, Fernando; Albornoz-Cabello, Manuel; Silva, Anabela; Rodríguez-Mansilla, Juan

2016-07-01

To assess the immediate effects of hamstrings stretching alone or combined with ischemic compression of the masseter muscle on hamstrings extensibility, active mouth opening and pain in athletes with temporomandibular dysfunction and hamstrings shortening. Forty-two participants were randomized to receive the stretching technique (n = 21) or the stretching plus the ischemic compression (n = 21). Outcome measures were: hamstrings extensibility, active mouth opening, pressure pain thresholds and pain intensity. Both interventions improved significantly active mouth opening (group 1: 35.7 ± 6.7 to 39.1 ± 7.6 mm, p Hamstrings stretching induced an acute improvement in hamstrings extensibility, active mouth opening and pain. Moreover, the addition of ischemic compression did not induce further improvements on the assessed parameters. Copyright © 2016. Published by Elsevier Ltd.

Influence of the stretch wrapping process on the mechanical behavior of a stretch film

Science.gov (United States)

Klein, Daniel; Stommel, Markus; Zimmer, Johannes

2018-05-01

Lightweight construction is an ongoing task in packaging development. Consequently, the stability of packages during transport is gaining importance. This study contributes to the optimization of lightweight packaging concepts regarding their stability. A very widespread packaging concept is the distribution of goods on a pallet whereas a Polyethylene (PE) stretch film stabilizes the lightweight structure during the shipment. Usually, a stretch wrapping machine applies this stretch film to the pallet. The objective of this study is to support packaging development with a method that predicts the result of the wrapping process, based on the mechanical characterization of the stretch film. This result is not only defined by the amount of stretch film, its spatial distribution on the pallet and its internal stresses that result in a containment force. More accurate, this contribution also considers the influence of the deformation history of the stretch film during the wrapping process. By focusing on similarities of stretch wrappers rather than on differences, the influence of generalized process parameters on stretch film mechanics and thereby on pallet stability can be determined experimentally. For a practical use, the predictive method is accumulated in an analytic model of the wrapping process that can be verified experimentally. This paves the way for experimental and numerical approaches regarding the optimization of pallet stability.

Tuning Piezo ion channels to detect molecular-scale movements relevant for fine touch

Science.gov (United States)

Poole, Kate; Herget, Regina; Lapatsina, Liudmila; Ngo, Ha-Duong; Lewin, Gary R.

2014-01-01

In sensory neurons, mechanotransduction is sensitive, fast and requires mechanosensitive ion channels. Here we develop a new method to directly monitor mechanotransduction at defined regions of the cell-substrate interface. We show that molecular-scale (~13 nm) displacements are sufficient to gate mechanosensitive currents in mouse touch receptors. Using neurons from knockout mice, we show that displacement thresholds increase by one order of magnitude in the absence of stomatin-like protein 3 (STOML3). Piezo1 is the founding member of a class of mammalian stretch-activated ion channels, and we show that STOML3, but not other stomatin-domain proteins, brings the activation threshold for Piezo1 and Piezo2 currents down to ~10 nm. Structure–function experiments localize the Piezo modulatory activity of STOML3 to the stomatin domain, and higher-order scaffolds are a prerequisite for function. STOML3 is the first potent modulator of Piezo channels that tunes the sensitivity of mechanically gated channels to detect molecular-scale stimuli relevant for fine touch. PMID:24662763

Short Durations of Static Stretching when Combined with Dynamic Stretching do not Impair Repeated Sprints and Agility.

Science.gov (United States)

Wong, Del P; Chaouachi, Anis; Lau, Patrick W C; Behm, David G

2011-01-01

This study aimed to compare the effect of different static stretching durations followed by dynamic stretching on repeated sprint ability (RSA) and change of direction (COD). Twenty-five participants performed the RSA and COD tests in a randomized order. After a 5 min aerobic warm up, participants performed one of the three static stretching protocols of 30 s, 60 s or 90 s total duration (3 stretches x 10 s, 20 s or 30 s). Three dynamic stretching exercises of 30 s duration were then performed (90 s total). Sit-and-reach flexibility tests were conducted before the aerobic warm up, after the combined static and dynamic stretching, and post- RSA/COD test. The duration of static stretching had a positive effect on flexibility with 36.3% and 85.6% greater sit-and-reach scores with the 60 s and 90 s static stretching conditions respectively than with the 30 s condition (p ≤ 0.001). However there were no significant differences in RSA and COD performance between the 3 stretching conditions. The lack of change in RSA and COD might be attributed to a counterbalancing of static and dynamic stretching effects. Furthermore, the short duration (≤ 90 s) static stretching may not have provided sufficient stimulus to elicit performance impairments. Key pointsThe duration of combined static and dynamic stretching had a positive effect on flexibility with 36.3% and 85.6% greater sit and reach scores with the 60 s and 90 s static stretching conditions respectively than with the 30 s condition (p ≤ 0.001).No significant differences in RSA and COD between the 3 stretching conditions.The lack of change in RSA and COD might be attributed to a counterbalancing of static and dynamic stretching effects.The short duration (≤ 90 s) static stretching may not have provided sufficient stimulus to elicit performance impairments.

Short Durations of Static Stretching when Combined with Dynamic Stretching do not Impair Repeated Sprints and Agility

Science.gov (United States)

Wong, Del P.; Chaouachi, Anis; Lau, Patrick W.C.; Behm, David G.

2011-01-01

This study aimed to compare the effect of different static stretching durations followed by dynamic stretching on repeated sprint ability (RSA) and change of direction (COD). Twenty-five participants performed the RSA and COD tests in a randomized order. After a 5 min aerobic warm up, participants performed one of the three static stretching protocols of 30 s, 60 s or 90 s total duration (3 stretches x 10 s, 20 s or 30 s). Three dynamic stretching exercises of 30 s duration were then performed (90 s total). Sit-and-reach flexibility tests were conducted before the aerobic warm up, after the combined static and dynamic stretching, and post- RSA/COD test. The duration of static stretching had a positive effect on flexibility with 36.3% and 85.6% greater sit-and-reach scores with the 60 s and 90 s static stretching conditions respectively than with the 30 s condition (p ≤ 0.001). However there were no significant differences in RSA and COD performance between the 3 stretching conditions. The lack of change in RSA and COD might be attributed to a counterbalancing of static and dynamic stretching effects. Furthermore, the short duration (≤ 90 s) static stretching may not have provided sufficient stimulus to elicit performance impairments. Key points The duration of combined static and dynamic stretching had a positive effect on flexibility with 36.3% and 85.6% greater sit and reach scores with the 60 s and 90 s static stretching conditions respectively than with the 30 s condition (p ≤ 0.001). No significant differences in RSA and COD between the 3 stretching conditions. The lack of change in RSA and COD might be attributed to a counterbalancing of static and dynamic stretching effects. The short duration (≤ 90 s) static stretching may not have provided sufficient stimulus to elicit performance impairments. PMID:24149890

Large conductance Ca2+-activated K+ (BK channel: Activation by Ca2+ and voltage

Directory of Open Access Journals (Sweden)

RAMÓN LATORRE

2006-01-01

Full Text Available Large conductance Ca2+-activated K+ (BK channels belong to the S4 superfamily of K+ channels that include voltage-dependent K+ (Kv channels characterized by having six (S1-S6 transmembrane domains and a positively charged S4 domain. As Kv channels, BK channels contain a S4 domain, but they have an extra (S0 transmembrane domain that leads to an external NH2-terminus. The BK channel is activated by internal Ca2+, and using chimeric channels and mutagenesis, three distinct Ca2+-dependent regulatory mechanisms with different divalent cation selectivity have been identified in its large COOH-terminus. Two of these putative Ca2+-binding domains activate the BK channel when cytoplasmic Ca2+ reaches micromolar concentrations, and a low Ca2+ affinity mechanism may be involved in the physiological regulation by Mg2+. The presence in the BK channel of multiple Ca2+-binding sites explains the huge Ca2+ concentration range (0.1 μM-100 μM in which the divalent cation influences channel gating. BK channels are also voltage-dependent, and all the experimental evidence points toward the S4 domain as the domain in charge of sensing the voltage. Calcium can open BK channels when all the voltage sensors are in their resting configuration, and voltage is able to activate channels in the complete absence of Ca2+. Therefore, Ca2+ and voltage act independently to enhance channel opening, and this behavior can be explained using a two-tiered allosteric gating mechanism.

Oriented Morphology and Anisotropic Transport in Uniaxially Stretched Perfluorosulfonate Ionomer Membranes

Energy Technology Data Exchange (ETDEWEB)

J Park; J Li; G Divoux; L Madsen; R Moore

2011-12-31

Relations between morphology and transport sensitively govern proton conductivity in perfluorsulfonate ionomers (PFSIs) and thus determine useful properties of these technologically important materials. In order to understand such relations, we have conducted a broad systematic study of H{sup +}-form PFSI membranes over a range of uniaxial extensions and water uptakes. On the basis of small-angle X-ray scattering (SAXS) and {sup 2}H NMR spectroscopy, uniaxial deformation induces a strong alignment of ionic domains along the stretching direction. We correlate ionic domain orientation to transport using pulsed-field-gradient {sup 1}H NMR measurements of water diffusion coefficients along the three orthogonal membrane directions. Intriguingly, we observe that uniaxial deformation enhances water transport in one direction (parallel-to-draw direction) while reducing it in the other two directions (two orthogonal directions relative to the stretching direction). We evaluate another important transport parameter, proton conductivity, along two orthogonal in-plane directions. In agreement with water diffusion experiments, orientation of ionic channels increases proton conduction along the stretching direction while decreasing it in the perpendicular direction. These findings provide valuable fodder for optimal application of PFSI membranes as well as for the design of next generation polymer electrolyte membranes.

SHORT DURATIONS OF STATIC STRETCHING WHEN COMBINED WITH DYNAMIC STRETCHING DO NOT IMPAIR REPEATED SPRINTS AND AGILITY

Directory of Open Access Journals (Sweden)

Del P. Wong

2011-06-01

Full Text Available This study aimed to compare the effect of different static stretching durations followed by dynamic stretching on repeated sprint ability (RSA and change of direction (COD. Twenty-five participants performed the RSA and COD tests in a randomized order. After a 5 min aerobic warm up, participants performed one of the three static stretching protocols of 30 s, 60 s or 90 s total duration (3 stretches x 10 s, 20 s or 30 s. Three dynamic stretching exercises of 30 s duration were then performed (90 s total. Sit-and-reach flexibility tests were conducted before the aerobic warm up, after the combined static and dynamic stretching, and post- RSA/COD test. The duration of static stretching had a positive effect on flexibility with 36.3% and 85.6% greater sit-and-reach scores with the 60 s and 90 s static stretching conditions respectively than with the 30 s condition (p < 0.001. However there were no significant differences in RSA and COD performance between the 3 stretching conditions. The lack of change in RSA and COD might be attributed to a counterbalancing of static and dynamic stretching effects. Furthermore, the short duration (< 90 s static stretching may not have provided sufficient stimulus to elicit performance impairments

Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension

Science.gov (United States)

Lewis, Amanda H; Grandl, Jörg

2015-01-01

Piezo1 ion channels mediate the conversion of mechanical forces into electrical signals and are critical for responsiveness to touch in metazoans. The apparent mechanical sensitivity of Piezo1 varies substantially across cellular environments, stimulating methods and protocols, raising the fundamental questions of what precise physical stimulus activates the channel and how its stimulus sensitivity is regulated. Here, we measured Piezo1 currents evoked by membrane stretch in three patch configurations, while simultaneously visualizing and measuring membrane geometry. Building on this approach, we developed protocols to minimize resting membrane curvature and tension prior to probing Piezo1 activity. We find that Piezo1 responds to lateral membrane tension with exquisite sensitivity as compared to other mechanically activated channels and that resting tension can drive channel inactivation, thereby tuning overall mechanical sensitivity of Piezo1. Our results explain how Piezo1 can function efficiently and with adaptable sensitivity as a sensor of mechanical stimulation in diverse cellular contexts. DOI: http://dx.doi.org/10.7554/eLife.12088.001 PMID:26646186

Polycystin-1 Is a Cardiomyocyte Mechanosensor That Governs L-Type Ca2+ Channel Protein Stability.

Science.gov (United States)

Pedrozo, Zully; Criollo, Alfredo; Battiprolu, Pavan K; Morales, Cyndi R; Contreras-Ferrat, Ariel; Fernández, Carolina; Jiang, Nan; Luo, Xiang; Caplan, Michael J; Somlo, Stefan; Rothermel, Beverly A; Gillette, Thomas G; Lavandero, Sergio; Hill, Joseph A

2015-06-16

L-type calcium channel activity is critical to afterload-induced hypertrophic growth of the heart. However, the mechanisms governing mechanical stress-induced activation of L-type calcium channel activity are obscure. Polycystin-1 (PC-1) is a G protein-coupled receptor-like protein that functions as a mechanosensor in a variety of cell types and is present in cardiomyocytes. We subjected neonatal rat ventricular myocytes to mechanical stretch by exposing them to hypo-osmotic medium or cyclic mechanical stretch, triggering cell growth in a manner dependent on L-type calcium channel activity. RNAi-dependent knockdown of PC-1 blocked this hypertrophy. Overexpression of a C-terminal fragment of PC-1 was sufficient to trigger neonatal rat ventricular myocyte hypertrophy. Exposing neonatal rat ventricular myocytes to hypo-osmotic medium resulted in an increase in α1C protein levels, a response that was prevented by PC-1 knockdown. MG132, a proteasomal inhibitor, rescued PC-1 knockdown-dependent declines in α1C protein. To test this in vivo, we engineered mice harboring conditional silencing of PC-1 selectively in cardiomyocytes (PC-1 knockout) and subjected them to mechanical stress in vivo (transverse aortic constriction). At baseline, PC-1 knockout mice manifested decreased cardiac function relative to littermate controls, and α1C L-type calcium channel protein levels were significantly lower in PC-1 knockout hearts. Whereas control mice manifested robust transverse aortic constriction-induced increases in cardiac mass, PC-1 knockout mice showed no significant growth. Likewise, transverse aortic constriction-elicited increases in hypertrophic markers and interstitial fibrosis were blunted in the knockout animals PC-1 is a cardiomyocyte mechanosensor that is required for cardiac hypertrophy through a mechanism that involves stabilization of α1C protein. © 2015 American Heart Association, Inc.

Modeling steady-state dynamics of macromolecules in exponential-stretching flow using multiscale molecular-dynamics-multiparticle-collision simulations.

Science.gov (United States)

Ghatage, Dhairyasheel; Chatterji, Apratim

2013-10-01

We introduce a method to obtain steady-state uniaxial exponential-stretching flow of a fluid (akin to extensional flow) in the incompressible limit, which enables us to study the response of suspended macromolecules to the flow by computer simulations. The flow field in this flow is defined by v(x) = εx, where v(x) is the velocity of the fluid and ε is the stretch flow gradient. To eliminate the effect of confining boundaries, we produce the flow in a channel of uniform square cross section with periodic boundary conditions in directions perpendicular to the flow, but simultaneously maintain uniform density of fluid along the length of the tube. In experiments a perfect elongational flow is obtained only along the axis of symmetry in a four-roll geometry or a filament-stretching rheometer. We can reproduce flow conditions very similar to extensional flow near the axis of symmetry by exponential-stretching flow; we do this by adding the right amounts of fluid along the length of the flow in our simulations. The fluid particles added along the length of the tube are the same fluid particles which exit the channel due to the flow; thus mass conservation is maintained in our model by default. We also suggest a scheme for possible realization of exponential-stretching flow in experiments. To establish our method as a useful tool to study various soft matter systems in extensional flow, we embed (i) spherical colloids with excluded volume interactions (modeled by the Weeks-Chandler potential) as well as (ii) a bead-spring model of star polymers in the fluid to study their responses to the exponential-stretched flow and show that the responses of macromolecules in the two flows are very similar. We demonstrate that the variation of number density of the suspended colloids along the direction of flow is in tune with our expectations. We also conclude from our study of the deformation of star polymers with different numbers of arms f that the critical flow gradient ε

Caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress.

Science.gov (United States)

Zhang, Qiang; Liu, Jianing; Chen, Shulan; Liu, Jing; Liu, Lijuan; Liu, Guirong; Wang, Fang; Jiang, Wenxin; Zhang, Caixia; Wang, Shuangyu; Yuan, Xiao

2016-04-01

It is well recognized that mandibular growth, which is caused by a variety of functional appliances, is considered to be the result of both neuromuscular and skeletal adaptations. Accumulating evidence has demonstrated that apoptosis plays an important role in the adaptation of skeletal muscle function. However, the underlying mechanism of apoptosis that is induced by stretch continues to be incompletely understood. Endoplasmic reticulum stress (ERS), a newly defined signaling pathway, initiates apoptosis. This study seeks to determine if caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress in myoblast and its underlying mechanism. Apoptosis was assessed by Hochest staining, DAPI staining and annexin V binding and PI staining. ER chaperones, such as GRP78, CHOP and caspase-12, were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Furthermore, caspase-12 inhibitor was used to value the mechanism of the caspase-12 pathway. Apoptosis of myoblast, which is subjected to cyclic stretch, was observed in a time-dependent manner. We found that GRP78 mRNA and protein were significantly increased and CHOP and caspase-12 were activated in myoblast that was exposed to cyclic stretch. Caspase-12 inhibition reduced stretch-induced apoptosis, and caspase-12 activated caspase-3 to induce apoptosis. We concluded that caspase-12 played an important role in stretch-induced apoptosis that is associated by endoplasmic reticulum stress by activating caspase-3.

Parallel Evolution of Sperm Hyper-Activation Ca2+ Channels.

Science.gov (United States)

Cooper, Jacob C; Phadnis, Nitin

2017-07-01

Sperm hyper-activation is a dramatic change in sperm behavior where mature sperm burst into a final sprint in the race to the egg. The mechanism of sperm hyper-activation in many metazoans, including humans, consists of a jolt of Ca2+ into the sperm flagellum via CatSper ion channels. Surprisingly, all nine CatSper genes have been independently lost in several animal lineages. In Drosophila, sperm hyper-activation is performed through the cooption of the polycystic kidney disease 2 (pkd2) Ca2+ channel. The parallels between CatSpers in primates and pkd2 in Drosophila provide a unique opportunity to examine the molecular evolution of the sperm hyper-activation machinery in two independent, nonhomologous calcium channels separated by > 500 million years of divergence. Here, we use a comprehensive phylogenomic approach to investigate the selective pressures on these sperm hyper-activation channels. First, we find that the entire CatSper complex evolves rapidly under recurrent positive selection in primates. Second, we find that pkd2 has parallel patterns of adaptive evolution in Drosophila. Third, we show that this adaptive evolution of pkd2 is driven by its role in sperm hyper-activation. These patterns of selection suggest that the evolution of the sperm hyper-activation machinery is driven by sexual conflict with antagonistic ligands that modulate channel activity. Together, our results add sperm hyper-activation channels to the class of fast evolving reproductive proteins and provide insights into the mechanisms used by the sexes to manipulate sperm behavior. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Role of TRP channels in the cardiovascular system.

Science.gov (United States)

Yue, Zhichao; Xie, Jia; Yu, Albert S; Stock, Jonathan; Du, Jianyang; Yue, Lixia

2015-02-01

The transient receptor potential (TRP) superfamily consists of a large number of nonselective cation channels with variable degree of Ca(2+)-permeability. The 28 mammalian TRP channel proteins can be grouped into six subfamilies: canonical, vanilloid, melastatin, ankyrin, polycystic, and mucolipin TRPs. The majority of these TRP channels are expressed in different cell types including both excitable and nonexcitable cells of the cardiovascular system. Unlike voltage-gated ion channels, TRP channels do not have a typical voltage sensor, but instead can sense a variety of other stimuli including pressure, shear stress, mechanical stretch, oxidative stress, lipid environment alterations, hypertrophic signals, and inflammation products. By integrating multiple stimuli and transducing their activity to downstream cellular signal pathways via Ca(2+) entry and/or membrane depolarization, TRP channels play an essential role in regulating fundamental cell functions such as contraction, relaxation, proliferation, differentiation, and cell death. With the use of targeted deletion and transgenic mouse models, recent studies have revealed that TRP channels are involved in numerous cellular functions and play an important role in the pathophysiology of many diseases in the cardiovascular system. Moreover, several TRP channels are involved in inherited diseases of the cardiovascular system. This review presents an overview of current knowledge concerning the physiological functions of TRP channels in the cardiovascular system and their contributions to cardiovascular diseases. Ultimately, TRP channels may become potential therapeutic targets for cardiovascular diseases. Copyright © 2015 the American Physiological Society.

Expression, purification and functional reconstitution of slack sodium-activated potassium channels.

Science.gov (United States)

Yan, Yangyang; Yang, Youshan; Bian, Shumin; Sigworth, Fred J

2012-11-01

The slack (slo2.2) gene codes for a potassium-channel α-subunit of the 6TM voltage-gated channel family. Expression of slack results in Na(+)-activated potassium channel activity in various cell types. We describe the purification and reconstitution of Slack protein and show that the Slack α-subunit alone is sufficient for potassium channel activity activated by sodium ions as assayed in planar bilayer membranes and in membrane vesicles.

Stretch strength of Al-Li alloy sheet

Energy Technology Data Exchange (ETDEWEB)

Sato, K.; Sawa, Y.; Yokoyama, T.; Fujimoto, S. [Science Univ. of Tokyo (Japan). Dept. of Mech. Eng.; Sakamoto, T. [Kobe Steel Works, Tokyo (Japan)

1998-07-01

Stretch test on Al-Li alloy sheet was carried out in stretch rate of 0.01 to 0.2 mm/sec. The limiting stretch depth was measured in various conditions and the following results were obtained. (1) Stretch rate does not affect the limiting stretch depth of Al-Li alloy. (2) The limiting stretch depth is increased with increase of the profile radius. (3) Strain hardening exponent(n-value) and r-value of Lankford do not affect the limiting stretch depth. (4) Rapture pattern in stretch test of Al is {alpha} type rapture and that of Al-Li alloy is straight line type rapture. (orig.) 4 refs.

Activation of purified calcium channels by stoichiometric protein phosphorylation

Energy Technology Data Exchange (ETDEWEB)

Nunoki, K.; Florio, V.; Catterall, W.A. (Univ. of Washington, Seattle (USA))

1989-09-01

Purified dihydropyridine-sensitive calcium channels from rabbit skeletal muscle were reconstituted into phosphatidylcholine vesicles to evaluate the effect of phosphorylation by cyclic AMP-dependent protein kinase (PK-A) on their function. Both the rate and extent of {sup 45}Ca{sup 2+} uptake into vesicles containing reconstituted calcium channels were increased severalfold after incubation with ATP and PK-A. The degree of stimulation of {sup 45}Ca{sup 2+} uptake was linearly proportional to the extent of phosphorylation of the alpha 1 and beta subunits of the calcium channel up to a stoichiometry of approximately 1 mol of phosphate incorporated into each subunit. The calcium channels activated by phosphorylation were determined to be incorporated into the reconstituted vesicles in the inside-out orientation and were completely inhibited by low concentrations of dihydropyridines, phenylalkylamines, Cd{sup 2+}, Ni{sup 2+}, and Mg{sup 2+}. The results demonstrate a direct relationship between PK-A-catalyzed phosphorylation of the alpha 1 and beta subunits of the purified calcium channel and activation of the ion conductance activity of the dihydropyridine-sensitive calcium channels.

Activation of purified calcium channels by stoichiometric protein phosphorylation

International Nuclear Information System (INIS)

Nunoki, K.; Florio, V.; Catterall, W.A.

1989-01-01

Purified dihydropyridine-sensitive calcium channels from rabbit skeletal muscle were reconstituted into phosphatidylcholine vesicles to evaluate the effect of phosphorylation by cyclic AMP-dependent protein kinase (PK-A) on their function. Both the rate and extent of 45 Ca 2+ uptake into vesicles containing reconstituted calcium channels were increased severalfold after incubation with ATP and PK-A. The degree of stimulation of 45 Ca 2+ uptake was linearly proportional to the extent of phosphorylation of the alpha 1 and beta subunits of the calcium channel up to a stoichiometry of approximately 1 mol of phosphate incorporated into each subunit. The calcium channels activated by phosphorylation were determined to be incorporated into the reconstituted vesicles in the inside-out orientation and were completely inhibited by low concentrations of dihydropyridines, phenylalkylamines, Cd 2+ , Ni 2+ , and Mg 2+ . The results demonstrate a direct relationship between PK-A-catalyzed phosphorylation of the alpha 1 and beta subunits of the purified calcium channel and activation of the ion conductance activity of the dihydropyridine-sensitive calcium channels

Atomic Stretch: Optimally bounded real-time stretching and beyond

DEFF Research Database (Denmark)

Jensen, Rasmus Ramsbøl; Nielsen, Jannik Boll

2016-01-01

Atomic Stretch is a plugin for your preferred Adobe video editing tool, allowing real-time smooth and optimally bounded retarget-ting from and to any aspect ratio. The plugin allows preserving of high interest pixels through a protected region, attention redirection through color-modification, co......Atomic Stretch is a plugin for your preferred Adobe video editing tool, allowing real-time smooth and optimally bounded retarget-ting from and to any aspect ratio. The plugin allows preserving of high interest pixels through a protected region, attention redirection through color...

Proton and non-proton activation of ASIC channels.

Directory of Open Access Journals (Sweden)

Ivan Gautschi

Full Text Available The Acid-Sensing Ion Channels (ASIC exhibit a fast desensitizing current when activated by pH values below 7.0. By contrast, non-proton ligands are able to trigger sustained ASIC currents at physiological pHs. To analyze the functional basis of the ASIC desensitizing and sustained currents, we have used ASIC1a and ASIC2a mutants with a cysteine in the pore vestibule for covalent binding of different sulfhydryl reagents. We found that ASIC1a and ASIC2a exhibit two distinct currents, a proton-induced desensitizing current and a sustained current triggered by sulfhydryl reagents. These currents differ in their pH dependency, their sensitivity to the sulfhydryl reagents, their ionic selectivity and their relative magnitude. We propose a model for ASIC1 and ASIC2 activity where the channels can function in two distinct modes, a desensitizing mode and a sustained mode depending on the activating ligands. The pore vestibule of the channel represents a functional site for binding non-proton ligands to activate ASIC1 and ASIC2 at neutral pH and to prevent channel desensitization.

Proton and non-proton activation of ASIC channels.

Science.gov (United States)

Gautschi, Ivan; van Bemmelen, Miguel Xavier; Schild, Laurent

2017-01-01

The Acid-Sensing Ion Channels (ASIC) exhibit a fast desensitizing current when activated by pH values below 7.0. By contrast, non-proton ligands are able to trigger sustained ASIC currents at physiological pHs. To analyze the functional basis of the ASIC desensitizing and sustained currents, we have used ASIC1a and ASIC2a mutants with a cysteine in the pore vestibule for covalent binding of different sulfhydryl reagents. We found that ASIC1a and ASIC2a exhibit two distinct currents, a proton-induced desensitizing current and a sustained current triggered by sulfhydryl reagents. These currents differ in their pH dependency, their sensitivity to the sulfhydryl reagents, their ionic selectivity and their relative magnitude. We propose a model for ASIC1 and ASIC2 activity where the channels can function in two distinct modes, a desensitizing mode and a sustained mode depending on the activating ligands. The pore vestibule of the channel represents a functional site for binding non-proton ligands to activate ASIC1 and ASIC2 at neutral pH and to prevent channel desensitization.

Hierarchically mesoporous silica materials prepared from the uniaxially stretched polypropylene membrane and surfactant templates

International Nuclear Information System (INIS)

Wang Xiaocong; Ma Jin; Liu Jin; Zhou Chen; Zhao, Yan; Yi Shouzhi; Yang Zhenzhong

2006-01-01

Hierarchically mesoporous silica materials with a bimodal distribution were template-prepared from uniaxially stretched polypropylene membrane in the presence of a surfactant via a sol-gel process. Their regularity and morphologies were characterized by transmission electron microscopy (TEM), x-ray diffraction and Brunauer-Emmett-Teller (BET) surface area analysis. The larger channel pores formed by removing the microfibrils of uniaxially stretched polypropylene membrane have a broad pore size distribution, and their size is around 13 nm. In contrast, the smaller mesopores formed by surfactant templates have a narrow distribution; their size is about 3.9 nm. The size of the smaller pores could be tuned from 2 to 6 nm by selecting different surfactants and by changing the concentration of reactants

BAD and KATP channels regulate neuron excitability and epileptiform activity.

Science.gov (United States)

Martínez-François, Juan Ramón; Fernández-Agüera, María Carmen; Nathwani, Nidhi; Lahmann, Carolina; Burnham, Veronica L; Danial, Nika N; Yellen, Gary

2018-01-25

Brain metabolism can profoundly influence neuronal excitability. Mice with genetic deletion or alteration of Bad ( B CL-2 a gonist of cell d eath) exhibit altered brain-cell fuel metabolism, accompanied by resistance to acutely induced epileptic seizures; this seizure protection is mediated by ATP-sensitive potassium (K ATP ) channels. Here we investigated the effect of BAD manipulation on K ATP channel activity and excitability in acute brain slices. We found that BAD's influence on neuronal K ATP channels was cell-autonomous and directly affected dentate granule neuron (DGN) excitability. To investigate the role of neuronal K ATP channels in the anticonvulsant effects of BAD, we imaged calcium during picrotoxin-induced epileptiform activity in entorhinal-hippocampal slices. BAD knockout reduced epileptiform activity, and this effect was lost upon knockout or pharmacological inhibition of K ATP channels. Targeted BAD knockout in DGNs alone was sufficient for the antiseizure effect in slices, consistent with a 'dentate gate' function that is reinforced by increased K ATP channel activity. © 2018, Martínez-François et al.

Regulation of KV channel voltage-dependent activation by transmembrane β subunits

Directory of Open Access Journals (Sweden)

Xiaohui eSun

2012-04-01

Full Text Available Voltage-activated K+ (KV channels are important for shaping action potentials and maintaining resting membrane potential in excitable cells. KV channels contain a central pore-gate domain (PGD surrounded by four voltage-sensing domains (VSD. The VSDs will change conformation in response to alterations of the membrane potential thereby inducing the opening of the PGD. Many KV channels are heteromeric protein complexes containing auxiliary β subunits. These β subunits modulate channel expression and activity to increase functional diversity and render tissue specific phenotypes. This review focuses on the KV β subunits that contain transmembrane (TM segments including the KCNE family and the β subunits of large conductance, Ca2+- and voltage-activated K+ (BK channels. These TM β subunits affect the voltage-dependent activation of KV α subunits. Experimental and computational studies have described the structural location of these β subunits in the channel complexes and the biophysical effects on VSD activation, PGD opening and VSD-PGD coupling. These results reveal some common characteristics and mechanistic insights into KV channel modulation by TM β subunits.

How to determine local stretching and tension in a flow-stretched DNA molecule

DEFF Research Database (Denmark)

Pedersen, Jonas Nyvold; Marie, Rodolphe; Kristensen, Anders

2016-01-01

We determine the nonuniform stretching of and tension in amega base pairs-long fragment of deoxyribonucleic acid (DNA) that is flow stretched in a nanofluidic chip. We use no markers, do not know the contour length of the DNA, and do not have the full DNA molecule inside our field of view. Instead......, we analyze the transverse thermal motion of the DNA. Tension at the center of the DNA adds up to 16 pN, giving almost fully stretched DNA. This method was devised for optical mapping of DNA, specifically, DNA denaturation patterns. It may be useful also for other studies, e.g., DNA......-protein interactions, specifically, their tension dependence. Generally, wherever long strands of DNA—e.g., native DNA extracted from human cells or bacteria—must be stretched with ease for inspection, this method applies....

EFFECT OF DIFFERENT STRETCHING PROTOCOLS ON VERTICAL JUMP PERFORMANCE

Directory of Open Access Journals (Sweden)

Emre Serin

2018-04-01

Full Text Available This study aimed to examine the effect of different stretching exercises on vertical jump performance. A total of 14 national male athletes sporting in the elite level took part in the study. The age average of the participants was 20.25±1.03 year, the average height was 1.80±.08 m, the average body weight was 77.14±18.91 kg, average of sporting age was 9.87±3.31 year and the average number of participation in international games was 10.0±3.31. As stretching protocol: Method 1 (5 minutes of jogging and 2 minutes of active rest followed by Method 2 (static stretching for 4 different muscle groups 3 repetitions for 15 seconds of static stretching, rest for 10 seconds between groups and then consecutively, Method 3 (Dynamic stretching exercises with 3 repetitions for 15 seconds and 10 seconds rest between different muscle groups were applied in the study. The vertical jump performance before and after different stretching exercises of the participants was determined by means of the vertical jump test using the smart speed lite system. Before and after the training of all athletes, HR was recorded with a heart rate monitor (RS 800, Polar Vantage NV, Polar Electro Oy, Finland with 5 seconds intervals. Before the study, the chest band of the heartbeat monitor was placed on the chest of the athlete and the HR was recorded from the monitor. SPSS 15.0 statistical package program was used for evaluation and calculation of the data. In this study in addition to descriptive statistics (mean and standard deviation paired samples t-test was used to determine the difference between the vertical jump performance of the participants before and after different stretching exercises. As a result, this study showed that; applying the dynamic and static stretching exercises consecutively affected the vertical jump performance 4.5 cm positively (p<.05. It is suggested that different dynamic and static stretching exercises should be included in the vertical jump.

Analysis of a filament stretching rheometer

DEFF Research Database (Denmark)

Kolte, Mette Irene; Rasmussen, Henrik K.; Hassager, Ole

1996-01-01

A finite element analysis of the stretching filament rheometer of Tirtaadmadja and Sridhar (1993) is presenetd. Simulations of the stretching of a filament of the polymet test solution, fluid A, between two plates are shown.......A finite element analysis of the stretching filament rheometer of Tirtaadmadja and Sridhar (1993) is presenetd. Simulations of the stretching of a filament of the polymet test solution, fluid A, between two plates are shown....

Activation of ERG2 potassium channels by the diphenylurea NS1643

DEFF Research Database (Denmark)

Elmedyb, Pernille; Olesen, Søren-Peter; Grunnet, Morten

2007-01-01

Three members of the ERG potassium channel family have been described (ERG1-3 or Kv 11.1-3). ERG1 is by far the best characterized subtype and it constitutes the molecular component of the cardiac I(Kr) current. All three channel subtypes are expressed in neurons but their function remains unclear....... The lack of functional information is at least partly due to the lack of specific pharmacological tools. The compound NS1643 has earlier been reported as an ERG1 channel activator. We found that NS1643 also activates the ERG2 channel; however, the molecular mechanism of the activation differs between...... the ERG1 and ERG2 channels. This is surprising since ERG1 and ERG2 channels have very similar biophysical and structural characteristics. For ERG2, NS1643 causes a left-ward shift of the activation curve, a faster time-constant of activation and a slower time-constant of inactivation as well...

Mechanically Gated Ion Channels in Mammalian Hair Cells

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Xufeng Qiu

2018-04-01

Full Text Available Hair cells in the inner ear convert mechanical stimuli provided by sound waves and head movements into electrical signal. Several mechanically evoked ionic currents with different properties have been recorded in hair cells. The search for the proteins that form the underlying ion channels is still in progress. The mechanoelectrical transduction (MET channel near the tips of stereociliary in hair cells, which is responsible for sensory transduction, has been studied most extensively. Several components of the sensory mechanotransduction machinery in stereocilia have been identified, including the multi-transmembrane proteins tetraspan membrane protein in hair cell stereocilia (TMHS/LHFPL5, transmembrane inner ear (TMIE and transmembrane channel-like proteins 1 and 2 (TMC1/2. However, there remains considerable uncertainty regarding the molecules that form the channel pore. In addition to the sensory MET channel, hair cells express the mechanically gated ion channel PIEZO2, which is localized near the base of stereocilia and not essential for sensory transduction. The function of PIEZO2 in hair cells is not entirely clear but it might have a role in damage sensing and repair processes. Additional stretch-activated channels of unknown molecular identity and function have been found to localize at the basolateral membrane of hair cells. Here, we review current knowledge regarding the different mechanically gated ion channels in hair cells and discuss open questions concerning their molecular composition and function.

Upper Limb Static-Stretching Protocol Decreases Maximal Concentric Jump Performance

Directory of Open Access Journals (Sweden)

Paulo H. Marchetti

2014-12-01

Full Text Available The purpose of the present study was to evaluate the acute effects of an upper limb static-stretching (SS protocol on the maximal concentric jump performance. We recruited 25 young healthy, male, resistance trained individuals (stretched group, n = 15 and control group, n = 10 in this study. The randomized between group experimental protocol consisted of a three trials of maximal concentric jump task, before and after a SS of the upper limb. Vertical ground reaction forces (vGRF and surface electromyography (sEMG of both gastrocnemius lateralis (GL and vastus lateralis (VL were acquired. An extensive SS was employed consisting of ten stretches of 30 seconds, with 15 seconds of rest, and 70-90% of the point of discomfort (POD. ANOVA (2x2 (group x condition was used for shoulder joint range of motion (ROM, vGRF and sEMG. A significant interaction for passive ROM of the shoulder joint revealed significant increases between pre- and post-SS protocol (p < 0.001. A significant interaction demonstrated decreased peak force and an increased peak propulsion duration between pre- and post-stretching only for stretch group (p = 0.021, and p = 0.024, respectively. There was a significant main effect between groups (stretch and control for peak force for control group (p = 0.045. Regarding sEMG variables, there were no significant differences between groups (control versus stretched or condition (pre-stretching versus post-stretching for the peak amplitude of RMS and IEMG for both muscles (VL and GL. In conclusion, an acute extensive SS can increase the shoulder ROM, and negatively affect both the propulsion duration and peak force of the maximal concentric jump, without providing significant changes in muscle activation.

Cyclic mechanical stretch enhances BMP9-induced osteogenic differentiation of mesenchymal stem cells.

Science.gov (United States)

Song, Yang; Tang, Yinhong; Song, Jinlin; Lei, Mingxing; Liang, Panpan; Fu, Tiwei; Su, Xudong; Zhou, Pengfei; Yang, Li; Huang, Enyi

2018-04-01

The purpose of this study was to investigate whether mechanical stretch can enhance the bone morphogenetic protein 9 (BMP9)-induced osteogenic differentiation in MSCs. Recombinant adenoviruses were used to overexpress the BMP9 in C3H10T1/2 MSCs. Cells were seeded onto six-well BioFlex collagen I-coated plates and subjected to cyclic mechanical stretch [6% elongation at 60 cycles/minute (1 Hz)] in a Flexercell FX-4000 strain unit for up to 12 hours. Immunostaining and confocal microscope were used to detect cytoskeleton organization. Cell cycle progression was checked by flow cytometry. Alkaline phosphatase activity was measured with a Chemiluminescence Assay Kit and was quantified with a histochemical staining assay. Matrix mineralization was examined by Alizarin Red S Staining. Mechanical stretch induces cytoskeleton reorganization and inhibits cell proliferation by preventing cells entry into S phase of the cell cycle. Although mechanical stretch alone does not induce the osteogenic differentiation of C3H10T1/2 MSCs, co-stimulation with mechanical stretch and BMP9 enhances alkaline phosphatase activity. The expression of key lineage-specific regulators (e.g., osteocalcin (OCN), SRY-related HMG-box 9, and runt-related transcription factor 2) is also increased after the co-stimulation, compared to the mechanical stretch stimulation along. Furthermore, mechanical stretch augments the BMP9-mediated bone matrix mineralization of C3H10T1/2 MSCs. Our results suggest that mechanical stretch enhances BMP9-induced osteoblastic lineage specification in C3H10T1/2 MSCs.

Flexibility and stretching physiology : responses and adaptations to different stretching intensities.

OpenAIRE

Freitas, Sandro Remo Martins Neves Ramos

2014-01-01

Doutoramento em Motricidade Humana, especialidade de Biomecânica Research and reported literature regarding the conceptual, methodological, and training effects of stretching with different intensities are scarce. The purposes of this thesis were to: i) explore and develop methodological conditions to achieve the second purpose (studies: 1 to 3); ii) characterize the acute and chronic effects induced by different stretching intensities on skeletal muscle and joint mechanical properti...

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

A structural view of ligand-dependent activation in thermoTRP channels

Directory of Open Access Journals (Sweden)

Ximena eSteinberg

2014-05-01

Full Text Available Transient Receptor Potential (TRP proteins are a large family of ion channels, grouped intoseven sub-families. Although great advances have been made regarding the activation andmodulation of TRP channel activity, detailed molecular mechanisms governing TRPchannel gating are still needed. Sensitive to electric, chemical, mechanical, and thermalcues, TRP channels are tightly associated with the detection and integration of sensoryinput, emerging as a model to study the polymodal activation of ion channel proteins.Among TRP channels, the temperature-activated kind constitute a subgroup by itself,formed by Vanilloid receptors 1-4, Melastatin receptors 2, 4, 5 and 8, TRPC5, and TRPA1.Some of the so-called thermoTRP channels participate in the detection of noxious stimulimaking them an interesting pharmacological target for the treatment of pain. However, thepoor specificity of the compounds available in the market represents an important obstacleto overcome. Understanding the molecular mechanics underlying ligand-dependentmodulation of TRP channels may help with the rational design of novel syntheticanalgesics. The present review focuses on the structural basis of ligand-dependentactivation of TRPV1 and TRPM8 channels. Special attention is drawn to the dissection ofligand-binding sites within TRPV1, PIP 2 -dependent modulation of TRP channels, and thestructure of natural and synthetic ligands.

Adding dimension to cellular mechanotransduction: Advances in biomedical engineering of multiaxial cell-stretch systems and their application to cardiovascular biomechanics and mechano-signaling.

Science.gov (United States)

Friedrich, O; Schneidereit, D; Nikolaev, Y A; Nikolova-Krstevski, V; Schürmann, S; Wirth-Hücking, A; Merten, A L; Fatkin, D; Martinac, B

2017-11-01

Hollow organs (e.g. heart) experience pressure-induced mechanical wall stress sensed by molecular mechano-biosensors, including mechanosensitive ion channels, to translate into intracellular signaling. For direct mechanistic studies, stretch devices to apply defined extensions to cells adhered to elastomeric membranes have stimulated mechanotransduction research. However, most engineered systems only exploit unilateral cellular stretch. In addition, it is often taken for granted that stretch applied by hardware translates 1:1 to the cell membrane. However, the latter crucially depends on the tightness of the cell-substrate junction by focal adhesion complexes and is often not calibrated for. In the heart, (increased) hemodynamic volume/pressure load is associated with (increased) multiaxial wall tension, stretching individual cardiomyocytes in multiple directions. To adequately study cellular models of chronic organ distension on a cellular level, biomedical engineering faces challenges to implement multiaxial cell stretch systems that allow observing cell reactions to stretch during live-cell imaging, and to calibrate for hardware-to-cell membrane stretch translation. Here, we review mechanotransduction, cell stretch technologies from uni-to multiaxial designs in cardio-vascular research, and the importance of the stretch substrate-cell membrane junction. We also present new results using our IsoStretcher to demonstrate mechanosensitivity of Piezo1 in HEK293 cells and stretch-induced Ca 2+ entry in 3D-hydrogel-embedded cardiomyocytes. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effect of warm-up, static stretching and dynamic stretching on hamstring flexibility in previously injured subjects.

LENUS (Irish Health Repository)

O'Sullivan, Kieran

2009-01-01

BACKGROUND: Warm-up and stretching are suggested to increase hamstring flexibility and reduce the risk of injury. This study examined the short-term effects of warm-up, static stretching and dynamic stretching on hamstring flexibility in individuals with previous hamstring injury and uninjured controls. METHODS: A randomised crossover study design, over 2 separate days. Hamstring flexibility was assessed using passive knee extension range of motion (PKE ROM). 18 previously injured individuals and 18 uninjured controls participated. On both days, four measurements of PKE ROM were recorded: (1) at baseline; (2) after warm-up; (3) after stretch (static or dynamic) and (4) after a 15-minute rest. Participants carried out both static and dynamic stretches, but on different days. Data were analysed using Anova. RESULTS: Across both groups, there was a significant main effect for time (p < 0.001). PKE ROM significantly increased with warm-up (p < 0.001). From warm-up, PKE ROM further increased with static stretching (p = 0.04) but significantly decreased after dynamic stretching (p = 0.013). The increased flexibility after warm-up and static stretching reduced significantly (p < 0.001) after 15 minutes of rest, but remained significantly greater than at baseline (p < 0.001). Between groups, there was no main effect for group (p = 0.462), with no difference in mean PKE ROM values at any individual stage of the protocol (p > 0.05). Using ANCOVA to adjust for the non-significant (p = 0.141) baseline difference between groups, the previously injured group demonstrated a greater response to warm-up and static stretching, however this was not statistically significant (p = 0.05). CONCLUSION: Warm-up significantly increased hamstring flexibility. Static stretching also increased hamstring flexibility, whereas dynamic did not, in agreement with previous findings on uninjured controls. The effect of warm-up and static stretching on flexibility was greater in those with reduced

Transient photoresponse in amorphous In-Ga-Zn-O thin films under stretched exponential analysis

Science.gov (United States)

Luo, Jiajun; Adler, Alexander U.; Mason, Thomas O.; Bruce Buchholz, D.; Chang, R. P. H.; Grayson, M.

2013-04-01

We investigated transient photoresponse and Hall effect in amorphous In-Ga-Zn-O thin films and observed a stretched exponential response which allows characterization of the activation energy spectrum with only three fit parameters. Measurements of as-grown films and 350 K annealed films were conducted at room temperature by recording conductivity, carrier density, and mobility over day-long time scales, both under illumination and in the dark. Hall measurements verify approximately constant mobility, even as the photoinduced carrier density changes by orders of magnitude. The transient photoconductivity data fit well to a stretched exponential during both illumination and dark relaxation, but with slower response in the dark. The inverse Laplace transforms of these stretched exponentials yield the density of activation energies responsible for transient photoconductivity. An empirical equation is introduced, which determines the linewidth of the activation energy band from the stretched exponential parameter β. Dry annealing at 350 K is observed to slow the transient photoresponse.

Two-photon activation of endogenous store-operated calcium channels without optogenetics

Science.gov (United States)

Cheng, Pan; Tang, Wanyi; He, Hao

2018-02-01

Store-operated calcium (SOC) channels, regulated by intracellular Ca2+ store, are the essential pathway of calcium signaling and participate in a wide variety of cellular activities such as gene expression, secretion and immune response1. However, our understanding and regulation of SOC channels are mainly based on pharmacological methods. Considering the unique advantages of optical control, optogenetic control of SOC channels has been developed2. However, the process of genetic engineering to express exogenous light-sensitive protein is complicated, which arouses concerns about ethic difficulties in some research of animal and applications in human. In this report, we demonstrate rapid, robust and reproducible two-photon activation of endogenous SOC channels by femtosecond laser without optogenetics. We present that the short-duration two-photon scanning on subcellular microregion induces slow Ca2+ influx from extracellular medium, which can be eliminated by removing extracellular Ca2+. Block of SOC channels using various pharmacological inhibitors or knockdown of SOC channels by RNA interference reduce the probability of two-photon activated Ca2+ influx. On the contrary, overexpression of SOC channels can increase the probability of Ca2+ influx by two-photon scanning. These results collectively indicate Ca2+ influx through two-photon activated SOC channels. Different from classical pathway of SOC entry activated by Ca2+ store depletion, STIM1, the sensor protein of Ca2+ level in endoplasmic reticulum, does not show any aggregation or migration in this two-photon activated Ca2+ influx, which rules out the possibility of intracellular Ca2+ store depletion. Thereby, we propose this all-optical method of two-photon activation of SOC channels is of great potential to be widely applied in the research of cell calcium signaling and related biological research.

Coassembly of big conductance Ca2+-activated K+ channels and L-type voltage-gated Ca2+ channels in rat brain

DEFF Research Database (Denmark)

Grunnet, Morten; Kaufmann, Walter A

2004-01-01

Based on electrophysiological studies, Ca(2+)-activated K(+) channels and voltage-gated Ca(2+) channels appear to be located in close proximity in neurons. Such colocalization would ensure selective and rapid activation of K(+) channels by local increases in the cytosolic calcium concentration...

Coupling Langevin Dynamics With Continuum Mechanics: Exposing the Role of Sarcomere Stretch Activation Mechanisms to Cardiac Function

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Takumi Washio

2018-04-01

Full Text Available High-performance computing approaches that combine molecular-scale and macroscale continuum mechanics have long been anticipated in various fields. Such approaches may enrich our understanding of the links between microscale molecular mechanisms and macroscopic properties in the continuum. However, there have been few successful examples to date owing to various difficulties associated with overcoming the large spatial (from 1 nm to 10 cm and temporal (from 1 ns to 1 ms gaps between the two scales. In this paper, we propose an efficient parallel scheme to couple a microscopic model using Langevin dynamics for a protein motor with a finite element continuum model of a beating heart. The proposed scheme allows us to use a macroscale time step that is an order of magnitude longer than the microscale time step of the Langevin model, without loss of stability or accuracy. This reduces the overhead required by the imbalanced loads of the microscale computations and the communication required when switching between scales. An example of the Langevin dynamics model that demonstrates the usefulness of the coupling approach is the molecular mechanism of the actomyosin system, in which the stretch-activation phenomenon can be successfully reproduced. This microscopic Langevin model is coupled with a macroscopic finite element ventricle model. In the numerical simulations, the Langevin dynamics model reveals that a single sarcomere can undergo spontaneous oscillation (15 Hz accompanied by quick lengthening due to cooperative movements of the myosin molecules pulling on the common Z-line. Also, the coupled simulations using the ventricle model show that the stretch-activation mechanism contributes to the synchronization of the quick lengthening of the sarcomeres at the end of the systolic phase. By comparing the simulation results given by the molecular model with and without the stretch-activation mechanism, we see that this synchronization contributes to

Piezo proteins are pore-forming subunits of mechanically activated channels.

Science.gov (United States)

Coste, Bertrand; Xiao, Bailong; Santos, Jose S; Syeda, Ruhma; Grandl, Jörg; Spencer, Kathryn S; Kim, Sung Eun; Schmidt, Manuela; Mathur, Jayanti; Dubin, Adrienne E; Montal, Mauricio; Patapoutian, Ardem

2012-02-19

Mechanotransduction has an important role in physiology. Biological processes including sensing touch and sound waves require as-yet-unidentified cation channels that detect pressure. Mouse Piezo1 (MmPiezo1) and MmPiezo2 (also called Fam38a and Fam38b, respectively) induce mechanically activated cationic currents in cells; however, it is unknown whether Piezo proteins are pore-forming ion channels or modulate ion channels. Here we show that Drosophila melanogaster Piezo (DmPiezo, also called CG8486) also induces mechanically activated currents in cells, but through channels with remarkably distinct pore properties including sensitivity to the pore blocker ruthenium red and single channel conductances. MmPiezo1 assembles as a ∼1.2-million-dalton homo-oligomer, with no evidence of other proteins in this complex. Purified MmPiezo1 reconstituted into asymmetric lipid bilayers and liposomes forms ruthenium-red-sensitive ion channels. These data demonstrate that Piezo proteins are an evolutionarily conserved ion channel family involved in mechanotransduction.

All-passive pixel super-resolution of time-stretch imaging

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Chan, Antony C. S.; Ng, Ho-Cheung; Bogaraju, Sharat C. V.; So, Hayden K. H.; Lam, Edmund Y.; Tsia, Kevin K.

2017-03-01

Based on image encoding in a serial-temporal format, optical time-stretch imaging entails a stringent requirement of state-of-the-art fast data acquisition unit in order to preserve high image resolution at an ultrahigh frame rate — hampering the widespread utilities of such technology. Here, we propose a pixel super-resolution (pixel-SR) technique tailored for time-stretch imaging that preserves pixel resolution at a relaxed sampling rate. It harnesses the subpixel shifts between image frames inherently introduced by asynchronous digital sampling of the continuous time-stretch imaging process. Precise pixel registration is thus accomplished without any active opto-mechanical subpixel-shift control or other additional hardware. Here, we present the experimental pixel-SR image reconstruction pipeline that restores high-resolution time-stretch images of microparticles and biological cells (phytoplankton) at a relaxed sampling rate (≈2-5 GSa/s)—more than four times lower than the originally required readout rate (20 GSa/s) — is thus effective for high-throughput label-free, morphology-based cellular classification down to single-cell precision. Upon integration with the high-throughput image processing technology, this pixel-SR time-stretch imaging technique represents a cost-effective and practical solution for large scale cell-based phenotypic screening in biomedical diagnosis and machine vision for quality control in manufacturing.

ACUTE EFFECTS OF STATIC STRETCHING, DYNAMIC EXERCISES, AND HIGH VOLUME UPPER EXTREMITY PLYOMETRIC ACTIVITY ON TENNIS SERVE PERFORMANCE

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Ertugrul Gelen

2012-12-01

Full Text Available The purpose of this study was to compare the acute effects of static stretching; dynamic exercises and high volume upper extremity plyometric activity on tennis serve performance. Twenty-six elite young tennis players (15.1 ± 4.2 years, 167.9 ± 5.8 cm and 61.6 ± 8.1 kg performed 4 different warm-up (WU routines in a random order on non-consecutive days. The WU methods consisted of traditional WU (jogging, rally and serve practice (TRAD; traditional WU and static stretching (TRSS; traditional WU and dynamic exercise (TRDE; and traditional WU and high volume upper extremity plyometric activity (TRPLYP. Following each WU session, subjects were tested on a tennis serve ball speed test. TRAD, TRSS, TRDE and TRPLYO were compared by repeated measurement analyses of variance and post-hoc comparisons. In this study a 1 to 3 percent increase in tennis serve ball speed was recorded in TRDE and TRPLYO when compared to TRAD (p 0.05. ICCs for ball speed showed strong reliability (0.82 to 0.93 for the ball speed measurements.The results of this study indicate that dynamic and high volume upper extremity plyometric WU activities are likely beneficial to serve speed of elite junior tennis players.

Membrane mechanisms and intracellular signalling in cell volume regulation

DEFF Research Database (Denmark)

Hoffmann, Else Kay; Dunham, Philip B.

1995-01-01

Volume regulation, Signal transduction, Calcium-calmodulin, Stretch-activated channels, Eicosanoids, Macromolecular crowding, Cytoskeleton, Protein phosphorylation, dephosphorylation.......Volume regulation, Signal transduction, Calcium-calmodulin, Stretch-activated channels, Eicosanoids, Macromolecular crowding, Cytoskeleton, Protein phosphorylation, dephosphorylation....

Activation of TRPM7 channels by small molecules under physiological conditions.

Science.gov (United States)

Hofmann, T; Schäfer, S; Linseisen, M; Sytik, L; Gudermann, T; Chubanov, V

2014-12-01

Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a cation channel covalently linked to a protein kinase domain. TRPM7 is ubiquitously expressed and regulates key cellular processes such as Mg(2+) homeostasis, motility, and proliferation. TRPM7 is involved in anoxic neuronal death, cardiac fibrosis, and tumor growth. The goal of this work was to identify small molecule activators of the TRPM7 channel and investigate their mechanism of action. We used an aequorin bioluminescence-based assay to screen for activators of the TRPM7 channel. Valid candidates were further characterized using patch clamp electrophysiology. We identified 20 drug-like compounds with various structural backbones that can activate the TRPM7 channel. Among them, the δ opioid antagonist naltriben was studied in greater detail. Naltriben's action was selective among the TRP channels tested. Naltriben activates TRPM7 currents without prior depletion of intracellular Mg(2+) even under conditions of low PIP2. Moreover, naltriben interfered with the effect of the TRPM7 inhibitor NS8593. Finally, our experiments with TRPM7 variants carrying mutations in the pore, TRP, and kinase domains indicate that the site of TRPM7 activation by this small-molecule ligand is most likely located in or near the TRP domain. In conclusion, we identified the first organic small-molecule activators of TRPM7 channels, thus providing new experimental tools to study TRPM7 function in native cellular environments.

Endovascular rescue method for undesirably stretched coil.

Science.gov (United States)

Cho, Jae Hoon

2014-10-01

Undesirable detachment or stretching of coils within the parent artery during aneurysm embolization can be related with thrombus formation, which can be caused occlusion of parent artery or embolic event(s). To escape from this situation, several rescue methods have been reported. A case with undesirably stretched coil in which another rescue method was used, is presented. When the stretched coil is still located in the coil delivery microcatheter, the stretched coil can be removed safely using a snare and a handmade monorail microcatheter. After a snare is lodged in the handmade monorail microcatheter, the snare is introduced over the coil delivery micorcatheter and located in the distal part of the stretched coil. After then, the handmade monorail microcatheter captures the stretched coil and the snare as one unit. This technique using a handmade monorail microcatheter and a snare can be a good rescue modality for the undesirably stretched coil, still remained within the coil delivery microcatheter.

The acute effect of static and dynamic stretching during warm-ups on anaerobic performance in trained women

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rouhollah haghshenas

2014-09-01

Full Text Available The purpose of this study was to investigate effects of static stretching, dynamic stretching and no stretching methods on power and speed in volleyball players. Therefore, Twenty-four volleyball players (height: 173.29 ± 7.81 m; mass: 62.12 ± 8.73 kg; age: 22.66 ± 4.02 years; experience: 3.27 ± 6.37 were tested for speed performance using the 20 meter sprint test and also for power using vertical jump test after static stretching, dynamic stretching and no stretching. The results analyzed using ANOVA showed that There was a significant increase in height jump after dynamic stretching against static stretching. But, there were no significant differences between no stretching and static stretching groups. In addition, there was a significant decrease in time 20 meter sprint after dynamic stretching against static stretching and no stretching groups. The results of this study suggest that it may be desirable for volleyball players to perform dynamic exercises before the performance of activities that require a high power output.

STRETCHING EXERCISES - EFFECT ON PASSIVE EXTENSIBILITY AND STIFFNESS IN SHORT HAMSTRINGS OF HEALTHY-SUBJECTS

NARCIS (Netherlands)

HALBERTSMA, JPK; GOEKEN, LNH

Passive muscle stretch tests are common practice in physical therapy and rehabilitation medicine. However, the effects of stretching exercises are not well known. With an instrumental straight-leg-raising set-up the extensibility, stiffness, and electromyographic activity of the hamstring muscles

Cell swelling activates cloned Ca(2+)-activated K(+) channels: a role for the F-actin cytoskeleton

DEFF Research Database (Denmark)

Jorgensen, Nanna K; Pedersen, Stine F; Rasmussen, Hanne B

2003-01-01

Cloned Ca(2+)-activated K(+) channels of intermediate (hIK) or small (rSK3) conductance were expressed in HEK 293 cells, and channel activity was monitored using whole-cell patch clamp. hIK and rSK3 currents already activated by intracellular calcium were further increased by 95% and 125......%, respectively, upon exposure of the cells to a 33% decrease in extracellular osmolarity. hIK and rSK3 currents were inhibited by 46% and 32%, respectively, by a 50% increase in extracellular osmolarity. Cell swelling and channel activation were not associated with detectable increases in [Ca(2+)](i), evidenced...... by population and single-cell measurements. In addition, inhibitors of IK and SK channels significantly reduced the rate of regulatory volume decrease (RVD) in cells expressing these channels. Cell swelling induced a decrease, and cell shrinkage an increase, in net cellular F-actin content. The swelling...

Dysfunctional Hyperpolarization-Activated Cyclic Nucleotide-gated Ion Channels in Cardiac Diseases

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Xiaoqi Zhao

Full Text Available Abstract Hyperpolarization-activated cyclic nucleotide-gated (HCN channels are reverse voltage-dependent, and their activation depends on the hyperpolarization of the membrane and may be directly or indirectly regulated by the cyclic adenosine monophosphate (cAMP or other signal-transduction cascades. The distribution, quantity and activation states of HCN channels differ in tissues throughout the body. Evidence exhibits that HCN channels play critical roles in the generation and conduction of the electrical impulse and the physiopathological process of some cardiac diseases. They may constitute promising drug targets in the treatment of these cardiac diseases. Pharmacological treatment targeting HCN channels is of benefit to these cardiac conditions.

The effect of warm-up, static stretching and dynamic stretching on hamstring flexibility in previously injured subjects

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Murray Elaine

2009-04-01

Full Text Available Abstract Background Warm-up and stretching are suggested to increase hamstring flexibility and reduce the risk of injury. This study examined the short-term effects of warm-up, static stretching and dynamic stretching on hamstring flexibility in individuals with previous hamstring injury and uninjured controls. Methods A randomised crossover study design, over 2 separate days. Hamstring flexibility was assessed using passive knee extension range of motion (PKE ROM. 18 previously injured individuals and 18 uninjured controls participated. On both days, four measurements of PKE ROM were recorded: (1 at baseline; (2 after warm-up; (3 after stretch (static or dynamic and (4 after a 15-minute rest. Participants carried out both static and dynamic stretches, but on different days. Data were analysed using Anova. Results Across both groups, there was a significant main effect for time (p 0.05. Using ANCOVA to adjust for the non-significant (p = 0.141 baseline difference between groups, the previously injured group demonstrated a greater response to warm-up and static stretching, however this was not statistically significant (p = 0.05. Conclusion Warm-up significantly increased hamstring flexibility. Static stretching also increased hamstring flexibility, whereas dynamic did not, in agreement with previous findings on uninjured controls. The effect of warm-up and static stretching on flexibility was greater in those with reduced flexibility post-injury, but this did not reach statistical significance. Further prospective research is required to validate the hypothesis that increased flexibility improves outcomes. Trial Registration ACTRN12608000638336

Regulation of cloned, Ca2+-activated K+ channels by cell volume changes

DEFF Research Database (Denmark)

Grunnet, Morten; MacAulay, Nanna; Jorgensen, Nanna K

2002-01-01

Ca2+-activated K+ channels of big (hBK), intermediate (hIK) or small (rSK3) conductance were co-expressed with aquaporin 1 (AQP1) in Xenopus laevis oocytes. hBK channels were activated by depolarization, whereas hIK and rSK3 channels were activated by direct injection of Ca2+ or Cd2+ into the ooc...

KCNQ4 channel activation by BMS-204352 and retigabine

DEFF Research Database (Denmark)

Schrøder, Rikke Louise K.; Jespersen, Thomas; Christophersen, P

2001-01-01

Activation of potassium channels generally reduces cellular excitability, making potassium channel openers potential drug candidates for the treatment of diseases related to hyperexcitabilty such as epilepsy, neuropathic pain, and neurodegeneration. Two compounds, BMS-204352 and retigabine, prese...

Mechanical stretch modulates microRNA 21 expression, participating in proliferation and apoptosis in cultured human aortic smooth muscle cells.

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Jian tao Song

Full Text Available OBJECTIVES: Stretch affects vascular smooth muscle cell proliferation and apoptosis, and several responsible genes have been proposed. We tested whether the expression of microRNA 21 (miR-21 is modulated by stretch and is involved in stretch-induced proliferation and apoptosis of human aortic smooth muscle cells (HASMCs. METHODS AND RESULTS: RT-PCR revealed that elevated stretch (16% elongation, 1 Hz increased miR-21 expression in cultured HASMCs, and moderate stretch (10% elongation, 1 Hz decreased the expression. BrdU incorporation assay and cell counting showed miR-21 involved in the proliferation of HASMCs mediated by stretch, likely by regulating the expression of p27 and phosphorylated retinoblastoma protein (p-Rb. FACS analysis revealed that the complex of miR-21 and programmed cell death protein 4 (PDCD4 participated in regulating apoptosis with stretch. Stretch increased the expression of primary miR-21 and pre-miR-21 in HASMCs. Electrophoretic mobility shift assay (EMSA demonstrated that stretch increased NF-κB and AP-1 activities in HASMCs, and blockade of AP-1 activity by c-jun siRNA significantly suppressed stretch-induced miR-21 expression. CONCLUSIONS: Cyclic stretch modulates miR-21 expression in cultured HASMCs, and miR-21 plays important roles in regulating proliferation and apoptosis mediated by stretch. Stretch upregulates miR-21 expression at least in part at the transcription level and AP-1 is essential for stretch-induced miR-21 expression.

Dynamic Contractility and Efficiency Impairments in Stretch-Shortening Cycle Are Stretch-Load-Dependent After Training-Induced Muscle Damage

NARCIS (Netherlands)

Vaczi, Mark; Racz, Levente; Hortobagyi, Tibor; Tihanyi, Jozsef

Vaczi, M, Racz, L, Hortobagyi, T, and Tihanyi, J. Dynamic contractility and efficiency impairments in stretch-shortening cycle are stretch-load-dependent after training-induced muscle damage. J Strength Cond Res 27(8): 2171-2179, 2013To determine the acute task and stretch-load dependency of

Fragile X mental retardation protein controls ion channel expression and activity.

Science.gov (United States)

Ferron, Laurent

2016-10-15

Fragile X-associated disorders are a family of genetic conditions resulting from the partial or complete loss of fragile X mental retardation protein (FMRP). Among these disorders is fragile X syndrome, the most common cause of inherited intellectual disability and autism. FMRP is an RNA-binding protein involved in the control of local translation, which has pleiotropic effects, in particular on synaptic function. Analysis of the brain FMRP transcriptome has revealed hundreds of potential mRNA targets encoding postsynaptic and presynaptic proteins, including a number of ion channels. FMRP has been confirmed to bind voltage-gated potassium channels (K v 3.1 and K v 4.2) mRNAs and regulates their expression in somatodendritic compartments of neurons. Recent studies have uncovered a number of additional roles for FMRP besides RNA regulation. FMRP was shown to directly interact with, and modulate, a number of ion channel complexes. The sodium-activated potassium (Slack) channel was the first ion channel shown to directly interact with FMRP; this interaction alters the single-channel properties of the Slack channel. FMRP was also shown to interact with the auxiliary β4 subunit of the calcium-activated potassium (BK) channel; this interaction increases calcium-dependent activation of the BK channel. More recently, FMRP was shown to directly interact with the voltage-gated calcium channel, Ca v 2.2, and reduce its trafficking to the plasma membrane. Studies performed on animal models of fragile X syndrome have revealed links between modifications of ion channel activity and changes in neuronal excitability, suggesting that these modifications could contribute to the phenotypes observed in patients with fragile X-associated disorders. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Biaxial stretching of film principles and applications

CERN Document Server

Demeuse, M T

2011-01-01

Biaxial (having two axes) stretching of film is used for a range of applications and is the primary manufacturing process by which products are produced for the food packaging industry. Biaxial stretching of film: principles and applications provides an overview of the manufacturing processes and range of applications for biaxially stretched films. Part one reviews the fundamental principles of biaxial stretching. After an introductory chapter which defines terms, chapters discuss equipment design and requirements, laboratory evaluations, biaxial film structures and typical industrial processes for the biaxial orientation of films. Additional topics include post production processing of biaxially stretched films, the stress-strain behaviour of poly(ethylene terephthalate) and academic investigations of biaxially stretched films. Part two investigates the applications of biaxial films including fresh cut produce, snack packaging and product labelling. A final chapter investigates potential future trends for bi...

Zinc-dependent multi-conductance channel activity in mitochondria isolated from ischemic brain.

Science.gov (United States)

Bonanni, Laura; Chachar, Mushtaque; Jover-Mengual, Teresa; Li, Hongmei; Jones, Adrienne; Yokota, Hidenori; Ofengeim, Dimitry; Flannery, Richard J; Miyawaki, Takahiro; Cho, Chang-Hoon; Polster, Brian M; Pypaert, Marc; Hardwick, J Marie; Sensi, Stefano L; Zukin, R Suzanne; Jonas, Elizabeth A

2006-06-21

Transient global ischemia is a neuronal insult that induces delayed cell death. A hallmark event in the early post-ischemic period is enhanced permeability of mitochondrial membranes. The precise mechanisms by which mitochondrial function is disrupted are, as yet, unclear. Here we show that global ischemia promotes alterations in mitochondrial membrane contact points, a rise in intramitochondrial Zn2+, and activation of large, multi-conductance channels in mitochondrial outer membranes by 1 h after insult. Mitochondrial channel activity was associated with enhanced protease activity and proteolytic cleavage of BCL-xL to generate its pro-death counterpart, deltaN-BCL-xL. The findings implicate deltaN-BCL-xL in large, multi-conductance channel activity. Consistent with this, large channel activity was mimicked by introduction of recombinant deltaN-BCL-xL to control mitochondria and blocked by introduction of a functional BCL-xL antibody to post-ischemic mitochondria via the patch pipette. Channel activity was also inhibited by nicotinamide adenine dinucleotide, indicative of a role for the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane. In vivo administration of the membrane-impermeant Zn2+ chelator CaEDTA before ischemia or in vitro application of the membrane-permeant Zn2+ chelator tetrakis-(2-pyridylmethyl) ethylenediamine attenuated channel activity, suggesting a requirement for Zn2+. These findings reveal a novel mechanism by which ischemic insults disrupt the functional integrity of the outer mitochondrial membrane and implicate deltaN-BCL-xL and VDAC in the large, Zn2+-dependent mitochondrial channels observed in post-ischemic hippocampal mitochondria.

SENSITIVE EFFECTS OF POTASSIUM AND CALCIUM CHANNEL BLOCKING AND ATP-SENSITIVE POTASSIUM CHANNEL ACTIVATORS ON SEMINAL VESICLE SMOOTH MUSCLE CONTRACTIONS

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H SADRAEI

2000-12-01

Full Text Available Background. Seminal vesicle smooth muscle contraction is mediated through sympathetic and parasympathetic neurons activity. Although seminal vesicle plays an important role in male fertility, but little attention is given to mechanism involved in contraction of this organ.
Methods. In this study effects of drugs which activate ATP - sensitive K channels and blockers of K and Ca channels were examined on contraction of guinea - pig isolated seminal vesicle due to electrical filled stimulation (EFS, noradrenaline, carbachol and KCI.
Results. The K channel blocker tetraethyl ammonium potentate the EFS responses at all frequencies, while, the ATP - sensitive K channel inhibitor glibenclamide and the K channel opener levcromakalim, diazoxide, minoxidil and Ca channel blocker nifedipine all had relaxant effect on guinea - pig seminal vesicle.
Discussion. This study indicate that activities of K and Ca channels is important in regulation of seminal vesicle contraction due to nerve stimulation, noradrenaline or carbachol.

Effectiveness of passive stretching versus hold relax technique in flexibility of hamstring muscle

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Gauri Shankar

2010-10-01

Full Text Available Aim: To compare the effectiveness of passive stretching and hold relax technique in the flexibility of hamstring muscle. Methods: A total of 80 normal healthy female subjects between age group 20-30 years referred to the department of physiotherapy, Sumandeep Vidyapeeth University, sampling method being convenient sampling. The subjects were randomly divided in two groups i.e. passive stretching group (n=40 and PNF group (n=40 and given passive stretching and proprioceptive neuromuscular facilitation technique respectively. Active knee extension range was measured before and after the intervention by goniometer. Results: t test showed a highly significant (p=0.000 increase in range of motion in PNF group. Conclusion: Proprioceptive neuromuscular facilitation technique is more effective in increasing hamstring flexibility than the passive stretching.

Correlation between structure and conductivity in stretched Nafion

Science.gov (United States)

Allahyarov, Elshad; Taylor, Philip

2008-03-01

We have used coarse-grained simulation methods to investigate the effect of stretching-induced structure orientation on the proton conductivity of Nafion-like polyelectrolyte membranes. Recent experimental data on the morphology of ionomers describe Nafion as an aggregation of polymeric backbone chains forming elongated objects embedded in a continuous ionic medium. Uniaxial stretching of a recast Nafion film causes a preferential orientation of these objects in the direction of stretching. Our simulations of humid Nafion show that this has a strong effect on the proton conductivity, which is enhanced along the stretching direction, while the conductivity perpendicular to the stretched polymer backbone is strongly reduced. Stretching also causes the perfluorinated side chains to orient perpendicular to the stretching axis. The sulphonate multiplets shrink in diameter as the stretching is increased and show a spatially periodic ordering in their distribution. This in turn affects the distribution of contained water at low water contents. The water forms a continuous network with narrow bridges between small water clusters absorbed in head-group multiplets. We find the morphological changes in the stretched Nafion to be retained upon removal of the uniaxial stress.

Characterization of mechanical behavior of a porcine pulmonary artery strip using a randomized uniaxial stretch and stretch-rate protocol

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Criscione John C

2008-01-01

Full Text Available Abstract Background Much of the experimental work in soft tissue mechanics has been focused on fitting approximate relations for specific tissue types from aggregate data on multiple samples of the tissue. Such relations are needed for modeling applications and have reasonable predictability – especially given the natural variance in specimens. There is, however, much theoretical and experimental work to be done in determining constitutive behaviors for particular specimens and tissues. In so doing, it may be possible to exploit the natural variation in tissue ultrastructure – so to relate ultrastructure composition to tissue behavior. Thus, this study focuses on an experimental method for determining constitutive behaviors and illustrates the method with analysis of a porcine pulmonary artery strip. The method characterizes the elastic part of the response (implicitly in terms of stretch and the inelastic part in terms of short term stretch history (i.e., stretch-rate Ht2, longer term stretch history Ht1, and time since the start of testing T. Methods A uniaxial testing protocol with a random stretch and random stretch-rate was developed. The average stress at a particular stretch was chosen as the hyperelastic stress response, and deviation from the mean at this particular stretch is chosen as the inelastic deviation. Multivariable Linear Regression Analysis (MLRA was utilized to verify if Ht2, Ht1, and T are important factors for characterizing the inelastic deviation. For acquiring Ht2 and Ht1, an integral function type of stretch history was employed with time constants chosen from the relaxation spectrum of an identical size strip from the same tissue with the same orientation. Finally, statistical models that characterize the inelasticity were developed at various, nominal values of stretch, and their predictive capability was examined. Results Inelastic deviation from hyperelasticity was high (31% for low stretch and declined

Intermolecular Interactions in the TMEM16A Dimer Controlling Channel Activity.

Science.gov (United States)

Scudieri, Paolo; Musante, Ilaria; Gianotti, Ambra; Moran, Oscar; Galietta, Luis J V

2016-12-08

TMEM16A and TMEM16B are plasma membrane proteins with Ca 2+ -dependent Cl - channel function. By replacing the carboxy-terminus of TMEM16A with the equivalent region of TMEM16B, we obtained channels with potentiation of channel activity. Progressive shortening of the chimeric region restricted the "activating domain" to a short sequence close to the last transmembrane domain and led to TMEM16A channels with high activity at very low intracellular Ca 2+ concentrations. To elucidate the molecular mechanism underlying this effect, we carried out experiments based on double chimeras, Forster resonance energy transfer, and intermolecular cross-linking. We also modeled TMEM16A structure using the Nectria haematococca TMEM16 protein as template. Our results indicate that the enhanced activity in chimeric channels is due to altered interaction between the carboxy-terminus and the first intracellular loop in the TMEM16A homo-dimer. Mimicking this perturbation with a small molecule could be the basis for a pharmacological stimulation of TMEM16A-dependent Cl - transport.

Acute effects of 15min static or contract-relax stretching modalities on plantar flexors neuromuscular properties.

Science.gov (United States)

Babault, Nicolas; Kouassi, Blah Y L; Desbrosses, Kevin

2010-03-01

The present study aimed to investigate the immediate effects of 15 min static or sub-maximal contract-relax stretching modalities on the neuromuscular properties of plantar flexor muscles. Ten male volunteers were tested before and immediately after 15 min static or contract-relax stretching programs of plantar flexor muscles (20 stretches). Static stretching consisted in 30s stretches to the point of discomfort. For the contract-relax stretching modality, subjects performed 6s sub-maximal isometric plantar flexion before 24s static stretches. Measurements included maximal voluntary isometric torque (MVT) and the corresponding electromyographic activity of soleus (SOL) and medial gastrocnemius (MG) muscles (RMS values), as well as maximal peak torque (Pt) elicited at rest by single supramaximal electrical stimulation of the tibial nerve. After 15 min stretching, significant MVT and SOL RMS decreases were obtained (-6.9+/-11.6% and -6.5+/-15.4%, respectively). No difference was obtained between stretching modalities. Pt remained unchanged after stretching. MG RMS changes were significantly different between stretching modalities (-9.4+/-18.3% and +3.5+/-11.6% after static and contract-relax stretching modalities, respectively). These findings indicated that performing 15 min static or contract-relax stretching had detrimental effects on the torque production capacity of plantar flexor muscles and should be precluded before competition. Mechanisms explaining this alteration seemed to be stretch modality dependent. Copyright 2009 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

[Current trends in the effects of stretching: application to physical exercise in the workplace].

Science.gov (United States)

Eguchi, Yasumasa; Ohta, Masanori; Yamato, Hiroshi

2011-09-01

A review of the Survey on the State of Employees' Health by the Ministry of Health, Labour and Welfare (2008) shows that the most commonly implemented aspect as an activity of worksite health promotion is "Health counseling", and the second is "Workplace physical exercise." Physical exercise, "Taiso", is acceptable and sustainable for workers, as it is easy to do in a group or alone. Various modes of stretching are implemented for workplace physical exercise. However, articles suggesting negative or contradictory effects of stretching have increased in recent years. Several review articles have revealed that static stretching may induce impairments of muscle power performance and no stretching will prevent or reduce muscle soreness after exercise. There are various aims of workplace physical exercise, so we have to consider the situational method when we apply stretching to occupational health.

Stretched polygons in a lattice tube

Energy Technology Data Exchange (ETDEWEB)

Atapour, M [Department of Mathematics and Statistics, York University, Toronto, ON M3J 1P3 (Canada); Soteros, C E [Department of Mathematics and Statistics, University of Saskatchewan, Saskatoon, SK S7N 5E6 (Canada); Whittington, S G [Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6 (Canada)], E-mail: atapour@mathstat.yorku.ca, E-mail: soteros@math.usask.ca, E-mail: swhittin@chem.utoronto.ca

2009-08-14

We examine the topological entanglements of polygons confined to a lattice tube and under the influence of an external tensile force f. The existence of the limiting free energy for these so-called stretched polygons is proved and then, using transfer matrix arguments, a pattern theorem for stretched polygons is proved. Note that the tube constraint allows us to prove a pattern theorem for any arbitrary value of f, while without the tube constraint it has so far only been proved for large values of f. The stretched polygon pattern theorem is used first to show that the average span per edge of a randomly chosen n-edge stretched polygon approaches a positive value, non-decreasing in f, as n {yields} {infinity}. We then show that the knotting probability of an n-edge stretched polygon confined to a tube goes to one exponentially as n {yields} {infinity}. Thus as n {yields} {infinity} when polygons are influenced by a force f, no matter its strength or direction, topological entanglements, as defined by knotting, occur with high probability. (fast track communication)

Stretched polygons in a lattice tube

International Nuclear Information System (INIS)

Atapour, M; Soteros, C E; Whittington, S G

2009-01-01

We examine the topological entanglements of polygons confined to a lattice tube and under the influence of an external tensile force f. The existence of the limiting free energy for these so-called stretched polygons is proved and then, using transfer matrix arguments, a pattern theorem for stretched polygons is proved. Note that the tube constraint allows us to prove a pattern theorem for any arbitrary value of f, while without the tube constraint it has so far only been proved for large values of f. The stretched polygon pattern theorem is used first to show that the average span per edge of a randomly chosen n-edge stretched polygon approaches a positive value, non-decreasing in f, as n → ∞. We then show that the knotting probability of an n-edge stretched polygon confined to a tube goes to one exponentially as n → ∞. Thus as n → ∞ when polygons are influenced by a force f, no matter its strength or direction, topological entanglements, as defined by knotting, occur with high probability. (fast track communication)

Intracellular long-chain acyl CoAs activate TRPV1 channels.

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Yi Yu

Full Text Available TRPV1 channels are an important class of membrane proteins that play an integral role in the regulation of intracellular cations such as calcium in many different tissue types. The anionic phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2 is a known positive modulator of TRPV1 channels and the negatively charged phosphate groups interact with several basic amino acid residues in the proximal C-terminal TRP domain of the TRPV1 channel. We and other groups have shown that physiological sub-micromolar levels of long-chain acyl CoAs (LC-CoAs, another ubiquitous anionic lipid, can also act as positive modulators of ion channels and exchangers. Therefore, we investigated whether TRPV1 channel activity is similarly regulated by LC-CoAs. Our results show that LC-CoAs are potent activators of the TRPV1 channel and interact with the same PIP2-binding residues in TRPV1. In contrast to PIP2, LC-CoA modulation of TRPV1 is independent of Ca2+i, acting in an acyl side-chain saturation and chain-length dependent manner. Elevation of LC-CoAs in intact Jurkat T-cells leads to significant increases in agonist-induced Ca2+i levels. Our novel findings indicate that LC-CoAs represent a new fundamental mechanism for regulation of TRPV1 channel activity that may play a role in diverse cell types under physiological and pathophysiological conditions that alter fatty acid transport and metabolism such as obesity and diabetes.

Antisense oligonucleotides suppress cell-volume-induced activation of chloride channels.

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Gschwentner, M; Nagl, U O; Wöll, E; Schmarda, A; Ritter, M; Paulmichl, M

1995-08-01

Cell volume regulation is an essential feature of most cells. After swelling in hypotonic media, the simultaneous activation of potassium and chloride channels is believed to be the initial, time-determining step in cell volume regulation. The activation of both pathways is functionally linked and enables the cells to lose ions and water, subsequently leading to cell shrinkage and readjustment of the initial volume. NIH 3T3 fibroblasts efficiently regulate their volume after swelling and bear chloride channels that are activated by decreasing extracellular osmolarity. The chloride current elicited in these cells after swelling is reminiscent of the current found in oocytes expressing an outwardly rectifying chloride current termed ICln. Introduction of antisense oligodeoxynucleotides complementary to the first 30 nucleotides of the coding region of the ICln channel into NIH 3T3 fibroblasts suppresses the activation of the swelling-induced chloride current. The experiments directly demonstrate an unambiguous link between a volume-activated chloride current and a cloned protein involved in chloride transport.

Bend, stretch, and touch: Locating a finger on an actively deformed transparent sensor array.

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Sarwar, Mirza Saquib; Dobashi, Yuta; Preston, Claire; Wyss, Justin K M; Mirabbasi, Shahriar; Madden, John David Wyndham

2017-03-01

The development of bendable, stretchable, and transparent touch sensors is an emerging technological goal in a variety of fields, including electronic skin, wearables, and flexible handheld devices. Although transparent tactile sensors based on metal mesh, carbon nanotubes, and silver nanowires demonstrate operation in bent configurations, we present a technology that extends the operation modes to the sensing of finger proximity including light touch during active bending and even stretching. This is accomplished using stretchable and ionically conductive hydrogel electrodes, which project electric field above the sensor to couple with and sense a finger. The polyacrylamide electrodes are embedded in silicone. These two widely available, low-cost, transparent materials are combined in a three-step manufacturing technique that is amenable to large-area fabrication. The approach is demonstrated using a proof-of-concept 4 × 4 cross-grid sensor array with a 5-mm pitch. The approach of a finger hovering a few centimeters above the array is readily detectable. Light touch produces a localized decrease in capacitance of 15%. The movement of a finger can be followed across the array, and the location of multiple fingers can be detected. Touch is detectable during bending and stretch, an important feature of any wearable device. The capacitive sensor design can be made more or less sensitive to bending by shifting it relative to the neutral axis. Ultimately, the approach is adaptable to the detection of proximity, touch, pressure, and even the conformation of the sensor surface.

Stretch Marks

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... completely without the help of a dermatologist or plastic surgeon. These doctors may use one of many types of treatments — from actual surgery to techniques like microdermabrasion and laser treatment — to reduce the appearance of stretch marks. These techniques are ...

Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor

Energy Technology Data Exchange (ETDEWEB)

Liu, Gang [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Hitomi, Hirofumi, E-mail: hitomi@kms.ac.jp [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Hosomi, Naohisa [Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa (Japan); Lei, Bai; Nakano, Daisuke [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Deguchi, Kazushi; Mori, Hirohito; Masaki, Tsutomu [Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Ma, Hong [Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Griendling, Kathy K. [Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA (United States); Nishiyama, Akira [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan)

2011-10-15

Insulin resistance and hypertension have been implicated in the pathogenesis of cardiovascular disease; however, little is known about the roles of insulin and mechanical force in vascular smooth muscle cell (VSMC) remodeling. We investigated the contribution of mechanical stretch to insulin-induced VSMC proliferation. Thymidine incorporation was stimulated by insulin in stretched VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose incorporation in both stretched and un-stretched VSMCs. Mechanical stretch augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)-1 receptor expression, although it did not alter the expression of insulin receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt activation, and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor. Mechanical stretch augments insulin-induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was also augmented in hypertensive rats. These results provide a basis for clarifying the molecular mechanisms of vascular remodeling in hypertensive patients with hyperinsulinemia. -- Highlights: {yields} Mechanical stretch augments insulin-induced VSMC proliferation via IGF-1 receptor. {yields} Src/EGFR-mediated ERK and Akt phosphorylation are augmented in stretched VSMCs. {yields} Similar to in vitro experiment, IGF-1 receptor is increased in hypertensive rats. {yields} Results provide possible mechanisms of vascular remodeling in hypertension with DM.

Intraplaque stretch in carotid atherosclerotic plaque--an effective biomechanical predictor for subsequent cerebrovascular ischemic events.

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Zhongzhao Teng

Full Text Available BACKGROUND: Stretch is a mechanical parameter, which has been proposed previously to affect the biological activities in different tissues. This study explored its utility in determining plaque vulnerability. METHODS: One hundred and six patients with mild to moderate carotid stenosis were recruited in this study (53 symptomatic and 53 asymptomatic. High resolution, multi-sequence magnetic resonance (MR imaging was performed to delineate various plaque components. Finite element method was used to predict high stretch concentration within the plaque. RESULTS: During a two-year follow-up, 11 patients in symptomatic group and 3 in asymptomatic group experienced recurrent cerebrovascular events. Plaque stretch at systole and stretch variation during one cardiac cycle was greater in symptomatic group than those in the asymptomatic. Within the symptomatic group, a similar trend was observed in patients with recurrent events compared to those without. CONCLUSION: Plaques with high stretch concentration and large stretch variation are associated with increased risk of future cerebrovascular events.

Intracellular zinc activates KCNQ channels by reducing their dependence on phosphatidylinositol 4,5-bisphosphate.

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Gao, Haixia; Boillat, Aurélien; Huang, Dongyang; Liang, Ce; Peers, Chris; Gamper, Nikita

2017-08-01

M-type (Kv7, KCNQ) potassium channels are proteins that control the excitability of neurons and muscle cells. Many physiological and pathological mechanisms of excitation operate via the suppression of M channel activity or expression. Conversely, pharmacological augmentation of M channel activity is a recognized strategy for the treatment of hyperexcitability disorders such as pain and epilepsy. However, physiological mechanisms resulting in M channel potentiation are rare. Here we report that intracellular free zinc directly and reversibly augments the activity of recombinant and native M channels. This effect is mechanistically distinct from the known redox-dependent KCNQ channel potentiation. Interestingly, the effect of zinc cannot be attributed to a single histidine- or cysteine-containing zinc-binding site within KCNQ channels. Instead, zinc dramatically reduces KCNQ channel dependence on its obligatory physiological activator, phosphatidylinositol 4,5-bisphosphate (PIP 2 ). We hypothesize that zinc facilitates interactions of the lipid-facing interface of a KCNQ protein with the inner leaflet of the plasma membrane in a way similar to that promoted by PIP 2 Because zinc is increasingly recognized as a ubiquitous intracellular second messenger, this discovery might represent a hitherto unknown native pathway of M channel modulation and provide a fresh strategy for the design of M channel activators for therapeutic purposes.

Mechanical stretching stimulates collagen synthesis via down-regulating SO2/AAT1 pathway

Science.gov (United States)

Liu, Jia; Yu, Wen; Liu, Yan; Chen, Selena; Huang, Yaqian; Li, Xiaohui; Liu, Cuiping; Zhang, Yanqiu; Li, Zhenzhen; Du, Jie; Tang, Chaoshu; Du, Junbao; Jin, Hongfang

2016-01-01

The aim of the study was to investigate the role of endogenous sulfur dioxide (SO2)/ aspartate aminotransferase 1 (AAT1) pathway in stretch-induced excessive collagen expression and its mechanism. The mechanical stretch downregulated SO2/AAT1 pathway and increased collagen I and III protein expression. Importantly, AAT1 overexpression blocked the increase in collagen I and III expression, transforming growth factor-β1 (TGF- β1) expression and phosphorylation of Smad2/3 induced by stretch, but AAT1 knockdown mimicked the increase in collagen I and III expression, TGF- β1 expression and phosphorylation of Smad2/3 induced by stretch. Mechanistically, SB431542, a TGF-β1/Smad2/3 inhibitor, eliminated excessive collagen I and III accumulation induced by AAT1 knockdown, stretch or stretch plus AAT1 knockdown. In a rat model of high pulmonary blood flow-induced pulmonary vascular collagen accumulation, AAT1 expression and SO2 content in lung tissues of rat were reduced in shunt rats with high pulmonary blood flow. Supplement of SO2 derivatives inhibited activation of TGF- β1/Smad2/3 pathway and alleviated the excessive collagen accumulation in lung tissues of shunt rats. The results suggested that deficiency of endogenous SO2/AAT1 pathway mediated mechanical stretch-stimulated abnormal collagen accumulation via TGF-β1/Smad2/3 pathway. PMID:26880260

Comparison of the effects of local cryotherapy and passive cross-body stretch on extensibility in subjects with posterior shoulder tightness.

Science.gov (United States)

Park, Kyue-Nam; Kwon, Oh-Yun; Weon, Jong-Hyuck; Choung, Sung-Dae; Kim, Si-Hyun

2014-01-01

The objective was to compare the immediate effects of local cryotherapy (LC) and passive cross-body stretch on the extensibility of the posterior shoulder muscle in individuals with posterior shoulder tightness. Eighty-seven healthy subjects with a between-shoulder difference in internal rotation (IR) range of motion (ROM) greater than 10° were randomly divided into three groups: LC group, stretching group, and control group (n = 29 in each group). Subjects in the LC group received LC on infraspinatus and posterior deltoid muscles and subjects in the stretching group performed passive cross-body stretch. Stretch sensation was measured at the end range of passive IR and horizontal adduction (HA) using numerical rating scale, and the pressure pain threshold (PPT) at the infraspinatus and posterior deltoid muscles was measured using pressure algometry. Passive and active ROM of IR and HA of the glenohumeral joint were measured using an inclinometer. All measurements were performed at pre-intervention, post- intervention, and 10-min follow-up. Stretch sensation was significantly decreased and PPT was significantly increased in the LC and stretching groups at post-intervention, and these effects were maintained at 10-min follow-up, compared to the control group. Both the LC group and stretching group had a significantly greater increase in passive and active ROM of IR and HA, compared to the control group at post-intervention and 10-min follow-up. However, there were no significant differences in stretch sensation, PPT, or ROM of IR and HA between the LC group and stretching group. LC can be used to decrease the stretch sensation and increase PPT and ROM of IR and HA as much as a stretching exercise. LC could be an alternative method for increasing the restricted ROM of glenohumeral IR and HA for individuals with posterior shoulder tightness, especially for patients and sports players who have severe stretching discomfort. Key PointsLocal cryotherapy (LC) decreased the

The effect of warm-ups with stretching on the isokinetic moments of collegiate men.

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Park, Hyoung-Kil; Jung, Min-Kyung; Park, Eunkyung; Lee, Chang-Young; Jee, Yong-Seok; Eun, Denny; Cha, Jun-Youl; Yoo, Jaehyun

2018-02-01

Performing warm-ups increases muscle temperature and blood flow, which contributes to improved exercise performance and reduced risk of injuries to muscles and tendons. Stretching increases the range of motion of the joints and is effective for the maintenance and enhancement of exercise performance and flexibility, as well as for injury prevention. However, stretching as a warm-up activity may temporarily decrease muscle strength, muscle power, and exercise performance. This study aimed to clarify the effect of stretching during warm-ups on muscle strength, muscle power, and muscle endurance in a nonathletic population. The subjects of this study consisted of 13 physically active male collegiate students with no medical conditions. A self-assessment questionnaire regarding how well the subjects felt about their physical abilities was administered to measure psychological readiness before and after the warm-up. Subjects performed a non-warm-up, warm-up, or warm-up regimen with stretching prior to the assessment of the isokinetic moments of knee joints. After the measurements, the respective variables were analyzed using nonparametric tests. First, no statistically significant intergroup differences were found in the flexor and extensor peak torques of the knee joints at 60°/sec, which were assessed to measure muscle strength. Second, no statistically significant intergroup differences were found in the flexor and extensor peak torques of the knee joints at 180°/sec, which were assessed to measure muscle power. Third, the total work of the knee joints at 240°/sec, intended to measure muscle endurance, was highest in the aerobic-stretch-warm-ups (ASW) group, but no statistically significant differences were found among the groups. Finally, the psychological readiness for physical activity according to the type of warm-up was significantly higher in ASW. Simple stretching during warm-ups appears to have no effect on variables of exercise physiology in nonathletes

[G-protein potentiates the activation of TNF-alpha on calcium-activated potassium channel in ECV304].

Science.gov (United States)

Lin, L; Zheng, Y; Qu, J; Bao, G

2000-06-01

Observe the effect of tumor necrosis factor-alpha (TNF-alpha) on calcium-activated potassium channel in ECV304 and the possible involvement of G-protein mediation in the action of TNF-alpha. Using the cell-attached configuration of patch clamp technique. (1) the activity of high-conductance calcium-activated potassium channel (BKca) was recorded. Its conductance is (202.54 +/- 16.62) pS; (2) the activity of BKca was potentiated by 200 U/ml TNF-alpha; (3) G-protein would intensify this TNF-alpha activation. TNF-alpha acted on vascular endothelial cell ECV304 could rapidly activate the activity of BKca. Opening of BKca resulted in membrane hyper-polarization which could increase electro-chemical gradient for the resting Ca2+ influx and open leakage calcium channel, thus resting cytoplasmic free Ca2+ concentration could be elevated. G-protein may exert an important regulation in this process.

Imaging large cohorts of single ion channels and their activity

Directory of Open Access Journals (Sweden)

Katia eHiersemenzel

2013-09-01

Full Text Available As calcium is the most important signaling molecule in neurons and secretory cells, amongst many other cell types, it follows that an understanding of calcium channels and their regulation of exocytosis is of vital importance. Calcium imaging using calcium dyes such as Fluo3, or FRET-based dyes that have been used widely has provided invaluable information, which combined with modeling has estimated the sub-types of channels responsible for triggering the exocytotic machinery as well as inferences about the relative distances away from vesicle fusion sites these molecules adopt. Importantly, new super-resolution microscopy techniques, combined with novel Ca2+ indicators and imaginative imaging approaches can now define directly the nanoscale locations of very large cohorts of single channel molecules in relation to single vesicles. With combinations of these techniques the activity of individual channels can be visualized and quantified using novel Ca2+ indicators. Fluorescently labeled specific channel toxins can also be used to localize endogenous assembled channel tetramers. Fluorescence lifetime imaging microscopy and other single-photon-resolution spectroscopic approaches offer the possibility to quantify protein-protein interactions between populations of channels and the SNARE protein machinery for the first time. Together with simultaneous electrophysiology, this battery of quantitative imaging techniques has the potential to provide unprecedented detail describing the locations, dynamic behaviours, interactions and conductance activities of many thousands of channel molecules and vesicles in living cells.

Stretched versus compressed exponential kinetics in α-helix folding

International Nuclear Information System (INIS)

Hamm, Peter; Helbing, Jan; Bredenbeck, Jens

2006-01-01

In a recent paper (J. Bredenbeck, J. Helbing, J.R. Kumita, G.A. Woolley, P. Hamm, α-helix formation in a photoswitchable peptide tracked from picoseconds to microseconds by time resolved IR spectroscopy, Proc. Natl. Acad. Sci USA 102 (2005) 2379), we have investigated the folding of a photo-switchable α-helix with a kinetics that could be fit by a stretched exponential function exp(-(t/τ) β ). The stretching factor β became smaller as the temperature was lowered, a result which has been interpreted in terms of activated diffusion on a rugged energy surface. In the present paper, we discuss under which conditions diffusion problems occur with stretched exponential kinetics (β 1). We show that diffusion problems do have a strong tendency to yield stretched exponential kinetics, yet, that there are conditions (strong perturbation from equilibrium, performing the experiment in the folding direction) under which compressed exponential kinetics would be expected instead. We discuss the kinetics on free energy surfaces predicted by simple initiation-propagation models (zipper models) of α-helix folding, as well as by folding funnel models. We show that our recent experiment has been performed under condition for which models with strong downhill driving force, such as the zipper model, would predict compressed, rather than stretched exponential kinetics, in disagreement with the experimental observation. We therefore propose that the free energy surface along a reaction coordinate that governs the folding kinetics must be relatively flat and has a shape similar to a 1D golf course. We discuss how this conclusion can be unified with the thermodynamically well established zipper model by introducing an additional kinetic reaction coordinate

Hyperglycemia Augments the Adipogenic Transdifferentiation Potential of Tenocytes and Is Alleviated by Cyclic Mechanical Stretch.

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Wu, Yu-Fu; Huang, Yu-Ting; Wang, Hsing-Kuo; Yao, Chung-Chen Jane; Sun, Jui-Sheng; Chao, Yuan-Hung

2017-12-28

Diabetes mellitus is associated with damage to tendons, which may result from cellular dysfunction in response to a hyperglycemic environment. Tenocytes express diminished levels of tendon-associated genes under hyperglycemic conditions. In contrast, mechanical stretch enhances tenogenic differentiation. However, whether hyperglycemia increases the non-tenogenic differentiation potential of tenocytes and whether this can be mitigated by mechanical stretch remains elusive. We explored the in vitro effects of high glucose and mechanical stretch on rat primary tenocytes. Specifically, non-tenogenic gene expression, adipogenic potential, cell migration rate, filamentous actin expression, and the activation of signaling pathways were analyzed in tenocytes treated with high glucose, followed by the presence or absence of mechanical stretch. We analyzed tenocyte phenotype in vivo by immunohistochemistry using an STZ (streptozotocin)-induced long-term diabetic mouse model. High glucose-treated tenocytes expressed higher levels of the adipogenic transcription factors PPAR γ and C/EBPs. PPARγ was also highly expressed in diabetic tendons. In addition, increased adipogenic differentiation and decreased cell migration induced by high glucose implicated a fibroblast-to-adipocyte phenotypic change. By applying mechanical stretch to tenocytes in high-glucose conditions, adipogenic differentiation was repressed, while cell motility was enhanced, and fibroblastic morphology and gene expression profiles were strengthened. In part, these effects resulted from a stretch-induced activation of ERK (extracellular signal-regulated kinases) and a concomitant inactivation of Akt. Our results show that mechanical stretch alleviates the augmented adipogenic transdifferentiation potential of high glucose-treated tenocytes and helps maintain their fibroblastic characteristics. The alterations induced by high glucose highlight possible pathological mechanisms for diabetic tendinopathy

Effects of contract-relax vs static stretching on stretch-induced strength loss and length-tension relationship

DEFF Research Database (Denmark)

Balle, S S; Magnusson, S P; McHugh, M P

2015-01-01

The purpose of this study was to determine the acute effects of contract-relax stretching (CRS) vs static stretching (SS) on strength loss and the length-tension relationship. We hypothesized that there would be a greater muscle length-specific effect of CRS vs SS. Isometric hamstring strength wa...

The temperature dependence of the BK channel activity - kinetics, thermodynamics, and long-range correlations.

Science.gov (United States)

Wawrzkiewicz-Jałowiecka, Agata; Dworakowska, Beata; Grzywna, Zbigniew J

2017-10-01

Large-conductance, voltage dependent, Ca 2+ -activated potassium channels (BK) are transmembrane proteins that regulate many biological processes by controlling potassium flow across cell membranes. Here, we investigate to what extent temperature (in the range of 17-37°C with ΔT=5°C step) is a regulating parameter of kinetic properties of the channel gating and memory effect in the series of dwell-time series of subsequent channel's states, at membrane depolarization and hyperpolarization. The obtained results indicate that temperature affects strongly the BK channels' gating, but, counterintuitively, it exerts no effect on the long-range correlations, as measured by the Hurst coefficient. Quantitative differences between dependencies of appropriate channel's characteristics on temperature are evident for different regimes of voltage. Examining the characteristics of BK channel activity as a function of temperature allows to estimate the net activation energy (E act ) and changes of thermodynamic parameters (ΔH, ΔS, ΔG) by channel opening. Larger E act corresponds to the channel activity at membrane hyperpolarization. The analysis of entropy and enthalpy changes of closed to open channel's transition suggest the entropy-driven nature of the increase of open state probability during voltage activation and supports the hypothesis about the voltage-dependent geometry of the channel vestibule. Copyright © 2017 Elsevier B.V. All rights reserved.

TRPV1 Channels and Gastric Vagal Afferent Signalling in Lean and High Fat Diet Induced Obese Mice.

Directory of Open Access Journals (Sweden)

Stephen J Kentish

Full Text Available Within the gastrointestinal tract vagal afferents play a role in control of food intake and satiety signalling. Activation of mechanosensitive gastric vagal afferents induces satiety. However, gastric vagal afferent responses to mechanical stretch are reduced in high fat diet mice. Transient receptor potential vanilloid 1 channels (TRPV1 are expressed in vagal afferents and knockout of TRPV1 reduces gastro-oesophageal vagal afferent responses to stretch. We aimed to determine the role of TRPV1 on gastric vagal afferent mechanosensitivity and food intake in lean and HFD-induced obese mice.TRPV1+/+ and -/- mice were fed either a standard laboratory diet or high fat diet for 20wks. Gastric emptying of a solid meal and gastric vagal afferent mechanosensitivity was determined.Gastric emptying was delayed in high fat diet mice but there was no difference between TRPV1+/+ and -/- mice on either diet. TRPV1 mRNA expression in whole nodose ganglia of TRPV1+/+ mice was similar in both dietary groups. The TRPV1 agonist N-oleoyldopamine potentiated the response of tension receptors in standard laboratory diet but not high fat diet mice. Food intake was greater in the standard laboratory diet TRPV1-/- compared to TRPV1+/+ mice. This was associated with reduced response of tension receptors to stretch in standard laboratory diet TRPV1-/- mice. Tension receptor responses to stretch were decreased in high fat diet compared to standard laboratory diet TRPV1+/+ mice; an effect not observed in TRPV1-/- mice. Disruption of TRPV1 had no effect on the response of mucosal receptors to mucosal stroking in mice on either diet.TRPV1 channels selectively modulate gastric vagal afferent tension receptor mechanosensitivity and may mediate the reduction in gastric vagal afferent mechanosensitivity in high fat diet-induced obesity.

Cross-bridge mechanism of residual force enhancement after stretching in a skeletal muscle.

Science.gov (United States)

Tamura, Youjiro

2018-01-01

A muscle model that uses a modified Langevin equation with actomyosin potentials was used to describe the residual force enhancement after active stretching. Considering that the new model uses cross-bridge theory to describe the residual force enhancement, it is different from other models that use passive stretching elements. Residual force enhancement was simulated using a half sarcomere comprising 100 myosin molecules. In this paper, impulse is defined as the integral of an excess force from the steady isometric force over the time interval for which a stretch is applied. The impulse was calculated from the force response due to fast and slow muscle stretches to demonstrate the viscoelastic property of the cross-bridges. A cross-bridge mechanism was proposed as a way to describe the residual force enhancement on the basis of the impulse results with reference to the compliance of the actin filament. It was assumed that the period of the actin potential increased by 0.5% and the amplitude of the potential decreased by 0.5% when the half sarcomere was stretched by 10%. The residual force enhancement after 21.0% sarcomere stretching was 6.9% of the maximum isometric force of the muscle; this value was due to the increase in the number of cross-bridges.

No evidence hip joint angle modulates intrinsically produced stretch reflex in human hopping.

Science.gov (United States)

Gibson, W; Campbell, A; Allison, G

2013-09-01

Motor output in activities such as walking and hopping is suggested to be mediated neurally by purported stretch reflex augmentation of muscle output. Reflex EMG activity during these tasks has been frequently investigated in the soleus muscle; with alterations in reflex amplitude being associated with changes in hip joint angle/phase of the gait cycle. Previous work has focussed on reflex activity induced by an artificial perturbation or by induction of H-reflexes. As such, it is currently unknown if stretch reflex activity induced intrinsically (as part of the task) is modulated by changes in hip joint angle. This study investigated whether hip joint angle modulated reflex EMG 'burst' activity during a hopping task performed on a custom-built partially reclined sleigh. Ten subjects participated; EMG and kinematic data (VICON motor capture system) was collected for each hop cycle. Participants completed 5 sets of 30s of self-paced hopping in (1) hip neutral and (2) hip 60° flexion conditions. There was no difference in EMG 'burst' activity or in sagittal plane kinematics (knee/ankle) in the hopping task between the two conditions. The results indicate that during a functional task such as hopping, changes in hip angle do not alter the stretch reflex-like activity associated with landing. Copyright © 2013 Elsevier B.V. All rights reserved.

Multiple-channel detection of cellular activities by ion-sensitive transistors

Science.gov (United States)

Machida, Satoru; Shimada, Hideto; Motoyama, Yumi

2018-04-01

An ion-sensitive field-effect transistor to record cellular activities was demonstrated. This field-effect transistor (bio transistor) includes cultured cells on the gate insulator instead of gate electrode. The bio transistor converts a change in potential underneath the cells into variation of the drain current when ion channels open. The bio transistor has high detection sensitivity to even minute variations in potential utilizing a subthreshold swing region. To open ion channels, a reagent solution (acetylcholine) was added to a human-originating cell cultured on the bio transistor. The drain current was successfully decreased with the addition of acetylcholine. Moreover, we attempted to detect the opening of ion channels using a multiple-channel measurement circuit containing several bio transistors. As a consequence, the drain current distinctly decreased only after the addition of acetylcholine. We confirmed that this measurement system including bio transistors enables to observation of cellular activities sensitively and simultaneously.

Channeled Scaffolds for Engineering Myocardium with Mechanical Stimulation

Science.gov (United States)

Zhang, Ting; Wan, Leo Q.; Xiong, Zhuo; Marsano, Anna; Maidhof, Robert; Park, Miri; Yan, Yongnian; Vunjak-Novakovic, Gordana

2011-01-01

The characteristics of the matrix (composition, structure, mechanical properties) and external culture environment (pulsatile perfusion, physical stimulation) are critically important for engineering functional myocardial tissue. We report the development of chitosan-collagen scaffolds with micro-pores and an array of parallel channels (~200 μm in diameter) that were specifically designed for cardiac tissue engineering with mechanical stimulation. The scaffolds were designed to have the structural and mechanical properties similar to those of the native human heart matrix. Scaffolds were seeded with neonatal rat heart cells and subjected to dynamic tensile stretch using a custom-designed bioreactor. The channels enhanced oxygen transport and facilitated the establishment of cell connections within the construct. The myocardial patches (14 mm in diameter, 1–2 mm thick) consisted of metabolically active cells and started to contract synchronously after 3 days of culture. Mechanical stimulation with high tensile stresses promoted cell alignment, elongation, and the expression of connexin-43 (Cx-43). This study confirms the importance of scaffold design and mechanical stimulation for the formation of contractile cardiac constructs. PMID:22081518

Stretching and jamming of finite automata

NARCIS (Netherlands)

Beijer, de N.; Kourie, D.G.; Watson, B.W.; Cleophas, L.G.W.A.; Watson, B.W.

2004-01-01

In this paper we present two transformations on automata, called stretching and jamming. These transformations will, under certain conditions, reduce the size of the transition table, and under other conditions reduce the string processing time. Given a finite automaton, we can stretch it by

Stretch-stimulated glucose transport in skeletal muscle is regulated by Rac1.

Science.gov (United States)

Sylow, Lykke; Møller, Lisbeth L V; Kleinert, Maximilian; Richter, Erik A; Jensen, Thomas E

2015-02-01

Rac1 regulates stretch-stimulated (i.e. mechanical stress) glucose transport in muscle. Actin depolymerization decreases stretch-induced glucose transport in skeletal muscle. Rac1 is a required part of the mechanical stress-component of the contraction-stimulus to glucose transport in skeletal muscle. An alternative to the canonical insulin signalling pathway for glucose transport is muscle contraction/exercise. Mechanical stress is an integrated part of the muscle contraction/relaxation cycle, and passive stretch stimulates muscle glucose transport. However, the signalling mechanism regulating stretch-stimulated glucose transport is not well understood. We recently reported that the actin cytoskeleton regulating GTPase, Rac1, was activated in mouse muscle in response to stretching. Rac1 is a regulator of contraction- and insulin-stimulated glucose transport, however, its role in stretch-stimulated glucose transport and signalling is unknown. We therefore investigated whether stretch-induced glucose transport in skeletal muscle required Rac1 and the actin cytoskeleton. We used muscle-specific inducible Rac1 knockout mice as well as pharmacological inhibitors of Rac1 and the actin cytoskeleton in isolated soleus and extensor digitorum longus muscles. In addition, the role of Rac1 in contraction-stimulated glucose transport during conditions without mechanical load on the muscles was evaluated in loosely hanging muscles and muscles in which cross-bridge formation was blocked by the myosin ATPase inhibitors BTS and Blebbistatin. Knockout as well as pharmacological inhibition of Rac1 reduced stretch-stimulated glucose transport by 30-50% in soleus and extensor digitorum longus muscle. The actin depolymerizing agent latrunculin B similarly decreased glucose transport in response to stretching by 40-50%. Rac1 inhibition reduced contraction-stimulated glucose transport by 30-40% in tension developing muscle but did not affect contraction-stimulated glucose transport in

ACTIVITY THEORY APPLIED AT CHANNEL EXPANSIONS IN SMALL AND MEDIUM ENTERPRISES

Directory of Open Access Journals (Sweden)

Siw Lundqvist

2017-06-01

Full Text Available Today’s commonly carried out channel expansions of commerce could be both costly and problematic to manage. Especially for small and medium-sized enterprises (SMEs that often suffer from a lack of digital competence, time and monetary resources in generally. Still, these transitions would be necessary to carry out because of customer demands and expectations concerning 24/7 availability, and access to digital commerce alternatives. Scarce resources are important reasons to search for how to carry out channel expansions with minimized problems. Activity theory (AT focuses on the whole in order to detect problems that hinder successful outcomes. Hence, this theory was applied to prior findings, from a project about SME’s channel expansions, highlighting several problems that could appear during these activities. Implications for research foremost involve issues connected to the use of AT; implications for practice particularly concern if and how AT could be used to support channel broadening activities.

Magnitude and duration of stretch modulate fibroblast remodeling.

Science.gov (United States)

Balestrini, Jenna L; Billiar, Kristen L

2009-05-01

Mechanical cues modulate fibroblast tractional forces and remodeling of extracellular matrix in healthy tissue, healing wounds, and engineered matrices. The goal of the present study is to establish dose-response relationships between stretch parameters (magnitude and duration per day) and matrix remodeling metrics (compaction, strength, extensibility, collagen content, contraction, and cellularity). Cyclic equibiaxial stretch of 2-16% was applied to fibroblast-populated fibrin gels for either 6 h or 24 h/day for 8 days. Trends in matrix remodeling metrics as a function of stretch magnitude and duration were analyzed using regression analysis. The compaction and ultimate tensile strength of the tissues increased in a dose-dependent manner with increasing stretch magnitude, yet remained unaffected by the duration in which they were cycled (6 h/day versus 24 h/day). Collagen density increased exponentially as a function of both the magnitude and duration of stretch, with samples stretched for the reduced duration per day having the highest levels of collagen accumulation. Cell number and failure tension were also dependent on both the magnitude and duration of stretch, although stretch-induced increases in these metrics were only present in the samples loaded for 6 h/day. Our results indicate that both the magnitude and the duration per day of stretch are critical parameters in modulating fibroblast remodeling of the extracellular matrix, and that these two factors regulate different aspects of this remodeling. These findings move us one step closer to fully characterizing culture conditions for tissue equivalents, developing improved wound healing treatments and understanding tissue responses to changes in mechanical environments during growth, repair, and disease states.

The effects of stretching on the flexibility, muscle performance and functionality of institutionalized older women

Directory of Open Access Journals (Sweden)

D. Gallon

2011-03-01

Full Text Available Stretching has been widely used to increase the range of motion. We assessed the effects of a stretching program on muscle-tendon length, flexibility, torque, and activities of daily living of institutionalized older women. Inclusion/exclusion criteria were according to Mini-Mental State Examination (MMSE (>13, Barthel Index (>13 and Lysholm Scoring Scale (>84. Seventeen 67 ± 9 year-old elderly women from a nursing home were divided into 2 groups at random: the control group (CG, N = 9 participated in enjoyable cultural activities; the stretching group (SG, N = 8 performed active stretching of hamstrings, 4 bouts of 1 min each. Both groups were supervised three times per week over a period of 8 weeks. Peak torque was assessed by an isokinetic method. Both groups were evaluated by a photogrammetric method to assess muscle-tendon length of uni- and biarticular hip flexors and hamstring flexibility. All measurements were analyzed before and after 8 weeks by two-way ANOVA with the level of significance set at 5%. Hamstring flexibility increased by 30% in the SG group compared to pre-training (76.5 ± 13.0° vs 59.5 ± 9.0°, P = 0.0002 and by 9.2% compared to the CG group (76.5 ± 13.0° vs 64.0 ± 12.0°, P = 0.0018. Muscle-tendon lengths of hip biarticular flexor muscles (124 ± 6.8° vs 118.3 ± 7.6°, 5.0 ± 7.0%, P = 0.031 and eccentric knee extensor peak torque were decreased in the CG group compared to pre-test values (-49.4 ± 16.8 vs -60.5 ± 18.9 Nm, -15.7 ± 20%, P = 0.048. The stretching program was sufficient to increase hamstring flexibility and a lack of stretching can cause reduction of muscle performance.

The Activation Effect of Hainantoxin-I, a Peptide Toxin from the Chinese Spider, Ornithoctonus hainana, on Intermediate-Conductance Ca2+-Activated K+ Channels

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Pengfei Huang

2014-08-01

Full Text Available Intermediate-conductance Ca2+-activated K+ (IK channels are calcium/calmodulin-regulated voltage-independent K+ channels. Activation of IK currents is important in vessel and respiratory tissues, rendering the channels potential drug targets. A variety of small organic molecules have been synthesized and found to be potent activators of IK channels. However, the poor selectivity of these molecules limits their therapeutic value. Venom-derived peptides usually block their targets with high specificity. Therefore, we searched for novel peptide activators of IK channels by testing a series of toxins from spiders. Using electrophysiological experiments, we identified hainantoxin-I (HNTX-I as an IK-channel activator. HNTX-I has little effect on voltage-gated Na+ and Ca2+ channels from rat dorsal root ganglion neurons and on the heterologous expression of voltage-gated rapidly activating delayed rectifier K+ channels (human ether-à-go-go-related gene; human ERG in HEK293T cells. Only 35.2% ± 0.4% of the currents were activated in SK channels, and there was no effect on BK channels. We demonstrated that HNTX-I was not a phrenic nerve conduction blocker or acutely toxic. This is believed to be the first report of a peptide activator effect on IK channels. Our study suggests that the activity and selectivity of HNTX-I on IK channels make HNTX-I a promising template for designing new drugs for cardiovascular diseases.

Foam topology. Bending versus stretching dominated architectures

International Nuclear Information System (INIS)

Deshpande, V.; Ashby, M.; Fleck, N.

2000-01-01

Cellular solids can deform by either the bending or stretching of the cell walls. While most cellular solids are bending-dominated, those that are stretching-dominated are much more weight-efficient for structural applications. In this study we have investigated the topological criteria that dictate the deformation mechanism of a cellular solid by analysing the rigidity (or otherwise) of pin-jointed frameworks comprising inextensional struts. We show that the minimum node connectivity for a special class of lattice structured materials to be stretching-dominated is 6 for 2D foams and 12 for 3D foams. Similarly, sandwich plates comprising of truss cores faced with planar trusses require a minimum node connectivity of 9 to undergo stretching-dominated deformation for all loading states. (author)

Cyclic mechanical stretch down-regulates cathelicidin antimicrobial peptide expression and activates a pro-inflammatory response in human bronchial epithelial cells

Directory of Open Access Journals (Sweden)

Harpa Karadottir

2015-12-01

Full Text Available Mechanical ventilation (MV of patients can cause damage to bronchoalveolar epithelium, leading to a sterile inflammatory response, infection and in severe cases sepsis. Limited knowledge is available on the effects of MV on the innate immune defense system in the human lung. In this study, we demonstrate that cyclic stretch of the human bronchial epithelial cell lines VA10 and BCi NS 1.1 leads to down-regulation of cathelicidin antimicrobial peptide (CAMP gene expression. We show that treatment of VA10 cells with vitamin D3 and/or 4-phenyl butyric acid counteracted cyclic stretch mediated down-regulation of CAMP mRNA and protein expression (LL-37. Further, we observed an increase in pro-inflammatory responses in the VA10 cell line subjected to cyclic stretch. The mRNA expression of the genes encoding pro-inflammatory cytokines IL-8 and IL-1β was increased after cyclic stretching, where as a decrease in gene expression of chemokines IP-10 and RANTES was observed. Cyclic stretch enhanced oxidative stress in the VA10 cells. The mRNA expression of toll-like receptor (TLR 3, TLR5 and TLR8 was reduced, while the gene expression of TLR2 was increased in VA10 cells after cyclic stretch. In conclusion, our in vitro results indicate that cyclic stretch may differentially modulate innate immunity by down-regulation of antimicrobial peptide expression and increase in pro-inflammatory responses.

Torres Strait: A channel clearing project

International Nuclear Information System (INIS)

Bankert, Stanley

1970-01-01

The Torres Strait is a reef-laden stretch of water lying south of New Guinea and north of the tip of the Cape York Peninsula of northeastern Australia. Because of its location and geologic structure it is particularly hazardous to shipping, and limits passage through the area. It was suggested that nuclear explosives might be used to create a safe shipping channel through the strait, and in this paper that possibility will be explored. While the construction of the Torres Strait Channel appears feasible from both a technical and an economic point of view, a great deal of further research will have to be done in a number of areas. The Channel would be a great economic boost to northwestern Australia and to trade between southeast Asia and Australia, but its effect on the Great Barrier Reef and the people of the region will require serious consideration

Torres Strait: A channel clearing project

Energy Technology Data Exchange (ETDEWEB)

Bankert, Stanley [Department of Applied Science, University of California - Davis (United States)

1970-05-15

The Torres Strait is a reef-laden stretch of water lying south of New Guinea and north of the tip of the Cape York Peninsula of northeastern Australia. Because of its location and geologic structure it is particularly hazardous to shipping, and limits passage through the area. It was suggested that nuclear explosives might be used to create a safe shipping channel through the strait, and in this paper that possibility will be explored. While the construction of the Torres Strait Channel appears feasible from both a technical and an economic point of view, a great deal of further research will have to be done in a number of areas. The Channel would be a great economic boost to northwestern Australia and to trade between southeast Asia and Australia, but its effect on the Great Barrier Reef and the people of the region will require serious consideration.

Mechanisms of Rose Bengal inhibition on SecA ATPase and ion channel activities.

Science.gov (United States)

Hsieh, Ying-Hsin; Huang, Ying-Ju; Jin, Jin-Shan; Yu, Liyan; Yang, Hsiuchin; Jiang, Chun; Wang, Binghe; Tai, Phang C

2014-11-14

SecA is an essential protein possessing ATPase activity in bacterial protein translocation for which Rose Bengal (RB) is the first reported sub-micromolar inhibitor in ATPase activity and protein translocation. Here, we examined the mechanisms of inhibition on various forms of SecA ATPase by conventional enzymatic assays, and by monitoring the SecA-dependent channel activity in the semi-physiological system in cells. We build on the previous observation that SecA with liposomes form active protein-conducting channels in the oocytes. Such ion channel activity is enhanced by purified Escherichia coli SecYEG-SecDF·YajC liposome complexes. Inhibition by RB could be monitored, providing correlation of in vitro activity and intact cell functionality. In this work, we found the intrinsic SecA ATPase is inhibited by RB competitively at low ATP concentration, and non-competitively at high ATP concentrations while the translocation ATPase with precursors and SecYEG is inhibited non-competitively by RB. The Inhibition by RB on SecA channel activity in the oocytes with exogenous ATP-Mg(2+), mimicking translocation ATPase activity, is also non-competitive. The non-competitive inhibition on channel activity has also been observed with SecA from other bacteria which otherwise would be difficult to examine without the cognate precursors and membranes. Copyright © 2014 Elsevier Inc. All rights reserved.

Passive Stretch Induces Structural and Functional Maturation of Engineered Heart Muscle as Predicted by Computational Modeling.

Science.gov (United States)

Abilez, Oscar J; Tzatzalos, Evangeline; Yang, Huaxiao; Zhao, Ming-Tao; Jung, Gwanghyun; Zöllner, Alexander M; Tiburcy, Malte; Riegler, Johannes; Matsa, Elena; Shukla, Praveen; Zhuge, Yan; Chour, Tony; Chen, Vincent C; Burridge, Paul W; Karakikes, Ioannis; Kuhl, Ellen; Bernstein, Daniel; Couture, Larry A; Gold, Joseph D; Zimmermann, Wolfram H; Wu, Joseph C

2018-02-01

The ability to differentiate human pluripotent stem cells (hPSCs) into cardiomyocytes (CMs) makes them an attractive source for repairing injured myocardium, disease modeling, and drug testing. Although current differentiation protocols yield hPSC-CMs to >90% efficiency, hPSC-CMs exhibit immature characteristics. With the goal of overcoming this limitation, we tested the effects of varying passive stretch on engineered heart muscle (EHM) structural and functional maturation, guided by computational modeling. Human embryonic stem cells (hESCs, H7 line) or human induced pluripotent stem cells (IMR-90 line) were differentiated to hPSC-derived cardiomyocytes (hPSC-CMs) in vitro using a small molecule based protocol. hPSC-CMs were characterized by troponin + flow cytometry as well as electrophysiological measurements. Afterwards, 1.2 × 10 6 hPSC-CMs were mixed with 0.4 × 10 6 human fibroblasts (IMR-90 line) (3:1 ratio) and type-I collagen. The blend was cast into custom-made 12-mm long polydimethylsiloxane reservoirs to vary nominal passive stretch of EHMs to 5, 7, or 9 mm. EHM characteristics were monitored for up to 50 days, with EHMs having a passive stretch of 7 mm giving the most consistent formation. Based on our initial macroscopic observations of EHM formation, we created a computational model that predicts the stress distribution throughout EHMs, which is a function of cellular composition, cellular ratio, and geometry. Based on this predictive modeling, we show cell alignment by immunohistochemistry and coordinated calcium waves by calcium imaging. Furthermore, coordinated calcium waves and mechanical contractions were apparent throughout entire EHMs. The stiffness and active forces of hPSC-derived EHMs are comparable with rat neonatal cardiomyocyte-derived EHMs. Three-dimensional EHMs display increased expression of mature cardiomyocyte genes including sarcomeric protein troponin-T, calcium and potassium ion channels, β-adrenergic receptors, and t

Channel Power in Multi-Channel Environments

NARCIS (Netherlands)

M.G. Dekimpe (Marnik); B. Skiera (Bernd)

2004-01-01

textabstractIn the literature, little attention has been paid to instances where companies add an Internet channel to their direct channel portfolio. However, actively managing multiple sales channels requires knowing the customers’ channel preferences and the resulting channel power. Two key

International Union of Basic and Clinical Pharmacology. C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels.

Science.gov (United States)

Kaczmarek, Leonard K; Aldrich, Richard W; Chandy, K George; Grissmer, Stephan; Wei, Aguan D; Wulff, Heike

2017-01-01

A subset of potassium channels is regulated primarily by changes in the cytoplasmic concentration of ions, including calcium, sodium, chloride, and protons. The eight members of this subfamily were originally all designated as calcium-activated channels. More recent studies have clarified the gating mechanisms for these channels and have documented that not all members are sensitive to calcium. This article describes the molecular relationships between these channels and provides an introduction to their functional properties. It also introduces a new nomenclature that differentiates between calcium- and sodium-activated potassium channels. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

A comprehensive search for calcium binding sites critical for TMEM16A calcium-activated chloride channel activity

Science.gov (United States)

Tien, Jason; Peters, Christian J; Wong, Xiu Ming; Cheng, Tong; Jan, Yuh Nung; Jan, Lily Yeh; Yang, Huanghe

2014-01-01

TMEM16A forms calcium-activated chloride channels (CaCCs) that regulate physiological processes such as the secretions of airway epithelia and exocrine glands, the contraction of smooth muscles, and the excitability of neurons. Notwithstanding intense interest in the mechanism behind TMEM16A-CaCC calcium-dependent gating, comprehensive surveys to identify and characterize potential calcium sensors of this channel are still lacking. By aligning distantly related calcium-activated ion channels in the TMEM16 family and conducting systematic mutagenesis of all conserved acidic residues thought to be exposed to the cytoplasm, we identify four acidic amino acids as putative calcium-binding residues. Alterations of the charge, polarity, and size of amino acid side chains at these sites alter the ability of different divalent cations to activate the channel. Furthermore, TMEM16A mutant channels containing double cysteine substitutions at these residues are sensitive to the redox potential of the internal solution, providing evidence for their physical proximity and solvent accessibility. DOI: http://dx.doi.org/10.7554/eLife.02772.001 PMID:24980701

Acute anal stretch inhibits NMDA-dependent pelvic-urethra reflex potentiation via spinal GABAergic inhibition in anesthetized rats.

Science.gov (United States)

Chen, Sung-Lang; Huang, Yu-Hui; Kao, Yu-Lin; Chen, Gin-Den; Cheng, Chen-Li; Peng, Hsien-Yu; Liao, Jiuan-Miaw; Huang, Pei-Chen; Tsai, Shih-Jei; Lin, Tzer-Bin

2008-10-01

The impact of acute anal stretch on the pelvic-urethra reflex potentiation was examined in urethane-anesthetized rats by recording the external urethra sphincter electromyogram activity evoked by the pelvic afferent stimulation. Test stimulation (1 stimulation/30 s) evoked a baseline reflex activity with a single action potential that was abolished by gallamine (5 mg/kg iv). On the other hand, the repetitive stimulation (1 stimulation/1 s) induced spinal reflex potentiation (SRP) that was attenuated by intrathecal 6-cyano-7-nitroquinoxaline-2,4-dione (a glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionat receptor antagonist, 100 microM, 10 microl) and d-2-amino-5-phosphonovalerate [a glutamatergic N-methyl-D-aspartate (NMDA) antagonist, 100 microM, 10 microl]. Acute anal stretch using a mosquito clamp with a distance of 4 mm exhibited no effect, whereas distances of 8 mm attenuated and 12 mm abolished the repetitive stimulation-induced SRP. Intrathecal NMDA (100 microM, 10 microl) reversed the abolition on SRP caused by anal stretch. On the other hand, pretreated bicuculline [gamma-aminobutyric acid (GABA) A receptor antagonist, 100 microM, 10 microl] but not hydroxysaclofen (GABAB receptor antagonist) counteracted the abolition on the repetitive stimulation-induced SRP caused by the anal stretch. All of the results suggested that anal stretch may be used as an adjunct to assist voiding dysfunction in patients with overactive urethra sphincter and that GABAergic neurotransmission is important in the neural mechanisms underlying external urethra sphincter activity inhibited by anal stretch.

Optofluidic time-stretch microscopy: recent advances

Science.gov (United States)

Lei, Cheng; Nitta, Nao; Ozeki, Yasuyuki; Goda, Keisuke

2018-04-01

Flow cytometry is an indispensable method for valuable applications in numerous fields such as immunology, pathology, pharmacology, molecular biology, and marine biology. Optofluidic time-stretch microscopy is superior to conventional flow cytometry methods for its capability to acquire high-quality images of single cells at a high-throughput exceeding 10,000 cells per second. This makes it possible to extract copious information from cellular images for accurate cell detection and analysis with the assistance of machine learning. Optofluidic time-stretch microscopy has proven its effectivity in various applications, including microalga-based biofuel production, evaluation of thrombotic disorders, as well as drug screening and discovery. In this review, we discuss the principles and recent advances of optofluidic time-stretch microscopy.

Stretch due to Penile Prosthesis Reservoir Migration

Directory of Open Access Journals (Sweden)

E. Baten

2016-03-01

Full Text Available A 43-year old patient presented to the emergency department with stretch, due to impossible deflation of the penile prosthesis, 4 years after successful implant. A CT-scan showed migration of the reservoir to the left rectus abdominis muscle. Refilling of the reservoir was inhibited by muscular compression, causing stretch. Removal and replacement of the reservoir was performed, after which the prosthesis was well-functioning again. Migration of the penile prosthesis reservoir is extremely rare but can cause several complications, such as stretch.

Modification of Spastic Stretch Reflexes at the Elbow by Flexion Synergy Expression in Individuals With Chronic Hemiparetic Stroke.

Science.gov (United States)

McPherson, Jacob G; Stienen, Arno H; Drogos, Justin M; Dewald, Julius P

2018-03-01

To systematically characterize the effect of flexion synergy expression on the manifestation of elbow flexor stretch reflexes poststroke, and to relate these findings to elbow flexor stretch reflexes in individuals without neurologic injury. Controlled cohort study. Academic medical center. Participants (N=20) included individuals with chronic hemiparetic stroke (n=10) and a convenience sample of individuals without neurologic or musculoskeletal injury (n=10). Participants with stroke were interfaced with a robotic device that precisely manipulated flexion synergy expression (by regulating shoulder abduction loading) while delivering controlled elbow extension perturbations over a wide range of velocities. This device was also used to elicit elbow flexor stretch reflexes during volitional elbow flexor activation, both in the cohort of individuals with stroke and in a control cohort. In both cases, the amplitude of volitional elbow flexor preactivation was matched to that generated involuntarily during flexion synergy expression. The amplitude of short- and long-latency stretch reflexes in the biceps brachii, assessed by electromyography, and expressed as a function of background muscle activation and stretch velocity. Increased shoulder abduction loading potentiated elbow flexor stretch reflexes via flexion synergy expression in the paretic arm. Compared with stretch reflexes in individuals without neurologic injury, paretic reflexes were larger at rest but were approximately equal to control muscles at matched levels of preactivation. Because flexion synergy expression modifies stretch reflexes in involved muscles, interventions that reduce flexion synergy expression may confer the added benefit of reducing spasticity during functional use of the arm. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Effectiveness of Manual Therapy and Stretching for Baseball Players With Shoulder Range of Motion Deficits.

Science.gov (United States)

Bailey, Lane B; Thigpen, Charles A; Hawkins, Richard J; Beattie, Paul F; Shanley, Ellen

Baseball players displaying deficits in shoulder range of motion (ROM) are at increased risk of arm injury. Currently, there is a lack of consensus regarding the best available treatment options to restore shoulder ROM. Instrumented manual therapy with self-stretching will result in clinically significant deficit reductions when compared with self-stretching alone. Controlled laboratory study. Shoulder ROM and humeral torsion were assessed in 60 active baseball players (mean age, 19 ± 2 years) with ROM deficits (nondominant - dominant, ≥15°). Athletes were randomly assigned to receive a single treatment of instrumented manual therapy plus self-stretching (n = 30) or self-stretching only (n = 30). Deficits in internal rotation, horizontal adduction, and total arc of motion were compared between groups immediately before and after a single treatment session. Treatment effectiveness was determined by mean comparison data, and a number-needed-to-treat (NNT) analysis was used for assessing the presence of ROM risk factors. Prior to intervention, players displayed significant ( P < 0.001) dominant-sided deficits in internal rotation (-26°), total arc of motion (-18°), and horizontal adduction (-17°). After the intervention, both groups displayed significant improvements in ROM, with the instrumented manual therapy plus self-stretching group displaying greater increases in internal rotation (+5°, P = 0.010), total arc of motion (+6°, P = 0.010), and horizontal adduction (+7°, P = 0.004) compared with self-stretching alone. For horizontal adduction deficits, the added use of instrumented manual therapy with self-stretching decreased the NNT to 2.2 (95% CI, 2.1-2.4; P = 0.010). Instrumented manual therapy with self-stretching significantly reduces ROM risk factors in baseball players with motion deficits when compared with stretching alone. The added benefits of manual therapy may help to reduce ROM deficits in clinical scenarios where stretching alone is

Effects of Combining Running and Practical Duration Stretching on Proprioceptive Skills of National Sprinters.

Science.gov (United States)

Romero-Franco, Natalia; Párraga-Montilla, Juan Antonio; Molina-Flores, Enrique M; Jiménez-Reyes, Pedro

2018-06-01

Romero-Franco, N, Párraga-Montilla, JA, Molina-Flores, EM, and Jiménez-Reyes, P. Effects of combining running and practical duration stretching on proprioceptive skills of national sprinters. J Strength Cond Res XX(X): 000-000, 2018-Practical duration stretching after aerobic activities is a recommended component of the first part of warm-up because of its effects on performance. However, its effects on proprioceptive skills are unknown. This study aimed to analyze the effects of running and practical duration static stretching (SS) and dynamic stretching (DS) on postural balance and the joint position sense (JPS) of national sprinters. Thirty-two national sprinters were randomly classified into a SS group (n = 11), DS group (n = 11), or control group (n = 10). Static stretching performed 5 minutes of running and short-duration (20 seconds) static stretches; DS performed 5 minutes of running and short-duration dynamic (20 seconds) stretches; and the control group performed 5 minutes of running. Before and after the intervention, unipedal static postural balance and knee JPS were evaluated. Static stretching exhibited a more centralized center of pressure in the medial-lateral plane for unipedal static postural balance in right-leg support after stretching (p = 0.005, d = 1.24), whereas DS showed values further from the center after stretching for the same unipedal support compared with baseline (p = 0.042, d = 0.49), and the control group remained stable (p > 0.05). Joint position sense did not show significant differences in any group (p > 0.05). In conclusion, combining running and practical duration SS may be beneficial for right-leg postural stabilization, whereas DS may be partly and slightly deleterious. Both SS and DS combined with running and running alone have neutral effects on knee JPS. Sports professionals should consider running and practical duration SS as part of the warm-up of sprinters to partly improve unipedal static postural balance.

Mechanical stretching for tissue engineering: two-dimensional and three-dimensional constructs.

Science.gov (United States)

Riehl, Brandon D; Park, Jae-Hong; Kwon, Il Keun; Lim, Jung Yul

2012-08-01

Mechanical cell stretching may be an attractive strategy for the tissue engineering of mechanically functional tissues. It has been demonstrated that cell growth and differentiation can be guided by cell stretch with minimal help from soluble factors and engineered tissues that are mechanically stretched in bioreactors may have superior organization, functionality, and strength compared with unstretched counterparts. This review explores recent studies on cell stretching in both two-dimensional (2D) and three-dimensional (3D) setups focusing on the applications of stretch stimulation as a tool for controlling cell orientation, growth, gene expression, lineage commitment, and differentiation and for achieving successful tissue engineering of mechanically functional tissues, including cardiac, muscle, vasculature, ligament, tendon, bone, and so on. Custom stretching devices and lab-specific mechanical bioreactors are described with a discussion on capabilities and limitations. While stretch mechanotransduction pathways have been examined using 2D stretch, studying such pathways in physiologically relevant 3D environments may be required to understand how cells direct tissue development under stretch. Cell stretch study using 3D milieus may also help to develop tissue-specific stretch regimens optimized with biochemical feedback, which once developed will provide optimal tissue engineering protocols.

Immediate effects of different types of stretching exercises on badminton jump smash.

Science.gov (United States)

Jang, Hwi S; Kim, Daeho; Park, Jihong

2018-01-01

Since different types of stretching exercises may alter athletic performance, we compared the effects of three types of stretching exercises on badminton jump smash. Sixteen male collegiate badminton players performed one of three different stretching exercises in a counterbalanced order on different days. Static stretching had seven typical stretches, while dynamic stretching involved nine dynamic movements, and resistance dynamic stretching was performed with weighted vests and dumbbells. Before and after each stretching exercise, subjects performed 20 trials of jump smashes. Dependent measurements were the jump heights during jump smashes, velocities of jump-smashed shuttlecocks, and drop point of jump-smashed shuttlecocks. To test the effects of each stretching exercise, we performed mixed model ANOVAs and calculated between-time effect sizes (ES). Each stretching exercise improved the jump heights during jump smashes (type main effect: F(2,75)=1.19, P=0.31; static stretching: 22.1%, Pjump-smashed shuttlecocks (type main effect: F(2,75)=2.18, P=0.12; static stretching: 5.7%, P=0.61, ES=0.39; dynamic stretching: 3.4%, P=0.94, ES=0.28; resistance dynamic stretching: 6%, P=0.50, ES=0.66). However, there were no differences among the stretching exercises for any measurement. The drop point of jump-smashed shuttlecocks did not change (interaction: F(2,75)=0.88, P=0.42). All stretching exercises improved badminton jump smash performance, but we could not determine the best protocol. Since badminton requires high-speed movement and explosive force, we suggest performing dynamic stretching or resistance dynamic stretching.

Modulation of KCNQ4 channel activity by changes in cell volume

DEFF Research Database (Denmark)

Hougaard, Charlotte; Klaerke, Dan A; Hoffmann, Else K

2004-01-01

KCNQ4 channels expressed in HEK 293 cells are sensitive to cell volume changes, being activated by swelling and inhibited by shrinkage, respectively. The KCNQ4 channels contribute significantly to the regulatory volume decrease (RVD) process following cell swelling. Under isoosmotic conditions...

Impact of the configuration of stretching and ocean-atmosphere coupling on tropical cyclone activity in the variable-resolution GCM ARPEGE

Energy Technology Data Exchange (ETDEWEB)

Daloz, Anne Sophie; Chauvin, Fabrice [CNRM-GAME, Groupe de Modelisation Grande Echelle et Climat, Toulouse Cedex 1 (France); Roux, Frank [Universite de Toulouse, Laboratoire d' Aerologie, Centre National de la Recherche Scientifique, Toulouse (France)

2012-11-15

This study starts by investigating the impact of the configuration of the variable-resolution atmospheric grid on tropical cyclone (TC) activity. The French atmospheric general circulation model ARPEGE, the grid of which is rotated and stretched over the North Atlantic basin, was used with prescribed sea surface temperatures. The study clearly shows that changing the position of the stretching pole strongly modifies the representation of TC activity over the North Atlantic basin. A pole in the centre of the North Atlantic basin provides the best representation of the TC activity for this region. In a second part, the variable-resolution climate model ARPEGE is coupled with the European oceanic global climate model NEMO in order to study the impact of ocean-atmosphere coupling on TC activity over the North Atlantic basin. Two pre-industrial runs, a coupled simulation and a simulation forced by the sea surface temperatures from the coupled one, are compared. The results show that the coupled simulation is more active in the Caribbean Sea and the Gulf of Mexico while the forced simulation is more active over eastern Florida and the eastern Atlantic. The difference in the distribution of TC activity is certainly linked with the location of TC genesis. In the forced simulation, tropical cyclogenesis is closer to the west African coast than in the coupled simulation. Moreover, the difference in TC activity over the eastern Atlantic seems to be related to two different mechanisms: the difference in African easterly wave activity over the west of Africa and the cooling produced, in the coupled simulation, by African easterly waves over the eastern Atlantic. Finally, the last part studies the impact of changing the frequency of ocean-atmosphere coupling on Atlantic TC activity. Increasing the frequency of coupling decreases the density of TC activity over the North Atlantic basin. However, it does not modify the spatial distribution of the TC activity. TC rainfalls are

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

Science.gov (United States)

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

2018-03-01

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

Up-Regulatory Effects of Curcumin on Large Conductance Ca2+-Activated K+ Channels

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Hei, Hongya; Li, Fangping; Wang, Yunman; Peng, Wen; Zhang, Xuemei

2015-01-01

Large conductance Ca2+-activated potassium channels (BK) are targets for research that explores therapeutic means to various diseases, owing to the roles of the channels in mediating multiple physiological processes in various cells and tissues. We investigated the pharmacological effects of curcumin, a compound isolated from the herb Curcuma longa, on BK channels. As recorded by whole-cell patch-clamp, curcumin increased BK (α) and BK (α+β1) currents in transfected HEK293 cells as well as the current density of BK in A7r5 smooth muscle cells in a dose-dependent manner. By incubating with curcumin for 24 hours, the current density of exogenous BK (α) in HEK293 cells and the endogenous BK in A7r5 cells were both enhanced notably, though the steady-state activation of the channels did not shift significantly, except for BK (α+β1). Curcumin up-regulated the BK protein expression without changing its mRNA level in A7r5 cells. The surface expression and the half-life of BK channels were also increased by curcumin in HEK293 cells. These effects of curcumin were abolished by MG-132, a proteasome inhibitor. Curcumin also increased ERK 1/2 phosphorylation, while inhibiting ERK by U0126 attenuated the curcumin-induced up-regulation of BK protein expression. We also observed that the curcumin-induced relaxation in the isolated rat aortic rings was significantly attenuated by paxilline, a BK channel specific blocker. These results show that curcumin enhances the activity of the BK channels by interacting with BK directly as well as enhancing BK protein expression through inhibiting proteasomal degradation and activating ERK signaling pathway. The findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and the underlying mechanisms. PMID:26672753

Up-Regulatory Effects of Curcumin on Large Conductance Ca2+-Activated K+ Channels.

Directory of Open Access Journals (Sweden)

Qijing Chen

Full Text Available Large conductance Ca2+-activated potassium channels (BK are targets for research that explores therapeutic means to various diseases, owing to the roles of the channels in mediating multiple physiological processes in various cells and tissues. We investigated the pharmacological effects of curcumin, a compound isolated from the herb Curcuma longa, on BK channels. As recorded by whole-cell patch-clamp, curcumin increased BK (α and BK (α+β1 currents in transfected HEK293 cells as well as the current density of BK in A7r5 smooth muscle cells in a dose-dependent manner. By incubating with curcumin for 24 hours, the current density of exogenous BK (α in HEK293 cells and the endogenous BK in A7r5 cells were both enhanced notably, though the steady-state activation of the channels did not shift significantly, except for BK (α+β1. Curcumin up-regulated the BK protein expression without changing its mRNA level in A7r5 cells. The surface expression and the half-life of BK channels were also increased by curcumin in HEK293 cells. These effects of curcumin were abolished by MG-132, a proteasome inhibitor. Curcumin also increased ERK 1/2 phosphorylation, while inhibiting ERK by U0126 attenuated the curcumin-induced up-regulation of BK protein expression. We also observed that the curcumin-induced relaxation in the isolated rat aortic rings was significantly attenuated by paxilline, a BK channel specific blocker. These results show that curcumin enhances the activity of the BK channels by interacting with BK directly as well as enhancing BK protein expression through inhibiting proteasomal degradation and activating ERK signaling pathway. The findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and the underlying mechanisms.

The effects of an active-assisted stretching program on functional performance in elderly persons: A pilot study

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Damian C Stanziano

2009-03-01

Full Text Available Damian C Stanziano1,2, Bernard A Roos1,2,3,4, Arlette C Perry1, Shenghan Lai5, Joseph F Signorile1,31Department of Exercise and Sport Sciences, University of Miami, Coral Gables, FL, USA; 2Stein Gerontological Institute, Miami Jewish Home and Hospital, Miami, FL, USA; 3Geriatric Research, Education, and Clinical Center, Miami VA Healthcare System, Miami, FL, USA; 4Departments of Medicine and Neurology, University of Miami Miller School of Medicine, Miami, FL, USA; 5Departments of Pathology and Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA Abstract: This study examined the impact of an eight-week active-assisted (AA stretching program on functionality, mobility, power, and range of motion (ROM in elderly residents of a residential retirement community. Seventeen volunteers (4 male, 13 female; 88.8 ± 5.36 years were randomly assigned to an AA or control group. The AA group performed 10 different AA stretches targeting the major joints of the body twice weekly for eight weeks. Controls attended classes requiring limited physical activity. All participants were assessed using four fl exibility and six functional tests, one week before and after the eight-week training period. A fully randomized repeated-measures ANCOVA with pretest scores as a covariate was used to detect differences between groups across time. The AA group demonstrated significant increases in ROM for most of the joints evaluated (p < 0.05 and significant increases in all performance measures (p < 0.05. Controls showed no improvements in functional or ROM measures (α = 0.05. Additionally, the AA group showed significantly better performance outcomes across the training period than controls. We conclude that our eight-week flexibility program effectively reduces age-related losses in ROM and improves functional performance in elderly persons with insufficient physical reserves to perform higher-intensity exercises.Keywords: proprioceptive neuromuscular

Lattice stretching bistability and dynamic heterogeneity

DEFF Research Database (Denmark)

Christiansen, Peter Leth; Savin, A. V.; Zolotaryuk, A. V.

2012-01-01

A simple one-dimensional lattice model is suggested to describe the experimentally observed plateau in force-stretching diagrams for some macromolecules. This chain model involves the nearest-neighbor interaction of a Morse-like potential (required to have a saturation branch) and a harmonic second......-neighbor coupling. Under an external stretching applied to the chain ends, the intersite Morse-like potential results in the appearance of a double-well potential within each chain monomer, whereas the interaction between the second neighbors provides a homogeneous bistable (degenerate) ground state, at least...... stretched bonds with a double-well potential. This case allows us to explain the existence of a plateau in the force-extension diagram for DNA and α-helix protein. Finally, the soliton dynamics are studied in detail....

Cell swelling activates separate taurine and chloride channels in Ehrlich mouse ascites tumor cells

DEFF Research Database (Denmark)

Lambert, Ian Henry; Hoffmann, Else Kay

1994-01-01

The taurine efflux from Ehrlich ascites tumor cells is stimulated by hypotonic cell swelling. The swelling-activated taurine efflux is unaffected by substitution of gluconate for extracellular Cl– but inhibited by addition of MK196 (anion channel blocker) and 4,4 -diisothiocyanostilbene-2......,2 -disulfonic acid (DIDS; anion channel and anion exchange blocker) and by depolarization of the cell membrane. This is taken to indicate that taurine does not leave the osmotically swollen Ehrlich cells in exchange for extracellular Cl–, i.e., via the anion exchanger but via a MK196- and DIDS-sensitive channel...... that is potential dependent. An additional stimulation of the swelling-activated taurine efflux is seen after addition of arachidonic acid and oleic acid. Cell swelling also activates a Mini Cl– channel. The Cl– efflux via this Cl– channel, in contrast to the swelling-activated taurine efflux, is unaffected by DIDS...

Comparing the effects of 3 weeks of upper-body vibration training, vibration and stretching, and stretching alone on shoulder flexibility in college-aged men.

Science.gov (United States)

Ferguson, Steven L; Kim, Eonho; Seo, Dong-Il; Bemben, Michael G

2013-12-01

This study compared the effects of 3 weeks of upper-body vibration training, vibration and stretching, and stretching alone on shoulder flexibility in college-aged men. Twenty-one men were randomly assigned to vibration-stretching (VS; n = 8), vibration only (VO; n = 6), or stretching only (SO; n = 7) groups that trained 3 times per week for 3 weeks. All 3 groups performed 9 total sets of 30-second stretches. The VS group performed four 30-second upper-body vibration exercises and five 30-second upper-body stretching exercises. The VO group performed nine 30-second upper-body vibration exercises. The SO group performed nine 30-second upper-body stretching exercises. Shoulder flexion (SF), shoulder extension (SE), and shoulder transverse extension (STE) were assessed by a Leighton Flexometer and back scratch tests bilaterally (BSR, BSL) were measured via tape measure. A 1-way analysis of variance (ANOVA) evaluated groups at baseline and a 2-way repeated-measures ANOVA evaluated the interventions over time. At baseline, there were no group differences in age, height, or weight. There was a significant (p alone or combined with stretching, is a viable alternative to a standard stretching routine when attempting to increase shoulder flexibility. Adding vibration training to a flexibility regimen may improve the likelihood of regularly performing flexibility sessions because of increased variety.

Comparison of the Effects of Local Cryotherapy and Passive Cross-Body Stretch on Extensibility in Subjects with Posterior Shoulder Tightness

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Kyue-nam Park

2014-03-01

Full Text Available The objective was to compare the immediate effects of local cryotherapy (LC and passive cross-body stretch on the extensibility of the posterior shoulder muscle in individuals with posterior shoulder tightness. Eighty-seven healthy subjects with a between-shoulder difference in internal rotation (IR range of motion (ROM greater than 10° were randomly divided into three groups: LC group, stretching group, and control group (n = 29 in each group. Subjects in the LC group received LC on infraspinatus and posterior deltoid muscles and subjects in the stretching group performed passive cross-body stretch. Stretch sensation was measured at the end range of passive IR and horizontal adduction (HA using numerical rating scale, and the pressure pain threshold (PPT at the infraspinatus and posterior deltoid muscles was measured using pressure algometry. Passive and active ROM of IR and HA of the glenohumeral joint were measured using an inclinometer. All measurements were performed at pre-intervention, post- intervention, and 10-min follow-up. Stretch sensation was significantly decreased and PPT was significantly increased in the LC and stretching groups at post-intervention, and these effects were maintained at 10-min follow-up, compared to the control group. Both the LC group and stretching group had a significantly greater increase in passive and active ROM of IR and HA, compared to the control group at post-intervention and 10-min follow-up. However, there were no significant differences in stretch sensation, PPT, or ROM of IR and HA between the LC group and stretching group. LC can be used to decrease the stretch sensation and increase PPT and ROM of IR and HA as much as a stretching exercise. LC could be an alternative method for increasing the restricted ROM of glenohumeral IR and HA for individuals with posterior shoulder tightness, especially for patients and sports players who have severe stretching discomfort.

Calcium-Activated Cl- Channel: Insights on the Molecular Identity in Epithelial Tissues.

Science.gov (United States)

Rottgen, Trey S; Nickerson, Andrew J; Rajendran, Vazhaikkurichi M

2018-05-10

Calcium-activated chloride secretion in epithelial tissues has been described for many years. However, the molecular identity of the channel responsible for the Ca 2+ -activated Cl − secretion in epithelial tissues has remained a mystery. More recently, TMEM16A has been identified as a new putative Ca 2+ -activated Cl − channel (CaCC). The primary goal of this article will be to review the characterization of TMEM16A, as it relates to the physical structure of the channel, as well as important residues that confer voltage and Ca 2+ -sensitivity of the channel. This review will also discuss the role of TMEM16A in epithelial physiology and potential associated-pathophysiology. This will include discussion of developed knockout models that have provided much needed insight on the functional localization of TMEM16A in several epithelial tissues. Finally, this review will examine the implications of the identification of TMEM16A as it pertains to potential novel therapies in several pathologies.

Multiple refraction switches realized by stretching elastomeric scatterers in sonic crystals

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Y. Huang

2015-02-01

Full Text Available The effect of out-of-plane pre-stretch on the 2D sonic crystal with stretchable elastomeric scatterers is explored. The hyperelastic scatterers are characterized by a compressible neo-Hookean model. The Dirichlet-to-Neumann (DtN map is adopted to obtain the band structure and equi-frequency contours. We focus on the first passband and find that a variety of switching functionalities for refraction behaviors can be realized in selected frequencies under a specific pre-stretch range. These refraction switches enable an active control of wave propagation and are applicable in advanced technologies where switchable and multifunctional sonic crystals are required.

5-HT1A receptors modulate small-conductance Ca2+-activated K+ channels

DEFF Research Database (Denmark)

Grunnet, Morten; Jespersen, Thomas; Perrier, Jean-François

2004-01-01

Small-conductance calcium-activated potassium channels (SK) are responsible for the medium afterhyperpolarisation (mAHP) following action potentials in neurons. Here we tested the ability of serotonin (5-HT) to modulate the activity of SK channels by coexpressing 5-HT1A receptors with different...

Ginseng gintonin activates the human cardiac delayed rectifier K+ channel: involvement of Ca2+/calmodulin binding sites.

Science.gov (United States)

Choi, Sun-Hye; Lee, Byung-Hwan; Kim, Hyeon-Joong; Jung, Seok-Won; Kim, Hyun-Sook; Shin, Ho-Chul; Lee, Jun-Hee; Kim, Hyoung-Chun; Rhim, Hyewhon; Hwang, Sung-Hee; Ha, Tal Soo; Kim, Hyun-Ji; Cho, Hana; Nah, Seung-Yeol

2014-09-01

Gintonin, a novel, ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, elicits [Ca(2+)]i transients in neuronal and non-neuronal cells via pertussis toxin-sensitive and pertussis toxin-insensitive G proteins. The slowly activating delayed rectifier K(+) (I(Ks)) channel is a cardiac K(+) channel composed of KCNQ1 and KCNE1 subunits. The C terminus of the KCNQ1 channel protein has two calmodulin-binding sites that are involved in regulating I(Ks) channels. In this study, we investigated the molecular mechanisms of gintonin-mediated activation of human I(Ks) channel activity by expressing human I(Ks) channels in Xenopus oocytes. We found that gintonin enhances IKs channel currents in concentration- and voltage-dependent manners. The EC50 for the I(Ks) channel was 0.05 ± 0.01 μg/ml. Gintonin-mediated activation of the I(Ks) channels was blocked by an LPA1/3 receptor antagonist, an active phospholipase C inhibitor, an IP3 receptor antagonist, and the calcium chelator BAPTA. Gintonin-mediated activation of both the I(Ks) channel was also blocked by the calmodulin (CaM) blocker calmidazolium. Mutations in the KCNQ1 [Ca(2+)]i/CaM-binding IQ motif sites (S373P, W392R, or R539W)blocked the action of gintonin on I(Ks) channel. However, gintonin had no effect on hERG K(+) channel activity. These results show that gintonin-mediated enhancement of I(Ks) channel currents is achieved through binding of the [Ca(2+)]i/CaM complex to the C terminus of KCNQ1 subunit.

Channelled scaffolds for engineering myocardium with mechanical stimulation.

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Zhang, Ting; Wan, Leo Q; Xiong, Zhuo; Marsano, Anna; Maidhof, Robert; Park, Miri; Yan, Yongnian; Vunjak-Novakovic, Gordana

2012-10-01

The characteristics of the matrix (composition, structure, mechanical properties) and external culture environment (pulsatile perfusion, physical stimulation) of the heart are important characteristics in the engineering of functional myocardial tissue. This study reports on the development of chitosan-collagen scaffolds with micropores and an array of parallel channels (~ 200 µm in diameter) that were specifically designed for cardiac tissue engineering using mechanical stimulation. The scaffolds were designed to have similar structural and mechanical properties of those of native heart matrix. Scaffolds were seeded with neonatal rat heart cells and subjected to dynamic tensile stretch using a custom designed bioreactor. The channels enhanced oxygen transport and facilitated the establishment of cell connections within the construct. The myocardial patches (14 mm in diameter, 1-2 mm thick) consisted of metabolically active cells that began to contract synchronously after 3 days of culture. Mechanical stimulation with high tensile stress promoted cell alignment, elongation, and expression of connexin-43 (Cx-43). This study confirms the importance of scaffold design and mechanical stimulation for the formation of contractile cardiac constructs. Copyright © 2011 John Wiley & Sons, Ltd.

Downregulation of Kv7.4 channel activity in primary and secondary hypertension

DEFF Research Database (Denmark)

Jepps, Thomas Andrew; Chadha, Preet S; Davis, Alison J

2011-01-01

Voltage-gated potassium (K(+)) channels encoded by KCNQ genes (Kv7 channels) have been identified in various rodent and human blood vessels as key regulators of vascular tone; however, nothing is known about the functional impact of these channels in vascular disease. We ascertained the effect of...... structurally different activators of Kv7.2 through Kv7.5 channels (BMS-204352, S-1, and retigabine) on blood vessels from normotensive and hypertensive animals.......Voltage-gated potassium (K(+)) channels encoded by KCNQ genes (Kv7 channels) have been identified in various rodent and human blood vessels as key regulators of vascular tone; however, nothing is known about the functional impact of these channels in vascular disease. We ascertained the effect of 3...

Biochemical and structural analysis of the hyperpolarization-activated K(+) channel MVP.

Science.gov (United States)

Randich, Amelia M; Cuello, Luis G; Wanderling, Sherry S; Perozo, Eduardo

2014-03-18

In contrast to the majority of voltage-gated ion channels, hyperpolarization-activated channels remain closed at depolarizing potentials and are activated at hyperpolarizing potentials. The basis for this reverse polarity is thought to be a result of differences in the way the voltage-sensing domain (VSD) couples to the pore domain. In the absence of structural data, the molecular mechanism of this reverse polarity coupling remains poorly characterized. Here we report the characterization of the structure and local dynamics of the closed activation gate (lower S6 region) of MVP, a hyperpolarization-activated potassium channel from Methanococcus jannaschii, by electron paramagnetic resonance (EPR) spectroscopy. We show that a codon-optimized version of MVP has high expression levels in Escherichia coli, is purified as a stable tetramer, and exhibits expected voltage-dependent activity when reconstituted in liposomes. EPR analysis of the mid to lower S6 region revealed positions exhibiting strong spin-spin coupling, indicating that the activation gate of MVP is closed at 0 mV. A comparison of local environmental parameters along the activation gate for MVP and KcsA indicates that MVP adopts a different closed conformation. These structural details set the stage for future evaluations of reverse electromechanical coupling in MVP.

Biochemical and Structural Analysis of the Hyperpolarization-Activated K+ Channel MVP

Science.gov (United States)

2015-01-01

In contrast to the majority of voltage-gated ion channels, hyperpolarization-activated channels remain closed at depolarizing potentials and are activated at hyperpolarizing potentials. The basis for this reverse polarity is thought to be a result of differences in the way the voltage-sensing domain (VSD) couples to the pore domain. In the absence of structural data, the molecular mechanism of this reverse polarity coupling remains poorly characterized. Here we report the characterization of the structure and local dynamics of the closed activation gate (lower S6 region) of MVP, a hyperpolarization-activated potassium channel from Methanococcus jannaschii, by electron paramagnetic resonance (EPR) spectroscopy. We show that a codon-optimized version of MVP has high expression levels in Escherichia coli, is purified as a stable tetramer, and exhibits expected voltage-dependent activity when reconstituted in liposomes. EPR analysis of the mid to lower S6 region revealed positions exhibiting strong spin–spin coupling, indicating that the activation gate of MVP is closed at 0 mV. A comparison of local environmental parameters along the activation gate for MVP and KcsA indicates that MVP adopts a different closed conformation. These structural details set the stage for future evaluations of reverse electromechanical coupling in MVP. PMID:24490868

Swell activated chloride channel function in human neutrophils

Energy Technology Data Exchange (ETDEWEB)

Salmon, Michael D. [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom); Ahluwalia, Jatinder, E-mail: j.ahluwalia@uel.ac.uk [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom)

2009-04-17

Non-excitable cells such as neutrophil granulocytes are the archetypal inflammatory immune cell involved in critical functions of the innate immune system. The electron current generated (I{sub e}) by the neutrophil NADPH oxidase is electrogenic and rapidly depolarises the membrane potential. For continuous function of the NADPH oxidase, I{sub e} has to be balanced to preserve electroneutrality, if not; sufficient depolarisation would prevent electrons from leaving the cell and neutrophil function would be abrogated. Subsequently, the depolarisation generated by the neutrophil NADPH oxidase I{sub e} must be counteracted by ion transport. The finding that depolarisation required counter-ions to compensate electron transport was followed by the observation that chloride channels activated by swell can counteract the NADPH oxidase membrane depolarisation. In this mini review, we discuss the research findings that revealed the essential role of swell activated chloride channels in human neutrophil function.

Acute effects of short and long duration dynamic stretching protocols on muscle strength

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Christiano Francisco dos Santos

Full Text Available Objective Compare the acute effects of dynamic stretching protocols on the isokinetic performance of the quadriceps and hamstring muscles at two velocities in adult males.Methodology Included the participation of 14 males (21 ± 2.6 years; 178 ± 0.4 cm; 73.2 ± 20.9 kg were assessed using an isokinetic dynamometer before and after following a short or long-duration dynamic stretching protocol or a control protocol. The results were assessed by a two-way ANOVA and a Scheffé’s post hoc test at a 5% significance level.Results No difference was found in the variables assessed at 180°/s after LDDS. At 60°/s, LDDS reduced the power of the knee flexors. The control protocol reduced the power of the knee flexors and increased the power of the extensors. At 60°/s, the work of the knee flexors exhibited a reduction after LDDS. The control protocol resulted in a reduction in the work of the flexors. The peak torque angle exhibited a reduction in the extensors and flexors after LDDS and SDDS.Conclusion Dynamic stretching did not cause any change in the peak torque, which points to its possible use in activities involving velocity and muscle strength. The executing dynamic stretching before physical activities such as running and high-intensity sports might be beneficial by promoting increases in heart rate and in body temperature.

BSDB: the Biomolecule Stretching Database

Science.gov (United States)

Cieplak, Marek; Sikora, Mateusz; Sulkowska, Joanna I.; Witkowski, Bartlomiej

2011-03-01

Despite more than a decade of experiments on single biomolecule manipulation, mechanical properties of only several scores of proteins have been measured. A characteristic scale of the force of resistance to stretching, Fmax , has been found to range between ~ 10 and 480 pN. The Biomolecule Stretching Data Base (BSDB) described here provides information about expected values of Fmax for, currently, 17 134 proteins. The values and other characteristics of the unfolding proces, including the nature of identified mechanical clamps, are available at www://info.ifpan.edu.pl/BSDB/. They have been obtained through simulations within a structure-based model which correlates satisfactorily with the available experimental data on stretching. BSDB also lists experimental data and results of the existing all-atom simulations. The database offers a Protein-Data-Bank-wide guide to mechano-stability of proteins. Its description is provided by a forthcoming Nucleic Acids Research paper. Supported by EC FUNMOL project FP7-NMP-2007-SMALL-1, and European Regional Development Fund: Innovative Economy (POIG.01.01.02-00-008/08).

Activation of protein kinase C alters the intracellular distribution and mobility of cardiac Na+ channels.

Science.gov (United States)

Hallaq, Haifa; Wang, Dao W; Kunic, Jennifer D; George, Alfred L; Wells, K Sam; Murray, Katherine T

2012-02-01

Na(+) current derived from expression of the cardiac isoform SCN5A is reduced by receptor-mediated or direct activation of protein kinase C (PKC). Previous work has suggested a possible role for loss of Na(+) channels at the plasma membrane in this effect, but the results are controversial. In this study, we tested the hypothesis that PKC activation acutely modulates the intracellular distribution of SCN5A channels and that this effect can be visualized in living cells. In human embryonic kidney cells that stably expressed SCN5A with green fluorescent protein (GFP) fused to the channel COOH-terminus (SCN5A-GFP), Na(+) currents were suppressed by an exposure to PKC activation. Using confocal microscopy, colocalization of SCN5A-GFP channels with the plasma membrane under control and stimulated conditions was quantified. A separate population of SCN5A channels containing an extracellular epitope was immunolabeled to permit temporally stable labeling of the plasma membrane. Our results demonstrated that Na(+) channels were preferentially trafficked away from the plasma membrane by PKC activation, with a major contribution by Ca(2+)-sensitive or conventional PKC isoforms, whereas stimulation of protein kinase A (PKA) had the opposite effect. Removal of the conserved PKC site Ser(1503) or exposure to the NADPH oxidase inhibitor apocynin eliminated the PKC-mediated effect to alter channel trafficking, indicating that both channel phosphorylation and ROS were required. Experiments using fluorescence recovery after photobleaching demonstrated that both PKC and PKA also modified channel mobility in a manner consistent with the dynamics of channel distribution. These results demonstrate that the activation of protein kinases can acutely regulate the intracellular distribution and molecular mobility of cardiac Na(+) channels in living cells.

A chimeric prokaryotic pentameric ligand–gated channel reveals distinct pathways of activation

Science.gov (United States)

Schmandt, Nicolaus; Velisetty, Phanindra; Chalamalasetti, Sreevatsa V.; Stein, Richard A.; Bonner, Ross; Talley, Lauren; Parker, Mark D.; Mchaourab, Hassane S.; Yee, Vivien C.; Lodowski, David T.

2015-01-01

Recent high resolution structures of several pentameric ligand–gated ion channels have provided unprecedented details of their molecular architecture. However, the conformational dynamics and structural rearrangements that underlie gating and allosteric modulation remain poorly understood. We used a combination of electrophysiology, double electron–electron resonance (DEER) spectroscopy, and x-ray crystallography to investigate activation mechanisms in a novel functional chimera with the extracellular domain (ECD) of amine-gated Erwinia chrysanthemi ligand–gated ion channel, which is activated by primary amines, and the transmembrane domain of Gloeobacter violaceus ligand–gated ion channel, which is activated by protons. We found that the chimera was independently gated by primary amines and by protons. The crystal structure of the chimera in its resting state, at pH 7.0 and in the absence of primary amines, revealed a closed-pore conformation and an ECD that is twisted with respect to the transmembrane region. Amine- and pH-induced conformational changes measured by DEER spectroscopy showed that the chimera exhibits a dual mode of gating that preserves the distinct conformational changes of the parent channels. Collectively, our findings shed light on both conserved and divergent features of gating mechanisms in this class of channels, and will facilitate the design of better allosteric modulators. PMID:26415570

Cholesterol regulates HERG K+ channel activation by increasing phospholipase C β1 expression.

Science.gov (United States)

Chun, Yoon Sun; Oh, Hyun Geun; Park, Myoung Kyu; Cho, Hana; Chung, Sungkwon

2013-01-01

Human ether-a-go-go-related gene (HERG) K(+) channel underlies the rapidly activating delayed rectifier K(+) conductance (IKr) during normal cardiac repolarization. Also, it may regulate excitability in many neuronal cells. Recently, we showed that enrichment of cell membrane with cholesterol inhibits HERG channels by reducing the levels of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] due to the activation of phospholipase C (PLC). In this study, we further explored the effect of cholesterol enrichment on HERG channel kinetics. When membrane cholesterol level was mildly increased in human embryonic kidney (HEK) 293 cells expressing HERG channel, the inactivation and deactivation kinetics of HERG current were not affected, but the activation rate was significantly decelerated at all voltages tested. The application of PtdIns(4,5)P2 or inhibitor for PLC prevented the effect of cholesterol enrichment, while the presence of antibody against PtdIns(4,5)P2 in pipette solution mimicked the effect of cholesterol enrichment. These results indicate that the effect of cholesterol enrichment on HERG channel is due to the depletion of PtdIns(4,5)P2. We also found that cholesterol enrichment significantly increases the expression of β1 and β3 isoforms of PLC (PLCβ1, PLCβ3) in the membrane. Since the effects of cholesterol enrichment on HERG channel were prevented by inhibiting transcription or by inhibiting PLCβ1 expression, we conclude that increased PLCβ1 expression leads to the deceleration of HERG channel activation rate via downregulation of PtdIns(4,5)P2. These results confirm a crosstalk between two plasma membrane-enriched lipids, cholesterol and PtdIns(4,5)P2, in the regulation of HERG channels.

Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

Science.gov (United States)

Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

2015-05-01

Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

The stretch reflex and the contributions of C David Marsden

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Kalyan B Bhattacharyya

2017-01-01

Full Text Available The stretch reflex or myotatic reflex refers to the contraction of a muscle in response to its passive stretching by increasing its contractility as long as the stretch is within physiological limits. For ages, it was thought that the stretch reflex was of short latency and it was synonymous with the tendon reflex, subserving the same spinal reflex arc. However, disparities in the status of the two reflexes in certain clinical situations led Marsden and his collaborators to carry out a series of experiments that helped to establish that the two reflexes had different pathways. That the two reflexes are dissociated has been proved by the fact that the stretch reflex and the tendon reflex, elicited by stimulation of the same muscle, have different latencies, that of the stretch reflex being considerably longer. They hypothesized that the stretch reflex had a transcortical course before it reached the spinal motor neurons for final firing. Additionally, the phenomenon of stimulus-sensitive cortical myoclonus lent further evidence to the presence of the transcortical loop where the EEG correlate preceded the EMG discharge. This concept has been worked out by later neurologists in great detail , and the general consensus is that indeed, the stretch reflex is endowed with a conspicuous transcortical component.

Randomized Trial of Modified Stretching Exercise Program for Menstrual Low Back Pain.

Science.gov (United States)

Chen, Huei-Mein; Hu, Hsou-Mei

2018-03-01

This study aimed to examine the effectiveness of a modified stretching exercise program on young women with menstrual low back pain. Overall, 127 young women were randomly assigned to the experimental ( n = 63) and control ( n = 64) groups. The experimental group followed the modified stretching exercise program, whereas the control group performed their usual activities. At 1, 4, 8, and 12 months, the experimental group had significantly lower scores on the visual analog scale for pain (95% confidence interval [CI] = [0.73, 1.96]; p < .05) and the Oswestry Low Back Pain Disability Questionnaire than the control group (95% CI = [0.68, 2.03]; p < .001). At 12 months, the experimental group showed significantly higher exercise self-efficacy than the control group (95% CI = [-6.87, 0.62]; p = .003). These findings can be used to enhance self-care capabilities by using the modified stretching exercise program for young women with menstrual low back pain.

Underwater image enhancement based on the dark channel prior and attenuation compensation

Science.gov (United States)

Guo, Qingwen; Xue, Lulu; Tang, Ruichun; Guo, Lingrui

2017-10-01

Aimed at the two problems of underwater imaging, fog effect and color cast, an Improved Segmentation Dark Channel Prior (ISDCP) defogging method is proposed to solve the fog effects caused by physical properties of water. Due to mass refraction of light in the process of underwater imaging, fog effects would lead to image blurring. And color cast is closely related to different degree of attenuation while light with different wavelengths is traveling in water. The proposed method here integrates the ISDCP and quantitative histogram stretching techniques into the image enhancement procedure. Firstly, the threshold value is set during the refinement process of the transmission maps to identify the original mismatching, and to conduct the differentiated defogging process further. Secondly, a method of judging the propagating distance of light is adopted to get the attenuation degree of energy during the propagation underwater. Finally, the image histogram is stretched quantitatively in Red-Green-Blue channel respectively according to the degree of attenuation in each color channel. The proposed method ISDCP can reduce the computational complexity and improve the efficiency in terms of defogging effect to meet the real-time requirements. Qualitative and quantitative comparison for several different underwater scenes reveals that the proposed method can significantly improve the visibility compared with previous methods.

Activation gating kinetics of GIRK channels are mediated by cytoplasmic residues adjacent to transmembrane domains.

Science.gov (United States)

Sadja, Rona; Reuveny, Eitan

2009-01-01

G-protein-coupled inwardly rectifying potassium channels (GIRK/Kir3.x) are involved in neurotransmission-mediated reduction of excitability. The gating mechanism following G protein activation of these channels likely proceeds from movement of inner transmembrane helices to allow K(+) ions movement through the pore of the channel. There is limited understanding of how the binding of G-protein betagamma subunits to cytoplasmic regions of the channel transduces the signal to the transmembrane regions. In this study, we examined the molecular basis that governs the activation kinetics of these channels, using a chimeric approach. We identified two regions as being important in determining the kinetics of activation. One region is the bottom of the outer transmembrane helix (TM1) and the cytoplasmic domain immediately adjacent (the slide helix); and the second region is the bottom of the inner transmembrane helix (TM2) and the cytoplasmic domain immediately adjacent. Interestingly, both of these regions are sufficient in mediating the kinetics of fast activation gating. This result suggests that there is a cooperative movement of either one of these domains to allow fast and efficient activation gating of GIRK channels.

Localization of Ca2+ -activated big-conductance K+ channels in rabbit distal colon

DEFF Research Database (Denmark)

Hay-Schmidt, Anders; Grunnet, Morten; Abrahamse, Salomon L

2003-01-01

Big-conductance Ca(2+)-activated K(+) channels (BK channels) may play an important role in the regulation of epithelial salt and water transport, but little is known about the expression level and the precise localization of BK channels in epithelia. The aim of the present study was to quantify a...

Immunolocalization and expression of small-conductance calcium-activated potassium channels in human myometrium

DEFF Research Database (Denmark)

Rosenbaum, Sofia T; Svalø, Julie; Nielsen, Karsten

2012-01-01

Small-conductance calcium-activated potassium (SK3) channels have been detected in human myometrium and we have previously shown a functional role of SK channels in human myometrium in vitro. The aims of this study were to identify the precise localization of SK3 channels and to quantify SK3 m....... This is the first report to provide evidence for a possible role of SK3 channels in human uterine telocytes....

Functional expression of TRPM8 and TRPA1 channels in rat odontoblasts.

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Maki Tsumura

Full Text Available Odontoblasts produce dentin during development, throughout life, and in response to pathological conditions by sensing stimulation of exposed dentin. The functional properties and localization patterns of transient receptor potential (TRP melastatin subfamily member 8 (TRPM8 and ankyrin subfamily member 1 (TRPA1 channels in odontoblasts remain to be clarified. We investigated the localization and the pharmacological, biophysical, and mechano-sensitive properties of TRPM8 and TRPA1 channels in rat odontoblasts. Menthol and icilin increased the intracellular free Ca(2+ concentration ([Ca(2+]i. Icilin-, WS3-, or WS12-induced [Ca(2+]i increases were inhibited by capsazepine or 5-benzyloxytriptamine. The increase in [Ca(2+]i elicited by allyl isothiocyanate (AITC was inhibited by HC030031. WS12 and AITC exerted a desensitizing effect on [Ca(2+]i increase. Low-temperature stimuli elicited [Ca(2+]i increases that are sensitive to both 5-benzyloxytriptamine and HC030031. Hypotonic stimulation-induced membrane stretch increased [Ca(2+]i; HC030031 but not 5-benzyloxytriptamine inhibited the effect. The results suggest that TRPM8 channels in rat odontoblasts play a role in detecting low-temperature stimulation of the dentin surface and that TRPA1 channels are involved in sensing membrane stretching and low-temperature stimulation. The results also indicate that odontoblasts act as mechanical and thermal receptor cells, detecting the stimulation of exposed dentin to drive multiple cellular functions, such as sensory transduction.

ALTERNATIVE EQUATIONS FOR DYNAMIC BEHAVIOR OF IONIC CHANNEL ACTIVATION AND INACTIVATION GATES

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Mahmut ÖZER

2003-03-01

Full Text Available In this paper, alternative equations for dynamics of ionic channel activation and inactivation gates are proposed based on the path probability method. Dynamic behavior of a voltage-gated ionic channel is modeled by the conventional Hodgkin-Huxley (H-H mathematical formalism. In that model, conductance of the channel is defined in terms of activation and inactivation gates. Dynamics of the activation and inactivation gates is modeled by first-order differential equations dependent on the gate variable and the membrane potential. In the new approach proposed in this study, dynamic behavior of activation and inactivation gates is modeled by a firstorder differential equation dependent on internal energy and membrane potential by using the path probability method which is widely used in statistical physics. The new model doesn't require the time constant and steadystate values which are used explicitly in the H-H model. The numerical results show validity of the proposed method.

The potent activation of Ca(2+)-activated K(+) current by NVP-AUY922 in the human pancreatic duct cell line (PANC-1) possibly independent of heat shock protein 90 inhibition.

Science.gov (United States)

Chiang, Nai-Jung; Wu, Sheng-Nan; Chen, Li-Tzong

2015-04-01

NVP-AUY922 (AUY) is a potent inhibitor of heat shock protein 90 (HSP90). Whether this compound can exert additional effects on membrane ion channels remains elusive. We investigated the effect of AUY on ion currents in human pancreatic duct epithelial cells (PDECs), including PANC-1 and MIA PaCa-2. AUY increased the amplitude of the K(+) current (IK) in PANC-1 cells shown by whole-cell configuration. Single-channel recordings revealed a large-conductance Ca(2+)-activated K(+) (BKCa) channel in PANC-1, but not in MIA PaCa-2. In cell-attached mode, AUY increased the probability of BKCa channel opening and also potentiated the activity of stretch-induced channels. However, other HSP inhibitors, 17-AAG or BIIB021 only slightly increased the activity of BKCa channels. In inside-out recordings, sodium hydrosulphide or caffeic acid phenethyl ester increased the activity of BKCa channels, but AUY did not. We further evaluated whether conductance of Ca(2+)-activated K(+) channels (IK(Ca)) influenced secretion of HCO3(-) and fluid in PDECs by using a modified Whitcomb-Ermentrout model. Simulation studies showed that an increase in IK(Ca) resulted in additional secretion of HCO3(-) and fluid by mimicking the effect of AUY in PDECs. Collectively, AUY can interact with the BKCa channel to largely increase IK(Ca) in PDECs. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Osteopontin activates the diabetes-associated potassium channel TALK-1 in pancreatic β-cells.

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Matthew T Dickerson

Full Text Available Glucose-stimulated insulin secretion (GSIS relies on β-cell Ca2+ influx, which is modulated by the two-pore-domain K+ (K2P channel, TALK-1. A gain-of-function polymorphism in KCNK16, the gene encoding TALK-1, increases risk for developing type-2 diabetes. While TALK-1 serves an important role in modulating GSIS, the regulatory mechanism(s that control β-cell TALK-1 channels are unknown. Therefore, we employed a membrane-specific yeast two-hybrid (MYTH assay to identify TALK-1-interacting proteins in human islets, which will assist in determining signaling modalities that modulate TALK-1 function. Twenty-one proteins from a human islet cDNA library interacted with TALK-1. Some of these interactions increased TALK-1 activity, including intracellular osteopontin (iOPN. Intracellular OPN is highly expressed in β-cells and is upregulated under pre-diabetic conditions to help maintain normal β-cell function; however, the functional role of iOPN in β-cells is poorly understood. We found that iOPN colocalized with TALK-1 in pancreatic sections and coimmunoprecipitated with human islet TALK-1 channels. As human β-cells express two K+ channel-forming variants of TALK-1, regulation of these TALK-1 variants by iOPN was assessed. At physiological voltages iOPN activated TALK-1 transcript variant 3 channels but not TALK-1 transcript variant 2 channels. Activation of TALK-1 channels by iOPN also hyperpolarized resting membrane potential (Vm in HEK293 cells and in primary mouse β-cells. Intracellular OPN was also knocked down in β-cells to test its effect on β-cell TALK-1 channel activity. Reducing β-cell iOPN significantly decreased TALK-1 K+ currents and increased glucose-stimulated Ca2+ influx. Importantly, iOPN did not affect the function of other K2P channels or alter Ca2+ influx into TALK-1 deficient β-cells. These results reveal the first protein interactions with the TALK-1 channel and found that an interaction with iOPN increased �

Structural mechanism underlying capsaicin binding and activation of TRPV1 ion channel

OpenAIRE

Yang, Fan; Xiao, Xian; Cheng, Wei; Yang, Wei; Yu, Peilin; Song, Zhenzhen; Yarov-Yarovoy, Vladimir; Zheng, Jie

2015-01-01

Capsaicin bestows spiciness by activating TRPV1 channel with exquisite potency and selectivity. Capsaicin-bound channel structure was previously resolved by cryo-EM at 4.2-to-4.5 ? resolution, however important details required for mechanistic understandings are unavailable: capsaicin was registered as a small electron density, reflecting neither its chemical structure nor specific ligand-channel interactions. We obtained the missing atomic-level details by iterative computation, which were c...

Summary of the stretching tectonics research

International Nuclear Information System (INIS)

Yu Dagan

1994-01-01

The rise of stretching tectonics is established on the basis of recent structural geology theory, the establishment of metamorphic nucleus complex structural model on one hand plays an important promoting art to the development of stretching structure, on the other hand, it needs constant supplement and perfection in practice. Metamorphic nucleus complex is the carrier of comparatively deep geological information in vertical section of the crust and has wide distribution in the era of south China. Evidently, it can be taken as the 'key' to understanding the deep and studying the basement, Strengthening the study will play the important promoting role to the deep prospecting. The study of stretching tectonics is not only limited within the range of structure and metamorphism, but combine with the studies of sedimentation, magmatism, metamorphism and mineralization, thus form a new field of tectonic geology of self-developing system

Melatonin mediates vasodilation through both direct and indirect activation of BKCa channels.

Science.gov (United States)

Zhao, T; Zhang, H; Jin, C; Qiu, F; Wu, Y; Shi, L

2017-10-01

Melatonin, synthesized primarily by the pineal gland, is a neuroendocrine hormone with high membrane permeability. The vascular effects of melatonin, including vasoconstriction and vasodilation, have been demonstrated in numerous studies. However, the mechanisms underlying these effects are not fully understood. Large-conductance Ca 2+ -activated K + (BK Ca ) channels are expressed broadly on smooth muscle cells and play an important role in vascular tone regulation. This study explored the mechanisms of myocyte BK Ca channels and endothelial factors underlying the action of melatonin on the mesenteric arteries (MAs). Vascular contractility and patch-clamp studies were performed on myocytes of MAs from Wistar rats. Melatonin induced significant vasodilation on MAs. In the presence of N ω -nitro-l-arginine methyl ester (l-NAME), a potent endothelial oxide synthase (eNOS) inhibitor, melatonin elicited concentration-dependent relaxation, with lowered pIC 50 The effect of melatonin was significantly attenuated in the presence of BK Ca channel blocker iberiotoxin or MT1/MT2 receptor antagonist luzindole in both (+) l-NAME and (-) l-NAME groups. In the (+) l-NAME group, iberiotoxin caused a parallel rightward shift of the melatonin concentration-relaxation curve, with pIC 50 lower than that of luzindole. Both inside-out and cell-attached patch-clamp recordings showed that melatonin significantly increased the open probability, mean open time and voltage sensitivity of BK Ca channels. In a cell-attached patch-clamp configuration, the melatonin-induced enhancement of BK Ca channel activity was significantly suppressed by luzindole. These findings indicate that in addition to the activation of eNOS, melatonin-induced vasorelaxation of MAs is partially attributable to its direct (passing through the cell membrane) and indirect (via MT1/MT2 receptors) activation of the BK Ca channels on mesenteric arterial myocytes. © 2017 Society for Endocrinology.

Cl- channels of the gastric parietal cell that are active at low pH.

Science.gov (United States)

Cuppoletti, J; Baker, A M; Malinowska, D H

1993-06-01

HCl secretion across mammalian gastric parietal cell apical membrane may involve Cl- channels. H(+)-K(+)-ATPase-containing membranes isolated from gastric mucosa of histamine-stimulated rabbits were fused to planar lipid bilayers. Channels were recorded with symmetric 800 mM CsCl solutions, pH 7.4. A linear current-voltage (I-V) relationship was obtained, and conductance was 28 +/- 1 pS at 800 mM CsCl. Conductance was 6.9 +/- 2 pS at 150 mM CsCl. Reversal potential was +22 mV with a fivefold cis-trans CsCl concentration gradient, indicating that the channel was anion selective with a discrimination ratio of 6:1 for Cl- over Cs+. Anion selectivity of the channel was I- > Cl- > or = Br- > NO3-, and gluconate was impermeant. Channels obtained at pH 7.4 persisted when pH of medium bathing the trans side of the bilayer (pHtrans) was reduced to pH 3, without a change in conductance, linearity of I-V relationship, or ion selectivity. In contrast, asymmetric reduction of pH of medium bathing the cis side of the bilayer from 7.4 to 3 always resulted in loss of channel activity. At pH 7.4, open probability (Po) of the channel was voltage dependent, i.e., predominantly open at +80 mV but mainly closed at -80 mV. In contrast, with low pHtrans, channel Po at -80 mV was increased 3.5-fold. The Cl- channel was Ca2+ indifferent. In absence of ionophores, ion selectivity for support of H(+)-K(+)-ATPase activity and H+ transport was consistent with that exhibited by the channel and could be limited by substitution with NO3-, whereas maximal H(+)-K(+)-ATPase activity was indifferent to anion present, demonstrating that anion transport can be rate limiting. Cl- channels with similar characteristics (conductance, linear I-V relationship, and ion selectivity) were also present in H(+)-K(+)-ATPase-containing vesicles isolated from resting (cimetidine-treated) gastric mucosa, exhibiting at -80 mV a pH-independent approximately 3.5-fold lower Po than stimulated vesicle channels. At -80 m

Effects of the small molecule HERG activator NS1643 on Kv11.3 channels.

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Arne Bilet

Full Text Available NS1643 is one of the small molecule HERG (Kv11.1 channel activators and has also been found to increase erg2 (Kv11.2 currents. We now investigated whether NS1643 is also able to act as an activator of Kv11.3 (erg3 channels expressed in CHO cells. Activation of rat Kv11.3 current occurred in a dose-dependent manner and maximal current increasing effects were obtained with 10 µM NS1643. At this concentration, steady-state outward current increased by about 80% and the current increase was associated with a significant shift in the voltage dependence of activation to more negative potentials by about 15 mV. In addition, activation kinetics were accelerated, whereas deactivation was slowed. There was no significant effect on the kinetics of inactivation and recovery from inactivation. The strong current-activating agonistic effect of NS1643 did not result from a shift in the voltage dependence of Kv11.3 channel inactivation and was independent from external Na(+ or Ca(2+. At the higher concentration of 20 µM, NS1643 induced clearly less current increase. The left shift in the voltage dependence of activation reversed and the voltage sensitivity of activation dramatically decreased along with a slowing of Kv11.3 channel activation. These data show that, in comparison to other Kv11 family members, NS1643 exerts distinct effects on Kv11.3 channels with especially pronounced partial antagonistic effects at higher concentration.

Slack sodium-activated potassium channel membrane expression requires p38 mitogen-activated protein kinase phosphorylation.

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Gururaj, Sushmitha; Fleites, John; Bhattacharjee, Arin

2016-04-01

p38 MAPK has long been understood as an inducible kinase under conditions of cellular stress, but there is now increasing evidence to support its role in the regulation of neuronal function. Several phosphorylation targets have been identified, an appreciable number of which are ion channels, implicating the possible involvement of p38 MAPK in neuronal excitability. The KNa channel Slack is an important protein to be studied as it is highly and ubiquitously expressed in DRG neurons and is important in the maintenance of their firing accommodation. We sought to examine if the Slack channel could be a substrate of p38 MAPK activity. First, we found that the Slack C-terminus contains two putative p38 MAPK phosphorylation sites that are highly conserved across species. Second, we show via electrophysiology experiments that KNa currents and further, Slack currents, are subject to tonic modulation by p38 MAPK. Third, biochemical approaches revealed that Slack channel regulation by p38 MAPK occurs through direct phosphorylation at the two putative sites of interaction, and mutating both sites prevented surface expression of Slack channels. Based on these results, we conclude that p38 MAPK is an obligate regulator of Slack channel function via the trafficking of channels into the membrane. The present study identifies Slack KNa channels as p38 MAPK substrates. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Japanese Stretching Intervention Can Modify Lumbar Lordosis Curvature.

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Kadono, Norio; Tsuchiya, Kazushi; Uematsu, Azusa; Kamoshita, Hiroshi; Kiryu, Kazunori; Hortobágyi, Tibor; Suzuki, Shuji

2017-08-01

Eighteen healthy male adults were assigned to either an intervention or control group. Isogai dynamic therapy (IDT) is one of Japanese stretching interventions and has been practiced for over 70 years. However, its scientific quantitative evidence remains unestablished. The objective of this study was to determine whether IDT could modify lumbar curvature in healthy young adults compared with stretching exercises used currently in clinical practice. None of previous studies have provided data that conventional stretching interventions could modify spinal curvatures. However, this study provides the first evidence that a specific form of a Japanese stretching intervention can acutely modify the spinal curvatures. We compared the effects of IDT, a Japanese stretching intervention (n=9 males), with a conventional stretching routine (n=9 males) used widely in clinics to modify pelvic tilt and lumbar lordosis (LL) angle. We measured thoracic kyphosis (TK) and LL angles 3 times during erect standing using the Spinal Mouse before and after each intervention. IDT consisted of: (1) hip joint correction, (2) pelvic tilt correction, (3) lumbar alignment correction, and (4) squat exercise stretch. The control group performed hamstring stretches while (1) standing and (2) sitting. IDT increased LL angle to 25.1 degrees (±5.9) from 21.2 degrees (±6.9) (P=0.047) without changing TK angle (pretest: 36.8 degrees [±6.9]; posttest: 36.1 degrees [±6.5]) (P=0.572). The control group showed no changes in TK (P=0.819) and LL angles (P=0.744). IDT can thus be effective for increasing LL angle, hence anterior pelvic tilt. Such modifications could ameliorate low back pain and improve mobility in old adults with an unfavorable pelvic position.

Dendritic calcium channels and their activation by synaptic signals in auditory coincidence detector neurons.

Science.gov (United States)

Blackmer, Trillium; Kuo, Sidney P; Bender, Kevin J; Apostolides, Pierre F; Trussell, Laurence O

2009-08-01

The avian nucleus laminaris (NL) encodes the azimuthal location of low-frequency sound sources by detecting the coincidence of binaural signals. Accurate coincidence detection requires precise developmental regulation of the lengths of the fine, bitufted dendrites that characterize neurons in NL. Such regulation has been suggested to be driven by local, synaptically mediated, dendritic signals such as Ca(2+). We examined Ca(2+) signaling through patch clamp and ion imaging experiments in slices containing nucleus laminaris from embryonic chicks. Voltage-clamp recordings of neurons located in the NL showed the presence of large Ca(2+) currents of two types, a low voltage-activated, fast inactivating Ni(2+) sensitive channel resembling mammalian T-type channels, and a high voltage-activated, slowly inactivating Cd(2+) sensitive channel. Two-photon Ca(2+) imaging showed that both channel types were concentrated on dendrites, even at their distal tips. Single action potentials triggered synaptically or by somatic current injection immediately elevated Ca(2+) throughout the entire cell. Ca(2+) signals triggered by subthreshold synaptic activity were highly localized. Thus when electrical activity is suprathreshold, Ca(2+) channels ensure that Ca(2+) rises in all dendrites, even those that are synaptically inactive.

The influence of stretching on tensile strength and solubility of poly(vinyl alcohol) fibres

NARCIS (Netherlands)

Heikens, D.; Bleijenberg, A.C.A.M.; Hoppenbrouwers, J.J.M.; Barentsen, W.M.

1971-01-01

The strength of wet-spun poly(vinyl alcohol) (pva) fibres is given as function of bath-stretching, wet-stretching and hot-stretching. In the two equations derived for strength of wet-stretching and hot-stretching the complex influence of the bath-stretching and hot-stretching is demonstrated. The

Mechanical stretching effect on the actuator performance of cellulose electroactive paper

International Nuclear Information System (INIS)

Kim, Jung-Hwan; Yun, Ki-Ju; Kim, Joo-Hyung; Kim, Jaehwan

2009-01-01

The mechanical stretching effect on the actuating performance of electroactive cellulose paper (EAPap) was studied. A lattice elongation of cellulose fibrils due to in-plane tensile stress along the stretching direction was observed by the x-ray diffraction method. The shrinkage of the fibril diameter as a function of stretching ratio was confirmed by surface and cross-sectional images. While the actuator performance in terms of bending displacement decreased as the stretching ratio increased, the resonance frequency linearly increased as the stretching ratio increased, which was compared with the theoretical frequency data found from a cantilever beam model. The actuator efficiency was evaluated from the electrical input power consumption and the mechanical output power of an EAPap actuator. It was revealed that the stretching process increased the electro-mechanical efficiency of the EAPap actuator. The mechanism of the influence of the stretching effect on the performance of an EAPap actuator is discussed

Spontaneous bending of pre-stretched bilayers.

Science.gov (United States)

DeSimone, Antonio

2018-01-01

We discuss spontaneously bent configurations of pre-stretched bilayer sheets that can be obtained by tuning the pre-stretches in the two layers. The two-dimensional nonlinear plate model we use for this purpose is an adaptation of the one recently obtained for thin sheets of nematic elastomers, by means of a rigorous dimensional reduction argument based on the theory of Gamma-convergence (Agostiniani and DeSimone in Meccanica. doi:10.1007/s11012-017-0630-4, 2017, Math Mech Solids. doi:10.1177/1081286517699991, arXiv:1509.07003, 2017). We argue that pre-stretched bilayer sheets provide us with an interesting model system to study shape programming and morphing of surfaces in other, more complex systems, where spontaneous deformations are induced by swelling due to the absorption of a liquid, phase transformations, thermal or electro-magnetic stimuli. These include bio-mimetic structures inspired by biological systems from both the plant and the animal kingdoms.

Optofluidic time-stretch quantitative phase microscopy.

Science.gov (United States)

Guo, Baoshan; Lei, Cheng; Wu, Yi; Kobayashi, Hirofumi; Ito, Takuro; Yalikun, Yaxiaer; Lee, Sangwook; Isozaki, Akihiro; Li, Ming; Jiang, Yiyue; Yasumoto, Atsushi; Di Carlo, Dino; Tanaka, Yo; Yatomi, Yutaka; Ozeki, Yasuyuki; Goda, Keisuke

2018-03-01

Innovations in optical microscopy have opened new windows onto scientific research, industrial quality control, and medical practice over the last few decades. One of such innovations is optofluidic time-stretch quantitative phase microscopy - an emerging method for high-throughput quantitative phase imaging that builds on the interference between temporally stretched signal and reference pulses by using dispersive properties of light in both spatial and temporal domains in an interferometric configuration on a microfluidic platform. It achieves the continuous acquisition of both intensity and phase images with a high throughput of more than 10,000 particles or cells per second by overcoming speed limitations that exist in conventional quantitative phase imaging methods. Applications enabled by such capabilities are versatile and include characterization of cancer cells and microalgal cultures. In this paper, we review the principles and applications of optofluidic time-stretch quantitative phase microscopy and discuss its future perspective. Copyright © 2017 Elsevier Inc. All rights reserved.

ACUTE EFFECTS OF THREE DIFFERENT STRETCHING PROTOCOLS ON THE WINGATE TEST PERFORMANCE

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Bruno L. Franco

2012-03-01

Full Text Available The purpose of this study was to examine the acute effects of different stretching exercises on the performance of the traditional Wingate test (WT. Fifteen male participants performed five WT; one for familiarization (FT, and the remaining four after no stretching (NS, static stretching (SS, dynamic stretching (DS, and proprioceptive neuromuscular facilitation (PNF. Stretches were targeted for the hamstrings, quadriceps, and calf muscles. Peak power (PP, mean power (MP, and the time to reach PP (TP were calculated. The MP was significantly lower when comparing the DS (7.7 ± 0.9 W/kg to the PNF (7.3 ± 0.9 W/kg condition (p < 0.05. For PP, significant differences were observed between more comparisons, with PNF stretching providing the lowest result. A consistent increase of TP was observed after all stretching exercises when compared to NS. The results suggest the type of stretching, or no stretching, should be considered by those who seek higher performance and practice sports that use maximal anaerobic power.

Eliminating electromechanical instability in dielectric elastomers by employing pre-stretch

International Nuclear Information System (INIS)

Jiang, Liang; Jerrams, Stephen; Betts, Anthony; Kennedy, David

2016-01-01

Electromechanical instability (EMI) is one of most common failure modes for dielectric elastomers (DEs). It has been reported that pre-stretching a DE sample can suppress EMI due to strain stiffening taking place for larger strains and a higher elastic modulus are achieved at high stretch ratios when a voltage is applied to the material. In this work, the influence of equi-biaxial stretch on DE secant modulus was studied using VHB 4910 and silicone rubber (SR) composites containing barium titanate (BaTiO 3 , BT) particles and also dopamine coated BT (DP-BT) particles. The investigation of equi-biaxial deformation and EMI failure for VHB 4910 was undertaken by introducing a voltage-stretch function. The results showed that EMI was suppressed by equi-biaxial pre-stretch for all the DEs fabricated and tested. The stiffening properties of the DE materials were also studied with respect to the secant modulus. Furthermore, a voltage-induced strain of above 200% was achieved for the polyacrylate film by applying a pre-stretch ratio of 2.0 without EMI occurring. However, a maximum voltage-induced strain in the polyacrylate film of 78% was obtained by the SR/20 wt% DP-BT composite for a lower applied pre-stretch ratio of 1.6 and again EMI was eliminated. (paper)

TRP channel proteins and signal transduction.

Science.gov (United States)

Minke, Baruch; Cook, Boaz

2002-04-01

TRP channel proteins constitute a large and diverse family of proteins that are expressed in many tissues and cell types. This family was designated TRP because of a spontaneously occurring Drosophila mutant lacking TRP that responded to a continuous light with a transient receptor potential (hence TRP). In addition to responses to light, TRPs mediate responses to nerve growth factor, pheromones, olfaction, mechanical, chemical, temperature, pH, osmolarity, vasorelaxation of blood vessels, and metabolic stress. Furthermore, mutations in several members of TRP-related channel proteins are responsible for several diseases, such as several tumors and neurodegenerative disorders. TRP-related channel proteins are found in a variety of organisms, tissues, and cell types, including nonexcitable, smooth muscle, and neuronal cells. The large functional diversity of TRPs is also reflected in their diverse permeability to ions, although, in general, they are classified as nonselective cationic channels. The molecular domains that are conserved in all members of the TRP family constitute parts of the transmembrane domains and in most members also the ankyrin-like repeats at the NH2 terminal of the protein and a "TRP domain" at the COOH terminal, which is a highly conserved 25-amino acid stretch with still unknown function. All of the above features suggest that members of the TRP family are "special assignment" channels, which are recruited to diverse signaling pathways. The channels' roles and characteristics such as gating mechanism, regulation, and permeability are determined by evolution according to the specific functional requirements.

Acute effect of different stretching methods on isometric muscle strength

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Gabriel Vasconcellos de Lima Costa e Silva

2014-03-01

This study investigated the acute effect of static stretching methods (SS and proprioceptive neuromuscular facilitation (PNF on the static muscle strength (SMS. Eleven young male subjects with strength training experience, performed 3 tests with a 48h interval between them, randomly selected, where each one subject carried out all procedures: a hand grip without stretching; b hand grip preceded by static stretching of wrist flexors muscles; c hand grip preceded by PNF stretching of wrist flexors muscles. The Shapiro-Wilk test verified the normality of data, and a one-way ANOVA with repeated measures, followed by Tukey’s post hoc test, evaluated the differences between the groups. The significance was set at p 0.05. In conclusion, both stretching methods had caused negative effects on isometric strength, reducing its levels.

Direct numerical simulation of a low momentum round jet in channel crossflow

Energy Technology Data Exchange (ETDEWEB)

Wu, Zhao, E-mail: zhao.wu@manchester.ac.uk; Laurence, Dominique; Afgan, Imran

2017-03-15

Highlights: • Detailed flow physics of jet in crossflow with low velocity ratio, R, is analysed. • The horseshoe vortex comes from the reversed jet fluid, different from high R JICF. • CVP comes from the stretching and reorientation of the injection-flow vorticity. • Recirculation is seen at the downstream low-pressure region. • The shear layer vortices are from shed crossflow boundary layer vortices. - Abstract: Results of a direct numerical simulation of a jet in crossflow with passive scalar mixing are presented. The laminar jet issues from a circular exit into the channel crossflow with a low jet-to-crossflow velocity ratio of 1/6. The governing equations are solved by Incompact3d, an open-source code combining the high-order compact scheme and Poisson spectral solver. An internal recycling approach is used to generate the fully turbulent channel flow profile. Four main flow structures are identified: 1) a large recirculation seen immediately downstream of the jet-exit; 2) a contour-rotating vortex pair formed from the stretching and reorientation of the injection-flow vorticity; 3) a horseshoe vortex generated as a result of the stretching of the vorticity at the jet-exit windward side; 4) shear layer vortices coming from the lifted and shed crossflow boundary layer vorticity. Passive scalar profiles show the mixing are strong in the shear layer where the crossflow fluid encounters the jet fluid. The database is made available online for public access.

Cyclic Mechanical Stretch Up-regulates Hepatoma-Derived Growth Factor Expression in Cultured Rat Aortic Smooth Muscle Cells.

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Kao, Ying-Hsien; Chen, Po-Han; Sun, Cheuk-Kwan; Chang, Yo-Chen; Lin, Yu-Chun; Tsai, Ming-Shian; Lee, Po-Huang; Cheng, Cheng-I

2018-02-21

Hepatoma-derived growth factor (HDGF) is a potent mitogen for vascular smooth muscle cells (SMCs) during embryogenesis and injury repair of vessel walls. Whether mechanical stimuli modulate HDGF expression remains unknown. This study aimed at investigating whether cyclic mechanical stretch plays a regulatory role in HDGF expression and regenerative cytokine production in aortic SMCs. A SMC cell line was grown on a silicone-based elastomer chamber with extracellular matrix coatings (either type I collagen or fibronectin) and received cyclic and uni-axial mechanical stretches with 10% deformation at frequency 1 Hz. Morphological observation showed that fibronectin coating provided better cell adhesion and spreading and that consecutive 6 hours of cyclic mechanical stretch remarkably induced reorientation and realignment of SMCs. Western blotting detection demonstrated that continuous mechanical stimuli elicited up-regulation of HDGF and PCNA, a cell proliferative marker. Signal kinetic profiling study indicated that cyclic mechanical stretch induced signaling activity in RhoA/ROCK and PI3K/Akt cascades. Kinase inhibition study further showed that blockade of PI3K activity suppressed the stretch-induced TNF-a, whereas RhoA/ROCK inhibition significantly blunted the IL-6 production and HDGF over-expression. Moreover, siRNA-mediated HDGF gene silencing significantly suppressed constitutive expression of IL-6, but not TNF-α, in SMCs. These findings support the role of HDGF in maintaining vascular expression of IL-6, which has been regarded a crucial regenerative factor for acute vascular injury. In conclusion, cyclic mechanical stretch may maintain constitutive expression of HDGF in vascular walls and be regarded an important biophysical regulator in vascular regeneration. ©2018 The Author(s).

cAMP-dependent kinase does not modulate the Slack sodium-activated potassium channel.

Science.gov (United States)

Nuwer, Megan O; Picchione, Kelly E; Bhattacharjee, Arin

2009-09-01

The Slack gene encodes a Na(+)-activated K(+) channel and is expressed in many different types of neurons. Like the prokaryotic Ca(2+)-gated K(+) channel MthK, Slack contains two 'regulator of K(+) conductance' (RCK) domains within its carboxy terminal, domains likely involved in Na(+) binding and channel gating. It also contains multiple consensus protein kinase C (PKC) and protein kinase A (PKA) phosphorylation sites and although regulated by protein kinase C (PKC) phosphorylation, modulation by PKA has not been determined. To test if PKA directly regulates Slack, nystatin-perforated patch whole-cell currents were recorded from a human embryonic kidney (HEK-293) cell line stably expressing Slack. Bath application of forskolin, an adenylate cyclase activator, caused a rapid and complete inhibition of Slack currents however, the inactive homolog of forskolin, 1,9-dideoxyforskolin caused a similar effect. In contrast, bath application of 8-bromo-cAMP did not affect the amplitude nor the activation kinetics of Slack currents. In excised inside-out patch recordings, direct application of the PKA catalytic subunit to patches did not affect the open probability of Slack channels nor was open probability affected by direct application of protein phosphatase 2B. Preincubation of cells with the protein kinase A inhibitor KT5720 also did not change current density. Finally, mutating the consensus phosphorylation site located between RCK domain 1 and domain 2 from serine to glutamate did not affect current activation kinetics. We conclude that unlike PKC, phosphorylation by PKA does not acutely modulate the function and gating activation kinetics of Slack channels.

Guidelines for Stretch Flanging Advanced High Strength Steels

International Nuclear Information System (INIS)

Sriram, S.; Chintamani, J.

2005-01-01

Advanced High Strength Steels (AHSS) are currently being considered for use in closure and structural panels in the automotive industry because of their high potential for affordable weight reduction and improved performance. AHSS such as dual phase steels are currently being used in some vehicle platforms. From a manufacturing perspective, stretch flanging during stamping is an important deformation mode requiring careful consideration of geometry and the die process. This paper presents some geometric and process guidelines for stretch flanging AHSS. Hole expansion experiments were conducted to determine the failure limit for a sheared edge condition. Effects of punching clearance, prestrain and prior strain path on hole expansion were explored in these experiments. In addition, dynamic explicit FE calculations using LS-DYNA were also conducted for a typical stretch flange by varying some key geometric parameters. The experimental and FEA results were then analyzed to yield process and geometric guidelines to enable successful stretch flanging of AHSS

Burst activity and ultrafast activation kinetics of CaV1.3 Ca²⁺ channels support presynaptic activity in adult gerbil hair cell ribbon synapses.

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Zampini, Valeria; Johnson, Stuart L; Franz, Christoph; Knipper, Marlies; Holley, Matthew C; Magistretti, Jacopo; Masetto, Sergio; Marcotti, Walter

2013-08-15

Auditory information transfer to afferent neurons relies on precise triggering of neurotransmitter release at the inner hair cell (IHC) ribbon synapses by Ca²⁺ entry through CaV1.3 Ca²⁺ channels. Despite the crucial role of CaV1.3 Ca²⁺ channels in governing synaptic vesicle fusion, their elementary properties in adult mammals remain unknown. Using near-physiological recording conditions we investigated Ca²⁺ channel activity in adult gerbil IHCs. We found that Ca²⁺ channels are partially active at the IHC resting membrane potential (-60 mV). At -20 mV, the large majority (>70%) of Ca²⁺ channel first openings occurred with an estimated delay of about 50 μs in physiological conditions, with a mean open time of 0.5 ms. Similar to other ribbon synapses, Ca²⁺ channels in IHCs showed a low mean open probability (0.21 at -20 mV), but this increased significantly (up to 0.91) when Ca²⁺ channel activity switched to a bursting modality. We propose that IHC Ca²⁺ channels are sufficiently rapid to transmit fast signals of sound onset and support phase-locking. Short-latency Ca²⁺ channel opening coupled to multivesicular release would ensure precise and reliable signal transmission at the IHC ribbon synapse.

Stretching skeletal muscle: chronic muscle lengthening through sarcomerogenesis.

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Alexander M Zöllner

Full Text Available Skeletal muscle responds to passive overstretch through sarcomerogenesis, the creation and serial deposition of new sarcomere units. Sarcomerogenesis is critical to muscle function: It gradually re-positions the muscle back into its optimal operating regime. Animal models of immobilization, limb lengthening, and tendon transfer have provided significant insight into muscle adaptation in vivo. Yet, to date, there is no mathematical model that allows us to predict how skeletal muscle adapts to mechanical stretch in silico. Here we propose a novel mechanistic model for chronic longitudinal muscle growth in response to passive mechanical stretch. We characterize growth through a single scalar-valued internal variable, the serial sarcomere number. Sarcomerogenesis, the evolution of this variable, is driven by the elastic mechanical stretch. To analyze realistic three-dimensional muscle geometries, we embed our model into a nonlinear finite element framework. In a chronic limb lengthening study with a muscle stretch of 1.14, the model predicts an acute sarcomere lengthening from 3.09[Formula: see text]m to 3.51[Formula: see text]m, and a chronic gradual return to the initial sarcomere length within two weeks. Compared to the experiment, the acute model error was 0.00% by design of the model; the chronic model error was 2.13%, which lies within the rage of the experimental standard deviation. Our model explains, from a mechanistic point of view, why gradual multi-step muscle lengthening is less invasive than single-step lengthening. It also explains regional variations in sarcomere length, shorter close to and longer away from the muscle-tendon interface. Once calibrated with a richer data set, our model may help surgeons to prevent muscle overstretch and make informed decisions about optimal stretch increments, stretch timing, and stretch amplitudes. We anticipate our study to open new avenues in orthopedic and reconstructive surgery and enhance

Structure-function relation of phospholamban: modulation of channel activity as a potential regulator of SERCA activity.

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Serena Smeazzetto

Full Text Available Phospholamban (PLN is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+-ATPase (SERCA in the sarcoplasmic reticulum. When reconstituted in planar lipid bilayers PLN exhibits ion channel activity with a low unitary conductance. From the effect of non-electrolyte polymers on this unitary conductance we estimate a narrow pore with a diameter of ca. 2.2 Å for this channel. This value is similar to that reported for the central pore in the structure of the PLN pentamer. Hence the PLN pentamer, which is in equilibrium with the monomer, is the most likely channel forming structure. Reconstituted PLN mutants, which either stabilize (K27A and R9C or destabilize (I47A the PLN pentamer and also phosphorylated PLN still generate the same unitary conductance of the wt/non-phosphorylated PLN. However the open probability of the phosphorylated PLN and of the R9C mutant is significantly lower than that of the respective wt/non-phosphorylated control. In the context of data on PLN/SERCA interaction and on Ca(2+ accumulation in the sarcoplasmic reticulum the present results are consistent with the view that PLN channel activity could participate in the balancing of charge during Ca(2+ uptake. A reduced total conductance of the K(+ transporting PLN by phosphorylation or by the R9C mutation may stimulate Ca(2+ uptake in the same way as an inhibition of K(+ channels in the SR membrane. The R9C-PLN mutation, a putative cause of dilated cardiomyopathy, might hence affect SERCA activity also via its inherent low open probability.

The Sodium-Activated Potassium Channel Slack Is Required for Optimal Cognitive Flexibility in Mice

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Bausch, Anne E.; Dieter, Rebekka; Nann, Yvette; Hausmann, Mario; Meyerdierks, Nora; Kaczmarek, Leonard K.; Ruth, Peter; Lukowski, Robert

2015-01-01

"Kcnt1" encoded sodium-activated potassium channels (Slack channels) are highly expressed throughout the brain where they modulate the firing patterns and general excitability of many types of neurons. Increasing evidence suggests that Slack channels may be important for higher brain functions such as cognition and normal intellectual…

Static versus dynamic stretching: Chronic and acute effects on Agility performance in male athletes

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Iman Taleb-Beydokhti

2015-04-01

Full Text Available The purpose of this study was to examine the acute and chronic effects of static & dynamic stretching protocols on agility performance in amateur handball players. Twelve male amateur handball players (age: 19.66 ± 4.02 years old, weight: 67.12 ± 8.73 kg, height: 178.29 ± 7.81 cm participated in this study. The athletes were randomly allocated into two groups: static stretching or dynamic stretching. All of them underwent an initial evaluation and were submitted to the first intervention. They were evaluated once again and at the end of 12 training sessions. The results analyzed using ANOVA showed that there was a significant decrease in agility time after dynamic stretching against no stretching in the acute phase; but, there were no significant differences between dynamic stretching and no stretching in the chronic phase. In addition, there was no a significant difference between no stretching and static stretching in the acute phase; while, There was a significant decrease in agility time after no stretching against static stretching in the chronic phase. It was concluded that acute dynamic stretching as part of a warm-up may decrease agility time performance, whereas static stretching seems to increase agility time performance. Consequently, the acute and chronic static stretching should not be performed prior to an explosive athletic performance. Keywords: Handball, Agility, Dynamic stretching, Static stretching

Intrinsic ankle stiffness during standing increases with ankle torque and passive stretch of the Achilles tendon

Science.gov (United States)

Gill, Jaspret

2018-01-01

Individuals may stand with a range of ankle angles. Furthermore, shoes or floor surfaces may elevate or depress their heels. Here we ask how these situations impact ankle stiffness and balance. We performed two studies (each with 10 participants) in which the triceps surae, Achilles tendon and aponeurosis were stretched either passively, by rotating the support surface, or actively by leaning forward. Participants stood freely on footplates which could rotate around the ankle joint axis. Brief, small stiffness-measuring perturbations (torque or passive stretch. Sway was minimally affected by stretch or lean, suggesting that this did not underlie the alterations in stiffness. In quiet stance, maximum ankle stiffness is limited by the tendon. As tendon strain increases, it becomes stiffer, causing an increase in overall ankle stiffness, which would explain the effects of leaning. However, stiffness also increased considerably with passive stretch, despite a modest torque increase. We discuss possible explanations for this increase. PMID:29558469

Filament stretching rheometer: inertia compensation revisited

DEFF Research Database (Denmark)

Szabo, Peter; McKinley, Gareth H.

2003-01-01

The necessary inertia compensation used in the force balance for the filament stretching rheometer is derived for an arbitrary frame of reference. This enables the force balance to be used to extract correctly the extensional viscosity from measurements of the tensile force at either end of the e......The necessary inertia compensation used in the force balance for the filament stretching rheometer is derived for an arbitrary frame of reference. This enables the force balance to be used to extract correctly the extensional viscosity from measurements of the tensile force at either end...

The Function of the Novel Mechanical Activated Ion Channel Piezo1 in the Human Osteosarcoma Cells

OpenAIRE

Jiang, Long; Zhao, Yi-ding; Chen, Wei-xiang

2017-01-01

Background The Piezo1 protein ion channel is a novel mechanical activated ion channel which is related to mechanical signal transduction. However, the function of the mechanically activated ion channel Piezo1 had not been explored. In this study, we explored the function of the Piezo1 ion channel in human osteosarcoma (OS) cells related to apoptosis, invasion, and the cell proliferation. Material/Methods Reverse transcription polymerase chain reaction (RT-PCR) and western-blotting were used t...

Ethanol affects network activity in cultured rat hippocampus: mediation by potassium channels.

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Eduard Korkotian

Full Text Available The effects of ethanol on neuronal network activity were studied in dissociated cultures of rat hippocampus. Exposure to low (0.25-0.5% ethanol concentrations caused an increase in synchronized network spikes, and a decrease in the duration of individual spikes. Ethanol also caused an increase in rate of miniature spontaneous excitatory postsynaptic currents. Higher concentrations of ethanol eliminated network spikes. These effects were reversible upon wash. The effects of the high, but not the low ethanol were blocked by the GABA antagonist bicuculline. The enhancing action of low ethanol was blocked by apamin, an SK potassium channel antagonist, and mimicked by 1-EBIO, an SK channel opener. It is proposed that in cultured hippocampal networks low concentration of ethanol is associated with SK channel activity, rather than the GABAergic receptor.

The antipsychotic drug loxapine is an opener of the sodium-activated potassium channel slack (Slo2.2).

Science.gov (United States)

Biton, B; Sethuramanujam, S; Picchione, Kelly E; Bhattacharjee, A; Khessibi, N; Chesney, F; Lanneau, C; Curet, O; Avenet, P

2012-03-01

Sodium-activated potassium (K(Na)) channels have been suggested to set the resting potential, to modulate slow after-hyperpolarizations, and to control bursting behavior or spike frequency adaptation (Trends Neurosci 28:422-428, 2005). One of the genes that encodes K(Na) channels is called Slack (Kcnt1, Slo2.2). Studies found that Slack channels were highly expressed in nociceptive dorsal root ganglion neurons and modulated their firing frequency (J Neurosci 30:14165-14172, 2010). Therefore, Slack channel openers are of significant interest as putative analgesic drugs. We screened the library of pharmacologically active compounds with recombinant human Slack channels expressed in Chinese hamster ovary cells, by using rubidium efflux measurements with atomic absorption spectrometry. Riluzole at 500 μM was used as a reference agonist. The antipsychotic drug loxapine and the anthelmintic drug niclosamide were both found to activate Slack channels, which was confirmed by using manual patch-clamp analyses (EC(50) = 4.4 μM and EC(50) = 2.9 μM, respectively). Psychotropic drugs structurally related to loxapine were also evaluated in patch-clamp experiments, but none was found to be as active as loxapine. Loxapine properties were confirmed at the single-channel level with recombinant rat Slack channels. In dorsal root ganglion neurons, loxapine was found to behave as an opener of native K(Na) channels and to increase the rheobase of action potential. This study identifies new K(Na) channel pharmacological tools, which will be useful for further Slack channel investigations.

Stretching single fibrin fibers hampers their lysis.

Science.gov (United States)

Li, Wei; Lucioni, Tomas; Li, Rongzhong; Bonin, Keith; Cho, Samuel S; Guthold, Martin

2017-09-15

Blood clots, whose main structural component is a mesh of microscopic fibrin fibers, experience mechanical strain from blood flow, clot retraction and interactions with platelets and other cells. We developed a transparent, striated and highly stretchable substrate made from fugitive glue (a styrenic block copolymer) to investigate how mechanical strain affects lysis of single, suspended fibrin fibers. In this suspended fiber assay, lysis manifested itself by fiber elongation, thickening (disassembly), fraying and collapse. Stretching single fibrin fibers significantly hampered their lysis. This effect was seen in uncrosslinked and crosslinked fibers. Crosslinking (without stretching) also hampered single fiber lysis. Our data suggest that strain is a novel mechanosensitive factor that regulates blood clot dissolution (fibrinolysis) at the single fiber level. At the molecular level of single fibrin molecules, strain may distort, or hinder access to, plasmin cleavage sites and thereby hamper lysis. Fibrin fibers are the major structural component of a blood clot. We developed a highly stretchable substrate made from fugitive glue and a suspended fibrin fiber lysis assay to investigate the effect of stretching on single fibrin fibers lysis. The key findings from our experiments are: 1) Fibers thicken and elongate upon lysis; 2) stretching strongly reduces lysis; 3) this effect is more pronounced for uncrosslinked fibers; and 4) stretching fibers has a similar effect on reducing lysis as crosslinking fibers. At the molecular level, strain may distort plasmin cleavage sites, or restrict access to those sites. Our results suggest that strain may be a novel mechanobiological factor that regulates fibrinolysis. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Characterizing the stretch-flangeability of hot rolled multiphase steels

International Nuclear Information System (INIS)

Pathak, N.; Butcher, C.; Worswick, M.; Gao, J.

2013-01-01

Hole expansion tests are commonly used to characterize the edge stretching limit of a material. Traditionally, a conical punch is used to expand a punched hole until a through-thickness crack appears. However, many automotive stretch flanging operations involve in-plane edge stretching that is best captured with a flat punch. In this paper, hole expansion tests were carried out on two different hot-rolled multiphase steels using both flat and conical punches. The fracture mechanisms for both punch types were investigated using scanning electron microscopy (SEM)

Phosphatidylinositol (4,5)bisphosphate inhibits K+-efflux channel activity in NT1 tobacco cultured cells.

Science.gov (United States)

Ma, Xiaohong; Shor, Oded; Diminshtein, Sofia; Yu, Ling; Im, Yang Ju; Perera, Imara; Lomax, Aaron; Boss, Wendy F; Moran, Nava

2009-02-01

In the animal world, the regulation of ion channels by phosphoinositides (PIs) has been investigated extensively, demonstrating a wide range of channels controlled by phosphatidylinositol (4,5)bisphosphate (PtdInsP2). To understand PI regulation of plant ion channels, we examined the in planta effect of PtdInsP2 on the K+-efflux channel of tobacco (Nicotiana tabacum), NtORK (outward-rectifying K channel). We applied a patch clamp in the whole-cell configuration (with fixed "cytosolic" Ca2+ concentration and pH) to protoplasts isolated from cultured tobacco cells with genetically manipulated plasma membrane levels of PtdInsP2 and cellular inositol (1,4,5)trisphosphate: "Low PIs" had depressed levels of these PIs, and "High PIs" had elevated levels relative to controls. In all of these cells, K channel activity, reflected in the net, steady-state outward K+ currents (IK), was inversely related to the plasma membrane PtdInsP2 level. Consistent with this, short-term manipulations decreasing PtdInsP2 levels in the High PIs, such as pretreatment with the phytohormone abscisic acid (25 microM) or neutralizing the bath solution from pH 5.6 to pH 7, increased IK (i.e. NtORK activity). Moreover, increasing PtdInsP2 levels in controls or in abscisic acid-treated high-PI cells, using the specific PI-phospholipase C inhibitor U73122 (2.5-4 microM), decreased NtORK activity. In all cases, IK decreases stemmed largely from decreased maximum attainable NtORK channel conductance and partly from shifted voltage dependence of channel gating to more positive potentials, making it more difficult to activate the channels. These results are consistent with NtORK inhibition by the negatively charged PtdInsP2 in the internal plasma membrane leaflet. Such effects are likely to underlie PI signaling in intact plant cells.

Enhanced Age Strengthening of Mg-Nd-Zn-Zr Alloy via Pre-Stretching

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Erjun Guo

2016-08-01

Full Text Available Pre-stretching was carried out to modify the microstructure of Mg-Nd-Zn-Zr alloy to enhance its age strengthening. The results indicated that more heterogeneous nucleation sites can be provided by the high density of dislocations caused by the plastic pre-stretching deformation, as well as speeding up the growth rate of precipitates. Comparison of microstructure in non-pre-stretched specimens after artificial aging showed that pre-stretched specimens exhibited a higher number density of precipitates. The fine and coarse plate-shaped precipitates were found in the matrix. Due to an increase in the number density of precipitates, the dislocation slipping during the deformation process is effectively hindered, and the matrix is strengthened. The yield strength stabilizes at 4% pre-stretching condition, and then the evolution is stable within the error bars. The 8% pre-stretched specimens can achieve an ultimate tensile strength of 297 MPa. However, further pre-stretching strains after 8% cannot supply any increase in strength. Tensile fracture surfaces of specimens subjected to pre-stretching strain mainly exhibit a trans-granular cleavage fracture. This work indicated that a small amount of pre-stretching strain can further increase strength of alloy and also effectively enhance the formation of precipitates, which can expand the application fields of this alloy.

Duration Dependent Effect of Static Stretching on Quadriceps and Hamstring Muscle Force

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Leyla Alizadeh Ebadi

2018-03-01

Full Text Available The aim of this study was to determine the acute effect of static stretching on hamstring and quadriceps muscles’ isokinetic strength when applied for various durations to elite athletes, to investigate the effect of different static stretching durations on isokinetic strength, and finally to determine the optimal stretching duration. Fifteen elite male athletes from two different sport branches (10 football and five basketball participated in this study. Experimental protocol was designed as 17 repetitive static stretching exercises for hamstring and quadriceps muscle groups according to the indicated experimental protocols; ((A 5 min jogging; (B 5 min jogging followed by 15 s static stretching; (C 5 min jogging followed by 30 s static stretching; (D 5 min jogging, followed by static stretching for 45 s. Immediately after each protocol, an isokinetic strength test consisting of five repetitions at 60°/s speed and 20 repetitions at 180°/s speed was recorded for the right leg by the Isomed 2000 device. Friedman variance analysis test was employed for data analysis. According to the analyzes, it was observed that 5 min jogging and 15 s stretching exercises increased the isokinetic strength, whereas 30 and 45 s stretching exercises caused a decrease.

Blockade of acid sensing ion channels attenuates the exercise pressor reflex in cats.

Science.gov (United States)

Hayes, Shawn G; Kindig, Angela E; Kaufman, Marc P

2007-06-15

Although thin fibre muscle afferents possess acid sensing ion channels (ASICs), their contribution to the exercise pressor reflex is not known. This lack of information is partly attributable to the fact that there is no known selective in vivo antagonist for ASICs. Although amiloride has been shown to antagonize ASICs, it also has been shown to antagonize voltage-gated sodium channels, thereby impairing impulse conduction in sensory nerves. Our aim was to test the hypothesis that lactic acid accumulation in exercising muscle acted on ASICs located on thin fibre muscle afferents to evoke the metabolic component of the exercise pressor reflex. To test this hypothesis, we determined in decerebrate cats if amiloride attenuated the pressor and cardioaccelerator responses to static contraction, to tendon stretch and to arterial injections of lactic acid and capsaicin. We found a dose of amiloride (0.5 microg kg(-1); i.a.) that attenuated the pressor and cardioaccelerator responses to both contraction and lactic acid injection, but had no effect on the responses to stretch and capsaicin. A higher dose of amiloride (5 microg kg(-1), i.a.) not only blocked the pressor and cardioaccelerator responses to lactic acid and contraction, but also attenuated the responses to stretch and to capsaicin, manoeuvers in which ASICs probably play no significant role. In addition, we found that the low dose of amiloride (0.5 microg kg(-1)) had no effect on the responses of muscle spindles to tendon stretch and to succinylcholine, whereas the high dose (5 microg kg(-1)) attenuated the responses to both. Our data suggest the low dose of amiloride used in our experiments selectively blocked ASICs, whereas the high dose blocked ASICs and impulse conduction in muscle afferents. We conclude that ASICs play a role in the metabolic component of the exercise pressor reflex.

The influence of foot position on stretching of the plantar fascia.

Science.gov (United States)

Flanigan, Ryan M; Nawoczenski, Deborah A; Chen, Linlin; Wu, Hulin; DiGiovanni, Benedict F

2007-07-01

A recent study found nonweightbearing stretching exercises specific to the plantar fascia to be superior to the standard program of weightbearing Achilles tendon-stretching exercises in patients with chronic plantar fasciitis. The present study used a cadaver model to demonstrate the influence of foot and ankle position on stretching of the plantar fascia. Twelve fresh-frozen lower-leg specimens were tested in 15 different configurations representing various combinations of ankle and metatarsophalangeal (MTP) joint dorsiflexion, midtarsal transverse plane abduction and adduction, and forefoot varus and valgus. Measurements were recorded by a differential variable reluctance transducer (DVRT) implanted into the medial band of the plantar fascia, and primary measurement was a percent deformation of the plantar fascia (stretch) with respect to a reference position (90 degrees ankle dorsiflexion, 0 degrees midtarsal and forefoot orientation, and 0 degrees MTP dorsiflexion). Ankle and MTP joint dorsiflexion produced a significant increase (14.91%) in stretch compared to the position of either ankle dorsiflexion alone (9.31% increase, p plantar fascia tissue-specific stretching exercises and lends support to the use of ankle and MTP joint dorsiflexion when employing stretching protocols for nonoperative treatment in patients with chronic proximal plantar fasciitis.

Respiratory muscle stretch gymnastics in patients with post coronary artery bypass grafting pain : Impact on respiratory muscle function, activity, mood and exercise capacity

OpenAIRE

會田, 信子; 渋谷, 優子; 吉野, 克樹; Komoda, Masaji; 井上, 智子

2002-01-01

A new rehabilitation (New-RH) program including respiratory muscle stretch gymnastics (RMSG) was developed to alleviate post-coronary artery bypass grafting pain (PCP). Effects on respiratory muscle function, pain, activities of daily living (ADL), mood and exercise capacity were investigated. Subjects were 16 consecutive patients undergoing median full sternotomy coronary artery bypass grafting (CABG), and were randomly divided into equal New-RH (S-group) and conventional therapy (C-group) g...

Experimental Study of the Effects of EIPA, Losartan, and BQ-123 on Electrophysiological Changes Induced by Myocardial Stretch.

Science.gov (United States)

Chorro, Francisco J; Canto, Irene Del; Brines, Laia; Such-Miquel, Luis; Calvo, Conrado; Soler, Carlos; Zarzoso, Manuel; Trapero, Isabel; Tormos, Álvaro; Such, Luis

2015-12-01

Mechanical response to myocardial stretch has been explained by various mechanisms, which include Na(+)/H(+) exchanger activation by autocrine-paracrine system activity. Drug-induced changes were analyzed to investigate the role of these mechanisms in the electrophysiological responses to acute myocardial stretch. Multiple epicardial electrodes and mapping techniques were used to analyze changes in ventricular fibrillation induced by acute myocardial stretch in isolated perfused rabbit hearts. Four series were studied: control (n = 9); during perfusion with the angiotensin receptor blocker losartan (1 μM, n = 8); during perfusion with the endothelin A receptor blocker BQ-123 (0.1 μM, n = 9), and during perfusion with the Na(+)/H(+) exchanger inhibitor EIPA (5-[N-ethyl-N-isopropyl]-amiloride) (1 μM, n = 9). EIPA attenuated the increase in the dominant frequency of stretch-induced fibrillation (control=40.4%; losartan=36% [not significant]; BQ-123=46% [not significant]; and EIPA=22% [PII receptor antagonist losartan and the endothelin A receptor blocker BQ-123 did not modify these effects. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Quantification and distribution of big conductance Ca2+-activated K+ channels in kidney epithelia

DEFF Research Database (Denmark)

Grunnet, Morten; Hay-Schmidt, Anders; Klaerke, Dan A

2005-01-01

and immunohistochemical studies. In cortical collecting ducts, BK channels were exclusively located in principal cells while no channels could be found in intercalated cells. The abundant and distinct distribution in kidney epithelia talks in favor for BK channels being important contributors in maintaining salt......Big conductance Ca2+ activated K+ channels (BK channels) is an abundant channel present in almost all kind of tissue. The accurate quantity and especially the precise distribution of this channel in kidney epithelia are, however, still debated. The aim of the present study has therefore been...... to examine the presence of BK channels in kidney epithelia and determine the actual number and distribution of these channels. For this purpose, a selective peptidyl ligand for BK channels called iberiotoxin or the radiolabeled double mutant analog 125I-IbTX-D19Y/Y36F has been employed. The presence of BK...

Interset stretching does not influence the kinematic profile of consecutive bench-press sets.

Science.gov (United States)

García-López, David; Izquierdo, Mikel; Rodríguez, Sergio; González-Calvo, Gustavo; Sainz, Nuria; Abadía, Olaia; Herrero, Azael J

2010-05-01

This study was undertaken to examine the role of interset stretching on the time course of acceleration portion AP and mean velocity profile during the concentric phase of 2 bench-press sets with a submaximal load (60% of the 1 repetition maximum). Twenty-five college students carried out, in 3 different days, 2 consecutive bench-press sets leading to failure, performing between sets static stretching, ballistic stretching, or no stretching. Acceleration portion and lifting velocity patterns of the concentric phase were not altered during the second set, regardless of the stretching treatment performed. However, when velocity was expressed in absolute terms, static stretching reduced significantly (p velocity during the second set compared to the first one. Therefore, if maintenance of a high absolute velocity over consecutive sets is important for training-related adaptations, static stretching should be avoided or replaced by ballistic stretching.

Comparison of the effects of hamstring stretching using proprioceptive neuromuscular facilitation with prior application of cryotherapy or ultrasound therapy

Science.gov (United States)

Magalhães, Francisco Elezier Xavier; Junior, Arlindo Rodrigues de Mesquita; Meneses, Harnold’s Tyson de Sousa; Moreira dos Santos, Rayele Pricila; Rodrigues, Ezaine Costa; Gouveia, Samara Sousa Vasconcelos; Gouveia, Guilherme Pertinni de Morais; Orsini, Marco; Bastos, Victor Hugo do Vale; Machado, Dionis de Castro Dutra

2015-01-01

[Purpose] Stretching using proprioceptive neuromuscular facilitation involve physiological reflex mechanisms through submaximal contraction of agonists which activate Golgi organ, promoting the relaxation reflex. The aim of this study was to evaluate the effects of proprioceptive neuromuscular facilitation alone and with prior application of cryotherapy and thermotherapy on hamstring stretching. [Subjects and Methods] The sample comprised of 32 young subjects with hamstring retraction of the right limb. The subjects were randomly allocated to four groups: the control, flexibility PNF, flexibility PNF associated with cryotherapy, flexibility PNF in association with ultrasound therapy. [Results] After 12 stretching sessions, experimental groups showed significant improvements compared to the control group. Moreover, we did not find any significant differences among the experimental groups indicating PNF stretching alone elicits similar results to PNF stretching with prior administration of cryotherapy or thermotherapy. [Conclusion] PNF without other therapy may be a more practical and less expensive choice for clinical care. PMID:26157261

Numerical and experimental investigation of stretch-flange forming

International Nuclear Information System (INIS)

Cinotti, N.; Shakeri, H.R.; Worswick, M.J.; Truttmann, S.; Finn, M.J.; Jain, M.; Lloyd, D.J.

2000-01-01

Simulations of stretch flange forming operations are undertaken using explicit dynamic finite element calculations incorporating anisotropic yield criteria. Simple circular stretch flanges utilizing a single circular punch to expand the cut-out were considered. Experiments were performed using 101mm diameter tooling on AA 5754 and AA 5182 aluminum alloy sheets, with varying cut-out and gauge size. Metallurgical aspects of the formability of these aluminum alloys and damage mechanisms were studied. Both optical and Scanning Electron Microscopy (SEM) were used to study ductile fracture behaviour in these materials during the forming operation. The limit strains obtained from the circular stretch flange formability experiments are compared to forming limit diagram (FLD) data from hemispherical dome specimens. (author)

Ion channel activity of membrane vesicles released from sea urchin sperm during the acrosome reaction

International Nuclear Information System (INIS)

Schulz, Joseph R.; Vega-Beltran, Jose L. de la; Beltran, Carmen; Vacquier, Victor D.; Darszon, Alberto

2004-01-01

The sperm acrosome reaction (AR) involves ion channel activation. In sea urchin sperm, the AR requires Ca 2+ and Na + influx and K + and H + efflux. During the AR, the plasma membrane fuses with the acrosomal vesicle membrane forming hybrid membrane vesicles that are released from sperm into the medium. This paper reports the isolation and preliminary characterization of these acrosome reaction vesicles (ARVs), using synaptosome-associated protein of 25 kDa (SNAP-25) as a marker. Isolated ARVs have a unique protein composition. The exocytosis regulatory proteins vesicle-associated membrane protein and SNAP-25 are inside ARVs, as judged by protease protection experiments, and membrane associated based on Triton X-114 partitioning. ARVs fused with planar bilayers display three main types of single channel activity. The most frequently recorded channel is cationic, weakly voltage dependent and has a low open probability that increases with negative potentials. This channel is activated by cAMP, blocked by Ba 2+ , and has a PK + /PNa + selectivity of 4.5. ARVs represent a novel membrane preparation suitable to deepen our understanding of ion channel activity in the AR and during fertilization

Mechanosensitive channels are activated by stress in the actin stress fibres, and could be involved in gravity sensing in plants.

Science.gov (United States)

Tatsumi, H; Furuichi, T; Nakano, M; Toyota, M; Hayakawa, K; Sokabe, M; Iida, H

2014-01-01

Mechanosensitive (MS) channels are expressed in a variety of cells. The molecular and biophysical mechanism involved in the regulation of MS channel activities is a central interest in basic biology. MS channels are thought to play crucial roles in gravity sensing in plant cells. To date, two mechanisms have been proposed for MS channel activation. One is that tension development in the lipid bilayer directly activates MS channels. The second mechanism proposes that the cytoskeleton is involved in the channel activation, because MS channel activities are modulated by pharmacological treatments that affect the cytoskeleton. We tested whether tension in the cytoskeleton activates MS channels. Mammalian endothelial cells were microinjected with phalloidin-conjugated beads, which bound to stress fibres, and a traction force to the actin cytoskeleton was applied by dragging the beads with optical tweezers. MS channels were activated when the force was applied, demonstrating that a sub-pN force to the actin filaments activates a single MS channel. Plants may use a similar molecular mechanism in gravity sensing, since the cytoplasmic Ca(2+) concentration increase induced by changes in the gravity vector was attenuated by potential MS channel inhibitors, and by actin-disrupting drugs. These results support the idea that the tension increase in actin filaments by gravity-dependent sedimentation of amyloplasts activates MS Ca(2+) -permeable channels, which can be the molecular mechanism of a Ca(2+) concentration increase through gravistimulation. We review recent progress in the study of tension sensing by actin filaments and MS channels using advanced biophysical methods, and discuss their possible roles in gravisensing. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

Effectiveness of Plantar Fascia-Specific Stretching Exercises in Plantar Fasciitis

Directory of Open Access Journals (Sweden)

Devrim Özer

2015-12-01

Full Text Available Aim: Plantar fasciitis (PF is a painful and disabling disease that affects the quality of life and daily activities of patients and it is the most common cause of heel pain in adults. In primary treatment, conservative treatment is suggested and different conservative options are described in the literature. In our study, we evaluated the efficacy of plantar fascia-specific stretching exercises in the treatment of PF. Methods: Twenty-nine feet - 21 patients with the mean age of 49.3 years were included in the study. The mean length of follow-up was 19.8 months and the mean length of exercise period was 4.94 months. Non-weight bearing plantar fascia-specific stretching exercise was done twice daily, for 10 times at each session. In addition to exercises, silicone heel pad and nonsteroidal anti-inflammatory drugs (NSAID were added. Visual analog scale (VAS was used for pain evaluation. Results: Full recovery detected in 15 feet in 10 patients (52% and a decrease in pain was seen in 10 feet in 8 patients (34%. There was no response in 4 feet in 3 patients (14%. There was statistically significant difference between pre-treatment and post-treatment visual analog scale scores (p=0.0001. Conclusion: Plantar fascia-specific stretching exercise is an effective treatment option in PF.

Active Dendrites and Differential Distribution of Calcium Channels Enable Functional Compartmentalization of Golgi Cells.

Science.gov (United States)

Rudolph, Stephanie; Hull, Court; Regehr, Wade G

2015-11-25

Interneurons are essential to controlling excitability, timing, and synaptic integration in neuronal networks. Golgi cells (GoCs) serve these roles at the input layer of the cerebellar cortex by releasing GABA to inhibit granule cells (grcs). GoCs are excited by mossy fibers (MFs) and grcs and provide feedforward and feedback inhibition to grcs. Here we investigate two important aspects of GoC physiology: the properties of GoC dendrites and the role of calcium signaling in regulating GoC spontaneous activity. Although GoC dendrites are extensive, previous studies concluded they are devoid of voltage-gated ion channels. Hence, the current view holds that somatic voltage signals decay passively within GoC dendrites, and grc synapses onto distal dendrites are not amplified and are therefore ineffective at firing GoCs because of strong passive attenuation. Using whole-cell recording and calcium imaging in rat slices, we find that dendritic voltage-gated sodium channels allow somatic action potentials to activate voltage-gated calcium channels (VGCCs) along the entire dendritic length, with R-type and T-type VGCCs preferentially located distally. We show that R- and T-type VGCCs located in the dendrites can boost distal synaptic inputs and promote burst firing. Active dendrites are thus critical to the regulation of GoC activity, and consequently, to the processing of input to the cerebellar cortex. In contrast, we find that N-type channels are preferentially located near the soma, and control the frequency and pattern of spontaneous firing through their close association with calcium-activated potassium (KCa) channels. Thus, VGCC types are differentially distributed and serve specialized functions within GoCs. Interneurons are essential to neural processing because they modulate excitability, timing, and synaptic integration within circuits. At the input layer of the cerebellar cortex, a single type of interneuron, the Golgi cell (GoC), carries these functions. The

Building channels for transparent risk assessment. Final report RISCOM pilot project

Energy Technology Data Exchange (ETDEWEB)

Andersson, Kjell [Karinta-Konsult, Taeby (Sweden); Espejo, R. [Syncho Ltd, Birmingham (United Kingdom); Wene, C.O. [Profu AB, Lund (Sweden)

1998-01-01

Recent developments in the Swedish programme for nuclear waste management have underlined the need for a broad consultation process with public participation. Decision procedures that provide transparency for people outside the groups of experts and political decision-makers must be developed. This report explores what this transparency means and how it could be enhanced. It is acknowledged that the concept of transparency includes three equally important aspects: factual issues, normative issues, and stakeholder``s authenticity. So far experts have dominated the decision process in the nuclear waste area. Value judgements of experts may appear as normative issues, for instance among other scientists; or they may be related to issues of authenticity, for instance when discussions take place with community stakeholders. The formal decision process must always be the basis for building transparency. Two dominant approaches are compared: the Swedish ``review/decide`` approach, and the ``inquiry/decide`` approach used in the UK. Suggestions are made as to how the best features of the two approaches could be combined. The report also includes a study on the systemic roles of SKI/SSI in the Swedish nuclear waste management system. This study identifies several systemic functions carried out by SKI/SSI. Awareness of these roles within SKI and SSI (and among other stakeholders) is crucial for transparency. This report argues that a key element in building transparency is to create mechanisms for ``stretching`` SKB. Various channels for stretching and providing new perspectives are explored. Among the procedures discussed are those concerned with hearings and dialogue. Environmental Impact Assessment (EIA) is seen as the umbrella under which most of the stretching activities can take place. Team Syntegrity was used as a method to compare the Swedish and UK procedures. It is a non-hierarchical approach that enhances the effective contribution of a wide variety of

Building channels for transparent risk assessment. Final report RISCOM pilot project

International Nuclear Information System (INIS)

Andersson, Kjell; Espejo, R.; Wene, C.O.

1998-01-01

Recent developments in the Swedish programme for nuclear waste management have underlined the need for a broad consultation process with public participation. Decision procedures that provide transparency for people outside the groups of experts and political decision-makers must be developed. This report explores what this transparency means and how it could be enhanced. It is acknowledged that the concept of transparency includes three equally important aspects: factual issues, normative issues, and stakeholder''s authenticity. So far experts have dominated the decision process in the nuclear waste area. Value judgements of experts may appear as normative issues, for instance among other scientists; or they may be related to issues of authenticity, for instance when discussions take place with community stakeholders. The formal decision process must always be the basis for building transparency. Two dominant approaches are compared: the Swedish ''review/decide'' approach, and the ''inquiry/decide'' approach used in the UK. Suggestions are made as to how the best features of the two approaches could be combined. The report also includes a study on the systemic roles of SKI/SSI in the Swedish nuclear waste management system. This study identifies several systemic functions carried out by SKI/SSI. Awareness of these roles within SKI and SSI (and among other stakeholders) is crucial for transparency. This report argues that a key element in building transparency is to create mechanisms for ''stretching'' SKB. Various channels for stretching and providing new perspectives are explored. Among the procedures discussed are those concerned with hearings and dialogue. Environmental Impact Assessment (EIA) is seen as the umbrella under which most of the stretching activities can take place. Team Syntegrity was used as a method to compare the Swedish and UK procedures. It is a non-hierarchical approach that enhances the effective contribution of a wide variety of

Convective Heat Transfer Scaling of Ignition Delay and Burning Rate with Heat Flux and Stretch Rate in the Equivalent Low Stretch Apparatus

Science.gov (United States)

Olson, Sandra

2011-01-01

To better evaluate the buoyant contributions to the convective cooling (or heating) inherent in normal-gravity material flammability test methods, we derive a convective heat transfer correlation that can be used to account for the forced convective stretch effects on the net radiant heat flux for both ignition delay time and burning rate. The Equivalent Low Stretch Apparatus (ELSA) uses an inverted cone heater to minimize buoyant effects while at the same time providing a forced stagnation flow on the sample, which ignites and burns as a ceiling fire. Ignition delay and burning rate data is correlated with incident heat flux and convective heat transfer and compared to results from other test methods and fuel geometries using similarity to determine the equivalent stretch rates and thus convective cooling (or heating) rates for those geometries. With this correlation methodology, buoyant effects inherent in normal gravity material flammability test methods can be estimated, to better apply the test results to low stretch environments relevant to spacecraft material selection.

Activation of human IK and SK Ca2+ -activated K+ channels by NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime)

DEFF Research Database (Denmark)

Strøbaek, Dorte; Teuber, Lene; Jørgensen, Tino D

2004-01-01

We have identified and characterized the compound NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) as a potent activator of human Ca2+ -activated K+ channels of SK and IK types, whereas it is devoid of effect on BK type channels. IK- and SK-channels have previously been reported to be activated...

Ca2+ Channel Re-localization to Plasma-Membrane Microdomains Strengthens Activation of Ca2+-Dependent Nuclear Gene Expression

Directory of Open Access Journals (Sweden)

Krishna Samanta

2015-07-01

Full Text Available In polarized cells or cells with complex geometry, clustering of plasma-membrane (PM ion channels is an effective mechanism for eliciting spatially restricted signals. However, channel clustering is also seen in cells with relatively simple topology, suggesting it fulfills a more fundamental role in cell biology than simply orchestrating compartmentalized responses. Here, we have compared the ability of store-operated Ca2+ release-activated Ca2+ (CRAC channels confined to PM microdomains with a similar number of dispersed CRAC channels to activate transcription factors, which subsequently increase nuclear gene expression. For similar levels of channel activity, we find that channel confinement is considerably more effective in stimulating gene expression. Our results identify a long-range signaling advantage to the tight evolutionary conservation of channel clustering and reveal that CRAC channel aggregation increases the strength, fidelity, and reliability of the general process of excitation-transcription coupling.

Pion scattering to 8- stretched states in 60Ni

International Nuclear Information System (INIS)

Clausen, B.L.

1988-03-01

Using the Energetic Pion Channel and Spectrometer at the Los Alamos Meson Physics Facility, differential cross sections for pion scattering were measured for ten previously known J/sup π/ = 8/sup /minus// stretched states in 60 Ni. A possible new pure isoscalar stretched state was also found. The data were taken near the /DELTA//sub 3,3/-resonance using 162 MeV incident pions and scattering angles of 65/degree/, 80/degree/, and 90/degree/ for π + and 65/degree/ and 80/degree/ for π/sup /minus//. The analysis of the 60 Ni data found that the use of Woods-Saxon wave functions in the theoretical calculations gave much better agreement with data than the use of the usual harmonic oscillator wave functions. The WS theory gave better predictions of: the angle at which the π/sup /minus// and π + angular distributions are maximum, the ratios of π/sup /minus// to π + cross sections for pure isovector states (which were much larger than unity), and the absolute size of the cross sections for all states (so that the normalization factor necessary to arrive at agreement of theory with data was closer to unity). The theoretical calculations used the distorted wave impulse approximation, including new methods for unbound states. The sensitivities of the calculations to input parameters were investigated. This analysis using WS wave functions was extended to five other nuclei ( 12 C, 14 C, 16 O, 28 Si, and 54 Fe) on which both pion scattering and electron scattering have been done. A significant improvement in arriving at a normalization factor close to unity was found when WS wave functions were consistently used for analyzing both pion and electron inelastic scattering data. 101 refs., 26 figs., 13 tabs

Milrinone-Induced Postconditioning Requires Activation of Mitochondrial Ca2+-sensitive Potassium (mBKCa) Channels

NARCIS (Netherlands)

Behmenburg, Friederike; Trefz, Lara; Dorsch, Marianne; Ströthoff, Martin; Mathes, Alexander; Raupach, Annika; Heinen, André; Hollmann, Markus W.; Berger, Marc M.; Huhn, Ragnar

2017-01-01

Cardioprotection by postconditioning requires activation of mitochondrial large-conductance Ca2+-sensitive potassium (mBKCa) channels. The involvement of these channels in milrinone-induced postconditioning is unknown. The authors determined whether cardioprotection by milrinone-induced

Effect of spinal manipulative therapy with stretching compared with stretching alone on full-swing performance of golf players: a randomized pilot trial☆

Science.gov (United States)

Costa, Soraya M.V.; Chibana, Yumi E.T.; Giavarotti, Leandro; Compagnoni, Débora S.; Shiono, Adriana H.; Satie, Janice; Bracher, Eduardo S.B.

2009-01-01

Abstract Objective There has been a steady growth of chiropractic treatment using spinal manipulative therapy (SMT) that aims to increase the performance of athletes in various sports. This study evaluates the effect of SMT by chiropractors on the performance of golf players. Methods Golfers of 2 golf clubs in São Paulo, Brazil, participated in this study. They were randomized to 1 of 2 groups: Group I received a stretch program, and group II received a stretch program in addition to SMT. Participants in both groups performed the same standardized stretching program. Spinal manipulative therapy to dysfunctional spinal segments was performed on group II only. All golfers performed 3 full-swing maneuvers. Ball range was considered as the average distance for the 3 shots. Treatment was performed after the initial measurement, and the same maneuvers were performed afterward. Each participant repeated these procedures for a 4-week period. Student t test, Mann-Whitney nonparametric test, and 1-way analysis of variance for repeated measures with significance level of 5% were used to analyze the study. Results Forty-three golfers completed the protocol. Twenty participants were allocated to group I and 23 to group II. Average age, handicap, and initial swing were comparable. No improvement of full-swing performance was observed during the 4 sessions on group I (stretch only). An improvement was observed at the fourth session of group II (P = .005); when comparing the posttreatment, group II had statistical significance at all phases (P = .003). Conclusions Chiropractic SMT in association with muscle stretching may be associated with an improvement of full-swing performance when compared with muscle stretching alone. PMID:19948307

TNF-α promotes cell survival through stimulation of K+ channel and NFκB activity in corneal epithelial cells

International Nuclear Information System (INIS)

Wang Ling; Reinach, Peter; Lu, Luo

2005-01-01

Tumor necrosis factor (TNF-α) in various cell types induces either cell death or mitogenesis through different signaling pathways. In the present study, we determined in human corneal epithelial cells how TNF-α also promotes cell survival. Human corneal epithelial (HCE) cells were cultured in DMEM/F-12 medium containing 10% FBS. TNF-α stimulation induced activation of a voltage-gated K + channel detected by measuring single channel activity using patch clamp techniques. The effect of TNF-α on downstream events included NFκB nuclear translocation and increases in DNA binding activities, but did not elicit ERK, JNK, or p38 limb signaling activation. TNF-α induced increases in p21 expression resulting in partial cell cycle attenuation in the G 1 phase. Cell cycle progression was also mapped by flow cytometer analysis. Blockade of TNF-α-induced K + channel activity effectively prevented NFκB nuclear translocation and binding to DNA, diminishing the cell-survival protective effect of TNF-α. In conclusion, TNF-α promotes survival of HCE cells through sequential stimulation of K + channel and NFκB activities. This response to TNF-α is dependent on stimulating K + channel activity because following suppression of K + channel activity TNF-α failed to activate NFκB nuclear translocation and binding to nuclear DNA

Investigating the role of musical genre in human perception of music stretching resistance

OpenAIRE

Chen, Jun; Wang, Chaokun

2017-01-01

To stretch a music piece to a given length is a common demand in people's daily lives, e.g., in audio-video synchronization and animation production. However, it is not always guaranteed that the stretched music piece is acceptable for general audience since music stretching suffers from people's perceptual artefacts. Over-stretching a music piece will make it uncomfortable for human psychoacoustic hearing. The research on music stretching resistance attempts to estimate the maximum stretchab...

Voltage-gated potassium channels regulate calcium-dependent pathways involved in human T lymphocyte activation.

Science.gov (United States)

Lin, C S; Boltz, R C; Blake, J T; Nguyen, M; Talento, A; Fischer, P A; Springer, M S; Sigal, N H; Slaughter, R S; Garcia, M L

1993-03-01

The role that potassium channels play in human T lymphocyte activation has been investigated by using specific potassium channel probes. Charybdotoxin (ChTX), a blocker of small conductance Ca(2+)-activated potassium channels (PK,Ca) and voltage-gated potassium channels (PK,V) that are present in human T cells, inhibits the activation of these cells. ChTX blocks T cell activation induced by signals (e.g., anti-CD2, anti-CD3, ionomycin) that elicit a rise in intracellular calcium ([Ca2+]i) by preventing the elevation of [Ca2+]i in a dose-dependent manner. However, ChTX has no effect on the activation pathways (e.g., anti-CD28, interleukin 2 [IL-2]) that are independent of a rise in [Ca2+]i. In the former case, both proliferative response and lymphokine production (IL-2 and interferon gamma) are inhibited by ChTX. The inhibitory effect of ChTX can be demonstrated when added simultaneously, or up to 4 h after the addition of the stimulants. Since ChTX inhibits both PK,Ca and PK,V, we investigated which channel is responsible for these immunosuppressive effects with the use of two other peptides, noxiustoxin (NxTX) and margatoxin (MgTX), which are specific for PK,V. These studies demonstrate that, similar to ChTX, both NxTX and MgTX inhibit lymphokine production and the rise in [Ca2+]i. Taken together, these data provide evidence that blockade of PK,V affects the Ca(2+)-dependent pathways involved in T lymphocyte proliferation and lymphokine production by diminishing the rise in [Ca2+]i that occurs upon T cell activation.

Equibiaxial cyclic stretch stimulates fibroblasts to rapidly remodel fibrin.

Science.gov (United States)

Balestrini, Jenna Leigh; Billiar, Kristen Lawrence

2006-01-01

Understanding the effects of the mechanical environment on wound healing is critical for developing more effective treatments to reduce scar formation and contracture. The aim of this study was to investigate the effects of dynamic mechanical stretch on cell-mediated early wound remodeling independent of matrix alignment which obscures more subtle remodeling mechanisms. Cyclic equibiaxial stretch (16% stretch at 0.2 Hz) was applied to fibroblast-populated fibrin gel in vitro wound models for eight days. Compaction, density, tensile strength, and collagen content were quantified as functional measures of remodeling. Stretched samples were approximately ten times stronger, eight-fold more dense, and eight times thinner than statically cultured samples. These changes were accompanied by a 15% increase in net collagen but no significant differences in cell number or viability. When collagen crosslinking was inhibited in stretched samples, the extensibility increased and the strength decreased. The apparent weakening was due to a reduction in compaction rather than a decrease in ability of the tissue to withstand tensile forces. Interestingly, inhibiting collagen crosslinking had no measurable effects on the statically cultured samples. These results indicate that amplified cell-mediated compaction and even a slight addition in collagen content play substantial roles in mechanically induced wound strengthening. These findings increase our understanding of how mechanical forces guide the healing response in skin, and the methods employed in this study may also prove valuable tools for investigating stretch-induced remodeling of other planar connective tissues and for creating mechanically robust engineered tissues.

To Stretch and Search for Better Ways

Science.gov (United States)

Moore, John W.

2000-06-01

Ambassadors. The response has been wonderful. Many people are willing and eager to show others what JCE has to offer and encourage them to subscribe. The program began in the latter half of 1999, and there were 37 Journal Ambassadors by year's end. Some are located as far away as South America and Europe, and requests for information packets for meetings and workshops now arrive several times a week. We thank everyone who has been involved in this program for getting it off to a great start. Our authors and reviewers actively search for better ways to teach chemistry and for better ways to communicate to other teachers what they have learned. This enriches their own classes first and then a much wider audience. Others have volunteered to help make JCE articles easier to find and more accessible on the Web. The ACS student affiliates at one college have taken on the project of assigning keywords to articles published in some of the years before 1995. We will add these to the JCE Index online, making it an even more effective means for finding articles on specified topics. There are many possibilities for collaboration with JCE. If you would like to contribute to an ongoing project or would like to initiate a new one, please let us know. We welcome anyone who would like to help us make this Journal better. It is important that students learn how to stretch and search for better ways. This will not happen unless we challenge them within a humane and supportive learning environment. We should expect more than memorization or unthinking application of algorithmic solutions to exercises. We should provide means by which those who do not succeed at first can try again and again. And we should provide an intellectual scaffold for those whose climb toward understanding is difficult. These are not easy goals to achieve, but the more we try and the more we communicate with others who are attempting similar tasks, the more likely we are to be successful. Most important of all is that

Activation of acid-sensing ion channels by localized proton transient reveals their role in proton signaling.

Science.gov (United States)

Zeng, Wei-Zheng; Liu, Di-Shi; Liu, Lu; She, Liang; Wu, Long-Jun; Xu, Tian-Le

2015-09-15

Extracellular transients of pH alterations likely mediate signal transduction in the nervous system. Neuronal acid-sensing ion channels (ASICs) act as sensors for extracellular protons, but the mechanism underlying ASIC activation remains largely unknown. Here, we show that, following activation of a light-activated proton pump, Archaerhodopsin-3 (Arch), proton transients induced ASIC currents in both neurons and HEK293T cells co-expressing ASIC1a channels. Using chimera proteins that bridge Arch and ASIC1a by a glycine/serine linker, we found that successful coupling occurred within 15 nm distance. Furthermore, two-cell sniffer patch recording revealed that regulated release of protons through either Arch or voltage-gated proton channel Hv1 activated neighbouring cells expressing ASIC1a channels. Finally, computational modelling predicted the peak proton concentration at the intercellular interface to be at pH 6.7, which is acidic enough to activate ASICs in vivo. Our results highlight the pathophysiological role of proton signalling in the nervous system.

Impact of mechanical stretch on the cell behaviors of bone and surrounding tissues

Directory of Open Access Journals (Sweden)

Hye-Sun Yu

2016-02-01

Full Text Available Mechanical loading is recognized to play an important role in regulating the behaviors of cells in bone and surrounding tissues in vivo. Many in vitro studies have been conducted to determine the effects of mechanical loading on individual cell types of the tissues. In this review, we focus specifically on the use of the Flexercell system as a tool for studying cellular responses to mechanical stretch. We assess the literature describing the impact of mechanical stretch on different cell types from bone, muscle, tendon, ligament, and cartilage, describing individual cell phenotype responses. In addition, we review evidence regarding the mechanotransduction pathways that are activated to potentiate these phenotype responses in different cell populations.

Impact of mechanical stretch on the cell behaviors of bone and surrounding tissues

Science.gov (United States)

Yu, Hye-Sun; Kim, Jung-Ju; Kim, Hae-Won; Lewis, Mark P; Wall, Ivan

2016-01-01

Mechanical loading is recognized to play an important role in regulating the behaviors of cells in bone and surrounding tissues in vivo. Many in vitro studies have been conducted to determine the effects of mechanical loading on individual cell types of the tissues. In this review, we focus specifically on the use of the Flexercell system as a tool for studying cellular responses to mechanical stretch. We assess the literature describing the impact of mechanical stretch on different cell types from bone, muscle, tendon, ligament, and cartilage, describing individual cell phenotype responses. In addition, we review evidence regarding the mechanotransduction pathways that are activated to potentiate these phenotype responses in different cell populations. PMID:26977284

Effects of special composite stretching on the swing of amateur golf players.

Science.gov (United States)

Lee, Joong-Chul; Lee, Sung-Wan; Yeo, Yun-Ghi; Park, Gi Duck

2015-04-01

[Purpose] The study investigated stretching for safer a golf swing compared to present stretching methods for proper swings in order to examine the effects of stretching exercises on golf swings. [Subjects] The subjects were 20 amateur golf club members who were divided into two groups: an experimental group which performed stretching, and a control group which did not. The subjects had no bone deformity, muscle weakness, muscle soreness, or neurological problems. [Methods] A swing analyzer and a ROM measuring instrument were used as the measuring tools. The swing analyzer was a GS400-golf hit ball analyzer (Korea) and the ROM measuring instrument was a goniometer (Korea). [Results] The experimental group showed a statistically significant improvement in driving distance. After the special stretching training for golf, a statistically significant difference in hit-ball direction deviation after swings were found between the groups. The experimental group showed statistically significant decreases in hit ball direction deviation. After the special stretching training for golf, statistically significant differences in hit-ball speed were found between the groups. The experimental group showed significant increases in hit-ball speed. [Conclusion] To examine the effects of a special stretching program for golf on golf swing-related factors, 20 male amateur golf club members performed a 12-week stretching training program. After the golf stretching training, statistically significant differences were found between the groups in hit-ball driving distance, direction deviation, deflection distance, and speed.

Inhibition of parathyroid hormone release by maitotoxin, a calcium channel activator

International Nuclear Information System (INIS)

Fitzpatrick, L.A.; Yasumoto, T.; Aurbach, G.D.

1989-01-01

Maitotoxin, a toxin derived from a marine dinoflagellate, is a potent activator of voltage-sensitive calcium channels. To further test the hypothesis that inhibition of PTH secretion by calcium is mediated via a calcium channel we studied the effect of maitotoxin on dispersed bovine parathyroid cells. Maitotoxin inhibited PTH release in a dose-dependent fashion, and inhibition was maximal at 1 ng/ml. Chelation of extracellular calcium by EGTA blocked the inhibition of PTH by maitotoxin. Maitotoxin enhanced the effects of the dihydropyridine calcium channel agonist (+)202-791 and increased the rate of radiocalcium uptake in parathyroid cells. Pertussis toxin, which ADP-ribosylates and inactivates a guanine nucleotide regulatory protein that interacts with calcium channels in the parathyroid cell, did not affect the inhibition of PTH secretion by maitotoxin. Maitotoxin, by its action on calcium channels allows entry of extracellular calcium and inhibits PTH release. Our results suggest that calcium channels are involved in the release of PTH. Inhibition of PTH release by maitotoxin is not sensitive to pertussis toxin, suggesting that maitotoxin may act distal to the site interacting with a guanine nucleotide regulatory protein, or maitotoxin could interact with other ions or second messengers to inhibit PTH release

Effects of Proprioceptive Neuromuscular Facilitation Stretching and Kinesiology Taping on Pelvic Compensation During Double-Knee Extension

Directory of Open Access Journals (Sweden)

Lee Seung-Woong

2015-12-01

Full Text Available Shortened hamstrings are likely to restrict the anterior pelvic tilt and induce a slumped posture due to the posterior pelvic tilt. This study was conducted to compare the effects of proprioceptive neuromuscular facilitation (PNF stretching and modified anterior pelvic tilt taping (APTT on hamstring shortness-associated pelvic compensation while executing seated double-knee extension. Male college students (28 healthy young adults; mean age: 21.4 ± 2.1 years with hamstring shortness were recruited as study subjects and randomly assigned to either the PNF stretching group (control group or the APTT group (experimental group. In all the subjects, changes in the movement distance of the centre of gluteal pressure (COGP as well as rectus abdominis (RA and semitendinosus (SEM muscle activities were measured during seated double-knee extension while the respective intervention method was applied. Both groups showed significant decreases in COGP distance and RA muscle activity compared with their respective baseline values (p < 0.05, however, no significant changes were observed in SEM muscle activity. We can infer that not only a direct intervention on the hamstring, such as PNF stretching, but also a modified APTT-mediated pelvic intervention may be used as a method for reducing pelvic compensation induced by hamstring shortness.

Stretching and folding mechanism in foams

International Nuclear Information System (INIS)

Tufaile, Alberto; Pedrosa Biscaia Tufaile, Adriana

2008-01-01

We have described the stretching and folding of foams in a vertical Hele-Shaw cell containing air and a surfactant solution, from a sequence of upside-down flips. Besides the fractal dimension of the foam, we have observed the logistic growth for the soap film length. The stretching and folding mechanism is present during the foam formation, and this mechanism is observed even after the foam has reached its respective maximum fractal dimension. Observing the motion of bubbles inside the foam, large bubbles present power spectrum associated with random walk motion in both directions, while the small bubbles are scattered like balls in a Galton board

Stretching and folding mechanism in foams

Energy Technology Data Exchange (ETDEWEB)

Tufaile, Alberto [Escola de Artes, Ciencias e Humanidades, Soft Matter Laboratory, Universidade de Sao Paulo, 03828-000 Sao Paulo, SP (Brazil)], E-mail: tufaile@usp.br; Pedrosa Biscaia Tufaile, Adriana [Escola de Artes, Ciencias e Humanidades, Soft Matter Laboratory, Universidade de Sao Paulo, 03828-000 Sao Paulo, SP (Brazil)

2008-10-13

We have described the stretching and folding of foams in a vertical Hele-Shaw cell containing air and a surfactant solution, from a sequence of upside-down flips. Besides the fractal dimension of the foam, we have observed the logistic growth for the soap film length. The stretching and folding mechanism is present during the foam formation, and this mechanism is observed even after the foam has reached its respective maximum fractal dimension. Observing the motion of bubbles inside the foam, large bubbles present power spectrum associated with random walk motion in both directions, while the small bubbles are scattered like balls in a Galton board.

Activity of Palythoa caribaeorum Venom on Voltage-Gated Ion Channels in Mammalian Superior Cervical Ganglion Neurons.

Science.gov (United States)

Lazcano-Pérez, Fernando; Castro, Héctor; Arenas, Isabel; García, David E; González-Muñoz, Ricardo; Arreguín-Espinosa, Roberto

2016-05-05

The Zoanthids are an order of cnidarians whose venoms and toxins have been poorly studied. Palythoa caribaeorum is a zoanthid commonly found around the Mexican coastline. In this study, we tested the activity of P. caribaeorum venom on voltage-gated sodium channel (NaV1.7), voltage-gated calcium channel (CaV2.2), the A-type transient outward (IA) and delayed rectifier (IDR) currents of KV channels of the superior cervical ganglion (SCG) neurons of the rat. These results showed that the venom reversibly delays the inactivation process of voltage-gated sodium channels and inhibits voltage-gated calcium and potassium channels in this mammalian model. The compounds responsible for these effects seem to be low molecular weight peptides. Together, these results provide evidence for the potential use of zoanthids as a novel source of cnidarian toxins active on voltage-gated ion channels.

Maintained inspiratory activity during proportional assist ventilation in surfactant-depleted cats early after surfactant instillation: phrenic nerve and pulmonary stretch receptor activity

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Schaller Peter

2006-03-01

Full Text Available Abstract Background Inspiratory activity is a prerequisite for successful application of patient triggered ventilation such as proportional assist ventilation (PAV. It has recently been reported that surfactant instillation increases the activity of slowly adapting pulmonary stretch receptors (PSRs followed by a shorter inspiratory time (Sindelar et al, J Appl Physiol, 2005 [Epub ahead of print]. Changes in lung mechanics, as observed in preterm infants with respiratory distress syndrome and after surfactant treatment, might therefore influence the inspiratory activity when applying PAV early after surfactant treatment. Objective To investigate the regulation of breathing and ventilatory response in surfactant-depleted young cats during PAV and during continuous positive airway pressure (CPAP early after surfactant instillation in relation to phrenic nerve activity (PNA and the activity of PSRs. Methods Seven anesthetized, endotracheally intubated young cats were exposed to periods of CPAP and PAV with the same end-expiratory pressure (0.2–0.5 kPa before and after lung lavage and after surfactant instillation. PAV was set to compensate for 75% of the lung elastic recoil. Results Tidal volume and respiratory rate were higher with lower PaCO2 and higher PaO2 during PAV than during CPAP both before and after surfactant instillation (p Conclusion PSR activity and the control of breathing are maintained during PAV in surfactant-depleted cats early after surfactant instillation, with a higher ventilatory response and a lower breathing effort than during CPAP.

Fatigue Crack Growth Characteristics of Cold Stretched STS 304 Welded Joint

Energy Technology Data Exchange (ETDEWEB)

Lee, Jeong Won; Na, Seong Hyeon; Yoon, Dong Hyun; Kim, Jae Hoon [Chungnam Nat’l Univ., Daejeon (Korea, Republic of); Kim, Young Kyun; Kim, Ki Dong [Korea Gas Coporation R& D Division, Daejeon (Korea, Republic of)

2017-09-15

STS 304 steel is used as pressure vessel material, and although it exhibits excellent mechanical characteristics at a low temperature, it is heavier than other materials. To address this issue, a method using cold-stretching techniques for STS 304 can be applied. In this study, a cold-stretching part and welded joint specimen were directly obtained from a cold-stretching pressure vessel manufactured according to ASME code. Fatigue crack propagation tests were carried out at room temperature and -170℃ using the compliance method for stress ratios of 0.1 and 0.5. The results indicate that crack growth rate of the welded joint is higher than that of the cold-stretching part within the same stress intensity factor range. The outcome of this work is expected to serve as a basis for the development of a cold-stretched STS 304 pressure vessel.

Simulated physiological stretch increases expression of extracellular matrix proteins in human bladder smooth muscle cells via integrin α4/αv-FAK-ERK1/2 signaling pathway.

Science.gov (United States)

Chen, Shulian; Peng, Chuandu; Wei, Xin; Luo, Deyi; Lin, Yifei; Yang, Tongxin; Jin, Xi; Gong, Lina; Li, Hong; Wang, Kunjie

2017-08-01

To investigate the effect of simulated physiological stretch on the expression of extracellular matrix (ECM) proteins and the role of integrin α4/αv, focal adhesion kinase (FAK), extracellular regulated protein kinases 1/2 (ERK1/2) in the stretch-induced ECM protein expression of human bladder smooth muscle cells (HBSMCs). HBSMCs were seeded onto silicone membrane and subjected to simulated physiological stretch at the range of 5, 10, and 15% elongation. Expression of primary ECM proteins in HBSMCs was analyzed by real-time polymerase chain reaction and Western blot. Specificity of the FAK and ERK1/2 was determined by Western blot with FAK inhibitor and ERK1/2 inhibitor (PD98059). Specificity of integrin α4 and integrin αv was determined with small interfering ribonucleic acid (siRNA) transfection. The expression of collagen I (Col1), collagen III (Col3), and fibronectin (Fn) was increased significantly under the simulated physiological stretch of 10 and 15%. Integrin α4 and αv, FAK, ERK1/2 were activated by 10% simulated physiological stretch compared with the static condition. Pretreatment of ERK1/2 inhibitor, FAK inhibitor, integrin α4 siRNA, or integrin αv siRNA reduced the stretch-induced expression of ECM proteins. And FAK inhibitor decreased the stretch-induced ERK1/2 activity and ECM protein expression. Integrin α4 siRNA or integrin αv siRNA inhibited the stretch-induced activity of FAK. Simulated physiological stretch increases the expression of ECM proteins in HBSMCs, and integrin α4/αv-FAK-ERK1/2 signaling pathway partly modulates the mechano-transducing process.

Taurine activates delayed rectifier KV channels via a metabotropic pathway in retinal neurons

Science.gov (United States)

Bulley, Simon; Liu, Yufei; Ripps, Harris; Shen, Wen

2013-01-01

Taurine is one of the most abundant amino acids in the retina, throughout the CNS, and in heart and muscle cells. In keeping with its broad tissue distribution, taurine serves as a modulator of numerous basic processes, such as enzyme activity, cell development, myocardial function and cytoprotection. Despite this multitude of functional roles, the precise mechanism underlying taurine's actions has not yet been identified. In this study we report findings that indicate a novel role for taurine in the regulation of voltage-gated delayed rectifier potassium (KV) channels in retinal neurons by means of a metabotropic receptor pathway. The metabotropic taurine response was insensitive to the Cl− channel blockers, picrotoxin and strychnine, but it was inhibited by a specific serotonin 5-HT2A receptor antagonist, MDL11939. Moreover, we found that taurine enhanced KV channels via intracellular protein kinase C-mediated pathways. When 5-HT2A receptors were expressed in human embryonic kidney cells, taurine and AL34662, a non-specific 5-HT2 receptor activator, produced a similar regulation of KIR channels. In sum, this study provides new evidence that taurine activates a serotonin system, apparently via 5-HT2A receptors and related intracellular pathways. PMID:23045337

The effectiveness of manual stretching in the treatment of plantar heel pain: a systematic review

Directory of Open Access Journals (Sweden)

Parish Ben

2011-06-01

Full Text Available Abstract Background Plantar heel pain is a commonly occurring foot complaint. Stretching is frequently utilised as a treatment, yet a systematic review focusing only on its effectiveness has not been published. This review aimed to assess the effectiveness of stretching on pain and function in people with plantar heel pain. Methods Medline, EMBASE, CINAHL, AMED, and The Cochrane Library were searched from inception to July 2010. Studies fulfilling the inclusion criteria were independently assessed, and their quality evaluated using the modified PEDro scale. Results Six studies including 365 symptomatic participants were included. Two compared stretching with a control, one study compared stretching to an alternative intervention, one study compared stretching to both alternative and control interventions, and two compared different stretching techniques and durations. Quality rating on the modified Pedro scale varied from two to eight out of a maximum of ten points. The methodologies and interventions varied significantly between studies, making meta-analysis inappropriate. Most participants improved over the course of the studies, but when stretching was compared to alternative or control interventions, the changes only reached statistical significance in one study that used a combination of calf muscle stretches and plantar fascia stretches in their stretching programme. Another study comparing different stretching techniques, showed a statistically significant reduction in some aspects of pain in favour of plantar fascia stretching over calf stretches in the short term. Conclusions There were too few studies to assess whether stretching is effective compared to control or other interventions, for either pain or function. However, there is some evidence that plantar fascia stretching may be more effective than Achilles tendon stretching alone in the short-term. Appropriately powered randomised controlled trials, utilizing validated outcome

General anesthetic octanol and related compounds activate wild-type and delF508 cystic fibrosis chloride channels

OpenAIRE

Marcet, Brice; Becq, Frédéric; Norez, Caroline; Delmas, Patrick; Verrier, Bernard

2004-01-01

Cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel is defective during cystic fibrosis (CF). Activators of the CFTR Cl− channel may be useful for therapy of CF. Here, we demonstrate that a range of general anesthetics like normal-alkanols (n-alkanols) and related compounds can stimulate the Cl− channel activity of wild-type CFTR and delF508-CFTR mutant.The effects of n-alkanols like octanol on CFTR activity were measured by iodide (125I) efflux and patch-clamp techniques o...

Weak depth and along-strike variations in stretching from a multi-episodic finite stretching model: Evidence for uniform pure-shear extension in the opening of the South China Sea

Science.gov (United States)

Chen, Lin; Zhang, Zhongjie; Song, Haibin

2013-12-01

The South China Sea is widely believed to have been opened by seafloor spreading during the Cenozoic. The details of its lithospheric extension are still being debated, and it is unknown whether pure, simple, or conjunct shears are responsible for the opening of the South China Sea. The depth-dependent and along-strike extension derived from the single-stage finite stretching model or instantaneous stretching model is inconsistent with the observation that the South China Sea proto-margins have experienced multi-episodic extension since the Late Cretaceous. Based on the multi-episodic finite stretching model, we present the amount of lithosphere stretching at the northern continental margin of the South China Sea for different depth scales (upper crust, whole crust and lithosphere) and along several transects. The stretching factors are estimated by integrating seven deep-penetration seismic profiles, the Moho distribution derived from gravity modeling, and the tectonic subsidence data for 41 wells. The results demonstrate that the amount of stretching increases rapidly from 1.1 at the continent shelf to over 3.5 at the lower slope, but the stretching factors at the crust and lithosphere scales are consistent within error (from the uncertainty in paleobathymetry and sea-level change). Furthermore, the along-strike variation in stretching factor is within the range of 1.11-1.9 in west-east direction, accompanied by significant west-east differences in the thickness of high-velocity layers (HVLs) within the lowermost crust. This weak along-strike variation of the stretching factor is most likely produced by the preexisting contrasts in the composition and thermal structure of the lithosphere. The above observations suggest that the continental extension in the opening of the South China Sea mainly takes the form of a uniform pure shear rather than depth-dependent stretching.

Blockade of TRPM7 channel activity and cell death by inhibitors of 5-lipoxygenase.

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Hsiang-Chin Chen

2010-06-01

Full Text Available TRPM7 is a ubiquitous divalent-selective ion channel with its own kinase domain. Recent studies have shown that suppression of TRPM7 protein expression by RNA interference increases resistance to ischemia-induced neuronal cell death in vivo and in vitro, making the channel a potentially attractive pharmacological target for molecular intervention. Here, we report the identification of the 5-lipoxygenase inhibitors, NDGA, AA861, and MK886, as potent blockers of the TRPM7 channel. Using a cell-based assay, application of these compounds prevented cell rounding caused by overexpression of TRPM7 in HEK-293 cells, whereas inhibitors of 12-lipoxygenase and 15-lipoxygenase did not prevent the change in cell morphology. Application of the 5-lipoxygenase inhibitors blocked heterologously expressed TRPM7 whole-cell currents without affecting the protein's expression level or its cell surface concentration. All three inhibitors were also effective in blocking the native TRPM7 current in HEK-293 cells. However, two other 5-lipoxygenase specific inhibitors, 5,6-dehydro-arachidonic acid and zileuton, were ineffective in suppressing TRPM7 channel activity. Targeted knockdown of 5-lipoxygenase did not reduce TRPM7 whole-cell currents. In addition, application of 5-hydroperoxyeicosatetraenoic acid (5-HPETE, the product of 5-lipoxygenase, or 5-HPETE's downstream metabolites, leukotriene B4 and leukotriene D4, did not stimulate TRPM7 channel activity. These data suggested that NDGA, AA861, and MK886 reduced the TRPM7 channel activity independent of their effect on 5-lipoxygenase activity. Application of AA861 and NDGA reduced cell death for cells overexpressing TRPM7 cultured in low extracellular divalent cations. Moreover, treatment of HEK-293 cells with AA861 increased cell resistance to apoptotic stimuli to a level similar to that obtained for cells in which TRPM7 was knocked down by RNA interference. In conclusion, NDGA, AA861, and MK886 are potent blockers of

Effect of antisymmetric C–H stretching excitation on the dynamics of O({sup 1}D) + CH{sub 4} → OH + CH{sub 3}

Energy Technology Data Exchange (ETDEWEB)

Pan, Huilin; Yang, Jiayue; Zhang, Dong; Shuai, Quan; Jiang, Bo [State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023 (China); Dai, Dongxu; Wu, Guorong, E-mail: wugr@dicp.ac.cn, E-mail: xmyang@dicp.ac.cn; Yang, Xueming, E-mail: wugr@dicp.ac.cn, E-mail: xmyang@dicp.ac.cn [State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023 (China); Synergetic Innovation Center of Quantum Information and Quantum Physics, University of Science and Technology of China, Hefei, Anhui 230026 (China)

2014-04-21

The effect of antisymmetric C–H stretching excitation of CH{sub 4} on the dynamics and reactivity of the O({sup 1}D) + CH{sub 4} → OH + CD{sub 3} reaction at the collision energy of 6.10 kcal/mol has been investigated using the crossed-beam and time-sliced velocity map imaging techniques. The antisymmetric C–H stretching mode excited CH{sub 4} molecule was prepared by direct infrared excitation. From the measured images of the CH{sub 3} products with the infrared laser on and off, the product translational energy and angular distributions were derived for both the ground and vibrationally excited reactions. Experimental results show that the vibrational energy of the antisymmetric stretching excited CH{sub 4} reagent is channeled exclusively into the vibrational energy of the OH co-products and, hence, the OH products from the excited-state reaction are about one vibrational quantum hotter than those from the ground-state reaction, and the product angular distributions are barely affected by the vibrational excitation of the CH{sub 4} reagent. The reactivity was found to be suppressed by the antisymmetric stretching excitation of CH{sub 4} for all observed CH{sub 3} vibrational states. The degree of suppression is different for different CH{sub 3} vibrational states: the suppression is about 40%–60% for the ground state and the umbrella mode excited CH{sub 3} products, while for the CH{sub 3} products with one quantum symmetric stretching mode excitation, the suppression is much less pronounced. In consequence, the vibrational state distribution of the CH{sub 3} product from the excited-state reaction is considerably different from that of the ground-state reaction.

Immediate Effects of Neurodynamic Sliding versus Muscle Stretching on Hamstring Flexibility in Subjects with Short Hamstring Syndrome

Science.gov (United States)

Castellote-Caballero, Yolanda; Valenza, Maríe C.; Puentedura, Emilio J.; Fernández-de-las-Peñas, César; Alburquerque-Sendín, Francisco

2014-01-01

Background. Hamstring injuries continue to affect active individuals and although inadequate muscle extensibility remains a commonly accepted factor, little is known about the most effective method to improve flexibility. Purpose. To determine if an isolated neurodynamic sciatic sliding technique would improve hamstring flexibility to a greater degree than stretching or a placebo intervention in asymptomatic subjects with short hamstring syndrome (SHS). Study Design. Randomized double-blinded controlled trial. Methods. One hundred and twenty subjects with SHS were randomized to 1 of 3 groups: neurodynamic sliding, hamstring stretching, and placebo control. Each subject's dominant leg was measured for straight leg raise (SLR) range of motion (ROM) before and after interventions. Data were analyzed with a 3 × 2 mixed model ANOVA followed by simple main effects analyses. Results. At the end of the study, more ROM was observed in the Neurodynamic and Stretching groups compared to the Control group and more ROM in the Neurodynamic group compared to Stretching group. Conclusion. Findings suggest that a neurodynamic sliding technique will increase hamstring flexibility to a greater degree than static hamstring stretching in healthy subjects with SHS. Clinical Relevance. The use of neurodynamic sliding techniques to improve hamstring flexibility in sports may lead to a decreased incidence in injuries; however, this needs to be formally tested. PMID:26464889

Activity of Palythoa caribaeorum Venom on Voltage-Gated Ion Channels in Mammalian Superior Cervical Ganglion Neurons

Directory of Open Access Journals (Sweden)

Fernando Lazcano-Pérez

2016-05-01

Full Text Available The Zoanthids are an order of cnidarians whose venoms and toxins have been poorly studied. Palythoa caribaeorum is a zoanthid commonly found around the Mexican coastline. In this study, we tested the activity of P. caribaeorum venom on voltage-gated sodium channel (NaV1.7, voltage-gated calcium channel (CaV2.2, the A-type transient outward (IA and delayed rectifier (IDR currents of KV channels of the superior cervical ganglion (SCG neurons of the rat. These results showed that the venom reversibly delays the inactivation process of voltage-gated sodium channels and inhibits voltage-gated calcium and potassium channels in this mammalian model. The compounds responsible for these effects seem to be low molecular weight peptides. Together, these results provide evidence for the potential use of zoanthids as a novel source of cnidarian toxins active on voltage-gated ion channels.

Stretching the Border

DEFF Research Database (Denmark)

Horstmann, Alexander

2014-01-01

In this paper, I hope to add a complementary perspective to James Scott’s recent work on avoidance strategies of subaltern mountain people by focusing on what I call the refugee public. The educated Karen elite uses the space of exile in the Thai borderland to reconstitute resources and to re-ent......-based organizations succeed to stretch the border by establishing a firm presence that is supported by the international humanitarian economy in the refugee camps in Northwestern Thailand....

Slick (Kcnt2 Sodium-Activated Potassium Channels Limit Peptidergic Nociceptor Excitability and Hyperalgesia

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Danielle L Tomasello

2017-09-01

Full Text Available The Slick (Kcnt2 sodium-activated potassium (K Na channel is a rapidly gating and weakly voltage-dependent and sodium-dependent potassium channel with no clearly defined physiological function. Within the dorsal root ganglia (DRGs, we show Slick channels are exclusively expressed in small-sized and medium-sized calcitonin gene–related peptide (CGRP-containing DRG neurons, and a pool of channels are localized to large dense-core vesicles (LDCV-containing CGRP. We stimulated DRG neurons for CGRP release and found Slick channels contained within CGRP-positive LDCV translocated to the neuronal membrane. Behavioral studies in Slick knockout (KO mice indicated increased basal heat detection and exacerbated thermal hyperalgesia compared with wild-type littermate controls during neuropathic and chronic inflammatory pain. Electrophysiologic recordings of DRG neurons from Slick KO mice revealed that Slick channels contribute to outward current, propensity to fire action potentials (APs, and to AP properties. Our data suggest that Slick channels restrain the excitability of CGRP-containing neurons, diminishing pain behavior after inflammation and injury.

Alkali pH directly activates ATP-sensitive K+ channels and inhibits insulin secretion in beta-cells.

Science.gov (United States)

Manning Fox, Jocelyn E; Karaman, Gunce; Wheeler, Michael B

2006-11-17

Glucose stimulation of pancreatic beta-cells is reported to lead to sustained alkalization, while extracellular application of weak bases is reported to inhibit electrical activity and decrease insulin secretion. We hypothesize that beta-cell K(ATP) channel activity is modulated by alkaline pH. Using the excised patch-clamp technique, we demonstrate a direct stimulatory action of alkali pH on recombinant SUR1/Kir6.2 channels due to increased open probability. Bath application of alkali pH similarly activates native islet beta-cell K(ATP) channels, leading to an inhibition of action potentials, and hyperpolarization of membrane potential. In situ pancreatic perfusion confirms that these cellular effects of alkali pH are observable at a functional level, resulting in decreases in both phase 1 and phase 2 glucose-stimulated insulin secretion. Our data are the first to report a stimulatory effect of a range of alkali pH on K(ATP) channel activity and link this to downstream effects on islet beta-cell function.

A Novel Non-Planar Transverse Stretching Process for Micro-Porous PTFE Membranes and Resulting Characteristics

KAUST Repository

Chang, Y.-H.

2018-02-26

Polytetrafluoroethylene (PTFE) micro-porous membranes were prepared from PTFE fine powder through extruding, rolling, and uniaxial longitudinally stretching. In contrast to conventional planar transverse stretching, a novel 3D mold design of non-planar transverse stretching process was employed in this study to produce micro-porous structure. The morphology, membrane thickness, mean pore size, and porosity of the PTFE membrane were investigated. The results show that the non-planar transverse stretched membranes exhibit more uniform average pore diameter with thinner membrane thickness. Morphological changes induced by planar and non-planar transverse stretching for pore characteristics were investigated. The stretching conditions, stretching temperature and rate, affect the stretched membrane. Increasing temperature facilitated the uniformity of pore size and uniformity of membrane thickness. Moreover, increase in stretching rate resulted in finer pore size and thinner membrane.

Increased anion channel activity is an unavoidable event in ozone-induced programmed cell death.

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Takashi Kadono

Full Text Available BACKGROUND: Ozone is a major secondary air pollutant often reaching high concentrations in urban areas under strong daylight, high temperature and stagnant high-pressure systems. Ozone in the troposphere is a pollutant that is harmful to the plant. PRINCIPAL FINDINGS: By exposing cells to a strong pulse of ozonized air, an acute cell death was observed in suspension cells of Arabidopsis thaliana used as a model. We demonstrated that O(3 treatment induced the activation of a plasma membrane anion channel that is an early prerequisite of O(3-induced cell death in A. thaliana. Our data further suggest interplay of anion channel activation with well known plant responses to O(3, Ca(2+ influx and NADPH-oxidase generated reactive oxygen species (ROS in mediating the oxidative cell death. This interplay might be fuelled by several mechanisms in addition to the direct ROS generation by O(3; namely, H(2O(2 generation by salicylic and abscisic acids. Anion channel activation was also shown to promote the accumulation of transcripts encoding vacuolar processing enzymes, a family of proteases previously reported to contribute to the disruption of vacuole integrity observed during programmed cell death. SIGNIFICANCE: Collectively, our data indicate that anion efflux is an early key component of morphological and biochemical events leading to O(3-induced programmed cell death. Because ion channels and more specifically anion channels assume a crucial position in cells, an understanding about the underlying role(s for ion channels in the signalling pathway leading to programmed cell death is a subject that warrants future investigation.

Theory of high-force DNA stretching and overstretching.

Science.gov (United States)

Storm, C; Nelson, P C

2003-05-01

Single-molecule experiments on single- and double-stranded DNA have sparked a renewed interest in the force versus extension of polymers. The extensible freely jointed chain (FJC) model is frequently invoked to explain the observed behavior of single-stranded DNA, but this model does not satisfactorily describe recent high-force stretching data. We instead propose a model (the discrete persistent chain) that borrows features from both the FJC and the wormlike chain, and show that it resembles the data more closely. We find that most of the high-force behavior previously attributed to stretch elasticity is really a feature of the corrected entropic elasticity; the true stretch compliance of single-stranded DNA is several times smaller than that found by previous authors. Next we elaborate our model to allow coexistence of two conformational states of DNA, each with its own stretch and bend elastic constants. Our model is computationally simple and gives an excellent fit through the entire overstretching transition of nicked, double-stranded DNA. The fit gives the first value for the bend stiffness of the overstretched state. In particular, we find the effective bend stiffness for DNA in this state to be about 12 nm k(B)T, a value quite different from either the B-form or single-stranded DNA.

The Acute Effects of Upper Extremity Stretching on Throwing Velocity in Baseball Throwers

Directory of Open Access Journals (Sweden)

Michael Williams

2013-01-01

Full Text Available Purpose. To examine the effects of static and proprioceptive neuromuscular facilitation (PNF stretching of the shoulder internal rotators on throwing velocity. Subjects. 27 male throwers (mean age = 25.1 years old, SD = 2.4 with adequate knowledge of demonstrable throwing mechanics. Study Design. Randomized crossover trial with repeated measures. Methods. Subjects warmed up, threw 10 pitches at their maximum velocity, were randomly assigned to 1 of 3 stretching protocols (static, PNF, or no stretch, and then repeated their 10 pitches. Velocities were recorded after each pitch and average and peak velocities were recorded after each session. Results. Data were analyzed using a repeated measures ANOVA. No significant interaction between stretching and throwing velocity was observed. Main effects for time were not statistically significant. Main effects for the stretching groups were statistically significant. Discussion. Results suggest that stretching of the shoulder internal rotators did not significantly affect throwing velocity immediately after stretching. This may be due to the complexity of the throwing task. Conclusions. Stretching may be included in a thrower's warm-up without any effects on throwing velocity. Further research should be performed using a population with more throwing experience and skill.

Efficacy of hamstring stretching programs in schoolchildren. A systematic review

Directory of Open Access Journals (Sweden)

Carlos-Alberto BECERRA FERNANDEZ

2017-03-01

Full Text Available The main purpose of the present review was to examine the scientific literature on the effects of physical education-based stretching programs on hamstring extensibility in schoolchildren aged 6-11 years. For this purpose relevant studies were searched from ten electronic databases dated up through May 2015. Of the 25 potentially relevant articles identified and retrieved for more detailed evaluation, only eight studies were included in the present review because they met the inclusion criteria. The overall results showed that incorporating hamstring stretching as a part of physical education classes produces a significant improvement in the scores of the tests: straight leg raise and classic sit-and-reach, for the experimental groups, but not for control groups. Stretching programs can be included in Physical Education classes, specifically during the warm-up and the cool down periods in order to improve hamstring extensibility. Although it seems that the stretching exercises in the warm-up period could be less effective in gaining flexibility in school children. Studies that use a stretching volume between 4 and 7 minutes per session and 2-4 training classes per week, obtain statistically significant improvements on the levels of hamstring flexibility in the experimental groups. However, after a five-week detraining period, children revert back to their initial flexibility levels. Therefore, it seems appropriate that physical education teachers should implement stretching programs to improve the students´ flexibility during the Physical Education classes.

Implementation of a controller for linear positioners applicable in optical fiber stretching

International Nuclear Information System (INIS)

Castrillo Piedra, Andres Rodolfo

2014-01-01

A low cost controller is implemented for linear positioners applicable in optic fiber stretching. The possibility of using a donated equipment is evaluated by the Escuela de Ingenieria Mecanica. The equipment is required by the non-linear photonic research laboratory (NLPR-LAB) for stretching of micro structured fiber. The process has required a slow and precise stretching, so the controllers must be precisely programmed to rotate the motors at different speeds. Donated equipment is evaluated to see if it is possible to use for fiber stretching [es

Damage percolation during stretch flange forming of aluminum alloy sheet

Science.gov (United States)

Chen, Zengtao; Worswick, Michael J.; Keith Pilkey, A.; Lloyd, David J.

2005-12-01

A multi-scale finite element (FE)-damage percolation model was employed to simulate stretch flange forming of aluminum alloys AA5182 and AA5754. Material softening and strain gradients were captured using a Gurson-based FE model. FE results were then fed into the so-called damage percolation code, from which the damage development was modelled within measured microstructures. The formability of the stretch flange samples was predicted based upon the onset of catastrophic failure triggered by profuse void coalescence within the measured second-phase particle field. Damage development is quantified in terms of crack and void areal fractions, and compared to metallographic results obtained from interrupted stretch flange specimens. Parametric study is conducted on the effect of void nucleation strain in the prediction of formability of stretch flanges to "calibrate" proper nucleation strains for both alloys.

Identification and characterization of Ca2+-activated K+ channels in granulosa cells of the human ovary

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Berg Ulrike

2009-04-01

Full Text Available Abstract Background Granulosa cells (GCs represent a major endocrine compartment of the ovary producing sex steroid hormones. Recently, we identified in human GCs a Ca2+-activated K+ channel (KCa of big conductance (BKCa, which is involved in steroidogenesis. This channel is activated by intraovarian signalling molecules (e.g. acetylcholine via raised intracellular Ca2+ levels. In this study, we aimed at characterizing 1. expression and functions of KCa channels (including BKCa beta-subunits, and 2. biophysical properties of BKCa channels. Methods GCs were obtained from in vitro-fertilization patients and cultured. Expression of mRNA was determined by standard RT-PCR and protein expression in human ovarian slices was detected by immunohistochemistry. Progesterone production was measured in cell culture supernatants using ELISAs. Single channels were recorded in the inside-out configuration of the patch-clamp technique. Results We identified two KCa types in human GCs, the intermediate- (IK and the small-conductance KCa (SK. Their functionality was concluded from attenuation of human chorionic gonadotropin-stimulated progesterone production by KCa blockers (TRAM-34, apamin. Functional IK channels were also demonstrated by electrophysiological recording of single KCa channels with distinctive features. Both, IK and BKCa channels were found to be simultaneously active in individual GCs. In agreement with functional data, we identified mRNAs encoding IK, SK1, SK2 and SK3 in human GCs and proteins of IK and SK2 in corresponding human ovarian cells. Molecular characterization of the BKCa channel revealed the presence of mRNAs encoding several BKCa beta-subunits (beta2, beta3, beta4 in human GCs. The multitude of beta-subunits detected might contribute to variations in Ca2+ dependence of individual BKCa channels which we observed in electrophysiological recordings. Conclusion Functional and molecular studies indicate the presence of active IK and SK

Effect of stretching and proprioceptive loading in hand function among patients with cerebellar tremor

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Hariharasudhan Ravichandran

2016-01-01

Full Text Available Background and Objective: Tremor, the most common form of abnormal involuntary movement, affects the performance of activities of daily living. Evidence on effective form of physiotherapy techniques which can help manage intentional tremor and improve hand function among cerebellar dysfunction patients in inconclusive. Hence, this study aims to establish the effectiveness of stretching and proprioceptive loading among cerebellar patients with intentional tremors. The objective of this study is to compare the efficacy of stretching and proprioceptive loading among patients with cerebellar intention tremor. Materials and Methods: A total of thirty patients with intention tremor due to cerebellar lesion were recruited for this study. They were randomized into two groups, Group I received stretching exercise and Group II received proprioceptive loading exercise. Pre- and post-test outcome measures were taken at the end of duration of 3 weeks intervention. Outcome measures were Fahn's tremor rating scale and nine hole peg test. Results: Statistical analyses were done by McNemar test, Wilcoxon's signed rank test, and Mann–Whitney test. Post-test scores of both groups were compared and found that Group II treated with proprioceptive loading exercise had higher significant result than the group treated with strengthening exercise program. Conclusion: Proprioceptive loading exercise has demonstrated signifi cant effect on reducing cerebellar tremor and improving muscle coordination in reaching activities.

Role of androgen receptor on cyclic mechanical stretch-regulated proliferation of C2C12 myoblasts and its upstream signals: IGF-1-mediated PI3K/Akt and MAPKs pathways.

Science.gov (United States)

Ma, Yiming; Fu, Shaoting; Lu, Lin; Wang, Xiaohui

2017-07-15

To detect the effects of androgen receptor (AR) on cyclic mechanical stretch-modulated proliferation of C2C12 myoblasts and its pathways: roles of IGF-1, PI3K and MAPK. C2C12 were randomly divided into five groups: un-stretched control, six or 8 h of fifteen percent stretch, and six or 8 h of twenty percent stretch. Cyclic mechanical stretch of C2C12 were completed using a computer-controlled FlexCell Strain Unit. Cell proliferation and IGF-1 concentration in medium were detected by CCK8 and ELISA, respectively. Expressions of AR and IGF-1R, and expressions and activities of PI3K, p38 and ERK1/2 in stretched C2C12 cells were determined by Western blot. ①The proliferation of C2C12 cells, IGF-1 concentration in medium, expressions of AR and IGF-1R, and activities of PI3K, p38 and ERK1/2 were increased by 6 h of fifteen percent stretch, while decreased by twenty percent stretch for six or 8 h ②The fifteen percent stretch-increased proliferation of C2C12 cells was reversed by AR inhibitor, Flutamide. ③The increases of AR expression, activities of PI3K, p38 and ERK1/2 resulted from fifteen percent stretch were attenuated by IGF-1 neutralizing antibody, while twenty percent stretch-induced decreases of the above indicators were enhanced by recombinant IGF-1. ④Specific inhibitors of p38, ERK1/2 and PI3K all decreased the expression of AR in fifteen percent and twenty percent of stretched C2C12 cells. Cyclic mechanical stretch modulated the proliferation of C2C12 cells, which may be attributed to the alterations of AR via IGF-1-PI3K/Akt and IGF-1-MAPK (p38, ERK1/2) pathways in C2C12 cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular, biophysical, and pharmacological properties of calcium-activated chloride channels.

Science.gov (United States)

Kamaleddin, Mohammad Amin

2018-02-01

Calcium-activated chloride channels (CaCCs) are a family of anionic transmembrane ion channels. They are mainly responsible for the movement of Cl - and other anions across the biological membranes, and they are widely expressed in different tissues. Since the Cl - flow into or out of the cell plays a crucial role in hyperpolarizing or depolarizing the cells, respectively, the impact of intracellular Ca 2+ concentration on these channels is attracting a lot of attentions. After summarizing the molecular, biophysical, and pharmacological properties of CaCCs, the role of CaCCs in normal cellular functions will be discussed, and I will emphasize how dysregulation of CaCCs in pathological conditions can account for different diseases. A better understanding of CaCCs and a pivotal regulatory role of Ca 2+ can shed more light on the therapeutic strategies for different neurological disorders that arise from chloride dysregulation, such as asthma, cystic fibrosis, and neuropathic pain. © 2017 Wiley Periodicals, Inc.

COMPARISON OF EFFECTS OF ABDOMINAL STRETCHING EXERCISE AND COLD COMPRESS THERAPY ON MENSTRUAL PAIN INTENSITY IN TEENAGE GIRLS

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Desta Ayu Cahya Rosyida

2017-07-01

Full Text Available Background: Pain during menstruation is not uncommon, especially in young women, which has an impact on their life activities. Objective: To examine the effect of abdominal stretching exercise and cold compress therapy on decreasing intensity of menstrual pain in teenage girls at SMK Bakti Indonesia Medika. Design: A Quasy Experimental Study with two group comparison pretest-postest design. There were 46 respondents selected in this study by consecutive sampling that consisted of 23 samples in the abdominal stretching exercise group and 23 samples in the cold compress group. The menstrual pain was measured using VAS (visual analog scale. Data were analyzed using Mann-Whitney, Chi-Square, and Wilcoxon test. Results: Findings showed that the mean of menstrual pain before intervention in the abdominal stretching exercise was 7.04 and in the cold compress therapy was 6.74 with p-value 0.211 (<0.05, which indicated that there was no mean difference of pain between both groups. However, after intervention, the menstrual pain was reduced from 7.04 to 1.91 (5.09 difference in the abdominal stretching exercise group; and from 6.74 to 5.52 (1.22 difference in the cold compress group with p-value 0.000 (<0.05, which indicated that there was statistically significant difference of menstrual pain before and after intervention, both abdominal stretching exercise and cold compress therapy. Conclusion: There were statistically significant effects of abdominal stretching exercise and cold compress therapy on menstrual pain in teenage girls. The abdominal stretching exercise is more effective than cold compress therapy in reducing menstrual pain intensity. Thus, it is suggested that abdominal stretching exercise can be an alternative choice of management of dysmenorrhea in teenage girls, and can be a part of subject in the education as non-pharmacological medicine.

Jack-knife stretching promotes flexibility of tight hamstrings after 4 weeks: a pilot study.

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Sairyo, Koichi; Kawamura, Takeshi; Mase, Yasuyoshi; Hada, Yasushi; Sakai, Toshinori; Hasebe, Kiyotaka; Dezawa, Akira

2013-08-01

Tight hamstrings are reported to be one of the causes of low back pain. However, there have been few reports on effective stretching procedures for the tight hamstrings. The so-called jack-knife stretch, an active-static type of stretching, can efficiently increase the flexibility of tight hamstrings. To evaluate hamstring tightness before and after the 4-week stretching protocol in healthy volunteer adults and patients aged under 18 years with low back pain. For understanding the hamstrings tightness, we measured two parameters including (1) finger to floor distance (FFD) and (2) pelvis forward inclination angle (PFIA). Eight healthy adult volunteers who had no lumbar or hip problems participated in this study (mean age: 26.8 years). All lacked flexibility and their FFD were positive before the experiment. Subjects performed 2 sets of the jack-knife stretch every day for 4 weeks. One set consisted of 5 repetitions, each held for 5 s. Before and during the 4-week experiment, the FFD and PFIA of toe-touching tests were measured weekly. For 17 of the sports players aged under 18, only FFD was measured. In adult volunteers, FFD was 14.1 ± 6.1 cm before the experiment and decreased to -8.1 ± 3.7 cm by the end of week 4, indicating a gain in flexibility of 22.2 cm. PFIA was 50.6 ± 8.2 before the experiment and 83.8 ± 5.8 degrees after. Before and after the experiment, the differences were significant (p hamstrings.

Purification of charybdotoxine, a specific inhibitor of the high-conductance Ca2+-activated K+ channel

International Nuclear Information System (INIS)

Smith, C.; Phillips, M.; Miller, C.

1986-01-01

Charybdotoxim is a high-affinity specific inhibitor of the high-conductance Ca 2+ -activated K + channel found in the plasma membranes of many vertebrate cell types. Using Ca 2+ -activated K + channels reconstituted into planar lipid bilayer membranes as an assay, the authors have purified the toxin from the venom of the scorpion Leiurus quinquestriatus by a two-step procedure involving chromatofocusing on SP-Sephadex, followed by reversed-phase high-performance liquid chromatography. Charybdotoxin is shown to be a highly basic protein with a mass of 10 kDa. Under the standard assay conditions, the purified toxin inhibits the Ca 2+ -activated K + channel with an apparent dissociation constant of 3.5 nM. The protein is unusually stable, with inhibitory potency being insensitive to boiling or exposure to organic solvents. The toxin's activity is sensitive to chymotrypsin treatment and to acylation of lysine groups. The protein may be radioiodinated without loss of activity

Coherent time-stretch transformation for real-time capture of wideband signals.

Science.gov (United States)

Buckley, Brandon W; Madni, Asad M; Jalali, Bahram

2013-09-09

Time stretch transformation of wideband waveforms boosts the performance of analog-to-digital converters and digital signal processors by slowing down analog electrical signals before digitization. The transform is based on dispersive Fourier transformation implemented in the optical domain. A coherent receiver would be ideal for capturing the time-stretched optical signal. Coherent receivers offer improved sensitivity, allow for digital cancellation of dispersion-induced impairments and optical nonlinearities, and enable decoding of phase-modulated optical data formats. Because time-stretch uses a chirped broadband (>1 THz) optical carrier, a new coherent detection technique is required. In this paper, we introduce and demonstrate coherent time stretch transformation; a technique that combines dispersive Fourier transform with optically broadband coherent detection.

NS309 decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating SK3 channels

Science.gov (United States)

Parajuli, Shankar P; Hristov, Kiril L; Soder, Rupal P; Kellett, Whitney F; Petkov, Georgi V

2013-01-01

Background and Purpose Overactive bladder (OAB) is often associated with abnormally increased detrusor smooth muscle (DSM) contractions. We used NS309, a selective and potent opener of the small or intermediate conductance Ca2+-activated K+ (SK or IK, respectively) channels, to evaluate how SK/IK channel activation modulates DSM function. Experimental Approach We employed single-cell RT-PCR, immunocytochemistry, whole cell patch-clamp in freshly isolated rat DSM cells and isometric tension recordings of isolated DSM strips to explore how the pharmacological activation of SK/IK channels with NS309 modulates DSM function. Key Results We detected SK3 but not SK1, SK2 or IK channels expression at both mRNA and protein levels by RT-PCR and immunocytochemistry in DSM single cells. NS309 (10 μM) significantly increased the whole cell SK currents and hyperpolarized DSM cell resting membrane potential. The NS309 hyperpolarizing effect was blocked by apamin, a selective SK channel inhibitor. NS309 inhibited the spontaneous phasic contraction amplitude, force, frequency, duration and tone of isolated DSM strips in a concentration-dependent manner. The inhibitory effect of NS309 on spontaneous phasic contractions was blocked by apamin but not by TRAM-34, indicating no functional role of the IK channels in rat DSM. NS309 also significantly inhibited the pharmacologically and electrical field stimulation-induced DSM contractions. Conclusions and Implications Our data reveal that SK3 channel is the main SK/IK subtype in rat DSM. Pharmacological activation of SK3 channels with NS309 decreases rat DSM cell excitability and contractility, suggesting that SK3 channels might be potential therapeutic targets to control OAB associated with detrusor overactivity. PMID:23145946

Single-channel kinetics of BK (Slo1 channels

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Yanyan eGeng

2015-01-01

Full Text Available Single-channel kinetics has proven a powerful tool to reveal information about the gating mechanisms that control the opening and closing of ion channels. This introductory review focuses on the gating of large conductance Ca2+- and voltage-activated K+ (BK or Slo1 channels at the single-channel level. It starts with single-channel current records and progresses to presentation and analysis of single-channel data and the development of gating mechanisms in terms of discrete state Markov (DSM models. The DSM models are formulated in terms of the tetrameric modular structure of BK channels, consisting of a central transmembrane pore-gate domain (PGD attached to four surrounding transmembrane voltage sensing domains (VSD and a large intracellular cytosolic domain (CTD, also referred to as the gating ring. The modular structure and data analysis shows that the Ca2+ and voltage dependent gating considered separately can each be approximated by 10-state two-tiered models with 5 closed states on the upper tier and 5 open states on the lower tier. The modular structure and joint Ca2+ and voltage dependent gating are consistent with a 50 state two-tiered model with 25 closed states on the upper tier and 25 open states on the lower tier. Adding an additional tier of brief closed (flicker states to the 10-state or 50-state models improved the description of the gating. For fixed experimental conditions a channel would gate in only a subset of the potential number of states. The detected number of states and the correlations between adjacent interval durations are consistent with the tiered models. The examined models can account for the single-channel kinetics and the bursting behavior of gating. Ca2+ and voltage activate BK channels by predominantly increasing the effective opening rate of the channel with a smaller decrease in the effective closing rate. Ca2+ and depolarization thus activate by mainly destabilizing the closed states.

Coupling of SK channels, L-type Ca2+ channels, and ryanodine receptors in cardiomyocytes.

Science.gov (United States)

Zhang, Xiao-Dong; Coulibaly, Zana A; Chen, Wei Chun; Ledford, Hannah A; Lee, Jeong Han; Sirish, Padmini; Dai, Gu; Jian, Zhong; Chuang, Frank; Brust-Mascher, Ingrid; Yamoah, Ebenezer N; Chen-Izu, Ye; Izu, Leighton T; Chiamvimonvat, Nipavan

2018-03-16

Small-conductance Ca 2+ -activated K + (SK) channels regulate the excitability of cardiomyocytes by integrating intracellular Ca 2+ and membrane potentials on a beat-to-beat basis. The inextricable interplay between activation of SK channels and Ca 2+ dynamics suggests the pathology of one begets another. Yet, the exact mechanistic underpinning for the activation of cardiac SK channels remains unaddressed. Here, we investigated the intracellular Ca 2+ microdomains necessary for SK channel activation. SK currents coupled with Ca 2+ influx via L-type Ca 2+ channels (LTCCs) continued to be elicited after application of caffeine, ryanodine or thapsigargin to deplete SR Ca 2+ store, suggesting that LTCCs provide the immediate Ca 2+ microdomain for the activation of SK channels in cardiomyocytes. Super-resolution imaging of SK2, Ca v 1.2 Ca 2+ channel, and ryanodine receptor 2 (RyR2) was performed to quantify the nearest neighbor distances (NND) and localized the three molecules within hundreds of nanometers. The distribution of NND between SK2 and RyR2 as well as SK2 and Ca v 1.2 was bimodal, suggesting a spatial relationship between the channels. The activation mechanism revealed by our study paved the way for the understanding of the roles of SK channels on the feedback mechanism to regulate the activities of LTCCs and RyR2 to influence local and global Ca 2+ signaling.

A proton-activated, outwardly rectifying chloride channel in human umbilical vein endothelial cells

International Nuclear Information System (INIS)

Ma Zhiyong; Zhang Wei; Chen Liang; Wang Rong; Kan Xiaohong; Sun Guizhen; Liu Chunxi; Li Li; Zhang Yun

2008-01-01

Extracellular acidic pH-activated chloride channel I Cl,acid , has been characterized in HEK 293 cells and mammalian cardiac myocytes. This study was designed to characterize I Cl,acid in human umbilical vein endothelial cells(HUVECs). The activation and deactivation of the current rapidly and repeatedly follows the change of the extracellular solution at pH 4.3, with the threshold pH 5.3. In addition, at very positive potentials, the current displays a time-dependent facilitation. pH-response relationship for I Cl,acid revealed that EC 50 is pH 4.764 with a threshold pH value of pH 5.3 and nH of 14.545. The current can be blocked by the Cl - channel inhibitor DIDS (100 μM). In summary, for the first time we report the presence of proton-activated, outwardly rectifying chloride channel in HUVECs. Because an acidic environment can develop in local myocardium under pathological conditions such as myocardial ischemia, I Cl,acid would play a role in regulation of EC function under these pathological conditions

A ligand channel through the G protein coupled receptor opsin.

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Peter W Hildebrand

Full Text Available The G protein coupled receptor rhodopsin contains a pocket within its seven-transmembrane helix (TM structure, which bears the inactivating 11-cis-retinal bound by a protonated Schiff-base to Lys296 in TM7. Light-induced 11-cis-/all-trans-isomerization leads to the Schiff-base deprotonated active Meta II intermediate. With Meta II decay, the Schiff-base bond is hydrolyzed, all-trans-retinal is released from the pocket, and the apoprotein opsin reloaded with new 11-cis-retinal. The crystal structure of opsin in its active Ops* conformation provides the basis for computational modeling of retinal release and uptake. The ligand-free 7TM bundle of opsin opens into the hydrophobic membrane layer through openings A (between TM1 and 7, and B (between TM5 and 6, respectively. Using skeleton search and molecular docking, we find a continuous channel through the protein that connects these two openings and comprises in its central part the retinal binding pocket. The channel traverses the receptor over a distance of ca. 70 A and is between 11.6 and 3.2 A wide. Both openings are lined with aromatic residues, while the central part is highly polar. Four constrictions within the channel are so narrow that they must stretch to allow passage of the retinal beta-ionone-ring. Constrictions are at openings A and B, respectively, and at Trp265 and Lys296 within the retinal pocket. The lysine enforces a 90 degrees elbow-like kink in the channel which limits retinal passage. With a favorable Lys side chain conformation, 11-cis-retinal can take the turn, whereas passage of the all-trans isomer would require more global conformational changes. We discuss possible scenarios for the uptake of 11-cis- and release of all-trans-retinal. If the uptake gate of 11-cis-retinal is assigned to opening B, all-trans is likely to leave through the same gate. The unidirectional passage proposed previously requires uptake of 11-cis-retinal through A and release of photolyzed all

Experience with ActiveX control for simple channel access

International Nuclear Information System (INIS)

Timossi, C.; Nishimura, H.; McDonald, J.

2003-01-01

Accelerator control system applications at Berkeley Lab's Advanced Light Source (ALS) are typically deployed on operator consoles running Microsoft Windows 2000 and utilize EPICS[2]channel access for data access. In an effort to accommodate the wide variety of Windows based development tools and developers with little experience in network programming, ActiveX controls have been deployed on the operator stations. Use of ActiveX controls for use in the accelerator control environment has been presented previously[1]. Here we report on some of our experiences with the use and development of these controls

Transient filament stretching rheometer II

DEFF Research Database (Denmark)

Kolte, Mette Irene; Rasmussen, Henrik K.; Hassager, Ole

1997-01-01

The Lagrangian sspecification is used to simulate the transient stretching filament rheometer. Simulations are performed for dilute PIB-solutions modeled as a four mode Oldroyd-B fluid and a semidilute PIB-solution modeled as a non-linear single integral equation. The simulations are compared...

Investing in a Large Stretch Press

Science.gov (United States)

Choate, M.; Nealson, W.; Jay, G.; Buss, W.

1986-01-01

Press for forming large aluminum parts from plates provides substantial economies. Study assessed advantages and disadvantages of investing in large stretch-forming press, and also developed procurement specification for press.

Levcromakalim- and isoprenaline-induced relaxation of human isolated airways--role of the epithelium and of K+ channel activation.

Science.gov (United States)

Black, J L; Johnson, P R; McKay, K O; Carey, D; Armour, C L

1994-06-01

In this study we have investigated the mechanism of action of levcromakalim and isoprenaline in human isolated airways with respect to the K+ channels they activate and the possibility that these smooth muscle relaxants activate K+ channels on the airway epithelium. Mechanical removal of the epithelial layer (mean percentage of epithelium present 20 +/- 3%, n = 20 tissues) did not affect the relaxation responses to levcromakalim or isoprenaline, either in terms of maximal relaxation or sensitivity. Whilst having no effect on isoprenaline-induced relaxation, studied from basal tone, the ATP-sensitive K+ channel blocker BRL 31660 (10, 30 and 50 microM) reduced relaxation responses induced (from basal tone) by levcromakalim from 74 +/- 6% (of the maximal response to isoprenaline) to 48 +/- 12% (n = 7), 9 +/- 9% (n = 4) and 0 (n = 4), respectively. Charybdotoxin, a blocker of high conductance Ca(2+)-activated K+ channels, at concentrations of 30 and 100 nM, had no effect on either levcromakalim- or or isoprenaline-induced relaxation responses and yet charybdotoxin was active at KCa channels in outside-out patches of hippocampal granule cells. Moreover, tetraethylammonium (10 mM) inhibited neither isoprenaline- nor levcromakalim-induced relaxation. This study has demonstrated that the relaxation responses elicited in human bronchus to isoprenaline and levcromakalim are likely to be the result of direct effects on the smooth muscle with no contribution from epithelial receptors or K+ channels. The actions of levcromakalim appear to be mediated only via activation of KATP channels. Further, we have made the important observation that, under the experimental conditions of our study, isoprenaline does not activate the KCa channel to produce relaxation in human bronchus.

Hydralazine-induced vasodilation involves opening of high conductance Ca2+-activated K+ channels

DEFF Research Database (Denmark)

Bang, Lone; Nielsen-Kudsk, J E; Gruhn, N

1998-01-01

The purpose of this study was to investigate whether high conductance Ca2+-activated K+ channels (BK(Ca)) are mediating the vasodilator action of hydralazine. In isolated porcine coronary arteries, hydralazine (1-300 microM), like the K+ channel opener levcromakalim, preferentially relaxed......M) suppressed this response by 82% (P opening of BK(Ca) takes part in the mechanism whereby...

Unfolding of a Temperature-Sensitive Domain Controls Voltage-Gated Channel Activation.

Science.gov (United States)

Arrigoni, Cristina; Rohaim, Ahmed; Shaya, David; Findeisen, Felix; Stein, Richard A; Nurva, Shailika Reddy; Mishra, Smriti; Mchaourab, Hassane S; Minor, Daniel L

2016-02-25

Voltage-gated ion channels (VGICs) are outfitted with diverse cytoplasmic domains that impact function. To examine how such elements may affect VGIC behavior, we addressed how the bacterial voltage-gated sodium channel (BacNa(V)) C-terminal cytoplasmic domain (CTD) affects function. Our studies show that the BacNa(V) CTD exerts a profound influence on gating through a temperature-dependent unfolding transition in a discrete cytoplasmic domain, the neck domain, proximal to the pore. Structural and functional studies establish that the BacNa(V) CTD comprises a bi-partite four-helix bundle that bears an unusual hydrophilic core whose integrity is central to the unfolding mechanism and that couples directly to the channel activation gate. Together, our findings define a general principle for how the widespread four-helix bundle cytoplasmic domain architecture can control VGIC responses, uncover a mechanism underlying the diverse BacNa(V) voltage dependencies, and demonstrate that a discrete domain can encode the temperature-dependent response of a channel. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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.

Optimal stretching in the reacting wake of a bluff body.

Science.gov (United States)

Wang, Jinge; Tithof, Jeffrey; Nevins, Thomas D; Colón, Rony O; Kelley, Douglas H

2017-12-01

We experimentally study spreading of the Belousov-Zhabotinsky reaction behind a bluff body in a laminar flow. Locations of reacted regions (i.e., regions with high product concentration) correlate with a moderate range of Lagrangian stretching and that range is close to the range of optimal stretching previously observed in topologically different flows [T. D. Nevins and D. H. Kelley, Phys. Rev. Lett. 117, 164502 (2016)]. The previous work found optimal stretching in a closed, vortex dominated flow, but this article uses an open flow and only a small area of appreciable vorticity. We hypothesize that optimal stretching is common in advection-reaction-diffusion systems with an excitation threshold, including excitable and bistable systems, and that the optimal range depends on reaction chemistry and not on flow shape or characteristic speed. Our results may also give insight into plankton blooms behind islands in ocean currents.

Stretching of material lines in pseudo-turbulence induced by small rising bubbles

International Nuclear Information System (INIS)

Tanaka, M; Tsujimura, Y; Kanatani, H

2011-01-01

Direct numerical simulations have been conducted for the stretching of material lines in pseudo-turbulence induced by small rising bubbles in order to understand the mixing characteristics of bubbly flows. Contaminated bubbles are considered and are treated as light solid particles. An immersed boundary method has been used for evaluating the coupling force between the bubbles and the surrounding fluid flows. Numerical results show that the total length of material lines increases exponentially in time as a result of stretching and folding due to the rising bubbles. The material lines tend to accumulate in the wake regions of the bubbles, and they are strongly stretched in the vertical direction there. It is also found that the stretching rate of material lines increases with the mean void fraction when it is normalized by the magnitude of the rate-of-strain tensor of liquid flow in pseudo-turbulence. In the case of high void fractions, material lines tend to align with the direction of maximum stretching, and are effectively stretched.

Stretching of material lines in pseudo-turbulence induced by small rising bubbles

Energy Technology Data Exchange (ETDEWEB)

Tanaka, M; Tsujimura, Y; Kanatani, H, E-mail: mtanaka@kit.ac.jp [Department of Mechanical and System Engineering, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585 (Japan)

2011-12-22

Direct numerical simulations have been conducted for the stretching of material lines in pseudo-turbulence induced by small rising bubbles in order to understand the mixing characteristics of bubbly flows. Contaminated bubbles are considered and are treated as light solid particles. An immersed boundary method has been used for evaluating the coupling force between the bubbles and the surrounding fluid flows. Numerical results show that the total length of material lines increases exponentially in time as a result of stretching and folding due to the rising bubbles. The material lines tend to accumulate in the wake regions of the bubbles, and they are strongly stretched in the vertical direction there. It is also found that the stretching rate of material lines increases with the mean void fraction when it is normalized by the magnitude of the rate-of-strain tensor of liquid flow in pseudo-turbulence. In the case of high void fractions, material lines tend to align with the direction of maximum stretching, and are effectively stretched.

Increased expression of the auxiliary beta(2-subunit of ventricular L-type Ca(2+ channels leads to single-channel activity characteristic of heart failure.

Directory of Open Access Journals (Sweden)

Roger Hullin

2007-03-01

Full Text Available Increased activity of single ventricular L-type Ca(2+-channels (L-VDCC is a hallmark in human heart failure. Recent findings suggest differential modulation by several auxiliary beta-subunits as a possible explanation.By molecular and functional analyses of human and murine ventricles, we find that enhanced L-VDCC activity is accompanied by altered expression pattern of auxiliary L-VDCC beta-subunit gene products. In HEK293-cells we show differential modulation of single L-VDCC activity by coexpression of several human cardiac beta-subunits: Unlike beta(1 or beta(3 isoforms, beta(2a and beta(2b induce a high-activity channel behavior typical of failing myocytes. In accordance, beta(2-subunit mRNA and protein are up-regulated in failing human myocardium. In a model of heart failure we find that mice overexpressing the human cardiac Ca(V1.2 also reveal increased single-channel activity and sarcolemmal beta(2 expression when entering into the maladaptive stage of heart failure. Interestingly, these animals, when still young and non-failing ("Adaptive Phase", reveal the opposite phenotype, viz: reduced single-channel activity accompanied by lowered beta(2 expression. Additional evidence for the cause-effect relationship between beta(2-subunit expression and single L-VDCC activity is provided by newly engineered, double-transgenic mice bearing both constitutive Ca(V1.2 and inducible beta(2 cardiac overexpression. Here in non-failing hearts induction of beta(2-subunit overexpression mimicked the increase of single L-VDCC activity observed in murine and human chronic heart failure.Our study presents evidence of the pathobiochemical relevance of beta(2-subunits for the electrophysiological phenotype of cardiac L-VDCC and thus provides an explanation for the single L-VDCC gating observed in human and murine heart failure.

Reduced Tonoplast Fast-Activating and Slow-Activating Channel Activity Is Essential for Conferring Salinity Tolerance in a Facultative Halophyte, Quinoa1[C][W][OA

Science.gov (United States)

Bonales-Alatorre, Edgar; Shabala, Sergey; Chen, Zhong-Hua; Pottosin, Igor

2013-01-01

Halophyte species implement a “salt-including” strategy, sequestering significant amounts of Na+ to cell vacuoles. This requires a reduction of passive Na+ leak from the vacuole. In this work, we used quinoa (Chenopodium quinoa) to investigate the ability of halophytes to regulate Na+-permeable slow-activating (SV) and fast-activating (FV) tonoplast channels, linking it with Na+ accumulation in mesophyll cells and salt bladders as well as leaf photosynthetic efficiency under salt stress. Our data indicate that young leaves rely on Na+ exclusion to salt bladders, whereas old ones, possessing far fewer salt bladders, depend almost exclusively on Na+ sequestration to mesophyll vacuoles. Moreover, although old leaves accumulate more Na+, this does not compromise their leaf photochemistry. FV and SV channels are slightly more permeable for K+ than for Na+, and vacuoles in young leaves express less FV current and with a density unchanged in plants subjected to high (400 mm NaCl) salinity. In old leaves, with an intrinsically lower density of the FV current, FV channel density decreases about 2-fold in plants grown under high salinity. In contrast, intrinsic activity of SV channels in vacuoles from young leaves is unchanged under salt stress. In vacuoles of old leaves, however, it is 2- and 7-fold lower in older compared with young leaves in control- and salt-grown plants, respectively. We conclude that the negative control of SV and FV tonoplast channel activity in old leaves reduces Na+ leak, thus enabling efficient sequestration of Na+ to their vacuoles. This enables optimal photosynthetic performance, conferring salinity tolerance in quinoa species. PMID:23624857

BAX channel activity mediates lysosomal disruption linked to Parkinson disease.

Science.gov (United States)

Bové, Jordi; Martínez-Vicente, Marta; Dehay, Benjamin; Perier, Celine; Recasens, Ariadna; Bombrun, Agnes; Antonsson, Bruno; Vila, Miquel

2014-05-01

Lysosomal disruption is increasingly regarded as a major pathogenic event in Parkinson disease (PD). A reduced number of intraneuronal lysosomes, decreased levels of lysosomal-associated proteins and accumulation of undegraded autophagosomes (AP) are observed in PD-derived samples, including fibroblasts, induced pluripotent stem cell-derived dopaminergic neurons, and post-mortem brain tissue. Mechanistic studies in toxic and genetic rodent PD models attribute PD-related lysosomal breakdown to abnormal lysosomal membrane permeabilization (LMP). However, the molecular mechanisms underlying PD-linked LMP and subsequent lysosomal defects remain virtually unknown, thereby precluding their potential therapeutic targeting. Here we show that the pro-apoptotic protein BAX (BCL2-associated X protein), which permeabilizes mitochondrial membranes in PD models and is activated in PD patients, translocates and internalizes into lysosomal membranes early following treatment with the parkinsonian neurotoxin MPTP, both in vitro and in vivo, within a time-frame correlating with LMP, lysosomal disruption, and autophagosome accumulation and preceding mitochondrial permeabilization and dopaminergic neurodegeneration. Supporting a direct permeabilizing effect of BAX on lysosomal membranes, recombinant BAX is able to induce LMP in purified mouse brain lysosomes and the latter can be prevented by pharmacological blockade of BAX channel activity. Furthermore, pharmacological BAX channel inhibition is able to prevent LMP, restore lysosomal levels, reverse AP accumulation, and attenuate mitochondrial permeabilization and overall nigrostriatal degeneration caused by MPTP, both in vitro and in vivo. Overall, our results reveal that PD-linked lysosomal impairment relies on BAX-induced LMP, and point to small molecules able to block BAX channel activity as potentially beneficial to attenuate both lysosomal defects and neurodegeneration occurring in PD.

Time stretch and its applications

Science.gov (United States)

Mahjoubfar, Ata; Churkin, Dmitry V.; Barland, Stéphane; Broderick, Neil; Turitsyn, Sergei K.; Jalali, Bahram

2017-06-01

Observing non-repetitive and statistically rare signals that occur on short timescales requires fast real-time measurements that exceed the speed, precision and record length of conventional digitizers. Photonic time stretch is a data acquisition method that overcomes the speed limitations of electronic digitizers and enables continuous ultrafast single-shot spectroscopy, imaging, reflectometry, terahertz and other measurements at refresh rates reaching billions of frames per second with non-stop recording spanning trillions of consecutive frames. The technology has opened a new frontier in measurement science unveiling transient phenomena in nonlinear dynamics such as optical rogue waves and soliton molecules, and in relativistic electron bunching. It has also created a new class of instruments that have been integrated with artificial intelligence for sensing and biomedical diagnostics. We review the fundamental principles and applications of this emerging field for continuous phase and amplitude characterization at extremely high repetition rates via time-stretch spectral interferometry.

Immediate Effects of Neurodynamic Sliding versus Muscle Stretching on Hamstring Flexibility in Subjects with Short Hamstring Syndrome

Directory of Open Access Journals (Sweden)

Yolanda Castellote-Caballero

2014-01-01

Full Text Available Background. Hamstring injuries continue to affect active individuals and although inadequate muscle extensibility remains a commonly accepted factor, little is known about the most effective method to improve flexibility. Purpose. To determine if an isolated neurodynamic sciatic sliding technique would improve hamstring flexibility to a greater degree than stretching or a placebo intervention in asymptomatic subjects with short hamstring syndrome (SHS. Study Design. Randomized double-blinded controlled trial. Methods. One hundred and twenty subjects with SHS were randomized to 1 of 3 groups: neurodynamic sliding, hamstring stretching, and placebo control. Each subject’s dominant leg was measured for straight leg raise (SLR range of motion (ROM before and after interventions. Data were analyzed with a 3×2 mixed model ANOVA followed by simple main effects analyses. Results. At the end of the study, more ROM was observed in the Neurodynamic and Stretching groups compared to the Control group and more ROM in the Neurodynamic group compared to Stretching group. Conclusion. Findings suggest that a neurodynamic sliding technique will increase hamstring flexibility to a greater degree than static hamstring stretching in healthy subjects with SHS. Clinical Relevance. The use of neurodynamic sliding techniques to improve hamstring flexibility in sports may lead to a decreased incidence in injuries; however, this needs to be formally tested.

Activation of the Ca2+-sensing receptors increases currents through inward rectifier K+ channels via activation of phosphatidylinositol 4-kinase

OpenAIRE

Liu, Chung-Hung; Chang, Hsueh-Kai; Lee, Sue-Ping; Shieh, Ru-Chi

2016-01-01

Inward rectifier K+ channels are important for maintaining normal electrical function in many cell types. The proper function of these channels requires the presence of membrane phosphoinositide 4,5-bisphosphate (PIP2). Stimulation of the Ca2+-sensing receptor CaR, a pleiotropic G protein-coupled receptor, activates both Gq/11, which decreases PIP2, and phosphatidylinositol 4-kinase (PI-4-K), which, conversely, increases PIP2. How membrane PIP2 levels are regulated by CaR activation and wheth...

Kaempferol enhances endothelium-dependent relaxation in the porcine coronary artery through activation of large-conductance Ca(2+) -activated K(+) channels.

Science.gov (United States)

Xu, Y C; Leung, S W S; Leung, G P H; Man, R Y K

2015-06-01

Kaempferol, a plant flavonoid present in normal human diet, can modulate vasomotor tone. The present study aimed to elucidate the signalling pathway through which this flavonoid enhanced relaxation of vascular smooth muscle. The effect of kaempferol on the relaxation of porcine coronary arteries to endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) relaxing agents was studied in an in vitro organ chamber setup. The whole-cell patch-clamp technique was used to determine the effect of kaempferol on potassium channels in porcine coronary artery smooth muscle cells (PCASMCs). At a concentration without direct effect on vascular tone, kaempferol (3 × 10(-6) M) enhanced relaxations produced by bradykinin and sodium nitroprusside. The potentiation by kaempferol of the bradykinin-induced relaxation was not affected by N(ω)-nitro-L-arginine methyl ester, an inhibitor of NO synthase (10(-4) M) or TRAM-34 plus UCL 1684, inhibitors of intermediate- and small-conductance calcium-activated potassium channels, respectively (10(-6) M each), but was abolished by tetraethylammonium chloride, a non-selective inhibitor of calcium-activated potassium channels (10(-3) M), and iberiotoxin, a selective inhibitor of large-conductance calcium-activated potassium channel (KCa 1.1; 10(-7) M). Iberiotoxin also inhibited the potentiation by kaempferol of sodium nitroprusside-induced relaxations. Kaempferol stimulated an outward-rectifying current in PCASMCs, which was abolished by iberiotoxin. The present results suggest that, in smooth muscle cells of the porcine coronary artery, kaempferol enhanced relaxations caused by endothelium-derived and exogenous NO as well as those due to endothelium-dependent hyperpolarization. This vascular effect of kaempferol involved the activation of KCa 1.1 channels. © 2015 The British Pharmacological Society.

Contact of a spherical probe with a stretched rubber substrate

Science.gov (United States)

Frétigny, Christian; Chateauminois, Antoine

2017-07-01

We report on a theoretical and experimental investigation of the normal contact of stretched neo-Hookean substrates with rigid spherical probes. Starting from a published formulation of surface Green's function for incremental displacements on a prestretched, neo-Hookean, substrate [J. Mech. Phys. Solids 56, 2957 (2008), 10.1016/j.jmps.2008.07.002], a model is derived for both adhesive and nonadhesive contacts. The shape of the elliptical contact area together with the contact load and the contact stiffness are predicted as a function of the in-plane stretch ratios λx and λy of the substrate. The validity of this model is assessed by contact experiments carried out using an uniaxally stretched silicone rubber. For stretch ratio below about 1.25, a good agreement is observed between theory and experiments. Above this threshold, some deviations from the theoretical predictions are induced as a result of the departure of the mechanical response of the silicone rubber from the neo-Hokeean description embedded in the model.

Expression and proliferation profiles of PKC, JNK and p38MAPK in physiologically stretched human bladder smooth muscle cells

International Nuclear Information System (INIS)

Wazir, Romel; Luo, De-Yi; Dai, Yi; Yue, Xuan; Tian, Ye; Wang, Kun-Jie

2013-01-01

Highlights: •Stretch induces proliferation in human bladder smooth muscle cells (HBSMC). •5% Equibiaxial elongation produces maximum proliferation. •Physiologic stretch decreases apoptotic cell death. •PKC is involved in functional modulation of bladder. •JNK and p38 are not involved in proliferating HBSMC. -- Abstract: Objective: To determine protein kinase C (PKC), c-Jun NH2-Terminal Kinase (JNK) and P38 mitogen-activated protein kinases (p38MAPK) expression levels and effects of their respective inhibitors on proliferation of human bladder smooth muscle cells (HBSMCs) when physiologically stretched in vitro. Materials and methods: HBSMCs were grown on silicone membrane and stretch was applied under varying conditions; (equibiaxial elongation: 2.5%, 5%, 10%, 15%, 20%, 25%), (frequency: 0.05, 0.1, 0.2, 0.5, 1 Hz). Optimal physiological stretch was established by assessing proliferation with 5-Bromo-2-deoxyuridine (BrdU) assay and flow cytometry. PKC, JNK and p38 expression levels were analyzed by Western blot. Specificity was maintained by employing specific inhibitors; (GF109203X for PKC, SP600125 for JNK and SB203580 for p38MAPK), in some experiments. Results: Optimum proliferation was observed at 5% equibiaxial stretch (BrdU: 0.837 ± 0.026 (control) to 1.462 ± 0.023)%, (P 0.05 SP600125) and (1.461 ± 0.01, P > 0.05 SB203580). These findings show that mechanical stretch can promote magnitude-dependent proliferative modulation through PKC and possibly JNK but not via p38MAPK in hBSMCs

Periostin inhibits mechanical stretch-induced apoptosis in osteoblast-like MG-63 cells.

Science.gov (United States)

Yu, Kai-Wen; Yao, Chung-Chen; Jeng, Jiiang-Huei; Shieh, Hao-Ying; Chen, Yi-Jane

2018-04-01

Appropriate mechanical stress plays an important role in regulating the proliferation and differentiation of osteoblasts, whereas high-level mechanical stress may be harmful and compromise cell survival. Periostin, a matricellular protein, is essential in maintaining functional integrity of bone and collagen-rich connective tissue in response to mechanical stress. This study investigated whether or not high-level mechanical stretch induces cell apoptosis and the regulatory role of periostin in mechanical stretch-induced apoptosis in osteoblastic cells. Osteoblast-like MG-63 cells were seeded onto Bio-Flex I culture plates and subjected to cyclic mechanical stretching (15% elongation, 0.1 Hz) in a Flexercell tension plus system-5000. The same process was applied to cells pre-treated with exogenous human recombinant periostin before mechanical stretching. We used a chromatin condensation and membrane permeability dead cell apoptosis kit to evaluate the stretch-induced cell responses. Expression of caspase-3 and cPARP was examined by immunofluorescent stain and flow cytometry. The expression of periostin in MG-63 cells is involved in the TGF-β signaling pathway. High-level cyclic mechanical stretch induced apoptotic responses in MG-63 osteoblastic cells. The percentages of apoptotic cells and cells expressing cPARP protein increased in the groups of cells subjected to mechanical stretch, but these responses were absent in the presence of exogenous periostin. Our study revealed that high-level mechanical stretch induces apoptotic cell death, and that periostin plays a protective role against mechanical stretch-induced apoptosis in osteoblastic cells. Copyright © 2017. Published by Elsevier B.V.

Structure-function of proteins interacting with the alpha1 pore-forming subunit of high voltage-activated calcium channel

Directory of Open Access Journals (Sweden)

Alan eNeely

2014-06-01

Full Text Available Openings of high-voltage-activated calcium channels lead to a transient increase in calcium concentration that in turn activate a plethora of cellular functions, including muscle contraction, secretion and gene transcription. To coordinate all these responses calcium channels form supramolecular assemblies containing effectors and regulatory proteins that couple calcium influx to the downstream signal cascades and to feedback elements. According to the original biochemical characterization of skeletal muscle Dihydropyridine receptors, high-voltage-activated calcium channels are multi-subunit protein complexes consisting of a pore-forming subunit (α1 associated with four additional polypeptide chains β, α2, δ and γ, often referred to as accessory subunits. Twenty-five years after the first purification of a high-voltage calcium channel, the concept of a flexible stoichiometry to expand the repertoire of mechanisms that regulate calcium channel influx has emerged. Several other proteins have been identified that associate directly with the α1-subunit, including calmodulin and multiple members of the small and large GTPase family. Some of these proteins only interact with a subset of α1-subunits and during specific stages of biogenesis. More strikingly, most of the α1-subunit interacting proteins, such as the β-subunit and small GTPases, regulate both gating and trafficking through a variety of mechanisms. Modulation of channel activity covers almost all biophysical properties of the channel. Likewise, regulation of the number of channels in the plasma membrane is performed by altering the release of the α1-subunit from the endoplasmic reticulum, by reducing its degradation or enhancing its recycling back to the cell surface. In this review, we discuss the structural basis, interplay and functional role of selected proteins that interact with the central pore-forming subunit of high-voltage-activated calcium channels.

Force encoding in muscle spindles during stretch of passive muscle.

Directory of Open Access Journals (Sweden)

Kyle P Blum

2017-09-01

Full Text Available Muscle spindle proprioceptive receptors play a primary role in encoding the effects of external mechanical perturbations to the body. During externally-imposed stretches of passive, i.e. electrically-quiescent, muscles, the instantaneous firing rates (IFRs of muscle spindles are associated with characteristics of stretch such as length and velocity. However, even in passive muscle, there are history-dependent transients of muscle spindle firing that are not uniquely related to muscle length and velocity, nor reproduced by current muscle spindle models. These include acceleration-dependent initial bursts, increased dynamic response to stretch velocity if a muscle has been isometric, and rate relaxation, i.e., a decrease in tonic IFR when a muscle is held at a constant length after being stretched. We collected muscle spindle spike trains across a variety of muscle stretch kinematic conditions, including systematic changes in peak length, velocity, and acceleration. We demonstrate that muscle spindle primary afferents in passive muscle fire in direct relationship to muscle force-related variables, rather than length-related variables. Linear combinations of whole muscle-tendon force and the first time derivative of force (dF/dt predict the entire time course of transient IFRs in muscle spindle Ia afferents during stretch (i.e., lengthening of passive muscle, including the initial burst, the dynamic response to lengthening, and rate relaxation following lengthening. Similar to acceleration scaling found previously in postural responses to perturbations, initial burst amplitude scaled equally well to initial stretch acceleration or dF/dt, though later transients were only described by dF/dt. The transient increase in dF/dt at the onset of lengthening reflects muscle short-range stiffness due to cross-bridge dynamics. Our work demonstrates a critical role of muscle cross-bridge dynamics in history-dependent muscle spindle IFRs in passive muscle

Force encoding in muscle spindles during stretch of passive muscle.

Science.gov (United States)

Blum, Kyle P; Lamotte D'Incamps, Boris; Zytnicki, Daniel; Ting, Lena H

2017-09-01

Muscle spindle proprioceptive receptors play a primary role in encoding the effects of external mechanical perturbations to the body. During externally-imposed stretches of passive, i.e. electrically-quiescent, muscles, the instantaneous firing rates (IFRs) of muscle spindles are associated with characteristics of stretch such as length and velocity. However, even in passive muscle, there are history-dependent transients of muscle spindle firing that are not uniquely related to muscle length and velocity, nor reproduced by current muscle spindle models. These include acceleration-dependent initial bursts, increased dynamic response to stretch velocity if a muscle has been isometric, and rate relaxation, i.e., a decrease in tonic IFR when a muscle is held at a constant length after being stretched. We collected muscle spindle spike trains across a variety of muscle stretch kinematic conditions, including systematic changes in peak length, velocity, and acceleration. We demonstrate that muscle spindle primary afferents in passive muscle fire in direct relationship to muscle force-related variables, rather than length-related variables. Linear combinations of whole muscle-tendon force and the first time derivative of force (dF/dt) predict the entire time course of transient IFRs in muscle spindle Ia afferents during stretch (i.e., lengthening) of passive muscle, including the initial burst, the dynamic response to lengthening, and rate relaxation following lengthening. Similar to acceleration scaling found previously in postural responses to perturbations, initial burst amplitude scaled equally well to initial stretch acceleration or dF/dt, though later transients were only described by dF/dt. The transient increase in dF/dt at the onset of lengthening reflects muscle short-range stiffness due to cross-bridge dynamics. Our work demonstrates a critical role of muscle cross-bridge dynamics in history-dependent muscle spindle IFRs in passive muscle lengthening conditions

Active Sites of Spinoxin, a Potassium Channel Scorpion Toxin, Elucidated by Systematic Alanine Scanning.

Science.gov (United States)

Peigneur, Steve; Yamaguchi, Yoko; Kawano, Chihiro; Nose, Takeru; Nirthanan, Selvanayagam; Gopalakrishnakone, Ponnampalam; Tytgat, Jan; Sato, Kazuki

2016-05-31

Peptide toxins from scorpion venoms constitute the largest group of toxins that target the voltage-gated potassium channel (Kv). Spinoxin (SPX) isolated from the venom of scorpion Heterometrus spinifer is a 34-residue peptide neurotoxin cross-linked by four disulfide bridges. SPX is a potent inhibitor of Kv1.3 potassium channels (IC50 = 63 nM), which are considered to be valid molecular targets in the diagnostics and therapy of various autoimmune disorders and cancers. Here we synthesized 25 analogues of SPX and analyzed the role of each amino acid in SPX using alanine scanning to study its structure-function relationships. All synthetic analogues showed similar disulfide bond pairings and secondary structures as native SPX. Alanine replacements at Lys(23), Asn(26), and Lys(30) resulted in loss of activity against Kv1.3 potassium channels, whereas replacements at Arg(7), Met(14), Lys(27), and Tyr(32) also largely reduced inhibitory activity. These results suggest that the side chains of these amino acids in SPX play an important role in its interaction with Kv1.3 channels. In particular, Lys(23) appears to be a key residue that underpins Kv1.3 channel inhibition. Of these seven amino acid residues, four are basic amino acids, suggesting that the positive electrostatic potential on the surface of SPX is likely required for high affinity interaction with Kv1.3 channels. This study provides insight into the structure-function relationships of SPX with implications for the rational design of new lead compounds targeting potassium channels with high potency.

Soleus stretch reflex during cycling

DEFF Research Database (Denmark)

Grey, Michael James; Pierce, C. W.; Milner, T. E.

2001-01-01

The modulation and strength of the human soleus short latency stretch reflex was investigated by mechanically perturbing the ankle during an unconstrained pedaling task. Eight subjects pedaled at 60 rpm against a preload of 10 Nm. A torque pulse was applied to the crank at various positions durin...

Optical tweezers stretching of chromatin

NARCIS (Netherlands)

Pope, L.H.; Bennink, Martin L.; Greve, Jan

2003-01-01

Recently significant success has emerged from exciting research involving chromatin stretching using optical tweezers. These experiments, in which a single chromatin fibre is attached by one end to a micron-sized bead held in an optical trap and to a solid surface or second bead via the other end,

Stretching Diagnostics and Mixing Properties In The Stratosphere

Science.gov (United States)

Legras, B.; Shuckburgh, E.

The "finite size Lyapunov exponent" and the "effective diffusivity" are two diagnos- tics of mixing which have been recently introduced to investigate atmospheric flows. Both have been used to successfully identify the barriers to transport, for instance at the edge of the stratospheric polar vortex. Here we compare the two diagnostics in detail. The equivalent length has the advantage of arising as a mixing quantification from a rigid theoretical framework, however it has the disadvantage of being an aver- age quantity (the average around a tracer contour). The finite size Lyapunov exponent may be defined at any point in the flow, and quantifies the stretching properties expe- rienced by a fluid parcel both in its past and future evolution. In particular, the lines of maximum stretching at any time delineate the building blocks of the chaotic stirring. However the interpretation of the finite size Lyapunov exponent as a mixing time is less direct and depends on the alignment of tracer contours with the stretching lines.

Hypotonic stimuli enhance proton-gated currents of acid-sensing ion channel-1b

International Nuclear Information System (INIS)

Ugawa, Shinya; Ishida, Yusuke; Ueda, Takashi; Yu, Yong; Shimada, Shoichi

2008-01-01

Acid-sensing ion channels (ASICs) are strong candidates for mammalian mechanoreceptors. We investigated whether mouse acid-sensing ion channel-1b (ASIC1b) is sensitive to mechanical stimuli using oocyte electrophysiology, because ASIC1b is located in the mechanosensory stereocilia of cochlear hair cells. Hypotonic stimuli that induced membrane stretch of oocytes evoked no significant current in ASIC1b-expressing oocytes at pH 7.5. However, acid (pH 4.0 or 5.0)-evoked currents in the oocytes were substantially enhanced by the hypotonicity, showing mechanosensitivity of ASIC1b and possible mechanogating of the channel in the presence of other components. Interestingly, the ASIC1b channel was permeable to K + (a principal charge carrier for cochlear sensory transduction) and the affinity of the channel for amiloride (IC 50 (inhibition constant) = approximately 48.3 μM) was quite similar to that described for the mouse hair cell mechanotransducer current. Taken together, these data raise the possibility that ASIC1b participates in cochlear mechanoelectrical transduction

Functional characterization of neurotransmitter activation and modulation in a nematode model ligand-gated ion channel.

Science.gov (United States)

Heusser, Stephanie A; Yoluk, Özge; Klement, Göran; Riederer, Erika A; Lindahl, Erik; Howard, Rebecca J

2016-07-01

The superfamily of pentameric ligand-gated ion channels includes neurotransmitter receptors that mediate fast synaptic transmission in vertebrates, and are targets for drugs including alcohols, anesthetics, benzodiazepines, and anticonvulsants. However, the mechanisms of ion channel opening, gating, and modulation in these receptors leave many open questions, despite their pharmacological importance. Subtle conformational changes in both the extracellular and transmembrane domains are likely to influence channel opening, but have been difficult to characterize given the limited structural data available for human membrane proteins. Recent crystal structures of a modified Caenorhabditis elegans glutamate-gated chloride channel (GluCl) in multiple states offer an appealing model system for structure-function studies. However, the pharmacology of the crystallographic GluCl construct is not well established. To establish the functional relevance of this system, we used two-electrode voltage-clamp electrophysiology in Xenopus oocytes to characterize activation of crystallographic and native-like GluCl constructs by L-glutamate and ivermectin. We also tested modulation by ethanol and other anesthetic agents, and used site-directed mutagenesis to explore the role of a region of Loop F which was implicated in ligand gating by molecular dynamics simulations. Our findings indicate that the crystallographic construct functionally models concentration-dependent agonism and allosteric modulation of pharmacologically relevant receptors. Specific substitutions at residue Leu174 in loop F altered direct L-glutamate activation, consistent with computational evidence for this region's role in ligand binding. These insights demonstrate conservation of activation and modulation properties in this receptor family, and establish a framework for GluCl as a model system, including new possibilities for drug discovery. In this study, we elucidate the validity of a modified glutamate

Possible stretched exponential parametrization for humidity absorption in polymers.

Science.gov (United States)

Hacinliyan, A; Skarlatos, Y; Sahin, G; Atak, K; Aybar, O O

2009-04-01

Polymer thin films have irregular transient current characteristics under constant voltage. In hydrophilic and hydrophobic polymers, the irregularity is also known to depend on the humidity absorbed by the polymer sample. Different stretched exponential models are studied and it is shown that the absorption of humidity as a function of time can be adequately modelled by a class of these stretched exponential absorption models.

Active Brownian motion in a narrow channel

Science.gov (United States)

Ao, X.; Ghosh, P. K.; Li, Y.; Schmid, G.; Hänggi, P.; Marchesoni, F.

2014-12-01

We review recent advances in rectification control of artificial microswimmers, also known as Janus particles, diffusing along narrow, periodically corrugated channels. The swimmer self-propulsion mechanism is modeled so as to incorporate a nonzero torque (propulsion chirality). We first summarize the effects of chirality on the autonomous current of microswimmers freely diffusing in channels of different geometries. In particular, left-right and upside-down asymmetric channels are shown to exhibit different transport properties. We then report new results on the dependence of the diffusivity of chiral microswimmers on the channel geometry and their own self-propulsion mechanism. The self-propulsion torque turns out to play a key role as a transport control parameter.

Volume Regulated Channels

DEFF Research Database (Denmark)

Klausen, Thomas Kjær

of volume perturbations evolution have developed system of channels and transporters to tightly control volume homeostasis. In the past decades evidence has been mounting, that the importance of these volume regulated channels and transporters are not restricted to the defense of cellular volume...... but are also essential for a number of physiological processes such as proliferation, controlled cell death, migration and endocrinology. The thesis have been focusing on two Channels, namely the swelling activated Cl- channel (ICl, swell) and the transient receptor potential Vanilloid (TRPV4) channel. I: Cl......- serves a multitude of functions in the mammalian cell, regulating the membrane potential (Em), cell volume, protein activity and the driving force for facilitated transporters giving Cl- and Cl- channels a major potential of regulating cellular function. These functions include control of the cell cycle...

Process Parameter Identification in Thin Film Flows Driven by a Stretching Surface

Directory of Open Access Journals (Sweden)

Satyananda Panda

2014-01-01

Full Text Available The flow of a thin liquid film over a heated stretching surface is considered in this study. Due to a potential nonuniform temperature distribution on the stretching sheet, a temperature gradient occurs in the fluid which produces surface tension gradient at the free surface of the thin film. As a result, the free surface deforms and these deformations are advected by the flow in the stretching direction. This work focuses on the inverse problem of reconstructing the sheet temperature distribution and the sheet stretch rate from observed free surface variations. This work builds on the analysis of Santra and Dandapat (2009 who, based on the long-wave expansion of the Navier-Stokes equations, formulate a partial differential equation which describes the evolution of the thickness of a film over a nonisothermal stretched surface. In this work, we show that after algebraic manipulation of a discrete form of the governing equations, it is possible to reconstruct either the unknown temperature field on the sheet and hence the resulting heat transfer or the stretching rate of the underlying surface. We illustrate the proposed methodology and test its applicability on a range of test problems.

Altered expression of two-pore domain potassium (K2P channels in cancer.

Directory of Open Access Journals (Sweden)

Sarah Williams

Full Text Available Potassium channels have become a focus in cancer biology as they play roles in cell behaviours associated with cancer progression, including proliferation, migration and apoptosis. Two-pore domain (K2P potassium channels are background channels which enable the leak of potassium ions from cells. As these channels are open at rest they have a profound effect on cellular membrane potential and subsequently the electrical activity and behaviour of cells in which they are expressed. The K2P family of channels has 15 mammalian members and already 4 members of this family (K2P2.1, K2P3.1, K2P9.1, K2P5.1 have been implicated in cancer. Here we examine the expression of all 15 members of the K2P family of channels in a range of cancer types. This was achieved using the online cancer microarray database, Oncomine (www.oncomine.org. Each gene was examined across 20 cancer types, comparing mRNA expression in cancer to normal tissue. This analysis revealed all but 3 K2P family members (K2P4.1, K2P16.1, K2P18.1 show altered expression in cancer. Overexpression of K2P channels was observed in a range of cancers including breast, leukaemia and lung while more cancers (brain, colorectal, gastrointestinal, kidney, lung, melanoma, oesophageal showed underexpression of one or more channels. K2P1.1, K2P3.1, K2P12.1, were overexpressed in a range of cancers. While K2P1.1, K2P3.1, K2P5.1, K2P6.1, K2P7.1 and K2P10.1 showed significant underexpression across the cancer types examined. This analysis supports the view that specific K2P channels may play a role in cancer biology. Their altered expression together with their ability to impact the function of other ion channels and their sensitivity to environmental stimuli (pO2, pH, glucose, stretch makes understanding the role these channels play in cancer of key importance.

Activation of the Ca2+-sensing receptors increases currents through inward rectifier K+ channels via activation of phosphatidylinositol 4-kinase.

Science.gov (United States)

Liu, Chung-Hung; Chang, Hsueh-Kai; Lee, Sue-Ping; Shieh, Ru-Chi

2016-11-01

Inward rectifier K + channels are important for maintaining normal electrical function in many cell types. The proper function of these channels requires the presence of membrane phosphoinositide 4,5-bisphosphate (PIP 2 ). Stimulation of the Ca 2+ -sensing receptor CaR, a pleiotropic G protein-coupled receptor, activates both G q/11 , which decreases PIP 2 , and phosphatidylinositol 4-kinase (PI-4-K), which, conversely, increases PIP 2 . How membrane PIP 2 levels are regulated by CaR activation and whether these changes modulate inward rectifier K + are unknown. In this study, we found that activation of CaR by the allosteric agonist, NPSR568, increased inward rectifier K + current (I K1 ) in guinea pig ventricular myocytes and currents mediated by Kir2.1 channels exogenously expressed in HEK293T cells with a similar sensitivity. Moreover, using the fluorescent PIP 2 reporter tubby-R332H-cYFP to monitor PIP 2 levels, we found that CaR activation in HEK293T cells increased membrane PIP 2 concentrations. Pharmacological studies showed that both phospholipase C (PLC) and PI-4-K are activated by CaR stimulation with the latter played a dominant role in regulating membrane PIP 2 and, thus, Kir currents. These results provide the first direct evidence that CaR activation upregulates currents through inward rectifier K + channels by accelerating PIP 2 synthesis. The regulation of I K1 plays a critical role in the stability of the electrical properties of many excitable cells, including cardiac myocytes and neurons. Further, synthetic allosteric modulators that increase CaR activity have been used to treat hyperparathyroidism, and negative CaR modulators are of potential importance in the treatment of osteoporosis. Thus, our results provide further insight into the roles played by CaR in the cardiovascular system and are potentially valuable for heart disease treatment and drug safety.

Low intensity 635 nm diode laser irradiation inhibits fibroblast-myofibroblast transition reducing TRPC1 channel expression/activity: New perspectives for tissue fibrosis treatment.

Science.gov (United States)

Sassoli, Chiara; Chellini, Flaminia; Squecco, Roberta; Tani, Alessia; Idrizaj, Eglantina; Nosi, Daniele; Giannelli, Marco; Zecchi-Orlandini, Sandra

2016-03-01

Low-level laser therapy (LLLT) or photobiomodulation therapy is emerging as a promising new therapeutic option for fibrosis in different damaged and/or diseased organs. However, the anti-fibrotic potential of this treatment needs to be elucidated and the cellular and molecular targets of the laser clarified. Here, we investigated the effects of a low intensity 635 ± 5 nm diode laser irradiation on fibroblast-myofibroblast transition, a key event in the onset of fibrosis, and elucidated some of the underlying molecular mechanisms. NIH/3T3 fibroblasts were cultured in a low serum medium in the presence of transforming growth factor (TGF)-β1 and irradiated with a 635 ± 5 nm diode laser (continuous wave, 89 mW, 0.3 J/cm(2) ). Fibroblast-myofibroblast differentiation was assayed by morphological, biochemical, and electrophysiological approaches. Expression of matrix metalloproteinase (MMP)-2 and MMP-9 and of Tissue inhibitor of MMPs, namely TIMP-1 and TIMP-2, after laser exposure was also evaluated by confocal immunofluorescence analyses. Moreover, the effect of the diode laser on transient receptor potential canonical channel (TRPC) 1/stretch-activated channel (SAC) expression and activity and on TGF-β1/Smad3 signaling was investigated. Diode laser treatment inhibited TGF-β1-induced fibroblast-myofibroblast transition as judged by reduction of stress fibers formation, α-smooth muscle actin (sma) and type-1 collagen expression and by changes in electrophysiological properties such as resting membrane potential, cell capacitance and inwardly rectifying K(+) currents. In addition, the irradiation up-regulated the expression of MMP-2 and MMP-9 and downregulated that of TIMP-1 and TIMP-2 in TGF-β1-treated cells. This laser effect was shown to involve TRPC1/SAC channel functionality. Finally, diode laser stimulation and TRPC1 functionality negatively affected fibroblast-myofibroblast transition by interfering with TGF-β1 signaling, namely reducing the

The Maths Arcade: A Tool for Supporting and Stretching Mathematics Undergraduates

OpenAIRE

Bradshaw, Noel-Ann

2017-01-01

The Maths Arcade is an activity which aims simultaneously to support those university mathematics learners who are having difficulties, stretch more confident learners, and encourage the development of a staff-student mathematical community. The first Maths Arcade was set up at the University of Greenwich in September 2010, funded initially by a University grant for innovative teaching and later by the Mathematical Sciences Curriculum Innovation Fund of the UK National Higher Education STEM P...

Identification of the functional binding pocket for compounds targeting small-conductance Ca2+-activated potassium channels

Science.gov (United States)

Zhang, Miao; Pascal, John M.; Schumann, Marcel; Armen, Roger S.; Zhang, Ji-fang

2012-01-01

Small- and intermediate-conductance Ca2+-activated potassium channels, activated by Ca2+-bound calmodulin, play an important role in regulating membrane excitability. These channels are also linked to clinical abnormalities. A tremendous amount of effort has been devoted to developing small molecule compounds targeting these channels. However, these compounds often suffer from low potency and lack of selectivity, hindering their potentials for clinical use. A key contributing factor is the lack of knowledge of the binding site(s) for these compounds. Here we demonstrate by X-ray crystallography that the binding pocket for the compounds of the 1-EBIO class is located at the calmodulin-channel interface. We show that, based on structure data and molecular docking, mutations of the channel can effectively change the potency of these compounds. Our results provide insight into the molecular nature of the binding pocket and its contribution to the potency and selectivity of the compounds of the 1-EBIO class. PMID:22929778

Cellular hyper-excitability caused by mutations that alter the activation process of voltage-gated sodium channels

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Mohamed-Yassine eAMAROUCH

2015-02-01

Full Text Available Voltage-gated sodium channels (Nav are widely expressed as macro-molecular complexes in both excitable and non-excitable tissues. In excitable tissues, the upstroke of the action potential is the result of the passage of a large and rapid influx of sodium ions through these channels. NaV dysfunction has been associated with an increasingly wide range of neurological, muscular and cardiac disorders. The purpose of this review is to summarize the recently identified sodium channel mutations that are linked to hyper-excitability phenotypes and associated with the alteration of the activation process of voltage gated sodium channels. Indeed, several clinical manifestations that demonstrate an alteration of tissue excitability were recently shown to be strongly associated with the presence of mutations that affect the activation process of the voltage-gated sodium channels. These emerging genotype-phenotype correlations have expanded the clinical spectrum of sodium channelopathies to include disorders which feature a hyper-excitability phenotype that may or may not be associated with a cardiomyopathy. The p.I141V mutation in SCN4A and SCN5A, as well as its homologous p.I136V mutation in SCN9A, are interesting examples of mutations that have been linked to inherited hyperexcitability myotonia, exercise-induced polymorphic ventricular arrhythmias and erythromelalgia, respectively. Regardless of which sodium channel isoform is investigated, the substitution of the isoleucine to valine in the locus 141 induces similar modifications in the biophysical properties of the voltage-gated sodium channels by shifting the voltage-dependence of steady state activation towards more negative potentials.

Kaempferol enhances endothelium-dependent relaxation in the porcine coronary artery through activation of large-conductance a2+-activated K+ channels

Science.gov (United States)

Xu, Y C; Leung, S W S; Leung, G P H; Man, R Y K

2015-01-01

Background and Purpose Kaempferol, a plant flavonoid present in normal human diet, can modulate vasomotor tone. The present study aimed to elucidate the signalling pathway through which this flavonoid enhanced relaxation of vascular smooth muscle. Experimental Approach The effect of kaempferol on the relaxation of porcine coronary arteries to endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) relaxing agents was studied in an in vitro organ chamber setup. The whole-cell patch-clamp technique was used to determine the effect of kaempferol on potassium channels in porcine coronary artery smooth muscle cells (PCASMCs). Key Results At a concentration without direct effect on vascular tone, kaempferol (3 × 10−6 M) enhanced relaxations produced by bradykinin and sodium nitroprusside. The potentiation by kaempferol of the bradykinin-induced relaxation was not affected by Nω-nitro-L-arginine methyl ester, an inhibitor of NO synthase (10−4 M) or TRAM-34 plus UCL 1684, inhibitors of intermediate- and small-conductance calcium-activated potassium channels, respectively (10−6 M each), but was abolished by tetraethylammonium chloride, a non-selective inhibitor of calcium-activated potassium channels (10−3 M), and iberiotoxin, a selective inhibitor of large-conductance calcium-activated potassium channel (KCa1.1; 10−7 M). Iberiotoxin also inhibited the potentiation by kaempferol of sodium nitroprusside-induced relaxations. Kaempferol stimulated an outward-rectifying current in PCASMCs, which was abolished by iberiotoxin. Conclusions and Implications The present results suggest that, in smooth muscle cells of the porcine coronary artery, kaempferol enhanced relaxations caused by endothelium-derived and exogenous NO as well as those due to endothelium-dependent hyperpolarization. This vascular effect of kaempferol involved the activation of KCa1.1 channels. PMID:25652142

Dynamics and structure of stretched flames

Energy Technology Data Exchange (ETDEWEB)

Law, C.K. [Princeton Univ., NJ (United States)

1993-12-01

This program aims to gain fundamental understanding on the structure, geometry, and dynamics of laminar premixed flames, and relate these understanding to the practical issues of flame extinction and stabilization. The underlying fundamental interest here is the recent recognition that the response of premixed flames can be profoundly affected by flame stretch, as manifested by flow nonuniformity, flame curvature, and flame/flow unsteadiness. As such, many of the existing understanding on the behavior of premixed flames need to be qualitatively revised. The research program consists of three major thrusts: (1) detailed experimental and computational mapping of the structure of aerodynamically-strained planar flames, with emphasis on the effects of heat loss, nonequidiffusion, and finite residence time on the flame thickness, extent of incomplete reaction, and the state of extinction. (2) Analytical study of the geometry and dynamics of stretch-affected wrinkled flame sheets in simple configurations, as exemplified by the Bunsen flame and the spatially-periodic flame, with emphasis on the effects of nonlinear stretch, the phenomena of flame cusping, smoothing, and tip opening, and their implications on the structure and burning rate of turbulent flames. (3) Stabilization and blowoff of two-dimensional inverted premixed and stabilization and determining the criteria governing flame blowoff. The research is synergistically conducted through the use of laser-based diagnostics, computational simulation of the flame structure with detailed chemistry and transport, and mathematical analysis of the flame dynamics.

Excluded Volume Effects in Gene Stretching

OpenAIRE

Lam, Pui-Man

2002-01-01

We investigate the effects excluded volume on the stretching of a single DNA in solution. We find that for small force F, the extension h is not linear in F but proportion to F^{\\chi}, with \\chi=(1-\

Proteolytic fragmentation of inositol 1,4,5-trisphosphate receptors: a novel mechanism regulating channel activity?

Science.gov (United States)

Wang, Liwei; Alzayady, Kamil J; Yule, David I

2016-06-01

Inositol 1,4,5-trisphosphate receptors (IP3 Rs) are a family of ubiquitously expressed intracellular Ca(2+) release channels. Regulation of channel activity by Ca(2+) , nucleotides, phosphorylation, protein binding partners and other cellular factors is thought to play a major role in defining the specific spatiotemporal characteristics of intracellular Ca(2+) signals. These properties are, in turn, believed pivotal for the selective and specific physiological activation of Ca(2+) -dependent effectors. IP3 Rs are also substrates for the intracellular cysteine proteases, calpain and caspase. Cleavage of the IP3 R has been proposed to play a role in apoptotic cell death by uncoupling regions important for IP3 binding from the channel domain, leaving an unregulated leaky Ca(2+) pore. Contrary to this hypothesis, we demonstrate following proteolysis that N- and C-termini of IP3 R1 remain associated, presumably through non-covalent interactions. Further, we show that complementary fragments of IP3 R1 assemble into tetrameric structures and retain their ability to be regulated robustly by IP3 . While peptide continuity is clearly not necessary for IP3 -gating of the channel, we propose that cleavage of the IP3 R peptide chain may alter other important regulatory events to modulate channel activity. In this scenario, stimulation of the cleaved IP3 R may support distinct spatiotemporal Ca(2+) signals and activation of specific effectors. Notably, in many adaptive physiological events, the non-apoptotic activities of caspase and calpain are demonstrated to be important, but the substrates of the proteases are poorly defined. We speculate that proteolytic fragmentation may represent a novel form of IP3 R regulation, which plays a role in varied adaptive physiological processes. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Effect of Twisting and Stretching on Magneto Resistance and Spin Filtration in CNTs

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Anil Kumar Singh

2017-08-01

Full Text Available Spin-dependent quantum transport properties in twisted carbon nanotube and stretched carbon nanotube are calculated using density functional theory (DFT and non-equilibrium green’s function (NEGF formulation. Twisting and stretching have no effect on spin transport in CNTs at low bias voltages. However, at high bias voltages the effects are significant. Stretching restricts any spin-up current in antiparallel configuration (APC, which results in higher magneto resistance (MR. Twisting allows spin-up current almost equivalent to the pristine CNT case, resulting in lower MR. High spin filtration is observed in PC and APC for pristine, stretched and twisted structures at all applied voltages. In APC, at low voltages spin filtration in stretched CNT is higher than in pristine and twisted ones, with pristine giving a higher spin filtration than twisted CNT.

Effect of Ankle Positioning During Hamstring Stretches for Improving Straight Leg Hip Flexion Motion.

Science.gov (United States)

Laudner, Kevin G; Benjamin, Peter J; Selkow, Noelle M

2016-03-01

To compare the effects of stretching the hamstrings with the ankle in either a plantar-flexed (PF) or dorsiflexed (DF) position for improving straight leg hip flexion range of motion (ROM) over a 4-week period. Randomized, single-blinded, pretest, posttest design. Athletic training facility. Each limb of 34 asymptomatic individuals (15 males, 19 females) was randomly assigned to one of the 3 groups. Twenty-four limbs received hamstring stretches with the ankle in DF, 24 limbs received hamstring stretches with the ankle in PF, and 20 limbs received no stretch (control). Ankle position (PF, DF) during hamstring stretching. We measured pretest and posttest passive straight leg hip flexion ROM with the test ankle in a neutral position. For the intervention groups, the test limb was passively stretched with the ankle held in end range DF or PF for their respective group. Each stretch was held for 30 seconds for a total of 3 applications. Two treatment sessions were completed per week for a total of 4 weeks. The control limbs received no stretching during the 4-week period. We conducted 1-way analyses of covariance to determine significant changes in ROM between groups (P hamstrings in either PF or DF improve straight leg hip ROM compared with a control group. The results of this study should be considered by clinicians when determining the optimal stretching techniques aimed at increasing hamstring length.

Acute Effect of Different Combined Stretching Methods on Acceleration and Speed in Soccer Players

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Amiri-Khorasani Mohammadtaghi

2016-04-01

Full Text Available The purpose of this study was to investigate the acute effect of different stretching methods, during a warm-up, on the acceleration and speed of soccer players. The acceleration performance of 20 collegiate soccer players (body height: 177.25 ± 5.31 cm; body mass: 65.10 ± 5.62 kg; age: 16.85 ± 0.87 years; BMI: 20.70 ± 5.54; experience: 8.46 ± 1.49 years was evaluated after different warm-up procedures, using 10 and 20 m tests. Subjects performed five types of a warm-up: static, dynamic, combined static + dynamic, combined dynamic + static, and no-stretching. Subjects were divided into five groups. Each group performed five different warm-up protocols in five non-consecutive days. The warm-up protocol used for each group was randomly assigned. The protocols consisted of 4 min jogging, a 1 min stretching program (except for the no-stretching protocol, and 2 min rest periods, followed by the 10 and 20 m sprint test, on the same day. The current findings showed significant differences in the 10 and 20 m tests after dynamic stretching compared with static, combined, and no-stretching protocols. There were also significant differences between the combined stretching compared with static and no-stretching protocols. We concluded that soccer players performed better with respect to acceleration and speed, after dynamic and combined stretching, as they were able to produce more force for a faster execution.

Flow of viscous fluid along an exponentially stretching curved surface

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N.F. Okechi

Full Text Available In this paper, we present the boundary layer analysis of flow induced by rapidly stretching curved surface with exponential velocity. The governing boundary value problem is reduced into self-similar form using a new similarity transformation. The resulting equations are solved numerically using shooting and Runge-Kutta methods. The numerical results depicts that the fluid velocity as well as the skin friction coefficient increases with the surface curvature, similar trend is also observed for the pressure. The dimensionless wall shear stress defined for this problem is greater than that of a linearly stretching curved surface, but becomes comparably less for a surface stretching with a power-law velocity. In addition, the result for the plane surface is a special case of this study when the radius of curvature of the surface is sufficiently large. The numerical investigations presented in terms of the graphs are interpreted with the help of underlying physics of the fluid flow and the consequences arising from the curved geometry. Keywords: Boundary layer flow, Curved surface, Exponential stretching, Curvature

Directional Cell Migration in Response to Repeated Substratum Stretching

Science.gov (United States)

Okimura, Chika; Iwadate, Yoshiaki

2017-10-01

Crawling migration plays an essential role in a variety of biological phenomena, including development, wound healing, and immune system function. Migration properties such as anterior-posterior polarity, directionality, and velocity are regulated not only by the reception of a chemoattractant but also by sensing mechanical inputs from the external environment. In this review, we describe the mechanical response of migrating cells, particularly under repeated stretching of the elastic substratum, highlighting the fact that there appear to be two independent mechanosensing systems that generate the polarity needed for migration. Cells that have no stress fibers, such as Dictyostelium cells and neutrophil-like differentiated HL-60 cells, migrate perpendicular to the stretching direction via myosin II localization. Cells that do possess stress fibers, however, such as fish keratocytes, migrate parallel to the stretching via a stress-fiber-dependent process.

Na+K+-ATPase activity and K+ channels differently contribute to vascular relaxation in male and female rats.

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Fernanda Moura Vargas Dias

Full Text Available Gender associated differences in vascular reactivity regulation might contribute to the low incidence of cardiovascular disease in women. Cardiovascular protection is suggested to depend on female sex hormones' effects on endothelial function and vascular tone regulation. We tested the hypothesis that potassium (K+ channels and Na+K+-ATPase may be involved in the gender-based vascular reactivity differences. Aortic rings from female and male rats were used to examine the involvement of K+ channels and Na+K+-ATPase in vascular reactivity. Acetylcholine (ACh-induced relaxation was analyzed in the presence of L-NAME (100 µM and the following K+ channels blockers: tetraethylammonium (TEA, 2 mM, 4-aminopyridine (4-AP, 5 mM, iberiotoxin (IbTX, 30 nM, apamin (0.5 µM and charybdotoxin (ChTX, 0.1 µM. The ACh-induced relaxation sensitivity was greater in the female group. After incubation with 4-AP the ACh-dependent relaxation was reduced in both groups. However, the dAUC was greater in males, suggesting that the voltage-dependent K+ channel (Kv participates more in males. Inhibition of the three types of Ca2+-activated K+ channels induced a greater reduction in Rmax in females than in males. The functional activity of the Na+K+-ATPase was evaluated by KCl-induced relaxation after L-NAME and OUA incubation. OUA reduced K+-induced relaxation in female and male groups, however, it was greater in males, suggesting a greater Na+K+-ATPase functional activity. L-NAME reduced K+-induced relaxation only in the female group, suggesting that nitric oxide (NO participates more in their functional Na+K+-ATPase activity. These results suggest that the K+ channels involved in the gender-based vascular relaxation differences are the large conductance Ca2+-activated K+ channels (BKCa in females and Kv in males and in the K+-induced relaxation and the Na+K+-ATPase vascular functional activity is greater in males.

Terbinafine is a novel and selective activator of the two-pore domain potassium channel TASK3.

Science.gov (United States)

Wright, Paul D; Veale, Emma L; McCoull, David; Tickle, David C; Large, Jonathan M; Ococks, Emma; Gothard, Gemma; Kettleborough, Catherine; Mathie, Alistair; Jerman, Jeffrey

2017-11-04

Two-pore domain potassium channels (K2Ps) are characterized by their four transmembrane domain and two-pore topology. They carry background (or leak) potassium current in a variety of cell types. Despite a number of important roles there is currently a lack of pharmacological tools with which to further probe K2P function. We have developed a cell-based thallium flux assay, using baculovirus delivered TASK3 (TWIK-related acid-sensitive K + channel 3, KCNK9, K2P9.1) with the aim of identifying novel, selective TASK3 activators. After screening a library of 1000 compounds, including drug-like and FDA approved molecules, we identified Terbinafine as an activator of TASK3. In a thallium flux assay a pEC50 of 6.2 ( ±0.12) was observed. When Terbinafine was screened against TASK2, TREK2, THIK1, TWIK1 and TRESK no activation was observed in thallium flux assays. Several analogues of Terbinafine were also purchased and structure activity relationships examined. To confirm Terbinafine's activation of TASK3 whole cell patch clamp electrophysiology was carried out and clear potentiation observed in both the wild type channel and the pathophysiological, Birk-Barel syndrome associated, G236R TASK3 mutant. No activity at TASK1 was observed in electrophysiology studies. In conclusion, we have identified the first selective activator of the two-pore domain potassium channel TASK3. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanical Stretching Promotes Skin Tissue Regeneration via Enhancing Mesenchymal Stem Cell Homing and Transdifferentiation.

Science.gov (United States)

Liang, Xiao; Huang, Xiaolu; Zhou, Yiwen; Jin, Rui; Li, Qingfeng

2016-07-01

Skin tissue expansion is a clinical procedure for skin regeneration to reconstruct cutaneous defects that can be accompanied by severe complications. The transplantation of mesenchymal stem cells (MSCs) has been proven effective in promoting skin expansion and helping to ameliorate complications; however, systematic understanding of its mechanism remains unclear. MSCs from luciferase-Tg Lewis rats were intravenously transplanted into a rat tissue expansion model to identify homing and transdifferentiation. To clarify underlying mechanisms, a systematic approach was used to identify the differentially expressed genes between mechanically stretched human MSCs and controls. The biological significance of these changes was analyzed through bioinformatic methods. We further investigated genes and pathways of interest to disclose their potential role in mechanical stretching-induced skin regeneration. Cross sections of skin samples from the expanded group showed significantly more luciferase(+) and stromal cell-derived factor 1α (SDF-1α)(+), luciferase(+)keratin 14(+), and luciferase(+)CD31(+) cells than the control group, indicating MSC transdifferentiation into epidermal basal cells and endothelial cells after SDF-1α-mediated homing. Microarray analysis suggested upregulation of genes related to hypoxia, vascularization, and cell proliferation in the stretched human MSCs. Further investigation showed that the homing of MSCs was blocked by short interfering RNA targeted against matrix metalloproteinase 2, and that mechanical stretching-induced vascular endothelial growth factor A upregulation was related to the Janus kinase/signal transducer and activator of transcription (Jak-STAT) and Wnt signaling pathways. This study determines that mechanical stretching might promote skin regeneration by upregulating MSC expression of genes related to hypoxia, vascularization, and cell proliferation; enhancing transplanted MSC homing to the expanded skin; and

Cholesterol up-regulates neuronal G protein-gated inwardly rectifying potassium (GIRK) channel activity in the hippocampus.

Science.gov (United States)

Bukiya, Anna N; Durdagi, Serdar; Noskov, Sergei; Rosenhouse-Dantsker, Avia

2017-04-14

Hypercholesterolemia is a well known risk factor for the development of neurodegenerative disease. However, the underlying mechanisms are mostly unknown. In recent years, it has become increasingly evident that cholesterol-driven effects on physiology and pathophysiology derive from its ability to alter the function of a variety of membrane proteins including ion channels. Yet, the effect of cholesterol on G protein-gated inwardly rectifying potassium (GIRK) channels expressed in the brain is unknown. GIRK channels mediate the actions of inhibitory brain neurotransmitters. As a result, loss of GIRK function can enhance neuron excitability, whereas gain of GIRK function can reduce neuronal activity. Here we show that in rats on a high-cholesterol diet, cholesterol levels in hippocampal neurons are increased. We also demonstrate that cholesterol plays a critical role in modulating neuronal GIRK currents. Specifically, cholesterol enrichment of rat hippocampal neurons resulted in enhanced channel activity. In accordance, elevated currents upon cholesterol enrichment were also observed in Xenopus oocytes expressing GIRK2 channels, the primary GIRK subunit expressed in the brain. Furthermore, using planar lipid bilayers, we show that although cholesterol did not affect the unitary conductance of GIRK2, it significantly enhanced the frequency of channel openings. Last, combining computational and functional approaches, we identified two putative cholesterol-binding sites in the transmembrane domain of GIRK2. These findings establish that cholesterol plays a critical role in modulating GIRK activity in the brain. Because up-regulation of GIRK function can reduce neuronal activity, our findings may lead to novel approaches for prevention and therapy of cholesterol-driven neurodegenerative disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Cryo-EM structures of the TMEM16A calcium-activated chloride channel.

Science.gov (United States)

Dang, Shangyu; Feng, Shengjie; Tien, Jason; Peters, Christian J; Bulkley, David; Lolicato, Marco; Zhao, Jianhua; Zuberbühler, Kathrin; Ye, Wenlei; Qi, Lijun; Chen, Tingxu; Craik, Charles S; Jan, Yuh Nung; Minor, Daniel L; Cheng, Yifan; Jan, Lily Yeh

2017-12-21

Calcium-activated chloride channels (CaCCs) encoded by TMEM16A control neuronal signalling, smooth muscle contraction, airway and exocrine gland secretion, and rhythmic movements of the gastrointestinal system. To understand how CaCCs mediate and control anion permeation to fulfil these physiological functions, knowledge of the mammalian TMEM16A structure and identification of its pore-lining residues are essential. TMEM16A forms a dimer with two pores. Previous CaCC structural analyses have relied on homology modelling of a homologue (nhTMEM16) from the fungus Nectria haematococca that functions primarily as a lipid scramblase, as well as subnanometre-resolution electron cryo-microscopy. Here we present de novo atomic structures of the transmembrane domains of mouse TMEM16A in nanodiscs and in lauryl maltose neopentyl glycol as determined by single-particle electron cryo-microscopy. These structures reveal the ion permeation pore and represent different functional states. The structure in lauryl maltose neopentyl glycol has one Ca 2+ ion resolved within each monomer with a constricted pore; this is likely to correspond to a closed state, because a CaCC with a single Ca 2+ occupancy requires membrane depolarization in order to open (C.J.P. et al., manuscript submitted). The structure in nanodiscs has two Ca 2+ ions per monomer and its pore is in a closed conformation; this probably reflects channel rundown, which is the gradual loss of channel activity that follows prolonged CaCC activation in 1 mM Ca 2+ . Our mutagenesis and electrophysiological studies, prompted by analyses of the structures, identified ten residues distributed along the pore that interact with permeant anions and affect anion selectivity, as well as seven pore-lining residues that cluster near pore constrictions and regulate channel gating. Together, these results clarify the basis of CaCC anion conduction.

Functional modifications of acid-sensing ion channels by ligand-gated chloride channels.

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Xuanmao Chen

Full Text Available Together, acid-sensing ion channels (ASICs and epithelial sodium channels (ENaC constitute the majority of voltage-independent sodium channels in mammals. ENaC is regulated by a chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR. Here we show that ASICs were reversibly inhibited by activation of GABA(A receptors in murine hippocampal neurons. This inhibition of ASICs required opening of the chloride channels but occurred with both outward and inward GABA(A receptor-mediated currents. Moreover, activation of the GABA(A receptors modified the pharmacological features and kinetic properties of the ASIC currents, including the time course of activation, desensitization and deactivation. Modification of ASICs by open GABA(A receptors was also observed in both nucleated patches and outside-out patches excised from hippocampal neurons. Interestingly, ASICs and GABA(A receptors interacted to regulate synaptic plasticity in CA1 hippocampal slices. The activation of glycine receptors, which are similar to GABA(A receptors, also modified ASICs in spinal neurons. We conclude that GABA(A receptors and glycine receptors modify ASICs in neurons through mechanisms that require the opening of chloride channels.

Inhibition of small-conductance Ca2+-activated K+ channels terminates and protects against atrial fibrillation

DEFF Research Database (Denmark)

Diness, Jonas Goldin; Sørensen, Ulrik S; Nissen, Jakob Dahl

2010-01-01

Recently, evidence has emerged that small-conductance Ca(2+)-activated K(+) (SK) channels are predominantly expressed in the atria in a number of species including human. In rat, guinea pig, and rabbit ex vivo and in vivo models of atrial fibrillation (AF), we used 3 different SK channel inhibito...