Cyclosporin A preferentially attenuates skeletal slow-twitch muscle regeneration

Calcineurin, a Ca2+/calmodulin-dependent phosphatase, is associated with muscle regeneration via NFATc1/GATA2-dependent pathways. However, it is not clear whether calcineurin preferentially affects the regeneration of slow- or fast-twitch muscles. We investigated the effect of a calcineurin inhibitor, cyclosporin A (CsA), on the morphology and fiber diameter of regenerating slow- and fast-twitch muscles. Adult Wistar rats (259.5 ± 9 g) maintained under standard conditions were treated with CsA (20 mg/kg body weight, ip) for 5 days, submitted to cryolesion of soleus and tibialis anterior (TA) muscles on the 6th day, and then treated with CsA for an additional 21 days. The muscles were removed, weighed, frozen, and stored in liquid nitrogen. Cryolesion did not alter the body weight gain of the animals after 21 days of regeneration (P = 0.001) and CsA significantly reduced the body weight gain (15.5%; P = 0.01) during the same period. All treated TA and soleus muscles showed decreased weights (17 and 29%, respectively, P < 0.05). CsA treatment decreased the cross-sectional area of both soleus and TA muscles of cryoinjured animals (TA: 2108 ± 930 vs 792 ± 640 µm²; soleus: 2209 ± 322 vs 764 ± 439 m²; P < 0.001). Histological sections of both muscles stained with Toluidine blue revealed similar regenerative responses after cryolesion. In addition, CsA was able to minimize these responses, i.e., centralized nuclei and split fibers, more efficiently so in TA muscle. These results indicate that calcineurin preferentially plays a role in regeneration of slow-twitch muscle.

Histochemical differences in the responses of predominantly fast-twitch glycolytic muscle and slow-twitch oxidative muscle to veratrine

The aim of this study was to investigate if the Na+-channel activating alkaloid veratrine is able to change the oxidative and m-ATPase activities of a fast-twitch glycolytic muscle (EDL, extensor digitorum longus) and slow-twitch oxidative muscle (SOL, soleus) in mice. Oxidative fibers and glycolytic fibers were more sensitive to veratrine than oxidative-glycolytic fibers 15, 30 and 60 min after the i.m. injection of veratrine (10 ng/kg) with both showing an increase in their metabolic activity in both muscles. In EDL, the m-ATPase reaction revealed a significant (p < 0.001) decrease (50%) in the number of type IIB fibers after 30 min while the number of type I fibers increased by 550%. Type I fibers decreased from 34% in control SOL to 17% (50% decrease) in veratrinized muscles, with a 10% decrease in type IIA fibers within 15 min. A third type of fiber appeared in SOL veratrinized muscle, which accounted for 28% of the fibers. Our work gives evidence that the changes in the percentage of the fiber types induced by veratrine may be the result, at least partially, from a direct effect of veratrine on muscle fibers and else from an interaction with the muscle type influencing distinctively the response of a same fiber type. Based on the results obtained in the present study the alterations in EDL may be related to the higher number of Na+ channels present in this muscle whereas those in SOL may involve an action of veratrine on mitochondria. Although it is unlikely that the shift of enzymes activities induced by veratrine involves genotypic expression changes an alternative explanation for the findings cannot be substantiated by the present experimental approach. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

Differential morphofunctional characteristics and gene expression in fast and slow muscle of rats with monocrotaline-induced heart failure

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

[comparative Study Between Fast And Slow Induction Of Propofol Given By Target-controlled Infusion: Expected Propofol Concentration At The Effect Site. Randomized Controlled Trial].

studies have shown that rate of propofol infusion may influence the predicted propofol concentration at the effect site (Es). The aim of this study was to evaluate the Es predicted by the Marsh pharmacokinetic model (ke0 0.26min(-1)) in loss of consciousness during fast or slow induction. the study included 28 patients randomly divided into two equal groups. In slow induction group (S), target-controlled infusion (TCI) of propofol with plasma, Marsh pharmacokinetic model (ke0 0.26min(-1)) with target concentration (Tc) at 2.0-μg.mL(-1) were administered. When the predicted propofol concentration at the effect site (Es) reached half of Es value, Es was increased to previous Es + 1μg.mL(-1), successively, until loss of consciousness. In rapid induction group (R), patients were induced with TCI of propofol with plasma (6.0μg.ml(-1)) at Es, and waited until loss of consciousness. in rapid induction group, Tc for loss of consciousness was significantly lower compared to slow induction group (1.67±0.76 and 2.50±0.56μg.mL(-1), respectively, p=0.004). the predicted propofol concentration at the effect site for loss of consciousness is different for rapid induction and slow induction, even with the same pharmacokinetic model of propofol and the same balance constant between plasma and effect site.

Fast and slow voltage modulation of apical Cl- permeability in toad skin at high [K+]

The influence of voltage on the conductance of toad skin was studied to identify the time course of the activation/deactivation dynamics of voltage-dependent Cl- channels located in the apical membrane of mitochondrion-rich cells in this tissue. Positive apical voltage induced an important conductance inhibition which took a few seconds to fully develop and was instantaneously released by pulse inversion to negative voltage, indicating a short-duration memory of the inhibiting factors. Sinusoidal stimulation at 23.4 mM [Cl-] showed hysteresis in the current versus voltage curves, even at very low frequency, suggesting that the rate of voltage application was also relevant for the inhibition/releasing effect to develop. We conclude that the voltage modulation of apical Cl- permeability is essentially a fast process and the apparent slow components of activation/deactivation obtained in the whole skin are a consequence of a gradual voltage build-up across the apical membrane due to voltage sharing between apical and basolateral membranes

Reversing the emotional Stroop effect reveals that it is not what it seems: the role of fast and slow components

The relative contributions of slow and fast (online) components in a modified emotional Stroop task were evaluated. The slow component, neglected in previous research, was shown to lead to the prediction of a reversed emotional intrusion effect using pseudorandomly mixed negative and neutral stimuli. This prediction was supported in Experiments 1 and 2. In Experiments 3 and 4, a new paradigm was developed that allowed a more direct observation of the nature of disruptive effects from negative stimuli. The results provided a clear demonstration of the presence of the slow component. The fast component, which has generally been assumed to be the source of the interference, was shown, in fact, to have little or no role in the disruption.

Fast and slow precipitation responses to individual climate forcers: a PDRMIP multi-model study

Precipitation is expected to respond differently to various drivers of anthropogenic climate change. We present the first results from the Precipitation Driver and Response Model Intercomparison Project (PDRMIP), where nine global climate models have perturbed CO2, CH4, black carbon, sulfate, and solar insolation. We divide the resulting changes to global mean and regional precipitation into fast responses that scale with changes in atmospheric absorption and slow responses scaling with surface temperature change. While the overall features are broadly similar between models, we find significant regional intermodel variability, especially over land. Black carbon stands out as a component that may cause significant model diversity in predicted precipitation change. Processes linked to atmospheric absorption are less consistently modeled than those linked to top-of-atmosphere radiative forcing. We identify a number of land regions where the model ensemble consistently predicts that fast precipitation responses to climate perturbations dominate over the slow, temperature-driven responses.

Fast and slow responses of Southern Ocean sea surface temperature to SAM in coupled climate models

We investigate how sea surface temperatures (SSTs) around Antarctica respond to the Southern An- nular Mode (SAM) on multiple timescales. To that end we examine the relationship between SAM and SST within unperturbed preindustrial control simulations of coupled general circulation models (GCMs) included in the Climate Modeling Intercomparison Project phase 5 (CMIP5). We develop a technique to extract the re- sponse of the Southern Ocean SST (55◦S−70◦S) to a hypothetical step increase in the SAM index. We demonstrate that in many GCMs, the expected SST step re- sponse function is nonmonotonic in time. Following a shift to a positive SAM anomaly, an initial cooling regime can transition into surface warming around Antarctica. However, there are large differences across the CMIP5 ensemble. In some models the step response function never changes sign and cooling persists, while in other GCMs the SST anomaly crosses over from negative to positive values only three years after a step increase in the SAM. This intermodel diversity can be related to differences in the models’ climatological thermal ocean stratification in the region of seasonal sea ice around Antarctica. Exploiting this relationship, we use obser- vational data for the time-mean meridional and vertical temperature gradients to constrain the real Southern Ocean response to SAM on fast and slow timescales.

Characterization of the transcriptome of fast and slow muscle myotomal fibres in the pacu (Piaractus mesopotamicus)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of fast and slow distillation on ethyl carbamate content and on coefficient of non-alcohol components in Brazilian sugarcane spirits

Ethyl carbamate is an impurity present in distilled beverages. Given the risk of it being a carcinogenic substance, Brazilian legislation has determined that its presence in distilled beverages, such as 'aguardente' and 'cachaca' (two types of sugarcane spirits), should be limited to a maximum of 150 mu g/L. Ordinary spirits usually contain variable amounts of ethyl carbamate, although in lower concentrations than the maximum determined by law. The finding that commercial spirits had a much lower concentration of this impurity (around 50 mu g/L) led the authors to research the reasons for the differences, and these are explored in this paper, with a focus on the speed of the distillation process and its influence on the spirit's composition. The team conducted research in a sugarcane distillery producing 'aguardente' using a simple pot still and measured the influence of fast and slow distillation on the presence of ethyl carbamate and non-alcohol components in the process. The results demonstrated that the speed of distillation was proportionally related to the concentration of ethyl carbamate and secondary components in the beverage's composition. Copyright (c) 2012 The Institute of Brewing & Distilling

Melody recognition at fast and slow tempos: Effects of age, experience, and familiarity

Eighty-one listeners defined by three age ranges (18–30, 31–59, and over 60 years) and three levels of musical experience performed an immediate recognition task requiring the detection of alterations in melodies. On each trial, a brief melody was presented, followed 5 sec later by a test stimulus that either was identical to the target or had two pitches changed, for a same–different judgment. Each melody pair was presented at 0.6 note/sec, 3.0 notes/sec, or 6.0 notes/sec. Performance was better with familiar melodies than with unfamiliar melodies. Overall performance declined slightly with age and improved substantially with increasing experience, in agreement with earlier results in an identification task. Tempo affected performance on familiar tunes (moderate was best), but not on unfamiliar tunes. We discuss these results in terms of theories of dynamic attending, cognitive slowing, and working memory in aging.

The acquisition of skilled motor performance: Fast and slow experience-driven changes in primary motor cortex

Behavioral and neurophysiological studies suggest that skill learning can be mediated by discrete, experience-driven changes within specific neural representations subserving the performance of the trained task. We have shown that a few minutes of daily practice on a sequential finger opposition task induced large, incremental performance gains over a few weeks of training. These gains did not generalize to the contralateral hand nor to a matched sequence of identical component movements, suggesting that a lateralized representation of the learned sequence of movements evolved through practice. This interpretation was supported by functional MRI data showing that a more extensive representation of the trained sequence emerged in primary motor cortex after 3 weeks of training. The imaging data, however, also indicated important changes occurring in primary motor cortex during the initial scanning sessions, which we proposed may reflect the setting up of a task-specific motor processing routine. Here we provide behavioral and functional MRI data on experience-dependent changes induced by a limited amount of repetitions within the first imaging session. We show that this limited training experience can be sufficient to trigger performance gains that require time to become evident. We propose that skilled motor performance is acquired in several stages: “fast” learning, an initial, within-session improvement phase, followed by a period of consolidation of several hours duration, and then “slow” learning, consisting of delayed, incremental gains in performance emerging after continued practice. This time course may reflect basic mechanisms of neuronal plasticity in the adult brain that subserve the acquisition and retention of many different skills.

Cytochrome c′ folding triggered by electron transfer: Fast and slow formation of four-helix bundles

Reduced (FeII) Rhodopseudomonas palustris cytochrome c′ (Cyt c′) is more stable toward unfolding ([GuHCl]1/2 = 2.9(1) M) than the oxidized (FeIII) protein ([GuHCl]1/2 = 1.9(1) M). The difference in folding free energies (ΔΔGf° = 70 meV) is less than half of the difference in reduction potentials of the folded protein (100 mV vs. NHE) and a free heme in aqueous solution (≈−150 mV). The spectroscopic features of unfolded FeII–Cyt c′ indicate a low-spin heme that is axially coordinated to methionine sulfur (Met-15 or Met-25). Time-resolved absorption measurements after CO photodissociation from unfolded FeII(CO)–Cyt c′ confirm that methionine can bind to the ferroheme on the microsecond time scale [kobs = 5(2) × 104 s−1]. Protein folding was initiated by photoreduction (two-photon laser excitation of NADH) of unfolded FeIII–Cyt c′ ([GuHCl] = 2.02–2.54 M). Folding kinetics monitored by heme absorption span a wide time range and are highly heterogeneous; there are fast-folding (≈103 s−1), intermediate-folding (102–101 s−1), and slow-folding (10−1 s−1) populations, with the last two likely containing methionine-ligated (Met-15 or Met-25) ferrohemes. Kinetics after photoreduction of unfolded FeIII–Cyt c′ in the presence of CO are attributable to CO binding [1.4(6) × 103 s−1] and FeII(CO)–Cyt c′ folding [2.8(9) s−1] processes; stopped-flow triggered folding of FeIII–Cyt c′ (which does not contain a protein-derived sixth ligand) is adequately described by a single kinetics phase with an estimated folding time constant of ≈4 ms [ΔGf° = −33(3) kJ mol−1] at zero denaturant.

Differential expression of muscle damage in humans following acute fast and slow velocity eccentric exercise

We sought to determine if the velocity of an acute bout of eccentric contractions influenced the duration and severity of several common indirect markers of muscle damage. Subjects performed 36 maximal fast (FST, n=8: 3.14 rad center dot s(-1)) or slow (SLW, n=7: 0.52 rad center dot s(-1)) velocity isokinetic eccentric contractions with the elbow flexors of the non-dominant arm. Muscle soreness, limb girth, plasma creatine kinase (CK) activity, isometric torque and concentric and eccentric torque at 0.52 and 3.14 rad center dot s(-1) were assessed prior to and for several days following the eccentric bout. Peak plasma CK activity was similar in SLW (4030 +/- 1029 U center dot l(-1)) and FST (5864 +/- 2664 U center dot l(-1)) groups, (p > 0.05). Both groups experienced similar decrement in all strength variables during the 48 hr following the eccentric bout. However, recovery occurred more rapidly in the FST group during eccentric (0.52 and 3.14 rad center dot s(-1)) and concentric (3.14 rad center dot s(-1)) post-testing. The severity of muscle soreness was similar in both groups. However, the FST group experienced peak muscle soreness 48 hr later than the SLW group (24 hr vs. 72 hr). The SLW group experienced a greater increase in upper arm girth than the FST group 20 min, 24 hr and 96 hr following the eccentric exercise bout. The contraction velocity of an acute bout of eccentric exercise differentially influences the magnitude and time course of several indirect markers of muscle damage.