The electrical response of pancreatic beta-cells to step increases in glucose concentration is biphasic, consisting of a prolonged depolarization with action potentials (Phase 1) followed by membrane ...potential oscillations known as bursts. We have proposed that the Phase 1 response results from the combined depolarizing influences of potassium channel closure and an inward, nonselective cation current (ICRAN) that activates as intracellular calcium stores empty during exposure to basal glucose (Bertram et al., 1995). The stores refill during Phase 1, deactivating ICRAN and allowing steady-state bursting to commence. We support this hypothesis with additional simulations and experimental results indicating that Phase 1 duration is sensitive to the filling state of intracellular calcium stores. First, the duration of the Phase 1 transient increases with duration of prior exposure to basal (2.8 mM) glucose, reflecting the increased time required to fill calcium stores that have been emptying for longer periods. Second, Phase 1 duration is reduced when islets are exposed to elevated K+ to refill calcium stores in the presence of basal glucose. Third, when extracellular calcium is removed during the basal glucose exposure to reduce calcium influx into the stores, Phase 1 duration increases. Finally, no Phase 1 is observed following hyperpolarization of the beta-cell membrane with diazoxide in the continued presence of 11 mm glucose, a condition in which intracellular calcium stores remain full. Application of carbachol to empty calcium stores during basal glucose exposure did not increase Phase 1 duration as the model predicts. Despite this discrepancy, the good agreement between most of the experimental results and the model predictions provides evidence that a calcium release-activated current mediates the Phase 1 electrical response of the pancreatic beta-cell.
This study examined the influence of a strength and power program on tackling ability in rugby league players. Twenty-four semiprofessional rugby league players (mean ± SD age, 23.4 ± 3.1 years) ...underwent tests of upper-body strength (3 repetition maximum RM bench press), lower-body strength (3RM squat), upper-body power (plyometric push-up), and lower-body power (countermovement jump CMJ). Muscular strength relative to body mass was also calculated. Tackling ability of the players was assessed using video analysis of a standardized one-on-one tackling drill. The players then underwent 8 weeks of strength and power training as part of their preseason training before being retested. Training resulted in significant (p ≤ 0.01) improvements in absolute and relative measures of squat, bench press, CMJ peak power, and plyometric push-up peak power. The strongest correlates of change in tackling ability were changes in 3RM squat (r = 0.60; p < 0.01) and squat relative to body mass (r = 0.54; p < 0.01). The players with the greatest improvements in 3RM squat and squat relative to body mass (i.e., responders) had significantly greater improvements in tackling ability than nonresponding players (p = 0.04; effect size ES ≥ 0.85). A small, nonsignificant difference (p = 0.20; ES = 0.56) in tackling ability was found between responders and nonresponders for lower-body power. The findings of this study demonstrate that the enhancement of lower-body muscular strength, and to a lesser extent muscular power, contribute to improvements in tackling ability in semiprofessional rugby league players.
Analysis of urine samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS) has previously revealed high rates of non-adherence to antihypertensive medication. It is unclear whether ...these rates represent those in the general population. This study aimed to investigate whether it is feasible to collect urine samples in a primary care setting and analyse them using LC-MS/MS to detect non-adherence to antihypertensive medication. This study used a prospective, observational cohort design. Consecutive patients were recruited opportunistically from five general practices in UK primary care. They were aged ≥65 years with hypertension and had at least one antihypertensive prescription. Participants were asked to provide a urine sample for analysis of medication adherence. Samples were sent to a laboratory via post and analysed using LC-MS/MS. Predictors of adherence to medication were explored with multivariable logistic regression. Of 349 consecutive patients approached for the study, 214 (61.3%) gave informed consent and 191 (54.7%) provided a valid urine sample for analysis. Participants were aged 76.2 ± 6.6 years and taking a median of 2 antihypertensive medications (IQR 1-3). A total of 27/191 participants (14.2%) reported not taking all of their medications on the day of urine sample collection. However, LC-MS/MS analysis of samples revealed only 4/27 (9/191 in total; 4.7%) were non-adherent to some of their medications. Patients prescribed more antihypertensive medications were less likely to be adherent (OR 0.24, 95%CI 0.09-0.65). Biochemical testing for antihypertensive medication adherence is feasible in routine primary care, although non-adherence to medication is generally low, and therefore widespread testing is not indicated.
Atomic-Scale Visualization of Inertial Dynamics Lindenberg, A. M; Larsson, J; Sokolowski-Tinten, K ...
Science (American Association for the Advancement of Science),
04/2005, Letnik:
308, Številka:
5720
Journal Article
Recenzirano
Odprti dostop
The motion of atoms on interatomic potential energy surfaces is fundamental to the dynamics of liquids and solids. An accelerator-based source of femtosecond x-ray pulses allowed us to follow ...directly atomic displacements on an optically modified energy landscape, leading eventually to the transition from crystalline solid to disordered liquid. We show that, to first order in time, the dynamics are inertial, and we place constraints on the shape and curvature of the transition-state potential energy surface. Our measurements point toward analogies between this nonequilibrium phase transition and the short-time dynamics intrinsic to equilibrium liquids.
Regulation of intestinal T-cell responses is crucial for immune homeostasis and prevention of inflammatory bowel disease (IBD). A vital cytokine in regulating intestinal T cells is transforming ...growth factor-β (TGFβ), which is secreted by cells as a latent complex that requires activation to function. However, how TGFβ activation is regulated in the human intestine, and how such pathways are altered in IBD is completely unknown. Here we show that a key activator of TGFβ, integrin αvβ8, is highly expressed on human intestinal dendritic cells (DCs), specifically on the CD1c
but not the CD141
intestinal DC subset. Expression was significantly upregulated on intestinal DC from IBD patients, indicating that inflammatory signals may upregulate expression of this key TGFβ-activating molecule. Indeed, we found that the Toll-like receptor 4 ligand lipopolysaccharide upregulates integrin αvβ8 expression and TGFβ activation by human DC. We also show that DC expression of integrin αvβ8 enhanced induction of FOXP3 in CD4
T cells, suggesting functional importance of integrin αvβ8 expression by human DC. These results show that microbial signals enhance the TGFβ-activating ability of human DC via regulation of integrin αvβ8 expression, and that intestinal inflammation may drive this pathway in patients with IBD.
An anesthesia system which integrates closed-loop control of ventilation, oxygen, nitrous oxide, and anesthetic agent delivery into a closed breathing circuit is described. Breathing circuit volume ...is regulated by controlling the sum of oxygen and nitrous oxide flow, and oxygen concentration in the breathing circuit is regulated by controlling the ratio of oxygen flow to the sum of oxygen and nitrous oxide flow. End-tidal anesthetic agent concentration is regulated by controlling the agent delivery, and end-tidal carbon dioxide concentration is regulated by controlling the ventilation. After tuning the ventilation and anesthetic delivery controllers in preliminary trials in ten dogs, the system was tested and evaluated in five dogs. All control loops were stable and exhibited time responses to step changes in setpoint or external disturbances which were clinically acceptable. The system makes available the advantages of closed-system anesthesia without encumbering the anesthesiologist with the control tasks associated with the technique.
Anomalocaris canadensis, a soft-bodied stem-group arthropod from the Burgess Shale, is considered the largest predator of the Cambrian period. Thanks to a series of lateral flexible lobes along its ...dorso-ventrally compressed body, it is generally regarded as an efficient swimmer, well-adapted to its predatory lifestyle. Previous theoretical hydrodynamic simulations have suggested a possible optimum in swimming performance when the lateral lobes performed as a single undulatory lateral fin, comparable to the pectoral fins in skates and rays. However, the role of the unusual fan-like tail of Anomalocaris has not been previously explored. Swimming efficiency and maneuverability deduced from direct hydrodynamic analysis are here studied in a towing tank facility using a three-vane physical model designed as an abstraction of the tail fin. Through direct force measurements, it was found that the model exhibited a region of steady-state lift and drag enhancement at angles of attack greater than 25° when compared with a triangular-shaped reference model. This would suggest that the resultant normal force on the tail fin of Anomalocaris made it well-suited for turning maneuvers, giving it the ability to turn quickly and through small radii of curvature. These results are consistent with an active predatory lifestyle, although detailed kinematic studies integrating the full organism, including the lateral lobes, would be required to test the effect of the tail fin on overall swimming performance. This study also highlights a possible example of evolutionary convergence between the tails of Anomalocaris and birds, which, in both cases, are well-adapted to efficient turning maneuvers.
Introduction: Particulate Matter (PM) air pollution has been associated with cardiovascular disease (CVD) in studies of long-term exposure; however, prior studies have had limited geographical ...variability and individual level information on prior medical history, and did not assess nonfatal events. We examined the association of long-term exposure to PM with CVD in the WHI-OS prospective cohort study. Methods: We assigned air pollution exposures to 66,801 postmenopausal US women with no history of CVD, using year 2000 averaged exposure data from the nearest representative PM sub(2.5) monitor (within 30 miles) of subject residential zipcode centroid. Monitor characteristics and annual average pollutant concentrations were obtained from EPA AirData database. Median follow-up was 6.0 years including events through August, 2003. Events were ascertained by review of hospital and medical records or death certificates with local adjudication according to standardized criteria. There were 421 fatal CVD events and 3061 incident nonfatal CVD events. Specific events included CHD death 162, cerebrovascular death 145, CVD death 114; nonfatal MI 597, angina 854, revascularization 165, coronary artery disease 148, CHF 382, stroke 570, and TIA 345. For the first incident event since enrollment, we calculated hazard ratios per 10 mu g/m super(3) increment of annual average PM sub(2.5) exposure using Cox proportional hazards regression, adjusting for age, smoking status, years smoked, cigarettes/day, diabetes, hypertension, systolic and diastolic blood pressure, BMI, and elevated cholesterol. Results: After adjustment for confounding factors, each 10 mu g/m super(3) of PM sub(2.5) was associated with a 17% increased risk of incident nonfatal and fatal CVD events, relative hazard (RH) 1.17 (95% CI: 1.06, 1.28). Risk was increased by 14% for incident nonfatal CVD events (RH 1.14; 95% CI 1.03, 1.26) and by 32% for fatal CVD events (RH 1.32; 95% CI: 1.01, 1.73). Further adjustment for second-hand smoke, occupation, SES, diet, exercise and medications did not appreciably change estimates. Discussion: Our results suggest that long-term exposure to PM sub(2.5) is associated with both CVD mortality and with nonfatal CVD events. Chronic air pollution exposure may influence CVD incidence in postmenopausal women.
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