Some elementary concepts of permutation groups

Call number: LD2668 .R4 1965 M17

Repeated supra-maximal sprint cycling with and without sodium bicarbonate supplementation induces endothelial microparticle release

Under normal homeostatic conditions, the endothelium releases microparticles (MP), which are known to increase under stressful conditions and in disease states. CD105 (endoglin) and CD106 (vascular cell adhesion molecule-1) are expressed on the surface of endothelial cells and increased expression in response to stress may be observed. A randomised-controlled double-blinded study aimed to examine the use of endothelial microparticles as a marker for the state of one’s endothelium, as well as whether maintaining acid-base homeostasis affects the release of these MP. This study tested seven healthy male volunteers, who completed a strenuous cycling protocol, with venous blood analysed for CD105+ and CD106+ MP by flow cytometry at regular intervals. Prior to each trial participants consumed either 0.3 g·kg-1 body mass of sodium bicarbonate (NaHCO3), or 0.045 g·kg-1 body mass of sodium chloride (NaCl). A significant rise in endothelial CD105+MP and CD106+MP (p < 0.05) was observed at 90 minutes post exercise. A significant trend was shown for these MP to return to resting levels 180 minutes post exercise in both groups. No significance was found between experimental groups, suggesting that maintaining acid-base variables closer to basal levels has little effect upon the endothelial stress response for this particular exercise mode. In conclusion, strenuous exercise is accompanied by MP release and the endothelium is able to rapidly recover in healthy individuals, whilst maintaining acid-base homeostasis does not attenuate the MP release from the endothelium after exercise

Implications of a pre-exercise alkalosis-mediated attenuation of HSP72 on its response to a subsequent bout of exercise

The aim of this study was to investigate if a pre-exercise alkalosis-mediated attenuation of HSP72 had any effect on the response of the same stress protein after a subsequent exercise. Seven physically active males [25.0 ± 6.5 years, 182.1 ± 6.0 cm, 74.0 ± 8.3 kg, peak aerobic power (PPO) 316 ± 46 W] performed a repeated sprint exercise (EXB1) following a dose of 0.3 g kg⁻¹ body mass of sodium bicarbonate (BICARB), or a placebo of 0.045 g kg⁻¹ body mass of sodium chloride (PLAC). Participants then completed a 90-min intermittent cycling protocol (EXB2). Monocyte expressed HSP72 was significantly attenuated after EXB1 in BICARB compared to PLAC, however, there was no difference in the HSP72 response to the subsequent EXB2 between conditions. Furthermore there was no difference between conditions for measures of oxidative stress (protein carbonyl and HSP32). These findings confirm the sensitivity of the HSP72 response to exercise-induced changes in acid–base status in vivo, but suggest that the attenuated response has little effect upon subsequent stress in the same day

Application of in silico and in vitro methods in the development of adverse outcome pathway constructs in wildlife

There is a long history of using both in silico and in vitro methods to predict adverse effects in humans and environmental species where toxicity data are lacking. Currently, there is a great deal of interest in applying these methods to the development of so-called ‘adverse outcome pathway’ (AOP) constructs. The AOP approach provides a framework for organizing information at the chemical and biological level, allowing evidence from both in silico and in vitro studies to be rationally combined to fill gaps in knowledge concerning toxicological events. Fundamental to this new paradigm is a greater understanding of the mechanisms of toxicity and, in particular, where these mechanisms may be conserved across taxa, such as between model animals and related wild species. This presents an opportunity to make predictions across diverse species, where empirical data are unlikely to become available as is the case for most species of wildlife

Comparative metabolism as a key driver of wildlife species sensitivity to human and veterinary pharmaceuticals

Human and veterinary drug development addresses absorption, distribution, metabolism, elimination and toxicology (ADMET) of the Active Pharmaceutical Ingredient (API) in the target species. Metabolism is an important factor in controlling circulating plasma and target tissue API concentrations and in generating metabolites which are more easily eliminated in bile, faeces and urine. The essential purpose of xenobiotic metabolism is to convert lipid-soluble, non-polar and non-excretable chemicals into water soluble, polar molecules that are readily excreted. Xenobiotic metabolism is classified into Phase I enzymatic reactions (which add or expose reactive functional groups on xenobiotic molecules), Phase II reactions (resulting in xenobiotic conjugation with large water-soluble, polar molecules) and Phase III cellular efflux transport processes. The human-fish plasma model provides a useful approach to understanding the pharmacokinetics of APIs (e.g. diclofenac, ibuprofen and propranolol) in freshwater fish, where gill and liver metabolism of APIs have been shown to be of importance. By contrast, wildlife species with low metabolic competency may exhibit zero-order metabolic (pharmacokinetic) profiles and thus high API toxicity, as in the case of diclofenac and the dramatic decline of vulture populations across the Indian subcontinent. A similar threat looms for African Cape Griffon vultures exposed to ketoprofen and meloxicam, recent studies indicating toxicity relates to zero-order metabolism (suggesting P450 Phase I enzyme system or Phase II glucuronidation deficiencies). While all aspects of ADMET are important in toxicity evaluations, these observations demonstrate the importance of methods for predicting API comparative metabolism as a central part of environmental risk assessment

Nonsupersymmetric smooth geometries and D1-D5-P bound states

We construct smooth nonsupersymmetric soliton solutions with D1-brane, D5-brane, and momentum charges in type IIB supergravity compactified on T4×S1, with the charges along the compact directions. This generalizes previous studies of smooth supersymmetric solutions. The solutions are obtained by considering a known family of U(1)×U(1) invariant metrics, and studying the conditions imposed by requiring smoothness. We discuss the relation of our solutions to states in the CFT describing the D1-D5 system and describe various interesting features of the geometry

Mid-infrared observations of the ultraluminous galaxies IRAS14348-1447, IRAS19254-7245, and IRAS23128-5919

We present a study of the three ultraluminous infrared galaxies IRAS14348-1447, IRAS19254-7245, and IRAS23128-5919, based on mid-infrared (MIR) spectro-imaging (5-18microns) observations performed with ISOCAM. We find that the MIR emission from each system, which consists of a pair of interacting late type galaxies, is principally confined to the nuclear regions with diameters of 1-2kpc and can account for more than 95% of their IRAS 12micron flux. In each interacting system, the galaxy hosting an active galactic nucleus (AGN) dominates the total spectrum and shows stronger dust continuum (12-16microns) relative to the Unidentified Infrared Band (UIB) emission (6-9microns), suggestive of its enhanced radiation field. The MIR dominant galaxy also exhibits elevated 15micron/Halpha and 15micron/K ratios which trace the high extinction due to the large quantities of molecular gas and dust present in its central regions. Using only diagnostics based on our mid-infrared spectra, we can establish that the Seyfert galaxy IRAS19254-7245 exhibits MIR spectral features of an AGN while the MIR spectrum of the Seyfert (or LINER) member of IRAS23128-5919 is characteristic of dust emission principally heated by star forming regions.Comment: Accepted for publication in Astronomy & Astrophysics, 13 pages, 9 figure

Resistance training leads to large improvements in strength and moderate improvements in physical function in adults who are overweight or obese: a systematic review

QuestionsWhat are the effects of resistance training on muscle strength, physical function and muscle power in adults who are overweight or obese? Which factors moderate the effects?DesignSystematic review of randomised controlled trials, with random effects meta-analyses and meta-regressions.ParticipantsAdults who are overweight or obese.InterventionResistance training lasting ≥ 4 weeks.Outcome measuresMuscle strength, muscle power and physical function.ResultsThirty trials with 1,416 participants met the eligibility criteria. Pooled analyses indicated that resistance training has a large beneficial effect on muscle strength (SMD 1.39, 95% CI 1.05 to 1.73, I2 = 85%) and a moderate effect on physical function (SMD 0.67, 95% CI 0.25 to 1.08, I2 = 71%) in adults who are overweight or obese. However, the effect of resistance training on muscle power was unclear (SMD 0.42, 95% CI −3.3 to 4.2, I2 = 46%). The effect of resistance training on strength was greatest for the upper body (versus lower/whole body: β = 0.35, 95% CI 0.05 to 0.66) and in dynamic strength tests (versus isometric/isokinetic: β = 1.20, 95% CI 0.60 to 1.81), although trials judged to have good methodological quality reported statistically smaller effects (versus poor/fair quality: β = −1.21, 95% CI −2.35 to −0.07). Concomitant calorie restriction did not modify strength gains but reduced the effect of resistance training on physical function (β = −0.79, 95% CI −1.41 to −0.17). Small study effects were evident for strength outcomes (β = 5.9, p < 0.001).ConclusionsResistance training has a large positive effect on muscle strength and a moderate effect on physical function in adults who are overweight or obese. However, the effect of resistance training on muscle power is uncertain. In addition, concomitant calorie restriction may compromise the functional adaptations to resistance training