Effects of lowering body temperature via hyperhydration, with and without glycerol ingestion and practical precooling on cycling time trial performance in hot and humid conditions

Background Hypohydration and hyperthermia are factors that may contribute to fatigue and impairment of endurance performance. The purpose of this study was to investigate the effectiveness of combining glycerol hyperhydration and an established precooling technique on cycling time trial performance in hot environmental conditions. Methods Twelve well-trained male cyclists performed three 46.4-km laboratory-based cycling trials that included two climbs, under hot and humid environmental conditions (33.3 ± 1.1°C; 50 ± 6% r.h.). Subjects were required to hyperhydrate with 25 g.kg-1 body mass (BM) of a 4°C beverage containing 6% carbohydrate (CON) 2.5 h prior to the time trial. On two occasions, subjects were also exposed to an established precooling technique (PC) 60 min prior to the time trial, involving 14 g.kg-1 BM ice slurry ingestion and applied iced towels over 30 min. During one PC trial, 1.2 g.kg-1 BM glycerol was added to the hyperhydration beverage in a double-blind fashion (PC+G). Statistics used in this study involve the combination of traditional probability statistics and a magnitude-based inference approach. Results Hyperhydration resulted in large reductions (−0.6 to −0.7°C) in rectal temperature. The addition of glycerol to this solution also lowered urine output (330 ml, 10%). Precooling induced further small (−0.3°C) to moderate (−0.4°C) reductions in rectal temperature with PC and PC+G treatments, respectively, when compared with CON (0.0°C, P<0.05). Overall, PC+G failed to achieve a clear change in cycling performance over CON, but PC showed a possible 2% (30 s, P=0.02) improvement in performance time on climb 2 compared to CON. This improvement was attributed to subjects’ lower perception of effort reported over the first 10 km of the trial, despite no clear performance change during this time. No differences were detected in any other physiological measurements throughout the time trial. Conclusions Despite increasing fluid intake and reducing core temperature, performance and thermoregulatory benefits of a hyperhydration strategy with and without the addition of glycerol, plus practical precooling, were not superior to hyperhydration alone. Further research is warranted to further refine preparation strategies for athletes competing in thermally stressful events to optimize health and maximize performance outcomes

Distal retinal ganglion cell axon transport loss and activation of p38 MAPK stress pathway following VEGF-A antagonism.

There is increasing evidence that VEGF-A antagonists may be detrimental to neuronal health following ocular administration. Here we investigated firstly the effects of VEGF-A neutralization on retinal neuronal survival in the Ins2(Akita) diabetic and JR5558 spontaneous choroidal neovascularization (CNV) mice, and then looked at potential mechanisms contributing to cell death. We detected elevated apoptosis in the ganglion cell layer in both these models following VEGF-A antagonism, indicating that even when vascular pathologies respond to treatment, neurons are still vulnerable to reduced VEGF-A levels. We observed that retinal ganglion cells (RGCs) seemed to be the cells most susceptible to VEGF-A antagonism, so we looked at anterograde transport in these cells, due to their long axons requiring optimal protein and organelle trafficking. Using cholera toxin B-subunit tracer studies, we found a distal reduction in transport in the superior colliculus following VEGF-A neutralization, which occurred prior to net RGC loss. This phenomenon of distal transport loss has been described as a feature of early pathological changes in glaucoma, Alzheimer's and Parkinson's disease models. Furthermore, we observed increased phosphorylation of p38 MAPK and downstream Hsp27 stress pathway signaling in the retinas from these experiments, potentially providing a mechanistic explanation for our findings. These experiments further highlight the possible risks of using VEGF-A antagonists to treat ocular neovascular disease, and suggest that VEGF-A may contribute to the maintenance and function of axonal transport in neurons of the retina.This work was funded by the Medical Research Council (G0901303) of the UK. We also wish to thank the Cambridge Eye Trust for their support.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/cddis.2016.11

Boolean network model predicts cell cycle sequence of fission yeast

A Boolean network model of the cell-cycle regulatory network of fission yeast (Schizosaccharomyces Pombe) is constructed solely on the basis of the known biochemical interaction topology. Simulating the model in the computer, faithfully reproduces the known sequence of regulatory activity patterns along the cell cycle of the living cell. Contrary to existing differential equation models, no parameters enter the model except the structure of the regulatory circuitry. The dynamical properties of the model indicate that the biological dynamical sequence is robustly implemented in the regulatory network, with the biological stationary state G1 corresponding to the dominant attractor in state space, and with the biological regulatory sequence being a strongly attractive trajectory. Comparing the fission yeast cell-cycle model to a similar model of the corresponding network in S. cerevisiae, a remarkable difference in circuitry, as well as dynamics is observed. While the latter operates in a strongly damped mode, driven by external excitation, the S. pombe network represents an auto-excited system with external damping.Comment: 10 pages, 3 figure

Admission to hospital following head injury in England: Incidence and socio-economic associations

BACKGROUND: Head injury in England is common. Evidence suggests that socio-economic factors may cause variation in incidence, and this variation may affect planning for services to meet the needs of those who have sustained a head injury. METHODS: Socio-economic data were obtained from the UK Office for National Statistics and merged with Hospital Episodes Statistics obtained from the Department of Health. All patients admitted for head injury with ICD-10 codes S00.0–S09.9 during 2001–2 and 2002–3 were included and collated at the level of the extant Health Authorities (HA) for 2002, and Primary Care Trust (PCT) for 2003. Incidence was determined, and cluster analysis and multiple regression analysis were used to look at patterns and associations. Results: 112,718 patients were admitted during 2001–2 giving a hospitalised incidence rate for England of 229 per 100,000. This rate varied across the English HA's ranging from 91–419 per 100,000. The rate remained unchanged for 2002–3 with a similar magnitude of variation across PCT's. Three clusters of HA's were identified from the 2001–2 data; those typical of London, those of the Shire counties, and those of Other Urban authorities. Socio-economic factors were found to account for a high proportion of the variance in incidence for 2001–2. The same pattern emerged for 2002–3 at the PCT level. The use of public transport for travel to work is associated with a decreased incidence and lifestyle indicators, such as the numbers of young unemployed, increase the incidence. CONCLUSION: Head injury incidence in England varies by a factor of 4.6 across HA's and PCT's. Planning head injury related services at the local level thus needs to be based on local incidence figures rather than regional or national estimates. Socio-economic factors are shown to be associated with admission, including travel to work patterns and lifestyle indicators, which suggests that incidence is amenable to policy initiatives at the macro level as well as preventive programmes targeted at key groups

Some Field Theoretic Issues Regarding the Chiral Magnetic Effect

In this paper, we shall address some field theoretic issues regarding the chiral magnetic effect. The general structure of the magnetic current consistent with the electromagnetic gauge invariance is obtained and the impact of the infrared divergence is examined. Some subtleties on the relation between the chiral magnetic effect and the axial anomaly are clarified through a careful examination of the infrared limit of the relevant thermal diagrams.Comment: 19 pages, 4 figures in Latex. Typos fixed, version accepted to be published in JHE

Pre-cooling for endurance exercise performance in the heat: a systematic review.

PMCID: PMC3568721The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/166. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endurance exercise capacity diminishes under hot environmental conditions. Time to exhaustion can be increased by lowering body temperature prior to exercise (pre-cooling). This systematic literature review synthesizes the current findings of the effects of pre-cooling on endurance exercise performance, providing guidance for clinical practice and further research

Coupling of alpha(1)-Adrenoceptors to ERK1/2 in the Human Prostate

Introduction: alpha(1)-Adrenoceptors are considered critical for the regulation of prostatic smooth muscle tone. However, previous studies suggested further alpha(1)-adrenoceptor functions besides contraction. Here, we investigated whether alpha(1)-adrenoceptors in the human prostate may activate extracellular signal-regulated kinases (ERK1/2). Methods: Prostate tissues from patients undergoing radical prostatectomy were stimulated in vitro. Activation of ERK1/2 was assessed by Western blot analysis. Expression of ERK1/2 was studied by immunohistochemistry. The effect of ERK1/2 inhibition by U0126 on phenylephrine-induced contraction was studied in organ-bath experiments. Results: Stimulation of human prostate tissue with noradrenaline (30 mu M) or phenylephrine (10 mu M) resulted in ERK activation. This was reflected by increased levels of phosphorylated ERK1/2. Expression of ERK1/2 in the prostate was observed in smooth muscle cells. Incubation of prostate tissue with U0126 (30 mu M) resulted in ERK1/2 inhibition. Dose-dependent phenylephrine-induced contraction of prostate tissue was not modulated by U0126. Conclusions: alpha(1)-Adrenoceptors in the human prostate are coupled to ERK1/2. This may partially explain previous observations suggesting a role of alpha(1)-adrenoceptors in the regulation of prostate growth. Copyright (C) 2011 S. Karger AG, Base

Shock waves in strongly coupled plasmas

Shock waves are supersonic disturbances propagating in a fluid and giving rise to dissipation and drag. Weak shocks, i.e., those of small amplitude, can be well described within the hydrodynamic approximation. On the other hand, strong shocks are discontinuous within hydrodynamics and therefore probe the microscopics of the theory. In this paper we consider the case of the strongly coupled N=4 plasma whose microscopic description, applicable for scales smaller than the inverse temperature, is given in terms of gravity in an asymptotically $AdS_5$ space. In the gravity approximation, weak and strong shocks should be described by smooth metrics with no discontinuities. For weak shocks we find the dual metric in a derivative expansion and for strong shocks we use linearized gravity to find the exponential tail that determines the width of the shock. In particular we find that, when the velocity of the fluid relative to the shock approaches the speed of light $v\to 1$ the penetration depth $\ell$ scales as $\ell\sim (1-v^2)^{1/4}$. We compare the results with second order hydrodynamics and the Israel-Stewart approximation. Although they all agree in the hydrodynamic regime of weak shocks, we show that there is not even qualitative agreement for strong shocks. For the gravity side, the existence of shock waves implies that there are disturbances of constant shape propagating on the horizon of the dual black holes.Comment: 47 pages, 8 figures; v2:typos corrected, references adde

Molecular basis of FIR-mediated c-myc transcriptional control

The far upstream element (FUSE) regulatory system promotes a peak in the concentration of c-Myc during cell cycle. First, the FBP transcriptional activator binds to the FUSE DNA element upstream of the c-myc promoter. Then, FBP recruits its specific repressor (FIR), which acts as an on/off transcriptional switch. Here we describe the molecular basis of FIR recruitment, showing that the tandem RNA recognition motifs of FIR provide a platform for independent FUSE DNA and FBP protein binding and explaining the structural basis of the reversibility of the FBP-FIR interaction. We also show that the physical coupling between FBP and FIR is modulated by a flexible linker positioned sequentially to the recruiting element. Our data explain how the FUSE system precisely regulates c-myc transcription and suggest that a small change in FBP-FIR affinity leads to a substantial effect on c-Myc concentration.MRC Grant-in-aid U11757455

The "Ram Effect": A "Non-Classical" Mechanism for Inducing LH Surges in Sheep

During spring sheep do not normally ovulate but exposure to a ram can induce ovulation. In some ewes an LH surge is induced immediately after exposure to a ram thus raising questions about the control of this precocious LH surge. Our first aim was to determine the plasma concentrations of oestradiol (E2) E2 in anoestrous ewes before and after the "ram effect" in ewes that had a "precocious" LH surge (starting within 6 hours), a "normal" surge (between 6 and 28h) and "late» surge (not detected by 56h). In another experiment we tested if a small increase in circulating E2 could induce an LH surge in anoestrus ewes. The concentration of E2 significantly was not different at the time of ram introduction among ewes with the three types of LH surge. "Precocious" LH surges were not preceded by a large increase in E2 unlike "normal" surges and small elevations of circulating E2 alone were unable to induce LH surges. These results show that the "precocious" LH surge was not the result of E2 positive feedback. Our second aim was to test if noradrenaline (NA) is involved in the LH response to the "ram effect". Using double labelling for Fos and tyrosine hydroxylase (TH) we showed that exposure of anoestrous ewes to a ram induced a higher density of cells positive for both in the A1 nucleus and the Locus Coeruleus complex compared to unstimulated controls. Finally, the administration by retrodialysis into the preoptic area, of NA increased the proportion of ewes with an LH response to ram odor whereas treatment with the α1 antagonist Prazosin decreased the LH pulse frequency and amplitude induced by a sexually active ram. Collectively these results suggest that in anoestrous ewes NA is involved in ram-induced LH secretion as observed in other induced ovulators