Allostasis, Homeostasis, and the Costs of Physiological Adaptation

Sarah Coste reviews Allostasis, Homeostasis, and the Costs of Physiological Adaptation (edited by Jay Schulkin) for the Quarterly Review of Biology

The Effects of Social Stress on Voluntary Running Behavior in Female Mice

Regular physical activity (PA) positively impacts physical and mental health outcomes. However, there is a reciprocal relationship wherein stress significantly reduces healthy levels of routine PA. We showed previously that voluntary running behavior of male mice essentially ceases following exposure to a resident-intruder social stress. Here we examined female mice. Female mice were divided into four groups (n=8/group): sedentary/control, voluntary running/control, sedentary/stress, and voluntary running/stress. Running groups were given unlimited access to a running wheel in the home cage for 9 weeks with a nightly average of 6.86 ± 2.5 km. During the ninth week, stress groups were exposed to a single, 6-hour bout of a female-specific, resident-intruder social stress. Plasma corticosterone significantly increased following stress (34.56 ± 13 ng/ml basal to 330.5 ± 95 ng/ml immediately post-stress). Nightly running dropped significantly to 1.72 ± 0.9 km. Unlike male mice where running levels were slow to recover, voluntary running in these female mice returned to normal levels by the second night (5.01 ± 2.5 km). This study shows the sensitivity of habitual running behavior to stress exposure and suggests the utility of this mouse model in exploring the means by which stress negatively impacts routine PA

The Effects of Physical Activity on Stress-induced Cardiac Fibrosis

Purpose: This study examined whether routine physical activity limits stress-induced tissue remodeling processes that lead to cardiac fibrosis. The study also explored whether the cardiac urocortin 2/corticotropin releasing factor receptor 2β pathway was activated during physical activity and involved in reducing fibrotic processes. Methods: C67BL/6J male mice were divided into four groups (n=8/group): sedentary/control, voluntary running/control, sedentary/stress and voluntary running/stress. Voluntary running groups were given 24-hour access to a running wheel in the home cage for 9 weeks. During the 9th week, stress groups were exposed to a 5-day resident-intruder stress paradigm that models human post-traumatic stress outcomes. Ventricular cardiac tissue was collected for analysis. Results: Mice ran an average of 4.75 ± 1 km each night. Interestingly, running behavior essentially ceased following stress. Running distance dropped to 0.31 km following the 1st stress day. Some habituation to stress occurred, as running distance increased to 1.12 km by the 5th day of stress but remained significantly lower than pre-stress running distances and distances recorded in non-stressed mice. Quantitative RT-PCR showed small changes in ventricular urocortin 2 and CRF-R2β expression in the running groups. TGF-β, a signaling molecule known to induce fibrosis, had comparable expression levels across groups over controls. Conclusion: Further work is planned to fully characterize urocortin 2/ CRF-R2β and fibrotic processes. Our running data lead us in a new direction, as we have stumbled upon a paradigm that will be useful to study underlying mechanisms by which stress exposure impairs physical activity behavior

Examination of the Monoamine Oxidase a Gene Promoter on Motivation to Exercise and Levels of Voluntary Physical Activity

Purpose: Monoamine oxidase A (MAO-A) is an enzyme that causes inactivation of monoamine neurotransmitters, such as dopamine. Polymorphisms in the promoter region of the MAO-A gene can change transcriptional activity and the amount of MAO-A produced, leading to alterations in available dopamine levels. MAO-A polymorphisms have been associated with physical activity level. This study examined whether motivation to exercise, and levels of voluntary physical activity are associated with MAO-A gene polymorphisms. Methods: Seventy-one participants (18-24 years, 13 males & 58 females) completed the Behavioral Regulation in Exercise Questionaire-2 (BREQ-2) to assess their motivation to exercise and the International Physical Activity Questionnaire (IPAQ) to assess their level of physical activity. DNA was isolated from a cheek cell sample. MAO-A 3/3 and 4/4 genotype individuals were used for analysis. Results: External motivation to exercise was significantly higher (p \u3c 0.01) in the high transcription 4/4 genotype (ave 1.17 ± 0.7) compared to the low transcription 3/3 genotype (ave 0.42 ± 0.5). Internal motivation to exercise, body mass index, and weekly MET minutes were comparable between genotypes. Conclusion: The results suggest a polymorphism in this monoamine pathway may play a role in increasing sensitivity to external factors that motivate individuals to exercise

Cessation of Nightly Voluntary Wheel Running Activity Following Exposure to a Mouse Model of Posttraumatic Stress

Regular physical activity (PA) is well known to positively impact physical and mental health outcomes. In our work to examine cardiovascular benefits of PA in a mouse model of posttraumatic stress, we stumbled upon the reciprocal relationship between PA and stress exposure, wherein stress significantly reduced healthy levels of routine PA. The aim of the present studies was to define the parameters of our paradigm. C67BL/6J male mice were divided into four groups (n=8/group): sedentary/control, voluntary running/control, sedentary/stress, and voluntary running/stress. Voluntary running groups were given unlimited access to a running wheel for 9 weeks. Stress groups were then exposed to a 5-day resident-intruder social stress that models human posttraumatic stress. Running behavior essentially ceased following stress. Habituation to stress occurred, as running distance increased by the 5th day of stress but remained significantly low. A separate study examined a single exposure to resident-intruder social stress. Plasma corticosterone significantly increased while nightly running dropped significantly but returned to normal by the 3rd night post-stress. These studies show the sensitivity of habitual running behavior to stress exposure and suggest the utility of this mouse model in exploring the means by which stress negatively impacts routine PA

Velocity, Distance and Shoulder Range of Motion in Two Throwing Programs

Success in baseball pitching is determined by throwing velocity and accuracy. Strength conditioning, as well as repetitive throwing programs, are used to improve the pitch. Recently, a weighted ball program has been developed and is believed to increase ball velocity with less potential injury. However, there is limited research examining the impact of this program on performance. The purpose of this study was to compare a traditional long toss program versus a weighted ball program. Baseline throwing velocity and distance as well as shoulder range of motion (ROM) were measured in collegiate baseball players. Participants were then randomized to either a six-week-long toss throwing program or weighted ball program. Following training, throwing velocity, distance, and shoulder ROM were measured again. Both training methods significantly improved throwing distance. However, throwing velocity did not change from pre-training measurements. All measurements of shoulder ROM (flexion, abduction, and external rotation) significantly improved in both groups, with abduction showing the greatest improvement in the long toss group. Our results suggest both training programs are beneficial for baseball performance

Exotic Grains in a Core from Cornwall, NY - Do They Have an Impact Source?

We have found seven discrete layers in a bog core from Cornwall, NY about 80 km away from the Atlantic Ocean. All but two layers contain material that is unlikely to be locally derived. In most cases, the material in the layers has been transported thousands of kilometers from its source area. Six out of the seven layers are difficult to explain except through impact processes. If all of these layers are derived from impacts that produced craters, the data imply a very high impact rate during late Holocene time. In addition, we have been able to associate two of the impact ejecta layers with dated tsunami events that span the Atlantic Ocean. If this discovery is validated by further research, it implies a much larger tsunami hazard in the Atlantic Ocean than previously reported

Using ordinal logistic regression to evaluate the performance of laser-Doppler predictions of burn-healing time

Background Laser-Doppler imaging (LDI) of cutaneous blood flow is beginning to be used by burn surgeons to predict the healing time of burn wounds; predicted healing time is used to determine wound treatment as either dressings or surgery. In this paper, we do a statistical analysis of the performance of the technique. Methods We used data from a study carried out by five burn centers: LDI was done once between days 2 to 5 post burn, and healing was assessed at both 14 days and 21 days post burn. Random-effects ordinal logistic regression and other models such as the continuation ratio model were used to model healing-time as a function of the LDI data, and of demographic and wound history variables. Statistical methods were also used to study the false-color palette, which enables the laser-Doppler imager to be used by clinicians as a decision-support tool. Results Overall performance is that diagnoses are over 90% correct. Related questions addressed were what was the best blood flow summary statistic and whether, given the blood flow measurements, demographic and observational variables had any additional predictive power (age, sex, race, % total body surface area burned (%TBSA), site and cause of burn, day of LDI scan, burn center). It was found that mean laser-Doppler flux over a wound area was the best statistic, and that, given the same mean flux, women recover slightly more slowly than men. Further, the likely degradation in predictive performance on moving to a patient group with larger %TBSA than those in the data sample was studied, and shown to be small. Conclusion Modeling healing time is a complex statistical problem, with random effects due to multiple burn areas per individual, and censoring caused by patients missing hospital visits and undergoing surgery. This analysis applies state-of-the art statistical methods such as the bootstrap and permutation tests to a medical problem of topical interest. New medical findings are that age and %TBSA are not important predictors of healing time when the LDI results are known, whereas gender does influence recovery time, even when blood flow is controlled for. The conclusion regarding the palette is that an optimum three-color palette can be chosen 'automatically', but the optimum choice of a 5-color palette cannot be made solely by optimizing the percentage of correct diagnoses

Mechanosensing is critical for axon growth in the developing brain.

During nervous system development, neurons extend axons along well-defined pathways. The current understanding of axon pathfinding is based mainly on chemical signaling. However, growing neurons interact not only chemically but also mechanically with their environment. Here we identify mechanical signals as important regulators of axon pathfinding. In vitro, substrate stiffness determined growth patterns of Xenopus retinal ganglion cell axons. In vivo atomic force microscopy revealed a noticeable pattern of stiffness gradients in the embryonic brain. Retinal ganglion cell axons grew toward softer tissue, which was reproduced in vitro in the absence of chemical gradients. To test the importance of mechanical signals for axon growth in vivo, we altered brain stiffness, blocked mechanotransduction pharmacologically and knocked down the mechanosensitive ion channel piezo1. All treatments resulted in aberrant axonal growth and pathfinding errors, suggesting that local tissue stiffness, read out by mechanosensitive ion channels, is critically involved in instructing neuronal growth in vivo.This work was supported by the German National Academic Foundation (scholarship to D.E.K.), Wellcome Trust and Cambridge Trusts (scholarships to A.J.T.), Winston Churchill Foundation of the United States (scholarship to S.K.F.), Herchel Smith Foundation (Research Studentship to S.K.F.), CNPq 307333/2013-2 (L.d.F.C.), NAP-PRP-USP and FAPESP 11/50761-2 (L.d.F.C.), UK EPSRC BT grant (J.G.), Wellcome Trust WT085314 and the European Research Council 322817 grants (C.E.H.); an Alexander von Humboldt Foundation Feodor Lynen Fellowship (K.F.), UK BBSRC grant BB/M021394/1 (K.F.), the Human Frontier Science Program Young Investigator Grant RGY0074/2013 (K.F.), the UK Medical Research Council Career Development Award G1100312/1 (K.F.) and the Eunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of Health under Award Number R21HD080585 (K.F.).This is the author accepted manuscript. The final version is available from Nature Publishing Group via https://doi.org/10.1038/nn.439

Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: Advances in Patient Reported Outcomes Research

A33-Effects of Out-of-Pocket (OOP) Payments and Financial Distress on Quality of Life (QoL) of People with Parkinson’s (PwP) and their Carer