Optimal Pacing for Running 400 m and 800 m Track Races

Physicists seeking to understand complex biological systems often find it rewarding to create simple "toy models" that reproduce system behavior. Here a toy model is used to understand a puzzling phenomenon from the sport of track and field. Races are almost always won, and records set, in 400 m and 800 m running events by people who run the first half of the race faster than the second half, which is not true of shorter races, nor of longer. There is general agreement that performance in the 400 m and 800 m is limited somehow by the amount of anaerobic metabolism that can be tolerated in the working muscles in the legs. A toy model of anaerobic metabolism is presented, from which an optimal pacing strategy is analytically calculated via the Euler-Lagrange equation. This optimal strategy is then modified to account for the fact that the runner starts the race from rest; this modification is shown to result in the best possible outcome by use of an elementary variational technique that supplements what is found in undergraduate textbooks. The toy model reproduces the pacing strategies of elite 400 m and 800 m runners better than existing models do. The toy model also gives some insight into training strategies that improve performance.Comment: 14 pages, 4 figures, submitted to the American Journal of Physic

Spurious diffusion in particle simulations of the Kolmogorov flow

Particle simulations of the Kolmogorov flow are analyzed by the Landau-Lifshitz fluctuating hydrodynamics. It is shown that a spurious diffusion of the center of mass corrupts the statistical properties of the flow. The analytical expression for the corresponding diffusion coefficient is derived.Comment: 10 pages, no figure

Evolution of Li, Be and B in the Galaxy

In this paper we study the production of Li, Be and B nuclei by Galactic cosmic ray spallation processes. We include three kinds of processes: (i) spallation by light cosmic rays impinging on interstellar CNO nuclei (direct processes); (ii) spallation by CNO cosmic ray nuclei impinging on interstellar p and 4He (inverse processes); and (iii) alpha-alpha fusion reactions. The latter dominate the production of 6Li and 7Li. We calculate production rates for a closed-box Galactic model, verifying the quadratic dependence of the Be and B abundances for low values of Z. These are quite general results and are known to disagree with observations. We then show that the multi-zone multi-population model we used previously for other aspects of Galactic evolution produces quite good agreement with the linear trend observed at low metallicities without fine tuning. We argue that reported discrepancies between theory and observations do not represent a nucleosynthetic problem, but instead are the consequences of inaccurate treatments of Galactic evolution.Comment: 26 pages, 5 figures, LaTeX. The Astrophysical Journal, in pres

Vascular risk factors, cognitve decline, and dementia

Dementia is one of the most important neurological disorders in the elderly. Aging is associated with a large increase in the prevalence and incidence of degenerative (Alzheimer’s disease) and vascular dementia, leading to a devastating loss of autonomy. In view of the increasing longevity of populations worldwide, prevention of dementia has turned into a major public health challenge. In the past decade, several vascular risk factors have been found to be associated with vascular dementia but also Alzheimer’s disease. Some longitudinal studies, have found significant associations between hypertension, diabetus mellitus, and metabolic syndrome, assessed at middle age, and dementia. Studies assessing the link between hypercholesterolemia, atrial fibrillation, smoking, and dementia have given more conflicting results. Furthermore, some studies have highlighted the possible protective effect of antihypertensive therapy on cognition and some trials are evaluating the effects of statins and treatments for insulin resistance. Vascular risk factors and their treatments are a promising avenue of research for prevention of dementia, and further long-term, placebo-controlled, randomized studies, need to be performed

Identification of Melatonin-Regulated Genes in the Ovine Pituitary Pars Tuberalis, a Target Site for Seasonal Hormone Control

The pars tuberalis (PT) of the pituitary gland expresses a high density of melatonin (MEL) receptors and is believed to regulate seasonal physiology by decoding changes in nocturnal melatonin secretion. Circadian clock genes are known to be expressed in the PT in response to the decline (Per1) and onset (Cry1) of MEL secretion, but to date little is known of other molecular changes in this key MEL target site. To identify transcriptional pathways that may be involved in the diurnal and photoperiod-transduction mechanism, we performed a whole genome transcriptome analysis using PT RNA isolated from sheep culled at three time points over the 24-h cycle under either long or short photoperiods. Our results reveal 153 transcripts where expression differs between photoperiods at the light-dark transition and 54 transcripts where expression level was more globally altered by photoperiod (all time points combined). Cry1 induction at night was associated with up-regulation of genes coding for NeuroD1 (neurogenic differentiation factor 1), Pbef / Nampt (nicotinamide phosphoribosyltransferase) , Hif1α (hypoxia-inducible factor-1α), and Kcnq5 (K channel) and down-regulation of Rorβ, a key clock gene regulator. Using in situ hybridization, we confirmed day-night differences in expression for Pbef / Nampt, NeuroD1, and Rorβ in the PT. Treatment of sheep with MEL increased PT expression for Cry1, Pbef / Nampt, NeuroD1, and Hif1α, but not Kcnq5. Our data thus reveal a cluster of Cry1-associated genes that are acutely responsive to MEL and novel transcriptional pathways involved in MEL action in the PT

Antibody-mediated inhibition of the FGFR1c isoform induces a catabolic lean state in Siberian hamsters

Hypothalamic tanycytes are considered to function as sensors of peripheral metabolism [1]. To facilitate this role, they express a wide range of receptors, including fibroblast growth factor receptor 1 (FGFR1). Using a monoclonal antibody (IMC-H7) that selectively antagonizes the FGFR1c isoform [2], we investigated possible actions of FGFR1c in a natural animal model of adiposity, the Siberian hamster. Infusion of IMC-H7 into the third ventricle suppressed appetite and increased energy expenditure. Likewise, peripheral treatment with IMC-H7 decreased appetite and body weight and increased energy expenditure and fat oxidation. A greater reduction in body weight and caloric intake was observed in response to IMC-H7 during the long-day fat state as compared to the short-day lean state. This enhanced response to IMC-H7 was also observed in calorically restricted hamsters maintained in long days, suggesting that it is the central photoperiodic state rather than the peripheral adiposity that determines the response to FGFR1c antagonism. Hypothalamic thyroid hormone availability is controlled by deiodinase enzymes (DIO2 and DIO3) expressed in tanycytes and is the key regulator of seasonal cycles of energy balance [3 and 4]. Therefore, we determined the effect of IMC-H7 on hypothalamic expression of these deiodinase enzymes. The reductions in food intake and body weight were always associated with decreased expression of DIO2 in the hypothalamic ependymal cell layer containing tanycytes. These data provide further support for the notion the tanycytes are an important component of the mechanism by which the hypothalamus integrates central and peripheral signals to regulate energy intake and expenditure

Genome-wide DNA methylation meta-analysis in the brains of suicide completers

Suicide is the second leading cause of death globally among young people representing a significant global health burden. Although the molecular correlates of suicide remains poorly understood, it has been hypothesised that epigenomic processes may play a role. The objective of this study was to identify suicide-associated DNA methylation changes in the human brain by utilising previously published and unpublished methylomic datasets. We analysed prefrontal cortex (PFC, n = 211) and cerebellum (CER, n = 114) DNA methylation profiles from suicide completers and non-psychiatric, sudden-death controls, meta-analysing data from independent cohorts for each brain region separately. We report evidence for altered DNA methylation at several genetic loci in suicide cases compared to controls in both brain regions with suicide-associated differentially methylated positions enriched among functional pathways relevant to psychiatric phenotypes and suicidality, including nervous system development (PFC) and regulation of long-term synaptic depression (CER). In addition, we examined the functional consequences of variable DNA methylation within a PFC suicide-associated differentially methylated region (PSORS1C3 DMR) using a dual luciferase assay and examined expression of nearby genes. DNA methylation within this region was associated with decreased expression of firefly luciferase but was not associated with expression of nearby genes, PSORS1C3 and POU5F1. Our data suggest that suicide is associated with DNA methylation, offering novel insights into the molecular pathology associated with suicidality.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.NA/Fondation Brain Canada (Fondation Neuro Canada) MR/K013807/1/MRC_/Medical Research Council/United Kingdom NIMH 1R21MH094771/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) MR/K013807/1/Brain and Behavior Research Foundation (Brain & Behavior Research Foundation) MR/K013807/1/RCUK | MRC | Medical Research Foundation NA/Fonds de Recherche du Québec-Société et Culture (FRQSC) R21 MH094771/MH/NIMH NIH HHS/United Statespublished version, accepted version, submitted versio

Photoperiod Regulates Lean Mass Accretion, but Not Adiposity, in Growing F344 Rats Fed a High Fat Diet

yesIn this study the effects of photoperiod and diet, and their interaction, were examined for their effects on growth and body composition in juvenile F344 rats over a 4-week period. On long (16L:8D), relative to short (8L:16D), photoperiod food intake and growth rate were increased, but percentage adiposity remained constant (ca 3-4%). On a high fat diet (HFD), containing 22.8% fat (45% energy as fat), food intake was reduced, but energy intake increased on both photoperiods. This led to a small increase in adiposity (up to 10%) without overt change in body weight. These changes were also reflected in plasma leptin and lipid levels. Importantly while both lean and adipose tissue were strongly regulated by photoperiod on a chow diet, this regulation was lost for adipose, but not lean tissue, on HFD. This implies that a primary effect of photoperiod is the regulation of growth and lean mass accretion. Consistent with this both hypothalamic GHRH gene expression and serum IGF-1 levels were photoperiod dependent. As for other animals and humans, there was evidence of central hyposomatotropism in response to obesity, as GHRH gene expression was suppressed by the HFD. Gene expression of hypothalamic AgRP and CRH, but not NPY nor POMC, accorded with the energy balance status on long and short photoperiod. However, there was a general dissociation between plasma leptin levels and expression of these hypothalamic energy balance genes. Similarly there was no interaction between the HFD and photoperiod at the level of the genes involved in thyroid hormone metabolism (Dio2, Dio3, TSHβ or NMU), which are important mediators of the photoperiodic response. These data suggest that photoperiod and HFD influence body weight and body composition through independent mechanisms but in each case the role of the hypothalamic energy balance genes is not predictable based on their known function.Scottish Government (Rural and Environment Science and Analytical Services Division, http://www.scotland.gov.uk/), AWR LR LMT PJM and the BBSRC, (http://www.bbsrc.ac.uk/home/home.aspx, grant BB/K001043/1), AWR GH PJ

Expansion in CD39(+) CD4(+) Immunoregulatory T Cells and Rarity of Th17 Cells in HTLV-1 Infected Patients Is Associated with Neurological Complications

HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develops HAM/TSP. CD4(+) T cells are the main target of infection and play a pivotal role in regulating immunity to HTLV and are hypothesized to participate in the pathogenesis of HAM/TSP. the CD39 ectonucleotidase receptor is expressed on CD4(+) T cells and based on co-expression with CD25, marks T cells with distinct regulatory (CD39(+)CD25(+)) and effector (CD39(+)CD25(-)) function. Here, we investigated the expression of CD39 on CD4(+) T cells from a cohort of HAM/TSP patients, HTLV-1 asymptomatic carriers (AC), and matched uninfected controls. the frequency of CD39(+)CD4(+) T cells was increased in HTLV-1 infected patients, regardless of clinical status. More importantly, the proportion of the immunostimulatory CD39(+)CD25(-) CD4+ T-cell subset was significantly elevated in HAM/TSP patients as compared to AC and phenotypically had lower levels of the immunoinhibitory receptor, PD-1. We saw no difference in the frequency of CD39(+)CD25(+) regulatory (Treg) cells between AC and HAM/TSP patients. However, these cells transition from being anergic to displaying a polyfunctional cytokine response following HTLV-1 infection. CD39(-)CD25(+) T cell subsets predominantly secreted the inflammatory cytokine IL-17. We found that HAM/TSP patients had significantly fewer numbers of IL-17 secreting CD4(+) T cells compared to uninfected controls. Taken together, we show that the expression of CD39 is upregulated on CD4(+) T cells HAM/TSP patients. This upregulation may play a role in the development of the proinflammatory milieu through pathways both distinct and separate among the different CD39 T cell subsets. CD39 upregulation may therefore serve as a surrogate diagnostic marker of progression and could potentially be a target for interventions to reduce the development of HAM/TSP.National Institute of Allergies and Infectious DiseasesNational Institutes of HealthUniversity of CaliforniaSan Francisco-Gladstone Institute of Virology & Immunology Center for AIDS ResearchFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)John E. Fogarty International CenterNational Center for Research ResourcesNational Institute of General Medical Sciences from the National Institutes of HealthUniv Calif San Francisco, Dept Med, Div Expt Med, San Francisco, CA 94143 USAUniv Hawaii, John A Burns Sch Med, Dept Trop Med, Hawaii Ctr AIDS, Honolulu, HI 96822 USAUniv São Paulo, Sch Med, Deparment Infect Dis, São Paulo, BrazilUniv São Paulo, Sch Med, Div Clin Immunol & Allergy, São Paulo, BrazilFuncacao Prosangue, Hemoctr São Paulo, Mol Biol Lab, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Translat Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Translat Med, São Paulo, BrazilSan Francisco-Gladstone Institute of Virology & Immunology Center for AIDS Research: P30 AI027763FAPESP: 04/15856-9/KallasFAPESP: 2010/05845-0/KallasFAPESP: 11/12297-2/SanabaniJohn E. Fogarty International Center: D43 TW00003National Center for Research Resources: 5P20RR016467-11National Institute of General Medical Sciences from the National Institutes of Health: 8P20GM103466-11Web of Scienc

Malignant Catarrhal Fever Induced by Alcelaphine herpesvirus 1 Is Associated with Proliferation of CD8+ T Cells Supporting a Latent Infection

Alcelaphine herpesvirus 1 (AlHV-1), carried by wildebeest asymptomatically, causes malignant catarrhal fever (WD-MCF) when cross-species transmitted to a variety of susceptible species of the Artiodactyla order. Experimentally, WD-MCF can be induced in rabbits. The lesions observed are very similar to those described in natural host species. Here, we used the rabbit model and in vivo 5-Bromo-2′-Deoxyuridine (BrdU) incorporation to study WD-MCF pathogenesis. The results obtained can be summarized as follows. (i) AlHV-1 infection induces CD8+ T cell proliferation detectable as early as 15 days post-inoculation. (ii) While the viral load in peripheral blood mononuclear cells remains below the detection level during most of the incubation period, it increases drastically few days before death. At that time, at least 10% of CD8+ cells carry the viral genome; while CD11b+, IgM+ and CD4+ cells do not. (iii) RT-PCR analyses of mononuclear cells isolated from the spleen and the popliteal lymph node of infected rabbits revealed no expression of ORF25 and ORF9, low or no expression of ORF50, and high or no expression of ORF73. Based on these data, we propose a new model for the pathogenesis of WD-MCF. This model relies on proliferation of infected CD8+ cells supporting a predominantly latent infection