The effects of exercise and two pre-exercise fluid amounts on cognition

Exercise is associated with elevated mood states and arousal. Observational studies support the claim that exercise can help individuals think more “clearly’ with reports of improved mood and feelings of psychological well-being following exercise. However, laboratory studies have produced equivocal results. The purpose of this study is to examine the effect of exercise intensity and two likely pre-exercise fluid amounts consumed by euhydrated athletes on cognitive performance. Fifteen college age students were randomly assigned to either a 150 ml or a 500 ml fluid condition on the first test day and received the other fluid condition on the second test day. Prior to exercise subjects completed baseline computerized cognitive tests then began a treadmill protocol of three 6 min stages at increasing intensity after which subjects completed cognitive tests. A second treadmill portion started at 7.5 mph for 2 min then speed was increased 0.5 mph every 30 s until voluntary exhaustion and final cognitive testing was completed. Our results demonstrate a facilitation of cognitive function in response to exercise with the exception of the match to sample cognitive test which showed lack of facilitation of cognition in the 500 ml condition at moderate exercise. Our research contributes to the growing field of exercise and its effects on cognition. Specifically working memory cognitive tests showed facilitation with exercise. These results may be applicable to a typical exercising population since our study included a common exercise mode (treadmill) at moderate and high intensities and likely fluid amounts

Joint inversion estimate of regional glacial isostatic adjustment in Antarctica considering a lateral varying Earth structure (ESA STSE Project REGINA)

A major uncertainty in determining the mass balance of the Antarctic ice sheet from measurements of satellite gravimetry, and to a lesser extent satellite altimetry, is the poorly known correction for the ongoing deformation of the solid Earth caused by glacial isostatic adjustment (GIA). Although much progress has been made in consistently modelling the ice-sheet evolution throughout the last glacial cycle, as well as the induced bedrock deformation caused by these load changes, forward models of GIA remain ambiguous due to the lack of observational constraints on the ice sheet's past extent and thickness and mantle rheology beneath the continent. As an alternative to forward modelling GIA, we estimate GIA from multiple space-geodetic observations: GRACE, Envisat/ICESat and GPS. Making use of the different sensitivities of the respective satellite observations to current and past surface mass (ice mass) change and solid Earth processes, we estimate GIA based on viscoelastic response functions to disc load forcing. We calculate and distribute the viscoelastic response functions according to estimates of the variability of lithosphere thickness and mantle viscosity in Antarctica. We compare our GIA estimate with published GIA corrections and evaluate its impact in determining the ice mass balance in Antarctica from GRACE and satellite altimetry. Particular focus is applied to the Amundsen Sea Sector in West Antarctica, where uplift rates of several cm/yr have been measured by GPS. We show that most of this uplift is caused by the rapid viscoelastic response to recent ice-load changes, enabled by the presence of a low-viscosity upper mantle in West Antarctica. This paper presents the second and final contribution summarizing the work carried out within a European Space Agency funded study, REGINA, (www.regina-science.eu)

Fat intake and injury in female runners

<p>Abstract</p> <p>Background</p> <p>Our purpose was to determine the relationship between energy intake, energy availability, dietary fat and lower extremity injury in adult female runners. We hypothesized that runners who develop overuse running-related injuries have lower energy intakes, lower energy availability and lower fat intake compared to non-injured runners.</p> <p>Methods</p> <p>Eighty-six female subjects, running a minimum of 20 miles/week, completed a food frequency questionnaire and informed us about injury incidence over the next year.</p> <p>Results</p> <p>Injured runners had significantly lower intakes of total fat (63 ± 20 vs. 80 ± 50 g/d) and percentage of kilocalories from fat (27 ± 5 vs. 30 ± 8 %) compared with non-injured runners. A logistic regression analysis found that fat intake was the best dietary predictor, correctly identifying 64% of future injuries. Lower energy intake and lower energy availability approached, but did not reach, a significant association with overuse injury in this study.</p> <p>Conclusion</p> <p>Fat intake is likely associated with injury risk in female runners. By documenting these associations, better strategies can be developed to reduce running injuries in women.</p

Exosomes containing HIV protein Nef reorganize lipid rafts potentiating inflammatory response in bystander cells.

HIV infection has a profound effect on "bystander" cells causing metabolic co-morbidities. This may be mediated by exosomes secreted by HIV-infected cells and containing viral factors. Here we show that exosomes containing HIV-1 protein Nef (exNef) are rapidly taken up by macrophages releasing Nef into the cell interior. This caused down-regulation of ABCA1, reduction of cholesterol efflux and sharp elevation of the abundance of lipid rafts through reduced activation of small GTPase Cdc42 and decreased actin polymerization. Changes in rafts led to re-localization of TLR4 and TREM-1 to rafts, phosphorylation of ERK1/2, activation of NLRP3 inflammasome, and increased secretion of pro-inflammatory cytokines. The effects of exNef on lipid rafts and on inflammation were reversed by overexpression of a constitutively active mutant of Cdc42. Similar effects were observed in macrophages treated with exosomes produced by HIV-infected cells or isolated from plasma of HIV-infected subjects, but not with exosomes from cells and subjects infected with ΔNef-HIV or uninfected subjects. Mice injected with exNef exhibited monocytosis, reduced ABCA1 in macrophages, increased raft abundance in monocytes and augmented inflammation. Thus, Nef-containing exosomes potentiated pro-inflammatory response by inducing changes in cholesterol metabolism and reorganizing lipid rafts. These mechanisms may contribute to HIV-associated metabolic co-morbidities

The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936

Background: The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, but it is currently unclear what drives individual differences. We examine cross-sectional and longitudinal associations between the epigenetic clock and four mortality-linked markers of physical and mental fitness: lung function, walking speed, grip strength and cognitive ability. Methods: DNA methylation-based age acceleration (residuals of the epigenetic clock estimate regressed on chronological age) were estimated in the Lothian Birth Cohort 1936 at ages 70 (n=920), 73 (n=299) and 76 (n=273) years. General cognitive ability, walking speed, lung function and grip strength were measured concurrently. Cross-sectional correlations between age acceleration and the fitness variables were calculated. Longitudinal change in the epigenetic clock estimates and the fitness variables were assessed via linear mixed models and latent growth curves. Epigenetic age acceleration at age 70 was used as a predictor of longitudinal change in fitness. Epigenome-wide association studies (EWASs) were conducted on the four fitness measures. Results: Cross-sectional correlations were significant between greater age acceleration and poorer performance on the lung function, cognition and grip strength measures (r range: -0.07 to -0.05, P range: 9.7 x 10 to 0.024). All of the fitness variables declined over time but age acceleration did not correlate with subsequent change over 6 years. There were no EWAS hits for the fitness traits. Conclusions: Markers of physical and mental fitness are associated with the epigenetic clock (lower abilities associated with age acceleration). However, age acceleration does not associate with decline in these measures, at least over a relatively short follow-up

Role for formin-like 1-dependent acto-myosin assembly in lipid droplet dynamics and lipid storage

Lipid droplets (LDs) are cellular organelles specialized in triacylglycerol (TG) storage undergoing homotypic clustering and fusion. In non-adipocytic cells with numerous LDs this is balanced by poorly understood droplet dissociation mechanisms. We identify non-muscle myosin IIa (NMIIa/MYH-9) and formin-like 1 (FMNL1) in the LD proteome. NMIIa and actin filaments concentrate around LDs, and form transient foci between dissociating LDs. NMIIa depletion results in decreased LD dissociations, enlarged LDs, decreased hydrolysis and increased storage of TGs. FMNL1 is required for actin assembly on LDs in vitro and for NMIIa recruitment to LDs in cells. We propose a novel acto-myosin structure regulating lipid storage: FMNL1-dependent assembly of myosin II-functionalized actin filaments on LDs facilitates their dissociation, thereby affecting LD surface-to-volume ratio and enzyme accessibility to TGs. In neutrophilic leucocytes from MYH9-related disease patients NMIIa inclusions are accompanied by increased lipid storage in droplets, suggesting that NMIIa dysfunction may contribute to lipid imbalance in man.Peer reviewe

The epigenetic clock and telomere length are independently associated with chronological age and mortality

Telomere length and DNA methylation have been proposed as biological clock measures that track chronological age. Whether they change in tandem, or contribute independently to the prediction of chronological age, is not known

Heterozygous SSBP1 start loss mutation co-segregates with hearing loss and the m.1555A>G mtDNA variant in a large multigenerational family.

The m.1555A>G mtDNA variant causes maternally inherited deafness, but the reasons for the highly variable clinical penetrance are not known. Exome sequencing identified a heterozygous start loss mutation in SSBP1, encoding the single stranded binding protein 1 (SSBP1), segregating with hearing loss in a multi-generational family transmitting m.1555A>G, associated with mtDNA depletion and multiple deletions in skeletal muscle. The SSBP1 mutation reduced steady state SSBP1 levels leading to a perturbation of mtDNA metabolism, likely compounding the intra-mitochondrial translation defect due to m.1555A>G in a tissue-specific manner. This family demonstrates the importance of rare trans-acting genetic nuclear modifiers in the clinical expression of mtDNA disease

Comparative effect of C3a and C5a on adhesion molecule expression on neutrophils and endothelial cells

Complement activation is known to enhance neutrophil binding to human umbilical vein endothelial cells (HUVECs). Recently, we have shown that recombinant human C5a upregulates P-selectin in HUVECs. Unstimulated human neutrophil binding is also increased on C5a stimulated HUVECs. We demonstrate in this report that C5a upregulates CD11b/CD18 in human neutrophils. Also shown is that synthetic C3a 57–77 and an analog 15 amino acid C3a peptide (C3a 15 ) neither upregulate CD11b/CD18 nor do the C3a peptides increase P-selectin, ICAM-1 or E-selectin in HUVECs. Thus C5a and not C3a is responsible for early (∼30 minutes) neutrophil adhesion to endothelial cells after complement activation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44514/1/10753_2005_Article_BF01487740.pd

Gene networks associated with conditional fear in mice identified using a systems genetics approach

<p>Abstract</p> <p>Background</p> <p>Our understanding of the genetic basis of learning and memory remains shrouded in mystery. To explore the genetic networks governing the biology of conditional fear, we used a systems genetics approach to analyze a hybrid mouse diversity panel (HMDP) with high mapping resolution.</p> <p>Results</p> <p>A total of 27 behavioral quantitative trait loci were mapped with a false discovery rate of 5%. By integrating fear phenotypes, transcript profiling data from hippocampus and striatum and also genotype information, two gene co-expression networks correlated with context-dependent immobility were identified. We prioritized the key markers and genes in these pathways using intramodular connectivity measures and structural equation modeling. Highly connected genes in the context fear modules included <it>Psmd6</it>, <it>Ube2a </it>and <it>Usp33</it>, suggesting an important role for ubiquitination in learning and memory. In addition, we surveyed the architecture of brain transcript regulation and demonstrated preservation of gene co-expression modules in hippocampus and striatum, while also highlighting important differences. <it>Rps15a, Kif3a, Stard7, 6330503K22RIK</it>, and <it>Plvap </it>were among the individual genes whose transcript abundance were strongly associated with fear phenotypes.</p> <p>Conclusion</p> <p>Application of our multi-faceted mapping strategy permits an increasingly detailed characterization of the genetic networks underlying behavior.</p