Physical inactivity in prevails in later life

The majority of people over 70 years may self-report themselves to be in good health but just being older means they are more likely to experience a range of health related ups and downs than in their younger years. One explanation for this is that the older population carries a progressively heavier burden of chronic disease and disability than their younger cohorts. With a changing demographic and in particular an ageing population, it is not surprising that politicians and health professionals are keen to intervene – mostly because of a presumed high cost of not-so-good health

A model for incorporating a clinically-feasible exercise test in paraplegic annual reviews : a tool for stratified cardiopulmonary stress performance classification and monitoring

To identify and characterize an exercise test for use in routine spinal cord injury clinical review, and (ii) to describe levels of, and factors affecting, cardiopulmonary stress performance during exercise in the chronic paraplegic population in Scotland, UK. Cross-sectional study Queen Elizabeth National Spinal Injuries Unit (Glasgow, Scotland) 48 subjects with chronic paraplegia resulting from spinal cord injury at neurological levels T2-L2 Peak oxygen uptake, peak power output, gas exchange threshold and peak heart rate were determined from an incremental arm-cranking exercise test. Using a general linear model, the effects of gender, high (injury level above T6) versus low paraplegia, time since injury, body mass and age on peak oxygen uptake and peak power output were investigated. All 48 subjects completed the arm-cranking exercise test, which was shown to be practical for fitness screening in paraplegia. Men (n=38) had a peak oxygen uptake of 1.302 +/- 0.326 l.min-1 (mean +/- s.d.) and peak power output of 81.6 +/- 23.2W, which was significantly higher than for women (n=10), at 0.832 +/- 0.277 l.min-1 and 50.1 +/- 27.8 W, respectively. There was large intersubject variability in cardiopulmonary performance during arm-cranking exercise testing, but the overall mean for the Scottish population was lower than reference values from other countries. Arm-cranking exercise tests are feasible in the clinical environment. The motivation for their implementation is threefold: (i) to determine cardiopulmonary stress performance of individual paraplegic patients, (ii) to stratify patients into cardiovascular risk categories, and (iii) to monitor the effects of targeted exercise prescription

Regional Diversity in the Postsynaptic Proteome of the Mouse Brain

The proteome of the postsynaptic terminal of excitatory synapses comprises over one thousand proteins in vertebrate species and plays a central role in behavior and brain disease. The brain is organized into anatomically distinct regions and whether the synapse proteome differs across these regions is poorly understood. Postsynaptic proteomes were isolated from seven forebrain and hindbrain regions in mice and their composition determined using proteomic mass spectrometry. Seventy-four percent of proteins showed differential expression and each region displayed a unique compositional signature. These signatures correlated with the anatomical divisions of the brain and their embryological origins. Biochemical pathways controlling plasticity and disease, protein interaction networks and individual proteins involved with cognition all showed differential regional expression. Combining proteomic and connectomic data shows that interconnected regions have specific proteome signatures. Diversity in synapse proteome composition is key feature of mouse and human brain structure

A data-based mathematical modelling study to quantify the effects of ciprofloxacin and ampicillin on the within-host dynamics of Salmonella enterica during treatment and relapse.

Antibiotic therapy has drastically reduced the mortality and sequelae of bacterial infections. From naturally occurring to chemically synthesized, different classes of antibiotics have been successfully used without detailed knowledge of how they affect bacterial dynamics in vivo. However, a proportion of patients receiving antimicrobial therapy develop recrudescent infections post-treatment. Relapsing infections are attributable to incomplete clearance of bacterial populations following antibiotic administration; the metabolic profile of this antibiotic-recalcitrant bacterial subpopulation, the spatio-temporal context of its emergence and the variance of antibiotic-bacterial interactions in vivo remain unclear. Here, we develop and apply a mechanistic mathematical model to data from a study comparing the effects of ciprofloxacin and ampicillin on the within-host dynamics of Salmonella enterica serovar Typhimurium in murine infections. Using the inferential capacity of our model, we show that the antibiotic-recalcitrant bacteria following ampicillin, but not ciprofloxacin, treatment belong to a non-replicating phenotype. Aligning with previous studies, we independently estimate that the lymphoid tissues and spleen are important reservoirs of non-replicating bacteria. Finally, we predict that post-treatment, the progenitors of the non-growing and growing bacterial populations replicate and die at different rates. Ultimately, the liver, spleen and mesenteric lymph nodes are all repopulated by progenitors of the previously non-growing phenotype in ampicillin-treated mice.Bursary from Cambridge Mathematical Placement

Comparison of stimulation patterns for FES-cycling using measures of oxygen cost and stimulation cost

<b>Aim</b><p></p> The energy efficiency of FES-cycling in spinal cord injured subjects is very much lower than that of normal cycling, and efficiency is dependent upon the parameters of muscle stimulation. We investigated measures which can be used to evaluate the effect on cycling performance of changes in stimulation parameters, and which might therefore be used to optimise them. We aimed to determine whether oxygen cost and stimulation cost measurements are sensitive enough to allow discrimination between the efficacy of different activation ranges for stimulation of each muscle group during constant-power cycling. <p></p> <b>Methods</b><p></p> We employed a custom FES-cycling ergometer system, with accurate control of cadence and stimulated exercise workrate. Two sets of muscle activation angles (“stimulation patterns”), denoted “P1” and “P2”, were applied repeatedly (eight times each) during constant-power cycling, in a repeated measures design with a single paraplegic subject. Pulmonary oxygen uptake was measured in real time and used to determine the oxygen cost of the exercise. A new measure of stimulation cost of the exercise is proposed, which represents the total rate of stimulation charge applied to the stimulated muscle groups during cycling. A number of energy-efficiency measures were also estimated. <p></p> <b>Results</b><p></p> Average oxygen cost and stimulation cost of P1 were found to be significantly lower than those for P2 (paired <i>t</i>-test, <i>p</i> < 0.05): oxygen costs were 0.56 ± 0.03 l min<sup>−1</sup> and 0.61 ± 0.04 l min<sup>−1</sup>(mean ± S.D.), respectively; stimulation costs were 74.91 ± 12.15 mC min<sup>−1</sup> and 100.30 ± 14.78 mC min<sup>−1</sup> (mean ± S.D.), respectively. Correspondingly, all efficiency estimates for P1 were greater than those for P2. <p></p> <b>Conclusion</b><p></p> Oxygen cost and stimulation cost measures both allow discrimination between the efficacy of different muscle activation patterns during constant-power FES-cycling. However, stimulation cost is more easily determined in real time, and responds more rapidly and with greatly improved signal-to-noise properties than the ventilatory oxygen uptake measurements required for estimation of oxygen cost. These measures may find utility in the adjustment of stimulation patterns for achievement of optimal cycling performance. <p></p&gt

Forty years studying British politics : the decline of Anglo-America

The still present belief some 40 years ago that British politics was both exceptional and superior has been replaced by more theoretically sophisticated analyses based on a wider and more rigorously deployed range of research techniques, although historical analysis appropriately remains important. The American influence on the study of British politics has declined, but the European Union dimension has not been fully integrated. The study of interest groups has been in some respects a fading paradigm, but important questions related to democratic health have still to be addressed. Public administration has been supplanted by public policy, but economic policy remains under-studied. A key challenge for the future is the study of the management of expectations

A high-fat diet induces rapid changes in the mouse hypothalamic proteome

Funding LMW, FMC, CG, ACM and C-DM were funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division (RESAS). FHM was supported by an EASTBIO DTP BBSRC studentship. DS was supported by a SULSA studentship. CR was supported by the HOTSTART Scholarship Programme from the School of Medicine, Medical Sciences and Nutrition, University of Aberdeen. Availability of data and materials All data generated or analysed during this study are included in this published article [and its Supplementary information files].Peer reviewedPublisher PD

Rapid and reversible impairment of episodic memory by a high-fat diet in mice.

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. This work was supported by an EASTBIO BBSRC PhD studentship to F.H.M., L.M.W., C.G., A.C.M., G.W.H. and F.M.C. are supported by Scottish Government’s Rural and Environment Science and Analytical Services Division (RESAS).Peer reviewedPublisher PD

Catalytic Determinants of Alkene Production by the Cytochrome P450 Peroxygenase OleTJE.

The Jeotgalicoccus sp. peroxygenase cytochrome P450 OleTJE (CYP152L1) is a hydrogen peroxide-driven oxidase that catalyzes oxidative decarboxylation of fatty acids, producing terminal alkenes with applications as fine chemicals and biofuels. Understanding mechanisms that favor decarboxylation over fatty acid hydroxylation in OleTJE could enable protein engineering to improve catalysis or to introduce decarboxylation activity into P450s with different substrate preferences. In this manuscript, we have focused on OleTJE active site residues Phe79, His85 and Arg245 to interrogate their roles in substrate binding and catalytic activity. His85 is a potential proton donor to reactive iron-oxo species during substrate decarboxylation. The H85Q mutant substitutes a glutamine found in several peroxygenases that favor fatty acid hydroxylation. H85Q OleTJE still favors alkene production, suggesting alternative protonation mechanisms. However, the mutant undergoes only minor substrate binding-induced heme iron spin-state shift towards high-spin by comparison with WT OleTJE, indicating His85's key role in this process. Phe79 interacts with His85, and Phe79 mutants showed diminished affinity for shorter chain (C10-C16) fatty acids and weak substrate-induced high-spin conversion. F79A OleTJE is least affected in substrate oxidation, while the F79W/Y mutants exhibit lower stability and cysteine thiolate protonation on reduction. Finally, Arg245 is crucial for binding the substrate carboxylate, and R245E/L mutations severely compromise activity and heme content, although alkene products are formed from some substrates, including stearic acid (C18:0). The results identify crucial roles for the active site amino acid trio in determining OleTJE catalytic efficiency in alkene production, and in regulating protein stability, heme iron coordination and spin-state

Crop Fertilization on Texas Blackland and Grand Prairie Soils.

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