Fit with good fat? The role of n-3 polyunsaturated fatty acids on exercise performance

N-3 PUFA (n-3) polyunsaturated fatty acids (PUFA) are a family of fatty acids mainly found in oily fish and fish oil supplements. The effects of n-3 PUFA on health are mainly derived from its anti-inflammatory proprieties and its influence on immune function. Lately an increased interest in n-3 PUFA supplementation has reached the world of sport nutrition, where the majority of athletes rely on nutrition strategies to improve their training and performance. A vast amount of attention is paid in increasing metabolic capacity, delaying the onset of fatigue, and improving muscle hypertrophy and neuromuscular function. Nutritional strategies are also frequently considered for enhancing recovery, improving immune function and decreasing oxidative stress. The current review of the literature shows that data regarding the effects of n-3PUFA supplementation are conflicting and we conclude that there is, therefore, not enough evidence supporting a beneficial role on the aforementioned aspects of exercise performance

Contraction intensity and sex differences in knee-extensor fatigability

Females are less fatigable than males during isometric contractions across various muscles and intensities. However, sex differences in knee-extensor fatigability remain relatively unexplored. Purpose: To determine the sex difference in performance fatigability for intermittent, isometric contractions of the knee-extensor muscles. Methods: Eighteen participants (10 males, 8 females) performed intermittent, isometric, knee-extensor contractions at 30% of their maximal voluntary force (MVC) for 30 min and in a separate session at 50% MVC until task-failure. During both fatiguing protocols a MVC was performed every 60s and electromyography (EMG) was recorded during all contractions. Results: At task completion males had a larger reduction in MVC force for the 30% MVC task (−32±15% vs. −15±16%, P=0.042) and the 50% MVC task (−34±8% vs. −24±1%, P=0.045). Furthermore, for the 50% MVC task, females had a longer task duration (937±525 s vs. 397±153 s, P=0.007). The rise in EMG activity and force fluctuations were more rapid for the males than females (P<0.05). When participants were matched for strength post-hoc (n=10), a sex difference in fatigability for both tasks was still evident. Conclusions: Females were less fatigable than males during intermittent, isometric, knee-extensor contractions at moderate relative forces and this difference was independent of strength

<i>Burkholderia pseudomallei</i> D-alanine-D-alanine ligase:detailed characterisation and assessment of a potential antibiotic drug target

Burkholderia pseudomallei is a serious, difficult to treat Gram-negative pathogen and an increase in the occurrence of drug resistant strains has been detected. We have directed efforts to identify and to evaluate potential drug targets relevant to treatment of infection by B. pseudomallei. We selected the essential enzyme D-alanine-D-alanine ligase (BpDdl), required for the ATP assisted biosynthesis of a peptidoglycan precursor, and have characterised the enzyme. A recombinant supply of protein supported high-resolution crystallographic and biophysical studies with ligands (AMP and AMP+D-Ala-D-Ala), and comparisons with orthologous enzymes suggest a ligand-induced conformational change occurs that might be relevant to the catalytic cycle. The detailed biochemical characterisation of the enzyme, development and optimisation of ligand binding assays supported the search for novel inhibitors by screening of selected compound libraries. In a similar manner to that observed previously in other studies, we note a paucity of hits that are worth follow up and then in combination with a computational analysis of the active site we conclude that this ligase represents a difficult target for drug discovery. Nevertheless, our reagents, protocols and data can underpin future efforts exploiting more diverse chemical libraries and structure-based approache

Doubly Robust Inference when Combining Probability and Non-probability Samples with High-dimensional Data

Non-probability samples become increasingly popular in survey statistics but may suffer from selection biases that limit the generalizability of results to the target population. We consider integrating a non-probability sample with a probability sample which provides high-dimensional representative covariate information of the target population. We propose a two-step approach for variable selection and finite population inference. In the first step, we use penalized estimating equations with folded-concave penalties to select important variables for the sampling score of selection into the non-probability sample and the outcome model. We show that the penalized estimating equation approach enjoys the selection consistency property for general probability samples. The major technical hurdle is due to the possible dependence of the sample under the finite population framework. To overcome this challenge, we construct martingales which enable us to apply Bernstein concentration inequality for martingales. In the second step, we focus on a doubly robust estimator of the finite population mean and re-estimate the nuisance model parameters by minimizing the asymptotic squared bias of the doubly robust estimator. This estimating strategy mitigates the possible first-step selection error and renders the doubly robust estimator root-n consistent if either the sampling probability or the outcome model is correctly specified

RNA-dependent RNA polymerase 1 in potato (Solanum tuberosum) and its relationship to other plant RNA-dependent RNA polymerases.

Cellular RNA-dependent RNA polymerases (RDRs) catalyze synthesis of double-stranded RNAs that can serve to initiate or amplify RNA silencing. Arabidopsis thaliana has six RDR genes; RDRs 1, 2 and 6 have roles in anti-viral RNA silencing. RDR6 is constitutively expressed but RDR1 expression is elevated following plant treatment with defensive phytohormones. RDR1 also contributes to basal virus resistance. RDR1 has been studied in several species including A. thaliana, tobacco (Nicotiana tabacum), N. benthamiana, N. attenuata and tomato (Solanum lycopersicum) but not to our knowledge in potato (S. tuberosum). StRDR1 was identified and shown to be salicylic acid-responsive. StRDR1 transcript accumulation decreased in transgenic potato plants constitutively expressing a hairpin construct and these plants were challenged with three viruses: potato virus Y, potato virus X, and tobacco mosaic virus. Suppression of StRDR1 gene expression did not increase the susceptibility of potato to these viruses. Phylogenetic analysis of RDR genes present in potato and in a range of other plant species identified a new RDR gene family, not present in potato and found only in Rosids (but apparently lost in the Rosid A. thaliana) for which we propose the name RDR7.LJRH was supported by a studentship co-funded by the James Hutton Institute (formerly Scottish Crop Research Institute) and the UK Biotechnological and Biological Sciences Research Council (BBSRC). Work in the JPC lab is funded by The Leverhulme Trust (RPG-2012-667), BBSRC (BB/D014376/1, BB/J011762/1) and the Cambridge University Newton Trust. SFB was funded by Leverhulme grant F/09-741/G to Professor Beverley Glover. KG was funded by an EMBO Short Term Fellowship. Work in the PP lab is funded by grant number NRF-2013R1A2A2A01016282 from the Korean National Research Foundation.This is the author accepted manuscript. The final version is available from Nature Publishing Group via https://doi.org/10.1038/srep2308

A structural and reactivity study of lithium molybdenum nitride

This thesis describes the preparation and reactivity of lithium molybdenum nitride samples and the preparation and characterisation of the nitride precursors. It has been shown that samples containing lithium molybdenum nitride (LiMoN2) can be formed from the direct ammonolysis of lithium molybdate (Li2MoO4), although it has proved challenging to produce the nitride as a single phase material. The “LiMoN2” samples were observed to be catalytically active for ammonia synthesis in reaction with nitrogen containing feed gas (25% N2/H2). An impurity, which cannot be indentified through powder X-ray diffraction, was demonstrated to be the likely active phase in the sample. The role of ‘lattice’ nitrogen in the ammonia synthesis reaction was investigated through reactions with a feed gas with no source of nitrogen present (25% Ar/H2). It was shown that this proposed active phase will produce ammonia, in the absence of nitrogen in the feed gas. One candidate impurity that could be responsible for this anomalous activity was lithium nitride. Reactions were conducted and it was seen that lithium nitride was very active in the production of ammonia. Subsequent investigations showed that the generation of ammonia probably originates from the direct decomposition of lithium amide

Increased diagnosis and treatment of hepatitis C in prison by universal offer of testing and use of telemedicine

With recent advances in anti‐viral therapy there is an opportunity to eliminate HCV from the UK population. HCV is common in incarcerated individuals, with previous estimates suggesting ~7% of the UK prison population is anti‐HCV antibody positive. Increasing diagnosis and treatment of HCV in prison is a priority in seeking to eliminate transmission in the general population. Thus the study aimed, to assess the impact implementation of: 1. A universal offer of blood borne virus testing (UOBBVT) using dry blood spot testing for prisoners at reception to increase diagnosis; 2. Telemedicine clinics (TC) within North East England (NEE) prisons to increase HCV treatment rates. UOBBVT was initially implemented at Her Majesty's Prison (HMP) Durham, commencing March 2016. From March 2016 to February 2017, 2,831 of 4,280 (66%) new receptions were offered BBV testing. Of these, 1,495 (53% of offered) accepted BBV testing, of whom 95 (6.4%) were HCV antibody positive, with 47 of those 95 (49.5%) HCV RNA positive, suggesting a prevalence of active infection in the tested population of 3.1% (95% CI 2.4% to 4.2%). Between August 2015 and October 2017, 80 individuals were seen in the TC and 57 (71%) commenced antiviral therapy. Of those with known outcome (n=29), 100% achieved sustained virological response. In the year prior to implementation, only 4 patients received HCV treatment. In conclusion, a universal offer of BBV testing to inmates presenting at HMP reception coupled with linkage into specialist care via TC can substantially increase rates of testing, diagnosis and treatment of HCV in this high prevalence population

BEYOND LINEARITY AND INDEPENDENCE

This brief lecture discusses statistical problems associated with postulating and fitting models in engineering and the sciences. Particular emphasis is placed on the two-model problem: the employment of both deterministic and stochastic components within a model. Further, the use of empirical versus theoretical models on the part of both statisticians and experimenters is examined

RNA-dependent RNA polymerase 1 in potato (Solanum tuberosum) and its relationship to other plant RNA-dependent RNA polymerases

Cellular RNA-dependent RNA polymerases (RDR) catalyze synthesis of double stranded RNAs that can serve to initiate or amplify RNA silencing. Arabidopsis thaliana has six RDR genes; RDRs 1, 2 and 6 have roles in anti-viral RNA silencing. RDR6 is constitutively expressed but RDR1 expression is elevated following plant treatment with defensive phytohormones. RDR1 also contributes to basal virus resistance. RDR1 has been studied in several species including A. thaliana, tobacco (Nicotiana tabacum), N. benthamiana, N. attenuata and tomato (Solanum lycopersicum) but not to our knowledge in potato (S. tuberosum). StRDR1 was identified and shown to be salicylic acid-responsive. StRDR1 transcript accumulation decreased in transgenic potato plants constitutively expressing a hairpin construct and these plants were challenged with three viruses: potato virus Y, potato virus X, and tobacco mosaic virus. Suppression of StRDR1 gene expression did not increase the susceptibility of potato to these viruses. Phylogenetic analysis of RDR genes present in potato and in a range of other plant species identified a new RDR gene family, not present in potato and found only in Rosids (but apparently lost in the Rosid A. thaliana) for which we propose the name RDR7.LJRH was supported by a studentship co-funded by the James Hutton Institute (formerly Scottish Crop Research Institute) and the UK Biotechnological and Biological Sciences Research Council (BBSRC). Work in the JPC lab is funded by The Leverhulme Trust (RPG-2012-667), BBSRC (BB/D014376/1, BB/J011762/1) and the Cambridge University Newton Trust. SFB was funded by Leverhulme grant F/09-741/G to Professor Beverley Glover. KG was funded by an EMBO Short Term Fellowship. Work in the PP lab is funded by grant number NRF-2013R1A2A2A01016282 from the Korean National Research Foundation.This is the author accepted manuscript. The final version is available from Nature Publishing Group via https://doi.org/10.1038/srep2308

Systematic review and network meta-analysis with individual participant data on cord management at preterm birth (iCOMP): study protocol

Introduction Timing of cord clamping and other cord management strategies may improve outcomes at preterm birth. However, it is unclear whether benefits apply to all preterm subgroups. Previous and current trials compare various policies, including time-based or physiology-based deferred cord clamping, and cord milking. Individual participant data (IPD) enable exploration of different strategies within subgroups. Network meta-analysis (NMA) enables comparison and ranking of all available interventions using a combination of direct and indirect comparisons. Objectives (1) To evaluate the effectiveness of cord management strategies for preterm infants on neonatal mortality and morbidity overall and for different participant characteristics using IPD meta-analysis. (2) To evaluate and rank the effect of different cord management strategies for preterm births on mortality and other key outcomes using NMA. Methods and analysis Systematic searches of Medline, Embase, clinical trial registries, and other sources for all ongoing and completed randomised controlled trials comparing cord management strategies at preterm birth (before 37 weeks’ gestation) have been completed up to 13 February 2019, but will be updated regularly to include additional trials. IPD will be sought for all trials; aggregate summary data will be included where IPD are unavailable. First, deferred clamping and cord milking will be compared with immediate clamping in pairwise IPD meta-analyses. The primary outcome will be death prior to hospital discharge. Effect differences will be explored for prespecified participant subgroups. Second, all identified cord management strategies will be compared and ranked in an IPD NMA for the primary outcome and the key secondary outcomes. Treatment effect differences by participant characteristics will be identified. Inconsistency and heterogeneity will be explored. Ethics and dissemination Ethics approval for this project has been granted by the University of Sydney Human Research Ethics Committee (2018/886). Results will be relevant to clinicians, guideline developers and policy-makers, and will be disseminated via publications, presentations and media releases