The Role of Eif6 in Skeletal Muscle Homeostasis Revealed by Endurance Training Co-expression Networks

Regular endurance training improves muscle oxidative capacity and reduces the risk of age-related disorders. Understanding the molecular networks underlying this phenomenon is crucial. Here, by exploiting the power of computational modeling, we show that endurance training induces profound changes in gene regulatory networks linking signaling and selective control of translation to energy metabolism and tissue remodeling. We discovered that knockdown of the mTOR-independent factor Eif6, which we predicted to be a key regulator of this process, affects mitochondrial respiration efficiency, ROS production, and exercise performance. Our work demonstrates the validity of a data-driven approach to understanding muscle homeostasis

Heritability of gastrointestinal nematode faecal egg counts in West African village N'Dama cattle and its relation to age

Offspring-dam regression was used to estimate the heritability of strongyle faecal egg counts (FEC) of traditionally raised West African N'Dama cattle in the Central River Division in The Gambia. Faecal samples were taken monthly from June-October 1992, and again from July-October 1993, including 179-463 dams and their calves sampled on each occasion. The only proven genetic relationship was the dam-offspring relationship. Gastrointestinal strongyle FEC was expressed as epg (eggs per gram faeces). Regression of offspring FEC on dam FEC, showed a heritability (h(2)) of 0.18 (95% Confidence Limits 0.10, 0.25). Heritabilities were higher at the beginning and end of the rainy season than during the months of the peak rainy season. This is in line with earlier suggestions that genetic control of faecal egg counts is most effective during periods of low parasite transmission. There was a significant (p<0.001) increase in heritability of 0.086+/-0.018 with each year of age of the corresponding offspring. In view of the virtual absence of national cattle breeding systems in West Africa, which are a precondition for exploitation of heritable traits in cattle, integrated control using improved management and strategic prophylaxis remain the methods of choice to control gastrointestinal nematodes in the given conditions

Investigation of IRGANOX® 1076 as a dosimeter for clinical X-ray, electron and proton beams and its EPR angular response

The suitability of IRGANOX ® 1076 in paraffin wax as a near-tissue equivalent radiation dosimeter was investigated for various radiotherapy beam types; kV and MV X-rays, electrons and protons over clinically-relevant doses (2 -20 Gy). The radical formed upon exposure to ionising radiations was measured by Electron Paramagnetic R esonance (EPR) spectroscopy, and the single peak signal obtained for solid solutions of IRGANOX ® 1076 in wax is attributed to the phenoxyl radical obtained by net loss of H • . Irradiation of solid IRGANOX ® 1076 gives a doublet consistent with the formation of the phenol cation radical, obtained by electron loss. Solid solutions of IRGANOX ® 1076 in paraffin wax give a linear dose response for all types of radiations examined, which was energy independent for MV, electron and proton beams, and energy-dependent for kV X-ray irradiation. Reliable dose measurements were obtained with exposures as low as 2 Gy, and comparisons with alanine wax-pellets containing the same amount of dosimeter material (w/w) gave similar responses for all beam types investigated. Post-irradiation measurements (up to 77 days for proton irradiation for samples stored in the dark and at room temperature) indicate good signal stability with minimal signal fading (between 1.6 to 3.8%). Relative to alanine dosimeters, solid solutions of IRGANOX ® 1076 in wax give EPR signals with better sensitivity at low dose and do not significantly change with the orientation of the sample. Solid solutions of IRGANOX ® 1076 are ideal for applications in radiotherapy dosimetry for X-rays and charged particles, as IRGANOX ® 1076 is relatively cheap, can easily and reproducibly prepared in wax and be moulded to different shapes

Effect of strategic gastrointestinal nematode control on faecal egg count in traditional African cattle

This paper reports on the effect of strategic anthelmintic treatments and other determinants on faecal egg counts (FEC) of Trichostrongyles in N'Dama cattle of a west African village. Initially, 527 animals from 13 private N'Dama cattle herds were monitored in a longitudinal study from October 1989 to December 1994. Each herd was stratified by age and animals were sequentially allocated to two groups with similar age distributions. One group received a single anthelmintic treatment of fenbendazole (7.5 mg/kg BW), in October 1989 (n = 250), whereas the other group remained untreated (n = 277) throughout the study. In the next rainy season (June to October), the treated animals were treated twice (in July and September). The same treatment schedule was used in the subsequent rainy seasons until December 1994. Biannual anthelmintic treatments decreased the level of FEC between 31% (late dry season) and 57 of FEC were found during the rainy season from June to October. FEC levels decreased until 4 years of age, after which they remained on a constant low level. The variability of returns to anthelmintic treatments between herds did not seem to be influenced by FEC at the herd level. The financial evaluation of anthelmintic interventions cannot be predicted from FEC and must necessarily rely on the direct monitoring of livestock productivity parameters

Dynamic analysis of stochastic transcription cycles

In individual mammalian cells the expression of some genes such as prolactin is highly variable over time and has been suggested to occur in stochastic pulses. To investigate the origins of this behavior and to understand its functional relevance, we quantitatively analyzed this variability using new mathematical tools that allowed us to reconstruct dynamic transcription rates of different reporter genes controlled by identical promoters in the same living cell. Quantitative microscopic analysis of two reporter genes, firefly luciferase and destabilized EGFP, was used to analyze the dynamics of prolactin promoter-directed gene expression in living individual clonal and primary pituitary cells over periods of up to 25 h. We quantified the time-dependence and cyclicity of the transcription pulses and estimated the length and variation of active and inactive transcription phases. We showed an average cycle period of approximately 11 h and demonstrated that while the measured time distribution of active phases agreed with commonly accepted models of transcription, the inactive phases were differently distributed and showed strong memory, with a refractory period of transcriptional inactivation close to 3 h. Cycles in transcription occurred at two distinct prolactin-promoter controlled reporter genes in the same individual clonal or primary cells. However, the timing of the cycles was independent and out-of-phase. For the first time, we have analyzed transcription dynamics from two equivalent loci in real-time in single cells. In unstimulated conditions, cells showed independent transcription dynamics at each locus. A key result from these analyses was the evidence for a minimum refractory period in the inactive-phase of transcription. The response to acute signals and the result of manipulation of histone acetylation was consistent with the hypothesis that this refractory period corresponded to a phase of chromatin remodeling which significantly increased the cyclicity. Stochastically timed bursts of transcription in an apparently random subset of cells in a tissue may thus produce an overall coordinated but heterogeneous phenotype capable of acute responses to stimuli

Privatising the green police: the role of NGOs in wildlife law enforcement

This article examines the role of NGOs in wildlife law enforcement, drawing on empirical research conducted within UK environmental law enforcement but also drawing on a review of the academic literature and policy debates concerning NGOs and pressure group activity. It examines the theoretical basis for NGO actions and different policy perspectives, the ideologies employed by NGO's and how these manifest themselves in law enforcement policies and practice. While the focus of this essay is UK and US NGO activity with its professional enforcement activity and policy networks, the impact of wildlife and environmental NGOs is significant in a range of jurisdictions and is a vital component in effective policing of wildlife legislation

Collaborative overview of coronaVIrus impact on ORTHopaedic training in the UK (COVI - ORTH UK)

Introduction COVID-19 was declared a pandemic by the World Health Organization on the 11th of March 2020 with the NHS deferring all non-urgent activity from the 15th of April 2020. The aim of our study was to assess the impact of COVID-19 on Trauma and Orthopaedic trainees nationally. Methods Trauma and Orthopaedic (T&O) specialty trainees nationally were asked to complete an electronic survey specifically on the impact of COVID-19 on their training. This UK based survey was conducted between May 2020 and July 2020. Results A total of 185 out of 975 (19%) T&O specialty trainees completed the survey. Redeployment was experienced by 25% of trainees. 84% of respondents had experienced a fall in total operating numbers in comparison with the same time period in 2019. 89% experienced a fall in elective operating and 63% experienced a fall in trauma operating. The pandemic has also had an effect on the delivery of teaching, with face to face teaching being replaced by webinar-based teaching. 63% of training programmes delivered regular weekly teaching, whilst 19% provided infrequent sessions and 11% provided no teaching. Conclusion This study has objectively demonstrated the significant impact of the COVID-19 pandemic on all aspects of T&O training