Starch digestion in ruminents - problems, solutions and opportunities

There have been significant advances in our understanding of starch fermentation and digestion in ruminants. The major problem in feeding starch to ruminants is the rapid fermentation of starch and the accumulation of acids in the gut which reduce the pH to the point where health and productivity are affected. Recent research has identified problems of hindgut acidosis which can be more common and as harmful as the better known problems of lactic acidosis in the rumen. The use of the antibiotic feed additive, virginiamycin, has been shown to reduce the risks of starch feeding to the extent where feeding cereal grain is safe and practical. These new feeding systems have the potential to deliver undigested starch post-ruminally for absorption as glucose. For this reason it has been appropriate to evaluate the effect of glucose on pathways of physiological and commercial importance such as glycogen and lipid synthesis. It is clear that intravenous infusions of glucose stimulate key enzymes involved in lipid synthesis including the citrate cleavage pathway which converts glucose to lipid and importantly acetlyCoA carboxylase, the rate limiting step for lipogenesis

Does exercise influence burn-induced inflammation: A cross-over randomised controlled feasibility trial

Background Burn injuries trigger a greater and more persistent inflammatory response than other trauma cases. Exercise has been shown to positively influence inflammation in healthy and diseased populations, however little is known about the latent effect of exercise on chronic inflammation in burn injured patients. The aims of the pilot study were to assess the feasibility of implementing a long duration exercise training program, in burn injured individuals including learnings associated with conducting a clinical trial in COVID-19 pandemic. Methods Fifteen participants with a burn injury between 5–20% total body surface area acquired greater than a year ago were randomised in a within-subject designed study, into one of two conditions, exercise–control or control–exercise. The exercise condition consisted of six weeks of resistance and cardiovascular exercises, completed remotely or supervised in a hospital gym. A comprehensive outcome measurement was completed at the initial, mid and end point of each exercise and control condition. To determine the success of implementation, the feasibility indicator for the data completeness across the comprehensive outcome battery was set at 80%. Results Half (49%) of eligible participants in the timeframe, were recruited and commenced the study. Six participants withdrew prior to completion and a total of 15 participants completed the study. Eight participants were randomised to the exercise-control and seven to the control exercise group. Five participants trained remotely and seven did supervised training. Three participants completed a mix of both supervised and remote training initiated due to COVID restrictions. Outcome measures were completed on 97% of protocolised occasions and 100% of participants completed the exercise training. Conclusions Conducting a long duration exercise training study on burn injured individuals is feasible using the described methods. The knowledge gained helps improve the methodology in larger-scale projects. Insights into the impact of COVID-19 on this clinical trial and success enhancing adaptations for the researcher, research practice and the participant, are presented

Analysis of the conversion of δ-(l-α-aminoadipoyl)-l-cysteinyl-d-α-aminobutyrate by active-site mutants of Aspergillus nidulans isopenicillin N synthase

AbstractBackground: Penicillins and cephalosporins constitute a major class of clinically useful antibiotics. A key step in their biosynthesis involves the oxidative cyclisation of δ-l-α-aminoadipoyl)-l-cysteinyl-d-valine to isopenicillin N by isopenicillin N synthase (IPNS). This chemically remarkable transformation has been extensively studied using substrate analogues. The conversion of an analogue in which the valine is replaced by a-aminobutyrate results in three products, two epimeric penams and a cepham. The ratio of these products in reactions catalysed by four different IPNS isozymes has been used previously to probe the thermicity of the chemical mechanism. But how IPNS restricts the products from the natural substrate to a single penam (isopenicillin N) has remained unknown.Results: A key active-site residue, Leu223, identified according to a model of enzyme-substrate binding, has been altered to sterically less demanding residues. As the steric constraints on the upper part of the active site are reduced, the ratio of the β-methyl penam to the cepham increases when the α-aminobutyrate-containing substrate analogue is used. These results suggest a mechanism for processing of the natural substrate in which IPNS uses steric control to restrict the conformational freedom of an intermediate such that the only product is the penam.Conclusions: Using steric pressure to control conformation, and hence to disfavour reactions leading to alternate products, is probably the result of evolutionary selection for a biologically active product at the expense of biologically inactive byproducts. It is likely that this sort of enzymatic catalysis is used in situations where substrate conversion is highly exothermic and a variety of products are possible

The effect of different dietary grains on the expression of ATP citrate lyase in the adipose tissue of sheep

This study examined the effects of feeding six grains on the biosynthesis of fat from glucose as assessed by the activity of ATP citrate lyase (ACL, EC 4.1.3.8) in subcutaneous adipose tissue of sheep

'Universal' FitzGerald Contractions

The model of a universe with a preferred frame, which nevertheless shares the main properties with traditional special and general relativity theories, is considered. We adopt Mach's interpretation of inertia and show that the energy balance equation, which includes the Machian energy of gravitational interactions with the universe, can imitate standard relativistic formulas.Comment: The version accepted by Eur. Phys. J.

Kepler-22b: A 2.4 Earth-radius Planet in the Habitable Zone of a Sun-like Star

A search of the time-series photometry from NASA's Kepler spacecraft reveals a transiting planet candidate orbiting the 11th magnitude G5 dwarf KIC 10593626 with a period of 290 days. The characteristics of the host star are well constrained by high-resolution spectroscopy combined with an asteroseismic analysis of the Kepler photometry, leading to an estimated mass and radius of 0.970 +/- 0.060 MSun and 0.979 +/- 0.020 RSun. The depth of 492 +/- 10ppm for the three observed transits yields a radius of 2.38 +/- 0.13 REarth for the planet. The system passes a battery of tests for false positives, including reconnaissance spectroscopy, high-resolution imaging, and centroid motion. A full BLENDER analysis provides further validation of the planet interpretation by showing that contamination of the target by an eclipsing system would rarely mimic the observed shape of the transits. The final validation of the planet is provided by 16 radial velocities obtained with HIRES on Keck 1 over a one year span. Although the velocities do not lead to a reliable orbit and mass determination, they are able to constrain the mass to a 3{\sigma} upper limit of 124 MEarth, safely in the regime of planetary masses, thus earning the designation Kepler-22b. The radiative equilibrium temperature is 262K for a planet in Kepler-22b's orbit. Although there is no evidence that Kepler-22b is a rocky planet, it is the first confirmed planet with a measured radius to orbit in the Habitable Zone of any star other than the Sun.Comment: Accepted to Ap

COVID-19: Rapid antigen detection for SARS-CoV-2 by lateral flow assay: A national systematic evaluation of sensitivity and specificity for mass-testing

Background Lateral flow device (LFD) viral antigen immunoassays have been developed around the world as diagnostic tests for SARS-CoV-2 infection. They have been proposed to deliver an infrastructure-light, cost-economical solution giving results within half an hour. Methods LFDs were initially reviewed by a Department of Health and Social Care team, part of the UK government, from which 64 were selected for further evaluation from 1st August to 15th December 2020. Standardised laboratory evaluations, and for those that met the published criteria, field testing in the Falcon-C19 research study and UK pilots were performed (UK COVID-19 testing centres, hospital, schools, armed forces). Findings 4/64 LFDs so far have desirable performance characteristics (orient Gene, Deepblue, Abbott and Innova SARS-CoV-2 Antigen Rapid Qualitative Test). All these LFDs have a viral antigen detection of >90% at 100,000 RNA copies/ml. 8951 Innova LFD tests were performed with a kit failure rate of 5.6% (502/8951, 95% CI: 5.1–6.1), false positive rate of 0.32% (22/6954, 95% CI: 0.20–0.48). Viral antigen detection/sensitivity across the sampling cohort when performed by laboratory scientists was 78.8% (156/198, 95% CI 72.4–84.3). Interpretation Our results suggest LFDs have promising performance characteristics for mass population testing and can be used to identify infectious positive individuals. The Innova LFD shows good viral antigen detection/sensitivity with excellent specificity, although kit failure rates and the impact of training are potential issues. These results support the expanded evaluation of LFDs, and assessment of greater access to testing on COVID-19 transmission. Funding Department of Health and Social Care. University of Oxford. Public Health England Porton Down, Manchester University NHS Foundation Trust, National Institute of Health Research