Mycoprotein represents a bioavailable and insulinotropic non-animal-derived dietary protein source: a dose-response study

This is the final version of the article. Available from CUP via the DOI in this record.The anabolic potential of a dietary protein is determined by its ability to elicit postprandial rises in circulating essential amino acids and insulin. Minimal data exist regarding the bioavailability and insulinotropic effects of non-animal-derived protein sources. Mycoprotein is a sustainable and rich source of non-animal-derived dietary protein. We investigated the impact of mycoprotein ingestion, in a dose-response manner, on acute postprandial hyperaminoacidaemia and hyperinsulinaemia. In all, twelve healthy young men completed five experimental trials in a randomised, single-blind, cross-over design. During each trial, volunteers consumed a test drink containing either 20 g milk protein (MLK20) or a mass matched (not protein matched due to the fibre content) bolus of mycoprotein (20 g; MYC20), a protein matched bolus of mycoprotein (40 g; MYC40), 60 g (MYC60) or 80 g (MYC80) mycoprotein. Circulating amino acid, insulin and uric acid concentrations, and clinical chemistry profiles, were assessed in arterialised venous blood samples during a 4-h postprandial period. Mycoprotein ingestion resulted in slower but more sustained hyperinsulinaemia and hyperaminoacidaemia compared with milk when protein matched, with overall bioavailability equivalent between conditions (P>0·05). Increasing the dose of mycoprotein amplified these effects, with some evidence of a plateau at 60-80 g. Peak postprandial leucine concentrations were 201 (sem 24) (30 min), 118 (sem 10) (90 min), 150 (sem 14) (90 min), 173 (sem 23) (45 min) and 201 (sem 21 (90 min) µmol/l for MLK20, MYC20, MYC40, MYC60 and MYC80, respectively. Mycoprotein represents a bioavailable and insulinotropic dietary protein source. Consequently, mycoprotein may be a useful source of dietary protein to stimulate muscle protein synthesis rates.The project was sponsored by Marlow Foods Ltd (B. T. W. as grant holder). The University of Exeter (B. T. W.) were responsible for the study design, data collection and analysis, decision to publish and preparation of the manuscript. The private partners have contributed to the project through regular discussion. M. V. D. is supported through the aforementioned grant, S. P. K. is supported from an internal studentship grant in collaboration with Maastricht University

Temporal Muscle-Specific Disuse Atrophy during One Week of Leg Immobilization

This is the author accepted manuscript. The final version is available from Wolters Kluwer via the DOI in this recordPurpose Musculoskeletal injuries necessitate periods of disuse (i.e. limb immobilization) during which rapid skeletal muscle atrophy occurs. The relative susceptibility of different muscles of the thigh to disuse atrophy remains uninvestigated. We assessed muscle disuse atrophy of individual thigh muscles throughout one week of unilateral knee immobilization. Methods Thirteen healthy, young (20.2±0.6 y) men underwent 7 days of unilateral leg immobilization via knee bracing. MRI scans were performed bilaterally prior to, and following 2 and 7 days of immobilization to determine the volume and anatomical cross-sectional area (aCSA) of the individual muscle groups of the upper legs. Results In contrast to the control leg, total thigh muscle volume had decreased by 1.7±0.3 (P<0.01) and 5.5±0.6% (P<0.001) in the immobilized leg after 2 and 7 days of disuse, respectively. Muscle loss was significantly greater in the M. quadriceps (day 2; 1.7±0.3 (P<0.05) and day 7; 6.7±0.6%) when compared with the M. hamstrings (day 2; 1.4±0.2% (P<0.01) and day 7; 3.5±0.3%) following 7 days of disuse (P<0.001). Individual muscles of the thigh exhibited different atrophy rates with the M. vastus lateralis aCSA showing the greater (2.6±0.4 and 7.2±0.8%), and the M. gracilis the lesser (1.1±0.7 and 2.3±1.0%) decline following 2 and 7 days of immobilization, respectively (P<0.01). Conclusion Thigh muscle disuse atrophy occurs rapidly and is already evident within 2 days of leg immobilization and progresses at a similar rate over the next 5 days (~0.8% muscle loss per day). M. quadriceps muscle shows more atrophy when compared with the M. hamstrings.University of MaastrichtRoyal SocietyUniversity of ExeterNational Institute for Health Research (NIHR

Dietary protein intake does not modulate daily myofibrillar protein synthesis rates or loss of muscle mass and function during short-term immobilization in young men: a randomized controlled trial.

This is the author accepted manuscript. The final version is available from American Society for Nutrition via the DOI in this record. BACKGROUND: Short-term ( 0.05). Immobilization led to 2.3 ± 0.4%, 2.7 ± 0.2%, and 2.0 ± 0.4% decreases in quadriceps muscle volume (P  0.05). D2O ingestion resulted in comparable plasma free [2H]-alanine enrichments during immobilization (∼2.5 mole percentage excess) across groups (P > 0.05). Daily MyoPS rates during immobilization were 30 ± 2% (HIGH), 26 ± 3% (LOW), and 27 ± 2% (NO) lower in the immobilized compared with the control leg, with no significant differences between groups (P > 0.05). CONCLUSIONS: Three days of muscle disuse induces considerable declines in muscle mass and daily MyoPS rates. However, daily protein intake does not modulate any of these muscle deconditioning responses.Clinical trial registry number: NCT03797781.Exeter UniversityMaastricht UniversityNIH

Plasmodium P-Type Cyclin CYC3 Modulates Endomitotic Growth during Oocyst Development in Mosquitoes

Cell-cycle progression and cell division in eukaryotes are governed in part by the cyclin family and their regulation of cyclin-dependent kinases (CDKs). Cyclins are very well characterised in model systems such as yeast and human cells, but surprisingly little is known about their number and role in Plasmodium, the unicellular protozoan parasite that causes malaria. Malaria parasite cell division and proliferation differs from that of many eukaryotes. During its life cycle it undergoes two types of mitosis: endomitosis in asexual stages and an extremely rapid mitotic process during male gametogenesis. Both schizogony (producing merozoites) in host liver and red blood cells, and sporogony (producing sporozoites) in the mosquito vector, are endomitotic with repeated nuclear replication, without chromosome condensation, before cell division. The role of specific cyclins during Plasmodium cell proliferation was unknown. We show here that the Plasmodium genome contains only three cyclin genes, representing an unusual repertoire of cyclin classes. Expression and reverse genetic analyses of the single Plant (P)-type cyclin, CYC3, in the rodent malaria parasite, Plasmodium berghei, revealed a cytoplasmic and nuclear location of the GFP-tagged protein throughout the lifecycle. Deletion of cyc3 resulted in defects in size, number and growth of oocysts, with abnormalities in budding and sporozoite formation. Furthermore, global transcript analysis of the cyc3-deleted and wild type parasites at gametocyte and ookinete stages identified differentially expressed genes required for signalling, invasion and oocyst development. Collectively these data suggest that cyc3 modulates oocyst endomitotic development in Plasmodium berghei

Short-term muscle disuse induces a rapid and sustained decline in daily myofibrillar protein synthesis rates

This is the author accepted manuscript. The final version is available from the American Physiological Society via the DOI in this recordIntroduction: Short-term muscle disuse has been reported to lower both post-absorptive and post-prandial myofibrillar protein synthesis rates. This study assessed the impact of disuse on daily myofibrillar protein synthesis rates following acute (2 days) and more prolonged (7 days) muscle disuse under free living conditions. Methods: Thirteen healthy young men (age, 20±1 y; BMI, 23±1 kg·m-2) underwent 7 days of unilateral leg immobilization via a knee brace with the non-immobilized leg acting as a control. Four days prior to immobilization participants ingested 400 mL 70% deuterated water, with 50 mL doses consumed daily thereafter. Upper leg bilateral MRI scans and muscle biopsies were collected before, and after 2 and 7 days of immobilization to determine quadriceps volume and daily myofibrillar protein synthesis rates. Results: Immobilization reduced quadriceps volume in the immobilized leg by 1.7±0.3 and 6.7±0.6 % after 2 and 7 days, respectively, with no changes in the control leg. Over the one week immobilization period myofibrillar protein synthesis rates were 36±4% lower in the immobilized (0.81±0.04%·d-1) compared with the control (1.26±0.04%·d-1) leg (P<0.001). Myofibrillar protein synthesis rates in the control leg did not change over time (P=0.775), but in the immobilized leg were numerically lower during the 0-2 day period (16±6%, 1.11±0.09%·d-1, P=0.153) and were significantly lower during the 2-7 day period (44±5%, 0.70±0.06%·d-1, P<0.001) when compared with the control leg. Conclusion: One week of muscle disuse induces a rapid and sustained decline in daily myofibrillar protein synthesis rates in healthy young men.University of MaastrichtRoyal SocietyUniversity of ExeterNational Institute for Health Research (NIHR

A Randomised, Placebo-Controlled, Crossover Study Investigating the Optimal Timing of a Caffeine-Containing Supplement for Exercise Performance.

This is the final version. Available from Springer via the DOI in this record.The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.BACKGROUND: Pre-exercise supplements containing low doses of caffeine improve endurance exercise performance, but the most efficacious time for consumption before intense endurance exercise remains unclear, as does the contribution of caffeine metabolism. METHODS: This study assessed the timing of a commercially available supplement containing 200 mg of caffeine, 1600 mg of β-alanine and 1000 mg of quercetin [Beachbody Performance Energize, Beachbody LLC, USA] on exercise performance, perception of effort and plasma caffeine metabolites. Thirteen cyclists (V̇O2max 64.5 ± 1.4 ml kg- 1 min- 1 (± SEM)) completed four experimental visits consisting of 30 min of steady-state exercise on a cycle ergometer at 83 ± 1% V̇O2max followed by a 15-min time trial, with perceived exertion measured regularly. On three of the visits, participants consumed caffeine either 35 min before steady-state exercise (PRE), at the onset of steady-state (ONS) or immediately before the time trial (DUR) phases, with a placebo consumed at the other two time points (i.e. three drinks per visit). The other visit (PLA) consisted of consuming the placebo supplement at all three time points. The placebo was taste-, colour- and calorie-matched. RESULTS: Total work performed during the time trial in PRE was 5% greater than PLA (3.53 ± 0.14 vs. 3.36 ± 0.13 kJ kg- 1 body mass; P = 0.0025), but not ONS (3.44 ± 0.13 kJ kg- 1; P = 0.3619) or DUR (3.39 ± 0.13 kJ kg- 1; P = 0.925), which were similar to PLA. Perceived exertion was lowest during steady-state exercise in the PRE condition (P < 0.05), which coincided with elevated plasma paraxanthine in PRE only (P < 0.05). CONCLUSION: In summary, ingestion of a pre-exercise supplement containing 200 mg caffeine 35 min before exercise appeared optimal for improved performance in a subsequent fatiguing time trial, possibly by reducing the perception of effort. Whether this was due to increased circulating paraxanthine requires further investigation. TRIAL REGISTRATION: ClinicalTrials.Gov, NCT02985606 ; 10/26/2016.Beachbod

Review for the generalist: evaluation of anterior knee pain

Anterior knee pain is common in children and adolescents. Evaluation and management is challenging and requires a thorough history and physical exam, and understanding of the pediatric skeleton. This article will review common causes of chronic anterior knee pain in the pediatric population with a focus on patellofemoral pain

Neuronal circuitry for pain processing in the dorsal horn

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region

Strong Neutral Spatial Effects Shape Tree Species Distributions across Life Stages at Multiple Scales

Traditionally, ecologists use lattice (regional summary) count data to simulate tree species distributions to explore species coexistence. However, no previous study has explicitly compared the difference between using lattice count and basal area data and analyzed species distributions at both individual species and community levels while simultaneously considering the combined scenarios of life stage and scale. In this study, we hypothesized that basal area data are more closely related to environmental variables than are count data because of strong environmental filtering effects. We also address the contribution of niche and the neutral (i.e., solely dependent on distance) factors to species distributions. Specifically, we separately modeled count data and basal area data while considering life stage and scale effects at the two levels with simultaneous autoregressive models and variation partitioning. A principal coordinates of neighbor matrix (PCNM) was used to model neutral spatial effects at the community level. The explained variations of species distribution data did not differ significantly between the two types of data at either the individual species level or the community level, indicating that the two types of data can be used nearly identically to model species distributions. Neutral spatial effects represented by spatial autoregressive parameters and the PCNM eigenfunctions drove species distributions on multiple scales, different life stages and individual species and community levels in this plot. We concluded that strong neutral spatial effects are the principal mechanisms underlying the species distributions and thus shape biodiversity spatial patterns

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation