Opinion on the role of protein in promoting athletic performance is divided along the lines of how much aerobic-based versus resistance-based activity the athlete undertakes. Athletes seeking to gain ...muscle mass and strength are likely to consume higher amounts of dietary protein than their endurance-trained counterparts. The main belief behind the large quantities of dietary protein consumption in resistance-trained athletes is that it is needed to generate more muscle protein. Athletes may require protein for more than just alleviation of the risk for deficiency, inherent in the dietary guidelines, but also to aid in an elevated level of functioning and possibly adaptation to the exercise stimulus. It does appear, however, that there is a good rationale for recommending to athletes protein intakes that are higher than the RDA. Our consensus opinion is that leucine, and possibly the other branched-chain amino acids, occupy a position of prominence in stimulating muscle protein synthesis; that protein intakes in the range of 1.3-1.8 g · kg
−1
· day
−1
consumed as 3-4 isonitrogenous meals will maximize muscle protein synthesis. These recommendations may also be dependent on training status: experienced athletes would require less, while more protein should be consumed during periods of high frequency/intensity training. Elevated protein consumption, as high as 1.8-2.0 g · kg
−1
· day
−1
depending on the caloric deficit, may be advantageous in preventing lean mass losses during periods of energy restriction to promote fat loss.
We have conducted a Galactic plane survey of methanol masers at 6668 MHz using a seven-beam receiver on the Parkes telescope. Here we present results from the first part, which provides sensitive ...unbiased coverage of a large region around the Galactic Centre. Details are given for 183 methanol maser sites in the longitude range 345° through the Galactic Centre to 6°. Within 6° of the Galactic Centre, we found 88 maser sites, of which more than half (48) are new discoveries. The masers are confined to a narrow Galactic latitude range, indicative of many sources at the Galactic Centre distance and beyond, and confined to a thin disc population; there is no high-latitude population that might be ascribed to the Galactic bulge. Within 2° of the Galactic Centre the maser velocities all lie between −60 and +77 km s−1, a range much smaller than the 540 km s−1 range observed in CO. Elsewhere, the maser with highest positive velocity (+107 km s−1) occurs, surprisingly, near longitude 355° and is probably attributable to the Galactic bar. The maser with the most negative velocity (−127 km s−1) is near longitude 346°, within the longitude–velocity locus of the near side of the ‘3-kpc arm’. It has the most extreme velocity of a clear population of masers associated with the near and far sides of the 3-kpc arm. Closer to the Galactic Centre the maser space density is generally low, except within 0.25 kpc of the Galactic Centre itself, the ‘Galactic Centre zone’, where it is 50 times higher, which is hinted at by the longitude distribution, and confirmed by the unusual velocities.
Gene therapy approaches using adeno-associated viral vectors have been successfully tested in the equine post-traumatic osteoarthritis (PTOA) model. Owing to differences in the levels of transgene ...expression and adverse tissue reactions observed in published studies, we sought to identify a safe therapeutic dose of scAAVIL-1ra in an inflamed and injured joint that would result in improved functional outcomes without any adverse events. scAAVIL-1ra was delivered intra-articularly over a 100-fold range, and horses were evaluated throughout and at the end of the 10-week study. A dose-related increase in IL-1ra levels with a decrease in PGE
levels was observed, with the peak IL-1ra concentration being observed 7 days post-treatment in all groups. Perivascular infiltration with mononuclear cells was observed within the synovial membrane of the joint treated with the highest viral dose of 5 × 10
vg, but this was absent in the lower-dosed joints. The second-highest dose of scAAVeqIL-1ra 5 × 10
vg demonstrated elevated IL-1ra levels without any cellular response in the synovium. Taken together, the data suggest that the 10-fold lower dose of 5 × 10
vg scAAVIL-1ra would be a safe therapeutic dose in an equine model of PTOA.
Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large ...EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC.
Although many phenotypes have been associated with variants in human leukocyte antigen (HLA) genes, the full phenotypic impact of HLA variants across all diseases is unknown. We imputed HLA genomic ...variation from two populations of 28,839 and 8431 European ancestry individuals and tested association of HLA variation with 1368 phenotypes. A total of 104 four-digit and 92 two-digit HLA allele phenotype associations were significant in both discovery and replication cohorts, the strongest being
and type 1 diabetes. Four previously unidentified associations were identified across the spectrum of disease with two- and four-digit HLA alleles and 10 with nonsynonymous variants. Some conditions associated with multiple HLA variants and stronger associations with more severe disease manifestations were identified. A comprehensive, publicly available catalog of clinical phenotypes associated with HLA variation is provided. Examining HLA variant disease associations in this large data set allows comprehensive definition of disease associations to drive further mechanistic insights.
Key points
Sleep restriction has previously been associated with the loss of muscle mass in both human and animal models.
The rate of myofibrillar protein synthesis (MyoPS) is a key variable in ...regulating skeletal muscle mass and can be increased by performing high‐intensity interval exercise (HIIE), although the effect of sleep restriction on MyoPS is unknown.
In the present study, we demonstrate that participants undergoing a sleep restriction protocol (five nights, with 4 h in bed each night) had lower rates of skeletal muscle MyoPS; however, rates of MyoPS were maintained at control levels by performing HIIE during this period.
Our data suggest that the lower rates of MyoPS in the sleep restriction group may contribute to the detrimental effects of sleep loss on muscle mass and that HIIE may be used as an intervention to counteract these effects.
The present study aimed to investigate the effect of sleep restriction, with or without high‐intensity interval exercise (HIIE), on the potential mechanisms underpinning previously‐reported sleep‐loss‐induced reductions to muscle mass. Twenty‐four healthy, young men underwent a protocol consisting of two nights of controlled baseline sleep and a five‐night intervention period. Participants were allocated into one of three parallel groups, matched for age, V̇O2peak, body mass index and habitual sleep duration; a normal sleep (NS) group 8 h time in bed (TIB) each night, a sleep restriction (SR) group (4 h TIB each night), and a sleep restriction and exercise group (SR+EX, 4 h TIB each night, with three sessions of HIIE). Deuterium oxide was ingested prior to commencing the study and muscle biopsies obtained pre‐ and post‐intervention were used to assess myofibrillar protein synthesis (MyoPS) and molecular markers of protein synthesis and degradation signalling pathways. MyoPS was lower in the SR group fractional synthetic rate (% day–1), mean ± SD, 1.24 ± 0.21 compared to both the NS (1.53 ± 0.09) and SR+EX groups (1.61 ± 0.14) (P < 0.05). However, there were no changes in the purported regulators of protein synthesis (i.e. p‐AKTser473 and p‐mTORser2448) and degradation (i.e. Foxo1/3 mRNA and LC3 protein) in any group. These data suggest that MyoPS is acutely reduced by sleep restriction, although MyoPS can be maintained by performing HIIE. These findings may explain the sleep‐loss‐induced reductions in muscle mass previously reported and also highlight the potential therapeutic benefit of HIIE to maintain myofibrillar remodelling in this context.
Key points
Sleep restriction has previously been associated with the loss of muscle mass in both human and animal models.
The rate of myofibrillar protein synthesis (MyoPS) is a key variable in regulating skeletal muscle mass and can be increased by performing high‐intensity interval exercise (HIIE), although the effect of sleep restriction on MyoPS is unknown.
In the present study, we demonstrate that participants undergoing a sleep restriction protocol (five nights, with 4 h in bed each night) had lower rates of skeletal muscle MyoPS; however, rates of MyoPS were maintained at control levels by performing HIIE during this period.
Our data suggest that the lower rates of MyoPS in the sleep restriction group may contribute to the detrimental effects of sleep loss on muscle mass and that HIIE may be used as an intervention to counteract these effects.
•Faecal cortisol metabolites’ relation with body temperature and behaviour was studied.•Faecal cortisol metabolites were related to indicators of heat stress.•Faecal cortisol metabolites were ...positively correlated with body surface temperature.•Faecal cortisol metabolites were positively correlated with standing, panting and drinking.•Respiration rate was the best indicator of the heat stress in cattle.
Feedlot cattle are at times exposed to high environmental temperatures. Faecal cortisol metabolites were related to possible indicators of heat stress that could be measured under field conditions: respiratory dynamics (respiration rate), body surface temperature and adaptive behaviours, such as water consumption, posture (standing, lying), and activity (eating, drinking and rumination). Twelve (12) yearling Black Angus steers were divided into two treatment groups: a hot treatment (HOT; n = 6) and a thermoneutral-treatment (TN; n = 6) and individually housed in a climate-controlled facility at The University of Queensland, Australia. In the TN treatment, all animals were exposed to an ambient temperature of 20.34 ± 0.25 °C, relative humidity 71.51 ± 3.26% and Temperature humidity index (THI) 66.91 ± 0.33 throughout. In the HOT treatment group, environmental conditions were exposed to different climatic phases from thermoneutral to hot conditions, where they remained for 7 d, and then returned to TN conditions in the recovery period. The dry bulb ambient temperature (TA) and relative humidity (RH) in the pens of cattle in the HOT treatment were increased from 28 °C (daily maximum ambient temperature) and 45% RH at 0700 h to a daily maximum TA and RH of 35 °C (daily maximum ambient temperature) and 50% (THI 77) at 1100 h, which was maintained until 1600 h, after which it declined until it reached the baseline at 2000 h. In both treatments, there was a significant decrease in faecal cortisol metabolite concentration from the start to the end of the experiments they adapted to the experimental facility. The concentration of faecal cortisol metabolites was greater in the HOT treatment, compared to the TN treatment during the heat exposure period, but there was no difference in the transition or recovery periods. Respiration rate was greater in the HOT treatment during heat exposure, and it increased with ambient dry bulb temperature above 26 °C, the latter being the upper critical temperature. Although positive correlations were detected between faecal cortisol metabolites and body surface temperature measurements, particularly the shoulder and rump, as well as standing time, panting score and drinking, a stepwise regression found that faecal cortisol metabolites were only significantly correlated with one variable, respiration rate. It is concluded that respiration rate is the best indicator of the stress induced by hot conditions for cattle.
The Australia Telescope Compact Array has been used to measure positions with arcsecond accuracy for 379 masers at the 22-GHz transition of water. The principal observation targets were 202 OH masers ...of the variety associated with star formation regions (SFRs) in the Southern Galactic plane. At a second epoch, most of these targets were observed again, and new targets of methanol masers were added. Many of the water masers reported here are new discoveries and others had been reported, with position uncertainties exceeding 10 arcsec, from Parkes telescope single-dish observations many years ago. Variability in the masers is often acute, with very few features directly corresponding to those discovered two decades ago. Within our current observations, less than a year apart, spectra are often dissimilar, but positions at the later epoch, even when measured for slightly different features, mostly correspond to the detected maser site measured earlier, to within the typical extent of the whole site, of a few arcseconds. The precise water positions show that approximately 79 per cent (160 of 202) of the OH maser sites show coincident water maser emission, the best estimate yet obtained for this statistic; however, there are many instances where additional water sites are present offset from the OH target, and consequently less than half of the water masers coincide with a 1665-MHz ground-state OH maser counterpart. Our less uniform sample of methanol targets is not suitable for a full investigation of their association with water masers, but we are able to explore differences between the velocities of peak emission from the three species and quantify the typically larger deviations shown by water maser peaks from systemic velocities. Clusters of two or three distinct but nearby sites, each showing one or several of the principal molecular masing transitions, are found to be common. We also report the detection of ultracompact H ii regions towards some of the sites. In combination with an investigation of correlations with IR sources from the Spitzer Galactic Legacy Infrared Mid-Plane Survey Extraordinaire (GLIMPSE) catalogue, these comparative studies allow further progress in the use of the maser properties to assign relative evolutionary stages in star formation to individual sites.
We have observed well-defined phase slips between quantized persistent current states around a toroidal atomic (23Na) Bose-Einstein condensate. These phase slips are induced by a weak link (a ...localized region of reduced superfluid density) rotated slowly around the ring. This is analogous to the behavior of a superconducting loop with a weak link in the presence of an external magnetic field. When the weak link is rotated more rapidly, well-defined phase slips no longer occur, and vortices enter into the bulk of the condensate. A noteworthy feature of this system is the ability to dynamically vary the current-phase relation of the weak link, a feature which is difficult to implement in superconducting or superfluid helium circuits.
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