AbstractBackgroundWe examined the metabolic, performance and gastrointestinal (GI) effects of supplementation with a natural food product (raisins) compared to a commercial product (sport chews).MethodsEleven male (29.3 ± 7.9 yrs; mean and SD) runners completed three randomized trials (raisins, chews and water only) separated by seven days. Each trial consisted of 80-min (75%VO2max) treadmill running followed by a 5-km time trial (TT). Heart rate (HR), respiratory exchange ratio (RER), blood lactate, serum free fatty acids (FFA), glycerol and insulin, plasma glucose and creatine kinase, GI symptoms and rating of perceived exertion (RPE) were recorded every 20-min. We employed a within-subject two-way analysis of variance (ANOVA) for repeated measures with a Fisher’s post hoc analysis to determine significant differences.ResultsVO2, HR, lactate, glycerol and RPE did not differ due to treatment. Average plasma glucose was maintained at resting levels (5.3 ± 0.4 mmol·L-1) during the sub-maximal exercise bout (5.9 ± 0.6, 5.7 ± 0.6 and 5.5 ± 0.5 mmol·L-1 for chews, raisins and water respectively), and was significantly higher with chews than water only. RER and % of non-protein macronutrient oxidation derived from carbohydrate was highest with chews, followed by raisins and water was the lowest (74.4 ± 6.4, 70.0 ± 7.0 and 65.1 ± 8.7% for chews, raisins and water respectively) during the sub-maximal exercise period. Serum FFA was higher in the water treatment versus both raisins and chews at 80 min of sub-maximal exercise. Serum insulin was higher with the chews than both raisins and water (5.1 ± 2.0, 3.1 ± 0.8, 1.9 ± 0.6 uU·ml-1 for chews, raisins and water respectively). Plasma creatine kinase, corrected for baseline values, for the last 40 min of the sub-maximal exercise bout, was higher with raisins compared to other treatments. The TT was faster for both carbohydrate supplements (20.6 ± 2.6, 20.7 ± 2.5, 21.6 ± 2.7 min for raisin, chews and water respectively). GI disturbance was mild for all treatments.ConclusionRaisins and chews promoted higher carbohydrate oxidation and improved running performance compared to water only. Running performance was similar between the raisins and chews, with no significant GI differences.

This study aimed to determine the effects of a betalain-rich concentrate (BRC) of red beets, containing antioxidant and anti-inflammatory properties, on performance and exercise-related muscle damage. Thirteen (25.3 ± 5.4 years) competitive male runners completed two double-blind, cross-over, randomized trials (BRC and control) separated by seven days. Each trial was preceded by six days of supplementation with 100 mg of BRC or control. On the seventh day, exercise trials commenced 150 min after supplementation with 50 mg BRC or control and consisted of 30 min of treadmill running (77 ± 4% VO₂max) followed by a 5-km time trial (TT). During exercise at the same intensity, BRC resulted in a 3% lower heart rate, a 15% lower rate of perceived exertion (RPE) and a 14% lower blood lactate concentration compared to the control (p = 0.05). Five-kilometer TT duration (23.0 ± 4.2 versus 23.6 ± 4.0 min) was faster in 10 of the 13 subjects, and RPE was lower (p < 0.05) with the BRC treatment compared to the control. Lactate dehydrogenase, a marker of muscle damage, increased less from baseline to immediately and 30 min after the 5-km TT with the BRC treatment, despite no differences in subjective measures of muscle soreness and fatigue. In summary, BRC supplementation improved 5-km performance time in male competitive runners.

Timing of nutrient intake for athletes may affect exercise performance and cardiometabolic factors. Our objective was to examine the effect of time-restricted eating (TRE) on cardiometabolic health. Using a cross-over study design, 15 endurance-trained male runners were randomized to either a normal dietary pattern (ND) first (12 h eating/fasting times) followed by time-restricted eating (TRE) pattern (16 h fast; 8 h eating) or the reverse, with a 4-week washout period between interventions. Body composition, resting energy expenditure, blood pressure and serum insulin, glucose and lipids were measured using standard laboratory methods. Exercise training and dietary intake (calories and macronutrients) were similar across interventions. No significant differences were observed in resting energy expenditure, markers of insulin resistance, serum lipids or blood pressure. Body composition did change significantly (p < 0.05) with whole body fat mass (-0.8 ± 1.3 kg with TRE vs. +0.1 ± 4.3 kg with ND), leg fat mass (-0.3 ± 0.5 kg with TRE vs. +0.1 ± 0.4 kg with ND), and percent body fat (-1.0 ± 1.5% with TRE vs. +0.1 ± 1.3% with ND) declining more in the TRE intervention, with no change in fat-free mass. This study is one of a few to investigate the effects of an isocaloric 16/8 TRE eating pattern in trained endurance athletes and confirms no change in cardiometabolic risk factors. In conclusion, TRE is not detrimental to cardiometabolic health in endurance-trained male runners but could be beneficial on exercise performance by reducing fat mass.

Time restricted Feeding (TRF) is a dietary pattern utilized by endurance athletes, but there is insufficient data regarding its effects on performance and metabolism in this population. The purpose of this investigation was to examine the effects of a 16/8 TRF dietary pattern on exercise performance in trained male endurance runners. A 4-week randomized crossover intervention was used to compare an 8-h TRF to a 12-h normal diet (ND) feeding window. Exercise training and dietary intake were similar across interventions. Runners completed a dual-energy X-ray absorptiometry (DXA) scan to assess body composition, a graded treadmill running test to assess substrate utilization, and ran a 10 km time trial to assess performance. There was a significant decrease in fat mass in the TRF intervention (-0.8 ± 1.3 kg with TRF (p = 0.05), vs. +0.1 ± 4.3 kg with ND), with no significant change in fat-free mass. Exercise carbon dioxide production (VCO2) and blood lactate concentration were significantly lower with the TRF intervention (p ≤ 0.02). No significant changes were seen in exercise respiratory exchange ratio or 10 km time trial performance (-00:20 ± 3:34 min:s TRF vs. -00:36 ± 2:57 min:s ND). This investigation demonstrated that adherence to a 4-week 16/8 TRF dietary intervention decreased fat mass and maintained fat-free mass, while not affecting running performance, in trained male endurance runners.

The domestic cat (Felis catus) numbers over 94 million in the USA alone, occupies households as a companion animal, and, like humans, suffers from cancer and common and rare diseases. However, genome-wide sequence variant information is limited for this species. To empower trait analyses, a new cat genome reference assembly was developed from PacBio long sequence reads that significantly improve sequence representation and assembly contiguity. The whole genome sequences of 54 domestic cats were aligned to the reference to identify single nucleotide variants (SNVs) and structural variants (SVs). Across all cats, 16 SNVs predicted to have deleterious impacts and in a singleton state were identified as high priority candidates for causative mutations. One candidate was a stop gain in the tumor suppressor FBXW7. The SNV is found in cats segregating for feline mediastinal lymphoma and is a candidate for inherited cancer susceptibility. SV analysis revealed a complex deletion coupled with a nearby potential duplication event that was shared privately across three unrelated cats with dwarfism and is found within a known dwarfism associated region on cat chromosome B1. This SV interrupted UDP-glucose 6-dehydrogenase (UGDH), a gene involved in the biosynthesis of glycosaminoglycans. Importantly, UGDH has not yet been associated with human dwarfism and should be screened in undiagnosed patients. The new high-quality cat genome reference and the compilation of sequence variation demonstrate the importance of these resources when searching for disease causative alleles in the domestic cat and for identification of feline biomedical models.

Disorders of sex development (DSD) and reproduction are not uncommon among horses, though knowledge about their molecular causes is sparse. Here we characterized a ~200 kb homozygous deletion in chromosome 29 at 29.7-29.9 Mb. The region contains AKR1C genes which function as ketosteroid reductases in steroid hormone biosynthesis, including androgens and estrogens. Mutations in AKR1C genes are associated with human DSDs. Deletion boundaries, sequence properties and gene content were studied by PCR and whole genome sequencing of select deletion homozygotes and control animals. Deletion analysis by PCR in 940 horses, including 622 with DSDs and reproductive problems and 318 phenotypically normal controls, detected 67 deletion homozygotes of which 79% were developmentally or reproductively abnormal. Altogether, 8-9% of all abnormal horses were homozygous for the deletion, with the highest incidence (9.4%) among cryptorchids. The deletion was found in ~4% of our phenotypically normal cohort, ~1% of global warmblood horses and ponies, and ~7% of draught breeds of general horse population as retrieved from published data. Based on the abnormal phenotype of the carriers, the functionally relevant gene content, and the low incidence in general population, we consider the deletion in chromosome 29 as a risk factor for equine DSDs and reproductive disorders.

The role of structurally dynamic genomic regions in speciation is poorly understood due to challenges inherent in diploid genome assembly. Here we reconstructed the evolutionary dynamics of structural variation in five cat species by phasing the genomes of three interspecies F1 hybrids to generate near-gapless single-haplotype assemblies. We discerned that cat genomes have a paucity of segmental duplications relative to great apes, explaining their remarkable karyotypic stability. X chromosomes were hotspots of structural variation, including enrichment with inversions in a large recombination desert with characteristics of a supergene. The X-linked macrosatellite DXZ4 evolves more rapidly than 99.5% of the genome clarifying its role in felid hybrid incompatibility. Resolved sensory gene repertoires revealed functional copy number changes associated with ecomorphological adaptations, sociality and domestication. This study highlights the value of gapless genomes to reveal structural mechanisms underpinning karyotypic evolution, reproductive isolation and ecological niche adaptation.

Clinical trials have established the benefit of androgen deprivation therapy (ADT) combined with radiotherapy in prostate cancer. ADT sensitizes prostate cancer to radiotherapy-induced death at least in part through inhibition of DNA repair machinery, but for unknown reasons, adjuvant ADT provides further survival benefits. Here, we show that androgen receptor (AR) expression and activity are durably upregulated following radiotherapy in multiple human prostate cancer models in vitro and in vivo. Moreover, the degree of AR upregulation correlates with survival in vitro and time to tumor progression in animal models. We also provide evidence of AR pathway upregulation, measured by a rise in serum levels of AR-regulated hK2 protein, in nearly 20% of patients after radiotherapy. Furthermore, these men were three-fold more likely to experience subsequent biochemical failure. Collectively, these data demonstrate that radiotherapy can upregulate AR signaling after therapy to an extent that negatively affects disease progression and/or survival.

The Greying with age phenotype in horses involves loss of hair pigmentation whereas skin pigmentation is not reduced, and a predisposition to melanoma. The causal mutation was initially reported as a duplication of a 4.6 kb intronic sequence in Syntaxin 17. The speed of greying varies considerably among Grey horses. Here we demonstrate the presence of two different Grey alleles, G2 carrying two tandem copies of the duplicated sequence and G3 carrying three. The latter is by far the most common allele, probably due to strong selection for the striking white phenotype. Our results reveal a remarkable dosage effect where the G3 allele is associated with fast greying and high incidence of melanoma whereas G2 is associated with slow greying and low incidence of melanoma. The copy number expansion transforms a weak enhancer to a strong melanocyte-specific enhancer that underlies hair greying (G2 and G3) and a drastically elevated risk of melanoma (G3 only). Our direct pedigree-based observation of the origin of a G2 allele from a G3 allele by copy number contraction demonstrates the dynamic evolution of this locus and provides the ultimate evidence for causality of the copy number variation of the 4.6 kb intronic sequence.