Significant Energy Deficit and Suboptimal Sleep During a Junior Academy Tennis Training Camp.

PURPOSE: To assess the training load, energy expenditure, dietary intake, and sleep quality and quantity of junior tennis players during a tennis training camp. METHODS: Ten junior academy tennis players (14 [1] y) completed a 6-day camp with daily morning and afternoon training. Players wore accelerometer watches to measure activity energy expenditure and sleep. Global positioning system units were worn to monitor external training load (distance covered, maximum velocity, and PlayerLoad™). Dietary intake was obtained from a food diary and supplementary food photography. RESULTS: Players covered significantly more distance and had higher PlayerLoad™ during morning sessions than afternoon sessions (5370 [505] m vs 4726 [697] m, P < .005, d = 3.2; 725 [109] a.u. vs 588 [96] a.u., P < .005, d = 4.0). Players also ran further (5624 [897] m vs 4933 [343] m, P < .05, d = 1.0) and reached higher maximum velocities (5.17 [0.44] m·s-1 vs 4.94 [0.39] m·s-1, P < .05, d = 0.3) during simulated match play compared with drill sessions. Mean daily energy expenditure was 3959 (630) kcal. Mean energy intake was 2526 (183) kcal, resulting in mean energy deficits of 1433 (683) kcal. Players obtained an average of 6.9 (0.8) hours of sleep and recorded 28 (7) nightly awakenings. CONCLUSIONS: Junior academy tennis players failed to achieve energy balance and recorded suboptimal sleep quantity and quality throughout the training camp.

Dietary Intake and Daily Distribution of Carbohydrate, Protein and Fat in Youth Tennis Players over a 7-Day Training and Competition Period.

During a 7-day training and/or competition period, macronutrient intake and distribution was assessed using food diaries, supported by remote food photography and 24-hr multiple pass recalls of youth tennis players categorised by under 12s, under 14s and under 16+ age groups (n = 27). Total energy did not differ between age groups nor type of day (training [TD], competition day [CD]), irrespective of a significant increase in body mass reported in the older players (U16+; p < 0.05). Average intakes were consistently below 2250 kcal·day-1 (range 1965 ± 317-2232 ± 612 kcal·day-1). Carbohydrate consumption was below guidelines for all groups (≤6g·kg-1). Conversely, protein intake met or exceeded guidelines throughout, with intakes ≥2 g·kg-1 for both the U12 and U14 age groups on both days. Protein intake was ~17% higher on TDs than CDs (p < 0.05), with protein intake at lunch significantly higher on TDs than CDs (p < 0.05). No further differences were observed between breakfast, lunch or dinner between group or day. Inconsistent snacking was reported, with players consuming snacks on less than half of the days reported (46 ± 12% of TDs and 43 ± 30% of CDs). In conclusion, youth tennis players present sub-optimal nutrition practices, appearing to under fuel and under consume carbohydrate for performance, adaptation, recovery and health.

Investigating the Nutritional and Recovery Habits of Tennis Players.

In this study, the nutritional and recovery habits of tennis players pre-, during, and post-match-play were investigated. Seventy tennis players completed a bespoke nutrition and recovery habits questionnaire, with questions related to the following areas: match preparation, intra-match nutritional habits, situation dependent variables, and post-match nutrition and recovery. On match day-1, the consumption of balanced meals consisting of carbohydrate (CHO), fat and protein, with some micronutrient considerations were reported by 51% of players. On match-days, CHOs were prioritised prior to match-play with CHO dominant meals consumed by the majority of players. During matches, all players adopted a nutritional strategy, with water (94%), banana(s) (86%) and sports drinks (50%) commonly used. Carbohydrate rich nutritional aids, including sports drinks (80%) and energy gels (26%) were utilised more readily during long matches (>2 h). The day after match-play, 39% of players reported the consumption of "nothing specific". Multiple post-match recovery strategies were adopted by 80% of players, with foam rolling (77%), ice baths (40%), protein shake intake (37%) and hot baths (26%) most used. Findings indicate highly variable eating and recovery habits in tennis players pre-, during and post-match-play, with scope for improved practices.

Mechanism of Action and Clinical Application of Tafamidis in Hereditary Transthyretin Amyloidosis.

Transthyretin (TTR) transports the retinol-binding protein-vitamin A complex and is a minor transporter of thyroxine in blood. Its tetrameric structure undergoes rate-limiting dissociation and monomer misfolding, enabling TTR to aggregate or to become amyloidogenic. Mutations in the TTR gene generally destabilize the tetramer and/or accelerate tetramer dissociation, promoting amyloidogenesis. TTR-related amyloidoses are rare, fatal, protein-misfolding disorders, characterized by formation of soluble aggregates of variable structure and tissue deposition of amyloid. The TTR amyloidoses present with a spectrum of manifestations, encompassing progressive neuropathy and/or cardiomyopathy. Until recently, the only accepted treatment to halt progression of hereditary TTR amyloidosis was liver transplantation, which replaces the hepatic source of mutant TTR with the less amyloidogenic wild-type TTR. Tafamidis meglumine is a rationally designed, non-NSAID benzoxazole derivative that binds with high affinity and selectivity to TTR and kinetically stabilizes the tetramer, slowing monomer formation, misfolding, and amyloidogenesis. Tafamidis is the first pharmacotherapy approved to slow the progression of peripheral neurologic impairment in TTR familial amyloid polyneuropathy. Here we describe the mechanism of action of tafamidis and review the clinical data, demonstrating that tafamidis treatment slows neurologic deterioration and preserves nutritional status, as well as quality of life in patients with early-stage Val30Met amyloidosis.

Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade.

The transthyretin amyloidoses (ATTR) are invariably fatal diseases characterized by progressive neuropathy and/or cardiomyopathy. ATTR are caused by aggregation of transthyretin (TTR), a natively tetrameric protein involved in the transport of thyroxine and the vitamin A-retinol-binding protein complex. Mutations within TTR that cause autosomal dominant forms of disease facilitate tetramer dissociation, monomer misfolding, and aggregation, although wild-type TTR can also form amyloid fibrils in elderly patients. Because tetramer dissociation is the rate-limiting step in TTR amyloidogenesis, targeted therapies have focused on small molecules that kinetically stabilize the tetramer, inhibiting TTR amyloid fibril formation. One such compound, tafamidis meglumine (Fx-1006A), has recently completed Phase II/III trials for the treatment of Transthyretin Type Familial Amyloid Polyneuropathy (TTR-FAP) and demonstrated a slowing of disease progression in patients heterozygous for the V30M TTR mutation. Herein we describe the molecular and structural basis of TTR tetramer stabilization by tafamidis. Tafamidis binds selectively and with negative cooperativity (K(d)s ~2 nM and ~200 nM) to the two normally unoccupied thyroxine-binding sites of the tetramer, and kinetically stabilizes TTR. Patient-derived amyloidogenic variants of TTR, including kinetically and thermodynamically less stable mutants, are also stabilized by tafamidis binding. The crystal structure of tafamidis-bound TTR suggests that binding stabilizes the weaker dimer-dimer interface against dissociation, the rate-limiting step of amyloidogenesis.

Systematic exploration of essential yeast gene function with temperature-sensitive mutants.

Conditional temperature-sensitive (ts) mutations are valuable reagents for studying essential genes in the yeast Saccharomyces cerevisiae. We constructed 787 ts strains, covering 497 (∼45%) of the 1,101 essential yeast genes, with ∼30% of the genes represented by multiple alleles. All of the alleles are integrated into their native genomic locus in the S288C common reference strain and are linked to a kanMX selectable marker, allowing further genetic manipulation by synthetic genetic array (SGA)-based, high-throughput methods. We show two such manipulations: barcoding of 440 strains, which enables chemical-genetic suppression analysis, and the construction of arrays of strains carrying different fluorescent markers of subcellular structure, which enables quantitative analysis of phenotypes using high-content screening. Quantitative analysis of a GFP-tubulin marker identified roles for cohesin and condensin genes in spindle disassembly. This mutant collection should facilitate a wide range of systematic studies aimed at understanding the functions of essential genes.

Biological characterization of MLN944: a potent DNA binding agent.

MLN944 (XR5944) is a novel bis-phenazine that has demonstrated exceptional efficacy against a number of murine and human tumor models. The drug was reported originally as a dual topoisomerase I/II poison, but a precise mechanism of action for this compound remains to be determined. Several lines of evidence, including the marginal ability of MLN944 to stabilize topoisomerase-dependent cleavage, and the sustained potency of MLN944 in mammalian cells with reduced levels of both topoisomerases, suggest that other activities of the drug exist. In this study, we show that MLN944 intercalates into DNA, but has no effect on the catalytic activity of either topoisomerase I or II. MLN944 displays no significant ability to stimulate DNA scission mediated by either topoisomerase I or II compared with camptothecin or etoposide, respectively. In addition, yeast genetic models also point toward a topoisomerase-independent mechanism of action. To examine cell cycle effects, synchronized human HCT116 cells were treated with MLN944, doxorubicin, camptothecin, or a combination of the latter two to mimic a dual topoisomerase poison. MLN944 treatment was found to induce a G(1) and G(2) arrest in cells that is unlike the typical G(2)-M arrest noted with known topoisomerase poisons. Finally, transcriptional profiling analysis of xenograft tumors treated with MLN944 revealed clusters of regulated genes distinct from those observed in irinotecan hydrochloride (CPT-11)-treated tumors. Taken together, these findings suggest that the primary mechanism of action of MLN944 likely involves DNA binding and intercalation, but does not appear to involve topoisomerase inhibition.

Complementary whole-genome technologies reveal the cellular response to proteasome inhibition by PS-341.

Although the biochemical targets of most drugs are known, the biological consequences of their actions are typically less well understood. In this study, we have used two whole-genome technologies in Saccharomyces cerevisiae to determine the cellular impact of the proteasome inhibitor PS-341. By combining population genomics, the screening of a comprehensive panel of bar-coded mutant strains, and transcript profiling, we have identified the genes and pathways most affected by proteasome inhibition. Many of these function in regulated protein degradation or a subset of mitotic activities. In addition, we identified Rpn4p as the transcription factor most responsible for the cell's ability to compensate for proteasome inhibition. Used together, these complementary technologies provide a general and powerful means to elucidate the cellular ramifications of drug treatment.