PSPI: A deep learning approach for prokaryotic small protein identification.

Small Proteins (SPs) are pivotal in various cellular functions such as immunity, defense, and communication. Despite their significance, identifying them is still in its infancy. Existing computational tools are tailored to specific eukaryotic species, leaving only a few options for SP identification in prokaryotes. In addition, these existing tools still have suboptimal performance in SP identification. To fill this gap, we introduce PSPI, a deep learning-based approach designed specifically for predicting prokaryotic SPs. We showed that PSPI had a high accuracy in predicting generalized sets of prokaryotic SPs and sets specific to the human metagenome. Compared with three existing tools, PSPI was faster and showed greater precision, sensitivity, and specificity not only for prokaryotic SPs but also for eukaryotic ones. We also observed that the incorporation of (n, k)-mers greatly enhances the performance of PSPI, suggesting that many SPs may contain short linear motifs. The PSPI tool, which is freely available at https://www.cs.ucf.edu/∼xiaoman/tools/PSPI/, will be useful for studying SPs as a tool for identifying prokaryotic SPs and it can be trained to identify other types of SPs as well.

Effective orifice diameter: a new sizing parameter of surgical valve prostheses to inform valve selection.

Background: The labeled sizes of surgical valve prostheses and their discordance with the physical internal valve orifice sizes has long been a controversy in the cardiac surgery community, leading many to believe it to be a contributing factor in prosthesis-patient mismatch following valvular replacement surgery. In an attempt to address this issue, the International Organization for Standardization (ISO) 5840-2:2021 standard for surgical valve prostheses recommends that a new sizing parameter, namely, the effective orifice diameter, be provided in labeling by all manufacturers as an indicator of the true flow-passing capacity of a prosthetic valve. Methods: The ISO Cardiac Valves Working Group conducted a multi-laboratory round-robin study to investigate whether the effective orifice diameter of a prosthetic surgical valve could be derived repeatably and reproducibly through steady forward-flow testing. A total of seven valve models, each with multiple sizes, were tested, including a mechanical heart valve and multiple biological heart valves. Results: The round-robin study confirmed that the steady forward-flow test had good intra-laboratory repeatability and inter-laboratory reproducibility in deriving the effective orifice diameters of surgical valve prostheses. On average, among the participating laboratories, the experimentally derived effective orifice diameter of a prosthetic heart valve was 3-12 mm smaller than its labeled size. Conclusions: The effective orifice diameter provides better characterization of the hydrodynamic characteristics of a surgical valve prosthesis and can be derived using a validated steady forward-flow test method. This new sizing parameter will soon be adopted by surgical valve manufacturers and provided in device labeling to inform valve selection by surgeons.

Intensity Gradients: A Novel Method for Interpreting External Loads in Football.

PURPOSE: Global navigation satellite system device-derived metrics are commonly represented by discrete zones with intensity often measured by standardizing volume to per-minute of activity duration. This approach is sensitive to imprecision in duration measurement and can lead to highly variable outcomes-transforming data from zones to a gradient may overcome this problem. The purpose of this study was to critically evaluate this approach for measuring team-sport activity demands. METHODS: Data were collected from 129 first-team and 73 academy matches from a Scottish Premiership football club. Gradients were calculated for velocity, acceleration, and deceleration zones, along with per-minute values for several commonly used metrics. Means and 95% CIs were calculated for playing level, as well as first-team positional groups. Within-subject coefficients of variation were also calculated for match level, position, and individual groups. RESULTS: The gradient approach showed consistency with per-minute metrics when measuring playing level and position groups. With coefficients of variation of 10.8% to 26.9%, the gradients demonstrated lower variability than most per-minute variables, which ranged from 10.7% to 84.5%. CONCLUSIONS: Gradients are a potentially useful way of describing intensity in team sports and compare favorably to existing intensity variables in their ability to distinguish between match types and position groups, providing evidence that gradient variables can be used to monitor match and training intensity in team sports.

Back to 'normal'? BMI, physical fitness and health-related quality of life of children from North East England before, during and after the COVID-19 lockdowns.

We assessed whether changes in children's body mass index (BMI), physical fitness and health-related quality of life observed post-2020 United Kingdom COVID-19 lockdown remained 12 and 18 months later. Twenty-metre shuttle run test (20mSRT), handgrip strength, standing broad jump, sit-and-reach, height, body mass, and health-related quality of life (Kidscreen27 questionnaire) were measured in 90 children (8-9 years) during October 2019 ("T0"), November 2020 ("T1"), November 2021 ("T2") and June 2022 ("T3"). Mixed-effects models showed age- and sex-normalised BMI increased from T0 (mean: 0.71) to T1 (0.97), remaining elevated at T2 (0.95) and T3 (0.89). Decreases in 20mSRT performance were observed from T0 (22.0) to T1 (19.3), then increased at T2 (23.5) and T3 (28.3). Standing broad jump and handgrip strength increased over time. The proportion of children with overweight/obesity increased from T0 (32%) to T3 (48%). Health-related quality of life decreased for "Physical Wellbeing" yet increased for "Autonomy & Parents". Our findings highlight that lockdowns may have had lasting implications for children's health, and the urgent need to reduce overweight and obesity in North East England. Improving health and fitness behaviours to maximise long-term health outcomes and build resilience to future emergencies and disruptions to health behaviours is also paramount.

Hyperactivity of mTORC1- and mTORC2-dependent signaling mediates epilepsy downstream of somatic PTEN loss.

Gene variants that hyperactivate PI3K-mTOR signaling in the brain lead to epilepsy and cortical malformations in humans. Some gene variants associated with these pathologies only hyperactivate mTORC1, but others, such as PTEN, PIK3CA, and AKT, hyperactivate both mTORC1- and mTORC2-dependent signaling. Previous work established a key role for mTORC1 hyperactivity in mTORopathies, however, whether mTORC2 hyperactivity contributes is not clear. To test this, we inactivated mTORC1 and/or mTORC2 downstream of early Pten deletion in a new mouse model of somatic Pten loss-of-function (LOF) in the cortex and hippocampus. Spontaneous seizures and epileptiform activity persisted despite mTORC1 or mTORC2 inactivation alone, but inactivating both mTORC1 and mTORC2 simultaneously normalized brain activity. These results suggest that hyperactivity of both mTORC1 and mTORC2 can cause epilepsy, and that targeted therapies should aim to reduce activity of both complexes.

Reliability of Measures of Lower-Body Strength and Speed in Academy Male Adolescent Soccer Players.

ABSTRACT: Ferguson, J, Gibson, NV, Weston, M, and McCunn, R. Reliability of measures of lower body strength and speed in academy male adolescent soccer players. J Strength Cond Res 38(3): e96-e103, 2024-The Nordbord and ForceFrame represent a practical and time efficient means of assessing eccentric hamstring and isometric adductor strength in the large number of squads and players associated with youth soccer academies, yet measurement reliability in this population is unexamined. Therefore, over a period of 4 days, with no less than 24 hours and no more than 48 hours between trials, 37 players (age: 14.7 ± 0.8 years, stature: 168.7 ± 7.8 cm, mass: 57.7 ± 9.1 kg, and maturity offset: 0.8 ± 0.9 years) were assessed for eccentric hamstring strength (force, torque), isometric adductor strength (long and short lever positions), and 30-m sprint (5, 10, and 20-m splits), using the Nordbord, ForceFrame, and electronic timing gates, respectively, on 3 separate occasions. Relative reliability (intraclass correlation coefficient) was rated as good for all Nordbord (range: 0.86-0.89) and ForceFrame (0.78-0.85) measures and ranged from moderate (0.53) to excellent (0.93) for the speed measures, improving with increased distance. Absolute reliability (standard error of the measurement [%SEM]) ranged from 7 to 8% (Nordbord), 3 to 11% (ForceFrame), and 1 to 4% (sprints). Our data provide the first Nordbord and ForceFrame reliability estimates in adolescent soccer academy players. To interpret test sensitivity, practitioners are encouraged to interpret our estimates of absolute reliability against meaningful change values derived from personal experience and evidence-based knowledge and not against absolute or standardized thresholds.

Hyperactivity of mTORC1 and mTORC2-dependent signaling mediate epilepsy downstream of somatic PTEN loss.

Gene variants that hyperactivate PI3K-mTOR signaling in the brain lead to epilepsy and cortical malformations in humans. Some gene variants associated with these pathologies only hyperactivate mTORC1, but others, such as PTEN, PIK3CA, and AKT, hyperactivate both mTORC1- and mTORC2-dependent signaling. Previous work established a key role for mTORC1 hyperactivity in mTORopathies, however, whether mTORC2 hyperactivity contributes is not clear. To test this, we inactivated mTORC1 and/or mTORC2 downstream of early Pten deletion in a new model of somatic Pten loss-of-function (LOF) in the cortex and hippocampus. Spontaneous seizures and epileptiform activity persisted despite mTORC1 or mTORC2 inactivation alone, but inactivating both mTORC1 and mTORC2 simultaneously normalized brain activity. These results suggest that hyperactivity of both mTORC1 and mTORC2 can cause epilepsy, and that targeted therapies should aim to reduce activity of both complexes.

The Effects of Repeated-Sprint Training on Physical Fitness and Physiological Adaptation in Athletes: A Systematic Review and Meta-Analysis.

BACKGROUND: Repeated-sprint training (RST) is a common training method for enhancing physical fitness in athletes. To advance RST prescription, it is important to understand the effects of programming variables on physical fitness and physiological adaptation. OBJECTIVES: This study (1) quantifies the pooled effects of running RST on changes in 10 and 20 m sprint time, maximal oxygen consumption (VO2max), Yo-Yo Intermittent Recovery Test Level 1 (YYIR1) distance, repeated-sprint ability (RSA), countermovement jump (CMJ) height and change of direction (COD) ability in athletes, and (2) examines the moderating effects of program duration, training frequency, weekly volume, sprint modality, repetition distance, number of repetitions per set and number of sets per session on changes in these outcome measures. METHODS: Pubmed, SPORTDiscus and Scopus databases were searched for original research articles up to 04 July 2023, investigating RST in healthy, able-bodied athletes, between 14 and 35 years of age, and a performance calibre of trained or above. RST interventions were limited to repeated, maximal running (land-based) sprints of ≤ 10 s duration, with ≤ 60 s recovery, performed for 2-12 weeks. A Downs and Black checklist was used to assess the methodological quality of the included studies. Eligible data were analysed using multi-level mixed-effects meta-analysis, with standardised mean changes determined for all outcomes. Standardised effects [Hedges G (G)] were evaluated based on coverage of their confidence (compatibility) intervals (CI) using a strength and conditioning specific reference value of G = 0.25 to declare an improvement (i.e. G > 0.25) or impairment (i.e. G < - 0.25) in outcome measures. Applying the same analysis, the effects of programming variables were then evaluated against a reference RST program, consisting of three sets of 6 × 30 m straight-line sprints performed twice per week for 6 weeks (1200 m weekly volume). RESULTS: 40 publications were included in our investigation, with data from 48 RST groups (541 athletes) and 19 active control groups (213 athletes). Across all studies, the effects of RST were compatible with improvements in VO2max (G 0.56, 90% CI 0.32-0.80), YYIR1 distance (G 0.61, 90% CI 0.43-0.79), RSA decrement (G - 0.61, 90% CI - 0.85 to - 0.37), linear sprint times (10 m: G - 0.35, 90% CI - 0.48 to - 0.22; 20 m: G - 0.48, 90% CI - 0.69 to - 0.27), RSA average time (G - 0.34, 90% CI - 0.49 to - 0.18), CMJ height (G 0.26, 90% CI 0.13-0.39) and COD ability (G - 0.32, 90% CI - 0.52 to - 0.12). Compared with the reference RST program, the effects of manipulating training frequency (+ 1 session per week), program duration (+ 1 extra training week), RST volume (+ 200 m per week), number of reps (+ 2 per set), number of sets per session (+ 1 set) or rep distance (+ 10 m per rep) were either non-substantial or comparable with an impairment in at least one outcome measure per programming variable. CONCLUSIONS: Running-based RST improves speed, intermittent running performance, VO2max, RSA, COD ability and CMJ height in trained athletes. Performing three sets of 6 × 30 m sprints, twice per week for 6 weeks is effective for enhancing physical fitness and physiological adaptation. Additionally, since our findings do not provide conclusive support for the manipulation of RST variables, further work is needed to better understand how programming factors can be manipulated to augment training-induced adaptations. STUDY REGISTRATION: Open Science Framework registration https://doi.org/10.17605/OSF.IO/RVNDW .

Heterozygous expression of a Kcnt1 gain-of-function variant has differential effects on SST- and PV-expressing cortical GABAergic neurons.

More than twenty recurrent missense gain-of-function (GOF) mutations have been identified in the sodium-activated potassium (KNa) channel gene KCNT1 in patients with severe developmental and epileptic encephalopathies (DEEs), most of which are resistant to current therapies. Defining the neuron types most vulnerable to KCNT1 GOF will advance our understanding of disease mechanisms and provide refined targets for precision therapy efforts. Here, we assessed the effects of heterozygous expression of a Kcnt1 GOF variant (Y777H) on KNa currents and neuronal physiology among cortical glutamatergic and GABAergic neurons in mice, including those expressing vasoactive intestinal polypeptide (VIP), somatostatin (SST), and parvalbumin (PV), to identify and model the pathogenic mechanisms of autosomal dominant KCNT1 GOF variants in DEEs. Although the Kcnt1-Y777H variant had no effects on glutamatergic or VIP neuron function, it increased subthreshold KNa currents in both SST and PV neurons but with opposite effects on neuronal output; SST neurons became hypoexcitable with a higher rheobase current and lower action potential (AP) firing frequency, whereas PV neurons became hyperexcitable with a lower rheobase current and higher AP firing frequency. Further neurophysiological and computational modeling experiments showed that the differential effects of the Y777H variant on SST and PV neurons are not likely due to inherent differences in these neuron types, but to an increased persistent sodium current in PV, but not SST, neurons. The Y777H variant also increased excitatory input onto, and chemical and electrical synaptic connectivity between, SST neurons. Together, these data suggest differential pathogenic mechanisms, both direct and compensatory, contribute to disease phenotypes, and provide a salient example of how a pathogenic ion channel variant can cause opposite functional effects in closely related neuron subtypes due to interactions with other ionic conductances.

Inconsistent Effect of Psychometric-Scale Familiarization on the Relationship Between Ratings of Perceived Exertion and External Load Measures in Elite Youth Soccer Players.

OBJECTIVES: To examine the moderating effect of familiarization on the relationship between external load and ratings of perceived exertion (RPEs) in elite youth soccer players. METHODS: Thirty-five elite male youth soccer players were monitored over a 31-week period. Players had no previous experience using the centiMax scale (arbitrary units [AU]). The final sample included familiarized (blackness test; n = 20) and nonfamiliarized players (n = 15) with the Borg centiMax scale. Players recorded a global RPE and differential RPEs (dRPE) for breathlessness (RPE-B) and leg-muscle exertion (RPE-L) 15 to 30 minutes following training sessions and competitive matches. Separate multivariable-adjusted random-effects generalized additive models with restricted maximum likelihood quantified familiarization versus no-familiarization differences in actual perceived exertion score (in AU) by number of accelerations, decelerations, and high-speed running distance (in meters) as predictor variables, respectively. RESULTS: Players improved their blackness test score from 39% to 78%. For explorations by number of accelerations, familiarization effects were not practically relevant for the RPE and RPE-B variables. The width and sign of the effects for the RPE-L variable at 30 efforts of 10 AU (95% CI, 4-16 AU) suggested that scores were lower for players who underwent familiarization versus players who did not. Familiarization effects were not practically relevant for any RPE variable irrespective of the number of deceleration efforts and high-speed running distance covered. CONCLUSION: Improved performance on the blackness test did not have a moderating effect on the relationship between proxy measures of external load and RPEs.

Distinct Features of Interictal Activity Predict Seizure Localization and Burden in a Mouse Model of Childhood Epilepsy.

The epileptic brain is distinguished by spontaneous seizures and interictal epileptiform discharges (IEDs). Basic patterns of mesoscale brain activity outside of seizures and IEDs are also frequently disrupted in the epileptic brain and likely influence disease symptoms, but are poorly understood. We aimed to quantify how interictal brain activity differs from that in healthy individuals, and identify what features of interictal activity influence seizure occurrence in a genetic mouse model of childhood epilepsy. Neural activity across the majority of the dorsal cortex was monitored with widefield Ca2+ imaging in mice of both sexes expressing a human Kcnt1 variant (Kcnt1m/m ) and wild-type controls (WT). Ca2+ signals during seizures and interictal periods were classified according to their spatiotemporal features. We identified 52 spontaneous seizures, which emerged and propagated within a consistent set of susceptible cortical areas, and were predicted by a concentration of total cortical activity within the emergence zone. Outside of seizures and IEDs, similar events were detected in Kcnt1m/m and WT mice, suggesting that the spatial structure of interictal activity is similar. However, the rate of events whose spatial profile overlapped with where seizures and IEDs emerged was increased, and the characteristic global intensity of cortical activity in individual Kcnt1m/m mice predicted their epileptic activity burden. This suggests that cortical areas with excessive interictal activity are vulnerable to seizures, but epilepsy is not an inevitable outcome. Global scaling of the intensity of cortical activity below levels found in the healthy brain may provide a natural mechanism of seizure protection.SIGNIFICANCE STATEMENT Defining the scope and structure of an epilepsy-causing gene variant's effects on mesoscale brain activity constitutes a major contribution to our understanding of how epileptic brains differ from healthy brains, and informs the development of precision epilepsy therapies. We provide a clear roadmap for measuring how severely brain activity deviates from normal, not only in pathologically active areas, but across large portions of the brain and outside of epileptic activity. This will indicate where and how activity needs to be modulated to holistically restore normal function. It also has the potential to reveal unintended off-target treatment effects and facilitate therapy optimization to deliver maximal benefit with minimal side-effect potential.

Quantifying Exposure and Intra-Individual Reliability of High-Speed and Sprint Running During Sided-Games Training in Soccer Players: A Systematic Review and Meta-analysis.

BACKGROUND: Sided games (i.e., small sided, medium sided, large sided) involve tactical, technical, physical, and psychological elements and are commonly implemented in soccer training. Although soccer sided-games research is plentiful, a meta-analytical synthesis of external load exposure during sided games is lacking. OBJECTIVE: The objective of this systematic review and meta-analysis was to: (1) synthesize the evidence on high-speed and sprint running exposure induced by sided games in adult soccer players, (2) establish pooled estimates and intra-individual reliability for high-speed and sprint running exposure, and (3) explore the moderating effects of game format and playing constraints. METHODS: A literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Four databases (PubMed/MEDLINE, Scopus, SPORTDiscus, Web of Science Core Collection) were systematically searched up to 25 January, 2022. Eligibility criteria were adult soccer players (population); training programs incorporating sided games (intervention); game manipulations including number of players, pitch dimension, and game orientation (comparator); and high-speed, very high-speed, and sprint relative (m[Formula: see text]min-1) running distances and associated intra-individual reliability (outcome). Eligible study risk of bias was evaluated using RoBANS. Pooled estimates for high-speed and sprint running exposure, and their intra-individual reliability, along with the moderating effect of tracking device running velocity thresholds, pitch dimension (i.e., area per player), and game orientation (i.e. score or possession), were determined via a multi-level mixed-effects meta-analysis. Estimate uncertainty is presented as 95% compatibility intervals (CIs) with the likely range of relative distances in similar future studies determined via 95% prediction intervals. RESULTS: A total of 104 and 7 studies met our eligibility criteria for the main and reliability analyses, respectively. The range of relative distances covered across small-sided games, medium-sided games, and large-sided games was 14.8 m[Formula: see text]min-1 (95% CI 12.3-17.4) to 17.2 m[Formula: see text]min-1 (95% CI 13.5-20.8) for high-speed running, 2.7 m[Formula: see text]min-1 (95% CI 1.8-3.5) to 3.6 m[Formula: see text]min-1 (95% CI 2.3-4.8) for very high-speed running, and 0.2 m[Formula: see text]min-1 (95% CI 0.1-0.4) to 0.7 m[Formula: see text]min-1 (95% CI 0.5-0.9) for sprinting. Across different game formats, 95% prediction intervals showed future exposure for high-speed, very high-speed running, and sprinting to be 0-46.5 m[Formula: see text]min-1, 0-14.2 m[Formula: see text]min-1, and 0-2.6 m[Formula: see text]min-1, respectively. High-speed, very high-speed running, and sprinting showed poor reliability with a pooled coefficient of variation of 22.8% with distances being moderated by device speed thresholds, pitch dimension, and game orientation. CONCLUSIONS: This review is the first to provide a detailed synthesis of exposure and intra-individual reliability of high-speed and sprint running during soccer sided games. Our estimates, along with the moderating influence of common programming variables such as velocity thresholds, area per player, and game orientation should be considered for informed planning of small-sided games, medium-sided games, and large-sided games soccer training. CLINICAL TRIAL REGISTRATION: Open Science Framework available through https://osf.io/a4xr2/ .

Influence of the COVID-19 pandemic on changes in aerobic fitness and injury incidence in elite male soccer players.

BACKGROUND: The SARS-CoV-2 agent initiated a global pandemic. The initial response to the pandemic was severe disruption to the public and private sector including sports. The resultant was that soccer clubs had to prescribe that the players trained in isolation for a prolonged period of time in an attempt to maintain fitness. The aim of the present study was to evaluate the impact of a 10-week period of training in isolation on aerobic fitness, body composition and injury incidence on the return to preseason team-training in a group of elite, male soccer players. METHODS: Twenty-two professional soccer players (age: 25.2±4.4 years) who played for an English Championship first team participated in this study. A weekly training program was sent to each player at the start of each week. Prior to the start of the isolated training period, all players underwent a maximal aerobic speed test (MAS), and Body Mass Index data (BMI) were obtained. These measurements were repeated on the return to team training. RESULTS: There was a significant (P<0.05) increase in MAS pre-post isolated training (pre: 4.71±0.15 vs. post: 4.92±0.17 m/s), no change in BMI (pre: 24.3±1.3 vs. post: 24.1±1.1 kg/m2) and a low non-contact, soft-tissue injury incidence on the return to team training. CONCLUSIONS: The evidence from this study suggests that a more prolonged preseason schedule can enhance aerobic conditioning and mitigate the injury risk on the return to competitive match-play in elite soccer players.

mTORC2 Inhibition Improves Morphological Effects of PTEN Loss, But Does Not Correct Synaptic Dysfunction or Prevent Seizures.

Hyperactivation of PI3K/PTEN-mTOR signaling during neural development is associated with focal cortical dysplasia (FCD), autism, and epilepsy. mTOR can signal through two major hubs, mTORC1 and mTORC2, both of which are hyperactive following PTEN loss of function (LOF). Here, we tested the hypothesis that genetic inactivation of the mTORC2 complex via deletion of Rictor is sufficient to rescue morphologic and electrophysiological abnormalities in the dentate gyrus caused by PTEN loss, as well as generalized seizures. An established, early postnatal mouse model of PTEN loss in male and female mice showed spontaneous seizures that were not prevented by mTORC2 inactivation. This lack of rescue occurred despite the normalization or amelioration of many morphologic and electrophysiological phenotypes. However, increased excitatory connectivity proximal to dentate gyrus granule neuron somas was not normalized by mTORC2 inactivation. Further studies demonstrated that, although mTORC2 inactivation largely rescued the dendritic arbor overgrowth caused by PTEN LOF, it increased synaptic strength and caused additional impairments of presynaptic function. These results suggest that a constrained increase in excitatory connectivity and co-occurring synaptic dysfunction is sufficient to generate seizures downstream of PTEN LOF, even in the absence of characteristic changes in morphologic properties.SIGNIFICANCE STATEMENT Homozygous deletion of the Pten gene in neuronal subpopulations in the mouse serves as a valuable model of epilepsy caused by mTOR hyperactivation. To better understand the physiological mechanisms downstream of Pten loss that cause epilepsy, as well as the therapeutic potential of targeted gene therapies, we tested whether genetic inactivation of the mTORC2 complex could improve the cellular, synaptic, and in vivo effects of Pten loss in the dentate gyrus. We found that mTORC2 inhibition improved or rescued all morphologic effects of Pten loss in the dentate gyrus, but synaptic changes and seizures persisted. These data suggest that synaptic dysfunction can drive epilepsy caused by hyperactivation of PI3K/PTEN-mTOR, and that future therapies should focus on this mechanistic link.

Symmetry-resolved CO desorption and oxidation dynamics on O/Ru(0001) probed at the C K-edge by ultrafast x-ray spectroscopy.

We report on carbon monoxide desorption and oxidation induced by 400 nm femtosecond laser excitation on the O/Ru(0001) surface probed by time-resolved x-ray absorption spectroscopy (TR-XAS) at the carbon K-edge. The experiments were performed under constant background pressures of CO (6 × 10-8 Torr) and O2 (3 × 10-8 Torr). Under these conditions, we detect two transient CO species with narrow 2π* peaks, suggesting little 2π* interaction with the surface. Based on polarization measurements, we find that these two species have opposing orientations: (1) CO favoring a more perpendicular orientation and (2) CO favoring a more parallel orientation with respect to the surface. We also directly detect gas-phase CO2 using a mass spectrometer and observe weak signatures of bent adsorbed CO2 at slightly higher x-ray energies than the 2π* region. These results are compared to previously reported TR-XAS results at the O K-edge, where the CO background pressure was three times lower (2 × 10-8 Torr) while maintaining the same O2 pressure. At the lower CO pressure, in the CO 2π* region, we observed adsorbed CO and a distribution of OC-O bond lengths close to the CO oxidation transition state, with little indication of gas-like CO. The shift toward "gas-like" CO species may be explained by the higher CO exposure, which blocks O adsorption, decreasing O coverage and increasing CO coverage. These effects decrease the CO desorption barrier through dipole-dipole interaction while simultaneously increasing the CO oxidation barrier.

Disruption of mTORC1 rescues neuronal overgrowth and synapse function dysregulated by Pten loss.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a negative regulator of AKT/mTOR signaling pathway. Mutations in PTEN are found in patients with autism, epilepsy, or macrocephaly. In mouse models, Pten loss results in neuronal hypertrophy, hyperexcitability, seizures, and ASD-like behaviors. The underlying molecular mechanisms of these phenotypes are not well delineated. We determined which of the Pten loss-driven aberrations in neuronal form and function are orchestrated by downstream mTOR complex 1 (mTORC1). Rapamycin-mediated inhibition of mTORC1 prevented increase in soma size, migration, spine density, and dendritic overgrowth in Pten knockout dentate gyrus granule neurons. Genetic knockout of Raptor to disrupt mTORC1 complex formation blocked Pten loss-mediated neuronal hypertrophy. Electrophysiological recordings revealed that genetic disruption of mTORC1 rescued Pten loss-mediated increase in excitatory synaptic transmission. We have identified an essential role for mTORC1 in orchestrating Pten loss-driven neuronal hypertrophy and synapse formation.

Inter-methodological quantification of the target change for performance test outcomes relevant to elite female soccer players.

INTRODUCTION: Valid and informed interpretations of changes in physical performance test data are important within athletic development programmes. At present, there is a lack of consensus regarding a suitable method for deeming whether a change in physical performance is practically relevant or not. METHODS: We compared true population variance in mean test scores between those derived from evidence synthesis of observational studies to those derived from practioner opinion (n = 30), and to those derived from a measurement error (minimal detectable change) quantification (n = 140). All these methods can help to obtain 'target' change score values for performance variables. RESULTS: We found that the conventional 'blanket' target change of 0.2 (between-subjects SD) systematically underestimated practically relevant and more informed changes derived for 5-m sprinting, 30-m sprinting, CMJ, and Yo-Yo Intermittent Recovery Level 1 (IR1) tests in elite female soccer players. CONCLUSIONS: For the first time in the field of sport and exercise sciences, we have illustrated the use of a principled approach for comparing different methods for the definition of changes in physical performance test variables that are practically relevant. Our between-method comparison approach provides preliminary guidance for arriving at target change values that may be useful for research purposes and tracking of individual female soccer player's physical performance.

Following the Crystallization of Amorphous Ice after Ultrafast Laser Heating.

Using time-resolved wide-angle X-ray scattering, we investigated the early stages (10 µs-1 ms) of crystallization of supercooled water, obtained by the ultrafast heating of high- and low-density amorphous ice (HDA and LDA) up to a temperature T = 205 K ± 10 K. We have determined that the crystallizing phase is stacking disordered ice (Isd), with a maximum cubicity of χ = 0.6, in agreement with predictions from molecular dynamics simulations at similar temperatures. However, we note that a growing small portion of hexagonal ice (Ih) was also observed, suggesting that within our timeframe, Isd starts annealing into Ih. The onset of crystallization, in both amorphous ice, occurs at a similar temperature, but the observed final crystalline fraction in the LDA sample is considerably lower than that in the HDA sample. We attribute this discrepancy to the thickness difference between the two samples.

Acute physiological and perceptual responses to a netball specific training session in professional female netball players.

The 24 h responses to professional female netball-specific training were examined. British Superleague players (n = 14) undertook a 90-min on-court training session incorporating key movement, technical, and scenario-specific match-play drills. Perceptual (mood, fatigue, soreness), neuromuscular (countermovement jump peak power output [PPO], PPO relative to mass [PPOrel], jump height [JH]), endocrine (salivary cortisol [C], testosterone [T] concentrations) and biochemical (creatine kinase concentrations [CK]) markers were assessed at baseline (immediately before; Pre), and immediately, two and 24 hours after (+0h, +2h, +24h) training. Session (sRPE) and differential (dRPE) ratings of perceived exertion were recorded at +0h. Identification of clear between time-point differences were based on the 95% confidence interval (CI) for mean differences relative to baseline values not overlapping. At +0h, C (raw unit mean difference from baseline; 95% CI: 0.16; 0.06 to 0.25 µg·dl-1), T (32; 20 to 45 pg⋅ml-1), CK (39; 28 to 50 u·L-1), PPOrel (2.4; 0.9 to 3.9 W·kg-1) and PPO (169; 52 to 286 W) increased. At +2h, fatigue (15; 7 to 24 AU), CK (49; 38 to 60 u·L-1), and soreness (14; 3 to 25 AU) increased, while T (-24; -37 to -11 pg⋅ml-1) and mood (-20; -27 to -12 AU) reduced. At +24h, CK increased (25; 13 to 36 u·L-1) whereas PPOrel (-1.6; -3.2 to -0.1 W·kg-1) and JH (-0.02; -0.03 to -0.08 m) reduced. Responses were variable specific, and recovery of all variables did not occur within 24h. The residual effects of the prior stimulus should be accounted for in the planning of training for professional female netball players.

Reference values for performance test outcomes relevant to English female soccer players.

The purpose of this study was to present reference standards for physical performance test outcomes relevant to elite female soccer players. We analysed mixed-longitudinal data (n = 1715 observations) from a sample of 479 elite youth and senior players as part of the English Football Association's national development programme (age range: 12.7 to 36.0 years). Semi-parametric generalized additive models for location, scale and shape (GAMLSS) estimated age-related reference centiles for 5-m sprinting, 30-m sprinting, countermovement jump (CMJ) height, and Yo-Yo Intermittent Recovery Test Level 1 (Yo-Yo IR1) performance. The estimated reference centiles indicated that the median of the distribution of physical performance test scores varied non-linearly with advancing chronological age, improving until around 25 years for each performance variable. These are the first reference ranges for performance test outcomes in elite English female soccer players. These data can assist practitioners when interpreting physical test performance outcomes to track an individual's progress over time and support decision-making regarding player recruitment and development.