Kevlar: A Mapping-Free Framework for Accurate Discovery of De Novo Variants.

De novo genetic variants are an important source of causative variation in complex genetic disorders. Many methods for variant discovery rely on mapping reads to a reference genome, detecting numerous inherited variants irrelevant to the phenotype of interest. To distinguish between inherited and de novo variation, sequencing of families (parents and siblings) is commonly pursued. However, standard mapping-based approaches tend to have a high false-discovery rate for de novo variant prediction. Kevlar is a mapping-free method for de novo variant discovery, based on direct comparison of sequences between related individuals. Kevlar identifies high-abundance k-mers unique to the individual of interest. Reads containing these k-mers are partitioned into disjoint sets by shared k-mer content for variant calling, and preliminary variant predictions are sorted using a probabilistic score. We evaluated Kevlar on simulated and real datasets, demonstrating its ability to detect both de novo single-nucleotide variants and indels with high accuracy

A Longitudinal Examination of Thriving in Sport Performers

To sustain success in sport, athletes need to function effectively in their competitive encounters and maintain this level over repeated events. Yet, to date, little is known about how athletes can continue to fully function (i.e., thrive) in their sporting encounters. Equally, there is a lack of research in relation to the factors that predict thriving. Testing the premise that basic psychological needs (i.e., for autonomy, competence, and relatedness) predict optimal functioning, the aim of this study was to provide the first longitudinal examination of thriving in sport. Sport performers (N = 268) completed questionnaires assessing thriving and basic psychological need satisfaction on three occasions across 28 days. Longitudinal structural equation modeling showed thriving to be highly predicted by both the experience of recent thriving and the perceived satisfaction of basic psychological needs. These findings highlight an important mechanism through which coaches and practitioners can initiate and maintain thriving in the athletes that they work with across a series of sporting encounters

The prediction of thriving in elite sport:A prospective examination of the role of psychological need satisfaction, challenge appraisal, and salivary biomarkers

ObjectivesTo examine (i) whether levels of, and changes in, athletes’ basic psychological need satisfaction (BPNS) and challenge appraisals predicted in-match thriving; and (ii) if salivary biomarkers could be defined that were related to thriving.DesignProspective study design.MethodsFifty-one elite male hockey players ( M age = 24.94 years, SD age = 4.73) completed questionnaires measuring their BPNS and challenge appraisals on seven consecutive days prior to a competitive match, as well as providing saliva samples immediately on waking, and then +0.5, +3, and +5.25 h on the day of the match. Saliva was assayed for catabolic (i.e., cortisol) and anabolic (i.e., dehydroepiandrosterone [DHEA]) hormones. In-match thriving was assessed retrospectively using measures of subjective performance and well-being.ResultsLatent growth curve modelling showed pre-match levels of BPNS and challenge appraisals to positively predict thriving. Although not statistically significant, small and moderate negative associations were found for thriving with cortisol concentration (+5.25 h sample) and total cortisol exposure across the morning of the match, respectively. DHEA concentration shared a small positive, yet non-significant, association with thriving.ConclusionsAthletes’ pre-match levels of BPNS and challenge appraisal predict in-match thriving; thus, offering potential mechanisms through which both high-level performance and the experience of well-being can be facilitated. Furthermore, associations suggest that total cortisol exposure across the morning of the match, and cortisol and DHEA levels in pre-match samples may offer sport science and sports medicine practitioners potential biomarkers for thriving. Future research is required to substantiate this initial finding.<br/

TAL Effector-Nucleotide Targeter (TALE-NT) 2.0: tools for TAL effector design and target prediction

Transcription activator-like (TAL) effectors are repeat-containing proteins used by plant pathogenic bacteria to manipulate host gene expression. Repeats are polymorphic and individually specify single nucleotides in the DNA target, with some degeneracy. A TAL effector-nucleotide binding code that links repeat type to specified nucleotide enables prediction of genomic binding sites for TAL effectors and customization of TAL effectors for use in DNA targeting, in particular as custom transcription factors for engineered gene regulation and as site-specific nucleases for genome editing. We have developed a suite of web-based tools called TAL Effector-Nucleotide Targeter 2.0 (TALE-NT 2.0; https://boglab.plp.iastate.edu/) that enables design of custom TAL effector repeat arrays for desired targets and prediction of TAL effector binding sites, ranked by likelihood, in a genome, promoterome or other sequence of interest. Search parameters can be set by the user to work with any TAL effector or TAL effector nuclease architecture. Applications range from designing highly specific DNA targeting tools and identifying potential off-target sites to predicting effector targets important in plant disease

PPARα contributes to protection against metabolic and inflammatory derangements associated with acute kidney injury in experimental sepsis

Abstract Sepsis‐associated acute kidney injury (AKI) is a significant problem in critically ill children and adults resulting in increased morbidity and mortality. Fundamental mechanisms contributing to sepsis‐associated AKI are poorly understood. Previous research has demonstrated that peroxisome proliferator‐activated receptor α (PPARα) expression is associated with reduced organ system failure in sepsis. Using an experimental model of polymicrobial sepsis, we demonstrate that mice deficient in PPARα have worse kidney function, which is likely related to reduced fatty acid oxidation and increased inflammation. Ultrastructural evaluation with electron microscopy reveals that the proximal convoluted tubule is specifically injured in septic PPARα deficient mice. In this experimental group, serum metabolomic analysis reveals unanticipated metabolic derangements in tryptophan‐kynurenine‐NAD+ and pantothenate pathways. We also show that a subgroup of children with sepsis whose genome‐wide expression profiles are characterized by repression of the PPARα signaling pathway has increased incidence of severe AKI. These findings point toward interesting associations between sepsis‐associated AKI and PPARα‐driven fatty acid metabolism that merit further investigation

Human thriving: A conceptual debate and literature review

Abstract. Human beings have an inherent drive for self-improvement and growth ( Maslow, 1965 ; Ryan &amp; Deci, 2002 ). In a quest to understand how human beings achieve fulfillment, researchers have sought to explain why some individuals thrive in certain situations, whereas others merely survive or succumb. The topic of thriving has become popular with scholars, resulting in a divergent body of literature and a lack of consensus on the key processes that underpin the construct. In view of such differences, the purpose of this paper is threefold: (i) to review a number of existing theoretical and conceptual debates, and to propose a conceptualization of thriving applicable across different populations and domains; (ii) to consolidate pertinent bodies of extant thriving research and identify key personal and contextual enablers to inform applied practice; and (iii) to identify noteworthy gaps within existing literature so as to make recommendations for future research and, ultimately, support the development of effective psychosocial interventions for thriving.</jats:p

Thriving on Pressure:A Factor Mixture Analysis of Sport Performers’ Responses to Competitive Encounters

Although considerable research exists on performers’ responses to sporting encounters, little is known about thriving in sport contexts. The current study examined if distinct response patterns existed between sport performers who thrived in competitive encounters compared with those who did not. Participants were 535 sport performers (134 women; Mage = 23.60 years, SDage = 8.08; Mcompeting = 11.84 years, SDcompeting = 7.11). Results of factor mixture analysis supported a four-profile solution comprising a thriving group (n = 146), a low-functioning group (n = 38), and two groups characterized by scores marginally above (n = 131) and below (n = 209) the sample mean. Profile membership was found to be predicted by personal enablers (viz., personal resilient qualities, psychological skills use) and process variables (viz., basic psychological need satisfaction and frustration, challenge appraisal). This examination of thriving in sport performers offers significant implications for research and practice.</jats:p

Measuring psychological need states in sport: Theoretical considerations and a new measure

© 2019 Elsevier Ltd Objectives: Research guided by Self-determination Theory (Deci & Ryan, 1985; Ryan & Deci, 2017) has repeatedly demonstrated the importance of focusing on both the bright (satisfaction) and dark (frustration) sides of the three basic psychological needs. Recently, researchers have also argued for the utility of assessing a third need state, that of “unfulfillment”. In this paper, we outline an effort to develop and provide initial validity evidence for scores of a new multidimensional and sport-specific measure, the Psychological Need States in Sport-Scale (PNSS-S), to assess the satisfaction, frustration, and unfulfillment of all three needs. Method: In Study 1, we developed 46 candidate items, and tested evidence for the factorial structure of the responses to the newly developed items, internal consistency and discriminant validity of the subscale scores. Following refinement, the replication of the favored model was tested using an independent sample of athletes in Study 2. Evidence for the nomological network of the subscales of the new measure was also demonstrated in Study 2. Results: Factor models incorporating all three need states showed poor fit with the data. However, following post-hoc modifications, a six-factor model assessing the need states of satisfaction and frustration, separately for autonomy, competence, and relatedness, was found to have good fit to the data. After refinement, the 29-item six-factor model was found to demonstrate good fit, good standardized factor loadings, factor correlations in the expected directions, and acceptable estimates of internal consistency in Study 2. Tests of nomological networks showed that the six need states were significantly predicted by contextual autonomy, competence, and relatedness support/thwarts as expected. Autonomy and competence need satisfaction were significantly associated with engagement; and competence and relatedness need satisfaction were significantly associated with positive affect. In addition, autonomy and competence need frustration were significantly associated with exhaustion and all three need frustration states significantly predicted negative affect. Conclusions: A tripartite conceptualization of the need states was not empirically supported. Nevertheless, the PNSS-S makes a unique contribution to the sport literature, as it represents the first sport-specific measure of six distinct, yet, correlated states of the satisfaction and frustration of autonomy, competence, and relatedness needs

Inclusive jet cross sections and dijet correlations in D∗±D^{*\pm} photoproduction at HERA

Inclusive jet cross sections in photoproduction for events containing a $D^*$ meson have been measured with the ZEUS detector at HERA using an integrated luminosity of $78.6 {\rm pb}^{-1}$. The events were required to have a virtuality of the incoming photon, $Q^2$, of less than 1 GeV$^2$, and a photon-proton centre-of-mass energy in the range $130<W_{\gamma p}<280 {\rm GeV}$. The measurements are compared with next-to-leading-order (NLO) QCD calculations. Good agreement is found with the NLO calculations over most of the measured kinematic region. Requiring a second jet in the event allowed a more detailed comparison with QCD calculations. The measured dijet cross sections are also compared to Monte Carlo (MC) models which incorporate leading-order matrix elements followed by parton showers and hadronisation. The NLO QCD predictions are in general agreement with the data although differences have been isolated to regions where contributions from higher orders are expected to be significant. The MC models give a better description than the NLO predictions of the shape of the measured cross sections.Comment: 43 pages, 12 figures, charm jets ZEU