Factorial validity and measurement invariance of the Athlete Burnout Questionnaire (ABQ).

The Athlete Burnout Questionnaire (ABQ) is the gold standard measure for burnout in athletes. However, previous assessments of factorial validity have: (a) tested overly restrictive measurement models; (b) provided mixed support for factorial validity; and (c) not been applied to assess measurement invariance across gender, sport type, or age. To address these issues, we used ABQ data provided by 914 athletes (Mage = 21.75 years, SD = 8.79) and examined factorial validity using confirmatory factor analysis (CFA) and exploratory structural equation modelling (ESEM) techniques. We also examined measurement invariance of the ABQ data across reported gender (female, male), sport type (individual, team), and age (≤18 years, >18 years) groups. The analyses revealed that an ESEM model provided superior fit over the corresponding CFA model. In terms of measurement invariance, support was provided for the equivalence of the ABQ across each group. This means that researchers using the ABQ can collect data across these groups and examine potential differences with confidence that the ABQ is approximately invariant. In all, we provide evidence that the majority of ABQ items are key target construct indicators and the burnout construct (as measured by the ABQ) has the same structure and meaning to different athlete groups.

UHRF1 ubiquitin ligase activity supports the maintenance of low-density CpG methylation.

The RING E3 ubiquitin ligase UHRF1 is an established cofactor for DNA methylation inheritance. Nucleosomal engagement through histone and DNA interactions directs UHRF1 ubiquitin ligase activity toward lysines on histone H3 tails, creating binding sites for DNMT1 through ubiquitin interacting motifs (UIM1 and UIM2). Here, we profile contributions of UHRF1 and DNMT1 to genome-wide DNA methylation inheritance and dissect specific roles for ubiquitin signaling in this process. We reveal DNA methylation maintenance at low-density CpGs is vulnerable to disruption of UHRF1 ubiquitin ligase activity and DNMT1 ubiquitin reading activity through UIM1. Hypomethylation of low-density CpGs in this manner induces formation of partially methylated domains (PMD), a methylation signature observed across human cancers. Furthermore, disrupting DNMT1 UIM2 function abolishes DNA methylation maintenance. Collectively, we show DNMT1-dependent DNA methylation inheritance is a ubiquitin-regulated process and suggest a disrupted UHRF1-DNMT1 ubiquitin signaling axis contributes to the development of PMDs in human cancers.

Molecular dynamics simulations provide insights into ULK-101 potency and selectivity toward autophagic kinases ULK1/2.

Kinase domains are highly conserved within protein kinases in both sequence and structure. Many factors, including phosphorylation, amino acid substitutions or mutations, and small molecule inhibitor binding, influence conformations of the kinase domain and enzymatic activity. The serine/threonine kinases ULK1 and ULK2 are highly conserved with N- and C-terminal domains, phosphate-binding P-loops, αC-helix, regulatory and catalytic spines, and activation loop DFG and APE motifs. Here, we performed molecular dynamics (MD) simulations to understand better the potency and selectivity of the ULK1/2 small molecule inhibitor, ULK-101. We observed stable bound states for ULK-101 to the adenosine triphosphate (ATP)-binding site of ULK2, coordinated by hydrogen bonding with the hinge backbone and the catalytic lysine sidechain. Notably, ULK-101 occupies a hydrophobic pocket associated with the N-terminus of the αC-helix. Large movements in the P-loop are also associated with ULK-101 inhibitor binding and exit from ULK2. Our data further suggests that ULK-101 could induce a folded P-loop conformation and hydrophobic pocket reflected in its nanomolar potency and kinome selectivity.

Don't look back in anger: A cross-sectional and dyadic examination of the Dark Triad, anger, and aggression in athletes.

OBJECTIVES: The Dark Triad (psychopathy, Machiavellianism, and narcissism) has been linked to anti-social behaviour in sport, and while anti-social behaviour often involves aggression and violence, no research to date has examined the relationship between the Dark Triad and anger and aggression in athletes. The current two-sample study sought to address this gap. DESIGN: Multi-sample cross-sectional design. METHOD: Sample 1 included 224 athletes (MAGE = 23.85) and Sample 2 included 98 coach-athlete dyads (196 total; athlete MAGE = 18.15, coaches MAGE = 34.84). In both samples, facets of the Dark Triad were related to anger and aggression. RESULTS: In Sample 1, regression analyses indicated that psychopathy positively predicted both anger and aggression and Machiavellianism positively predicted aggression. In Sample 2, actor-partner interdependence models indicated a combination of dyadic relationships (i.e., both actor [coach and athlete personality predicted their own anger and aggression] and partner effects [coach and athlete personality predicted the other's anger and aggression]). In this regard, actor effects were found between psychopathy and both anger and aggression and narcissism and aggression. Coach to athlete partner effects were found for narcissism and anger and Machiavellianism and aggression. CONCLUSIONS: Overall, the findings provide evidence for personal and interpersonal relationships between the Dark Triad and anger and aggression and highlight the potential for the darker side of both athlete and coach personality to influence athlete emotions.

Streamlined quantitative analysis of histone modification abundance at nucleosome-scale resolution with siQ-ChIP version 2.0.

We recently introduced an absolute and physical quantitative scale for chromatin immunoprecipitation followed by sequencing (ChIP-seq). The scale itself was determined directly from measurements routinely made on sequencing samples without additional reagents or spike-ins. We called this approach sans spike-in quantitative ChIP, or siQ-ChIP. Herein, we extend those results in several ways. First, we simplified the calculations defining the quantitative scale, reducing practitioner burden. Second, we reveal a normalization constraint implied by the quantitative scale and introduce a new scheme for generating 'tracks'. The constraint requires that tracks are probability distributions so that quantified ChIP-seq is analogous to a mass distribution. Third, we introduce some whole-genome analyses that allow us, for example, to project the IP mass (immunoprecipitated mass) onto the genome to evaluate how much of any genomic interval was captured in the IP. We applied siQ-ChIP to p300/CBP inhibition and compare our results to those of others. We detail how the same data-level observations are misinterpreted in the literature when tracks are not understood as probability densities and are compared without correct quantitative scaling, and we offer new interpretations of p300/CBP inhibition outcomes.

Membrane Protein Binding Interactions Studied in Live Cells via Diethylpyrocarbonate Covalent Labeling Mass Spectrometry.

Membrane proteins are vital in the human proteome for their cellular functions and make up a majority of drug targets in the U.S. However, characterizing their higher-order structures and interactions remains challenging. Most often membrane proteins are studied in artificial membranes, but such artificial systems do not fully account for the diversity of components present in cell membranes. In this study, we demonstrate that diethylpyrocarbonate (DEPC) covalent labeling mass spectrometry can provide binding site information for membrane proteins in living cells using membrane-bound tumor necrosis factor α (mTNFα) as a model system. Using three therapeutic monoclonal antibodies that bind TNFα, our results show that residues that are buried in the epitope upon antibody binding generally decrease in DEPC labeling extent. Additionally, serine, threonine, and tyrosine residues on the periphery of the epitope increase in labeling upon antibody binding because of a more hydrophobic microenvironment that is created. We also observe changes in labeling away from the epitope, indicating changes to the packing of the mTNFα homotrimer, compaction of the mTNFα trimer against the cell membrane, and/or previously uncharacterized allosteric changes upon antibody binding. Overall, DEPC-based covalent labeling mass spectrometry offers an effective means of characterizing structure and interactions of membrane proteins in living cells.

Analysis of histone antibody specificity directly in sequencing data using siQ-ChIP.

We previously developed sans spike-in quantitative chromatin immunoprecipitation sequencing (siQ-ChIP), a technique that introduces an absolute quantitative scale to ChIP-seq data without reliance on spike-in normalization approaches. The physical model of siQ-ChIP predicted that the IP step of ChIP would produce a classical binding isotherm when antibody or epitope was titrated. Here, we define experimental conditions in which this titration is observable for antibodies that recognize modified states of histone proteins. We show that minimally sequenced points along an isotherm can reveal differential binding specificities that are associated with on- and off-target epitope interactions. This work demonstrates that the interpretation of histone post-translational modification distribution from ChIP-seq data has a dependence on antibody concentration. Collectively, these studies introduce a simplified and reproducible experimental method to generate quantitative ChIP-seq data without spike-in normalization and demonstrate that histone antibody specificity can be analyzed directly in ChIP-seq experiments.

Psychometric properties of the Cystic Fibrosis Eating Attitudes and Behaviours scale (CFEAB) in an adult population.

OBJECTIVES: Individuals with Cystic Fibrosis (CF) may be at an increased risk of developing a range of eating difficulties. Scales designed to measure disordered eating in the general population do not cover CF-specific behaviours resulting in a knowledge gap. The CFEAB was developed as a CF-specific measure assessing eating behaviours and attitudes however little evidence exists regarding its psychometric quality. The aim of this cross-sectional study was to provide a robust assessment of its internal consistency, structural validity, and criterion validity. METHODS: One-hundred and thirty-two people with CF completed self-report scales pertaining to mental health, eating disorders, and the Cystic Fibrosis Eating Attitudes and Behaviours (CFEAB). RESULTS: Results of exploratory structural equation modelling indicated that a three-factor structure produced good fit with the 24-item CFEAB but a purified 12-item CFEAB displayed superior fit and internal consistency. Also, the 12-item scale predicted significant amounts of variance for anxiety, depression, and eating disorders showing enhanced relevance for clinical use. Conclusions These findings add emphasis to the importance of the validation and development of CF-specific measures and the possible inclusion at clinics to help improve CF patient care.

The complex, dynamic SpliceOme of the small GTPase transcripts altered by technique, sex, genetics, tissue specificity, and RNA base editing.

The small GTPase family is well-studied in cancer and cellular physiology. With 162 annotated human genes, the family has a broad expression throughout cells of the body. Members of the family have multiple exons that require splicing. Yet, the role of splicing within the family has been underexplored. We have studied the splicing dynamics of small GTPases throughout 41,671 samples by integrating Nanopore and Illumina sequencing techniques. Within this work, we have made several discoveries. 1). Using the GTEx long read data of 92 samples, each small GTPase gene averages two transcripts, with 83 genes (51%) expressing two or more isoforms. 2). Cross-tissue analysis of GTEx from 17,382 samples shows 41 genes (25%) expressing two or more protein-coding isoforms. These include protein-changing transcripts in genes such as RHOA, RAB37, RAB40C, RAB4B, RAB5C, RHOC, RAB1A, RAN, RHEB, RAC1, and KRAS. 3). The isolation and library technique of the RNAseq influences the abundance of non-sense-mediated decay and retained intron transcripts of small GTPases, which are observed more often in genes than appreciated. 4). Analysis of 16,243 samples of "Blood PAXgene" identified seven genes (3.7%; RHOA, RAB40C, RAB4B, RAB37, RAB5B, RAB5C, RHOC) with two or more transcripts expressed as the major isoform (75% of the total gene), suggesting a role of genetics in altering splicing. 5). Rare (ARL6, RAB23, ARL13B, HRAS, NRAS) and common variants (GEM, RHOC, MRAS, RAB5B, RERG, ARL16) can influence splicing and have an impact on phenotypes and diseases. 6). Multiple genes (RAB9A, RAP2C, ARL4A, RAB3A, RAB26, RAB3C, RASL10A, RAB40B, and HRAS) have sex differences in transcript expression. 7). Several exons are included or excluded for small GTPase genes (RASEF, KRAS, RAC1, RHEB, ARL4A, RHOA, RAB30, RHOBTB1, ARL16, RAP1A) in one or more forms of cancer. 8). Ten transcripts are altered in hypoxia (SAR1B, IFT27, ARL14, RAB11A, RAB10, RAB38, RAN, RIT1, RAB9A) with RHOA identified to have a transient 3'UTR RNA base editing at a conserved site found in all of its transcripts. Overall, we show a remarkable and dynamic role of splicing within the small GTPase family that requires future explorations.

Explaining individual differences in cognitive performance: The role of anxiety, social support and living arrangements during COVID-19.

The present study investigated the relationship between anxiety, social support, living arrangements and cognitive performance of university students during the global pandemic. Two hundred and fifteen students participated by completing online questionnaires. Separate moderated multiple regression models were used to test whether social support (Family, Friends, Significant Other subscales of the Multidimensional Scale of Perceived Social Support) moderated the relationship between anxiety (Anxiety subscale of Depression, Anxiety Stress Scale), living arrangements (Living Alone vs Living with Friends and Family) and cognitive performance (Cognitive Failures Questionnaire), after controlling for comorbid depression. The results for each level of perceived social support suggested that anxiety was negatively associated with cognitive performance. Our most significant finding was that for students living alone, social support from a significant other offered a protective factor, whereby buffering the anxiety related cognitive deficits prevalent in those who reported lower social support. These data have important practical implications for supporting the social-emotional and academic needs of university students during the global pandemic.

Chemical Biology Screening Identifies a Vulnerability to Checkpoint Kinase Inhibitors in TSC2-Deficient Renal Angiomyolipomas.

The tuberous sclerosis complex (TSC) is a rare genetic syndrome and multisystem disease resulting in tumor formation in major organs. A molecular hallmark of TSC is a dysregulation of the mammalian target of rapamycin (mTOR) through loss-of-function mutations in either tumor suppressor TSC1 or TSC2. Here, we sought to identify drug vulnerabilities conferred by TSC2 tumor-suppressor loss through cell-based chemical biology screening. Our small-molecule chemical screens reveal a sensitivity to inhibitors of checkpoint kinase 1/2 (CHK1/2), regulators of cell cycle, and DNA damage response, in both in vitro and in vivo models of TSC2-deficient renal angiomyolipoma (RA) tumors. Further, we performed transcriptional profiling on TSC2-deficient RA cell models and discovered that these recapitulate some of the features from TSC patient kidney tumors compared to normal kidneys. Taken together, our study provides a connection between mTOR-dependent tumor growth and CHK1/2, highlighting the importance of CHK1/2 inhibition as a potential antitumor strategy in TSC2-deficient tumors.

Influence of personality and emotional competences on academic performance: direct and indirect pathways mediated by perceived stress.

BACKGROUND: Among the factors influencing academic performance (AP), individual differences at the trait level such as personality and emotional competences (EC) have been found to play a critical role, similarly to state variables such as perceived stress (PS). Participants And Procedure: The aim of this study was to clarify whether the influence of personality (Big Five) and EC on AP (general point average) is direct and/or mediated via PS. 537 undergraduate students from a French university (112 male and 425 female, Mage = 19.84 years, SDage = 1.74 years, range = 18-30 years; first year: n = 293, 55%; second year: n = 162, 30%, third year: n = 82, 15%) filled out the test battery around three weeks before the final examination. RESULTS: Path analysis showed that AP was directly predicted by conscientiousness (+), neuroticism (+), extraversion (-) and perceived stress (-), while perceived stress was predicted by neuroticism (+) and by intrapersonal EC (-). CONCLUSIONS: The results illustrate the robust influence of conscientiousness on AP, while EC was not found to influence AP directly, but indirectly via its effect on PS.

A trivalent nucleosome interaction by PHIP/BRWD2 is disrupted in neurodevelopmental disorders and cancer.

Mutations in the PHIP/BRWD2 chromatin regulator cause the human neurodevelopmental disorder Chung-Jansen syndrome, while alterations in PHIP expression are linked to cancer. Precisely how PHIP functions in these contexts is not fully understood. Here we demonstrate that PHIP is a chromatin-associated CRL4 ubiquitin ligase substrate receptor and is required for CRL4 recruitment to chromatin. PHIP binds to chromatin through a trivalent reader domain consisting of a H3K4-methyl binding Tudor domain and two bromodomains (BD1 and BD2). Using semisynthetic nucleosomes with defined histone post-translational modifications, we characterize PHIPs BD1 and BD2 as respective readers of H3K14ac and H4K12ac, and identify human disease-associated mutations in each domain and the intervening linker region that likely disrupt chromatin binding. These findings provide new insight into the biological function of this enigmatic chromatin protein and set the stage for the identification of both upstream chromatin modifiers and downstream targets of PHIP in human disease.

Emotional Intelligence Training: Influence of a Brief Slow-Paced Breathing Exercise on Psychophysiological Variables Linked to Emotion Regulation.

Designing emotional intelligence training programs requires first testing the effectiveness of techniques targeting its main dimensions. The aim of this study was to investigate the effects of a brief slow-paced breathing (SPB) exercise on psychophysiological variables linked to emotion regulation, namely cardiac vagal activity (CVA), as well as perceived stress intensity, emotional arousal, and emotional valence. A total of 61 participants completed a 5-min SPB exercise and a control condition of a 5-min rest measurement. CVA was indexed with the root mean square of successive differences (RMSSD). Participants were also asked to rate their perceived stress intensity, emotional arousal, and emotional valence. Results showed that CVA was higher during SPB in comparison to the control condition. Contrary to our hypothesis, perceived stress intensity and emotional arousal increased after SPB, and perceived emotional valence was less positive after SPB. This could be explained by experiencing dyspnea (i.e., breathing discomfort), and the need to get acclimatized to SPB. Consequently, we may conclude that although physiological benefits of SPB on CVA are immediate, training may be required in order to perceive psychological benefits.

Executive Function and Mood: The Moderating Role of Athletic Expertise.

Executive function (EF) is known to be influenced by mood, but whether this relationship holds for populations of athletes and whether athletic expertise moderates it is uncertain. Thus, in the current study, we examined relationships between positive and negative affect (i.e., mood), the lower-order cortical aspects of executive function (i.e., inhibition, shifting and updating), and athletic expertise. A sample of 256 participants (55.08% male; Mage = 20.69) completed a self-report mood measure and computerized tests of EF. Individuals with more athletic expertise reported higher positive affect and better EF scores, whereas those with less athletic expertise reported higher negative affect. Structural equation modelling indicated that positive affect was related to better inhibition, shifting, and updating performance but was not related to performance errors. Similarly, negative affect was related to better EF, except for the inhibition latency score. Athletic expertise moderated all significant associations between mood and EF and higher expertise facilitated higher EF performance. Together, athletic expertise is an important individual differences factor in understanding the influence of mood on EF performance.

Inhibitory Control Across Athletic Expertise and Its Relationship With Sport Performance.

Inhibitory control may be vital in elite sport. The authors examined the link between athletic expertise, inhibitory control, and sport performance in a two-part quasi experiment. Inhibitory control was indexed using the Stop-Signal Task, athlete expertise was categorized on literary recommendations, and sport performance was assessed using athlete and coach ratings. Study 1 examined cross-sectional and longitudinal patterns of inhibitory control across athletic expertise. Study 2 investigated whether the inhibitory control-sport performance relationship was moderated by expertise. Study 1 showed that expertise was linked to greater inhibitory control cross-sectionally and longitudinally. Study 2 revealed that expertise was related to superior performance on the Stop-Signal Task and athlete and coach performance ratings, and this relationship was moderated by athletic expertise. Inhibitory control relates to sport performance, increases with greater athlete expertise, and develops longitudinally. Long-term participation in sport may bring about changes in inhibitory control, which may lead to improved sport performance.

The winner takes it all: The mediating role of competitive orientations in the Dark Triad and sport task performance relationship.

The Dark Triad traits (Machiavellianism, narcissism, and psychopathy) are prevalent in athletes. However, currently, we do not know whether the Dark Triad confers any competitive advantages in sport. To address this issue, the present study had two aims. First, to examine whether the Dark Triad predicted task performance in a basketball free throw task. Second, to examine whether competitive orientations explained (i.e. mediated) this relationship. A sample of 189 athletes (mean age = 19.11 years) completed measures of the Dark Triad, competitive orientations, and task performance (basketball free throw task). Regression analyses indicated that the Dark Triad predicted better task performance. In addition, mediation analyses indicated that the Dark Triad-performance relationship was explained by both hypercompetitive and self-developmental competitive orientations. The present study provides the first evidence that the Dark Triad may lead to better task performance in sport, and that this effect may be driven by athletes' competitive orientations.

Hitchhiking: Associations With Big Five and Emotional Competences.

After a decrease in its practice, the interest in hitchhiking is currently renewed. However, so far, very little is known about the personality characteristics of hitchhikers. Consequently, the aim of this study was to investigate the associations between hitchhiking and personality traits, with the Big Five and emotional competences. Five hundred and seventy-eight travellers (452 hitchhikers, Mage = 28.4 years old; and 126 non-hitchhikers, Mage = 27.7 years old) took part in the study. Participants completed an online survey including hitchhiking behaviour, the Big Five Inventory, and the Profile for Emotional Competences. After controlling for sociodemographic factors, hitchhiking was found to be positively associated with openness, and negatively associated with neuroticism. No associations were found with emotional competences. These findings improve our understanding of the personality characteristics associated with hitchhiking, however longitudinal studies are required to understand how hitchhiking is related to personality.

Attention, working-memory control, working-memory capacity, and sport performance: The moderating role of athletic expertise.

The aim of this research was to detangle the association between attention, working-memory (focusing on both control and capacity functions), and sport performance across athletic expertise. Specifically, the mediating effect of working-memory-control and working-memory-capacity on the attention and performance relationship will be investigated, and whether this effect differs across athlete expertise. A sample of 359 athletes (Mage = 18.91 ± SD = 1.01; 54.87% male) with a range of athletic expertise (novice n = 99, amateur n = 92, elite n = 87, and super-elite n = 81) completed a battery of neurocognitive tasks assessing attention, working-memory-control, working-memory-capacity, and a cognitively engaging motor task (e.g. basketball free-throw task). Athletes with more expertise performed better on tasks of attention, working-memory-control and working-memory-capacity. Results of structural equation modelling indicated a positive association between the cognitive measures and sport performance. Specifically, working-memory-control and working-memory-capacity mediated the attention and sport performance relationship. Additionally, invariance testing indicated larger effects for those with more athletic expertise. These findings provide a better understanding of how attention and the control and capacity functions of working-memory interact to predict performance. Theoretical and practical implications of these results are discussed.

Reflection-impulsivity in athletes: A cross-sectional and longitudinal investigation.

Reflection-impulsivity is a dimension of cognitive or decision-making style. We conducted two quasi-experimental studies to examine reflection-impulsivity in athletes using an information sampling task. In Study 1 (n = 108; Mage = 22.7 ± SDage = 1.42; 50% female), we used a cross-sectional design to compare performance across athletic expertise (super-elite, elite, amateur, novice or non-athlete) and sport type (external-paced or self-paced). In Study 2 (Time 1 n = 106; Mage = 21.32 ± SDage = 5.77; 53% female and Time 2 n = 64; Mage = 21.19 ± SDage = 5.12; 44% female), we examined changes in reflection-impulsivity across a 16-week playing season. Study 1 showed more accurate and more efficient performance as athletic expertise increased. Study 2 revealed better effectiveness and efficiency following sport participation, a 16-week playing season, most notably in elite-level performers. No sport-type differences were noted. Taken together, the studies demonstrate an association between reflection-impulsivity and athletic expertise, while also providing evidence that competitive sports participation leads to efficient decisions based on reflection, without sacrificing accuracy, which is often a consequence of impulsive decision-making.