Enhanced Sensorimotor Kinematics of the Baseball Swing in Elite Batters During a Known Pitch Type

The interceptive task of hitting a baseball requires temporal and spatial precision through effective pitch tracking strategies and swing mechanics to achieve success. Overall, these factors dictate the quality of the contact and therefore successful performance of the task. The permitted response time for a batter to visually react and analyze the trajectory of the ball, produce the movement of the swing, and create quality contact is a fraction of a second. In this study, temporal analysis and the measurement of sensorimotor factors indicative of skill was completed in different pitch conditions to understand the changes that occur as a result of whether the pitch type is known. Additionally, correlations between sensory and motor kinematics of the baseball swing were examined. Sixteen participants were divided in to two subgroups based on their highest level of baseball experience. The sub-elite group consisted of individuals whose highest level of playing experience was at the high school varsity level, while the elite group included collegiate players up to the NCAA Division I level. Utilizing live pitching in an indoor batting facility, a 12-camera motion capture system, and eye tracking glasses, each subject completed 20 totals trials across a known fastball, known curveball, and unknown mixed conditions. For the fastball trials only, pelvis rotation and angular velocities along with the load phase, load-release difference, land phase, launch phase, and swing duration were measured and represent the motor variables while head and eye rotation and average angular velocity represent the sensory variables measured. Results demonstrated significant differences in head rotation, average head angular velocity, pelvis rotation, and load-release difference between the known and unknown conditions, significant differences in the load phase, land phase, and total swing durations, as well as the load-release difference between elite and sub-elite batters, along with a significant interaction between skill level and pelvis rotation for pitch condition (p < 0.05). Additionally, relationships were found between eye and head rotation with pelvis and swing phase kinematics for both the elite and sub-elite groups (p < 0.05). Overall, understanding the kinematic differences between pitch conditions and skill level can lead to more effective training strategies to enhance performance

In Vivo Fluorescent Detection of Fe-S Clusters Coordinated by Human GRX2

A major challenge to studying Fe-S cluster biosynthesis in higher eukaryotes is the lack of simple tools for imaging metallocluster binding to proteins. We describe the first fluorescent approach for in vivo detection of 2Fe2S clusters that is based upon the complementation of Venus fluorescent protein fragments via human glutaredoxin 2 (GRX2) coordination of a 2Fe2S cluster. We show that Escherichia coli and mammalian cells expressing Venus fragments fused to GRX2 exhibit greater fluorescence than cells expressing fragments fused to a C37A mutant that cannot coordinate a metallocluster. In addition, we find that maximal fluorescence in the cytosol of mammalian cells requires the iron-sulfur cluster assembly proteins ISCU and NFS1. These findings provide evidence that glutaredoxins can dimerize within mammalian cells through coordination of a 2Fe2S cluster as observed with purified recombinant proteins

Hsp70 chaperones: Cellular functions and molecular mechanism

Hsp70 proteins are central components of the cellular network of molecular chaperones and folding catalysts. They assist a large variety of protein folding processes in the cell by transient association of their substrate binding domain with short hydrophobic peptide segments within their substrate proteins. The substrate binding and release cycle is driven by the switching of Hsp70 between the low-affinity ATP bound state and the high-affinity ADP bound state. Thus, ATP binding and hydrolysis are essential in vitro and in vivo for the chaperone activity of Hsp70 proteins. This ATPase cycle is controlled by co-chaperones of the family of J-domain proteins, which target Hsp70s to their substrates, and by nucleotide exchange factors, which determine the lifetime of the Hsp70-substrate complex. Additional co-chaperones fine-tune this chaperone cycle. For specific tasks the Hsp70 cycle is coupled to the action of other chaperones, such as Hsp90 and Hsp100

A large-scale genome-wide association study meta-analysis of cannabis use disorder

Summary Background Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10−9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10−9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10−21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.Peer reviewe

A large-scale genome-wide association study meta-analysis of cannabis use disorder

Background: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50-70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07-1·15, p=1·84 × 10-9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86-0·93, p=6·46 × 10-9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10-21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder

Enhanced Sensorimotor Kinematics of the Baseball Swing in Elite Batters During a Known Pitch Type

The interceptive task of hitting a baseball requires temporal and spatial precision through effective pitch tracking strategies and swing mechanics to achieve success. Overall , these factors dictate the quality of the contact and therefore successful performance of the task. The permitted response time for a batter to visually react and analyze the trajectory of the ball , produce the movement of the swing , and create quality contact is a fraction of a second. In this study , temporal analysis and the measurement of sensorimotor factors indicative of skill was completed in different pitch conditions to understand the changes that occur as a result of whether the pitch type is known. Additionally , correlations between sensory and motor kinematics of the baseball swing were examined. Sixteen participants were divided in to two subgroups based on their highest level of baseball experience. The sub-elite group consisted of individuals whose highest level of playing experience was at the high school varsity level , while the elite group included collegiate players up to the NCAA Division I level. Utilizing live pitching in an indoor batting facility , a 12-camera motion capture system , and eye tracking glasses , each subject completed 20 totals trials across a known fastball , known curveball , and unknown mixed conditions. For the fastball trials only , pelvis rotation and angular velocities along with the load phase , load-release difference , land phase , launch phase , and swing duration were measured and represent the motor variables while head and eye rotation and average angular velocity represent the sensory variables measured. Results demonstrated significant differences in head rotation , average head angular velocity , pelvis rotation , and load-release difference between the known and unknown conditions , significant differences in the load phase , land phase , and total swing durations , as well as the load-release difference between elite and sub-elite batters , along with a significant interaction between skill level and pelvis rotation for pitch condition (p &lt; 0.05). Additionally , relationships were found between eye and head rotation with pelvis and swing phase kinematics for both the elite and sub-elite groups (p &lt; 0.05). Overall , understanding the kinematic differences between pitch conditions and skill level can lead to more effective training strategies to enhance performance