Reductive activation and structural rearrangement in superoxide reductase: a combined infrared spectroscopic and computational study

Superoxide reductases (SOR) are a family of non-heme iron enzymes that limit oxidative stress by catalysing the reduction of superoxide to hydrogen peroxide and, thus, represent model systems for the detoxification of reactive oxygen species. In several enzymes of this type, reductive activation of the active site involves the reversible dissociation of a glutamate from the proposed substrate binding site at the iron. In this study we have employed IR spectroscopic and theoretical methods to gain insights into redox-linked structural changes of 1Fe-type superoxide reductases, focusing on the enzyme from the archaeon Ignicoccus hospitalis. Guided by crystal structure data and complemented by spectra calculation for an active site model, the main IR difference signals could be assigned. These signals reflect redox-induced structural changes in the first coordination sphere of the iron centre, adjacent loop and helical regions, and more remote β-sheets. By comparison with the spectra obtained for the E23A mutant of Ignicoccus hospitalis SOR, it is shown that glutamate E23 dissociates reversibly from the ferrous iron during reductive activation of the wild type enzyme. Moreover, this process is found to trigger a global conformational transition of the protein that is strictly dependent on the presence of E23. Similar concerted structural changes can be inferred from the IR spectra of related SORs such as that from Archaeoglobus fulgidus, indicating a widespread mechanism. A possible functional role of this process in terms of synergistic effects during reductive activation of the homotetrameric enzyme is proposed.DFG, EXC 314, Unifying Concepts in Catalysi

A Skill Acquisition Perspective on the Impact of Exergaming Technology on Foundational Movement Skill Development in Children 3–12 Years: A Systematic Review and Meta-analysis

Background: Sedentary, digital screen time in children represents a major concern due to its detrimental effect on children’s development. Nowadays, however, advances in technology allow children to actively interact with a digital screen using their whole body (e.g., exergaming), providing potential for movement learning. Exergaming technology may prove valuable in supporting children’s development of foundational movement skills (FMS). Objective: To examine the impact of exergaming technology on the development of FMS in children 3–12 years through a skill acquisition lens. Methods: Systematic review and meta-analysis were conducted following the PRISMA guidelines. Web of Science, PubMed, PsycINFO and SPORTDiscus databases were searched between 2007 and 2022. Studies were eligible if they conducted an exergaming intervention to improve FMS in typically developing children aged three to twelve with a control group, using a baseline and post-intervention assessment design. FMS outcomes were pooled with a random effects model. Results: Nine trials (4 RCTs, 2 cluster RCTs and 3 non-randomized trials) of varying methodological quality (2 had low, 6 had some concerns, and 1 had a high risk of bias) were included, with a total of 783 participants. FMS outcome measures across studies comprised object control skills, locomotor skills, coordination, agility, balance and balance-related skills. The meta-analysis included showed a small positive effect in favor of the exergaming intervention  = 0.24 [95% confidence interval: 0.11–0.36]). Conclusion: Our results indicate that screen-based technology that requires an active engagement of the child can promote the development of FMS. Considering that FMS are the foundation of a child’s physical, mental, health and academic development, this finding could lead to a reshaping of the perception of digital screen-based technology and the role this should play in children’s lives. We speculate that the observed benefits most likely depend upon the quality of information–movement coupling specificity and the motor learning strategies built into the exergame and/or the intervention design. We do not believe this is dependent on the type of FMS being performed or the amount of practice. We recommend therefore that future research should examine how practitioners (school teachers, coaches and parents) can facilitate the interaction between a child and exergaming technology

Effect of Linear and Nonlinear Pedagogy Physical Education Interventions on Children’s Physical Activity: A Cluster Randomized Controlled Trial (SAMPLE-PE)

Background: School-based interventions are a key opportunity to improve children’s physical activity (PA); however, there is lack of evidence about how pedagogical approaches to motor learning in physical education (PE) might affect PA in children. Therefore, this study aimed to assess how different pedagogical approaches in PE might affect children’s PA. Methods: Participants (n = 360, 5–6 years) from 12 primary schools within the SAMPLE-PE randomized controlled trial were randomly allocated to either Linear Pedagogy (LP: n = 3) or Nonlinear Pedagogy (NP: n = 3) interventions, where schools received a 15-week PE intervention delivered by trained coaches, or to a control group (n = 6), where schools followed usual practice. ActiGraph GT9X accelerometers were used to assess PA metrics (moderate-to-vigorous PA, mean raw acceleration and lowest acceleration over the most active hour and half hour) over whole and segmented weeks at baseline, immediately post-intervention and 6 months follow-up. Intention to treat analysis employing multilevel modelling was used to assess intervention effects. Results: LP and NP interventions did not significantly affect children’s PA levels compared to the control group. Conclusion: PE interventions based on LP and NP alone might not be effective in improving habitual PA in children

Foundational Movement Skills and Play Behaviors during Recess among Preschool Children: A Compositional Analysis

This study aimed to examine the associations between play behaviors during preschool recess and foundational movement skills (FMS) in typically developing preschool children. One hundred and thirty-three children (55% male; mean age 4.7 ± 0.5 years) from twelve preschools were video-assessed for six locomotor and six object-control FMS using the Champs Motor Skill Protocol. A modified System for Observing Children’s Activity and Relationships during Play assessed play behaviors during preschool recess. Associations between the composition of recess play behaviors with FMS were analyzed using compositional data analysis and linear regression. Results: Relative to time spent in other types of play behaviors, time spent in play without equipment was positively associated with total and locomotor skills, while time spent in locomotion activities was negatively associated with total and locomotor skills. No associations were found between activity level and group size play behavior compositions and FMS. The findings suggest that activity type play behaviors during recess are associated with FMS. While active games without equipment appear beneficial, preschool children may need a richer playground environment, including varied fixed and portable equipment, to augment the play-based development of FM

The study design of UDRIVE: the Naturalistic Driving Study across Europe for cars, trucks and scooters

Purpose: UDRIVE is the first large-scale European Naturalistic Driving Study on cars, trucks and powered two wheelers. The acronym stands for "European naturalistic Driving and Riding for Infrastructure & Vehicle safety and Environment". The purpose of the study is to gain a better understanding of what happens on the road in everyday traffic situations. Methods: The paper describes Naturalistic Driving Studies, a method which provides insight into the actual real-world behaviour of road users, unaffected by experimental conditions and related biases. Naturalistic driving can be defined as a study undertaken to provide insight into driver behaviour during everyday trips by recording details of the driver, the vehicle and the surroundings through unobtrusive data gathering equipment and without experimental control. Data collection will take place in six EU Member States. Results: Road User Behaviour will be studied with a focus on both safety and environment. The UDRIVE project follows the steps of the FESTA-V methodology, which was originally designed for Field Operational Tests. Conclusions: Defining research questions forms the basis of the study design and the specification of the recording equipment. Both will be described in this paper. Although the project has just started collecting data from drivers, we consider the process of designing the study as a major result which may help other initiatives to set up similar studies

Musculoskeletal Response to Whole-Body Vibration During Fracture Healing in Intact and Ovariectomized Rats

This study investigated the effect of vibration on bone healing and muscle in intact and ovariectomized rats. Thirty ovariectomized (at 3 months of age) and 30 intact 5-month old female Sprague-Dawley rats underwent bilateral metaphyseal osteotomy of tibia. Five days later, half of the ovariectomized and of the intact rats were exposed to whole-body vertical vibration (90 Hz, 0.5 mm, 4 × g acceleration) for 15 min twice a day during 30 days. The other animals did not undergo vibration. After decapitation of rats, one tibia was used for computed tomographic, biomechanical, and histological analyses; the other was used for gene expression analyses of alkaline phosphatase (Alp), osteocalcin (Oc), tartrate-resistant acid phosphatase 1, and insulinlike growth factor 1. Serum Alp and Oc were measured. Mitochondrial activity, fiber area and distribution, and capillary densities were analyzed in M. gastrocnemius and M. longissimus. We found that vibration had no effect on body weight and food intake, but it improved cortical and callus densities (97 vs. 99%, 72 vs. 81%), trabecular structure (9 vs. 14 trabecular nodes), blood supply (1.7 vs. 2.1 capillaries/fiber), and oxidative metabolism (17 vs. 23 pmol O2/s/mg) in ovariectomized rats. Vibration generally increased muscle fiber size. Tibia biomechanical properties were diminished after vibration. Oc gene expression was higher in vibrated rats. Serum Alp was increased in ovariectomized rats. In ovariectomized rats, vibration resulted in an earlier bridging; in intact rats, callus bridging occurred later after vibration. The chosen vibration regimen (90 Hz, 0.5 mm, 4 × g acceleration, 15 min twice a day) was effective in improving musculoskeletal tissues in ovariectomized rats but was not optimal for fracture healing

Toxicity Testing in the 21st Century: Defining New Risk Assessment Approaches Based on Perturbation of Intracellular Toxicity Pathways

The approaches to quantitatively assessing the health risks of chemical exposure have not changed appreciably in the past 50 to 80 years, the focus remaining on high-dose studies that measure adverse outcomes in homogeneous animal populations. This expensive, low-throughput approach relies on conservative extrapolations to relate animal studies to much lower-dose human exposures and is of questionable relevance to predicting risks to humans at their typical low exposures. It makes little use of a mechanistic understanding of the mode of action by which chemicals perturb biological processes in human cells and tissues. An alternative vision, proposed by the U.S. National Research Council (NRC) report Toxicity Testing in the 21st Century: A Vision and a Strategy, called for moving away from traditional high-dose animal studies to an approach based on perturbation of cellular responses using well-designed in vitro assays. Central to this vision are (a) “toxicity pathways” (the innate cellular pathways that may be perturbed by chemicals) and (b) the determination of chemical concentration ranges where those perturbations are likely to be excessive, thereby leading to adverse health effects if present for a prolonged duration in an intact organism. In this paper we briefly review the original NRC report and responses to that report over the past 3 years, and discuss how the change in testing might be achieved in the U.S. and in the European Union (EU). EU initiatives in developing alternatives to animal testing of cosmetic ingredients have run very much in parallel with the NRC report. Moving from current practice to the NRC vision would require using prototype toxicity pathways to develop case studies showing the new vision in action. In this vein, we also discuss how the proposed strategy for toxicity testing might be applied to the toxicity pathways associated with DNA damage and repair

Crowdsourcing hypothesis tests: Making transparent how design choices shape research results

To what extent are research results influenced by subjective decisions that scientists make as they design studies? Fifteen research teams independently designed studies to answer fiveoriginal research questions related to moral judgments, negotiations, and implicit cognition. Participants from two separate large samples (total N > 15,000) were then randomly assigned to complete one version of each study. Effect sizes varied dramatically across different sets of materials designed to test the same hypothesis: materials from different teams renderedstatistically significant effects in opposite directions for four out of five hypotheses, with the narrowest range in estimates being d = -0.37 to +0.26. Meta-analysis and a Bayesian perspective on the results revealed overall support for two hypotheses, and a lack of support for three hypotheses. Overall, practically none of the variability in effect sizes was attributable to the skill of the research team in designing materials, while considerable variability was attributable to the hypothesis being tested. In a forecasting survey, predictions of other scientists were significantly correlated with study results, both across and within hypotheses. Crowdsourced testing of research hypotheses helps reveal the true consistency of empirical support for a scientific claim.</div

Mental Practice Ability Among Stroke Survivors: Investigation of Gender and Age

BACKGROUND: Mental practice refers to the imaginary representation of a motor action. Mental practice interventions are frequently used among stroke survivors to improve motor function. Individual characteristics that may determine whether a person is able to mentally perform a specific movement have been mainly spared in research. AIMS: The aim of the present study is to examine whether gender and age are related to mental practice ability. METHODS: The study has a cross-sectional design. Data collection was done via self-report questionnaires on mental practice ability, sociodemographic information, and perceived stroke impact. Data analysis was conducted in R using descriptive statistics and regression analysis. N = 44 stroke survivors (M = 65.8 years, SD = 11.4, range 48–88), n = 19 of which were female were recruited in two German neurologic rehabilitation facilities. RESULTS: Age (β = −0.13, p = 0.057) and gender (β = 0.17, p = 0.260) were not associated with mental practice ability, when controlling for time since stroke and perceived stroke impact (Stroke Impact Scale). Perceived stroke impact was significantly related to mental practice ability (β = 0.44, p = 0.004). Those who reported less stroke impact showed better mental practice ability. CONCLUSION: Mental practice ability may be preserved in stroke patients, irrespective of age and gender. We report cross-sectional data on mental practice ability in this study, thus the direction of the relationship between mental practice ability and perceived stroke impact is of interest. Future studies should aim at using a longitudinal design and bigger sample sizes