How did you perform? Investigating football players' perception of self-regulated passing performances under auditory noise environments.

Introduction: This paper deals with the question on how sport performances may be influenced by internal, emotional processes, which stem from outside feedback. Methods: In terms of methods, players' subjective performance ratings for four experimental auditory cue conditions were examined; these included both 'positive' and 'negative' stadium noise, 'no (auditory) conditions,' and a control/'baseline' condition. This resulted in a qualitative-analytic data set that was obtained succeeding each auditory cue condition using a unique football training machine (i.e., known as 'Footbonaut'). Without having received any coaching/performance feedback, players were asked to rate and individually comment on their perceived performance ratings for each experimental auditory condition. Results: Findings indicate stronger and more significant correlations between auditory conditions and subjective ratings compared to the non-auditory condition and its subjective rating. Furthermore, data provides initial insight into players' emotional experiences during each of the practice conditions. Discussion: These noteworthy findings on players' abilities to accurately judge their performances based on selfmonitoring and intrinsic feedback are discussed from an Ecological Dynamics perspective, linked to a Nonlinear Pedagogy for coaching. Here, representative and affective learning designs for skill learning and performance preparation are presented. Finally, a hypothetical catalyst effect of auditory stadium noise on subjective performance rating is proposed.

HDAC1/2 and HDAC3 play distinct roles in controlling adult Meibomian gland homeostasis.

PURPOSE: To investigate the roles of HDAC1/2 and HDAC3 in adult Meibomian gland (MG) homeostasis. METHODS: HDAC1/2 or HDAC3 were inducibly deleted in MG epithelial cells of adult mice. The morphology of MG was examined. Proliferation, apoptosis, and expression of MG acinus and duct marker genes, meibocyte differentiation genes, and HDAC target genes, were analyzed via immunofluorescence, TUNEL assay, and RNA in situ hybridization. RESULTS: Co-deletion of HDAC1/2 in MG epithelium caused gradual loss of acini and formation of cyst-like structures in the central duct. These phenotypes required homozygous deletion of both HDAC1 and HDAC2, indicating that they function redundantly in the adult MG. Short-term deletion of HDAC1/2 in MG epithelium had little effect on meibocyte maturation but caused decreased proliferation of acinar basal cells, excessive DNA damage, ectopic apoptosis, and increased p53 acetylation and p16 expression in the MG. By contrast, HDAC3 deletion in MG epithelium caused dilation of central duct, atrophy of acini, defective meibocyte maturation, increased acinar basal cell proliferation, and ectopic apoptosis and DNA damage. Levels of p53 acetylation and p21 expression were elevated in HDAC3-deficient MGs, while the expression of the differentiation regulator PPARγ and the differentiation markers PLIN2 and FASN was downregulated. CONCLUSIONS: HDAC1 and HDAC2 function redundantly in adult Meibomian gland epithelial progenitor cells and are essential for their proliferation and survival, but not for acinar differentiation, while HDAC3 is required to limit acinar progenitor cell proliferation and permit differentiation. HDAC1/2 and HDAC3 have partially overlapping roles in maintaining survival of MG cells.

Wnt/ß-catenin signaling controls mouse eyelid growth by mediating epithelial-mesenchymal interactions.

PURPOSE: To investigate the role of Wnt/ß-catenin signaling in mouse eyelid development. METHODS: Wnt/ß-catenin signaling was disrupted by deleting supraorbital mesenchymal ß-catenin or epithelial Wls. p63 was removed to determine whether the expression of Wnts is affected. The eyelid morphology was examined at different stages. Proliferation, apoptosis, and expression of Wnt ligands and their target genes were analyzed via immunofluorescence staining, TUNEL assay, and in situ hybridization. RESULTS: Deletion of ß-catenin in supraorbital mesenchyme abolishes eyelid growth by causing decreased proliferation in supraorbital epithelium and underlying mesenchyme. Inhibition of Wnt secretion by deleting Wls in supraorbital epithelium results in failure of eyelid development, similar to the effects of deleting mesenchymal ß-catenin. Knockout of p63 results in formation of hypoplastic eyelids and reduced expression of several Wnt ligands in eyelid epithelium. CONCLUSIONS: Epithelial Wnt ligands activate mesenchymal Wnt/ß-catenin signaling to control eyelid growth and their expression is partially regulated by p63.

Dedifferentiation maintains melanocyte stem cells in a dynamic niche.

For unknow reasons, the melanocyte stem cell (McSC) system fails earlier than other adult stem cell populations1, which leads to hair greying in most humans and mice2,3. Current dogma states that McSCs are reserved in an undifferentiated state in the hair follicle niche, physically segregated from differentiated progeny that migrate away following cues of regenerative stimuli4-8. Here we show that most McSCs toggle between transit-amplifying and stem cell states for both self-renewal and generation of mature progeny, a mechanism fundamentally distinct from those of other self-renewing systems. Live imaging and single-cell RNA sequencing revealed that McSCs are mobile, translocating between hair follicle stem cell and transit-amplifying compartments where they reversibly enter distinct differentiation states governed by local microenvironmental cues (for example, WNT). Long-term lineage tracing demonstrated that the McSC system is maintained by reverted McSCs rather than by reserved stem cells inherently exempt from reversible changes. During ageing, there is accumulation of stranded McSCs that do not contribute to the regeneration of melanocyte progeny. These results identify a new model whereby dedifferentiation is integral to homeostatic stem cell maintenance and suggest that modulating McSC mobility may represent a new approach for the prevention of hair greying.

FZD2 regulates limb development by mediating ß-catenin-dependent and -independent Wnt signaling pathways.

Human Robinow syndrome (RS) and dominant omodysplasia type 2 (OMOD2), characterized by skeletal limb and craniofacial defects, are associated with heterozygous mutations in the Wnt receptor FZD2. However, as FZD2 can activate both canonical and non-canonical Wnt pathways, its precise functions and mechanisms of action in limb development are unclear. To address these questions, we generated mice harboring a single-nucleotide insertion in Fzd2 (Fzd2em1Smill), causing a frameshift mutation in the final Dishevelled-interacting domain. Fzd2em1Smill mutant mice had shortened limbs, resembling those of RS and OMOD2 patients, indicating that FZD2 mutations are causative. Fzd2em1Smill mutant embryos displayed decreased canonical Wnt signaling in developing limb mesenchyme and disruption of digit chondrocyte elongation and orientation, which is controlled by the ß-catenin-independent WNT5A/planar cell polarity (PCP) pathway. In line with these observations, we found that disruption of FZD function in limb mesenchyme caused formation of shortened bone elements and defects in Wnt/ß-catenin and WNT5A/PCP signaling. These findings indicate that FZD2 controls limb development by mediating both canonical and non-canonical Wnt pathways and reveal causality of pathogenic FZD2 mutations in RS and OMOD2 patients.

A quantitative analysis of factors which influence supplement use and doping among adolescent athletes in New Zealand.

Objectives: Doping is a maladaptive behaviour which poses numerous risks and potentially enhances athletic performance while supplement use poses threats of positive, yet inadvertent, doping control results. Investigation is required to understand factors that influence adolescent supplement use and doping in New Zealand (NZ). Design: A survey was completed by 660 athletes aged 13 to 18 years, of any gender, who competed at any level of any sport in NZ. Forty-three independent variables measured autonomy, confidence sources, motivational climate, social norms and age. Methods: Multivariate, ordinal, and binary logistic regression models measured associations between independent variables and five dependant variables: supplement use, doping, doping considerations and intent (soon and in the next year). Results: Confidence through mastery, internally perceived locus of control (IPLOC) and volition decreased the odds of doping while confidence through self-presentation, subjective and descriptive norms increased the odds of supplement use and doping. Conclusion: To decrease the odds of doping, adolescent autonomy should be increased in sport through opportunities for volitional decision making and exposure to mastery as a confidence source.

Cell-autonomous requirement for ACE2 across organs in lethal mouse SARS-CoV-2 infection.

Angiotensin-converting enzyme 2 (ACE2) is the cell-surface receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). While its central role in Coronavirus Disease 2019 (COVID-19) pathogenesis is indisputable, there remains significant debate regarding the role of this transmembrane carboxypeptidase in the disease course. These include the role of soluble versus membrane-bound ACE2, as well as ACE2-independent mechanisms that may contribute to viral spread. Testing these roles requires in vivo models. Here, we report humanized ACE2-floxed mice in which hACE2 is expressed from the mouse Ace2 locus in a manner that confers lethal disease and permits cell-specific, Cre-mediated loss of function, and LSL-hACE2 mice in which hACE2 is expressed from the Rosa26 locus enabling cell-specific, Cre-mediated gain of function. Following exposure to SARS-CoV-2, hACE2-floxed mice experienced lethal cachexia, pulmonary infiltrates, intravascular thrombosis and hypoxemia-hallmarks of severe COVID-19. Cre-mediated loss and gain of hACE2 demonstrate that neuronal infection confers lethal cachexia, hypoxemia, and respiratory failure in the absence of lung epithelial infection. In this series of genetic experiments, we demonstrate that ACE2 is absolutely and cell-autonomously required for SARS-CoV-2 infection in the olfactory epithelium, brain, and lung across diverse cell types. Therapies inhibiting or blocking ACE2 at these different sites are likely to be an effective strategy towards preventing severe COVID-19.

The Value of Sport: Wellbeing Benefits of Sport Participation during Adolescence.

Insight into the unique benefits of sport participation above and beyond those associated with participation in other physical activities among adolescents is limited in Aotearoa New Zealand (NZ). The purpose of this study was to examine the association between wellbeing and organised sport participation among adolescents whilst accounting for demographic characteristics and other recreational physical activity. Demographic characteristics (age, gender, ethnicity, deprivation, (dis)ability status), organized sport, recreational physical activity, and wellbeing were assessed in cohorts of NZ adolescents (11-17 years) between 2017 and 2019. After adjusting for demographics, better wellbeing was associated with participation in any recreational physical activity (OR = 2.49, 95%CI = 1.97-3.13), meeting physical activity recommendations (OR = 1.63, 95%CI = 1.47-1.81), and each additional hour of recreational physical activity (OR = 1.03, 95%CI = 1.02-1.04). After adjusting for demographics and overall recreational physical activity participation, better wellbeing was also associated with participation in any organized sport (OR = 1.66, 95%CI = 1.49-1.86), and each additional hour of organized sport (OR = 1.09, 95%CI = 1.07-1.11). Although participation in recreational physical activity appears to be beneficial for wellbeing, organized sport appears to offer unique additional wellbeing benefits. Positive experiences of organized sport participation may offer additional wellbeing value above and beyond other recreational physical activity types in young people who are active.

"Balance Is Better": The Wellbeing Benefits of Participating in a Breadth of Sports across a Variety of Settings during Adolescence.

The purpose of this study was to examine how wellbeing is associated with the setting in which sport participation takes place and the breadth of sport participation. Demographic characteristics (age, gender, ethnicity, deprivation, (dis)ability status), recreational physical activity, and wellbeing were assessed in cohorts of adolescents (11-17 years) between 2017 and 2019 in Aotearoa, New Zealand. Better wellbeing was associated with participation in any sport vs. none (OR = 1.57, 95% CI = 1.30-1.90). Better wellbeing was also associated with participating in any coached sport training (OR = 1.48, 95% CI = 1.33-1.66), competitive sport (OR = 1.33, 95% CI = 1.18-1.49), social sport (OR = 1.33, 95% CI = 1.18-1.49), and uncoached sport training (OR = 1.16, 95% CI = 1.03-1.31) compared to non-participation in the given setting. Wellbeing was not associated with participation in physical education or solo sport. Participating in sport in three to five different settings (3 settings: OR = 1.21, 95% CI = 1.01-1.44; 4 settings: OR = 1.33, 95% CI = 1.09-1.62; 5 settings: OR = 1.37, 95% CI = 1.07-1.75) or sports (3 sports: OR = 1.25, 95% CI = 1.04-1.51; 4 sports: OR = 1.31, 95% CI = 1.06-1.61; 5 sports: OR = 1.33, 95% CI = 1.05-1.69) was associated with better wellbeing compared to participation in a single setting or sport, respectively. A balanced approach to participating across a variety of sport settings and sports that are facilitated by quality coaches may offer the largest additional wellbeing value.

Verification of Bound Aminoguanidine as the Marker Residue for the Banned Antibiotic, Nitrovin, in Pig Tissues.

Nitrovin (NTV) belongs to a class of antibiotics called nitrofurans, which are classified as nonallowed pharmacologically active substances that do not have a maximum residue limit listed in EU legislation. The objectives of this study were to confirm aminoguanidine (AGN) as a suitable marker residue to monitor NTV abuse and to investigate its persistence in porcine tissues. In this work, pigs were fed with NTV-medicated feed (50 mg/kg), and tissues (kidney, muscle, and liver) and plasma were collected on different withdrawal days. All samples were analyzed for bound AGN, total AGN, and the parent drug NTV itself. The highest concentrations of AGN residues were found in the liver, while the lowest were in muscle. Parent NTV was only detected in the kidney at low levels on day 0 of withdrawal. The findings are in support of using AGN as the marker residue for monitoring the illegal use of NTV in animal-derived products.

NF-κB perturbation reveals unique immunomodulatory functions in Prx1+ fibroblasts that promote development of atopic dermatitis.

Skin is composed of diverse cell populations that cooperatively maintain homeostasis. Up-regulation of the nuclear factor κB (NF-κB) pathway may lead to the development of chronic inflammatory disorders of the skin, but its role during the early events remains unclear. Through analysis of single-cell RNA sequencing data via iterative random forest leave one out prediction, an explainable artificial intelligence method, we identified an immunoregulatory role for a unique paired related homeobox-1 (Prx1)+ fibroblast subpopulation. Disruption of Ikkb-NF-κB under homeostatic conditions in these fibroblasts paradoxically induced skin inflammation due to the overexpression of C-C motif chemokine ligand 11 (CCL11; or eotaxin-1) characterized by eosinophil infiltration and a subsequent TH2 immune response. Because the inflammatory phenotype resembled that seen in human atopic dermatitis (AD), we examined human AD skin samples and found that human AD fibroblasts also overexpressed CCL11 and that perturbation of Ikkb-NF-κB in primary human dermal fibroblasts up-regulated CCL11. Monoclonal antibody treatment against CCL11 was effective in reducing the eosinophilia and TH2 inflammation in a mouse model. Together, the murine model and human AD specimens point to dysregulated Prx1+ fibroblasts as a previously unrecognized etiologic factor that may contribute to the pathogenesis of AD and suggest that targeting CCL11 may be a way to treat AD-like skin lesions.

HDAC1/2 Control Proliferation and Survival in Adult Epidermis and Pre‒Basal Cell Carcinoma through p16 and p53.

HDAC inhibitors show therapeutic promise for skin malignancies; however, the roles of specific HDACs in adult epidermal homeostasis and in disease are poorly understood. We find that homozygous epidermal codeletion of Hdac1 and Hdac2 in adult mouse epidermis causes reduced basal cell proliferation, apoptosis, inappropriate differentiation, and eventual loss of Hdac1/2-null keratinocytes. Hdac1/2-deficient epidermis displays elevated acetylated p53 and increased expression of the senescence gene p16. Loss of p53 partially restores basal proliferation, whereas p16 deletion promotes long-term survival of Hdac1/2-null keratinocytes. In activated GLI2-driven pre-basal cell carcinoma, Hdac1/2 deletion dramatically reduces proliferation and increases apoptosis, and knockout of either p53 or p16 partially rescues both proliferation and basal cell viability. Topical application of the HDAC inhibitor romidepsin to the normal epidermis or to GLI2ΔN-driven lesions produces similar defects to those caused by genetic Hdac1/2 deletion, and these are partially rescued by loss of p16. These data reveal essential roles for HDAC1/2 in maintaining proliferation and survival of adult epidermal and basal cell carcinoma progenitors and suggest that the efficacy of therapeutic HDAC1/2 inhibition will depend in part on the mutational status of p53 and p16.

SARS-CoV-2 infection of olfactory epithelial cells and neurons drives acute lung injury and lethal COVID-19 in mice.

Lethal COVID-19 is associated with respiratory failure that is thought to be caused by acute respiratory distress syndrome (ARDS) secondary to pulmonary infection. To date, the cellular pathogenesis has been inferred from studies describing the expression of ACE2, a transmembrane protein required for SARS-CoV-2 infection, and detection of viral RNA or protein in infected humans, model animals, and cultured cells. To functionally test the cellular mechanisms of COVID-19, we generated hACE2 fl animals in which human ACE2 (hACE2) is expressed from the mouse Ace2 locus in a manner that permits cell-specific, Cre-mediated loss of function. hACE2 fl animals developed lethal weight loss and hypoxemia within 7 days of exposure to SARS-CoV-2 that was associated with pulmonary infiltrates, intravascular thrombosis and patchy viral infection of lung epithelial cells. Deletion of hACE2 in lung epithelial cells prevented viral infection of the lung, but not weight loss, hypoxemia or death. Inhalation of SARS-CoV-2 by hACE2 fl animals resulted in early infection of sustentacular cells with subsequent infection of neurons in the neighboring olfactory bulb and cerebral cortexâ€" events that did not require lung epithelial cell infection. Pharmacologic ablation of the olfactory epithelium or Foxg1 Cre mediated deletion of hACE2 in olfactory epithelial cells and neurons prevented lethality and neuronal infection following SARS-CoV-2 infection. Conversely, transgenic expression of hACE2 specifically in olfactory epithelial cells and neurons in Foxg1 Cre ; LSL- hACE2 mice was sufficient to confer neuronal infection associated with respiratory failure and death. These studies establish mouse loss and gain of function genetic models with which to genetically dissect viral-host interactions and demonstrate that lethal disease due to respiratory failure may arise from extrapulmonary infection of the olfactory epithelium and brain. Future therapeutic efforts focused on preventing olfactory epithelial infection may be an effective means of protecting against severe COVID-19.

20 years of Developmental Cell: Looking back.

In our 20th anniversary year, we reflect on how the cell and developmental biology fields have changed since the publication of Developmental Cell's first few issues. In this collection of Voices, authors who published in our early issues discuss the advances that helped shape their field over the past two decades.

Teachers' Perceptions of Applying Contemporary Skill Acquisition Approaches in High School Physical Education.

Using contemporary skill acquisition approaches to skill learning appears to be a worthwhile pedagogical option for teachers and coaches in sports and Physical Education (PE). However, PE at the High School level in New Zealand has assessment components that are still underpinned by traditional and outdated skill learning theories. In response to this challenge, two motivated Heads of Department in PE undertook a department-wide professional development initiative to teach the national standard assessment via the use of a contemporary skill acquisition approach, which is student-centred, with an emphasis on enhancing exploratory learning and encouraging autonomy. Each department worked together over a 10-week period with a Higher Education specialist in skill acquisition to design and teach using contemporary skill acquisition approaches. Qualitative data was collected via semi-structured focus group interviews. Insightful data on the influence of teaching using contemporary skill acquisition approaches was acquired from the teachers in the two PE departments. It was found that substantial pedagogical practice changes were achieved by the teachers (e.g., less focus on ideal technique and more on varying the context). They also enjoyed the learning experience that the contemporary skill acquisition approach offered as compared to their previous experience of more traditional teaching approaches, which have a focus on knowledge acquirement with little opportunities for exploratory learning. In addition, from a practical perspective, teachers were observed to demonstrate greater engagement in professional conversations around learning and could see greater relevance in the transfer of learning in the use of contemporary skill acquisition approaches to other teaching contexts.

What do you hear? The effect of stadium noise on football players' passing performances.

Stadium noise - created by spectators and fans - plays a critical part in the reality of professional sports. Due to a lack of research on the impact of these auditory cues and multimodal environments on motor performance, it is currently unclear how professional athletes experience and perceive stadium noise and how this potentially affects performance in practice. In order to explore the effect of stadium noise on athletes' performance, this paper presents an experimental design using the unique and standardised football training tool known as the "Footbonaut". Specifically, fifteen skilled German football players engaged in a standardised football-specific technical training programme while subjected to four different auditory training conditions; these included both "positive" and "negative" stadium noise conditions, a "baseline" condition providing auditory guidance, and a "no (auditory) cue" condition. Performance data for passing accuracy and passing time were measured for training in each auditory condition. A repeated measures MANOVA revealed a significant main effect for passing time. Specifically, participants showed faster passing times in the baseline compared to the negative and no auditory cue conditions. Findings are presented and discussed from a constraints-led perspective, allied to principles of ecological dynamics and nonlinear pedagogy. Particularly, the use of representative training experiences (including multimodal sensory and emotional information) appears to underline training to refine expert athletes' adaptive coordination of complex motor actions.

Author Correction: MiR-31 promotes mammary stem cell expansion and breast tumorigenesis by suppressing Wnt signaling antagonists.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

When and How to Provide Feedback and Instructions to Athletes?-How Sport Psychology and Pedagogy Insights Can Improve Coaching Interventions to Enhance Self-Regulation in Training.

In specialist sports coaching, the type and manner of augmented information that the coach chooses to use in communicating and training with individual athletes can have a significant impact on skill development and performance. Informed by insights from psychology, pedagogy, and sport science, this position paper presents a practitioner-based approach in response to the overarching question: When, why, and how could coaches provide information to athletes during coaching interventions? In an ecological dynamics rationale, practice is seen as a search for functional performance solutions, and augmented feedback is outlined as instructional constraints to guide athletes' self-regulation of action in practice. Using the exemplar of team sports, we present a Skill Training Communication Model for practical application in the context of the role of a specialist coach, using a constraints-led approach (CLA). Further based on principles of a non-linear pedagogy and using the recently introduced Periodization of Skill Training (PoST) framework, the proposed model aims to support practitioners' understanding of the pedagogical constraints of feedback and instruction during practice. In detail, the PoST framework's three skill development and training stages work to (1) directly impact constraint manipulations in practice designs and (2) indirectly affect coaches' choices of external (coach-induced) information. In turn, these guide practitioners on how and when to apply different verbal instruction methodologies and aim to support the design of effective skill learning environments. Finally, several practical guidelines in regard to sports coaches' feedback and instruction processes are proposed.