Evolutionary rate covariation is pervasive between glycosylation pathways and points to potential disease modifiers.

Mutations in glycosylation pathways, such as N-linked glycosylation, O-linked glycosylation, and GPI anchor synthesis, lead to Congenital Disorders of Glycosylation (CDG). CDG typically present with seizures, hypotonia, and developmental delay but display large clinical variability with symptoms affecting every system in the body. This variability suggests modifier genes might influence the phenotypes. Because of the similar physiology and clinical symptoms, there are likely common genetic modifiers between CDG. Here, we use evolution as a tool to identify common modifiers between CDG and glycosylation genes. Protein glycosylation is evolutionarily conserved from yeast to mammals. Evolutionary rate covariation (ERC) identifies proteins with similar evolutionary rates that indicate shared biological functions and pathways. Using ERC, we identified strong evolutionary rate signatures between proteins in the same and different glycosylation pathways. Genome-wide analysis of proteins showing significant ERC with GPI anchor synthesis proteins revealed strong signatures with ncRNA modification proteins and DNA repair proteins. We also identified strong patterns of ERC based on cellular sub-localization of the GPI anchor synthesis enzymes. Functional testing of the highest scoring candidates validated genetic interactions and identified novel genetic modifiers of CDG genes. ERC analysis of disease genes and biological pathways allows for rapid prioritization of potential genetic modifiers, which can provide a better understanding of disease pathophysiology and novel therapeutic targets.

Identification of CNTN2 as a genetic modifier of PIGA-CDG through pedigree analysis of a family with incomplete penetrance and functional testing in Drosophila.

Loss of function mutations in the X-linked PIGA gene lead to PIGA-CDG, an ultra-rare congenital disorder of glycosylation (CDG), typically presenting with seizures, hypotonia, and neurodevelopmental delay. We identified two brothers (probands) with PIGA-CDG, presenting with epilepsy and mild developmental delay. Both probands carry PIGA S132C , an ultra-rare variant predicted to be damaging. Strikingly, the maternal grandfather and a great-uncle also carry PIGA S132C , but neither presents with symptoms associated with PIGA-CDG. We hypothesized genetic modifiers may contribute to this reduced penetrance. Using whole genome sequencing and pedigree analysis, we identified possible susceptibility variants found in the probands and not in carriers and possible protective variants found in the carriers and not in the probands. Candidate variants included heterozygous, damaging variants in three genes also involved directly in GPI-anchor biosynthesis and a few genes involved in other glycosylation pathways or encoding GPI-anchored proteins. We functionally tested the predicted modifiers using a Drosophila eye-based model of PIGA-CDG. We found that loss of CNTN2 , a predicted protective modifier, rescues loss of PIGA in Drosophila eye-based model, like what we predict in the family. Further testing found that loss of CNTN2 also rescues patient-relevant phenotypes, including seizures and climbing defects in Drosophila neurological models of PIGA-CDG. By using pedigree information, genome sequencing, and in vivo testing, we identified CNTN2 as a strong candidate modifier that could explain the incomplete penetrance in this family. Identifying and studying rare disease modifier genes in human pedigrees may lead to pathways and targets that may be developed into therapies.

"It made me feel like a shit parent": an intersectional analysis of pandemic mothering.

The COVID-19 pandemic brought to the fore the everyday and exceptional challenges for mothers. Rarely, however, did research or social commentary acknowledge the multiplicities of motherhood during this prolonged period of risk, disruption, and uncertainty. This paper draws upon interviews with 24 mothers living in Aotearoa New Zealand during the pandemic, including women who were pregnant and gave birth during lockdowns, teenage mothers, single and low-income mothers, and working mothers. The sample was intentionally diverse, including Maori, Pacific, Asian and migrant mothers. Engaging an intersectional lens on motherhood and women's health, this paper builds upon and extends feminist research on mothers' experiences during the pandemic, highlighting the many different challenges facing mothers of diverse social, cultural, and economic positionalities and during various stages of motherhood. Across the sample, we reveal the significant emotional toll on mothers, particularly with the absence of critical social, medical and health support systems during lockdown periods and sustained social restrictions. Many of the women described how the pandemic affected their feelings about motherhood, prompting new reflections on their relationships with the home, family, work, and broader society. Despite some similarities, the pandemic experiences of Maori, Pacific, migrant and single mothers were further intensified by various forms of isolation, judgement, and discrimination. In this way, the pandemic shed light on the gendering of everyday maternal life, but also the need for more intersectional culturally and gender-responsive policies that acknowledge the multi-layered complexities of mothers' lives.

Moving from ethnic exclusions to cultural safety: how is athlete ethnicity discussed in research on menstrual health in sports? A scoping review.

OBJECTIVE: This study aims to investigate how athlete ethnicity is discussed in the inclusion and exclusion criteria, methodology, findings, and conclusions of research focused on menstrual health in sports science and medicine. DESIGN: A scoping review of sports-based research conducted on athletes related to (1) menstrual health and ethnicity, (2) how researchers include/exclude participants based on ethnicity and (3) how ethnicity is discussed. DATA SOURCES: Electronic search of PubMed and ProQuest. ELIGIBILITY CRITERIA: Articles were included if they met the following criteria: (1) published before September 2023, (2) published in peer-reviewed journals, (3) participants were women athletes, (4) published in English and (5) relating to menstrual health. Articles were assessed as good, fair or poor quality using the Inclusion of Participant Ethnicity Quality Assessment Criteria. RESULTS: From the 1089 studies available from the initial database search, 55 studies considered ethnicity. Nine studies met the inclusion criteria and were assessed as either good (22%), fair (44%) or poor (33%) in quality in their consideration of athlete ethnicity. 81% of research articles on menstrual health in sports do not consider athlete ethnicity, and when ethnicity is discussed, it rarely meets the criteria for cultural safety in the research process. Most studies did not factor ethnicity into the analysis and lacked cultural considerations in the research design and interventions. CONCLUSION: More careful inclusion of ethnicity in sports menstrual health-related research and recognition of social and cultural influences on health and research outcomes for indigenous and other ethnic minority groups is needed. Such research is required to support coaches, medical personnel and support staff in designing culturally safe environments for sportswomen from diverse cultural and ethnic backgrounds.

Drosophila models of phosphatidylinositol glycan biosynthesis class A congenital disorder of glycosylation (PIGA-CDG) mirror patient phenotypes.

Mutations in the phosphatidylinositol glycan biosynthesis class A (PIGA) gene cause a rare, X-linked recessive congenital disorder of glycosylation. Phosphatidylinositol glycan biosynthesis class A congenital disorder of glycosylation (PIGA-CDG) is characterized by seizures, intellectual and developmental delay, and congenital malformations. The PIGA gene encodes an enzyme involved in the first step of glycosylphosphatidylinositol (GPI) anchor biosynthesis. There are over 100 GPI-anchored proteins that attach to the cell surface and are involved in cell signaling, immunity, and adhesion. Little is known about the pathophysiology of PIGA-CDG. Here, we describe the first Drosophila model of PIGA-CDG and demonstrate that loss of PIG-A function in Drosophila accurately models the human disease. As expected, complete loss of PIG-A function is larval lethal. Heterozygous null animals appear healthy but, when challenged, have a seizure phenotype similar to what is observed in patients. To identify the cell-type specific contributions to disease, we generated neuron- and glia-specific knockdown of PIG-A. Neuron-specific knockdown resulted in reduced lifespan and a number of neurological phenotypes but no seizure phenotype. Glia-knockdown also reduced lifespan and, notably, resulted in a very strong seizure phenotype. RNA sequencing analyses demonstrated that there are fundamentally different molecular processes that are disrupted when PIG-A function is eliminated in different cell types. In particular, loss of PIG-A in neurons resulted in upregulation of glycolysis, but loss of PIG-A in glia resulted in upregulation of protein translation machinery. Here, we demonstrate that Drosophila is a good model of PIGA-CDG and provide new data resources for future study of PIGA-CDG and other GPI anchor disorders.

Drosophila models of PIGA-CDG mirror patient phenotypes.

Mutations in the phosphatidylinositol glycan biosynthesis class A (PIGA) gene cause a rare, X-linked recessive congenital disorder of glycosylation (CDG). PIGA-CDG is characterized by seizures, intellectual and developmental delay, and congenital malformations. The PIGA gene encodes an enzyme involved in the first step of GPI anchor biosynthesis. There are over 100 GPI anchored proteins that attach to the cell surface and are involved in cell signaling, immunity, and adhesion. Little is known about the pathophysiology of PIGA-CDG. Here we describe the first Drosophila model of PIGA-CDG and demonstrate that loss of PIG-A function in Drosophila accurately models the human disease. As expected, complete loss of PIG-A function is larval lethal. Heterozygous null animals appear healthy, but when challenged, have a seizure phenotype similar to what is observed in patients. To identify the cell-type specific contributions to disease, we generated neuron- and glia-specific knockdown of PIG-A. Neuron-specific knockdown resulted in reduced lifespan and a number of neurological phenotypes, but no seizure phenotype. Glia-knockdown also reduced lifespan and, notably, resulted in a very strong seizure phenotype. RNAseq analyses demonstrated that there are fundamentally different molecular processes that are disrupted when PIG-A function is eliminated in different cell types. In particular, loss of PIG-A in neurons resulted in upregulation of glycolysis, but loss of PIG-A in glia resulted in upregulation of protein translation machinery. Here we demonstrate that Drosophila is a good model of PIGA-CDG and provide new data resources for future study of PIGA-CDG and other GPI anchor disorders.

Reconceptualizing Women's Wellbeing During the Pandemic: Sport, Fitness and More-Than-Human Connection.

This paper explores the gendered, disruptive effects and affective intensities of COVID-19 and the ways that women working in the sport and fitness sector were prompted to establish more-than-human connection through technologies, the environment, and objects. Bringing together theoretical and embodied insights from object interviews with 17 women sport and fitness professionals (i.e., athletes, coaches, instructors) in Aotearoa New Zealand, this paper advances a relational understanding of the multiple human and nonhuman forces that shape and transform women's wellbeing during pandemic. Drawing upon particular feminist materialisms (i.e., Barad, Braidotti, Bennett), we reconceptualize wellbeing to move beyond biomedical formulations of health or illness. Through our analysis and discussion, we trace embodied ways of knowing that produce wellbeing as a more-than-human entanglement, a gendered phenomenon that can be understood as an ongoing negotiation of affective, material, cultural, technological and environmental forces during a period of disruption and uncertainty.

The transdisciplinary health research apparatus: A Baradian account of knowledge boundaries and beyond.

This paper engages with new materialist theory to reimagine transdisciplinary health research. In particular, we draw upon Karen Barad's theory of agential realism and concept of apparatus to rethink the processes of doing transdisciplinary research. A Baradian inspired approach to transdisciplinarity encourages us to not only explore ways of knowing health phenomena differently by working across disciplines, but also to pay close attention to the politics and practices in such research. We offer a case study based on a two-year transdisciplinary research project focused on the health condition known as Low Energy Availability (LEA) in sportswomen. Through this case we highlight three key ways that Barad's concept of apparatus helped us know transdisciplinarity differently: (1) Reading disciplines through each other, (2) Intra-actions and the everyday performativity of disciplinary boundaries, and (3) Troubling the boundaries of the apparatus. Ultimately this paper illustrates the value in feminist new materialist conceptual tools for encouraging different questions of transdisciplinary research as ethico-onto-epistemological practices, processes, and politics of knowledge production.

Advancing feminist innovation in sport studies: A transdisciplinary dialogue on gender, health and wellbeing.

Athlete health and wellbeing requires a holistic, multidimensional approach to understanding, supporting, and treating individual athletes. Building more supportive, inclusive, and equitable environments for the health and wellbeing of women and gender expansive people further requires gender-responsive approaches that promote broader cultural change. Feminist sport and exercise medicine practitioners, sports scientists, and social science researchers are increasingly coming together in their efforts to do this work. However, working across disciplines inevitably includes an array of ontological, epistemological, and political challenges. In this paper, we offer a curated 'dialogue' with a group of feminist scholars engaged in research and practice across disciplines, bringing them together to discuss some of the most pressing gendered issues in sport today (i.e., ACL injury, concussion, menstruation in sport, mental health, gender categories). In so doing, we amplify the voices of those working (empirically and clinically) at the disciplinary intersections of gender, sport and health, and learn about some of the current and future possibilities for transdisciplinary innovations and strategies for building (responsiveness to) cultural change.

Case Study: Energy Availability and Endocrine Markers in Elite Male Track Cyclists.

AIM: To highlight energy availability status, resting metabolic rate measures, dietary protein intake, and testosterone concentration in 4 elite male track cycling athletes (mean [SD]: age: 20.8 [1.5] y, body mass: 76.3 [3.6] kg, height: 181.8 [2.9] cm). METHOD: A cross-sectional observation included measures of energy availability (energy intake minus exercise energy expenditure, divided by fat-free mass), resting metabolic rate from indirect calorimetry, dietary protein intake from food records, blood analysis to assess sex hormone status, and performance markers. RESULTS: Midrange testosterone (16.9-19.8 nmol/L), lowered resting metabolic rate ratio (0.76-0.98), varied luteinizing hormone (4-10 U/L), and suboptimal energy availability (26-41 kcal/kg fat-free mass/d, range) were observed in the male track cyclists. Protein intakes ranged from 2.0 g to 2.8 g protein/kg/d. CONCLUSION: The current cohort may have within-day energy deficiency, putting them in a catabolic state.

"A 15% Reduction in Physical Inactivity Will Be Achieved in Australasia by 2030"-Audience Votes Negative in Online Debate.

The Australasian Society for Physical Activity aims to advance the science and practice of physical activity in Australia, New Zealand, the Pacific Islands, East Asia, South Asia, Southeast Asia, and Oceania. Fun, enjoyment, and cross-disciplinary discourse are important to ensure the network of physical activity professionals and our collective voice continues to grow. In May 2021, Australasian Society for Physical Activity's Early Career Network curated an engaging online Physical Activity Debate attended by 206 professionals. This commentary provides a synopsis of the debate and the central arguments presented by the affirmative and negatives teams. The authors describe the debate format and interactive design of the online Physical Activity Debate to provide insights for future online events that aim to boost interaction among physical activity professionals from various disciplines.

Toward More-Than-Human Understandings of Sport and the Environment: A New Materialist Analysis of Everyday Fitness Practices.

Sport and fitness have long been linked with healthy lifestyles, yet most sporting events and consumption practices are highly detrimental to the environment. While academics have examined the harmful effects of sporting mega-events and the production and consumption of sport equipment and clothing, there has been less engagement with the "mundane," everyday activities of consuming, laundering, and recycling of fitness objects. In this paper, we explore the potential in feminist new materialisms for rethinking the complex relationships between sport, fitness, and the environment. In particular, we explain how our engagement with Karen Barad's theory of agential realism led us to rethink women's habitual fitness practices as connected to environmental degradation. Working with Barad's concept of entanglement, we came to notice new human-clothing-environment relationships, focusing on how athleisure clothing itself is an active, vital force that intra-acts with other non-human (and human) matter within the environment. Adopting a diffractive methodology that included reading interviews with women about their activewear practices, our own experiences, new materialist theory, and environmental literature through each other, we focus on two examples that emerged through this process: laundering and disposal practices. Through these examples, we demonstrate the ways in which new materialisms encouraged us to move toward non-anthropocentric understandings of the sport-environment relationship and toward new ethical practices in our everyday fitness lifestyles.

Biological and Socio-Cultural Factors Have the Potential to Influence the Health and Performance of Elite Female Athletes: A Cross Sectional Survey of 219 Elite Female Athletes in Aotearoa New Zealand.

Health is a pre-requisite for optimal performance yet the parameters which govern health and performance of elite female athletes are little understood. The aim of this study was to quantify the health status of elite female athletes, and understand sociocultural factors influencing that status. The survey addressed demographic, health and athletic performance history, training load, contraceptive use, sport-specific appearance and performance pressures, and communication barriers. Three hundred and fifty-seven elite New Zealand female athletes were recruited to complete an on-line survey. Two hundred and nineteen athletes completed the survey. Oligomenorrhea/amenorrhea had been diagnosed in only 12% of athletes compared with 50% of athletes not on hormonal contraception who reported symptoms consistent with this diagnosis. Stress fractures and iron deficiency were common and associated with oligomenorrhoea/amenorrhea (P = 0.002), disordered eating (P = 0.009) or menorrhagia (P = 0.026). Athletes involved in individual sports (P = 0.047) and with higher training volumes (P < 0.001) were more likely to report a medical illness. Seventy-three percent of athletes felt pressured by their sport to alter their physical appearance to conform to gender ideals with 15% engaging in disordered eating practices. Barriers to communicating female health issues included male coaches and support staff, and lack of quality information pertaining to health. Elite female athletes may fail to reach peak performance due to specific health issues and undiagnosed pathology. Sociocultural factors influence the effectiveness of support of female's health and performance. Organizational and cultural change is required if elite female athletes are to combine optimal health with best performance.

Where are all the men? Low energy availability in male cyclists: A review.

Most of the low energy availability (LEA) research has been conducted in female populations. The occurrence of LEA in male athletes is not well known, even with an understanding of the components involved in and contributing to LEA. Cycling is a major risk factor for LEA due to inherent sports characteristics: low impact, high energy demands, and a common perception that leanness is a performance advantage. The purpose of this review is to discuss the cycling-specific studies that have documented components of RED-S. The review demonstrates male cyclists (1) experience energy deficits daily, weekly and throughout a season; (2) exhibit lower bone mineral density at the spine compared to the hip, and low bone mineral density correlating with LEA and; (3) demonstrate downregulation of the endocrine system with elevated cortisol, reduced testosterone and insulin-like growth factor 1. The complexity of LEA is further explored by the socio-psychological contribution that may impact eating behaviours, and therefore increase the risk of developing LEA. Future research directions include applying multifaceted research methods to gain a greater understanding of this syndrome and the effect of LEA on male cyclists.

Hepcidin and iron: novel findings for elite female rugby Sevens players.

BACKGROUND: Iron deficiency is a common deficiency disease worldwide with athletes at increased risk. METHODS: A proposed new mechanism of exercise-induced iron deficiency in athletes involves the iron-regulatory hormone hepcidin, however, there is limited information on this amongst elite athletes. This study describes iron status in elite female rugby Sevens players. RESULTS: Blood samples were collected at the start and mid-season and analyzed for serum iron, serum ferritin (SF), soluble transferring receptor (sTfR), high sensitivity C-reactive Protein (hsCRP) and hepcidin. Of the 17 players 18% were iron deficient (SF<30 µg/L) with 29-35% of players with sub-optimal iron stores at some point during the study (SF<45 µg/L). Serum hepcidin was strongly correlated with SF (r=0.61, P=0.0001). CONCLUSIONS: Some elite female rugby Sevens players have sub-optimal iron stores over the course of a season.