LRP5, Bone Density, and Mechanical Stress: A Case Report and Literature Review

The Wnt-β-catenin pathway receptor, low-density lipoprotein receptor-related protein 5 (LRP5), is a known regulator of bone mineral density. It has been hypothesized that specific human polymorphisms in LRP5 impact bone density, in part, by altering the anabolic response of bone to mechanical loading. Although experiments in animal models support this hypothesis, there is limited evidence that LRP5 polymorphisms can alter the anabolic response of bone to mechanical loading in humans. Herein, we report a young male who harbors a rare LRP5 missense mutation (A745V) and who provides potential proof of principle for this mechanotransduction hypothesis for low bone density. The subject had no history of fractures until age 18, a year into a career in competitive distance running. As he continued to run over the following 2 years, his mileage threshold to fracture steadily and rapidly decreased until he was diagnosed with severe osteoporosis (lumbar spine BMD Z-score of −3.2). By contextualizing this case within the existing LRP5 and mechanical stress literature, we speculate that this represents the first documented case of an individual in whom a genetic mutation altered the anabolic response of bone to mechanical stress in a manner sufficient to contribute to osteoporosis

"Makeup on Empty Space": a Celebration of Anne Waldman: An Exhibit

"Makeup on empty space" celebrates the opening of the Anne Waldman archive at the University of Michigan Library. This archive is as exciting and dynamic as the poet herself, showing many fascinating examples of how Anne Waldman works through her correspondence, working manuscripts, published books, audio and video tapes, and photographs covering her life and career.http://deepblue.lib.umich.edu/bitstream/2027.42/120261/1/makeup_on_empty_space_02.pd

Feminae: an international multi-site innovative project for female athletes.

Sufficient high-quality studies in sport science using women as participants are lacking, meaning that our knowledge and understanding of female athletes in relation to their ovarian hormone profiles is limited. Consortia can be used to pool talent, expertise, and data, thus accelerating our learning on a given topic and reducing research waste through collaboration. To this end, we have assembled an international multi-site team, described herein, to investigate the effects of the menstrual cycle and oral contraceptive pill phase on aspects of exercise physiology and sports performance in female athletes. We intend to produce an adequately powered, high-quality dataset which can be used to inform the practices of female athletes. Our approach will also employ research transparency – through the inclusion of a process evaluation - and reproducibility – through a standardised study protocol

Managing female athlete health : Auditing the representation of female versus male participants among research in supplements to manage diagnosed micronutrient issues

Micronutrient deficiencies and sub-optimal intakes among female athletes are a concern and are commonly prevented or treated with medical supplements. However, it is unclear how well women have been considered in the research underpinning current supplementation practices. We conducted an audit of the literature supporting the use of calcium, iron, and vitamin D. Of the 299 studies, including 25,171 participants, the majority (71%) of participants were women. Studies with exclusively female cohorts (37%) were also more prevalent than those examining males in isolation (31%). However, study designs considering divergent responses between sexes were sparse, accounting for 7% of the literature. Moreover, despite the abundance of female participants, the quality and quantity of the literature specific to female athletes was poor. Just 32% of studies including women defined menstrual status, while none implemented best-practice methodologies regarding ovarian hormonal control. Additionally, only 10% of studies included highly trained female athletes. Investigations of calcium supplementation were particularly lacking, with just two studies conducted in highly trained women. New research should focus on high-quality investigations specific to female athletes, alongside evaluating sex-based differences in the response to calcium, iron, and vitamin D, thus ensuring the specific needs of women have been considered in current protocols involving medical supplements

Irisin Levels Are Lower in Young Amenorrheic Athletes Compared with Eumenorrheic Athletes and Non-Athletes and Are Associated with Bone Density and Strength Estimates

Irisin and FGF21 are novel hormones implicated in the “browning” of white fat, thermogenesis, and energy homeostasis. However, there are no data regarding these hormones in amenorrheic athletes (AA) (a chronic energy deficit state) compared with eumenorrheic athletes (EA) and non-athletes. We hypothesized that irisin and FGF21 would be low in AA, an adaptive response to low energy stores. Furthermore, because (i) brown fat has positive effects on bone, and (ii) irisin and FGF21 may directly impact bone, we hypothesized that bone density, structure and strength would be positively associated with these hormones in athletes and non-athletes. To test our hypotheses, we studied 85 females, 14–21 years [38 AA, 24 EA and 23 non-athletes (NA)]. Fasting serum irisin and FGF21 were measured. Body composition and bone density were assessed using dual energy X-ray absorptiometry, bone microarchitecture using high resolution peripheral quantitative CT, strength estimates using finite element analysis, resting energy expenditure (REE) using indirect calorimetry and time spent exercising/week by history. Subjects did not differ for pubertal stage. Fat mass was lowest in AA. AA had lower irisin and FGF21 than EA and NA, even after controlling for fat and lean mass. Across subjects, irisin was positively associated with REE and bone density Z-scores, volumetric bone mineral density (total and trabecular), stiffness and failure load. FGF21 was negatively associated with hours/week of exercise and cortical porosity, and positively with fat mass and cortical volumetric bone density. Associations of irisin (but not FGF21) with bone parameters persisted after controlling for potential confounders. In conclusion, irisin and FGF21 are low in AA, and irisin (but not FGF21) is independently associated with bone density and strength in athletes

Effect of Menstrual Cycle Phase and Hormonal Contraceptives on Resting Metabolic Rate and Body Composition

The cyclical changes in sex hormones across the menstrual cycle (MC) are associated with various biological changes that may alter resting metabolic rate (RMR) and body composition estimates. Hormonal contraceptive (HC) use must also be considered given their impact on endogenous sex hormone concentrations and synchronous exogenous profiles. The purpose of this study was to determine if RMR and dual-energy X-ray absorptiometry body composition estimates change across the MC and differ compared with HC users. This was accomplished during a 5-week training camp involving naturally cycling athletes (n = 11) and HC users (n = 7 subdermal progestin implant, n = 4 combined monophasic oral contraceptive pill, n = 1 injection) from the National Rugby League Indigenous Women's Academy. MC phase was retrospectively confirmed via serum estradiol and progesterone concentrations and a positive ovulation test. HC users had serum estradiol and progesterone concentrations assessed at the time point of testing. Results were analyzed using general linear mixed model. There was no effect of MC phase on absolute RMR (p = .877), relative RMR (p = .957), or dual-energy X-ray absorptiometry body composition estimates (p > .05). There was no effect of HC use on absolute RMR (p = .069), relative RMR (p = .679), or fat mass estimates (p = .766), but HC users had a greater fat-free mass and lean body mass than naturally cycling athletes (p = .028). Our findings suggest that RMR and dual-energy X-ray absorptiometry body composition estimates do not significantly differ due to changes in sex hormones in a group of athletes, and measurements can be compared between MC phases or with HC usage without variations in sex hormones causing additional noise

Il tensore energia-impulso per un fluido perfetto in relatività ristretta e generale

Con questo lavoro si vuole discutere la connessione esistente tra l' equazione di continuità e l'equazione del moto di un fluido perfetto in Relatività Ristretta e Generale. Dapprima forniremo una breve introduzione sulle basi della Relatività Ristretta , introducendo il tensore energia-impulso ed analizzando in maniera specifica tale tensore per un fluido perfetto, ricavandone le equazioni del moto. Forniremo un secondo esempio di tensore Energia-Impulso per la materia incoerente. Conclusa questa argomentazione ci concentreremo sulla Relatività Generale, analizzandone i principi che sono alla base e privilegiando tra questi il Principio di Covarianza Generale come linea guida per le argomentazioni logiche. In maniera analoga a quanto fatto per la Relatività Ristretta riprenderemo la discussione per il tensore energia-impulso per un fluido perfetto dal punto di vista della Relatività Generale , soffermandoci nel caso di equilibrio idrostatico. Sempre nel contesto della Relatività Generale verrà in ultima analisi discusso il concetto di fluido incoerente e moto geodetico. L'ultimo capitolo è dedicato ad una appendice matematica nel quale vengono ricordati alcuni risultati dell'analisi tensoriali utili nel seguire i calcoli effettuati

Physiology and evolution of nitrate acquisition in Prochlorococcus

Prochlorococcus is the numerically dominant phototroph in the oligotrophic subtropical ocean and carries out a significant fraction of marine primary productivity. Although field studies have provided evidence for nitrate uptake by Prochlorococcus, little is known about this trait because axenic cultures capable of growth on nitrate have not been available. Additionally, all previously sequenced genomes lacked the genes necessary for nitrate assimilation. Here we introduce three Prochlorococcus strains capable of growth on nitrate and analyze their physiology and genome architecture. We show that the growth of high-light (HL) adapted strains on nitrate is ~17% slower than their growth on ammonium. By analyzing 41 Prochlorococcus genomes, we find that genes for nitrate assimilation have been gained multiple times during the evolution of this group, and can be found in at least three lineages. In low-light adapted strains, nitrate assimilation genes are located in the same genomic context as in marine Synechococcus. These genes are located elsewhere in HL adapted strains and may often exist as a stable genetic acquisition as suggested by the striking degree of similarity in the order, phylogeny and location of these genes in one HL adapted strain and a consensus assembly of environmental Prochlorococcus metagenome sequences. In another HL adapted strain, nitrate utilization genes may have been independently acquired as indicated by adjacent phage mobility elements; these genes are also duplicated with each copy detected in separate genomic islands. These results provide direct evidence for nitrate utilization by Prochlorococcus and illuminate the complex evolutionary history of this trait.Gordon and Betty Moore Foundation (Grant GBMF495)National Science Foundation (U.S.) (Grant OCE-1153588)National Science Foundation (U.S.) (Grant DBI-0424599

Fueling the female athlete: auditing her representation in studies of acute carbohydrate intake for exercise

Purpose The aim of this audit was to assess the representation of female athletes within the literature that has led to current guidelines for carbohydrate (CHO) intake in the acute periods surrounding exercise and the quality of this research. Methods We conducted a standardized audit of research assessing CHO loading protocols, CHO mouth rinse, and CHO intake before, during, and after exercise. Results A total of 937 studies were identified in this audit. There were a total of 11,202 participants across these studies, with only 11% being women. Most studies involved male-only cohorts (79%), with a mere 38 studies (4%) involving female-only cohorts and 14 studies (2%) including a methodological design for comparison of sex-based responses. The frequent use of incorrect terminology surrounding menstrual status and the failure of most studies (69%) to provide sufficient information on the menstrual status of participants suggests incomplete understanding and concern for female-specific considerations among researchers. Of the 197 studies that included women, only 13 (7%) provided evidence of acceptable methodological control of ovarian hormones, and no study met all best-practice recommendations. Of these 13 studies, only half also provided sufficient information regarding the athletic caliber of participants. The topics that received such scrutiny were CHO loading protocols and CHO intake during exercise. Conclusions The literature that underpins the current guidelines for CHO intake in the acute periods around exercise is lacking in high-quality research that can contribute knowledge specific to the female athlete and sex-based differences. New research that considers ovarian hormones and sex-based differences is needed to ensure that the recommendations for acute CHO fueling provided to female athletes are evidence based