522 research outputs found

    Reproductive dysfunction and associated pathology in women undergoing military training

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    Evidence from civilian athletes raises the question of whether reproductive dysfunction may be seen in female soldiers as a result of military training. Such reproductive dysfunction consists of impaired ovulation with or without long term subfertility. We critically review pertinent evidence, which points towards reduced energy availability as the most likely explanation for exercise-induced reproductive dysfunction. Evidence also suggests reproductive dysfunction is mediated by activation of the hypothalamic-pituitary-adrenal axis and suppression of the hypothalamic-pituitary-gonadal axis, with elevated ghrelin and reduced leptin likely to play an important role. The observed reproductive dysfunction exists as part of a female athletic triad, together with osteopenia and disordered eating. If this phenomenon was shown to exist with UK military training this would be of significant concern. We hypothesise that the nature of military training and possibly field exercises may contribute to greater risk of reproductive dysfunction among female military trainees compared with exercising civilian controls. We discuss the features of military training and its participants, such as energy availability, age at recruitment, body phenotype, type of physical training, psychogenic stressors, altered sleep pattern and elemental exposure as contributors to reproductive dysfunction. We identify lines of future research to more fully characterise reproductive dysfunction in military women, and suggest possible interventions which, if indicated, could improve their future wellbeing

    Exploring the interplay between Buddhism and career development : a study of highly skilled women workers in Sri Lanka

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    This article adopts a socio cultural lens to examine the role of Buddhism in highly skilled women workers’ careers in Sri Lanka. While Buddhism enabled women’s career development by giving them strength to cope with difficult situations in work, it also seemed to restrict their agency and constrain their career advancement. Based on our findings, we argue that being perceived as a good Buddhist woman worked as a powerful form of career capital for the respondents in our sample, who used their faith to combat gender disadvantage in their work settings

    Sex differences in energy balance, body composition, and metabolic and endocrine markers during prolonged arduous military training

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    Energy deficits are common in military training and can result in endocrine and metabolic disturbances. This study provides first investigation of sex differences in energy balance, body composition, and endocrine and metabolic markers in response to prolonged and arduous military training. Men experienced greater energy deficits than women due to higher energy expenditure, which was not compensated for by increased energy intake. These energy deficits were not associated with decreases in fat or lean mass or metabolic or endocrine function

    The potential impact of climate change on Australia's soil organic carbon resources

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    BACKGROUND: Soil organic carbon (SOC) represents a significant pool of carbon within the biosphere. Climatic shifts in temperature and precipitation have a major influence on the decomposition and amount of SOC stored within an ecosystem and that released into the atmosphere. We have linked net primary production (NPP) algorithms, which include the impact of enhanced atmospheric CO(2 )on plant growth, to the SOCRATES terrestrial carbon model to estimate changes in SOC for the Australia continent between the years 1990 and 2100 in response to climate changes generated by the CSIRO Mark 2 Global Circulation Model (GCM). RESULTS: We estimate organic carbon storage in the topsoil (0–10 cm) of the Australian continent in 1990 to be 8.1 Gt. This equates to 19 and 34 Gt in the top 30 and 100 cm of soil, respectively. By the year 2100, under a low emissions scenario, topsoil organic carbon stores of the continent will have increased by 0.6% (49 Mt C). Under a high emissions scenario, the Australian continent becomes a source of CO(2 )with a net reduction of 6.4% (518 Mt) in topsoil carbon, when compared to no climate change. This is partially offset by the predicted increase in NPP of 20.3% CONCLUSION: Climate change impacts must be studied holistically, requiring integration of climate, plant, ecosystem and soil sciences. The SOCRATES terrestrial carbon cycling model provides realistic estimates of changes in SOC storage in response to climate change over the next century, and confirms the need for greater consideration of soils in assessing the full impact of climate change and the development of quantifiable mitigation strategies

    Female reproductive, adrenal and metabolic changes during an Antarctic traverse

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    Purpose To explore the effects of the first all-female transantarctic expedition on hormonal axes pertinent to reproductive and metabolic function. Methods Six females (age, 28–36 yr; body mass index, 24.2 ± 0.97 kg·m−2) hauled 80-kg sledges 1700 km in 61 d. Estimated average energy intake was 20.8 ± 0.1 MJ·d−1 (4970 ± 25 kcal·d−1). Whole and regional body composition was measured by dual-energy x-ray absorptiometry 1 and 2 months before and 15 d after, the expedition. Body fat was also estimated by skinfold and bioimpedance immediately before and after the expedition. Basal metabolic and endocrine blood markers and, after 0.25 mg dexamethasone suppression, 1-h 10-μg gonadorelin and 1.0 μg adrenocortiocotrophin-(1–24) tests were completed, 39–38 d preexpedition and 4 to 5 d and 15 to 16 d postexpedition. Cortisol was assessed in hair (monthly average concentrations) and saliva (five-point day curves and two-point diurnal sampling). Results Average body mass loss was 9.37 ± 2.31 kg (P < 0.0001), comprising fat mass only; total lean mass was maintained. Basal sex steroids, corticosteroids, and metabolic markers were largely unaffected by the expedition except leptin, which decreased during the expedition and recovered after 15 d, a proportionately greater change than body fat. Luteinizing hormone reactivity was suppressed before and during the expedition, but recovered after 15 d, whereas follicle-stimulating hormone did not change during or after the expedition. Cortisol reactivity did not change during or after the expedition. Basal (suppressed) cortisol was 73.25 ± 45.23 mmol·L−1 before, 61.66 ± 33.11 mmol·L−1 5 d postexpedition and 54.43 ± 28.60 mmol·L−1 16 d postexpedition (P = 0.7). Hair cortisol was elevated during the expedition. Conclusions Maintenance of reproductive and hypothalamic-pituitary-adrenal axis function in women after an extreme physical endeavor, despite energy deficiency, suggests high female biological capacity for extreme endurance exercise

    Challenges of clinical trial design when there is lack of clinical equipoise: use of a response-conditional crossover design

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    Clinical equipoise is widely accepted as the basis of ethics in clinical research and requires investigators to be uncertain of the relative therapeutic merits of trial comparators. When clinical equipoise is in question, innovative trial designs are needed to reduce ethical tension while satisfying regulators’ requirements. We report a novel response-conditional crossover study design used in a Phase 3, randomized, double-blind, placebo-controlled clinical trial of intravenous 10% caprylate-chromatography purified immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy. During the initial 24-week period, patients crossed over to the alternative treatment at the first sign of deterioration or if they failed to improve or were unable to maintain improvement at any time after 6 weeks. This trial design addressed concerns about lack of equipoise raised by physicians interested in trial participation and proved acceptable to regulatory authorities. The trial design may be applicable to other studies where clinical equipoise is in question

    The extraordinary evolutionary history of the reticuloendotheliosis viruses

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    The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events

    Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity

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    TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5α but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations

    Combined inhibition of DNA methylation and histone acetylation enhances gene re-expression and drug sensitivity in vivo

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    Histone deacetylation and DNA methylation have a central role in the control of gene expression in tumours, including transcriptional repression of tumour suppressor genes and genes involved in sensitivity to chemotherapy. Treatment of cisplatin-resistant cell lines with an inhibitor of DNA methyltransferases, 2-deoxy-5′azacytidine (decitabine), results in partial reversal of DNA methylation, re-expression of epigenetically silenced genes including hMLH1 and sensitisation to cisplatin both in vitro and in vivo. We have investigated whether the combination of decitabine and a clinically relevant inhibitor of histone deacetylase activity (belinostat, PXD101) can further increase the re-expression of genes epigenetically silenced by DNA methylation and enhance chemo-sensitisation in vivo at well-tolerated doses. The cisplatin-resistant human ovarian cell line A2780/cp70 has the hMLH1 gene methylated and is resistant to cisplatin both in vitro and when grown as a xenograft in mice. Treatment of A2780/cp70 with decitabine and belinostat results in a marked increase in expression of epigenetically silenced MLH1 and MAGE-A1 both in vitro and in vivo when compared with decitabine alone. The combination greatly enhanced the effects of decitabine alone on the cisplatin sensitivity of xenografts. As the dose of decitabine that can be given to patients and hence the maximum pharmacodynamic effect as a demethylating agent is limited by toxicity and eventual re-methylation of genes, we suggest that the combination of decitabine and belinostat could have a role in the efficacy of chemotherapy in tumours that have acquired drug resistance due to DNA methylation and gene silencing

    Seasonal variations in carbon, nitrogen and phosphorus concentrations and C:N:P stoichiometry in different organs of a Larix principis-rupprechtii Mayr. plantation in the Qinling Mountains, China

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    Understanding how concentrations of elements and their stoichiometry change with plant growth and age is critical for predicting plant community responses to environmental change. Weusedlong-term field experiments to explore how the leaf, stem and root carbon (C), nitrogen (N) and phosphorous (P) concentrations and their stoichiometry changed with growth and stand age in a L.principis-rupprechtii Mayr. plantation from 2012–2015 in the Qinling Mountains, China. Our results showed that the C, N and P concentrations and stoichiometric ratios in different tissues of larch stands were affected by stand age, organ type andsampling month and displayed multiple correlations with increased stand age in different growing seasons. Generally, leaf C and N concentrations were greatest in the fast-growing season, but leaf P concentrations were greatest in the early growing season. However, no clear seasonal tendencies in the stem and root C, N and P concentrations were observed with growth. In contrast to N and P, few differences were found in organ-specific C concentrations. Leaf N:P was greatest in the fast-growing season, while C:N and C:P were greatest in the late-growing season. No clear variations were observed in stem and root C:N, C:P andN:Pthroughout the entire growing season, but leaf N:P was less than 14, suggesting that the growth of larch stands was limited by N in our study region. Compared to global plant element concentrations and stoichiometry, the leaves of larch stands had higher C, P, C:NandC:PbutlowerNandN:P,andtherootshadgreater PandC:NbutlowerN,C:Pand N:P. Our study provides baseline information for describing the changes in nutritional elements with plant growth, which will facilitates plantation forest management and restoration, and makes avaluable contribution to the global data pool on leaf nutrition and stoichiometry
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