Ferredoxin 1b deficiency leads to testis disorganization, impaired spermatogenesis and feminization in zebrafish

The roles of steroids in zebrafish sex differentiation, gonadal development and function of the adult gonad are poorly understood. Herein, we have employed a ferredoxin 1b (fdx1b) mutant zebrafish to explore such processes. Fdx1b is an essential electron-providing cofactor to mitochondrial steroidogenic enzymes, which are crucial for glucocorticoid and androgen production in vertebrates. Fdx1b-/- zebrafish mutants develop into viable adults, in which concentrations of androgens and the glucocorticoid, cortisol, are significantly reduced. Adult fdx1b-/- mutant zebrafish display predominantly female secondary sex characteristics but may possess either ovaries or testes, confirming that androgen signaling is dispensable for testicular differentiation in this species, as previously demonstrated in androgen receptor mutant zebrafish. Adult male fdx1b-/- mutant zebrafish do not exhibit characteristic breeding behaviors, and sperm production is reduced, resulting in infertility in standard breeding scenarios. However, eggs collected from wild-type females can be fertilized by the sperm of fdx1b-/- mutant males by IVF. The testes of fdx1b-/- mutant males are disorganized and lack defined seminiferous tubule structure. Expression of several pro-male and spermatogenic genes is decreased in the testes of fdx1b-/- mutant males, including pro-male transcription factor SRY-box 9a (sox9a) and spermatogenic genes insulin-like growth factor 3 (igf3) and insulin-like 3 (insl3). This study establishes an androgen- and cortisol-deficient fdx1b zebrafish mutant as a model for understanding the impacts of steroid deficiency on sex development and reproductive function. This model will be particularly useful for further investigation of the roles of steroids in spermatogenesis, gonadal development and regulation of reproductive behavior, thus enabling further elucidation of the physiological consequences of endocrine disruption in vertebrates

Together, yet still not equal? Sex integration in equestrian sport

Sex segregation is a core organising principle of most modern sports and is a key element in the marginalisation and subordination of girls and women in sport and beyond. In this article I explore the only Olympic-level sport which is not organised around sex segregation – equestrian sport – in order to consider the implications of sex integration for female participants. I draw on a study conducted on elite riders that found that although sex integration in equestrian sport does not lead to female participants being excluded from high-level competition, men continue to perform disproportionately well. This suggests that although sex integration may be an important step towards breaking down gender hierarchies in sport, without accompanying wider changes in gender norms and expectations, sex integration alone will not be enough to achieve greater gender equality in equestrian sport

Risk accuracy of type 2 diabetes in middle aged adults: Associations with sociodemographic, clinical, psychological and behavioural factors

Objective To identify the proportion of individuals with an accurate perception of their risk of type 2 diabetes (T2D) prior to, immediately after and eight weeks after receiving a personalised risk estimate. Additionally, we aimed to explore what factors are associated with underestimation and overestimation immediately post-intervention. Methods Cohort study based on the data collected in the Diabetes Risk Communication Trial. We included 379 participants (mean age 48.9 (SD 7.4) years; 55.1 women) who received a genotypic or phenotypic risk estimate for T2D. Results While only 1.3 of participants perceived their risk accurately at baseline, this increased to 24.7 immediately after receiving a risk estimate and then dropped to 7.3 at eight weeks. Those who overestimated their risk at baseline continued to overestimate it, whereas those who underestimated their risk at baseline improved their risk accuracy. We did not identify any other characteristics associated with underestimation or overestimation immediately after receiving a risk estimate. Conclusion Understanding a received risk estimate is challenging for most participants with many continuing to have inaccurate risk perception after receiving the estimate. Practice implications Individuals who overestimate or underestimate their T2D risk before receiving risk information might require different approaches for altering their risk perception. © 2017 The Author

Effect of interventions incorporating personalised cancer risk information on intentions and behaviour: A systematic review and meta-analysis of randomised controlled trials

Objective To provide a comprehensive review of the impact on intention to change health-related behaviours and health-related behaviours themselves, including screening uptake, of interventions incorporating information about cancer risk targeted at the general adult population. Design A systematic review and random-effects meta-analysis. Data sources An electronic search of MEDLINE, EMBASE, CINAHL and PsycINFO from 1 January 2000 to 1 July 2017. Inclusion criteria Randomised controlled trials of interventions including provision of a personal estimate of future cancer risk based on two or more non-genetic variables to adults recruited from the general population that include at least one behavioural outcome. Results We included 19 studies reporting 12 outcomes. There was significant heterogeneity in interventions and outcomes between studies. There is evidence that interventions incorporating personalised cancer risk information do not affect intention to attend or attendance at screening (relative risk 1.00 (0.97-1.03)). There is limited evidence that they increase smoking abstinence, sun protection, adult skin self-examination and breast examination, and decrease intention to tan. However, they do not increase smoking cessation, parental child skin examination or intention to protect skin. No studies assessed changes in diet, alcohol consumption or physical activity. Conclusions Interventions incorporating personalised cancer risk information do not affect uptake of screening, but there is limited evidence of effect on some health-related behaviours. Further research, ideally including objective measures of behaviour, is needed before cancer risk information is incorporated into routine practice for health promotion in the general population. Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted

The associations between the response efficacy and objective and subjective change in physical activity and diet in the Information and Risk Modification trial

Objectives: Many health promotion campaigns and interventions focussing on improving health-related behaviours have been based on targeting response efficacy. This is based on the assumption that response efficacy is an important modifiable determinant of behaviour change. This study aimed to quantify the association between response efficacy and objective and subjective measures of physical activity and diet. Study design: Prospective cohort analysis of data from a randomised controlled trial. Methods: A total of 953 participants were assessed for response efficacy at baseline and 12 weeks following randomisation to interventions to increase physical activity and improve diet. Subjective measures were collected via a self-report questionnaire that included two questions used to derive the Cambridge Index of physical activity and questions about daily or weekly fruit and vegetable, whole grain, meat and fish intake, based on the dietary guidelines to lower cardiovascular risk. Objective measures were quantified using accelerometers and plasma carotenoids. Results: The mean change in response efficacy for physical activity was +0.5 (standard deviation SD 2.0) and for diet was +0.5 (SD 2.1).There were no clinically or statistically significant associations between baseline or change in response efficacy and objective and subjective measures of physical activity or objective measures of diet. There was a small statistically significant association between baseline response efficacy and change in self-reported wholegrain consumption, but this is unlikely to be clinically significant. Conclusions: Response efficacy is not a fundamental determinant of diet and physical activity and should not be the main focus of interventions targeting these behaviours. © 2018 The Author(s

Model based optimization criteria for the generation of deep compressive residual stress fields in high elastic limit metallic alloys by ns-laser shock processing

Laser Shock Processing (LSP) is based on the application of a high intensity pulsed Laser beam (IN1 GW/cm2; τb50 ns) on a metallic target forcing a sudden vaporization of its surface into a high temperature and density plasma that immediately develops inducing a shock wave propagating into the material. The main acknowledged advantages of LSP consist on its capability of inducing a relatively deep compression residual stresses field into metallic alloy pieces allowing an improved mechanical behavior, explicitly, the life improvement of the treated specimens against wear, crack growth and stress corrosion cracking. Due to these specific advantages, Laser Shock Processing is considered as a competitive alternative technology to classical treatments for improving fatigue, corrosion cracking and wear resistance of metallic materials, and is being developed as a practical process amenable to production technology. In this paper, a model based systematization of process optimization criteria and a practical assessment on the real possibilities of the technique is presented along with practical results at laboratory scale on the application of LSP to characteristic high elastic limit metallic alloys, showing the induced residual stresses fields and the corresponding results on mechanical properties improvement induced by the treatment. The homogeneity of the residual stress fields distribution following the laser treatment spatial density will be specially analyzed

The depinning transition of a driven interface in the random-field Ising model around the upper critical dimension

We investigate the depinning transition for driven interfaces in the random-field Ising model for various dimensions. We consider the order parameter as a function of the control parameter (driving field) and examine the effect of thermal fluctuations. Although thermal fluctuations drive the system away from criticality the order parameter obeys a certain scaling law for sufficiently low temperatures and the corresponding exponents are determined. Our results suggest that the so-called upper critical dimension of the depinning transition is five and that the systems belongs to the universality class of the quenched Edward-Wilkinson equation.Comment: accepted for publication in Phys. Rev.

Making things happen : a model of proactive motivation

Being proactive is about making things happen, anticipating and preventing problems, and seizing opportunities. It involves self-initiated efforts to bring about change in the work environment and/or oneself to achieve a different future. The authors develop existing perspectives on this topic by identifying proactivity as a goal-driven process involving both the setting of a proactive goal (proactive goal generation) and striving to achieve that proactive goal (proactive goal striving). The authors identify a range of proactive goals that individuals can pursue in organizations. These vary on two dimensions: the future they aim to bring about (achieving a better personal fit within one’s work environment, improving the organization’s internal functioning, or enhancing the organization’s strategic fit with its environment) and whether the self or situation is being changed. The authors then identify “can do,” “reason to,” and “energized to” motivational states that prompt proactive goal generation and sustain goal striving. Can do motivation arises from perceptions of self-efficacy, control, and (low) cost. Reason to motivation relates to why someone is proactive, including reasons flowing from intrinsic, integrated, and identified motivation. Energized to motivation refers to activated positive affective states that prompt proactive goal processes. The authors suggest more distal antecedents, including individual differences (e.g., personality, values, knowledge and ability) as well as contextual variations in leadership, work design, and interpersonal climate, that influence the proactive motivational states and thereby boost or inhibit proactive goal processes. Finally, the authors summarize priorities for future researc

Impact of liver fat on the differential partitioning of hepatic triacylglycerol into VLDL subclasses on high and low sugar diets.

Dietary sugars are linked to the development of non-alcoholic fatty liver disease (NAFLD) and dyslipidaemia, but it is unknown if NAFLD itself influences the effects of sugars on plasma lipoproteins. To study this further, men with NAFLD (n=11) and low liver fat 'controls' (n= 14) were fed two iso-energetic diets, high or low in sugars (26% or 6% total energy) for 12 weeks, in a randomised, cross-over design. Fasting plasma lipid and lipoprotein kinetics were measured after each diet by stable isotope trace-labelling. There were significant differences in the production and catabolic rates of VLDL subclasses between men with NAFLD and controls, in response to the high and low sugar diets. Men with NAFLD had higher plasma concentrations of VLDL1-triacylglycerol (TAG) after the high ( P <0.02) and low sugar ( P <0.0002) diets, a lower VLDL1-TAG fractional catabolic rate after the high sugar diet ( P <0.01), and a higher VLDL1-TAG production rate after the low sugar diet ( P <0.01), relative to controls. An effect of the high sugar diet, was to channel hepatic TAG into a higher production of VLDL1-TAG ( P <0.02) in the controls, but in contrast, a higher production of VLDL2-TAG ( P <0.05) in NAFLD. These dietary effects on VLDL subclass kinetics could be explained, in part, by differences in the contribution of fatty acids from intra-hepatic stores, and de novo lipogenesis. This study provides new evidence that liver fat accumulation leads to a differential partitioning of hepatic TAG into large and small VLDL subclasses, in response to high and low intakes of sugars.The work was supported by a UK government grant from the Biological Biotechnology Scientific Research Council (Grant no. BB/G009899/1); University of Surrey PhD scholarship for AM; Medical Research Council (body composition measurements) and infrastructure support from the National Institute of Health Research at the Cambridge Biomedical Research Centre

Genetic predisposition influences plasma lipids of participants on habitual diet, but not the response to reductions in dietary intake of saturated fatty acids

Objective: SNPs identified from genome wide association studies associate with lipid risk markers of cardiovascular disease. This study investigated whether these SNPs altered the plasma lipid response to diet in the ‘RISCK’ study cohort. Methods: Participants (n = 490) from a dietary intervention to lower saturated fat by replacement with carbohydrate or monounsaturated fat, were genotyped for 39 lipid-associated SNPs. The association of each individual SNP, and of the SNPs combined (using genetic predisposition scores), with plasma lipid concentrations was assessed at baseline, and on change in response to 24 weeks on diets. Results: The associations between SNPs and lipid concentrations were directionally consistent with previous findings. The genetic predisposition scores were associated with higher baseline concentrations of plasma total(P = 0.02) and LDL (P = 0.002) cholesterol, triglycerides (P = 0.001) and apolipoprotein B (P = 0.004), and with lower baseline concentrations of HDL cholesterol (P < 0.001) and apolipoprotein A-I (P < 0.001). None of the SNPs showed significant association with the reduction of plasma lipids in response to the dietary interventions and there was no evidence of diet-gene interactions. Conclusion: Results from this exploratory study have shown that increased genetic predisposition was associated with an unfavourable plasma lipid profile at baseline, but did not influence the improvement in lipid profiles by the low-saturated-fat diets