Evolution of hindlimb muscle anatomy across the tetrapod water-to-land transition, including comparisons with forelimb anatomy

Tetrapod limbs are a key innovation implicated in the evolutionary success of the clade. Although musculoskeletal evolution of the pectoral appendage across the fins‐to‐limbs transition is fairly well documented, that of the pelvic appendage is much less so. The skeletal elements of the pelvic appendage in some tetrapodomorph fish and the earliest tetrapods are relatively smaller and/or qualitatively less similar to those of crown tetrapods than those of the pectoral appendage. However, comparative and developmental works have suggested that the musculature of the tetrapod forelimb and hindlimb was initially very similar, constituting a “similarity bottleneck” at the fins‐to‐limbs transition. Here we used extant phylogenetic bracketing and phylogenetic character optimization to reconstruct pelvic appendicular muscle anatomy in several key taxa spanning the fins‐to‐limbs and water‐to‐land transitions. Our results support the hypothesis that transformation of the pelvic appendages from fin‐like to limb‐like lagged behind that of the pectoral appendages. Compared to similar reconstructions of the pectoral appendages, the pelvic appendages of the earliest tetrapods had fewer muscles, particularly in the distal limb (shank). In addition, our results suggest that the first tetrapods had a greater number of muscle‐muscle topological correspondences between the pectoral and pelvic appendages than tetrapodomorph fish had. However, ancestral crown‐group tetrapods appear to have had an even greater number of similar muscles (both in terms of number and as a percentage of the total number of muscles), indicating that the main topological similarity bottleneck between the paired appendages may have occurred at the origin of the tetrapod crown group

Nuclear localization and function of polypeptide ligands and their receptors: a new paradigm for hormone specificity within the mammary gland?

The specific effects triggered by polypeptide hormone/growth factor stimulation of mammary cells were considered mediated solely by receptor-associated signaling networks. A compelling body of new data, however, clearly indicates that polypeptide ligands and/or their receptors are transported into the nucleus, where they function directly to regulate the expression of specific transcription factors and gene loci. The intranuclear function of these complexes may contribute to the explicit functions associated with a given ligand, and may serve as new targets for pharmacologic intervention

Is adolescent body mass index and waist circumference associated with the food environments surrounding schools and homes? A longitudinal analysis

Background: There has been considerable interest in the role of access to unhealthy food options as a determinant of weight status. There is conflict across the literature as to the existence of such an association, partly due to the dominance of cross-sectional study designs and inconsistent definitions of the food environment. The aim of our study is to use longitudinal data to examine if features of the food environment are associated to measures of adolescent weight status. Methods: Data were collected from secondary schools in Leeds (UK) and included measurements at school years 7 (ages 11/12), 9 (13/14), and 11 (15/16). Outcome variables, for weight status, were standardised body mass index and standardised waist circumference. Explanatory variables included the number of fast food outlets, supermarkets and ‘other retail outlets’ located within a 1 km radius of an individual’s home or school, and estimated travel route between these locations (with a 500 m buffer). Multi-level models were fit to analyse the association (adjusted for confounders) between the explanatory and outcome variables. We also examined changes in our outcome variables between each time period. Results: We found few associations between the food environment and measures of adolescent weight status. Where significant associations were detected, they mainly demonstrated a positive association between the number of amenities and weight status (although effect sizes were small). Examining changes in weight status between time periods produced mainly non-significant or inconsistent associations. Conclusions: Our study found little consistent evidence of an association between features of the food environment and adolescent weight status. It suggests that policy efforts focusing on the food environment may have a limited effect at tackling the high prevalence of obesity if not supported by additional strategies

Overweight, Obesity and Underweight Is Associated with Adverse Psychosocial and Physical Health Outcomes among 7-Year-Old Children: The 'Be Active, Eat Right' Study

Background:Limited studies have reported on associations between overweight, and physical and psychosocial health outcomes among younger children. This study evaluates associations between overweight, obesity and underweight in 5-year-old children, and parent-reported health outcomes at age 7 years.Methods:Data were used from the 'Be active, eat right' study. Height and weight were measured at 5 and 7 years. Parents reported on child physical and psychosocial health outcomes (e.g. respiratory symptoms, general health, happiness, insecurity and adverse treatment). Regression models, adjusted for potential confounders, were fitted to predict health outcomes at age 7 years.Results:The baseline study sample consisted of 2,372 children mean age 5.8 (SD 0.4) years; 6.2% overweight, 1.6% obese and 15.0% underweight. Based on parent-report, overweight, obese and underweight children had an odds ratio (OR) of 5.70 (95% CI: 4.10 to 7.92), 35.34 (95% CI: 19.16; 65.17) and 1.39 (95% CI: 1.05 to 1.84), respectively, for being treated adversely compared to normal weight children. Compared to children with a low stable body mass index (BMI), parents of children with a high stable BMI reported their child to have an OR of 3.87 (95% CI: 1.75 to 8.54) for visiting the general practitioner once or more, an OR of 15.94 (95% CI: 10.75 to 23.64) for being treated adversely, and an OR of 16.35 (95% CI: 11.08 to 24.36) for feeling insecure.Conclusion:This study shows that overweight, obesity and underweight at 5 years of age is associated with more parent-reported adverse treatment of the child. Qualitative research examining underlying mechanisms is recommended. Healthcare providers should be aware of the possible adverse effects of childhood overweight and also relative underweight, and provide parents and children with appropriate counseling

Metabolic power in hurling with respect to position and halves of match-play.

The current investigation compared the metabolic power and energetic characteristics in team sports with respect to positional lines and halves of match-play. Global positioning system (GPS) technology data were collected from 22 elite competitive hurling matches over a 3-season period. A total of 250 complete match-files were recorded with players split into positional groups of full-back; half-back; midfield; half-forward; full-forward. Raw GPS data were exported into a customized spreadsheet that provided estimations of metabolic power and speed variables across match-play events (average metabolic power [Pmet], high metabolic load distance [HMLD], total distance, relative distance, high-speed distance, maximal speed, accelerations, and deceleration). Pmet, HMLD, total, relative and high-speed distance were 8.9 ± 1.6 W·kg-1, 1457 ± 349 m, 7506 ± 1364 m, 107 ± 20 m·min-1 and 1169 ± 260 m respectively. Half-backs, midfielders and half-forwards outperformed full-backs (Effect Size [ES] = 1.03, 1.22 and 2.07 respectively), and full-forwards in Pmet (Effect Size [ES] = 1.70, 2.07 and 1.28 respectively), and HMLD (full-backs: ES = -1.23, -1.37 and -0.84 respectively, and full-forwards: ES = -1.77, -2.00 and -1.38 respectively). Half-backs (ES = -0.60), midfielders (ES = -0.81), and half-forwards (ES = -0.74) experienced a second-half temporal decrement in HMLD. The current investigation demonstrates that metabolic power may increase our understanding of the match-play demands placed on elite hurling players. Coaches may utilize these findings to construct training drills that replicate match-play demands

Common variation near ROBO2 is associated with expressive vocabulary in infancy

Twin studies suggest that expressive vocabulary at ~24 months is modestly heritable. However, the genes influencing this early linguistic phenotype are unknown. Here we conduct a genome-wide screen and follow-up study of expressive vocabulary in toddlers of European descent from up to four studies of the EArly Genetics and Lifecourse Epidemiology consortium, analysing an early (15–18 months, ‘one-word stage’, NTotal=8,889) and a later (24–30 months, ‘two-word stage’, NTotal=10,819) phase of language acquisition. For the early phase, one single-nucleotide polymorphism (rs7642482) at 3p12.3 near ​ROBO2, encoding a conserved axon-binding receptor, reaches the genome-wide significance level (P=1.3 × 10−8) in the combined sample. This association links language-related common genetic variation in the general population to a potential autism susceptibility locus and a linkage region for dyslexia, speech-sound disorder and reading. The contribution of common genetic influences is, although modest, supported by genome-wide complex trait analysis (meta-GCTA h215–18-months=0.13, meta-GCTA h224–30-months=0.14) and in concordance with additional twin analysis (5,733 pairs of European descent, h224-months=0.20)

Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation

Many drugs and xenobiotics are lipophilic and they should be transformed into more polar water soluble compounds to be excreted. Cimetidine inhibits cytochrome P450. The aim of this study was to investigate the preventive and/or reversal action of cimetidine on cytochrome P450 induction and other metabolic alterations provoked by the carcinogen p-dimethylaminoazobenzene. A group of male CF1 mice received a standard laboratory diet and another group was placed on dietary p-dimethylaminoazobenzene (0.5% w w−1). After 40 days of treatment, animals of both groups received p-dimethylaminoazobenzene and two weekly doses of cimetidine (120 mg kg−1, i.p.) during a following period of 35 days. Cimetidine prevented and reversed δ-aminolevulinate synthetase induction and cytochrome P450 enhancement provoked by p-dimethylaminoazobenzene. However, cimetidine did not restore haem oxygenase activity decreased by p-dimethylaminoazobenzene. Enhancement in glutathione S-transferase activity provoked by p-dimethylaminoazobenzene, persisted in those animals then treated with cimetidine. This drug did not modify either increased lipid peroxidation or diminution of the natural antioxidant defence system (inferred by catalase activity) induced by p-dimethylaminoazobenzene. In conclusion, although cimetidine treatment partially prevented and reversed cytochrome P450 induction, and alteration on haem metabolism provoked by p-dimethylaminoazobenzene AB, it did not reverse liver damage or lipid peroxidation. These results further support our hypothesis on the necessary existence of a multiple biochemical pathway disturbance for the onset of hepatocarcinogenesis initiation

"I won't be staying here for long": a qualitative study on the retention of migrant nurses in Ireland

<p>Abstract</p> <p>Background</p> <p>Although international nurse recruitment campaigns have succeeded in attracting large numbers of migrant nurses to countries such as Ireland, where domestic supply has not kept pace with demand, the long-term success of such initiatives from a workforce planning perspective will depend on the extent to which these nurses can be retained in destination countries.</p> <p>Methods</p> <p>This paper draws on qualitative, in-depth interviews undertaken with 21 migrant nurses in Ireland, focusing specifically on their future migration intentions.</p> <p>Results</p> <p>Our findings indicate that more than half of the respondents are considering migration onwards, for the most part because the destination country has failed to provide them with sufficient stability, particularly in terms of citizenship and family reunification. In considering onward migration, factors outside the health system were of most concern to those interviewed.</p> <p>Conclusion</p> <p>This demonstrates the need for destination countries to take a broader and more long-term approach to international nurse recruitment, rather than regarding it as an inexpensive way to fill gaps within the health care system.</p