34 research outputs found

    Sequencing of Pax6 loci from the elephant shark reveals a family of Pax6 genes in vertebrate genomes, forged by ancient duplications and divergences

    Get PDF
    Pax6 is a developmental control gene essential for eye development throughout the animal kingdom. In addition, Pax6 plays key roles in other parts of the CNS, olfactory system, and pancreas. In mammals a single Pax6 gene encoding multiple isoforms delivers these pleiotropic functions. Here we provide evidence that the genomes of many other vertebrate species contain multiple Pax6 loci. We sequenced Pax6-containing BACs from the cartilaginous elephant shark (Callorhinchus milii) and found two distinct Pax6 loci. Pax6.1 is highly similar to mammalian Pax6, while Pax6.2 encodes a paired-less Pax6. Using synteny relationships, we identify homologs of this novel paired-less Pax6.2 gene in lizard and in frog, as well as in zebrafish and in other teleosts. In zebrafish two full-length Pax6 duplicates were known previously, originating from the fish-specific genome duplication (FSGD) and expressed in divergent patterns due to paralog-specific loss of cis-elements. We show that teleosts other than zebrafish also maintain duplicate full-length Pax6 loci, but differences in gene and regulatory domain structure suggest that these Pax6 paralogs originate from a more ancient duplication event and are hence renamed as Pax6.3. Sequence comparisons between mammalian and elephant shark Pax6.1 loci highlight the presence of short- and long-range conserved noncoding elements (CNEs). Functional analysis demonstrates the ancient role of long-range enhancers for Pax6 transcription. We show that the paired-less Pax6.2 ortholog in zebrafish is expressed specifically in the developing retina. Transgenic analysis of elephant shark and zebrafish Pax6.2 CNEs with homology to the mouse NRE/Pα internal promoter revealed highly specific retinal expression. Finally, morpholino depletion of zebrafish Pax6.2 resulted in a "small eye" phenotype, supporting a role in retinal development. In summary, our study reveals that the pleiotropic functions of Pax6 in vertebrates are served by a divergent family of Pax6 genes, forged by ancient duplication events and by independent, lineage-specific gene losses

    The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

    Get PDF
    Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

    The Science Performance of JWST as Characterized in Commissioning

    Full text link
    This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

    Data from: Choosy cannibals preferentially consume siblings with relatively low fitness prospects

    No full text
    When an individual can selfishly cannibalize a relative or altruistically set it free, the benefits of altruism will be positively associated with the relative's fitness prospects (the benefits it receives from altruism). We tested the prediction that altruism should be preferentially directed toward high-quality relatives using larvae of the New Mexican spadefoot toad (Spea multiplicata), a species in which tadpoles plastically express omnivore and carnivore ecomorphs. In a no-choice design, we presented carnivores with sibling or nonsibling omnivores varying in developmental stage, which is positively associated with survival in this toad's ephemeral larval environment. There was a significant interaction between relatedness and developmental stage on the probability of cannibalism: carnivores were overall more likely to cannibalize less developed omnivores, but this effect was exaggerated when the potential victim was a sibling. This evidence that altruists favor relatives with high fitness prospects highlights the numerous factors shaping altruism's payoffs

    Results of experimental cannibalism trials

    No full text
    Data include information about carnivore id and sibship of origin, as well as information about omnivore (potential victim) sibship and morphology. Cannibalism is scored as a binary variable

    Limited lipid-lowering effects of regular consumption of whole soybean foods

    Full text link
    AIM: To examine cardiovascular health benefits of foods containing a whole soybean extract. METHODS: The study design was a randomized, placebo-controlled crossover trial of consuming soy-based milk and yoghurt (treatment) or equivalent dairy products (control) for 5 weeks each. Twenty-six mildly hypercholesterolaemic and/or hypertensive volunteers were recruited from the community as study volunteers, of which 23 completed. Main outcome measures included clinic and ambulatory blood pressure, arterial compliance, lipids, fatty acids and isoflavones in fasted blood and 24-hour urinary isoflavone excretion. Nutrient intakes were assessed initially and after each 5-week period. Multiple regression analyses were used to determine predictor variables in statistical models; order effects were tested by repeated measures ANOVA. Changes in Lp(a) were determined by Wilcoxon signed ranks tests; other differences between treatment and control were assessed by t tests. RESULTS: Plasma and urinary isoflavones were markedly increased by whole soy supplementation but there were no overall differences in plasma lipids, blood pressure or arterial compliance between the soy and dairy diets. However, in 8 equol-positive subjects (equol detected in either plasma or urine), retrospective analysis revealed significant reductions in total cholesterol (8.5%), LDL cholesterol (10%), LDL:HDL ratio (13.5%), plasma triglycerides (21%) and lipoprotein(a) (11%) with the soy diet. These reductions were independent of changes in polyunsaturated fat and other macronutrient intakes. CONCLUSIONS: Regular consumption of whole soybean milk and yogurt products had no effect on plasma lipids, blood pressure or arterial compliance in at-risk subjects, despite substantially increasing isoflavone levels in blood and urine. Retrospective analysis suggests that improvement of plasma lipids may have been limited to equol-positive subjects

    Lipid gymnastics

    No full text
    corecore