Inferring Gene Family Histories in Yeast Identifies Lineage Specific Expansions

PublishedThe complement of genes found in the genome is a balance between gene gain and gene loss. Knowledge of the specific genes that are gained and lost over evolutionary time allows an understanding of the evolution of biological functions. Here we use new evolutionary models to infer gene family histories across complete yeast genomes; these models allow us to estimate the relative genome-wide rates of gene birth, death, innovation and extinction (loss of an entire family) for the first time. We show that the rates of gene family evolution vary both between gene families and between species. We are also able to identify those families that have experienced rapid lineage specific expansion/contraction and show that these families are enriched for specific functions. Moreover, we find that families with specific functions are repeatedly expanded in multiple species, suggesting the presence of common adaptations and that these family expansions/contractions are not random. Additionally, we identify potential specialisations, unique to specific species, in the functions of lineage specific expanded families. These results suggest that an important mechanism in the evolution of genome content is the presence of lineage-specific gene family changes.This work is funded by BBSRC grant BB/I020489/1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

M.I.T./Canadian Vestibular Experiments on the Spacelab-1 Mission. Part 1: Sensory Adaptation to Weightlessness and Readaptation to One-G: An Overview

Experiments on human spatial orientation were conducted on four crewmembers of Space Shuttle Spacelab Mission 1. The conceptual background of the project, the relationship among the experiments, and their relevance to a 'sensory reinterpretation hypothesis' are presented. Detailed experiment procedures and results are presented in the accompanying papers in this series. The overall findings are discussed as they pertain to the following aspects of hypothesized sensory reinterpretation in weightlessness: (1) utricular otolith afferent signals are reinterpreted as indicating head translation rather than tilt, (2) sensitivity of reflex responses to footward acceleration is reduced, and (3) increased weighting is given to visual and tactile cues in orientation perception and posture control. Results suggest increased weighting of visual cues and reduced weighting of graviceptor signals in weightlessness

Determining the evolutionary history of gene families

PublishedMotivation: Recent large-scale studies of individuals within a population have demonstrated that there is widespread variation in copy number in many gene families. In addition, there is increasing evidence that the variation in gene copy number can give rise to substantial phenotypic effects. In some cases, these variations have been shown to be adaptive. These observations show that a full understanding of the evolution of biological function requires an understanding of gene gain and gene loss. Accurate, robust evolutionary models of gain and loss events are, therefore, required. Results: We have developed weighted parsimony and maximum likelihood methods for inferring gain and loss events. To test these methods, we have used Markov models of gain and loss to simulate data with known properties. We examine three models: a simple birth–death model, a single rate model and a birth–death innovation model with parameters estimated from Drosophila genome data. We find that for all simulations maximum likelihood-based methods are very accurate for reconstructing the number of duplication events on the phylogenetic tree, and that maximum likelihood and weighted parsimony have similar accuracy for reconstructing the ancestral state. Our implementations are robust to different model parameters and provide accurate inferences of ancestral states and the number of gain and loss events. For ancestral reconstruction, we recommend weighted parsimony because it has similar accuracy to maximum likelihood, but is much faster. For inferring the number of individual gene loss or gain events, maximum likelihood is noticeably more accurate, albeit at greater computational cost.Biotechnology and Biological Sciences Research Council, UK

Urinary bisphenol a concentration and angiography-defined coronary artery stenosis.

PublishedResearch Support, Non-U.S. Gov'tThis is the final version of the article. Available from PLoS via the DOI in this record.BACKGROUND: Bisphenol A is widely used in food and drinks packaging. There is evidence of associations between raised urinary bisphenol A (uBPA) and increased incidence of reported cardiovascular diagnoses. METHODOLOGY/PRINCIPAL FINDINGS: To estimate associations between BPA exposure and angiographically graded coronary atherosclerosis. 591 patients participating in The Metabonomics and Genomics in Coronary Artery Disease (MaGiCAD) study in Cambridgeshire UK, comparing urinary BPA (uBPA) with grades of severity of coronary artery disease (CAD) on angiography. Linear models were adjusted for BMI, occupational social class and diabetes status. Severe (one to three vessel) CAD was present in 385 patients, 86 had intermediate disease (n=86) and 120 had normal coronary arteries. The (unadjusted) median uBPA concentration was 1.28 ng/mL with normal coronary arteries, and 1.53 ng/mL with severe CAD. Compared to those with normal coronary arteries, uBPA concentration was significantly higher in those with severe CAD (OR per uBPA SD=5.96 ng/ml OR=1.43, CI 1.03 to 1.98, p=0.033), and near significant for intermediate disease (OR=1.69, CI 0.98 to 2.94, p=0.061). There was no significant uBPA difference between patients with severe CAD (needing surgery) and the remaining groups combined. CONCLUSIONS/SIGNIFICANCE: BPA exposure was higher in those with severe coronary artery stenoses compared to those with no vessel disease. Larger studies are needed to estimate true dose response relationships. The mechanisms underlying the association remain to be established.David Melzer and Tamara Galloway’s work on BPA has been supported by unrestricted funds from the University of Exeter (www.exeter.ac.uk), the Peninsula Clinical Research facility (www.peninsulacrf.org) and by grant funding from the British Heart Foundation (www.bhf.org.uk - grant reference PG/09/097). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Is there still a place for the concept of therapeutic regression in psychoanalysis?

The author uses his own failure to find a place for the idea of therapeutic regression in his clinical thinking or practice as the basis for an investigation into its meaning and usefulness. He makes a distinction between three ways the term ‘regression’ is used in psychoanalytic discourse: as a way of evoking a primitive level of experience; as a reminder in some clinical situations of the value of non-intervention on the part of the analyst; and as a description of a phase of an analytic treatment with some patients where the analyst needs to put aside normal analytic technique in order to foster a regression in the patient. It is this third meaning, which the author terms “therapeutic regression” that this paper examines, principally by means of an extended discussion of two clinical examples of a patient making a so-called therapeutic regression, one given by Winnicott and the other by Masud Khan. The author argues that in these examples the introduction of the concept of therapeutic regression obscures rather than clarifies the clinical process. He concludes that, as a substantial clinical concept, the idea of therapeutic regression has outlived its usefulness. However he also notes that many psychoanalytic writers continue to find a use for the more generic concept of regression, and that the very engagement with the more particular idea of therapeutic regression has value in provoking questions as to what is truly therapeutic in psychoanalytic treatment

Urinary bisphenol A concentration and risk of future coronary artery disease in apparently healthy men and women

addresses: Epidemiology and Public Health Group, Peninsula College of Medicine and Dentistry, Barrack Road, Exeter, United Kingdom. [email protected]: Comparative Study; Journal Article; Research Support, Non-U.S. Gov'tThe endocrine-disrupting chemical bisphenol A (BPA) is widely used in food and beverage packaging. Higher urinary BPA concentrations were cross-sectionally associated with heart disease in National Health and Nutrition Examination Survey (NHANES) 2003-2004 and NHANES 2005-2006, independent of traditional risk factors.Medical Research Council UKCancer Research UKBritish Heart FoundationPeninsula Medical School, University of ExeterEuropean Regional Development FundEuropean Social Fund Convergence Programme for Cornwall and the Isles of ScillyNational Institute for Health Research Collaborations for Leadership in Applied Health Research and Car

Team-taught versus individually taught undergraduate education: A qualitative study of student experiences and preferences

Team teaching is becoming more common in undergraduate programmes of study although the relative merits to the more traditional individually taught courses have not been determined for best practice. For this study, 15 final year undergraduate students were interviewed to gain insight into their learning experiences. A thematic analysis of the interview data identified the perceived advantages and disadvantages of each mode of teaching. The advantages of individually taught courses included: Consistency of content delivery and advice, Familiarity with the lecturer’s teaching style and better Continuity of the subject content. The disadvantage of individually taught modules included Missing knowledge, compared to a team approach. Advantages of team taught modules included: Greater insight into a topic delivered by multiple team members. Disadvantages included: Content overlap, Conflicting messages relating to assessment, team members not taking Ownership of their roles and responsibilities and a belief that overall Team failure is worse than individual failure to deliver a module well. The results revealed that individually taught modules were generally preferred to team taught modules. A set of best practice recommendations are proposed to address the challenges when delivering team-taught teaching and become more student focused

Completion of fit notes by GPs: a mixed methods study

Aims: The aim of this study was to investigate the completion of fit notes by UK general practitioners (GPs). A series of actual fit notes issued to employed patients were examined, and their GPs’ reflections and experiences of fit note completion explored. Methods: A mixed-methods design was used. Data were collected from copies of 94 fit notes issued to employed patients by 11 GPs, and from 86 questionnaires completed by these GPs reflecting on the fit notes they had issued. Face-to-face interviews were then conducted with each GP. Results: Fit note completion is not meeting expectations for a number of reasons. These include the following: limited knowledge and awareness of the guidance in fit note completion; problems with the fit note format; lack of mandatory training in completing fit notes; lack of incentive to change practice; incomplete implementation of the electronic fit note; GPs’ lack of confidence in, and doubts about the appropriateness of performing this role. Conclusion: If UK GPs are to continue their contractual responsibility for completing fit notes, further consideration of their education and training needs is urgently required. Weaknesses in the design and format of the fit note and the availability of the electronic version also need to be addressed