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

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

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

Assessing Online-form Complexity for the Development of Assistive Technologies for Older Adults

Although cognitive declines occur as a natural product of the ageing process, the majority of online-forms do not cater specifically for the needs of older adult users. As a consequence, online-forms pose significant usability challenges to this target user group. The Delivering Inclusive Access to Disabled and Elderly Members of the community (DIADEM) project aims to develop a plug-in to a web browser that adapts existing online-form content so that it is more accessible and usable for older adults with cognitive decline. In order to identify requirements for developing the DIADEM application, it is necessary to observe users interacting with online-forms, and identify the usability challenges that occur as a result of this. However, the format and functionality of online-form content presented on the web varies greatly. Identifying a representative sample of online-forms that may be presented to users within a trials setting to elicit key usability challenges, has proved to be a non-trivial task. Consequently, we have developed a set of Bespoke Online-form Selection (BOFS) criteria which are used to help identify appropriate and representative candidate online-forms that may be used within the user trials setting to formulate initial requirements for developing the DIADEM application. In the context of the DIADEM project, BOFS has proved to be a valuable tool which has been used to successfully identify online-forms for use in our user trials. This paper presents the BOFS criteria, and shows how these are aligned with cognitive declines that are typically presented by the older adult user group, and demonstrates how BOFS has been of value within the context of the DIADEM project.</p

Revisiting white labourism: new debates on working-class whiteness in twentieth-century Southern Africa

This article is a contribution to and reassessment of the debate about the concept of ‘white labourism’ hosted in this journal in 2010. White labourism is a concept formulated by Jonathan Hyslop to describe an ideology combining an anti-capitalist critique with racial segregation that he argued was dominant in a transnational white working class in the British Empire in the early twentieth century. The debate about this concept has focused on the appeal and extent of this ideology in South Africa during the early twentieth century. In light of recent scholarship on Southern Africa, we take a longer-term perspective to critically examine the concept and the debate. Specifically, we make three interventions into this debate: we consider the role of white workers outside British imperial networks; we examine how radical and revolutionary ideas disappeared from white-working class politics in the mid-twentieth century; and we reassess the connection between transnational flows of people and ideas. Racial divisions in the working class and labour movement in Southern Africa were persistent and enduring. We argue that racial segregation had an enduring appeal to white workers in Southern Africa, and the sources of this appeal were more varied and locally rooted than simply transnational migration to the region.ASC – Publicaties niet-programma gebonde

The 1922 Rand Revolt: white workers’ Marikana?

ASC – Publicaties niet-programma gebonde

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 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

Initial multicenter experience with double nucleoside therapy for human immunodeficiency virus infection during pregnancy.

OBJECTIVE: To study maternal and neonatal effects of combination nucleoside analog therapy administered to human immunodeficiency virus (HIV)-infected pregnant women for maternal indications. METHODS: A multicenter, prospective observational study was undertaken at six perinatal centers in the United States and Canada that supported regional referral programs for the treatment of HIV-infected pregnant women. Demographic, laboratory, and pregnancy outcome data were collected for 39 women whose antiretroviral treatment regimens were expanded to include more than one nucleoside analog for maternal indications. The 40 newborns were monitored at pediatric referral centers through at least three months of age to ascertain their HIV infection status. RESULTS: For all 39 women, zidovudine (ZDV) therapy was instituted at 13.4 +/- 8.2 weeks, with a second agent (lamivudine [3TC] in 85% of cases) being added at a mean gestational age of 17.6 weeks. Duration of therapy with two agents was 20.6 +/- 10.4 weeks overall, with no women stopping medications because of side effects or toxicity. No significant changes in maternal laboratory values were seen, except for an increase in mean corpuscular volume, over the course of pregnancy. No clinically significant adverse neonatal outcomes were noted, with all but the three preterm newborns leaving hospital with their mothers. Neonatal anemia (hematocrit < 50%) was seen in 62% of newborns, with no children needing transfusion; mild elevations of liver function tests, primarily aspartate aminotransferase, were noted in 58% of newborns tested, though none were clinically jaundiced. Overall rate of neonatal HIV infection was 2.5% (95% confidence interval: 0.1-13.2%). CONCLUSION: Combination antiretroviral therapy during pregnancy with two nucleoside analogs was well-tolerated by mothers and newborns, with no significant short-term toxicities or side effects noted. Surveillance of exposed newborns' hematologic and liver function appears warranted