Rampant Adaptive Evolution in Regions of Proteins with Unknown Function in Drosophila simulans

Adaptive protein evolution is pervasive in Drosophila. Genomic studies, thus far, have analyzed each protein as a single entity. However, the targets of adaptive events may be localized to particular parts of proteins, such as protein domains or regions involved in protein folding. We compared the population genetic mechanisms driving sequence polymorphism and divergence in defined protein domains and non-domain regions. Interestingly, we find that non-domain regions of proteins are more frequent targets of directional selection. Protein domains are also evolving under directional selection, but appear to be under stronger purifying selection than non-domain regions. Non-domain regions of proteins clearly play a major role in adaptive protein evolution on a genomic scale and merit future investigations of their functional properties

An accurate test for homogeneity of odds ratios based on Cochran's Q-statistic

Background: A frequently used statistic for testing homogeneity in a meta-analysis of K independent studies is Cochran's Q. For a standard test of homogeneity the Q statistic is referred to a chi-square distribution with K - 1 degrees of freedom. For the situation in which the effects of the studies are logarithms of odds ratios, the chi-square distribution is much too conservative for moderate size studies, although it may be asymptotically correct as the individual studies become large. Methods: Using a mixture of theoretical results and simulations, we provide formulas to estimate the shape and scale parameters of a gamma distribution to t the distribution of Q. Results: Simulation studies show that the gamma distribution is a good approximation to the distribution for Q. Conclusions: : Use of the gamma distribution instead of the chi-square distribution for Q should eliminate inaccurate inferences in assessing homogeneity in a meta-analysis. (A computer program for implementing this test is provided.) This hypothesis test is competitive with the Breslow-Day test both in accuracy of level and in power

Institutional Experience with Voriconazole Compared with Liposomal Amphotericin B as Empiric Therapy for Febrile Neutropenia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90034/1/phco.27.7.970.pd

Fluctuating Finite Element Analysis (FFEA): A continuum mechanics software tool for mesoscale simulation of biomolecules

Fluctuating Finite Element Analysis (FFEA) is a software package designed to perform continuum mechanics simulations of proteins and other globular macromolecules. It combines conventional finite element methods with stochastic thermal noise, and is appropriate for simulations of large proteins and protein complexes at the mesoscale (length-scales in the range of 5 nm to 1 μm), where there is currently a paucity of modelling tools. It requires 3D volumetric information as input, which can be low resolution structural information such as cryo-electron tomography (cryo-ET) maps or much higher resolution atomistic co-ordinates from which volumetric information can be extracted. In this article we introduce our open source software package for performing FFEA simulations which we have released under a GPLv3 license. The software package includes a C ++ implementation of FFEA, together with tools to assist the user to set up the system from Electron Microscopy Data Bank (EMDB) or Protein Data Bank (PDB) data files. We also provide a PyMOL plugin to perform basic visualisation and additional Python tools for the analysis of FFEA simulation trajectories. This manuscript provides a basic background to the FFEA method, describing the implementation of the core mechanical model and how intermolecular interactions and the solvent environment are included within this framework. We provide prospective FFEA users with a practical overview of how to set up an FFEA simulation with reference to our publicly available online tutorials and manuals that accompany this first release of the package

An Investigation into the Poor Survival of an Endangered Coho Salmon Population

To investigate reasons for the decline of an endangered population of coho salmon (O. kisutch), 190 smolts were acoustically tagged during three consecutive years and their movements and survival were estimated using the Pacific Ocean Shelf Tracking project (POST) array. Median travel times of the Thompson River coho salmon smolts to the lower Fraser River sub-array were 16, 12 and 10 days during 2004, 2005 and 2006, respectively. Few smolts were recorded on marine arrays. Freshwater survival rates of the tagged smolts during their downstream migration were 0.0–5.6% (0.0–9.0% s.e.) in 2004, 7.0% (6.2% s.e.) in 2005, and 50.9% (18.6% s.e.) in 2006. Overall smolt-to-adult return rates exhibited a similar pattern, which suggests that low freshwater survival rates of out-migrating smolts may be a primary reason for the poor conservation status of this endangered coho salmon population

Light echoes reveal an unexpectedly cool Eta Carinae during its 19th-century Great Eruption

Eta Carinae (Eta Car) is one of the most massive binary stars in the Milky Way. It became the second-brightest star in the sky during its mid-19th century "Great Eruption," but then faded from view (with only naked-eye estimates of brightness). Its eruption is unique among known astronomical transients in that it exceeded the Eddington luminosity limit for 10 years. Because it is only 2.3 kpc away, spatially resolved studies of the nebula have constrained the ejected mass and velocity, indicating that in its 19th century eruption, Eta Car ejected more than 10 M_solar in an event that had 10% of the energy of a typical core-collapse supernova without destroying the star. Here we report the discovery of light echoes of Eta Carinae which appear to be from the 1838-1858 Great Eruption. Spectra of these light echoes show only absorption lines, which are blueshifted by -210 km/s, in good agreement with predicted expansion speeds. The light-echo spectra correlate best with those of G2-G5 supergiant spectra, which have effective temperatures of ~5000 K. In contrast to the class of extragalactic outbursts assumed to be analogs of Eta Car's Great Eruption, the effective temperature of its outburst is significantly cooler than allowed by standard opaque wind models. This indicates that other physical mechanisms like an energetic blast wave may have triggered and influenced the eruption.Comment: Accepted for publication by Nature; 4 pages, 4 figures, SI: 6 pages, 3 figures, 5 table

The combined diabetes and renal control trial (C-DIRECT) - a feasibility randomised controlled trial to evaluate outcomes in multi-morbid patients with diabetes and on dialysis using a mixed methods approach

Background: This cluster randomised controlled trial set out to investigate the feasibility and acceptability of the “Combined Diabetes and Renal Control Trial” (C-DIRECT) intervention, a nurse-led intervention based on motivational interviewing and self-management in patients with coexisting end stage renal diseases and diabetes mellitus (DM ESRD). Its efficacy to improve glycaemic control, as well as psychosocial and self-care outcomes were also evaluated as secondary outcomes. Methods: An assessor-blinded, clustered randomised-controlled trial was conducted with 44 haemodialysis patients with DM ESRD and ≥ 8% glycated haemoglobin (HbA1c), in dialysis centres across Singapore. Patients were randomised according to dialysis shifts. 20 patients were assigned to intervention and 24 were in usual care. The C-DIRECT intervention consisted of three weekly chair-side sessions delivered by diabetes specialist nurses. Data on recruitment, randomisation, and retention, and secondary outcomes such as clinical endpoints, emotional distress, adherence, and self-management skills measures were obtained at baseline and at 12 weeks follow-up. A qualitative evaluation using interviews was conducted at the end of the trial. Results: Of the 44 recruited at baseline, 42 patients were evaluated at follow-up. One patient died, and one discontinued the study due to deteriorating health. Recruitment, retention, and acceptability rates of C-DIRECT were generally satisfactory HbA1c levels decreased in both groups, but C-DIRECT had more participants with HbA1c < 8% at follow up compared to usual care. Significant improvements in role limitations due to physical health were noted for C-DIRECT whereas levels remained stable in usual care. No statistically significant differences between groups were observed for other clinical markers and other patient-reported outcomes. There were no adverse effects. Conclusions: The trial demonstrated satisfactory feasibility. A brief intervention delivered on bedside as part of routine dialysis care showed some benefits in glycaemic control and on QOL domain compared with usual care, although no effect was observed in other secondary outcomes. Further research is needed to design and assess interventions to promote diabetes self-management in socially vulnerable patients

The emerging structure of the Extended Evolutionary Synthesis: where does Evo-Devo fit in?

The Extended Evolutionary Synthesis (EES) debate is gaining ground in contemporary evolutionary biology. In parallel, a number of philosophical standpoints have emerged in an attempt to clarify what exactly is represented by the EES. For Massimo Pigliucci, we are in the wake of the newest instantiation of a persisting Kuhnian paradigm; in contrast, Telmo Pievani has contended that the transition to an EES could be best represented as a progressive reformation of a prior Lakatosian scientific research program, with the extension of its Neo-Darwinian core and the addition of a brand-new protective belt of assumptions and auxiliary hypotheses. Here, we argue that those philosophical vantage points are not the only ways to interpret what current proposals to ‘extend’ the Modern Synthesis-derived ‘standard evolutionary theory’ (SET) entail in terms of theoretical change in evolutionary biology. We specifically propose the image of the emergent EES as a vast network of models and interweaved representations that, instantiated in diverse practices, are connected and related in multiple ways. Under that assumption, the EES could be articulated around a paraconsistent network of evolutionary theories (including some elements of the SET), as well as models, practices and representation systems of contemporary evolutionary biology, with edges and nodes that change their position and centrality as a consequence of the co-construction and stabilization of facts and historical discussions revolving around the epistemic goals of this area of the life sciences. We then critically examine the purported structure of the EES—published by Laland and collaborators in 2015—in light of our own network-based proposal. Finally, we consider which epistemic units of Evo-Devo are present or still missing from the EES, in preparation for further analyses of the topic of explanatory integration in this conceptual framework

Psychometric evaluation of the Problem Areas in Diabetes (PAID) survey in Southern, rural African American women with Type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>The Problem Areas in Diabetes (PAID) survey is a measure of diabetes-related stress for which reported use has been in largely Caucasian populations. Our purpose was to assess the psychometric properties of the PAID in Southern rural African American women with Type 2 diabetes.</p> <p>Methods</p> <p>A convenience sample of African American women (N = 131) ranging from 21–50 years of age and diagnosed with Type 2 diabetes were recruited for a survey study from two rural Southern community health centers. Participants completed the PAID, Center for Epidemiological Studies-Depression Scale (CES-D), and the Summary of Diabetes Self-Care Activities Scale (SDSCA). Factor analysis, Cronbach's coefficient alpha, and construct validation facilitated psychometric evaluation.</p> <p>Results</p> <p>A principle component factor analysis of the PAID yielded two factors, 1) a lack of confidence subscale, and 2) a negative emotional consequences subscale. The Lack of Confidence and Negative Emotional Consequences subscales, but not the overall PAID scale, were associated with glycemic control and body mass index, respectively. Relationships with measures of depression and diabetes self-care supported construct validity of both subscales. Both subscales had acceptable (alpha = 0.85 and 0.94) internal consistency measures.</p> <p>Conclusion</p> <p>A psychometrically sound two-factor solution to the PAID survey is identified in Southern, rural African American women with Type 2 diabetes. Lack of confidence in and negative emotional consequences of diabetes self-care implementation provide a better understanding of determinants of glycemic control and weight than an aggregate of the two scales.</p