Divergence and evolution of assortative mating in a polygenic trait model of speciation with gene flow

Assortative mating is an important driver of speciation in populations with gene flow and is predicted to evolve under certain conditions in few-locus models. However, the evolution of assortment is less understood for mating based on quantitative traits, which are often characterized by high genetic variability and extensive linkage disequilibrium between trait loci. We explore this scenario for a two-deme model with migration, by considering a single polygenic trait subject to divergent viability selection across demes, as well as assortative mating and sexual selection within demes, and investigate how trait divergence is shaped by various evolutionary forces. Our analysis reveals the existence of sharp thresholds of assortment strength, at which divergence increases dramatically. We also study the evolution of assortment via invasion of modifiers of mate discrimination and show that the ES assortment strength has an intermediate value under a range of migration-selection parameters, even in diverged populations, due to subtle effects which depend sensitively on the extent of phenotypic variation within these populations. The evolutionary dynamics of the polygenic trait is studied using the hypergeometric and infinitesimal models. We further investigate the sensitivity of our results to the assumptions of the hypergeometric model, using individual-based simulations

Polygenic local adaptation in metapopulations: A stochastic eco‐evolutionary model

This paper analyses the conditions for local adaptation in a metapopulation with infinitely many islands under a model of hard selection, where population size depends on local fitness. Each island belongs to one of two distinct ecological niches or habitats. Fitness is influenced by an additive trait which is under habitat‐dependent directional selection. Our analysis is based on the diffusion approximation and accounts for both genetic drift and demographic stochasticity. By neglecting linkage disequilibria, it yields the joint distribution of allele frequencies and population size on each island. We find that under hard selection, the conditions for local adaptation in a rare habitat are more restrictive for more polygenic traits: even moderate migration load per locus at very many loci is sufficient for population sizes to decline. This further reduces the efficacy of selection at individual loci due to increased drift and because smaller populations are more prone to swamping due to migration, causing a positive feedback between increasing maladaptation and declining population sizes. Our analysis also highlights the importance of demographic stochasticity, which exacerbates the decline in numbers of maladapted populations, leading to population collapse in the rare habitat at significantly lower migration than predicted by deterministic arguments

Genetic load and extinction in peripheral populations: The roles of migration, drift and demographic stochasticity

We analyse how migration from a large mainland influences genetic load and population numbers on an island, in a scenario where fitness-affecting variants are unconditionally deleterious, and where numbers decline with increasing load. Our analysis shows that migration can have qualitatively different effects, depending on the total mutation target and fitness effects of deleterious variants. In particular, we find that populations exhibit a genetic Allee effect across a wide range of parameter combinations, when variants are partially recessive, cycling between low-load (large-population) and high-load (sink) states. Increased migration reduces load in the sink state (by increasing heterozygosity) but further inflates load in the large-population state (by hindering purging). We identify various critical parameter thresholds at which one or other stable state collapses, and discuss how these thresholds are influenced by the genetic versus demographic effects of migration. Our analysis is based on a ‘semi-deterministic’ analysis, which accounts for genetic drift but neglects demographic stochasticity. We also compare against simulations which account for both demographic stochasticity and drift. Our results clarify the importance of gene flow as a key determinant of extinction risk in peripheral populations, even in the absence of ecological gradients. This article is part of the theme issue ‘Species’ ranges in the face of changing environments (part I)’

Synthesis, characterization and prediction of anticancer potentiality of some novel green nanoparticles by molecular docking and ADMET techniques

ABSTRACT. Anticancer potentiality of some newly synthesized Nano-Biginelli compounds with the help of enzyme extracted naturally from plants is reported. The biological synthesis of nanoparticles via nano biotechnology processes have a significant potential to enhance the production without the use of harsh, toxic, and expensive chemicals commonly used in conventional physical and chemical processes. The compounds have been characterized on the basis of UV, FTIR, XRD and SEM studies in order to depict the formation of nanoparticles. Using the combination of docking and ADMET techniques, we have tried to predict the anti-cancer potentiality as well as its area of target, i.e. cancer cell to trigger the anti-cancer reaction. Results indicate that the compound 1 (ethyl-6-methyl-2-oxo-4-(4-methoxyphenyl)-1,2,3,4-tetrahydropyrimidin-5-carboxylate) has possible virtual leads to design novel human Aurora B kinase inhibitor.               KEY WORDS: Nano biotechnology, Green chemistry, Enzymes, Drug research Bull. Chem. Soc. Ethiop. 2019, 33(3), 493-504.DOI: https://dx.doi.org/10.4314/bcse.v33i3.1

The 606 at Three: Trends in Use of Chicago\u27s Elevated Rail-Trail

The 606, Chicago’s 2.7-mile, $95 million trail, is the only elevated, multiuse trail in the US. Opened to use in June 2015 after more than 15 years in planning and development, The 606 was designed to provide residents of nearby neighborhoods having major open space deficits with a safe, attractive place for recreation, fitness, commuting, and other purposes. Above all, The 606 was designed to be used, incorporating features to address concerns of local residents and facilitate walking, jogging, bicycling, and other activities. To better understand its use, we studied trends and patterns in trail traffic during the first three full years of operation (2016-2018). Based on analyses of counts taken with infrared sensors at two locations along the trail, our data show that, while The 606 is heavily used, total use declined in both 2017 and 2018. Cumulative trail traffic volume on the western, less affluent end of the trail declined 16.1% from 1.2 million in 2016 to just over 1 million in 2018. Cumulative volume on the eastern, more affluent end of the trail declined 11.9% from nearly 1.4 million in 2016 to just over 1.2 million in 2018. Despite these declines, patterns of use have remained consistent, with much higher use in summer and “shoulder” seasons than in winter, higher use on weekends than weekdays, and different hourly patterns on weekends than weekdays. A statistical model shows that approximately 78% of the variation in daily use is associated with variation in weather and day-of-week. We hypothesize that the declines in use could be associated with differences in weather patterns over the years, congestion on the trail during peak periods of use, a novelty effect that has worn off over time, or changes user perceptions and preferences, perhaps associated with the resource. Research strategies to test these hypotheses are outlined

Evaluating variation in use of definitive therapy and risk-adjusted prostate cancer mortality in England and the USA.

OBJECTIVES: Prostate cancer mortality (PCM) in the USA is among the lowest in the world, whereas PCM in England is among the highest in Europe. This paper aims to assess the association of variation in use of definitive therapy on risk-adjusted PCM in England as compared with the USA. DESIGN: Observational study. SETTING: Cancer registry data from England and the USA. PARTICIPANTS: Men diagnosed with non-metastatic prostate cancer (PCa) in England and the USA between 2004 and 2008. OUTCOME MEASURES: Competing-risks survival analyses to estimate subhazard ratios (SHR) of PCM adjusted for age, ethnicity, year of diagnosis, Gleason score (GS) and clinical tumour (cT) stage. RESULTS: 222,163 men were eligible for inclusion. Compared with American patients, English patients were more likely to present at an older age (70-79 years: England 44.2%, USA 29.3%, p<0.001), with higher tumour stage (cT3-T4: England 25.1%, USA 8.6%, p<0.001) and higher GS (GS 8-10: England 20.7%, USA 11.2%, p<0.001). They were also less likely to receive definitive therapy (England 38%, USA 77%, p<0.001). English patients were more likely to die of PCa (SHR=1.9, 95% CI 1.7 to 2.0, p<0.001). However, this difference was no longer statistically significant when also adjusted for use of definitive therapy (SHR=1.0, 95% CI 1.0 to 1.1, p=0.3). CONCLUSIONS: Risk-adjusted PCM is significantly higher in England compared with the USA. This difference may be explained by less frequent use of definitive therapy in England

Sarcoidosis presenting as Wallenberg syndrome and panuveitis

© 2018 The Authors Sarcoidosis is a multi-system disease with neurological involvement being one of the more rare manifestations. We report a case of a patient who presented with the lateral medullary syndrome and panuveitis as her initial manifestation of sarcoidosis. The patient\u27s course was further complicated by renal involvement. Lacrimal gland and renal biopsies showed noncaseating granulomas without evidence of infection, establishing the diagnosis. Intracranial vertebral artery involvement was confirmed by brain imaging. Bilateral hilar lymphadenopathy with upper lobe predominant nodules on chest imaging was consistent with asymptomatic pulmonary involvement. Systemic steroid therapy is indicated for treatment of ocular sarcoidosis, with standard stroke management indicated for the treatment of lateral medullary syndrome

Probing Reactivity and Substrate Specificity of Both Subunits of the Dimeric \u3ci\u3eMycobacterium tuberculosis\u3c/i\u3e FabH Using alkyl-CoA Disulfide Inhibitors and acyl-CoA Substrates

The dimeric Mycobacterium tuberculosis FabH (mtFabH) catalyses a Claisen-type condensation between an acyl-CoA and malonyl-acyl carrier protein (ACP) to initiate the Type II fatty acid synthase cycle. To analyze the initial covalent acylation of mtFabH with acyl-CoA, we challenged it with mixture of C6-C20 acyl-CoAs and the ESI-MS analysis showed reaction at both subunits and a strict specificity for C12 acyl CoA. Crystallographic and ESI-MS studies of mtFabH with a decyl-CoA disulfide inhibitor revealed a decyl chain bound in acyl-binding channels of both subunits through disulfide linkage to the active site cysteine. These data provide the first unequivocal evidence that both subunits of mtFabH can react with substrates or inhibitor. The discrepancy between the observed C12 acyl-CoA substrate specificity in the initial acylation step and the higher catalytic efficiency of mtFabH for C18-C20 acyl-CoA substrates in the overall mtFabH catalyzed reaction suggests a role for M. tuberculosis ACP as a specificity determinant in this reaction

Prostate Brachytherapy Seed Migration to the Heart Seen on Cardiovascular Computed Tomographic Angiography

Brachytherapy consists of placing radioactive sources into or adjacent to tumors, to deliver conformal radiation treatment. The technique is used for treatment of primary malignancies and for salvage in recurrent disease. Permanent prostate brachytherapy seeds are small metal implants containing radioactive sources of I-125, Pd-103, or Cs-131 encased in a titanium shell. They can embolize through the venous system to the lungs or heart and subsequently be detected by cardiovascular computed tomography. Cardiovascular imagers should be aware of the appearance of migrated seeds, as their presence in the chest is generally benign, so that unnecessary worry and testing are avoided. We report a case of a patient who underwent brachytherapy for prostate cancer and developed a therapeutic seeds embolus to the right ventricle

Separate Entrance and Exit Portals for Ligand Traffic in Mycobacterium tuberculosis FabH

SummaryMycobacterium tuberculosis FabH initiates type II fatty acid synthase-catalyzed formation of the long chain (C16–C22) acyl-coenzyme A (CoA) precursors of mycolic acids, which are major constituents of the bacterial cell envelope. Crystal structures of M. tuberculosis FabH (mtFabH) show the substrate binding site to be a buried, extended L-shaped channel with only a single solvent access portal. Entrance of an acyl-CoA substrate through the solvent portal would require energetically unfavorable reptational threading of the substrate to its reactive position. Using a class of FabH inhibitors, we have tested an alternative hypothesis that FabH exists in an “open” form during substrate binding and product release, and a “closed” form in which catalysis and intermediate steps occur. This hypothesis is supported by mass spectrometric analysis of the product profile and crystal structures of complexes of mtFabH with these inhibitors