72,880 research outputs found

    Positive selection underlies Faster-Z evolution of gene expression in birds.

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    The elevated rate of evolution for genes on sex chromosomes compared to autosomes (Fast-X or Fast-Z evolution) can result either from positive selection in the heterogametic sex, or from non-adaptive consequences of reduced relative effective population size. Recent work in birds suggests that Fast-Z of coding sequence is primarily due to relaxed purifying selection resulting from reduced relative effective population size. However, gene sequence and gene expression are often subject to distinct evolutionary pressures, therefore we tested for Fast-Z in gene expression using next-generation RNA-sequencing data from multiple avian species. Similar to studies of Fast-Z in coding sequence, we recover clear signatures of Fast-Z in gene expression, however in contrast to coding sequence, our data indicate that Fast-Z in expression is due to positive selection acting primarily in females. In the soma, where gene expression is highly correlated between the sexes, we detected Fast-Z in both sexes, although at a higher rate in females, suggesting that many positively selected expression changes in females are also expressed in males. In the gonad, where inter-sexual correlations in expression are much lower, we detected Fast-Z for female gene expression, but crucially, not males. This suggests that a large amount of expression variation is sex-specific in its effects within the gonad. Taken together, our results indicate that Fast-Z evolution of gene expression is the product of positive selection acting on recessive beneficial alleles in the heterogametic sex. More broadly, our analysis suggests that the adaptive potential of Z chromosome gene expression may be much greater than that of gene sequence, results which have important implications for the role of sex chromosomes in speciation and sexual selection

    The Epidemiology of Multiple Sclerosis in Scotland: Inferences from Hospital Admissions

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    PMCID: PMC3029296This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

    The estimated prevalence and incidence of late stage age related macular degeneration in the UK

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    BACKGROUND: UK estimates of age related macular degeneration (AMD) occurrence vary. AIMS: To estimate prevalence, number and incidence of AMD by type in the UK population aged ≥50 years. METHODS: Age-specific prevalence rates of AMD obtained from a Bayesian meta-analysis of AMD prevalence were applied to UK 2007-2009 population data. Incidence was estimated from modelled age-specific prevalence. RESULTS: Overall prevalence of late AMD was 2.4% (95% credible interval (CrI) 1.7% to 3.3%), equivalent to 513 000 cases (95% CrI 363 000 to 699 000); estimated to increase to 679 000 cases by 2020. Prevalences were 4.8% aged ≥65 years, 12.2% aged ≥80 years. Geographical atrophy (GA) prevalence rates were 1.3% (95% CrI 0.9% to 1.9%), 2.6% (95% CrI 1.8% to 3.7%) and 6.7% (95% CrI 4.6% to 9.6%); neovascular AMD (NVAMD) 1.2% (95% CrI 0.9% to 1.7%), 2.5% (95% CrI 1.8% to 3.4%) and 6.3% (95% CrI 4.5% to 8.6%), respectively. The estimated number of prevalent cases of late AMD were 60% higher in women versus men (314 000 cases in women, 192 000 men). Annual incidence of late AMD, GA and NVAMD per 1000 women was 4.1 (95% CrI 2.4% to 6.8%), 2.4 (95% CrI 1.5% to 3.9%) and 2.3 (95% CrI 1.4% to 4.0%); in men 2.6 (95% CrI 1.5% to 4.4%), 1.7 (95% CrI 1.0% to 2.8%) and 1.4 (95% CrI 0.8% to 2.4%), respectively. 71 000 new cases of late AMD were estimated per year. CONCLUSIONS: These estimates will guide health and social service provision for those with late AMD and enable estimation of the cost of introducing new treatments

    The complexity of dominating set reconfiguration

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    Suppose that we are given two dominating sets DsD_s and DtD_t of a graph GG whose cardinalities are at most a given threshold kk. Then, we are asked whether there exists a sequence of dominating sets of GG between DsD_s and DtD_t such that each dominating set in the sequence is of cardinality at most kk and can be obtained from the previous one by either adding or deleting exactly one vertex. This problem is known to be PSPACE-complete in general. In this paper, we study the complexity of this decision problem from the viewpoint of graph classes. We first prove that the problem remains PSPACE-complete even for planar graphs, bounded bandwidth graphs, split graphs, and bipartite graphs. We then give a general scheme to construct linear-time algorithms and show that the problem can be solved in linear time for cographs, trees, and interval graphs. Furthermore, for these tractable cases, we can obtain a desired sequence such that the number of additions and deletions is bounded by O(n)O(n), where nn is the number of vertices in the input graph

    Deep Projective 3D Semantic Segmentation

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    Semantic segmentation of 3D point clouds is a challenging problem with numerous real-world applications. While deep learning has revolutionized the field of image semantic segmentation, its impact on point cloud data has been limited so far. Recent attempts, based on 3D deep learning approaches (3D-CNNs), have achieved below-expected results. Such methods require voxelizations of the underlying point cloud data, leading to decreased spatial resolution and increased memory consumption. Additionally, 3D-CNNs greatly suffer from the limited availability of annotated datasets. In this paper, we propose an alternative framework that avoids the limitations of 3D-CNNs. Instead of directly solving the problem in 3D, we first project the point cloud onto a set of synthetic 2D-images. These images are then used as input to a 2D-CNN, designed for semantic segmentation. Finally, the obtained prediction scores are re-projected to the point cloud to obtain the segmentation results. We further investigate the impact of multiple modalities, such as color, depth and surface normals, in a multi-stream network architecture. Experiments are performed on the recent Semantic3D dataset. Our approach sets a new state-of-the-art by achieving a relative gain of 7.9 %, compared to the previous best approach.Comment: Submitted to CAIP 201

    An analysis by metabolic labelling of the encephalomyocarditis virus ribosomal frameshifting efficiency and stimulators

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    Programmed −1 ribosomal frameshifting is a mechanism of gene expression whereby specific signals within messenger RNAs direct a proportion of ribosomes to shift −1 nt and continue translating in the new reading frame. Such frameshifting normally depends on an RNA structure stimulator 3^\prime-adjacent to a ‘slippery’ heptanucleotide shift site sequence. Recently we identified an unusual frameshifting mechanism in encephalomyocarditis virus, where the stimulator involves a trans\textit{trans}-acting virus protein. Thus, in contrast to other examples of −1 frameshifting, the efficiency of frameshifting in encephalomyocarditis virus is best studied in the context of virus infection. Here we use metabolic labelling to analyse the frameshifting efficiency of wild-type and mutant viruses. Confirming previous results, frameshifting depends on a G_GUU_UUU shift site sequence and a 3^\prime-adjacent stem-loop structure, but is not appreciably affected by the ‘StopGo’ sequence present ~30 nt upstream. At late timepoints, frameshifting was estimated to be 46–76 % efficient.Wellcome Trust [088789, 106207], UK Biotechnology and Biological Research Council (BBSRC) [BB/J007072/1], European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme [grant agreement No (646891)]

    Leptin: A cardiovascular perspective

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    The development of obesity, as well as resultant type 2 diabetes, hypertension and cardiovascular disease, is causing concern in South Africa. Following the discovery of leptin in 1994, hopes were raised that the manipulation of the leptin axis might yield successful therapy for obesity. Although hope still remains, the role of leptin is more complex than was first envisaged. Strong evidence indicates that there is an important role for leptin in obesityrelated hypertension, although the net effects of hyperleptinaemia on cardiovascular pathophysiology remain complex and are not clearly understood. Therefore, the cardiovascular side-effects of leptin as a possible antiobesity drug deserve greater attention
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