58 research outputs found

    A Method for the Simultaneous Estimation of Selection Intensities in Overlapping Genes

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    Inferring the intensity of positive selection in protein-coding genes is important since it is used to shed light on the process of adaptation. Recently, it has been reported that overlapping genes, which are ubiquitous in all domains of life, seem to exhibit inordinate degrees of positive selection. Here, we present a new method for the simultaneous estimation of selection intensities in overlapping genes. We show that the appearance of positive selection is caused by assuming that selection operates independently on each gene in an overlapping pair, thereby ignoring the unique evolutionary constraints on overlapping coding regions. Our method uses an exact evolutionary model, thereby voiding the need for approximation or intensive computation. We test the method by simulating the evolution of overlapping genes of different types as well as under diverse evolutionary scenarios. Our results indicate that the independent estimation approach leads to the false appearance of positive selection even though the gene is in reality subject to negative selection. Finally, we use our method to estimate selection in two influenza A genes for which positive selection was previously inferred. We find no evidence for positive selection in both cases

    Mutations in Zebrafish lrp2 Result in Adult-Onset Ocular Pathogenesis That Models Myopia and Other Risk Factors for Glaucoma

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    The glaucomas comprise a genetically complex group of retinal neuropathies that typically occur late in life and are characterized by progressive pathology of the optic nerve head and degeneration of retinal ganglion cells. In addition to age and family history, other significant risk factors for glaucoma include elevated intraocular pressure (IOP) and myopia. The complexity of glaucoma has made it difficult to model in animals, but also challenging to identify responsible genes. We have used zebrafish to identify a genetically complex, recessive mutant that shows risk factors for glaucoma including adult onset severe myopia, elevated IOP, and progressive retinal ganglion cell pathology. Positional cloning and analysis of a non-complementing allele indicated that non-sense mutations in low density lipoprotein receptor-related protein 2 (lrp2) underlie the mutant phenotype. Lrp2, previously named Megalin, functions as an endocytic receptor for a wide-variety of bioactive molecules including Sonic hedgehog, Bone morphogenic protein 4, retinol-binding protein, vitamin D-binding protein, and apolipoprotein E, among others. Detailed phenotype analyses indicated that as lrp2 mutant fish age, many individuals—but not all—develop high IOP and severe myopia with obviously enlarged eye globes. This results in retinal stretch and prolonged stress to retinal ganglion cells, which ultimately show signs of pathogenesis. Our studies implicate altered Lrp2-mediated homeostasis as important for myopia and other risk factors for glaucoma in humans and establish a new genetic model for further study of phenotypes associated with this disease

    Search for gravitational waves associated with gamma-ray bursts detected by Fermi and Swift during the LIGO–Virgo run O3b

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    We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC–2020 March 27 17:00 UTC). We conduct two independent searches: a generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate

    Cervical human papillomavirus infection and shedding of human immunodeficiency virus in cervicovaginal fluids: a cross-sectional study.

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    We evaluated the association between human papillomavirus cervical infection and HIV shedding in cervicovaginal lavage fluid (CVL), studying 89 HIV-infected women recruited at the Department of Infectious Diseases of Brescia (Italy). HIV shedding in CVL was found in a similar proportion of women with (30%; 21/70) and without (31.6%; 6/19) cervical human papillomavirus infection. A statistically significant correlation was found between HIV viral load in serum and CVL among the 27 women with detectable HIV in CVL (r = 0.4; P = 0.04). However, women on highly active antiretroviral therapy were more likely to have detectable HIV-RNA in CVL despite negative viremia (80% vs. 8%; P < 0.005). © 2012 Lippincott Williams & Wilkins

    The profile of professionals in health and education fields at work in their communities Perfil de profissionais nas áreas de saúde e educação atuando em suas comunidades

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    Social roles mold attitudes of actors who play the part in the community, and affect behavioral and moral attitudes and social conscience. There is a diversity of behaviors that demonstrates the extension to which individuals are in constant participation in the community life. A group profile of professional's health and education may supply information on the disciplinary approach in Community Health. Objective: to examine the profile of professionals at work in the Health and Education fields. Subjects participated in answering questions concerning professional work, leisure/religious activities, feeding/sleep habits, prevention and contraceptive methods, medical and/or psychological treatment and medicine/herbal use. Characteristics of the professional group regarding life style and the paradox of the practice of safe sex behavior were recorded. There exists the possibility to improve the quality of life for people in communities by reducing the sources of stress and tension by promoting physical and mental health. Methods should be investigated to allow for the promotion of a quality of life in a small fraction of the population engaged in health and education work in their own communities.<br>Papéis sociais moldam as atitudes dos atores que participam na comunidade e afetam as atitudes comportamentais, morais e a consciência social. Há uma diversidade de comportamentos que demonstra a extensão em que os indivíduos estão em constante participação na vida da comunidade. O perfil de um grupo de profissionais em saúde e educação poderia fornecer informação disciplinar sobre a saúde da comunidade. Objetivo: examinar o perfil de profissionais da saúde e da educação. Os sujeitos participaram respondendo questões sobre trabalho profissional, atividades de lazer e religiosas, hábitos de alimentação e sono, métodos de prevenção e de contracepção, tratamento médico e/ou psicológico e uso de medicamentos/plantas medicinais. Observaram-se características do grupo de profissionais relacionadas com o estilo de vida e também o paradoxo do comportamento quanto à prática de sexo seguro. Existem condições de vida para as pessoas melhorarem suas comunidades, reduzindo fontes de estresse e tensão e promovendo saúde física e mental. Métodos poderiam ser investigados para tornar possível a promoção da qualidade de vida de uma pequena fração da população engajada no trabalho em saúde e educação em suas próprias comunidades

    The Excess of Small Inverted Repeats in Prokaryotes

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    Recent analyses have shown that there is a large excess of perfect inverted repeats in many prokaryotic genomes but not in eukaryotic ones. This difference could be due to a genuine difference between prokaryotes and eukaryotes or to differences in the methods and types of data analyzed ¿ full genome versus protein coding sequences. We used simulations to show that the method used previously tends to underestimate the expected number of inverted repeats. However, this bias is not large and cannot explain the excess of inverted repeats observed in real data. In contrast, our method is unbiased. When both methods are applied to bacterial protein coding sequences they both detect an excess of inverted repeats, which is much lower than previously reported in whole prokaryotic genomes. This suggests that the reported large excess of inverted repeats is due to repeats found in intergenic regions. These repeats could be due to transcription factor binding sites, or other types of repetitive DNA, on opposite strands of the DNA sequence. In contrast, the smaller, but significant, excess of inverted repeats that we report in protein coding sequences may be due to sequence-directed mutagenesis (SDM). SDM is a process where one copy of a small, imperfect, inverted repeat corrects the other copy via strand misalignment, resulting in a perfect repeat and a series of mutations. We show by simulation that even very low levels of SDM, relative to the rate of point mutation, can generate a substantial excess of inverted repeats
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