Evidence for Limited Genetic Compartmentalization of HIV-1 between Lung and Blood

BACKGROUND:HIV-1 is frequently detected in the lungs of infected individuals and is likely important in the development of pulmonary opportunistic infections. The unique environment of the lung, rich in alveolar macrophages and with specialized local immune responses, may contribute to differential evolution or selection of HIV-1. METHODOLOGY AND FINDINGS:We characterized HIV-1 in the lung in relation to contemporaneous viral populations in the blood. The C2-V5 region of HIV-1 env was sequenced from paired lung (induced sputum or bronchoalveolar lavage) and blood (plasma RNA and proviral DNA from sorted or unsorted PBMC) from 18 subjects. Compartmentalization between tissue pairs was assessed using 5 established tree or distance-based methods, including permutation tests to determine statistical significance. We found statistical evidence of compartmentalization between lung and blood in 10/18 subjects, although lung and blood sequences were intermingled on phylogenetic trees in all subjects. The subject showing the greatest compartmentalization contained many nearly identical sequences in BAL sample, suggesting clonal expansion may contribute to reduced viral diversity in the lung in some cases. However, HIV-1 sequences in lung were not more homogeneous overall, nor were we able to find a lung-specific genotype associated with macrophage tropism in V3. In all four subjects in whom predicted X4 genotypes were found in blood, predicted X4 genotypes were also found in lung. CONCLUSIONS:Our results support a picture of continuous migration of HIV-1 between circulating blood and lung tissue, with perhaps a very limited degree of localized evolution or clonal replication

A Complex Cell Division Machinery Was Present in the Last Common Ancestor of Eukaryotes

Background: The midbody is a transient complex structure containing proteins involved in cytokinesis. Up to now, it has been described only in Metazoa. Other eukaryotes present a variety of structures implied in the last steps of cell division, such as the septum in fungi or the phragmoplast in plants. However, it is unclear whether these structures are homologous (derive from a common ancestral structure) or analogous (have distinct evolutionary origins). Recently, the proteome of the hamster midbody has been characterized and 160 proteins identified. Methodology/Principal Findings: Using phylogenomic approaches, we show here that nearly all of these 160 proteins (95%) are conserved across metazoan lineages. More surprisingly, we show that a large part of the mammalian midbody components (91 proteins) were already present in the last common ancestor of all eukaryotes (LECA) and were most likely involved in the construction of a complex multi-protein assemblage acting in cell division. Conclusions/Significance: Our results indicate that the midbodies of non-mammalian metazoa are likely very similar to the mammalian one and that the ancestor of Metazoa possessed a nearly modern midbody. Moreover, our analyses support the hypothesis that the midbody and the structures involved in cytokinesis in other eukaryotes derive from a large and complex structure present in LECA, likely involved in cytokinesis. This is an additional argument in favour of the idea of a comple

Novel Sex Cells and Evidence for Sex Pheromones in Diatoms

BACKGROUND: Diatoms belong to the stramenopiles, one of the largest groups of eukaryotes, which are primarily characterized by a presence of an anterior flagellum with tubular mastigonemes and usually a second, smooth flagellum. Based on cell wall morphology, diatoms have historically been divided into centrics and pennates, of which only the former have flagella and only on the sperm. Molecular phylogenies show the pennates to have evolved from among the centrics. However, the timing of flagellum loss--whether before the evolution of the pennate lineage or after--is unknown, because sexual reproduction has been so little studied in the 'araphid' basal pennate lineages, to which Pseudostaurosira belongs. METHODS/PRINCIPAL FINDING: Sexual reproduction of an araphid pennate, Pseudostaurosira trainorii, was studied with light microscopy (including time lapse observations and immunofluorescence staining observed under confocal scanning laser microscopy) and SEM. We show that the species produces motile male gametes. Motility is mostly associated with the extrusion and retrieval of microtubule-based 'threads', which are structures hitherto unknown in stramenopiles, their number varying from one to three per cell. We also report experimental evidence for sex pheromones that reciprocally stimulate sexualization of compatible clones and orientate motility of the male gametes after an initial 'random walk'. CONCLUSIONS/SIGNIFICANCE: The threads superficially resemble flagella, in that both are produced by male gametes and contain microtubules. However, one striking difference is that threads cannot beat or undulate and have no motility of their own, and they do not bear mastigonemes. Threads are sticky and catch and draw objects, including eggs. The motility conferred by the threads is probably crucial for sexual reproduction of P. trainorii, because this diatom is non-motile in its vegetative stage but obligately outbreeding. Our pheromone experiments are the first studies in which gametogenesis has been induced in diatoms by cell-free exudates, opening new possibilities for molecular 'dissection' of sexualization

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

Statement to Congress, March 4, 1993(credit crunch and availability of credit for small businesses)

Credit ; Mullins, David W. ; Small business