8 research outputs found

    Virus Movements on the Plasma Membrane Support Infection and Transmission between Cells

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    How viruses are transmitted across the mucosal epithelia of the respiratory, digestive, or excretory tracts, and how they spread from cell to cell and cause systemic infections, is incompletely understood. Recent advances from single virus tracking experiments have revealed conserved patterns of virus movements on the plasma membrane, including diffusive motions, drifting motions depending on retrograde flow of actin filaments or actin tail formation by polymerization, and confinement to submicrometer areas. Here, we discuss how viruses take advantage of cellular mechanisms that normally drive the movements of proteins and lipids on the cell surface. A concept emerges where short periods of fast diffusive motions allow viruses to rapidly move over several micrometers. Coupling to actin flow supports directional transport of virus particles during entry and cell-cell transmission, and local confinement coincides with either nonproductive stalling or infectious endocytic uptake. These conserved features of virus–host interactions upstream of infectious entry offer new perspectives for anti-viral interference

    Subtyping of common complex diseases and disorders by integrating heterogeneous data. Identifying clusters among women with lower urinary tract symptoms in the LURN study

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    We present a methodology for subtyping of persons with a common clinical symptom complex by integrating heterogeneous continuous and categorical data. We illustrate it by clustering women with lower urinary tract symptoms (LUTS), who represent a heterogeneous cohort with overlapping symptoms and multifactorial etiology. Data collected in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN), a multi-center observational study, included self-reported urinary and non-urinary symptoms, bladder diaries, and physical examination data for 545 women. Heterogeneity in these multidimensional data required thorough and non-trivial preprocessing, including scaling by controls and weighting to mitigate data redundancy, while the various data types (continuous and categorical) required novel methodology using a weighted Tanimoto indices approach. Data domains only available on a subset of the cohort were integrated using a semi-supervised clustering approach. Novel contrast criterion for determination of the optimal number of clusters in consensus clustering was introduced and compared with existing criteria. Distinctiveness of the clusters was confirmed by using multiple criteria for cluster quality, and by testing for significantly different variables in pairwise comparisons of the clusters. Cluster dynamics were explored by analyzing longitudinal data at 3- and 12-month follow-up. Five clusters of women with LUTS were identified using the developed methodology. None of the clusters could be characterized by a single symptom, but rather by a distinct combination of symptoms with various levels of severity. Targeted proteomics of serum samples demonstrated that differentially abundant proteins and affected pathways are different across the clusters. The clinical relevance of the identified clusters is discussed and compared with the current conventional approaches to the evaluation of LUTS patients. The rationale and thought process are described for the selection of procedures for data preprocessing, clustering, and cluster evaluation. Suggestions are provided for minimum reporting requirements in publications utilizing clustering methodology with multiple heterogeneous data domains.http://deepblue.lib.umich.edu/bitstream/2027.42/192155/2/Subtyping of common complex diseases and disorders by integrating heterogeneous data. Identifying clusters among women with .pdfPublished versio

    Status, trends and drivers of kelp forests in Europe: an expert assessment

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    A comprehensive expert consultation was conducted in order to assess the status, trends and the most important drivers of change in the abundance and geographical distribution of kelp forests in European waters. This consultation included an on-line questionnaire, results from a workshop and data provided by a selected group of experts working on kelp forest mapping and eco-evolutionary research. Differences in status and trends according to geographical areas, species identity and small-scale variations within the same habitat where shown by assembling and mapping kelp distribution and trend data. Significant data gaps for some geographical regions, like the Mediterranean and the southern Iberian Peninsula, were also identified. The data used for this study confirmed a general trend with decreasing abundance of some native kelp species at their southern distributional range limits and increasing abundance in other parts of their distribution (Saccharina latissima and Saccorhiza polyschides). The expansion of the introduced species Undaria pinnatifida was also registered. Drivers of observed changes in kelp forests distribution and abundance were assessed using experts' opinions. Multiple possible drivers were identified, including global warming, sea urchin grazing, harvesting, pollution and fishing pressure, and their impact varied between geographical areas. Overall, the results highlight major threats for these ecosystems but also opportunities for conservation. Major requirements to ensure adequate protection of coastal kelp ecosystems along European coastlines are discussed, based on the local to regional gaps detected in the study

    Platelet Serotonin Transporter Function Predicts Default-Mode Network Activity

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