Vesicular sorting controls the polarity of expanding membranes in the C. elegans intestine

Biological tubes consist of polarized epithelial cells with apical membranes building the central lumen and basolateral membranes contacting adjacent cells or the extracellular matrix. Cellular polarity requires distinct inputs from outside the cell, e.g., the matrix, inside the cell, e.g., vesicular trafficking and the plasma membrane and its junctions.1 Many highly conserved polarity cues have been identified, but their integration during the complex process of polarized tissue and organ morphogenesis is not well understood. It is assumed that plasma-membrane-associated polarity determinants, such as the partitioning-defective (PAR) complex, define plasma membrane domain identities, whereas vesicular trafficking delivers membrane components to these domains, but lacks the ability to define them. In vitro studies on lumenal membrane biogenesis in mammalian cell lines now indicate that trafficking could contribute to defining membrane domains by targeting the polarity determinants, e.g., the PARs, themselves.2 This possibility suggests a mechanism for PARs’ asymmetric distribution on membranes and places vesicle-associated polarity cues upstream of membrane-associated polarity determinants. In such an upstream position, trafficking might even direct multiple membrane components, not only polarity determinants, an original concept of polarized plasma membrane biogenesis3,4that was largely abandoned due to the failure to identify a molecularly defined intrinsic vesicular sorting mechanism. Our two recent studies on C. elegans intestinal tubulogenesis reveal that glycosphingolipids (GSLs) and the well-recognized vesicle components clathrin and its AP-1 adaptor are required for targeting multiple apical molecules, including polarity regulators, to the expanding apical/lumenal membrane.5,6 These findings support GSLs’ long-proposed role in in vivo polarized epithelial membrane biogenesis and development and identify a novel function in apical polarity for classical post-Golgi vesicle components. They are also compatible with a vesicle-intrinsic sorting mechanism during membrane biogenesis and suggest a model for how vesicles could acquire apical directionality during the assembly of the functionally critical polarized lumenal surfaces of epithelial tubes

More than simple facts: : cross-linguistic differences in place-value processing in arithmetic fact retrieval

Linguistic specificities such as the inversion property of number words (e.g., in German 43 is spoken dreiundvierzig, literally three and forty) moderate Arabic number processing. So far, cross-linguistic studies have mostly focused on inversion-related effects on simple (number comparison) and calculation-based (multi-digit addition) magnitude processing of numerical information. Despite the assumption that multiplication facts are represented in verbal format, not much attention has been paid to inversion-related influences on multiplication fact retrieval. Accordingly, the current study evaluated inversion-related effects on the processing of place-value information in multiplication. In a verification paradigm, the decade consistency effect (i.e., more errors when the decade of a solution probe shares the decade digit with the correct solution) was larger for English- than German-speaking participants for table-related probes. Processing of decade digits might be prioritised in English-speaking participants because the decade-digit is named first in English number words whereas in German number words the unit-digit is named first. Our results indicate that i) the influence of specificities of a verbal number word formation on place-value processing generalise to arithmetic fact retrieval and ii) inversion of number words might even be advantageous in specific cases

Benchmarking whole exome sequencing in the German Network for Personalized Medicine

Introduction Whole Exome Sequencing (WES) has emerged as an efficient tool in clinical cancer diagnostics to broaden the scope from panel-based diagnostics to screening of all genes and enabling robust determination of complex biomarkers in a single analysis. Methods To assess concordance, six formalin-fixed paraffin-embedded (FFPE) tissue specimens and four commercial reference standards were analyzed by WES as matched tumor-normal DNA at 21 NGS centers in Germany, each employing local wet-lab and bioinformatics investigating somatic and germline variants, copy-number alteration (CNA), and different complex biomarkers. Somatic variant calling was performed in 494 diagnostically relevant cancer genes. In addition, all raw data were re-analyzed with a central bioinformatic pipeline to separate wet- and dry-lab variability. Results The mean positive percentage agreement (PPA) of somatic variant calling was 76% and positive predictive value (PPV) 89% compared a consensus list of variants found by at least five centers. Variant filtering was identified as the main cause for divergent variant calls. Adjusting filter criteria and re-analysis increased the PPA to 88% for all and 97% for clinically relevant variants. CNA calls were concordant for 82% of genomic regions. Calls of homologous recombination deficiency (HRD), tumor mutational burden (TMB), and microsatellite instability (MSI) status were concordant for 94%, 93%, and 93% respectively. Variability of CNAs and complex biomarkers did not increase considerably using the central pipeline and was hence attributed to wet-lab differences. Conclusion Continuous optimization of bioinformatic workflows and participating in round robin tests are recommend

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future

Purpose Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design Meta-analysis of prevalence data. Participants A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures Prevalence of early and late AMD, BCVA, and number of AMD cases. Results Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95%

Neamine dimers targeting the HIV-1 TAR RNA.

International audienc

inDAgo - ein Mobilitätsunterstützungssystem für Senioren auf dem Weg in die Praxis

Inklusion und soziale Teilhabe sind zentrale Themen in der Ambient Assisted Living (AAL) Forschung und eine Voraussetzung für soziale Teilhabe ist Mobilität. Im Rahmen der Initiative "Mobil bis ins hohe Alter" fördert das Bundes-ministerium für Bildung und Forschung (BMBF) verschiedene nationale Forschungsprojekte, die zum Ziel haben, Mobilitätsunterstützungssysteme für Senioren zu entwickeln. Eines dieser Projekte ist das inDAgo-Projekt, das im Herbst 2013 kurz vor der Vorstellung seiner Ergebnisse steht. In diesem Beitrag präsentieren wir das Konzept von inDAgo und den aktuellen Entwicklungsstand des Systems. Inclusion and participation are core topics of Ambient Assisted Living (AAL) related research. A prerequisite for one's ability to participate is individual mobility. In this regard, the German Federal Ministry of Education and Research (BMBF) funds a group of national research projects that shares the common goal to provide supportive mobility services to the elderly. One of these projects is the inDAgo project, which, as of late 2013, is nearing the presentation stage. This article presents the concept that the inDAgo system is based on and provides an inside look on the development progress

inDAgo - ein Mobilitätsunterstützungssystem für Senioren auf dem Weg in die Praxis

Inklusion und soziale Teilhabe sind zentrale Themen in der Ambient Assisted Living (AAL) Forschung und eine Voraussetzung für soziale Teilhabe ist Mobilität. Im Rahmen der Initiative "Mobil bis ins hohe Alter" fördert das Bundes-ministerium für Bildung und Forschung (BMBF) verschiedene nationale Forschungsprojekte, die zum Ziel haben, Mobilitätsunterstützungssysteme für Senioren zu entwickeln. Eines dieser Projekte ist das inDAgo-Projekt, das im Herbst 2013 kurz vor der Vorstellung seiner Ergebnisse steht. In diesem Beitrag präsentieren wir das Konzept von inDAgo und den aktuellen Entwicklungsstand des Systems. Inclusion and participation are core topics of Ambient Assisted Living (AAL) related research. A prerequisite for one's ability to participate is individual mobility. In this regard, the German Federal Ministry of Education and Research (BMBF) funds a group of national research projects that shares the common goal to provide supportive mobility services to the elderly. One of these projects is the inDAgo project, which, as of late 2013, is nearing the presentation stage. This article presents the concept that the inDAgo system is based on and provides an inside look on the development progress

Conceptualization and implementation of the central information portal on rare diseases: Protocol for a qualitative study

Background: Recently, public and political interest has focused on people living with rare diseases and their health concerns. Due to the large number of different types of rare diseases and the sizable number of patients, taking action to improve the life of those affected is gaining importance. In 2013, the federal government of Germany adopted a national action plan for rare diseases, including the call to establish a central information portal on rare diseases (Zentrales Informationsportal über seltene Erkrankungen, ZIPSE). Objective: The objective of this study, therefore, was to conduct scientific research on how such a portal must be designed to meet the needs of patients, their families, and medical professionals, and to provide high-quality information for information seekers. Methods: We chose a 3-step procedure to develop a needs-based prototype of a central information portal. In the first step, we determined the information needs of patients with rare diseases, their relatives, and health care professionals by means of qualitative interviews and their content-analytical evaluation. On the basis of this, we developed the basic structure of the portal. In the second step, we identified quality criteria for websites on rare diseases to ensure that the information linked with ZIPSE meets the quality demands. Therefore, we gathered existing criteria catalogs and discussed them in an expert workshop. In the third step, we implemented and tested the developed prototypical information portal. Results: A portal page was configured and made accessible on the Web. The structure of ZIPSE was based on the findings from 108 qualitative interviews with patients, their relatives, and health care professionals, through which numerous information needs were identified. We placed particularly important areas of information, such as symptoms, therapy, research, and advisory services, on the start page. Moreover, we defined 13 quality criteria, referring to factors such as author information, creation date, and privacy, enabling links with high-quality information. Moreover, 19 users tested all the developed routines based on usability and comprehensibility. Subsequently, we improved the visual presentation of search results and other important search functions. Conclusions: The implemented information portal, ZIPSE, provides high-quality information on rare diseases from a central point of access. By integrating the targeted groups as well as different experts on medical information during the construction, the website can assure an improved search for information for users. ZIPSE can also serve as a model for other Web-based information systems in the field of rare diseases

Metadata correction : conceptualization and implementation of the central information portal on rare diseases: protocol for a qualitative study

Correction of: http://www.researchprotocols.org/2018/5/e112