INPPO Actions and Recognition as a Driving Force for Progress in Plant Proteomics: Change of Guard,INPPO Update,and Upcoming Activities

The International Plant Proteomics Organization (INPPO) is a non‐profit organization whose members are scientists involved or interested in plant proteomics. Since the publication of the first INPPO highlights in 2012, continued progress on many of the organization's mandates/goals has been achieved. Two major events are emphasized in this second INPPO highlights. First, the change of guard at the top, passing of the baton from Dominique Job, INPPO founding President to Ganesh Kumar Agrawal as the incoming President. Ganesh K. Agrawal, along with Dominique Job and Randeep Rakwal initiated the INPPO. Second, the most recent INPPO achievements and future targets, mainly the organization of first the INPPO World Congress in 2014, tentatively planned for Hamburg (Germany), are mentioned.     

Completeness of Reporting of Patient-Relevant Clinical Trial Outcomes: Comparison of Unpublished Clinical Study Reports with Publicly Available Data

Background

Access to unpublished clinical study reports (CSRs) is currently being discussed as a means to allow unbiased evaluation of clinical research. The Institute for Quality and Efficiency in Health Care (IQWiG) routinely requests CSRs from manufacturers for its drug assessments.Our objective was to determine the information gain from CSRs compared to publicly available sources (journal publications and registry reports) for patient-relevant outcomes included in IQWiG health technology assessments (HTAs) of drugs.

Methods and Findings

We used a sample of 101 trials with full CSRs received for 16 HTAs of drugs completed by IQWiG between 15 January 2006 and 14 February 2011, and analyzed the CSRs and the publicly available sources of these trials. For each document type we assessed the completeness of information on all patient-relevant outcomes included in the HTAs (benefit outcomes, e.g., mortality, symptoms, and health-related quality of life; harm outcomes, e.g., adverse events). We dichotomized the outcomes as “completely reported” or “incompletely reported.” For each document type, we calculated the proportion of outcomes with complete information per outcome category and overall.We analyzed 101 trials with CSRs; 86 had at least one publicly available source, 65 at least one journal publication, and 50 a registry report. The trials included 1,080 patient-relevant outcomes. The CSRs provided complete information on a considerably higher proportion of outcomes (86%) than the combined publicly available sources (39%). With the exception of health-related quality of life (57%), CSRs provided complete information on 78% to 100% of the various benefit outcomes (combined publicly available sources: 20% to 53%). CSRs also provided considerably more information on harms. The differences in completeness of information for patient-relevant outcomes between CSRs and journal publications or registry reports (or a combination of both) were statistically significant for all types of outcomes.The main limitation of our study is that our sample is not representative because only CSRs provided voluntarily by pharmaceutical companies upon request could be assessed. In addition, the sample covered only a limited number of therapeutic areas and was restricted to randomized controlled trials investigating drugs.

Conclusions

In contrast to CSRs, publicly available sources provide insufficient information on patient-relevant outcomes of clinical trials. CSRs should therefore be made publicly available. Please see later in the article for the Editors'' Summary     

The larva of Rhyacophila ferox Graf, 2006 (Trichoptera: Rhyacophilidae) from the Eastern Alps (Carinthia,Austria)

The hitherto unknown larva of Rhyacophila ferox Graf, 2006, is described and discussed in the context of contemporary Rhyacophilidae keys. In addition, zoogeographical and ecological notes are included.     

Description of the female and new data on the distribution of Annitella apfelbecki Klapálek, 1899 (Insecta: Trichoptera)

Annitella apfelbecki is one of three Annitella species with distribution ranges restricted to the Balkan Peninsula. In this paper, we describe the hitherto unknown female of A. apfelbecki and give the most important morphological features to enable its identification and separation from the other Annitella females. Additionally, we provide new data on distribution and discuss zoogeography, life cycle and ecology of this species.     

Crustacea subterranea aus Argentinien

En el curso de las investigaciones sobre la fauna de las aguas subterráneas límnicas de la Argentina, se encontraron en pocas muestras una sorprendente cantidad de especies de crustáceos.

Una de las especies (Leptobathynella richerti) fué descubierta poco antes en Paraguay y 3 especies (Parastygocaris goerssi, P. andina e Ingolfiella uspallatae) ya han sido publicadas por el autor. Aqui se describen, se ilustran y se discuten 2 especies del género Parabathynella, 1 Nitocrella y 12 Parastenocaris como nuevas para la ciencia. Se completa la descripción de Leptobathynella richerti. Por falta de material, otras 5 especies aún no se han podido determinar.

Por consiguiente, la fauna de las aguas subterráneas neotropicales prueba ser abun‐dante y representada por mudias especies también en la Argentina. Un análisis biogeo‐gráfico del material aparecerá en otra oportunidad con relaciones más ámplias.

Las investigaciones serán continuadas.     

A call to order at the spirochaetal host–pathogen interface

As the Lyme disease spirochaete Borrelia burgdorferi shuttles back and forth between arthropod vector and vertebrate host, it encounters vastly different and hostile environments. Major mechanisms contributing to the success of this pathogen throughout this complex transmission cycle are phase and antigenic variation of abundant and serotype‐defining surface lipoproteins. These peripherally membrane‐anchored virulence factors mediate niche‐specific interactions with vector/host factors and protect the spirochaete from the perils of the mammalian immune response. In this issue of Molecular Microbiology, Tilly, Bestor and Rosa redefine the roles of two lipoproteins, OspC and VlsE, during mammalian infection. Using a variety of promoter fusions in combination with a sensitive in vivo ‘use it or lose it’ gene complementation assay, the authors demonstrate that proper sequential expression of OspC followed by VlsE indeed matters. A previously suggested general functional redundancy between these and other lipoproteins is shown to be limited and dependent on an immunodeficient experimental setting that is arguably of diminished ecological relevance. These data reinforce the notion that OspC plays a unique role during initial infection while the antigenically variant VlsE proteins allow for persistence in the mammalian host.     

Endothelial Protein C Receptor Function in Murine and Human Breast Cancer Development

Several markers identify cancer stem cell-like populations, but little is known about the functional roles of stem cell surface receptors in tumor progression. Here, we show that the endothelial protein C receptor (EPCR), a stem cell marker in hematopoietic, neuronal and epithelial cells, is crucial for breast cancer growth in the orthotopic microenvironment of the mammary gland. Mice with a hypomorphic allele of EPCR show reduced tumor growth in the PyMT-model of spontaneous breast cancer development and deletion of EPCR in established PyMT tumor cells significantly attenuates transplanted tumor take and growth. We find expansion of EPCR⁺ cancer stem cell-like populations in aggressive, mammary fat pad-enhanced human triple negative breast cancer cells. In this model, EPCR-expressing cells have markedly increased mammosphere- and tumor-cell initiating activity compared to another stable progenitor-like subpopulation present at comparable frequency. We show that receptor blocking antibodies to EPCR specifically attenuate in vivo tumor growth initiated by either EPCR⁺ cells or the heterogenous mixture of EPCR⁺ and EPCR^- cells. Furthermore, we have identified tumor associated macrophages as a major source for recognized ligands of EPCR, suggesting a novel mechanism by which cancer stem cell-like populations are regulated by innate immune cells in the tumor microenvironment.