University of Münster

About: University of Münster is a education organization based out in Münster, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 35609 authors who have published 69059 publications receiving 2278534 citations. The organization is also known as: University of Munster & University of Muenster.

GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice

Abstract: Inflammatory cell recruitment after myocardial infarction needs to be tightly controlled to permit infarct healing while avoiding fatal complications such as cardiac rupture. Growth differentiation factor-15 (GDF-15), a transforming growth factor-β (TGF-β)-related cytokine, is induced in the infarcted heart of mice and humans. We show that coronary artery ligation in Gdf15-deficient mice led to enhanced recruitment of polymorphonuclear leukocytes (PMNs) into the infarcted myocardium and an increased incidence of cardiac rupture. Conversely, infusion of recombinant GDF-15 repressed PMN recruitment after myocardial infarction. In vitro, GDF-15 inhibited PMN adhesion, arrest under flow and transendothelial migration. Mechanistically, GDF-15 counteracted chemokine-triggered conformational activation and clustering of β(2) integrins on PMNs by activating the small GTPase Cdc42 and inhibiting activation of the small GTPase Rap1. Intravital microscopy in vivo in Gdf15-deficient mice showed that Gdf-15 is required to prevent excessive chemokine-activated leukocyte arrest on the endothelium. Genetic ablation of β(2) integrins in myeloid cells rescued the mortality of Gdf15-deficient mice after myocardial infarction. To our knowledge, GDF-15 is the first cytokine identified as an inhibitor of PMN recruitment by direct interference with chemokine signaling and integrin activation. Loss of this anti-inflammatory mechanism leads to fatal cardiac rupture after myocardial infarction.

EAA/EMQN best practice guidelines for molecular diagnosis of Y‐chromosomal microdeletions: state‐of‐the‐art 2013

Abstract: The molecular diagnosis of Y-chromosomal microdeletions is a common routine genetic test which is part of the diagnostic workup of azoospermic and severe oligozoospermic men. Since 1999, the European Academy of Andrology (EAA) and the European Molecular Genetics Quality Network (EMQN) have been actively involved in supporting the improvement of the quality of the diagnostic assays by publication of the laboratory guidelines for molecular diagnosis of Y-chromosomal microdeletions and by offering external quality assessment trials. The present revision of the 2004 laboratory guidelines summarizes all the clinical novelties related to the Y chromosome (classic, partial and gene-specific deletions, genotype–phenotype correlations, methodological issues) and provides an update on the results of the quality control programme. These aspects also reflect the consensus of a large group of specialists present at a round table session during the recent Florence-Utah-Symposium on ‘Genetics of male infertility’ (Florence, 19–21 September, 2013). During the last 10 years the gr/gr deletion has been demonstrated as a significant risk factor for impaired sperm production. However, the screening for this deletion type in the routine diagnostic setting is still a debated issue among experts. The original basic protocol based on two multiplex polymerase chain reactions remains fully valid and appropriate for accurate diagnosis of complete AZF deletions and it requires only a minor modification in populations with a specific Y chromosome background. However, in light of novel data on genotype–phenotype correlations, the extension analysis for the AZFa and AZFb deletions is now routinely recommended. Novel methods and kits with excessively high number of markers do not improve the sensitivity of the test, may even complicate the interpretation of the results and are not recommended. Annual participation in an external quality control programme is strongly encouraged. The 12-year experience with the EMQN/EAA scheme has shown a steep decline in diagnostic (genotyping) error rate and a simultaneous improvement on reporting practice.

Measuring the Cost of Cybercrime.

Abstract: This chapter documents what we believe to be the first systematic study of the costs of cybercrime. The initial workshop paper was prepared in response to a request from the UK Ministry of Defence following scepticism that previous studies had hyped the problem. For each of the main categories of cybercrime we set out what is and is not known of the direct costs, indirect costs and defence costs – both to the UK and to the world as a whole. We distinguish carefully between traditional crimes that are now “cyber” because they are conducted online (such as tax and welfare fraud); transitional crimes whose modus operandi has changed substantially as a result of the move online (such as credit card fraud); new crimes that owe their existence to the Internet; and what we might call platform crimes such as the provision of botnets which facilitate other crimes rather than being used to extract money from victims directly. As far as direct costs are concerned, we find that traditional offences such as tax and welfare fraud cost the typical citizen in the low hundreds of pounds/euros/dollars a year; transitional frauds cost a few pounds/euros/dollars; while the new computer crimes cost in the tens of pence/cents. However, the indirect costs and defence costs are much higher for transitional and new crimes. For the former they may be roughly comparable to what the criminals earn, while for the latter they may be an order of magnitude more. As a striking example, the botnet behind a third of the spam sent in 2010 earned its owners around $2.7 million, while worldwide expenditures on spam prevention probably exceeded a billion dollars. We are extremely inefficient at fighting cybercrime; or to put it another way, cyber-crooks are like terrorists or metal thieves in that their activities impose disproportionate costs on society. Some of the reasons for this are well-known: cybercrimes are global and have strong externalities, while traditional crimes such as burglary and car theft are local, and the associated equilibria have emerged after many years of optimisation. As for the more direct question of what should be done, our figures suggest that we should spend less in anticipation of cybercrime (on antivirus, firewalls, etc.) and more in response – that is, on the prosaic business of hunting down cyber-criminals and throwing them in jail.