Inhibition der durch Lysophophatidylsäure induzierten Superoxidanionen-Sekretion in humanen neutrophilen Granulozyten durch Lokalanästhetika

Neutrophile Granulozyten (PMNs) sorgen als unspezifische Abwehr bei angemessener Stimulation für eine adäquate Produktion von Sauerstoffmetaboliten (z.B. Superoxidanionen (O2-)) zur Abtötung von Pathogenen. Eine exzessive Stimulation jedoch führt zu einer übermäßigen Sekretion dieser Produkte und damit auch zu systemischen Zellschädigungen (vgl. MOF, SIRS). Durch Lysophosphatidylsäure (LPA) als Priming-Substanz, kann ein zweiter, ansonsten harmloser Stimulus, zu einer überschießenden O2--Produktion führen. Lokalanästhetika (LA) dagegen sind bekannt für die Inhibition der metabolischen Aktivität von PMNs. In dieser in vitro-Studie wurden humane PMNs über 10min bzw. 1h mit Lidocain, Ropivacain (S-) und Tetracain inkubiert, bevor sie einem Priming mit LPA (10-4M) und anschließender Aktivierung mit formylierten Peptiden bzw. Phorbolestern unterzogen wurden. Alle LA reduzierten in Konzentrationen von 10-6 - 10-4M die durch LPA-Priming potenzierte O2--Produktion in Abhängigkeit von der Inkubationszeit

Mechanistic Insights into Electronic Current Flow through Quinone Devices

Molecular switches based on functionalized graphene nanoribbons (GNRs) are of great interest in the development of nanoelectronics. In experiment, it was found that a significant difference in the conductance of an anthraquinone derivative can be achieved by altering the pH value of the environment. Building on this, in this work we investigate the underlying mechanism behind this effect and propose a general design principle for a pH based GNR-based switch. The electronic structure of the investigated systems is calculated using density functional theory and the transport properties at the quasi-stationary limit are described using nonequilibrium Green’s function and the Landauer formalism. This approach enables the examination of the local and the global transport through the system. The electrons are shown to flow along the edges of the GNRs. The central carbonyl groups allow for tunable transport through control of the oxidation state via the pH environment. Finally, we also test different types of GNRs (zigzag vs. armchair) to determine which platform provides the best transport switchability

Uptake and release kinetics of 22 polar organic chemicals in the Chemcatcher passive sampler

The Chemcatcher passive sampler, which uses Empore™ disks as sampling phase, is frequently used to monitor polar organic chemicals in river water and effluents. Uptake kinetics need to be quantified to calculate time-weighted average concentrations from Chemcatcher field deployments. Information on release kinetics is needed if performance reference compounds (PRCs) are used to quantify the influence of environmental conditions on the uptake. In a series of uptake and elimination experiments, we used Empore™ SDB disks (poly(styrenedivinylbenzene) copolymer modified with sulfonic acid groups) as a sampling phase and 22 compounds with a logK ow (octanol-water partitioning coefficient) range from −2.6 to 3.8. Uptake experiments were conducted in river water or tap water and lasted up to 25days. Only 1 of 22 compounds (sulfamethoxazole) approached equilibrium in the uptake trials. Other compounds showed continuing non-linear uptake, even after 25days. All compounds could be released from SDB disks, and desorption was proportionally higher in disks loaded for shorter periods. Desorption showed two-phase characteristics, and desorption was proportionally higher for passively sorbed compounds compared to actively loaded compounds (active loading was performed by pulling spiked river water over SDB disks using vacuum). We hypothesise that the two-phase kinetics and better retention of actively loaded compounds—and compounds loaded for a longer period—may be caused by slow diffusion of chemicals within the polymer. As sorption and desorption did not show isotropic kinetics, it is not possible to develop robust PRCs for adsorbent material like SDB disk

Assay validity of point-of-care platelet function tests in thrombocytopenic blood samples

Point-of-care (POC) platelet function tests are faster and easier to perform than in-depth assessment by flow cytometry. At low platelet counts, however, POC tests are prone to assess platelet function incorrectly. Lower limits of platelet count required to obtain valid test results were defined and a testing method to facilitate comparability between different tests was established. We assessed platelet function in whole blood samples of healthy volunteers at decreasing platelet counts (> 100, 80-100, 50-80, 30-50 and < 30 x109/L) using two POC tests: impedance aggregometry and in-vitro bleeding time. Flow cytometry served as the gold standard. The number of platelets needed to reach 50% of the maximum function (ED50) and the lower reference limit (EDref) were calculated to define limits of test validity. The minimal platelet count required for reliable test results was 100 x109/L for impedance aggregometry and in-vitro bleeding time but only 30 x109/L for flow cytometry. Comparison of ED50 and EDref showed significantly lower values for flow cytometry than either POC test (P value < 0.05) but no difference between POC tests nor between the used platelet agonists within a test method. Calculating the ED50 and EDref provides an effective way to compare values from different platelet function assays. Flow cytometry enables correct platelet function testing as long as platelet count is > 30 x109/L whereas impedance aggregometry and in-vitro bleeding time are inconsistent unless platelet count is > 100 x109/L

5-teilige Sonderausgabe des KOBV-Newsletters – 24. bis 30. Oktober 2016

An der internationalen Open-Access-Woche 2016 vom 24.-28. Oktober war der KOBV erstmalig mit einem Online „Publishing Event“ beteiligt. An fünf aufeinanderfolgenden Tagen erschien täglich eine Sonderausgabe des KOBV- Newsletters zu ausgewählten Open-Access-Themen. Die einzelnen Beiträge sind in dieser Sonderedition als Online-Reader zusammengestellt. Der aktuelle Diskussionsstand zum jeweiligen Thema wird von Expertinnen und Experten in kurzen Übersichtsartikeln vorgestellt und mit Praxistipps ergänzt. Zielgruppe sind vor allem Bibliothekare und Bibliothekarinnen, die sich einen schnellen Überblick zu Open Access verschaffen wollen

CellCognition : time-resolved phenotype annotation in high-throughput live cell imaging

Author Posting. © The Authors, 2010. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Methods 7 (2010): 747-754, doi:10.1038/nmeth.1486.Fluorescence time-lapse imaging has become a powerful tool to investigate complex dynamic processes such as cell division or intracellular trafficking. Automated microscopes generate time-resolved imaging data at high throughput, yet tools for quantification of large-scale movie data are largely missing. Here, we present CellCognition, a computational framework to annotate complex cellular dynamics. We developed a machine learning method that combines state-of-the-art classification with hidden Markov modeling for annotation of the progression through morphologically distinct biological states. The incorporation of time information into the annotation scheme was essential to suppress classification noise at state transitions, and confusion between different functional states with similar morphology. We demonstrate generic applicability in a set of different assays and perturbation conditions, including a candidate-based RNAi screen for mitotic exit regulators in human cells. CellCognition is published as open source software, enabling live imaging-based screening with assays that directly score cellular dynamics.Work in the Gerlich laboratory is supported by Swiss National Science Foundation (SNF) research grant 3100A0-114120, SNF ProDoc grant PDFMP3_124904, a European Young Investigator (EURYI) award of the European Science Foundation, an EMBO YIP fellowship, and a MBL Summer Research Fellowship to D.W.G., an ETH TH grant, a grant by the UBS foundation, a Roche Ph.D. fellowship to M.H.A.S, and a Mueller fellowship of the Molecular Life Sciences Ph.D. program Zurich to M.H. M.H. and M.H.A.S are fellows of the Zurich Ph.D. Program in Molecular Life Sciences. B.F. was supported by European Commission’s seventh framework program project Cancer Pathways. Work in the Ellenberg laboratory is supported by a European Commission grant within the Mitocheck consortium (LSHG-CT-2004-503464). Work in the Peter laboratory is supported by the ETHZ, Oncosuisse, SystemsX.ch (LiverX) and the SNF

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Ebola-Verdachtsfälle - eine Herausforderung für die Krankenhäuser: Vorbereitungen und Bedarfsberechnung am Beispiel der Oldenburger Krankenhäuser

Die Ebola-Krise in Westafrika ist nicht beendet. Mit dem Fortgang der Epidemie in Liberia, Sierra Leone und Guinea und den ersten Fällen in Mali besteht weiterhin ein zwar geringes, aber dennoch relevantes Risiko, dass auch in Deutschland die Zahl der Ebola-Verdachtsfälle steigt. Bis zum Jahresbeginn 2015 wurden vier Ebola-Patienten zur Behandlung nach Deutschland gebracht. In der gesetzlichen Pflicht, eine medizinische Erstversorgung zu gewährleisten, resultiert für die Notaufnahmen der Krankenhäuser daraus die Notwendigkeit, Vorkehrungen zu treffen für den Fall, dass Patienten mit dem Verdacht einer Ebola-Infektion medizinische Hilfe suchen. Drei Oldenburger Krankenhäuser haben, unter der Koordination des gemeinsam getragenen Instituts für Krankenhaushygiene Oldenburg, einen Infektionsalarmplan festgelegt. Die Autoren zeigen die Vorbereitungen für das Management von möglichen Ebola-Verdachtsfällen bis zur Verlegung in das zuständige Behandlungszentrum an diesem Beispiel auf