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- Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit (ZAFES) (9)
- Biochemie, Chemie und Pharmazie (8)
- Georg-Speyer-Haus (8)
- Mathematik (8)
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- MPI für Hirnforschung (6)
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- Institute for Law and Finance (ILF) (5)
- Philosophie und Geschichtswissenschaften (5)
- Hessische Stiftung für Friedens- und Konfliktforschung (HSFK) (4)
- Informatik und Mathematik (3)
- Katholische Theologie (3)
- LOEWE-Schwerpunkt Außergerichtliche und gerichtliche Konfliktlösung (3)
- Starker Start ins Studium: Qualitätspakt Lehre (3)
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- Zentrum für Biomolekulare Magnetische Resonanz (BMRZ) (2)
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- Akademie für Bildungsforschung und Lehrerbildung (bisher: Zentrum für Lehrerbildung und Schul- und Unterrichtsforschung) (1)
- Center for Membrane Proteomics (CMP) (1)
- Cornelia Goethe Centrum für Frauenstudien und die Erforschung der Geschlechterverhältnisse (CGC) (1)
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- Europäische Akademie der Arbeit in der Universität Frankfurt am Main (1)
- Geowissenschaften / Geographie (1)
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- MPI für empirische Ästhetik (1)
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Background: Hundreds of West African healthcare workers (HCW) have become ill with Ebola virus disease (EVD) and died during the recent outbreak. The occurrence of occupational infections in laboratories could be due to the lack of use of personal protective equipment, the failure to implement specific regulations about the use of equipment and how to work with hazardous materials. Our study attempted to assess the information as well as training level of HCW of a German high level isolation unit and their concern over an occupationally acquired EVD.
Methods: During the recent Ebola virus outbreak a survey was conducted among HCWs, using an anonymous questionnaire.
Results: Although 70% of our total study population stated that they have all the information needed to care for Ebola patients, only 18.2% of laboratory workers and 29.4% of the HCW of the virology department felt sufficiently trained. The HCW rated the Internet (64.3%) and the daily press (54.3%) as the most important sources of information. Medical literature (45.7%) and official institutions (40.4%) were rated less often.
Conclusions: Formulated pointedly, the HCW turned to popular science to get the information they need to feel safe. Further in house training regarding practical skills and reference to scientific literature would be a better solution to ensure workplace safety.
Erikson, Elina ; Wratil, Paul Robin ; Frank, Martin ; Ambiel, Ina ; Pahnke, Katharina ; Pino, Maria ; Azadi, Parastoo ; Izquierdo-Useros, Nuria ; Martinez-Picado, Javier ; Meier, Chris ; Schnaar, Ronald L. ; Crocker, Paul R. ; Reutter, Werner ; Keppler, Oliver Till
Siglec-1 (sialoadhesin, CD169) is a surface receptor on human cells that mediates trans-enhancement of HIV-1 infection through recognition of sialic acid moieties in virus membrane gangliosides. Here, we demonstrate that mouse Siglec-1, expressed on the surface of primary macrophages in an interferon-α-responsive manner, captures murine leukemia virus (MLV) particles and mediates their transfer to proliferating lymphocytes. The MLV infection of primary B-cells was markedly more efficient than that of primary T-cells. The major structural protein of MLV particles, Gag, frequently co-localized with Siglec-1, and trans-infection, primarily of surface-bound MLV particles, efficiently occurred. To explore the role of sialic acid for MLV trans-infection at a submolecular level, we analyzed the potential of six sialic acid precursor analogs to modulate the sialylated ganglioside-dependent interaction of MLV particles with Siglec-1. Biosynthetically engineered sialic acids were detected in both the glycolipid and glycoprotein fractions of MLV producer cells. MLV released from cells carrying N-acyl-modified sialic acids displayed strikingly different capacities for Siglec-1-mediated capture and trans-infection; N-butanoyl, N-isobutanoyl, N-glycolyl, or N-pentanoyl side chain modifications resulted in up to 92 and 80% reduction of virus particle capture and trans-infection, respectively, whereas N-propanoyl or N-cyclopropylcarbamyl side chains had no effect. In agreement with these functional analyses, molecular modeling indicated reduced binding affinities for non-functional N-acyl modifications. Thus, Siglec-1 is a key receptor for macrophage/lymphocyte trans-infection of surface-bound virions, and the N-acyl side chain of sialic acid is a critical determinant for the Siglec-1/MLV interaction.
Low interest rates are becoming a threat to the stability of the life insurance industry, especially in countries such as Germany, where products with relatively high guaranteed returns sold in the past still represent a prominent share of the total portfolio. This contribution aims to assess and quantify the effects of the current low interest rate phase on the balance sheet of a representative German life insurer, given the current asset allocation and the outstanding liabilities. To do so, we generate a stochastic term structure of interest rates as well as stock market returns to simulate investment returns of a stylized life insurance business portfolio in a multi-period setting. Based on empirically calibrated parameters, we can observe the evolution of the life insurers’ balance sheet over time with a special focus on their solvency situation. To account for different scenarios and in order to check the robustness of our findings, we calibrate different capital market settings and different initial situations of capital endowment. Our results suggest that a prolonged period of low interest rates would markedly affect the solvency situation of life insurers, leading to a relatively high cumulative probability of default, especially for less capitalized companies. In addition, the new reform of the German life insurance regulation has a beneficial effect on the cumulative probability of default, as a direct consequence of the reduction of the payouts to policyholders.
Haenisch, Frieder ; Cooper, Jason D. ; Reif, Andreas ; Kittel-Schneider, Sarah ; Steiner, Johann ; Leweke, F. Markus ; Rothermundt, Matthias ; Beveren, Nico J. M. van ; Crespo-Facorro, Benedicto ; Niebuhr, David W. ; Cowan, David N. ; Weber, Natalya S. ; Yolken, Robert H. ; Penninx, Brenda W. J. H. ; Bahn, Sabine
Highlights
• A panel of 20 biomarkers was identified capable of differentiating BD patients from controls.
• Excellent discrimination between established BD patients and controls.
• Good to excellent discrimination between misdiagnosed BD patients and first onset MDD patients.
• Fair to good discrimination between pre-diagnostic BD patients and controls.
• Study demonstrates the potential utility of a protein biomarker panel as a diagnostic test for BD.
Abstract
Background: Bipolar disorder (BD) is a costly, devastating and life shortening mental disorder that is often misdiagnosed, especially on initial presentation. Misdiagnosis frequently results in ineffective treatment. We investigated the utility of a biomarker panel as a diagnostic test for BD.
Methods and findings: We performed a meta-analysis of eight case-control studies to define a diagnostic biomarker panel for BD. After validating the panel on established BD patients, we applied it to undiagnosed BD patients. We analysed 249 BD, 122 pre-diagnostic BD, 75 pre-diagnostic schizophrenia and 90 first onset major depression disorder (MDD) patients and 371 controls. The biomarker panel was identified using ten-fold cross-validation with lasso regression applied to the 87 analytes available across the meta-analysis studies.
We identified 20 protein analytes with excellent predictive performance [area under the curve (AUC) ⩾ 0.90]. Importantly, the panel had a good predictive performance (AUC 0.84) to differentiate 12 misdiagnosed BD patients from 90 first onset MDD patients, and a fair to good predictive performance (AUC 0.79) to differentiate between 110 pre-diagnostic BD patients and 184 controls. We also demonstrated the disease specificity of the panel.
Conclusions: An early and accurate diagnosis has the potential to delay or even prevent the onset of BD. This study demonstrates the potential utility of a biomarker panel as a diagnostic test for BD.
This paper investigates systemic risk in the insurance industry. We first analyze the systemic contribution of the insurance industry vis-à-vis other industries by applying 3 measures, namely the linear Granger causality test, conditional value at risk and marginal expected shortfall, on 3 groups, namely banks, insurers and non-financial companies listed in Europe over the last 14 years. We then analyze the determinants of the systemic risk contribution within the insurance industry by using balance sheet level data in a broader sample. Our evidence suggests that i) the insurance industry shows a persistent systemic relevance over time and plays a subordinate role in causing systemic risk compared to banks, and that ii) within the industry, those insurers which engage more in non-insurance-related activities tend to pose more systemic risk. In addition, we are among the first to provide empirical evidence on the role of diversification as potential determinant of systemic risk in the insurance industry. Finally, we confirm that size is also a significant driver of systemic risk, whereas price-to-book ratio and leverage display counterintuitive results.
We compiled an NMR data set consisting of exact nuclear Overhauser enhancement (eNOE) distance limits, residual dipolar couplings (RDCs) and scalar (J) couplings for GB3, which forms one of the largest and most diverse data set for structural characterization of a protein to date. All data have small experimental errors, which are carefully estimated. We use the data in the research article Vogeli et al., 2015, Complementarity and congruence between exact NOEs and traditional NMR probes for spatial decoding of protein dynamics, J. Struct. Biol., 191, 3, 306–317, doi:10.1016/j.jsb.2015.07.008 [1] for cross-validation in multiple-state structural ensemble calculation. We advocate this set to be an ideal test case for molecular dynamics simulations and structure calculations.
The solution structure of the lantibiotic immunity protein NisI and its interactions with nisin
(2015)
Hacker, Carolin ; Christ, Nina A. ; Duchardt-Ferner, Elke ; Korn, Sophie ; Göbl, Christoph ; Berninger, Lucija ; Düsterhus, Stefanie ; Hellmich, Ute ; Madl, Tobias ; Kötter, Peter ; Entian, Karl-Dieter ; Wöhnert, Jens
Many Gram-positive bacteria produce lantibiotics, genetically encoded and posttranslationally modified peptide antibiotics, which inhibit the growth of other Gram-positive bacteria. To protect themselves against their own lantibiotics these bacteria express a variety of immunity proteins including the LanI lipoproteins. The structural and mechanistic basis for LanI-mediated lantibiotic immunity is not yet understood. Lactococcus lactis produces the lantibiotic nisin, which is widely used as a food preservative. Its LanI protein NisI provides immunity against nisin but not against structurally very similar lantibiotics from other species such as subtilin from Bacillus subtilis. To understand the structural basis for LanI-mediated immunity and their specificity we investigated the structure of NisI. We found that NisI is a two-domain protein. Surprisingly, each of the two NisI domains has the same structure as the LanI protein from B. subtilis, SpaI, despite the lack of significant sequence homology. The two NisI domains and SpaI differ strongly in their surface properties and function. Additionally, SpaI-mediated lantibiotic immunity depends on the presence of a basic unstructured N-terminal region that tethers SpaI to the membrane. Such a region is absent from NisI. Instead, the N-terminal domain of NisI interacts with membranes but not with nisin. In contrast, the C-terminal domain specifically binds nisin and modulates the membrane affinity of the N-terminal domain. Thus, our results reveal an unexpected structural relationship between NisI and SpaI and shed light on the structural basis for LanI mediated lantibiotic immunity.
Hypoxia potentiates palmitate-induced pro-inflammatory activation of primary human macrophages
(2015)
Snodgrass, Ryan G. ; Boß, Marcel ; Zezina, Ekaterina ; Weigert, Andreas ; Dehne, Nathalie ; Fleming, Ingrid ; Brüne, Bernhard ; Namgaladze, Dmitry
Pro-inflammatory cytokines secreted by adipose tissue macrophages (ATMs) contribute to chronic low-grade inflammation and obesity-induced insulin resistance. Recent studies have shown that adipose tissue hypoxia promotes an inflammatory phenotype in ATMs. However, our understanding of how hypoxia modulates the response of ATMs to free fatty acids within obese adipose tissue is limited. We examined the effects of hypoxia (1% O2) on the pro-inflammatory responses of human monocyte-derived macrophages to the saturated fatty acid palmitate. Compared with normoxia, hypoxia significantly increased palmitate-induced mRNA expression and protein secretion of IL-6 and IL-1β. Although palmitate-induced endoplasmic reticulum stress and nuclear factor κB pathway activation were not enhanced by hypoxia, hypoxia increased the activation of JNK and p38 mitogen-activated protein kinase signaling in palmitate-treated cells. Inhibition of JNK blocked the hypoxic induction of pro-inflammatory cytokine expression, whereas knockdown of hypoxia-induced transcription factors HIF-1α and HIF-2α alone or in combination failed to reduce IL-6 and only modestly reduced IL-1β gene expression in palmitate-treated hypoxic macrophages. Enhanced pro-inflammatory cytokine production and JNK activity under hypoxia were prevented by inhibiting reactive oxygen species generation. In addition, silencing of dual-specificity phosphatase 16 increased normoxic levels of IL-6 and IL-1β and reduced the hypoxic potentiation in palmitate-treated macrophages. The secretome of hypoxic palmitate-treated macrophages promoted IL-6 and macrophage chemoattractant protein 1 expression in primary human adipocytes, which was sensitive to macrophage JNK inhibition. Our results reveal that the coexistence of hypoxia along with free fatty acids exacerbates macrophage-mediated inflammation.
Viele Städte in Deutschland stehen aktuell vor komplexen ökonomischen, ökologischen und sozialen Herausforderungen, die mit klassischen ressortbezogenen Planungskonzepten nicht zu bewältigen sind. Integrierte Stadtentwicklungskonzepte erleben deshalb vielerorts eine Renaissance in der städtischen Planungspraxis. Die in diesem Zusammenhang diskutierten Planungsleitbilder geben jedoch nur selten direkt umsetzbare Handlungskonzepte vor. In diesem Beitrag werden deshalb am Beispiel der Stadt Leipzig konkrete Handlungsoptionen für eine an nachhaltiger Mobilität orientierte Stadtentwicklung vorgestellt. Aufbauend auf bisherigen Erkenntnissen zu integrierten Stadtentwicklungskonzepten werden zunächst infrastrukturbezogene Konzepte zur Förderung des Wohnens im Innenbereich, zur Stärkung städtischer Zentren sowie zur Förderung der Nahmobilität dargestellt. Darüber hinaus werden auch politische, organisatorische und kommunikative Handlungsoptionen aufgezeigt. Diese umfassen Maßnahmen zur Verbesserung der übergeordneten Rahmenbedingungen, Konzepte zur Stärkung der inter- und intrakommunalen Kooperation sowie integrierte städtische Mobilitätskonzepte. Das Beispiel Leipzig macht dabei deutlich, dass infrastrukturelle Ansätze für eine an nachhaltiger Mobilitätsgestaltung orientierte Stadtentwicklung nicht ausreichend sind. Vielmehr ist eine bessere Abstimmung der Stadt- und Verkehrsplanung auf die Bedürfnisse der Bevölkerung erforderlich; dazu gehört auch die Integration von Mobilitätsmanagementmaßnahmen in städtische Verkehrskonzepte. Für eine wirksame Umsetzung integrierter Stadtentwicklungskonzepte erscheinen außerdem eine an Nachhaltigkeitszielen orientierte Gestaltung der rechtlichen und politischen Rahmenbedingungen sowie eine stärkere Berücksichtigung regionaler Verknüpfungen in städtischen Planungen notwendig.