Unsicherheit, Ungewissheit, Risiko: die aktuelle wissenschaftliche Diskussion über die Bestimmung von Risiken

Manche nennen sie Schwarze Schwäne, andere Unknown Unknowns: So unterschiedlichen Ereignissen wie dem Attentat auf ein Regierungsgebäude in Oslo und ein Feriencamp der norwegischen Jungsozialisten, dem anhaltenden arabischen Frühling, dem Nuklearunfall im japanischen Fukushima oder der weltweiten Finanz- und Wirtschaftskrise ist gemeinsam, dass sie für viele Beobachter und Betroffene überraschend kamen. Sie geben Anlass zu der Frage, ob wir Risiken, die aus unsicheren Entwicklungen resultieren, hinreichend bestimmen können. Zuletzt wurde diese Frage intensiv nach den Terroranschlägen des 11. September 2001 diskutiert. Mit den genannten Ereignissen hat das Thema neuen Aufwind erhalten. Die ausgewählten Publikationen bieten verschiedene Definitionen von Risiko und Unsicherheit. Sie zeigen, dass eine wachsende Zahl von wissenschaftlichen Beobachtern das rational-objektive Risikoverständnis in Frage stellt und für eine stärkere Berücksichtigung von Ungewissheiten plädiert. (Autorenreferat

A Novel Likely Pathogenic Variant in the BLOC1S5 Gene Associated with Hermansky-Pudlak Syndrome Type 11 and an Overview of Human BLOC-1 Deficiencies

Hermansky-Pudlak syndrome (HPS) is a heterogeneous disorder combining oculocutaneous albinism (OCA) and a platelet function disorder of varying severity as its most prominent features. The genes associated with HPS encode for different BLOC- (biogenesis of lysosome-related organelles complex) complexes and for the AP-3 (adaptor protein-3) complex, respectively. These proteins are involved in maturation, trafficking, and the function of lysosome-related organelles (LROs) such as melanosomes and platelet δ-granules. Some patients with different types of HPS can develop additional complications and symptoms like pulmonary fibrosis, granulomatous colitis, and immunodeficiency. A new type of HPS has recently been identified associated with genetic alterations in the BLOC1S5 gene, which encodes the subunit Muted of the BLOC-1 complex. Our aim was to unravel the genetic defect in two siblings with a suspected HPS diagnosis (because of OCA and bleeding symptoms) using next generation sequencing (NGS). Platelet functional analysis revealed reduced platelet aggregation after stimulation with ADP and a severe secretion defect in platelet δ-granules. NGS identified a novel homozygous essential splice site variant in the BLOC1S5 gene present in both affected siblings who are descendants of a consanguine marriage. The patients exhibited no additional symptoms. Our study confirms that pathogenic variants of BLOC1S5 cause the recently described HPS type 11

Alterations in ubiquitin ligase SIAH-2 and its corepressor N-COR after P-mapa immunotherapy and anti-androgen therapy: new therapeutic opportunities for non-muscle invasive bladder cancer

The present study describes the role of the ubiquitin ligase Siah-2 and corepressor N-CoR in controlling androgen receptor (AR) and estrogen receptors (ERa and ER beta) signaling in an appropriate animal model (Fischer 344 female rats) of non-muscle invasive bladder cancer (NMIBC), especially under conditions of anti-androgen therapy with flutamide. Furthermore, this study describes the mechanisms of a promising therapeutic alternative for NMIBC based on Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride (P-MAPA) intravesical immunotherapy combined with flutamide, involving the interaction among steroid hormone receptors, their regulators and Toll-like receptors (TLRs). Our results demonstrated that increased Siah-2 and AR protein levels and decreased N-CoR, cytochrome P450 (CYP450) and estrogen receptors levels played a critical role in the urothelial carcinogenesis, probably leading to escape of urothelial cancer cells from immune system attack. P-MAPA immunotherapy led to distinct activation of innate immune system TLRs 2 and 4-mediated, resulting in increase of interferon signaling pathway, which was more effective in recovering the immunosuppressive tumor immune microenvironment and in recovering the bladder histology features than BCG (Bacillus Calmette-Guerin) treatments. The AR blockade therapy was important in the modulating of downstream molecules of TLR2 and TLR4 signaling pathway, decreasing the inflammatory cytokines signaling and enhancing the interferon signaling pathway when associated with P-MAPA. Taken together, the data obtained suggest that interferon signaling pathway activation and targeting AR and Siah-2 signals by P-MAPA intravesical immunotherapy alone and/or in combination with AR blockade may provide novel therapeutic approaches for NMIBC8544274443CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP490519/2011-32012/20706-2; 2012/13585-

Organic carbon content and carbon isotope variations across the Permo-Triassic boundary in the Gartnerkofel-1 borehole, Carnic Alps, Austria

The Gartnerkofel borehole is one of the most thoroughly studied and described Permo-Triassic sections in the world. Detailed bulk organic carbon isotope studies show a negative base shift from − 24‰ to − 28‰ in the Latest Permian which latter value persists into the Earliest Triassic after which it decreases slightly to − 26‰. Two strongly negative peaks of > − 38‰ in the Latest Permian and a lesser peak of − 31‰ in the Early Triassic are too negative to be due to a greater proportion of more negative organic matter and must be due to very negative methane effects. The overall change to more negative values across the Bulla/Tesero boundary fits the relative rise in sea level for this transition based on the facies changes. A positive shift in organic carbon isotope values at the Late Permian Event Horizon may be due to an increase in land-derived organic detritus at this level—a feature shown by all Tethyan Permo-Triassic boundary sections though these other sections do not have the same values. Carbonate carbon isotope trends are similar in all sections dropping by 2–3 units across the Permo-Triassic boundary. Gartnerkofel carbonate oxygen values are surprisingly, considering the ubiquitous dolomitization, compatible with values elsewhere and indicate reasonable tropical temperatures of 60 °C in the Latest Permian sabkhas to 20–40 °C in the overlying marine transition beds. Increased land-derived input at the Late Permian Event Horizon may be due to offshore transport by tsunamis whose deposits have been recognized in India at this level

Rotating savings and credit association (ROSCAs): Selbsthilfepotential und Foerderungspolitiken

Available from Bibliothek des Instituts fuer Weltwirtschaft, ZBW, Duesternbrook Weg 120, D-24105 Kiel W 546 (32) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Experimental and modeling approach to study sorption of dissolved hydrophobic organic contaminants to microbial biofilms

A biofilm reactor was developed to investigate the sorption of polycyclic aromatic hydrocarbons (PAH) as model compounds for hydrophobic organic contaminants (HOC) to intact microbial biofilms at environmentally realistic concentrations. When operated as a differential column batch reactor, the system can be used to study the thermodynamics as well as the kinetics of the exchange of HOC between an aqueous phase and microbial biofilms. Organic carbon normalized partition coefficients (Koc) for phenanthrene, fluoranthene and pyrene were at the lower end of those known for other organic sorbents. Intra-biofilm diffusion coefficients (D) were calculated from decrease in solute concentration over time using a model for diffusion through a plane sheet and ranged from 0.23 to 0.45×10−9 cm2 s−1 for the three PAH. These diffusion coefficients are about four orders of magnitude lower than those reported in literature for free aqueous solution. These data and the experimental approach presented here are useful to assess the importance of microbial biofilms for exchange processes of HOC in heterogeneous systems such as water distribution systems, membranes and aquifers, sewer systems or surface soils