Martin Luther University of Halle-Wittenberg

About: Martin Luther University of Halle-Wittenberg is a education organization based out in Halle, Germany. It is known for research contribution in the topics: Population & Liquid crystal. The organization has 20232 authors who have published 38773 publications receiving 965004 citations. The organization is also known as: MLU & University of Wittenberg.

Selective Sirt2 inhibition by ligand-induced rearrangement of the active site.

Abstract: Sirtuins are a highly conserved class of NAD(+)-dependent lysine deacylases. The human isotype Sirt2 has been implicated in the pathogenesis of cancer, inflammation and neurodegeneration, which makes the modulation of Sirt2 activity a promising strategy for pharmaceutical intervention. A rational basis for the development of optimized Sirt2 inhibitors is lacking so far. Here we present high-resolution structures of human Sirt2 in complex with highly selective drug-like inhibitors that show a unique inhibitory mechanism. Potency and the unprecedented Sirt2 selectivity are based on a ligand-induced structural rearrangement of the active site unveiling a yet-unexploited binding pocket. Application of the most potent Sirtuin-rearranging ligand, termed SirReal2, leads to tubulin hyperacetylation in HeLa cells and induces destabilization of the checkpoint protein BubR1, consistent with Sirt2 inhibition in vivo. Our structural insights into this unique mechanism of selective sirtuin inhibition provide the basis for further inhibitor development and selective tools for sirtuin biology.

Integrated urban flood risk assessment – adapting a multicriteria approach to a city

Abstract: . Flood risk assessment is an essential part of flood risk management. As part of the new EU flood directive it is becoming increasingly more popular in European flood policy. Particularly cities with a high concentration of people and goods are vulnerable to floods. This paper introduces the adaptation of a novel method of multicriteria flood risk assessment, that was recently developed for the more rural Mulde river basin, to a city. The study site is Leipzig, Germany. The "urban" approach includes a specific urban-type set of economic, social and ecological flood risk criteria, which focus on urban issues: population and vulnerable groups, differentiated residential land use classes, areas with social and health care but also ecological indicators such as recreational urban green spaces. These criteria are integrated using a "multicriteria decision rule" based on an additive weighting procedure which is implemented into the software tool FloodCalc urban. Based on different weighting sets we provide evidence of where the most flood-prone areas are located in a city. Furthermore, we can show that with an increasing inundation extent it is both the social and the economic risks that strongly increase.

FieF (YiiP) from Escherichia coli mediates decreased cellular accumulation of iron and relieves iron stress

Abstract: The Escherichia coli yiiP gene encodes an iron transporter, ferrous iron efflux (FieF), which belongs to the cation diffusion facilitator family (CDF). Transcription of fieF correlated with iron concentration; however, expression appeared to be independent of the ferrous iron uptake regulator Fur. Absence of FieF led to decreased growth of E. coli cells in complex growth medium but only if fur was additionally deleted. The presence of EDTA was partially able to relieve this growth deficiency. Expression of fieF in trans rendered the double deletion strain more tolerant to iron. Furthermore, E. coli cells exhibited reduced accumulation of (55)Fe when FieF was expressed in trans. FieF catalyzed active efflux of Zn(II) in antiport with protons energized by NADH via the transmembrane pH gradient in everted membrane vesicles. Using the iron-sensitive fluorescent indicator PhenGreen-SK encapsulated in proteoliposomes, transmembrane fluxes of iron cations were measured with purified and reconstituted FieF by fluorescence quenching. This suggests that FieF is an iron and zinc efflux system, which would be the first example of iron detoxification by efflux in any organism.