University of Würzburg

About: University of Würzburg is a education organization based out in Wurzburg, Bayern, Germany. It is known for research contribution in the topics: Population & CAS Registry Number. The organization has 31437 authors who have published 62203 publications receiving 2337033 citations. The organization is also known as: Julius-Maximilians-Universität Würzburg & Würzburg University.

Mechanism of SARS-CoV-2 polymerase stalling by remdesivir.

Abstract: Remdesivir is the only FDA-approved drug for the treatment of COVID-19 patients. The active form of remdesivir acts as a nucleoside analog and inhibits the RNA-dependent RNA polymerase (RdRp) of coronaviruses including SARS-CoV-2. Remdesivir is incorporated by the RdRp into the growing RNA product and allows for addition of three more nucleotides before RNA synthesis stalls. Here we use synthetic RNA chemistry, biochemistry and cryo-electron microscopy to establish the molecular mechanism of remdesivir-induced RdRp stalling. We show that addition of the fourth nucleotide following remdesivir incorporation into the RNA product is impaired by a barrier to further RNA translocation. This translocation barrier causes retention of the RNA 3'-nucleotide in the substrate-binding site of the RdRp and interferes with entry of the next nucleoside triphosphate, thereby stalling RdRp. In the structure of the remdesivir-stalled state, the 3'-nucleotide of the RNA product is matched and located with the template base in the active center, and this may impair proofreading by the viral 3'-exonuclease. These mechanistic insights should facilitate the quest for improved antivirals that target coronavirus replication.

Circulation dynamics of Mediterranean precipitation variability 1948–98

Abstract: Canonical correlation analysis is used to identify main coupled circulation–rainfall patterns and to relate recent variability and trends of Mediterranean precipitation to large-scale circulation dynamics. Analyses are based on geopotential heights (500 and 1000 hPa levels) for the North Atlantic–European area (National Centers for Environmental Prediction–National Center for Atmospheric Research reanalysis) and on highly resolved (0.5° × 0.5° ) monthly rainfall grids (Climatic Research Unit, Norwich) selected for the Mediterranean area during the 1948–98 period. Combining monthly analyses with similar characteristics to seasonal samples yields winter (October–March), spring (April–May) and summer (June–September) types of coupled variability; a particular autumn type for the whole Mediterranean does not occur on the monthly time scale. Coupled patterns specifically linked to one or two seasons include an east Atlantic jet (EA-Jet) related pattern for summer and a Mediterranean meridional circulation (MMC) pattern for winter and spring. The most important pattern recurring with dynamical adjustments throughout the whole year reflects the seasonal cycle of the Mediterranean oscillation (MO), which is linked (with seasonal dependence) to the Northern Hemisphere teleconnection modes of the Arctic oscillation (AO) and North Atlantic oscillation (NAO). Winter rainfall trends of the recent decades marked by widespread decreases in the Mediterranean area and by opposite conditions in the southeastern part are linked to particular changes over time in several of the associated circulation patterns. Thus, different regional rainfall changes are integrated into an overall interrelation between Mediterranean rainfall patterns and large-scale atmospheric circulation dynamics. Copyright © 2003 Royal Meteorological Society

Mechanisms of collective cell migration at a glance.

Abstract: This article is part of a Minifocus on collective cell migration. For further reading, please see related articles: `Wound repair at a glance' by Tanya Shaw and Paul Martin ( J. Cell Sci. 122 , [3209-3213][1]) and `Collective cell migration in development' by Cornelis Weijer ( J. Cell Sci. 122 , [

Triple-Bond Covalent Radii

Abstract: A system of additive covalent radii is proposed for σ2 π4 triple bonds involving elements from Be to E 112 (eka-mercury). Borderline cases with weak multiple bonding are included. Only the elements in Group 1, the elements Zn–Hg in Group 12 and Ne in Group 18 are then totally excluded. Gaps are left at late actinides and some lanthanides. The standard deviation for the 324 included data points is 3.2 pm.

Brain iron pathways and their relevance to Parkinson's disease.

Abstract: A central role of iron in the pathogenesis of Parkinson's disease (PD), due to its increase in substantia nigra pars compacta dopaminergic neurons and reactive microglia and its capacity to enhance production of toxic reactive oxygen radicals, has been discussed for many years. Recent transcranial ultrasound findings and the observation of the ability of iron to induce aggregation and toxicity of α-synuclein have reinforced the critical role of iron in the pathogenesis of nigrostriatal injury. Presently the mechanisms involved in the disturbances of iron metabolism in PD remain obscure. In this review we summarize evidence from recent studies suggesting disturbances of iron metabolism in PD at possibly different levels including iron uptake, storage, intracellular metabolism, release and post-transcriptional control. Moreover we outline that the interaction of iron with other molecules, especially α-synuclein, may contribute to the process of neurodegeneration. Because many neurodegenerative diseases show increased accumulation of iron at the site of neurodegeneration, it is believed that maintenance of cellular iron homeostasis is crucial for the viability of neurons.