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Lubeck, Germany

The University of Lübeck is a research university in Northern Germany which focuses almost entirely on medicine and science with applications in medicine. In both 2006 and 2009, the University of Lübeck was ranked No. 1 in medicine among all universities in Germany, Austria and Switzerland according to the CHE Hochschulranking. In Computer Science and Molecular Life Science, the University was ranked No. 2 in the 2009 evaluation. Wikipedia.

This review focuses on the important contributions that macromolecular crystallography has made over the past 12 years to elucidating structures and mechanisms of the essential proteases of coronaviruses, the main protease (M(pro) ) and the papain-like protease (PL(pro) ). The role of X-ray crystallography in structure-assisted drug discovery against these targets is discussed. Aspects dealt with in this review include the emergence of the SARS coronavirus in 2002-2003 and of the MERS coronavirus 10 years later and the origins of these viruses. The crystal structure of the free SARS coronavirus M(pro) and its dependence on pH is discussed, as are efforts to design inhibitors on the basis of these structures. The mechanism of maturation of the enzyme from the viral polyprotein is still a matter of debate. The crystal structure of the SARS coronavirus PL(pro) and its complex with ubiquitin is also discussed, as is its orthologue from MERS coronavirus. Efforts at predictive structure-based inhibitor development for bat coronavirus M(pro) s to increase the preparedness against zoonotic transmission to man are described as well. The paper closes with a brief discussion of structure-based discovery of antivirals in an academic setting. © 2014 FEBS. Source

Autoantibody immune complexes and cellular infiltrates drive nephritis in patients with systemic lupus erythematosus (SLE) and in murine lupus. The chemokine receptor CXCR3 is assumed to promote cellular infiltration of inflamed tissues. Moreover, CXCR3 deficiency ameliorates lupus nephritis in the MRL/MpJ-Fas(lpr) (MRL/lpr) mouse model of SLE. Hence, CXCR3 blockade has been suggested as a novel therapeutic strategy for the treatment of lupus nephritis. We undertook this study to test the effect of CXCR3 in the (NZB × NZW)F(1) (NZB/NZW) mouse model of SLE. CXCR3(-/-) NZB/NZW mice were generated and monitored for survival, proteinuria, and kidney infiltration. Anti-double-stranded DNA (anti-dsDNA) and total IgG1, IgG2a, and IgG2b antibody levels were determined by enzyme-linked immunosorbent assay. T cell and plasma cell infiltrates in the kidneys and interferon-γ production were determined by flow cytometry. Plasma cell infiltrates were measured using enzyme-linked immunospot assay. Kidney tissue was evaluated for pathologic changes. CXCR3(-/-) NZB/NZW mice exhibited reduced production of total and anti-dsDNA antibodies of the IgG1 subclass, but had normal titers of IgG2a and IgG2b antibodies compared to CXCR3(+/+) NZB/NZW mice. Cellular infiltrates and glomerulonephritis were not reduced in CXCR3(-/-) mice. CXCR3 has an effect on (auto)antibody production but is not essential for lupus pathogenesis in NZB/NZW mice, indicating that the effect of CXCR3 on the development of kidney disease varies between MRL/lpr and NZB/NZW mice. These results suggest that CXCR3-dependent and -independent mechanisms can mediate lupus nephritis. Hence, therapeutic CXCR3 blockade could be beneficial for only a subgroup of patients with SLE. Copyright © 2012 by the American College of Rheumatology. Source

University of Hamburg and University of Lübeck | Date: 2011-06-30

A method for crystallizing a substance dissolved in a solvent, including the following steps: introducing a solvent volume containing the substance into a chamber having a preset temperature, humidity, and gas composition, adding a predetermined volume of a precipitant to the solvent volume containing the substance, allowing the solvent to evaporate while simultaneously observing structural changes in the solvent volume containing the substance and the precipitant by means of dynamic light scattering, detecting weight changes and determining the molarities, making an association with the location in the phase diagram on the basis of the DLS measurement and the results of the molarity determination, allowing a predetermined number of crystal nuclei to form by adding solvent or adding precipitant, putting the solvent volume containing the substance and the precipitant into a metastable state by adding solvent and/or protein solution or by allowing the concentration of the dissolved substance to decrease by allowing nucleation cores to form, maintaining the metastable state by adding a predetermined amount of the substance to the solvent volume containing the substance and the precipitant or allowing the solvent to evaporate until at least one crystal of a predetermined size is formed.

University of Lübeck and Max Planck Gesellschaft zur Forderung der Wissenschaften e.V. | Date: 2013-04-08

The present invention relates to a (poly)peptide or a peptidomimetic thereof having the biological activity of Conkunitzin-S1, wherein said (poly)peptide is selected from (a) a polypeptide comprising or having the amino acid sequence of SEQ ID NO: 1; (b) a polypeptide having at least 85% sequence identity to SEQ ID NO:1; or (c) a fragment of a) or b); wherein said (poly)peptide or peptidomimetic specifically modulates the activity of a channel having the activity of a Kv1.7 containing channel, for the treatment or prevention of metabolic diseases or conditions, or secondary diseases or conditions related to said metabolic diseases or conditions.

University of Lübeck | Date: 2011-12-16

The invention relates to a real time-capable analysis of a sequence of electronic images for estimating the pose of a movable object captured by means of the images. The invention further relates to implementing the invention in software and, in this connection, to a computer-readable medium that stores commands, the execution of which causes the method according to the invention to be carried out. The invention proceeds from a skeleton model, which is described by a small number of nodes in 3D space and permits a good data compression of the image information when the co-ordinates of the nodes describe at any time the position of predetermined parts of the moving object. The skeleton model simultaneously represents previous knowledge of the object, by defining e.g. node pairs and optionally also node triplets in the skeleton model that describe cohesive object parts or optionally object surfaces, which are contained in the measured 2-D image information, i.e. are visible to the camera. The skeleton model is to be fitted quickly and accurately into the image information. The fitting is effected between two images of an image sequence by the continuous displacement of the nodes and the continuous updating of the skeleton model.

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