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Wurzburg, Germany

The Julius Maximilians University of Würzburg is a public research university in Würzburg, Germany.The University of Wurzburg is one of the oldest institutions of higher learning in Germany having beenfounded in 1402. The University initially had a brief foundation and was closed in 1415, until it was permanently reopened in 1582 under the initiative of Julius Echter von Mespelbrunn. Today, the University is named for Julius Echter von Mespelbrunn and Maximilian Joseph.The University of Wurzburg is one of the leading universities in Germany being part of the U15 group of research-intensive German universities. The university is also a member of the distinguished Coimbra Group. Wikipedia.

Kuhn M.,University of Wurzburg
Physiological reviews | Year: 2016

cGMP controls many cellular functions ranging from growth, viability, and differentiation to contractility, secretion, and ion transport. The mammalian genome encodes seven transmembrane guanylyl cyclases (GCs), GC-A to GC-G, which mainly modulate submembrane cGMP microdomains. These GCs share a unique topology comprising an extracellular domain, a short transmembrane region, and an intracellular COOH-terminal catalytic (cGMP synthesizing) region. GC-A mediates the endocrine effects of atrial and B-type natriuretic peptides regulating arterial blood pressure/volume and energy balance. GC-B is activated by C-type natriuretic peptide, stimulating endochondral ossification in autocrine way. GC-C mediates the paracrine effects of guanylins on intestinal ion transport and epithelial turnover. GC-E and GC-F are expressed in photoreceptor cells of the retina, and their activation by intracellular Ca(2+)-regulated proteins is essential for vision. Finally, in the rodent system two olfactorial GCs, GC-D and GC-G, are activated by low concentrations of CO2and by peptidergic (guanylins) and nonpeptidergic odorants as well as by coolness, which has implications for social behaviors. In the past years advances in human and mouse genetics as well as the development of sensitive biosensors monitoring the spatiotemporal dynamics of cGMP in living cells have provided novel relevant information about this receptor family. This increased our understanding of the mechanisms of signal transduction, regulation, and (dys)function of the membrane GCs, clarified their relevance for genetic and acquired diseases and, importantly, has revealed novel targets for therapies. The present review aims to illustrate these different features of membrane GCs and the main open questions in this field. Copyright © 2016 the American Physiological Society.

Schneider C.,University of Wurzburg
Nature Photonics | Year: 2016

Coherent control of individual two-level systems is at the heart of any quantum information protocol. In solids, two-level systems generated by bound electron–hole excitonic states, trapped in semiconductor quantum dots, display a robust coupling with light, enabling their optical manipulation via avant-garde approaches of nonlinear spectroscopy. Here, we develop a novel toolbox for coherent control of a quantum dot exciton based on the nonlinear wave-mixing responses, which are enhanced by a photonic nanostructure. By employing three, short, resonant laser pulses, we show that we can manipulate, at will, the intrinsic coherence of the quantum dot dipole and therefore engineer the spectro-temporal shape of its coherent emission. Multi-pulse quantum control sequences, which have been successful in NMR spectroscopy and quantum computation, can now be applied to optically active solid-state quantum bits with application in high-order nonlinear spectroscopy, ultrafast quantum optoelectronics and spread spectrum technology at the single emitter level. © 2016 Nature Publishing Group

Blood platelets are anuclear cell fragments that are essential for blood clotting. Platelets are produced by bone marrow megakaryocytes (MKs), which extend protrusions, or so-called proplatelets, into bone marrow sinusoids. Proplatelet formation requires a profound reorganization of the MK actin and tubulin cytoskeleton. Rho GTPases, such as RhoA, Rac1, and Cdc42, are important regulators of cytoskeletal rearrangements in platelets; however, the specific roles of these proteins during platelet production have not been established. Using conditional knockout mice, we show here that Rac1 and Cdc42 possess redundant functions in platelet production and function. In contrast to a single-deficiency of either protein, a double-deficiency of Rac1 and Cdc42 in MKs resulted in macrothrombocytopenia, abnormal platelet morphology, and impaired platelet function. Double-deficient bone marrow MKs matured normally in vivo but displayed highly abnormal morphology and uncontrolled fragmentation. Consistently, a lack of Rac1/Cdc42 virtually abrogated proplatelet formation in vitro. Strikingly, this phenotype was associated with severely defective tubulin organization, whereas actin assembly and structure were barely affected. Together, these results suggest that the combined action of Rac1 and Cdc42 is crucial for platelet production, particularly by regulating microtubule dynamics.

Sauer M.,University of Wurzburg
Journal of Cell Science | Year: 2013

Super-resolution fluorescence imaging by single-molecule photoactivation or photoswitching and position determination (localization microscopy) has the potential to fundamentally revolutionize our understanding of how cellular function is encoded at the molecular level. Among all powerful, high-resolution imaging techniques introduced in recent years, localization microscopy excels because it delivers single-molecule information about molecular distributions, even giving absolute numbers of proteins present in subcellular compartments. This provides insight into biological systems at a molecular level that can yield direct experimental feedback for modeling the complexity of biological interactions. In addition, efficient new labeling methods and strategies to improve localization are emerging that promise to achieve true molecular resolution. This raises localization microscopy as a powerful complementary method for correlative light and electron microscopy experiments. © 2013. Published by The Company of Biologists Ltd.

Koepsell H.,University of Wurzburg
Molecular Aspects of Medicine | Year: 2013

The SLC22 family contains 13 functionally characterized human plasma membrane proteins each with 12 predicted α-helical transmembrane domains. The family comprises organic cation transporters (OCTs), organic zwitterion/cation transporters (OCTNs), and organic anion transporters (OATs). The transporters operate as (1) uniporters which mediate facilitated diffusion (OCTs, OCTNs), (2) anion exchangers (OATs), and (3) Na+/zwitterion cotransporters (OCTNs). They participate in small intestinal absorption and hepatic and renal excretion of drugs, xenobiotics and endogenous compounds and perform homeostatic functions in brain and heart. Important endogeneous substrates include monoamine neurotransmitters, l-carnitine, α-ketoglutarate, cAMP, cGMP, prostaglandins, and urate. It has been shown that mutations of the SLC22 genes encoding these transporters cause specific diseases like primary systemic carnitine deficiency and idiopathic renal hypouricemia and are correlated with diseases such as Crohn's disease and gout. Drug-drug interactions at individual transporters may change pharmacokinetics and toxicities of drugs. © 2012 Elsevier Ltd. All rights reserved.

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