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.

Retraining automatic action-tendencies to approach alcohol in hazardous drinkers

Abstract: Aims The main aim of this study was to test whether automatic action-tendencies to approach alcohol can be modified, and whether this affects drinking behaviour. Design and participants Forty-two hazardous drinkers were assigned randomly to a condition in which they were implicitly trained to avoid or to approach alcohol, using a training variety of the alcohol Approach Avoidance Test (AAT). Participants pushed or pulled a joystick in response to picture-format (landscape or portrait). The pictures depicted alcoholic or non-alcoholic drinks. Participants in the avoid-alcohol condition pushed most alcoholic and pulled most non-alcoholic drinks. For participants in the approach-alcohol condition these contingencies were reversed. After the implicit training, participants performed a taste test, including beers and soft drinks. Automatic action tendencies at post-test were assessed with the AAT, including both trained and untrained pictures, and with a different test (Implicit Association Test, IAT). We further tested effects on subjective craving. Results Action tendencies for alcohol changed in accordance with training condition, with the largest effects in the clinically relevant avoid-alcohol condition. These effects occurred outside subjective awareness and generalized to new pictures in the AAT and to an entirely different test using words, rather than pictures (IAT). In relatively heavy drinking participants who demonstrated changed action tendencies in accordance with their training condition, effects were found on drinking behaviour, with participants in the approach-alcohol condition drinking more alcohol than participants in the avoid-alcohol condition. No effect was found on subjective craving. Conclusions Retraining automatic processes may help to regain control over addictive impulses, which points to new treatment possibilities.

Ca2+/calmodulin-dependent protein kinase II regulates cardiac Na+ channels

Abstract: In heart failure (HF), Ca2+/calmodulin kinase II (CaMKII) expression is increased. Altered Na+ channel gating is linked to and may promote ventricular tachyarrhythmias (VTs) in HF. Calmodulin regulates Na+ channel gating, in part perhaps via CaMKII. We investigated effects of adenovirus-mediated (acute) and Tg (chronic) overexpression of cytosolic CaMKIIδC on Na+ current (INa) in rabbit and mouse ventricular myocytes, respectively (in whole-cell patch clamp). Both acute and chronic CaMKIIδC overexpression shifted voltage dependence of Na+ channel availability by –6 mV (P < 0.05), and the shift was Ca2+ dependent. CaMKII also enhanced intermediate inactivation and slowed recovery from inactivation (prevented by CaMKII inhibitors autocamtide 2–related inhibitory peptide [AIP] or KN93). CaMKIIδC markedly increased persistent (late) inward INa and intracellular Na+ concentration (as measured by the Na+ indicator sodium-binding benzofuran isophthalate [SBFI]), which was prevented by CaMKII inhibition in the case of acute CaMKIIδC overexpression. CaMKII coimmunoprecipitates with and phosphorylates Na+ channels. In vivo, transgenic CaMKIIδC overexpression prolonged QRS duration and repolarization (QT intervals), decreased effective refractory periods, and increased the propensity to develop VT. We conclude that CaMKII associates with and phosphorylates cardiac Na+ channels. This alters INa gating to reduce availability at high heart rate, while enhancing late INa (which could prolong action potential duration). In mice, enhanced CaMKIIδC activity predisposed to VT. Thus, CaMKII-dependent regulation of Na+ channel function may contribute to arrhythmogenesis in HF.

Quantum-dot spin-photon entanglement via frequency downconversion to telecom wavelength

Abstract: Future quantum networks will combine ideally stationary quantum bits (qubits), such as single electron spins, with 'flying' qubits, which are photons that transfer quantum states between distant qubits. It has therefore been a long-standing challenge in the field of quantum computation and communication to couple a single electron spin to a single photon in a solid-state platform. Two groups working independently have now achieved that goal, by demonstrating entanglement between a photon and a single electron spin trapped in a semiconductor 'quantum dot' structure. The quantum dot acts as the stationary node. This achievement is a small step towards eventual implementation of quantum networks that can support long-distance quantum communication.

Hemagglutinin protein of wild-type measles virus activates toll-like receptor 2 signaling

Abstract: In the course of acute measles, an efficient virus-specific immune response is generated which mediates viral clearance from the host and confers protection against reinfection. Paradoxically, a general immunosuppression is also induced favoring secondary infections, which are the major reason for the annual high morbidity and mortality rates associated with measles. The magnitude and duration of immune activation and immune suppression differ between natural or experimental infection and vaccination (20, 60). Studies addressing measles virus (MV)-induced immune suppression mainly have focused on alterations of T-cell functions and viability as a consequence of direct MV infection or contact-mediated signaling (53). In vitro observations suggest that MV infection also enhances apoptosis of monocytes and dendritic cells (DC) and affects their antigen-presenting capacity and cytokine release (31, 53). MV interaction with DC and monocytes is, however, also associated with their maturation or activation, respectively, and thus is important for induction of virus-specific immune responses (32, 39, 45, 54, 56). Strains expressing an MV wild-type-derived hemagglutinin (H) protein reveal a particular tropism for DC and are more efficient in inducing both DC maturation and immunosuppression (32, 48, 54). The mechanisms by which MV leads to these functional alterations are largely unknown. Downregulation of interleukin-12 (IL-12) production in monocytes was linked to MV- or antibody-mediated cross-linking of CD46, the receptor for certain MV strains (29). Lymphotropic MV wild-type strains and clinical isolates, with few known exceptions (43), fail to interact with CD46 but require CD150 for cell entry (15, 26, 49, 59). This molecule is absent from unstimulated monocytes and immature DC (33, 45, 48), and it is thus unknown how infection of these cells by CD150-dependent MV strains occurs. Mammalian Toll-like receptors (TLRs) were implicated in the innate immune recognition of a variety of bacterial pathogens and bacterial products (2). Ten TLR family members were discovered, and several of these appear to play important roles in the activation of cells by various bacterial products. TLR2 is responsible for recognition of gram-positive bacteria (57, 65), bacterial lipoproteins (12, 42), and lipoteichoic acid (38, 55). TLR4 appears to be the main receptor for lipopolysaccharide (LPS) lipid A from gram-negative bacteria (41), TLR6 might be a coreceptor for TLR2 in recognizing certain bacterial structures (50, 58), and TLR9 and TLR3 mediate responses to CpG bacterial DNA and double-stranded RNA (dsRNA), respectively (3, 24). Hence, these receptors are able to discriminate between different bacteria and bacterial structures and thereby direct a proper immune response to a specific pathogen. Intracellular domains of the TLRs share motifs with the protein families of the IL-1 receptors, and a common intracellular pathway leading to activation of NF-κB and mitogen-activated protein kinases involves MyD88, IRAK, and TRAF6 (2). However, other signaling pathways upstream of NF-κB have been described which also include utilization of the phosphatidylinositol-3/Akt-kinase pathway by TLR2 (4). It has recently been demonstrated that mammalian TLR signaling can also be regulated by viral gene products. Vaccinia virus encodes gene products that interfere with proximal TLR signaling in the cytoplasm (11), and the fusion protein of respiratory syncytial virus (RSV) was found to activate cells via TLR4 and CD14 (35). Using CHO cells stably overexpressing TLR2 or TLR4, we found that MV wild-type strains specifically activated cells via TLR2, and this was dependent on the expression of the H protein of the MV wild-type strain, WTF. The failure of attenuated MV strains to induce TLR2 activation correlated with a single amino acid exchange at position 481 which is, in turn, essential for the usage of CD46 as receptor by these strains. Importantly, MV expressing the wild-type H protein induced activation of TLR-responsive genes such as IL-1α/β, IL-6, and IL-12 p40 in monocytes and also the expression of CD150, the receptor for all MV strains. Activation of TLR signaling by wild-type MV H protein may thus essentially contribute to the immune activation during measles, and loss of the capability to activate TLR2 may be considered as an attenuation marker.

A crucial role of glycoprotein VI for platelet recruitment to the injured arterial wall in vivo

Abstract: Platelet adhesion and aggregation at sites of vascular injury is crucial for hemostasis but may lead to arterial occlusion in the setting of atherosclerosis and precipitate diseases such as myocardial infarction. A current hypothesis suggests that platelet glycoprotein (GP) Ib interaction with von Willebrand factor recruits flowing platelets to the injured vessel wall, where subendothelial fibrillar collagens support their firm adhesion and activation. However, so far this hypothesis has not been tested in vivo. Here, we demonstrate by intravital fluorescence microscopy of the mouse carotid artery that inhibition or absence of the major platelet collagen receptor, GPVI, abolishes platelet-vessel wall interactions after endothelial denudation. Unexpectedly, inhibition of GPVI by the monoclonal antibody JAQ1 reduced platelet tethering to the subendothelium by approximately 89%. In addition, stable arrest and aggregation of platelets was virtually abolished under these conditions. Using different models of arterial injury, the strict requirement for GPVI in these processes was confirmed in GPVI-deficient mice, where platelets also failed to adhere and aggregate on the damaged vessel wall. These findings reveal an unexpected role of GPVI in the initiation of platelet attachment at sites of vascular injury and unequivocally identify platelet-collagen interactions (via GPVI) as the major determinant of arterial thrombus formation.