University of Hamburg

About: University of Hamburg is a education organization based out in Hamburg, Germany. It is known for research contribution in the topics: Population & Laser. The organization has 45564 authors who have published 89286 publications receiving 2850161 citations. The organization is also known as: Hamburg University.

Host DNases prevent vascular occlusion by neutrophil extracellular traps

Abstract: Platelet and fibrin clots occlude blood vessels in hemostasis and thrombosis. Here we report a noncanonical mechanism for vascular occlusion based on neutrophil extracellular traps (NETs), DNA fibers released by neutrophils during inflammation. We investigated which host factors control NETs in vivo and found that two deoxyribonucleases (DNases), DNase1 and DNase1-like 3, degraded NETs in circulation during sterile neutrophilia and septicemia. In the absence of both DNases, intravascular NETs formed clots that obstructed blood vessels and caused organ damage. Vascular occlusions in patients with severe bacterial infections were associated with a defect to degrade NETs ex vivo and the formation of intravascular NET clots. DNase1 and DNase1-like 3 are independently expressed and thus provide dual host protection against deleterious effects of intravascular NETs.

Snapshots of cooperative atomic motions in the optical suppression of charge density waves

Abstract: The development of tabletop femtosecond electron diffraction sources has provided an alternative way of observing atomic motions in crystalline materials. This technique has now been applied to the charge-density-wave material 1T-TaS2, in which modulation of the electron density is accompanied by a periodic lattice distortion. Previous time-resolved studies have revealed the dynamics of the electronic charge density wave, but until now the dynamics of the lattice system has been only indirectly inferred. In this new experiment, atomic motions were observed in response to a 140 femtosecond optical pulse. Periodic lattice distortion was seen to collapse on an exceptionally fast timescale (about 250 fs), indicative of an electronically driven process involving a high degree of cooperativity. The surprisingly high degree of cooperation in the observed structural dynamics between the electronic and lattice system illustrates the potential for the technique in studies of strongly correlated systems.

Paullones are potent inhibitors of glycogen synthase kinase‐3β and cyclin‐dependent kinase 5/p25

Abstract: Paullones constitute a new family of benzazepinones with promising antitumoral properties. They were recently described as potent, ATP-competitive, inhibitors of the cell cycle regulating cyclin-dependent kinases (CDKs). We here report that paullones also act as very potent inhibitors of glycogen synthase kinase-3b (GSK-3b) (IC50: 4‐80 nm) and the neuronal CDK5/p25 (IC50: 20‐200 nm). These two enzymes are responsible for most of the hyperphosphorylation of the microtubule-binding protein tau, a feature observed in the brains of patients with Alzheimer’s disease and other neurodegenerative ‘taupathies’. Alsterpaullone, the most active paullone, was demonstrated to act by competing with ATP for binding to GSK-3b. Alsterpaullone inhibits the phosphorylation of tau in vivo at sites which are typically phosphorylated by GSK-3b in Alzheimer’s disease. Alsterpaullone also inhibits the CDK5/p25-dependent phosphorylation of DARPP-32 in mouse striatum slices in vitro. This dual specificity of paullones may turn these compounds into very useful tools for the study and possibly treatment of neurodegenerative and proliferative disorders.

Outcome parameters for trials in atrial fibrillation: executive summary.

Abstract: Atrial fibrillation (AF), the most common atrial arrhythmia, has a complex aetiology and causes relevant morbidity and mortality due to different mechanisms, including but not limited to stroke, heart failure, and tachy- or bradyarrhythmia. Current therapeutic options (rate control, rhythm control, antithrombotic therapy, ‘upstream therapy’) only prevent a part of this burden of disease. Several new treatment modalities are therefore under evaluation in controlled trials. Given the multifold clinical consequences of AF, trials in AF patients should assess the effect of therapy in each of the main outcome domains. This paper describes an expert consensus of required outcome parameters in seven relevant outcome domains, namely death, stroke, symptoms and quality of life, rhythm, left ventricular function, cost, and emerging outcome parameters. In addition to these ‘requirements’ for outcome assessment in AF trials, further, more detailed outcome parameters are described. In addition to a careful selection of a relevant primary outcome parameter, coverage of outcomes in all major domains of AF-related morbidity and mortality is desirable for any clinical trial in AF.