High Speed - slow motion: Experimente unter der (Zeit-)lupe

Hochgeschwindigkeitsaufnahmen physikalischer Phänomene erforderten früher sehr teures Equipment. Dank digitaler Kameratechnik wird es zunehmend erschwinglich. Im Folgenden wird ein Experiment beispielhaft beschrieben sowie eine Literaturübersicht gegeben

High-sensitivity cardiac troponin T and copeptin assays to improve diagnostic accuracy of exercise stress test in patients with suspected coronary artery disease

Background: The average diagnostic sensitivity of exercise stress tests (ESTs) is lower than that of other non-invasive cardiac stress tests. The aim of the study was to examine whether high-sensitivity cardiac troponin T (hs-cTnT) or copeptin concentrations rise in response to inducible myocardial ischaemia and may improve the diagnostic accuracy of ESTs. Methods and results: An EST was performed stepwise on a bicycle ergometer by 383 consecutive patients with suspected or progression of coronary artery disease (CAD). In addition venous blood samples for measurement of hs-cTnT and copeptin were collected prior to EST, at peak exercise, and 4 h after EST. Coronary angiography was assessed for all patients. Patients with significant CAD (n=224) were more likely to be male and older compared to patients with non-significant CAD (n=169). Positive EST was documented in 125 (55.8%) patients with significant CAD and in 69 (43.4%) patients with non-significant CAD. Copeptin and hs-cTnT concentrations at baseline were higher in patients with significant CAD (copeptin: 10.8 pmol/l (interquartile range (IQR) 8.1–15.6) vs 9.4 pmol/l (IQR 7.1–13.9); p=0.04; hs-cTnT: 3.0 ng/l (IQR <3.0–5.4) vs <3.0 ng/l (IQR <3.0); p=0.006). Hs-cTnT improved sensitivity (61.6% vs 55.8%), specificity (67.7% vs 56.6%) and the positive predictive value (PPV) (72.3% vs 64.4%) and negative (55.2% vs 47.6%) predictive value (NPV) of EST. Copeptin could not improve sensitivity (55.4% vs 55.8%) and reduced specificity, PPV and NPV. Conclusions: The measurement of hs-cTnT during EST improves sensitivity, specificity, and positive and negative predictive values. In contrast, measurement of copeptin does not improve diagnostic sensitivity and reduces specificity

Baltic cod recruitment – the impact of climate variability on key processes

Large-scale climatic conditions prevailing over the central Baltic Sea resulted in declining salinity and oxygen concentrations in spawning areas of the eastern Baltic cod stock. These changes in hydrography reduced the reproductive success and, combined with high fishing pressure, caused a decline of the stock to the lowest level on record in the early 1990s. The present study aims at disentangling the interactions between reproductive effort and hydrographic forcing leading to variable recruitment. Based on identified key processes, stock dynamics is explained using updated environmental and life stage-specific abundance and production time-series. Declining salinities and oxygen concentrations caused high egg mortalities and indirectly increased egg predation by clupeid fish. Low recruitment, despite enhanced hydrographic conditions for egg survival in the mid-1990s, was due to food limitation for larvae, caused by the decline in the abundance of the copepod Pseudocalanus sp. The case of the eastern Baltic cod stock exemplifies the multitude effects climatic variability may have on a fish stock and underscores the importance of knowledge of these processes for understanding stock dynamics

Predation risk triggers copepod small-scale behavior in the Baltic Sea

Predators not only have direct impact on biomass but also indirect, non-consumptive effects on the behavior their prey organisms. A characteristic response of zooplankton in aquatic ecosystems is predator avoidance by diel vertical migration (DVM), a behavior which is well studied on the population level. A wide range of behavioral diversity and plasticity has been observed both between- as well as within-species and, hence, investigating predator–prey interactions at the individual level seems therefore essential for a better understanding of zooplankton dynamics. Here we applied an underwater imaging instrument, the video plankton recorder (VPR), which allows the non-invasive investigation of individual, diel adaptive behavior of zooplankton in response to predators in the natural oceanic environment, providing a finely resolved and continuous documentation of the organisms’ vertical distribution. Combing observations of copepod individuals observed with the VPR and hydroacoustic estimates of predatory fish biomass, we here show (i) a small-scale DVM of ovigerous Pseudocalanus acuspes females in response to its main predators, (ii) in-situ observations of a direct short-term reaction of the prey to the arrival of the predator and (iii) in-situ evidence of pronounced individual variation in this adaptive behavior with potentially strong effects on individual performance and ecosystem functioning

A controlled trial of rivaroxaban after transcatheter aortic-valve replacement

Background: whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear. Methods: we randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns. Results: after a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P = 0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P = 0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53). Conclusions: in patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO ClinicalTrials.gov number, NCT02556203.)

Novel insight into the reaction of nitro, nitroso and hydroxylamino benzothiazinones and of benzoxacinones with Mycobacterium tuberculosis DprE1

Abstract Nitro-substituted 1,3-benzothiazinones (nitro-BTZs) are mechanism-based covalent inhibitors of Mycobacterium tuberculosis decaprenylphosphoryl-β-D-ribose-2′-oxidase (DprE1) with strong antimycobacterial properties. We prepared a number of oxidized and reduced forms of nitro-BTZs to probe the mechanism of inactivation of the enzyme and to identify opportunities for further chemistry. The kinetics of inactivation of DprE1 was examined using an enzymatic assay that monitored reaction progress up to 100 min, permitting compound ranking according to k inact/K i values. The side-chain at the 2-position and heteroatom identity at the 1-position of the BTZs were found to be important for inhibitory activity. We obtained crystal structures with several compounds covalently bound. The data suggest that steps upstream from the covalent end-points are likely the key determinants of potency and reactivity. The results of protein mass spectrometry using a 7-chloro-nitro-BTZ suggest that nucleophilic reactions at the 7-position do not operate and support a previously proposed mechanism in which BTZ activation by a reduced flavin intermediate is required. Unexpectedly, a hydroxylamino-BTZ showed time-dependent inhibition and mass spectrometry corroborated that this hydroxylamino-BTZ is a mechanism-based suicide inhibitor of DprE1. With this BTZ derivative, we propose a new covalent mechanism of inhibition of DprE1 that takes advantage of the oxidation cycle of the enzyme