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Reactive oxygen species regulate early development of the intestinal macrophage-microbiome interface
No full textTree species richness only weakly controls carrion decomposition in a subtropical forest experiment in China
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Dartellung und Vermittlung von Vergangenheitsbewältigung und memoria histórica in spanischen Schulbüchern
No full textImplicit central difference approximations of averaged dynamics of highly oscillatory systems with applications to direct optimal control
No full textTrajectory optimization of highly oscillatory systems can require huge computational efforts if the horizon of the problem is much larger than the duration of a single cycle. To alleviate this effort, stroboscopic averaging methods can be used, which utilize local single-cycle simulations of the oscillatory dynamics to then approximate the average dynamics of the system and integrate them with integration steps much larger than a single cycle. Targeting especially the field of direct optimal control, where, after discretization, the simulation of the dynamics is often included implicitly in the equality constraints of the nonlinear programming problem, we introduce an implicit central difference scheme for the approximation of the average dynamics. In the introduced implicit central difference methods, we solve a nonlinear system of equations that connects − 1 single-cycle simulations of the oscillatory dynamics in order to approximate the average dynamics from a linear combination of points in state-space. We derive the accuracy order for this generalized -point central difference approximation of the average dynamics and confirm the claims in numerical experiments. Compared to existing explicit approaches, the introduced methods are up to twice as efficient while maintaining the same level of accuracy
Pools of independently cycling inositol phosphates revealed by pulse labeling with 18O-water
No full textInositol phosphates control many central processes in eukaryotic cells including nutrient availability, growth, and motility. Kinetic resolution of a key modulator of their signaling functions, the turnover of the phosphate groups on the inositol ring, has been hampered by slow uptake, high dilution, and constraining growth conditions in radioactive pulse-labeling approaches. Here, we demonstrate a rapid (seconds to minutes) and nonradioactive labeling strategy of inositol polyphosphates through 18O-water in yeast, human cells, and amoeba, which can be applied in any media. In combination with capillary electrophoresis and mass spectrometry, 18O-water labeling simultaneously dissects the in vivo phosphate group dynamics of a broad spectrum of even rare inositol phosphates. The good temporal resolution allowed us to discover vigorous phosphate group exchanges in some inositol polyphosphates and pyrophosphates, whereas others remain remarkably inert. We propose a model in which the biosynthetic pathway of inositol polyphosphates and pyrophosphates is organized in distinct, kinetically separated pools. While transfer of compounds between those pools is slow, each pool undergoes rapid internal phosphate cycling. This might enable the pools to perform distinct signaling functions while being metabolically connected
On the reciprocity of ‚ressentiment‘ and geopolitics : understanding the affective dispositions of german far-right geopolitical discourse in the context of the Russo-Ukrainian war
No full textCystathionine [beta]-synthase deficiency in the E‐HOD registry - part II: dietary and pharmacological treatment
No full textCystathionine β-synthase (CBS) deficiency (classical homocystinuria) has a wide range of severity. Mildly affected patients typically present as adults with thromboembolism and respond to treatment with pyridoxine. Severely affected patients usually present during childhood with learning difficulties, ectopia lentis and skeletal abnormalities; they are pyridoxine non-responders (NR) or partial responders (PR) and require treatment with a low-methionine diet and/or betaine. The European network and registry for Homocystinurias and methylation Defects (E-HOD) has published management guidelines for CBS deficiency and recommended keeping plasma total homocysteine (tHcy) concentrations below 100 μmol/L. We have now analysed data from 311 patients in the registry to see how closely treatment follows the guidelines. Pyridoxine-responsive patients generally achieved tHcy concentrations below 50 μmol/L, but many NRs and PRs had a mean tHcy considerably above 100 μmol/L. Most NRs were managed with betaine and a special diet. This usually involved severe protein restriction and a methionine-free amino acid mixture, but some patients had a natural protein intake substantially above the WHO safe minimum. Work is needed on the methionine content of dietary protein as estimates vary widely. Contrary to the guidelines, most NRs were on pyridoxine, sometimes at dangerously high doses. tHcy concentrations were similar in groups prescribed high or low betaine doses and natural protein intakes. High tHcy levels were probably often due to poor compliance. Comparing time-to-event graphs for NR patients detected by newborn screening and those ascertained clinically showed that treatment could prevent thromboembolism (risk ratio 0.073) and lens dislocation (risk ratio 0.069)