A three-species model explaining cyclic dominance of pacific salmon

The four-year oscillations of the number of spawning sockeye salmon (Oncorhynchus nerka) that return to their native stream within the Fraser River basin in Canada are a striking example of population oscillations. The period of the oscillation corresponds to the dominant generation time of these fish. Various - not fully convincing - explanations for these oscillations have been proposed, including stochastic influences, depensatory fishing, or genetic effects. Here, we show that the oscillations can be explained as a stable dynamical attractor of the population dynamics, resulting from a strong resonance near a Neimark Sacker bifurcation. This explains not only the long-term persistence of these oscillations, but also reproduces correctly the empirical sequence of salmon abundance within one period of the oscillations. Furthermore, it explains the observation that these oscillations occur only in sockeye stocks originating from large oligotrophic lakes, and that they are usually not observed in salmon species that have a longer generation time.Comment: 7 pages, 5 figure

Cytosolic re-localization and optimization of valine synthesis and catabolism enables increased isobutanol production with the yeast Saccharomyces cerevisiae

Background: The branched chain alcohol isobutanol exhibits superior physicochemical properties as an alternative biofuel. The yeast Saccharomyces cerevisiae naturally produces low amounts of isobutanol as a by-product during fermentations, resulting from the catabolism of valine. As S. cerevisiae is widely used in industrial applications and can easily be modified by genetic engineering, this microorganism is a promising host for the fermentative production of higher amounts of isobutanol. Results: Isobutanol production could be improved by re-locating the valine biosynthesis enzymes Ilv2, Ilv5 and Ilv3 from the mitochondrial matrix into the cytosol. To prevent the import of the three enzymes into yeast mitochondria, N-terminally shortened Ilv2, Ilv5 and Ilv3 versions were constructed lacking their mitochondrial targeting sequences. SDS-PAGE and immunofluorescence analyses confirmed expression and re-localization of the truncated enzymes. Growth tests or enzyme assays confirmed enzymatic activities. Isobutanol production was only increased in the absence of valine and the simultaneous blockage of the mitochondrial valine synthesis pathway. Isobutanol production could be even more enhanced after adapting the codon usage of the truncated valine biosynthesis genes to the codon usage of highly expressed glycolytic genes. Finally, a suitable ketoisovalerate decarboxylase, Aro10, and alcohol dehydrogenase, Adh2, were selected and overexpressed. The highest isobutanol titer was 0.63 g/L at a yield of nearly 15 mg per g glucose. Conclusion: A cytosolic isobutanol production pathway was successfully established in yeast by re-localization and optimization of mitochondrial valine synthesis enzymes together with overexpression of Aro10 decarboxylase and Adh2 alcohol dehydrogenase. Driving forces were generated by blocking competition with the mitochondrial valine pathway and by omitting valine from the fermentation medium. Additional deletion of pyruvate decarboxylase genes and engineering of co-factor imbalances should lead to even higher isobutanol production

Flux control of cytochrome c oxidase in human skeletal muscle

In the present work, by titrating cytochrome c oxidase (COX) with the specific inhibitor KCN, the flux control coefficient and the metabolic reserve capacity of COX have been determined in human saponin-permeabilized muscle fibers. In the presence of the substrates glutamate and malate, a 2.3 ± 0.2-fold excess capacity of COX was observed in ADP-stimulated human skeletal muscle fibers. This value was found to be dependent on the mitochondrial substrate supply. In the combined presence of glutamate, malate, and succinate, which supported an approximately 1.4-fold higher rate of respiration, only a 1.4 ± 0.2-fold excess capacity of COX was determined. In agreement with these findings, the flux control of COX increased, in the presence of the three substrates, from 0.27 ± 0.03 to 0.36 ± 0.08. These results indicate a tight in vivo control of respiration by COX in human skeletal muscle. This tight control may have significant implications for mitochondrial myopathies. In support of this conclusion, the analysis of skeletal muscle fibers from two patients with chronic progressive external ophthalmoplegia, which carried deletions in 11 and 49% of their mitochondrial DNA, revealed a substantially lowered reserve capacity and increased flux control coefficient of COX, indicating severe rate limitations of oxidative phosphorylation by this enzyme

Implementation of force distribution analysis for molecular dynamics simulations

<p>Abstract</p> <p>Background</p> <p>The way mechanical stress is distributed inside and propagated by proteins and other biopolymers largely defines their function. Yet, determining the network of interactions propagating internal strain remains a challenge for both, experiment and theory. Based on molecular dynamics simulations, we developed force distribution analysis (FDA), a method that allows visualizing strain propagation in macromolecules.</p> <p>Results</p> <p>To be immediately applicable to a wide range of systems, FDA was implemented as an extension to Gromacs, a commonly used package for molecular simulations. The FDA code comes with an easy-to-use command line interface and can directly be applied to every system built using Gromacs. We provide an additional R-package providing functions for advanced statistical analysis and presentation of the FDA data.</p> <p>Conclusions</p> <p>Using FDA, we were able to explain the origin of mechanical robustness in immunoglobulin domains and silk fibers. By elucidating propagation of internal strain upon ligand binding, we previously also successfully revealed the functionality of a stiff allosteric protein. FDA thus has the potential to be a valuable tool in the investigation and rational design of mechanical properties in proteins and nano-materials.</p

Prescribing and medical non-adherence after myocardial infarction: qualitative interviews with general practitioners in Germany

Background: An increasing prevalence of having survived a myocardial infarction increases the importance of medical secondary prevention. Although preventive medication reduces mortality, prescribing and adherence are known to be frequently insufficient. General practitioners are the most important prescriber. However, their perspective on prescribing and medical non-adherence following myocardial infarction has not yet been explored. Thus, the aim of this study was to explore the general practitioners' perspective on long-term care after myocardial infarction focussing on medical prevention. Methods: In this qualitative interview study we conducted episodic interviews with sixteen general practitioners from rural and urban surgeries in Germany. Framework analysis with focus on general practitioners' prescribing and patients' non-adherence was performed. Results: Almost all general practitioners reported following guidelines for myocardial infarction aftercare and prescribing the medication that was initiated in the hospital; however, they described deviating from guidelines because of drugs' side effects or patients' intolerances. Some questioned the benefits of medical secondary prevention for the oldest of patients. General practitioners perceived good adherence among their patients who had had an MI while they regarded their methods for assessing medical non-adherence as limited. They perceived diverse reasons for non-adherence, particularly side effects, patients' freedom from symptoms and patients' indifference to health. They attributed mainly negative characteristics, like lack of knowledge and understanding, to non-adherent patients. These characteristics contribute to the difficulty of convincing these patients to take medications as prescribed. General practitioners improved adherence by preventing side effects, explaining the medication's necessity, facilitating intake and involving patients in decision-making. However, about half of the general practitioners reported threatening their patients with negative consequences of non-adherence. Conclusions: General practitioners should be aware that discharge medication can be insufficient and thus, should always check hospital recommendations for accordance with guideline recommendations. Improving physicians' communication skills and informing and motivating patients in an adequate manner, for example in simple language, should be an important goal in the hospital and the general practitioner setting. General practitioners should assess patients' motivations through motivational interviewing, which no general practitioner mentioned during the interviews, and talk with them about adherence and long-term treatment goals regularly