Upwelling events, coastal offshore exchange, links to biogeochemical processes - Highlights from the Baltic Sea Sciences Congress at Rostock University, Germany, 19-22 March 2007

The Baltic Sea Science Congress was held at Rostock University, Germany, from 19 to 22 March 2007. In the session entitled"Upwelling events, coastal offshore exchange, links to biogeochemical processes" 20 presentations were given,including 7 talks and 13 posters related to the theme of the session.This paper summarises new findings of the upwelling-related studies reported in the session. It deals with investigationsbased on the use of in situ and remote sensing measurements as well as numerical modelling tools. The biogeochemicalimplications of upwelling are also discussed.Our knowledge of the fine structure and dynamic considerations of upwelling has increased in recent decades with the advent ofhigh-resolution modern measurement techniques and modelling studies. The forcing and the overall structure, duration and intensity ofupwelling events are understood quite well. However, the quantification of related transports and the contribution to the overall mixingof upwelling requires further research. Furthermore, our knowledge of the links between upwelling and biogeochemical processes is stillincomplete. Numerical modelling has advanced to the extent that horizontal resolutions of c. 0.5 nautical miles can now be applied,which allows the complete spectrum of meso-scale features to be described. Even the development of filaments can be describedrealistically in comparison with high-resolution satellite data.But the effect of upwelling at a basin scale and possible changes under changing climatic conditions remain open questions

Predictive evolution of metabolic phenotypes using model-designed environments

Adaptive evolution under controlled laboratory conditions has been highly effective in selecting organisms with beneficial phenotypes such as stress tolerance. The evolution route is particularly attractive when the organisms are either difficult to engineer or the genetic basis of the phenotype is complex. However, many desired traits, like metabolite secretion, have been inaccessible to adaptive selection due to their trade-off with cell growth. Here, we utilize genome-scale metabolic models to design nutrient environments for selecting lineages with enhanced metabolite secretion. To overcome the growth-secretion trade-off, we identify environments wherein growth becomes correlated with a secondary trait termed tacking trait. The latter is selected to be coupled with the desired trait in the application environment where the trait manifestation is required. Thus, adaptive evolution in the model-designed selection environment and subsequent return to the application environment is predicted to enhance the desired trait. We experimentally validate this strategy by evolving Saccharomyces cerevisiae for increased secretion of aroma compounds, and confirm the predicted flux-rerouting using genomic, transcriptomic, and proteomic analyses. Overall, model-designed selection environments open new opportunities for predictive evolution.This work was sponsored by the ERASysAPP project WINESYS (the German Ministry of Education and Research grant no. 031A605; the Research Council of Norway (Norges Forskningsråd) grant no. 245160) and by the Ministry of Science, Innovation and Universities, Spain (España, Ministerio de Ciencia e Innovación (MCIN)) (Project CoolWine, PCI2018‐092962), under the call ERA‐NET ERA COBIOTECH. PJ acknowledges funding from the Academy of Finland, decision numbers 310514, 314125, and 329930. KRP received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Grant agreement No. 866028). T. Tenkanen and G. Riddihough are acknowledged for comments on the manuscript. We acknowledge the support of the following core facilities at the European Molecular Biology Laboratory (Heidelberg, Germany): Genomics (V. Benes and R. Hercog), and Proteomics (M. Rettel and F. Stein)

Validation of three-dimensional hydrodynamic models of the Gulf of Finland

A model-intercomparison study was conducted, the first of its kind for the Baltic Sea, whose aim was to systematically simulate the basic three-dimensional hydrographic properties of a realistic, complex basin. Simulations of the hydrographic features of the Gulf of Finland for the summer–autumn of 1996 by six three-dimensional hydrodynamic models were compared. Validation was undertaken using more than 300 vertical hydrographic profiles of salinity and temperature. The analysis of model performance, including averaging of the ensemble results, was undertaken with a view to assessing the potential suitability of the models in reproducing the physics of the Baltic Sea accurately enough to serve as a basis for accurate simulations of biogeochemistry once ecosystem models are incorporated. The performance of the models was generally satisfactory. Nevertheless, all the models had some difficulties in correctly simulating vertical profiles of temperature and salinity, and hence mixed layer dynamics, particularly in the eastern Gulf of Finland. Results emphasized the need for high resolution in both vertical and horizontal directions in order to resolve the complex dynamics and bathymetry of the Baltic Sea. Future work needs to consider the choice of mixing and advection schemes, moving to higher resolution, high-frequency forcing, and the accurate representation of river discharges and boundary conditions

Impact of stoichiometry representation on simulation of genotype-phenotype relationships in metabolic networks.

<div><p>Genome-scale metabolic networks provide a comprehensive structural framework for modeling genotype-phenotype relationships through flux simulations. The solution space for the metabolic flux state of the cell is typically very large and optimization-based approaches are often necessary for predicting the active metabolic state under specific environmental conditions. The objective function to be used in such optimization algorithms is directly linked with the biological hypothesis underlying the model and therefore it is one of the most relevant parameters for successful modeling. Although linear combination of selected fluxes is widely used for formulating metabolic objective functions, we show that the resulting optimization problem is sensitive towards stoichiometry representation of the metabolic network. This undesirable sensitivity leads to different simulation results when using numerically different but biochemically equivalent stoichiometry representations and thereby makes biological interpretation intrinsically subjective and ambiguous. We hereby propose a new method, Minimization of Metabolites Balance (MiMBl), which decouples the artifacts of stoichiometry representation from the formulation of the desired objective functions, by casting objective functions using metabolite turnovers rather than fluxes. By simulating perturbed metabolic networks, we demonstrate that the use of stoichiometry representation independent algorithms is fundamental for unambiguously linking modeling results with biological interpretation. For example, MiMBl allowed us to expand the scope of metabolic modeling in elucidating the mechanistic basis of several genetic interactions in <em>Saccharomyces cerevisiae</em>.</p> </div

Identification of target genes to reduce acetate yield by Saccharomyces cerevisiae under aerobic conditions

Trabajo presentado en Congreso Nacional de Biotecnología (BIOTEC 2019), celebrado en Vigo (España), del 10 al 13 de junio de 2019Excessive acetic acid production is a key problem in winemaking processes aiming to reduce ethanol content of wine (1). It is related to a boost in acetate yields observed for Saccharomyces cerevisiae and some other yeasts under aerobic fermentation conditions. However, the biochemical mechanisms underlying this problem are unclear. We therefore used a genomic-scale modelling approach, combined with experimentally determined uptake/secretion rates, to gain insights into the metabolic rewiring of S. cerevisiae in response to oxygen under conditions relevant for winemaking. The model was also used to identify gene deletion targets affecting the production of acetic acid under aerobic conditions. Several gene knock-out with expected reduction in acetic acid production were thus identified as targets using MoMa and MiMBl algorithms. The predictions were tested using strains from the prototrophic yeast knockout collection for the fermentation of natural grape must under aerobic conditions. Although many of the prediction did not show any reduction in acetic acid yield, and increased yield was observed in some cases, significant acetate reduction was obtained for three gene deletion strains, ald6¿, mdh3¿ and rip1¿. The involvement of ALD6 on aerobic acetic acid production could be expected from results by other authors. However, the results for MDH3 and RIP1 could not be easily anticipated and thus provide new insights into yeast metabolism concerning acetic acid production, a major concern for the wine industry.We acknowledge funding by MINECO (AGL2015-63629-R and PhD training contract for AJR

Efficacy of Ivabradine in Combination with Beta-Blocker Versus Uptitration of Beta-Blocker in Patients with Stable Angina

Purpose The antianginal and anti-ischemic efficacy of the selective If inhibitor ivabradine is established in patients with stable angina in monotherapy and in combination with other antianginals, including beta-blocker. This pilot study compared the antianginal and anti-ischemic efficacy and hemodynamic profile of ivabradine plus 5 mg bisoprolol versus those of 10 mg bisoprolol in patients with stable angina. Patients and methods Twenty-nine patients with stable angina and moderate left ventricular systolic dysfunction already on bisoprolol 5 mg od were randomized into 2 groups. Group 1 (n=17) received ivabradine (5–7.5 mg bid) in addition to bisoprolol 5 mg od, while in group 2 (n=12) bisoprolol was uptitrated first to 7.5 mg and then 10 mg od. Patients underwent a treadmill test, 6-minute walking test, and echocardiography at baseline and after 2 months. Results Mean resting heart rate decreased in both groups, from 76.6±4.6 bpm to 59.3±2.5 bpm (P<0.001) in group 1 and from 75.9±3.0 bpm to 60.5±2.3 bpm (P=0.002) in group 2. The effect on resting heart rate did not differ significantly between the two groups. However, more patients became asymptomatic in group 1 than in group 2. Addition of ivabradine also improved exercise capacity, as shown by the results of the 6-minute walking and exercise tolerance tests, whereas in group 2 neither parameter was significantly affected. Chronotropic reserve significantly improved with ivabradine, but not with bisoprolol 10 mg. Conclusions These results suggest that combining ivabradine with low dose bisoprolol in stable angina patients produces additional antianginal and anti-ischemic benefits and improves chronotropic reserve

Polarization of microbial communities between competitive and cooperative metabolism

Resource competition and metabolic cross-feeding are among the main drivers of microbial community assembly. Yet the degree to which these two conflicting forces are reflected in the composition of natural communities has not been systematically investigated. Here, we use genome-scale metabolic modelling to assess the potential for resource competition and metabolic cooperation in large co-occurring groups (up to 40 members) across thousands of habitats. Our analysis reveals two distinct community types, which are clustered at opposite ends of a spectrum in a trade-off between competition and cooperation. At one end are highly cooperative communities, characterized by smaller genomes and multiple auxotrophies. At the other end are highly competitive communities, which feature larger genomes and overlapping nutritional requirements, and harbour more genes related to antimicrobial activity. The latter are mainly present in soils, whereas the former are found in both free-living and host-associated habitats. Community-scale flux simulations show that, whereas competitive communities can better resist species invasion but not nutrient shift, cooperative communities are susceptible to species invasion but resilient to nutrient change. We also show, by analysing an additional data set, that colonization by probiotic species is positively associated with the presence of cooperative species in the recipient microbiome. Together, our results highlight the bifurcation between competitive and cooperative metabolism in the assembly of natural communities and its implications for community modulation

MiMBl shows robust simulation results while using alternative stoichiometry representations – illustration using a toy-model.

<p><b>a</b>) Toy-model: <i>R1</i> to <i>R7</i> and <i>A</i> to <i>D</i> represent reactions and metabolites, respectively. In the wild-type, or reference, flux goes from <i>A</i> to <i>D</i> via <i>R5</i>. <i>R6</i> and <i>R2–R3–R4</i> are two alternative pathways for flux re-distribution after deletion of <i>R5</i>. <b>b</b>) Flux through reactions <i>R2</i> (full symbols) and <i>R6</i> (open symbols) obtained after simulation of minimization of metabolic adjustment with lMoMA (black), quadratic MoMA (qMoMA, gray) and MiMBl (red) using numerically different but biochemically equivalent representations of reaction <i>R6</i> (given by different scaling factor θ<i>_R6</i>, <b><a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002758#s3" target="_blank">Methods</a></b>). <b>c</b>) Formulation of objective functions of minimization of metabolic adjustment for lMoMA, qMoMA and MiMBl (<b><a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002758#s3" target="_blank">Methods</a></b>). <b>d</b>) Optimal objective function value (distance) obtained for minimization of metabolic adjustment using lMoMA (black), qMoMA (gray) and MiMBl (red) as function of θ<i>_R6</i>.</p