Differential forms via the Bernstein-Gelfand-Gelfand resolution for quantized irreducible flag manifolds

The quantum group version of the Bernstein-Gelfand-Gelfand resolution is used to construct a double complex of U_q(g)-modules with exact rows and columns. The locally finite dual of its total complex is identified with the de Rham complex for quantized irreducible flag manifolds.Comment: LaTeX2e, 44 page

Emergence of robust growth laws from optimal regulation of ribosome synthesis

Bacteria must constantly adapt their growth to changes in nutrient availability; yet despite large‐scale changes in protein expression associated with sensing, adaptation, and processing different environmental nutrients, simple growth laws connect the ribosome abundance and the growth rate. Here, we investigate the origin of these growth laws by analyzing the features of ribosomal regulation that coordinate proteome‐wide expression changes with cell growth in a variety of nutrient conditions in the model organism Escherichia coli. We identify supply‐driven feedforward activation of ribosomal protein synthesis as the key regulatory motif maximizing amino acid flux, and autonomously guiding a cell to achieve optimal growth in different environments. The growth laws emerge naturally from the robust regulatory strategy underlying growth rate control, irrespective of the details of the molecular implementation. The study highlights the interplay between phenomenological modeling and molecular mechanisms in uncovering fundamental operating constraints, with implications for endogenous and synthetic design of microorganisms.ISSN:1744-429

Improving the batch-to-batch reproducibility in microbial cultures during recombinant protein production by guiding the process along a predefined total biomass profile

In industry Escherichia coli is the preferred host system for the heterologous biosynthesis of therapeutic proteins that do not need posttranslational modifications. In this report, the development of a robust high-cell-density fed-batch procedure for the efficient production of a therapeutic hormone is described. The strategy is to guide the process along a predefined profile of the total biomass that was derived from a given specific growth rate profile. This profile might have been built upon experience or derived from numerical process optimization. A surprisingly simple adaptive procedure correcting for deviations from the desired path was developed. In this way the batch-to-batch reproducibility can be drastically improved as compared to the process control strategies typically applied in industry. This applies not only to the biomass but, as the results clearly show, to the product titer also

Growth-Rate Dependence Reveals Design Principles of Plasmid Copy Number Control

Genetic circuits in bacteria are intimately coupled to the cellular growth rate as many parameters of gene expression are growth-rate dependent. Growth-rate dependence can be particularly pronounced for genes on plasmids; therefore the native regulatory systems of a plasmid such as its replication control system are characterized by growth-rate dependent parameters and regulator concentrations. This natural growth-rate dependent variation of regulator concentrations can be used for a quantitative analysis of the design of such regulatory systems. Here we analyze the growth-rate dependence of parameters of the copy number control system of ColE1-type plasmids in E. coli. This analysis allows us to infer the form of the control function and suggests that the Rom protein increases the sensitivity of control

Tuning fresh: radiation through rewiring of central metabolism in streamlined bacteria

Most free-living planktonic cells are streamlined and in spite of their limitations in functional flexibility, their vast populations have radiated into a wide range of aquatic habitats. Here we compared the metabolic potential of subgroups in the Alphaproteobacteria lineage SAR11 adapted to marine and freshwater habitats. Our results suggest that the successful leap from marine to freshwaters in SAR11 was accompanied by a loss of several carbon degradation pathways and a rewiring of the central metabolism. Examples for these are C1 and methylated compounds degradation pathways, the Entner–Doudouroff pathway, the glyoxylate shunt and anapleuretic carbon fixation being absent from the freshwater genomes. Evolutionary reconstructions further suggest that the metabolic modules making up these important freshwater metabolic traits were already present in the gene pool of ancestral marine SAR11 populations. The loss of the glyoxylate shunt had already occurred in the common ancestor of the freshwater subgroup and its closest marine relatives, suggesting that the adaptation to freshwater was a gradual process. Furthermore, our results indicate rapid evolution of TRAP transporters in the freshwater clade involved in the uptake of low molecular weight carboxylic acids. We propose that such gradual tuning of metabolic pathways and transporters toward locally available organic substrates is linked to the formation of subgroups within the SAR11 clade and that this process was critical for the freshwater clade to find and fix an adaptive phenotype.This work was supported by the Swedish Research Council (Grant Numbers 2012-4592 to AE and 2012-3892 to SB) and the Communiy Sequencing Programme of the US Department of Energy Joint Genome Institute. The work conducted by the US Department of Energy Joint Genome Institute, a DOE Office of Science User Facility, is supported under Contract No. DE-AC02-05CH11231

Stability of Metabolic Correlations under Changing Environmental Conditions in Escherichia coli – A Systems Approach

Background: Biological systems adapt to changing environments by reorganizing their cellular and physiological program with metabolites representing one important response level. Different stresses lead to both conserved and specific responses on the metabolite level which should be reflected in the underlying metabolic network. Methodology/Principal Findings: Starting from experimental data obtained by a GC-MS based high-throughput metabolic profiling technology we here develop an approach that: (1) extracts network representations from metabolic condition-dependent data by using pairwise correlations, (2) determines the sets of stable and condition-dependent correlations based on a combination of statistical significance and homogeneity tests, and (3) can identify metabolites related to the stress response, which goes beyond simple observations about the changes of metabolic concentrations. The approach was tested with Escherichia coli as a model organism observed under four different environmental stress conditions (cold stress, heat stress, oxidative stress, lactose diauxie) and control unperturbed conditions. By constructing the stable network component, which displays a scale free topology and small-world characteristics, we demonstrated that: (1) metabolite hubs in this reconstructed correlation networks are significantly enriched for those contained in biochemical networks such as EcoCyc, (2) particular components of the stable network are enriched for functionally related biochemical pathways, and (3) independently of the response scale, based on their importance in the reorganization of the correlation network a set of metabolites can be identified which represent hypothetical candidates for adjusting to a stress-specific response. Conclusions/Significance: Network-based tools allowed the identification of stress-dependent and general metabolic correlation networks. This correlation-network-based approach does not rely on major changes in concentration to identify metabolites important for stress adaptation, but rather on the changes in network properties with respect to metabolites. This should represent a useful complementary technique in addition to more classical approaches

Qualification of ship doctors: a German approach

Background: While a steady growth of cruise tourism since the 1970s created an increasing demand for ship doctors medical postgraduate specialty training did not sufficiently reflect the scope of skills and knowledge required from a physician being left to himself at sea. The German Maritime Health Association therefore tasked a working group with analysing the situation and coming up with suggestions for an adequate postgraduate training for ship doctors. Materials and methods: The working group consisted of 19 experts with various backgrounds in maritime medicine. A literature review was done on cruise ship epidemiology as well as an assessment of tasks and environmental factors influencing medical care on board of cruise ships. Necessary knowledge and skills were derived and compared with those imparted by standard German medical education. Results: Mandatory knowledge and skills were identified as well as elements of standard medical education contributing to these goals. Those aspects that would or could not be adequately covered by German standard education were catalogued and summarised in a course curriculum. Conclusions: In 2013 after approval by its board of directors the German Maritime Health Association published a qualification and training recommendation addressing colleagues planning to muster as ship doctors

Drittmitteleinwerbungen als Forschungsindikator Ergebnisbericht zum Teil II des Projektes 'Vergleichende Bewertung von Leistungen der Hochschulen'

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