Machine Learning Predicts the Yeast Metabolome from the Quantitative Proteome of Kinase Knockouts

A challenge in solving the genotype-to-phenotype relationship is to predict a cell\u27s metabolome, believed to correlate poorly with gene expression. Using comparative quantitative proteomics, we found that differential protein expression in 97 Saccharomyces cerevisiae kinase deletion strains is non-redundant and dominated by abundance changes in metabolic enzymes. Associating differential enzyme expression landscapes to corresponding metabolomes using network models provided reasoning for poor proteome-metabolome correlations; differential protein expression redistributes flux control between many enzymes acting in concert, a mechanism not captured by one-to-one correlation statistics. Mapping these regulatory patterns using machine learning enabled the prediction of metabolite concentrations, as well as identification of candidate genes important for the regulation of metabolism. Overall, our study reveals that a large part of metabolism regulation is explained through coordinated enzyme expression changes. Our quantitative data indicate that this mechanism explains more than half of metabolism regulation and underlies the interdependency between enzyme levels and metabolism, which renders the metabolome a predictable phenotype. Predicting metabolomes from gene expression data is a key challenge in understanding the genotype-phenotype relationship. Studying the enzyme expression proteome in kinase knockouts, we reveal the importance of a so far overlooked metabolism-regulatory mechanism. Enzyme expression changes are impacting on metabolite levels through many changes acting in concert. We show that one can map regulatory enzyme expression patterns using machine learning and use them to predict the metabolome of kinase-deficient cells on the basis of their enzyme expression proteome. Our study quantifies the role of enzyme abundance in the regulation of metabolism and by doing so reveals the potential of machine learning in gaining understanding about complex metabolism regulation

Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan

Metabolism is deeply intertwined with aging. Effects of metabolic interventions on aging have been explained with intracellular metabolism, growth control, and signaling. Studying chronological aging in yeast, we reveal a so far overlooked metabolic property that influences aging via the exchange of metabolites. We observed that metabolites exported by young cells are re-imported by chronologically aging cells, resulting in cross-generational metabolic interactions. Then, we used self-establishing metabolically cooperating communities (SeMeCo) as a tool to increase metabolite exchange and observed significant lifespan extensions. The longevity of the SeMeCo was attributable to metabolic reconfigurations in methionine consumer cells. These obtained a more glycolytic metabolism and increased the export of protective metabolites that in turn extended the lifespan of cells that supplied them with methionine. Our results establish metabolite exchange interactions as a determinant of cellular aging and show that metabolically cooperating cells can shape the metabolic environment to extend their lifespan

World Ocean Review 2015 : living with the oceans 3. Marine resources - opportunities and risks

The third issue of the World Ocean Review, WOR 3, is devoted to marine resources – metals and energy – and their utilization. It gives the facts about the extraction of known oil and gas deposits below the ocean floor and examines the impacts upon flora and fauna. It explains how gas hydrates form on continental shelves and what potential they hold. The review further explores in detail the opportunities and risks presented and posed by extracting mineral resources from the seabed: manganese nodules, cobalt crusts and massive sulphides

World Ocean Review 2015 : Mit den Meeren leben 3. Rohstoffe aus dem Meer - Chancen und Risiken

Die dritte Ausgabe des „World Ocean Review“ widmet sich den metallischen und energetischen Ressourcen des Meeres und ihrer Nutzung. Er liefert Fakten über den Abbau der bekannten Öl- und Gasvorkommen unterhalb des Meeresbodens und beleuchtet die Auswirkungen auf Flora und Fauna. Er erklärt die Entstehung und Potenziale der Gashydratvorkommen an den Kontinentalrändern und liefert detaillierte Informationen über Chancen und Risiken der Nutzung mineralischer Rohstoffe: Manganknollen, Kobaltkrusten und Massivsulfide

Humanity on the move: Unlocking the transformative power of cities

The momentum of urbanization and its impacts are so massive that we must face up to this trend. In view of the existing cognitive, technical, economic and institutional path dependencies, a policy of business as usual – i.e. an unstructured, quasi-automatic urbanization – would lead to a non-sustainable ‘world cities society’. Only if cities and urban societies are sufficiently empowered can they make use of the opportunities for sustainability and successfully follow the urban transformation pathways. The success or failure of the Great Transformation will be decided in the cities. The WBGU discusses the relevant conditions for the success of this transformation in this report

Der Umzug der Menschheit: Die transformative Kraft der Städte

Die Wucht der derzeitigen Urbanisierungsdynamik und ihre Auswirkungen sind so groß, dass sich weltweit Städte, Stadtgesellschaften, Regierungen und Internationale Organisationen diesem Trend stellen müssen. Ein „Weiter so wie bisher“, würde ohne gestaltende Urbanisierungspolitik zu einer nicht-nachhaltigen Welt-Städte-Gesellschaft führen. Nur wenn Städte und Stadtgesellschaften ausreichend handlungsfähig werden, können sie ihre Kraft für eine nachhaltige Entwicklung entfalten: In den Städten wird sich entscheiden, ob die Große Transformation zur Nachhaltigkeit gelingt. In diesem Buch werden die Erfolgsbedingungen dafür diskutiert

Towards Our Common Digital Future. Flagship Report.

In the report “Towards Our Common Digital Future”, the WBGU makes it clear that sustainability strategies and concepts need to be fundamentally further developed in the age of digitalization. Only if digital change and the Transformation towards Sustainability are synchronized can we succeed in advancing climate and Earth-system protection and in making social progress in human development. Without formative political action, digital change will further accelerate resource and energy consumption, and exacerbate damage to the environment and the climate. It is therefore an urgent political task to create the conditions needed to place digitalization at the service of sustainable development

An intra-cerebral drug delivery system for freely moving animals

Abstract Microinfusions of drugs directly into the central nervous system of awake animals represent a widely used means of unravelling brain functions related to behaviour. However, current approaches generally use tethered liquid infusion systems and a syringe pump to deliver drugs into the brain, which often interfere with behaviour. We address this shortfall with a miniaturised electronically-controlled drug delivery system (20×17.5×5 mm 3 ) designed to be skull-mounted in rats. The device features a micropump connected to two 8-mm-long silicon microprobes with a cross section of 250×250 μm 2 and integrated fluid microchannels. Using an external electronic control unit, the device allows infusion of 16 metered doses (0.25 μL each, 8 per silicon shaft). Each dosage requires 3.375 Ws of electrical power making the device additionally compatible with state-of-the-art wireless headstages. A dosage precision of 0.25±0.01 μL was determined in vitro before in vivo tests were carried out in awake rats. No passive leakage from the loaded devices into the brain could be detected using methylene blue dye. Finally, the device was used to investigate the effects of the NMDA-receptor antagonist 3-((R)-2-Carboxypiperazin-4-yl)-propyl-1-phosphonic acid, (R)-CPP, administered directly into the prefrontal cortex of rats during performance on a task to assess visual attention and impulsivity. In agreement with previous findings using conventional tethered infusion systems, acute (R)-CPP administration produced a marked increase in impulsivity

Physarum nitric oxide synthases: genomic structures and enzymology of recombinant proteins

Physarum polycephalum expresses two closely related, calcium-independent NOSs (nitric oxide synthases). In our previous work, we showed that both NOSs are induced during starvation and apparently play a functional role in sporulation. In the present study, we characterized the genomic structures of both Physarum NOSs, expressed both enzymes recombinantly in bacteria and characterized their biochemical properties. Whereas the overall genomic organization of Physarum NOS genes is comparable with various animal NOSs, none of the exon–intron boundaries are conserved. Recombinant expression of clones with various N-termini identified N-terminal amino acids essential for enzyme activity, but not required for haem binding or dimerization, and suggests the usage of non-AUG start codons for Physarum NOSs. Biochemical characterization of the two Physarum isoenzymes revealed different affinities for L-arginine, FMN and 6R-5,6,7,8-tetrahydro-L-biopterin