Novel biocatalysts by identification and design

Enzymes produced from bacteria and eukaryotic organisms are presently being used for a large variety of different biotechnological applications. The rapidly increasing demand for enzymes which are active towards novel and often non-natural substrates has triggered the development of novel molecular biological methods of enzyme isolation and design. The metagenome approach is a cultivation-independent method which allows the direct cloning and expression of environmental DNA thereby providing access to a wealth of so-far unknown biocatalysts. Additionally, newly identified or existing biocatalysts can be further optimized by different methods of directed evolution. Here, the principle of the metagenome approach is outlined and a strategy is presented for the optimization of a bacterial lipase using a combination of rational design and directed evolution.

Experimental transmission of Zika virus by mosquitoes from central Europe

Mosquitoes collected in Germany in 2016, including Culex pipiens pipiens biotype pipiens, Culex torrentium and Aedes albopictus, as well as Culex pipiens pipiens biotype molestus (in colony since 2011) were experimentally infected with Zika virus (ZIKV) at 18 degrees C or 27 degrees C. None of the Culex taxa showed vector competence for ZIKV. In contrast, Aedes albopictus were susceptible for ZIKV but only at 27 degrees C, with transmission rates similar to an Aedes aegypti laboratory colony tested in parallel.Peer reviewe

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

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

Functional characterization of the PHT1 family transporters of foxtail millet with development of a novel Agrobacterium-mediated transformation procedure

Phosphate is an essential nutrient for plant growth and is acquired from the environment and distributed within the plant in part through the action of phosphate transporters of the PHT1 family. Foxtail millet (Setaria italica) is an orphan crop essential to the food security of many small farmers in Asia and Africa and is a model system for other millets. A novel Agrobacterium-mediated transformation and direct plant regeneration procedure was developed from shoot apex explants and used to downregulate expression of 3 members of the PHT1 phosphate transporter family SiPHT1;2 SiPHT1;3 and SiPHT1;4. Transformants were recovered with close to 10% efficiency. The downregulation of individual transporters was confirmed by RT-PCR. Downregulation of individual transporters significantly reduced the total and inorganic P contents in shoot and root tissues and increased the number of lateral roots and root hairs showing they have non-redundant roles. Downregulation of SiPHT1;2 had the strongest effect on total and inorganic P in shoot and root tissues. Complementation experiments in S. cerevisiae provide evidence for the ability of SiPHT1;1, 1;2, 1;3, 1;7 and 1;8 to function as high affinity Pi transporters. This work will aid development of improved millet varieties for global food security

Der virtuelle Raum als Double - oder: zur Persistenz hierarchischer Gesellschaftsstruktur im Netz

Der raumsoziologische Beitrag diskutiert, was die mit der Technologie des Internets einhergehende Virtualisierung für eine sich ändernde Gesellschaftsordnung bedeuten kann. Anhand ihres methodologischen RaumZeit-Modells zeigt die Autorin, dass die virtuelle Realität des Internets eine doppelte materiale Gestalt hervorbringt. Als Double ergänzt der virtuelle Raum den realen. Die Ausgangsannahme lautet, dass die bürgerlich-moderne Gesellschaft Raum als Zweidimensionalität und als Behälter sowie Zeit als messbar und linear hervorgebracht hat. Entgegen vielfach geäußerter Einschätzungen revolutioniert das Internet nicht Vorstellungen und Praxis von Raum und Zeit, sondern es perfektioniert die bürgerliche Konstruktion des ideal beherrschbaren Lebens. Der Hypothese folgend, dass die neuen virtuellen Realitäten veränderte Materialitäten etablieren, werden verschiedene Zukunftsszenarien am Beispiel des Geschlechterverhältnisses durchgespielt

Development and justice through transformation: The Four Big ‘I’s. Special Report

2015 saw a historic double success for sustainability and climate policy. The 2030 Agenda for Sustainable Development, with its Sustainable Development Goals (SDGs), and the Paris Agreement on climate ­protection establish a system of ambitious policy goals for the world. The group of twenty major ­industrialized and emerging economies (G20) now needs to resolutely advance implementation of both agreements, seizing the opportunity of this ‘Great Transformation’ to sustainability as a unique ­modernization project that could offer substantial economic development opportunities. Complete ­decarbonization of the world economy, which is necessary to avoid the gravest climate risks, can only be achieved by profoundly ­transforming energy systems and other high-emissions infrastructures. This transformation could inspire ­Innovation and channel Investment into sustainability and climate protection, and into the kinds of ­sustainable Infrastructures that need to be ­established and expanded. At the same time, the transformation could combat inequality and promote ­Inclusion within societies and globally, thus becoming an equity project

Molecular Cloning, Characterization and Expression Analysis of Two Members of the Pht1 Family of Phosphate Transporters in Glycine max

BACKGROUND: Phosphorus is one of the macronutrients essential for plant growth and development. The acquisition and translocation of phosphate are pivotal processes of plant growth. In a large number of plants, phosphate uptake by roots and translocation within the plant are presumed to occur via a phosphate/proton cotransport mechanism. PRINCIPAL FINDINGS: We cloned two cDNAs from soybean (Glycine max), GmPT1 and GmPT2, which show homology to the phosphate/proton cotransporter PHO84 from the budding yeast Saccharomyces cerevisiae. The amino acid sequence of the products predicted from GmPT1 and GmPT2 share 61% and 63% identity, respectively, with the PHO84 in amino acid sequence. The deduced structure of the encoded proteins revealed 12 membrane-spanning domains with a central hydrophilic region. The molecular mass values are ∼58.7 kDa for GmPT1 and ∼58.6 kDa for GmPT2. Transiently expressed GFP-protein fusions provide direct evidence that the two Pi transporters are located in the plasma membrane. Uptake of radioactive orthophosphate by the yeast mutant MB192 showed that GmPT1 and GmPT2 are dependent on pH and uptake is reduced by the addition of uncouplers of oxidative phosphorylation. The K(m) for phosphate uptake by GmPT1 and GmPT2 is 6.65 mM and 6.63 mM, respectively. A quantitative real time RT-PCR assay indicated that these two genes are expressed in the roots and shoots of seedlings whether they are phosphate-deficient or not. Deficiency of phosphorus caused a slight change of the expression levels of GmPT1 and GmPT2. CONCLUSIONS: The results of our experiments show that the two phosphate transporters have low affinity and the corresponding genes are constitutively expressed. Thereby, the two phosphate transporters can perform translocation of phosphate within the plant

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.