Antileishmanial activity of indole alkaloids from Aspidosperma ramiflorum

The present study was designated to evaluate the antileishmanial activity of acid and basic fractions that were obtained after acid-basic extraction, from ethanolic 70% crude extract and pure compounds from the stem bark of Aspidosperma ramiflorum. The basic alkaloidal fraction presented a good activity against the extracellular form (promastigotes) of Leishmania (L.) amazonensis (LD(50) value<47 microg/ml). Based on these findings, the basic fraction was fractionated on silica gel column chromatography in a bioassay-guided fractionation affording individual purified ramiflorines A and B. Both ramiflorines A and B showed significant activity against Leishmania (L.) amazonensis (LD(50) values of 16.3+/-1.6 microg/ml and 4.9+/-0.9 microg/ml, respectively). Our results are promising, showing that these compounds are biologically active against Gram-positive bacteria.     

Natural nitrogen filter fails in polluted raised bogs

Raised bogs are among the ecosystems most susceptible to atmospheric nitrogen pollution. Based on global data ranging from pristine to heavily polluted areas, a conceptual model is presented to explain the logistic response of these terrestrial carbon reservoirs to increased airborne nitrogen fluxes.     

Global Food Demand Scenarios for the 21st Century

Long-term food demand scenarios are an important tool for studying global food security and for analysing the environmental impacts of agriculture. We provide a simple and transparent method to create scenarios for future plant-based and animal-based calorie demand, using time-dependent regression models between calorie demand and income. The scenarios can be customized to a specific storyline by using different input data for gross domestic product (GDP) and population projections and by assuming different functional forms of the regressions. Our results confirm that total calorie demand increases with income, but we also found a non-income related positive time-trend. The share of animal-based calories is estimated to rise strongly with income for low-income groups. For high income groups, two ambiguous relations between income and the share of animal-based products are consistent with historical data: First, a positive relation with a strong negative time-trend and second a negative relation with a slight negative time-trend. The fits of our regressions are highly significant and our results compare well to other food demand estimates. The method is exemplarily used to construct four food demand scenarios until the year 2100 based on the storylines of the IPCC Special Report on Emissions Scenarios (SRES). We find in all scenarios a strong increase of global food demand until 2050 with an increasing share of animal-based products, especially in developing countries.     

Letter to the Editor

Regarding Paper “Sample size determination in clinical trials with multiple co‐primary endpoints including mixed continuous and binary variables” by T. Sozu , T. Sugimoto , and T. Hamasaki Biometrical Journal (2012) 54 (5): 716–729 Article: http://dx.doi.org/10.1002/bimj.201100221 Authors' Reply: http://dx.doi.org/10.1002/bimj.201300032 This paper recently introduced a methodology for calculating the sample size in clinical trials with multiple mixed binary and continuous co‐primary endpoints modeled by the so‐called conditional grouped continuous model (CGCM). The purpose of this note is to clarify certain aspects of the methodology and propose an alternative approach based on latent means tests for the binary endpoints. We demonstrate that our approach is more powerful, yielding smaller sample sizes at powers comparable to those used in the paper.     

Vorwort

Ohne Zusammenfassung     

Ernest H. Starling

Ohne Zusammenfassung     

Protection of translation initiation factor eIF2 phosphorylation correlates with eIF2-associated glycoprotein p67 levels and requires the lysine-rich domain I of p67.

The rate of protein synthesis in mammals is largely regulated by phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 (eIF2) that is modulated by the cellular glycoprotein, p67, due to its protection of eIF2alpha phosphorylation (POEP) activity. At the N-terminus of p67, there are three unique domains, and at the C-terminus there is a conserved amino acid sequence. To analyze the importance of these domains, C-terminal deletion mutants of rat p67 were expressed constitutively in KRC-7 cells. In these cells, the phosphorylation level of the alpha-subunit of eIF2 was determined, and it was found that expression of the 1-97 amino acid segment of rat p67 increases POEP activity in vivo, and induces the endogenous levels of p67. These cells also show increased growth rate, and efficient translation of chloramphenicol acetyltransferase and beta-galactosidase reporter genes. At the N-terminus of p67, there are two unique domains: a lysine-rich domain I with the sequence (36)KKKRRKKKK(44), and an acidic residue-rich domain with the sequence (77)EEKEKDDDDEDGDGD(91). Substitution of lysine-rich domain I with (36)NMKSGNKTQ(44) in rat recombinant p67 resulted in the inhibition of its POEP activity, and substitution of the acidic residue-rich domain with (77)QNIQKALEPEAGDGA(91), resulted in no inhibition of POEP activity in KRC-7 cells. Taken together, our data suggest that protection of translation initiation factor eIF2 phosphorylation correlates with eIF2-associated glycoprotein p67 levels and requires the lysine-rich domain I of p67.