Superstolide A : a potent cytotoxic macrolide of a new type from the New Caledonian deep water marine sponge Neosiphonia superstes

A highly cytotoxic macrolide, superstolide A (1), has been isolated from the deep water marine sponge Neosiphonia superstes, collected off New Caledonia. The gross structure was determined by extensive 2D NMR experiments on the lactone 1 and on its opened-ring-derived methyl esters 2 and 3. The relative stereochemistries of the decaline moiety and of the C22-C26 fragment were determined by a combination of NMR data and acetonide analysis on 2. Absolute stereostructure of the decaline portion of 1 has been determined on the basis of GLC-modified Horeau's methodology applied to 4, whereas the results of the application of the modified Mosher's method to 1 and 3 allowed us to propose for the C22-C26 fragment the 22R, 23R, 24R, 25S, 26R configuration. We also propose the solution conformations of superstolide A (1) based on molecular dynamics and mechanics calculations using NMR-derived constraints

Crop-Specific EU Aid and Smallholder Food Security in Sierra Leone

The article analyses the viability of promoting crop-specific programs as a mean to improve smallholder net farm income and food security. The case study explores the relevance of European Union Stabilisation of Export Earnings (STABEX) funds in supporting Sierra Leone’s agricultural development agenda. By analysing the drivers of food security for a number of targeted smallholders in the two most important agricultural zones of Sierra Leone, it is possible to compare the suitability of crop-specific support (in rice, cocoa and coffee) versus general aid programs (public infrastructure, on and off farm diversification opportunities, sustainable practices, access to productive assets, etc.). The results indicate that crop diversification strategies are widespread and closely related to risk minimisation and enhanced food security among smallholders. Similarly, crop-specific programs mainly focusing on commercialisation tend to overlook important constraints associated to self-consumption and productivity

Metabolites of the new Caledonian sponge Cladocroce incurvata

The deep-water New Caledonian sponge #Cladocroce incurvata$ contains two "polyketide" metabolites. Cladocrocin A (1) appears to be derived from fatty acid with ethyl side chains, thus incorporating butyrate units. Cladocroic acid (2) is a straight chain fatty acid which incorporates a terminal enyne functionality and a cycloproprane ring directly attached to the carboxylic acid function. The structures were elucidated by interpretation of spectral data, and the cis stereochemistry of the cyclopropane ring in cladocroic acid (2) was derived after the synthesis of cis - and trans - 2, 3 - methanohexanoic acid models and nmr spectral comparisons. (Résumé d'auteur

Molecular basis of phospholipase A2 inhibition by petrosaspongiolide M.

Petrosaspongiolide M (PM) is an anti-inflammatory marine metabolite that displays a potent inhibitory activity toward group II and III secretory phospholipase A2 (PLA2) enzymes. The details of the mechanism, which leads to a covalent adduct between PLA2 and γ-hydroxybutenolide-containing molecules such as PM, are still a matter of debate. In this paper the covalent binding of PM to bee venom PLA2 has been investigated by mass spectrometry and molecular modeling. The mass increment observed for the PM-PLA2 adduct is consistent with the formation of a Schiff base by reaction of a PLA2 amino group with the hemiacetal function (masked aldehyde) at the C-25 atom of the PM γ-hydroxybutenolide ring. Proteolysis of the modified PLA2 by the endoprotease LysC followed by HPLC MS analysis allowed us to establish that the PLA2 α-amino terminal group of the lle-1 residue was the only covalent binding site for PM. The stoichiometry of the reaction between PM and PLA2 was also monitored and results showed that even with excess inhibitor, the prevalent product is a 1:1 (inhibitor:enzyme) adduct, although a 2:1 adduct is present as a minor component. The 2:1 adduct was also characterized, which showed that the second site of reaction is located at the ε-amino group of the Lys-85 residue. Similar results in terms of the reaction profile, mass increments, and location of the PLA2 binding site were obtained for manoalide, a paradigm for irreversible PLA2 inhibitors, which suggests that the present results may be considered of more general interest within the field of anti-inflammatory sesterterpenes that contain the γ-hydroxybutenolide pharmacophore. Finally, a 3D model, constrained by the above experimental results, was obtained by docking the inhibitor molecule into the PLA2 binding site through AFFINITY calculations. The model provides an interesting insight into the PM-PLA2 inhibition process and may prove useful in the design of new anti-inflammatory agents that target PLA2 secretory enzymes

Sustainability and Production Costs in the Global Farming Sector: Comparative Analysis and Methodologies

This report constitutes a comprehensive compilation and synthesis of the principle issues and outcomes of the joint Institute for prospective Technological Studies / Directorate-General for Agriculture and Rural Development workshop on "Sustainability and Production Costs in the Global Farming Sector: Comparative Analysis and Methodologies" held in Brussels between 21-22 June 2011. Gathering a range of international experts and specialists in the field of production costs analysis and development, covering a range of strategic agricultural sectors of global importance, the workshop aimed to review methodologies and approaches to calculating production costs used in various sectors nationally and globally, with emphasis on exploring the applicability for effective international comparisons. A special attention was given to the methodologies and approaches for data collection and processing, factor market structure and policy inter-linkages, sectoral coverage, horizontal technical issues, and the implications for global agricultural markets. Based on the participant deliberations and discussions, a number of practically based policy recommendations towards achieving such comparisons were highlighted. The production of this report, following completion of the workshop, has been the responsibility of the IPTS. This task has been facilitated through collaboration with four internationally recognised experts (Folkhard Isermeyer, von Thünen-Institute, Germany (Chapter 2), Dan L. Cunningham, University of Georgia, USA (Chapter 3), Jean-François Garnier, ARVALIS, France (Chapter 4), Ashok K. Mishra, Louisiana State University, USA (Chapter 5)) acting as rapporteurs for each of the workshop's four technical sessions, whose efforts in capturing the principle issues and outcomes of their respective session has been instrumental towards realisation of this report. Stephen Langrell, Pavel Ciaian and Sergio Gomez y Paloma acted as Editors and compiled Chapters 1 and 6. This report constitutes a particular and comprehensive technical overview of the state of production costs calculations for the sectors under consideration at global level, and a consideration of the prospects for effective international comparison. It reviews methodologies applied for production costs calculation at national and global level followed by the discussion on methodologies used for animal and arable crop sectors. Finally, the report discusses horizontal issues related to production costs calculations. The report closes with policy-relevant conclusions as a basis for policy recommendations. It is envisaged that this report will provide a valuable source of technical and conceptual information for on-going policy considerations, both at EU and third country/international level.JRC.J.4-Agriculture and Life Sciences in the Econom

Income elasticities for food, calories and nutrients across Africa : A meta-analysis

This work was supported by the European Commission’s Joint Research Centre (JRC), Directorate of Sustainable Resources, Unit D.4 Economics of Agriculture and DG DEVCO as part of the TS4FNS (Technical Support for Food and Nutrition Security) project (contract JRC 154328).Peer reviewedPublisher PD

Antibody recognition of the glycoprotein g of viral haemorrhagic septicemia virus (VHSV) purified in large amounts from insect larvae

<p>Abstract</p> <p>Background</p> <p>There are currently no purification methods capable of producing the large amounts of fish rhabdoviral glycoprotein G (gpG) required for diagnosis and immunisation purposes or for studying structure and molecular mechanisms of action of this molecule (ie. pH-dependent membrane fusion). As a result of the unavailability of large amounts of the gpG from viral haemorrhagic septicaemia rhabdovirus (VHSV), one of the most dangerous viruses affecting cultured salmonid species, research interests in this field are severely hampered. Previous purification methods to obtain recombinant gpG from VHSV in <it>E. coli</it>, yeast and baculovirus grown in insect cells have not produced soluble conformations or acceptable yields. The development of large-scale purification methods for gpGs will also further research into other fish rhabdoviruses, such as infectious haematopoietic necrosis virus (IHNV), spring carp viremia virus (SVCV), hirame rhabdovirus (HIRRV) and snakehead rhabdovirus (SHRV).</p> <p>Findings</p> <p>Here we designed a method to produce milligram amounts of soluble VHSV gpG. Only the transmembrane and carboxy terminal-deleted (amino acid 21 to 465) gpG was efficiently expressed in insect larvae. Recognition of G21-465 by ß-mercaptoethanol-dependent neutralizing monoclonal antibodies (N-MAbs) and pH-dependent recognition by sera from VHSV-hyperimmunized or VHSV-infected rainbow trout (<it>Oncorhynchus mykiss</it>) was demonstrated.</p> <p>Conclusions</p> <p>Given that the purified G21-465 conserved some of its most important properties, this method might be suitable for the large-scale production of fish rhabdoviral gpGs for use in diagnosis, fusion and antigenicity studies.</p