Tuning self-assembled nanostructures through enzymatic degradation of a peptide amphiphile

The enzymatic cleavage of a peptide amphiphile (PA) is investigated. The self-assembly of the cleaved products is distinct from that of the PA substrate. The PA C16-KKFFVLK is cleaved by α-chymotrypsin at two sites leading to products C16-KKF with FVLK and C16-KKFF with VLK. The PA C16-KKFFVLK forms nanotubes and helical ribbons at room temperature. Both PAs C16-KKF and C16-KKFF corresponding to cleavage products instead self-assemble into 5-6 nm diameter spherical micelles, while peptides FVLK and VLK do not adopt well-defined aggregate structures. The secondary structures of the PAs and peptides are examined by FTIR and circular dichroism spectroscopy and X-ray diffraction. Only C16-KKFFVLK shows substantial β-sheet secondary structure, consistent with its self-assembly into extended aggregates, based on PA layers containing hydrogen-bonded peptide headgroups. This PA also exhibits a thermoreversible transition to twisted tapes on heating.

An evidence-based review on the likely economic and environmental impact of genetically modified cereals and oilseeds for UK agriculture

An evidence-based review of the potential impact that the introduction of genetically-modified (GM) cereal and oilseed crops could have for the UK was carried out. The inter-disciplinary research project addressed the key research questions using scenarios for the uptake, or not, of GM technologies. This was followed by an extensive literature review, stakeholder consultation and financial modelling. The world area of canola, oilseed rape (OSR) low in both erucic acid in the oil and glucosinolates in the meal, was 34M ha in 2012 of which 27% was GM; Canada is the lead producer but it is also grown in the USA, Australia and Chile. Farm level effects of adopting GM OSR include: lower production costs; higher yields and profits; and ease of farm management. Growing GM OSR instead of conventional OSR reduces both herbicide usage and environmental impact. Some 170M ha of maize was grown in the world in 2011 of which 28% was GM; the main producers are the USA, China and Brazil. Spain is the main EU producer of GM maize although it is also grown widely in Portugal. Insect resistant (IR) and herbicide tolerant (HT) are the GM maize traits currently available commercially. Farm level benefits of adopting GM maize are lower costs of production through reduced use of pesticides and higher profits. GM maize adoption results in less pesticide usage than on conventional counterpart crops leading to less residues in food and animal feed and allowing increasing diversity of bees and other pollinators. In the EU, well-tried coexistence measures for growing GM crops in the proximity of conventional crops have avoided gene flow issues. Scientific evidence so far seems to indicate that there has been no environmental damage from growing GM crops. They may possibly even be beneficial to the environment as they result in less pesticides and herbicides being applied and improved carbon sequestration from less tillage. A review of work on GM cereals relevant for the UK found input trait work on: herbicide and pathogen tolerance; abiotic stress such as from drought or salinity; and yield traits under different field conditions. For output traits, work has mainly focussed on modifying the nutritional components of cereals and in connection with various enzymes, diagnostics and vaccines. Scrutiny of applications submitted for field trial testing of GM cereals found around 9000 applications in the USA, 15 in Australia and 10 in the EU since 1996. There have also been many patent applications and granted patents for GM cereals in the USA for both input and output traits;an indication of the scale of such work is the fact that in a 6 week period in the spring of 2013, 12 patents were granted relating to GM cereals. A dynamic financial model has enabled us to better understand and examine the likely performance of Bt maize and HT OSR for the south of the UK, if cultivation is permitted in the future. It was found that for continuous growing of Bt maize and HT OSR, unless there was pest pressure for the former and weed pressure for the latter, the seed premia and likely coexistence costs for a buffer zone between other crops would reduce the financial returns for the GM crops compared with their conventional counterparts. When modelling HT OSR in a four crop rotation, it was found that gross margins increased significantly at the higher levels of such pest or weed pressure, particularly for farm businesses with larger fields where coexistence costs would be scaled down. The impact of the supply of UK-produced GM crops on the wider supply chain was examined through an extensive literature review and widespread stakeholder consultation with the feed supply chain. The animal feed sector would benefit from cheaper supplies of raw materials if GM crops were grown and, in the future, they might also benefit from crops with enhanced nutritional profile (such as having higher protein levels) becoming available. This would also be beneficial to livestock producers enabling lower production costs and higher margins. Whilst coexistence measures would result in increased costs, it is unlikely that these would cause substantial changes in the feed chain structure. Retailers were not concerned about a future increase in the amount of animal feed coming from GM crops. To conclude, we (the project team) feel that the adoption of currently available and appropriate GM crops in the UK in the years ahead would benefit farmers, consumers and the feed chain without causing environmental damage. Furthermore, unless British farmers are allowed to grow GM crops in the future, the competitiveness of farming in the UK is likely to decline relative to that globally.

Prostate cancer: important steps and considerations in the design of therapeutic vaccines

Vaccine-based immunotherapy can increase the overall survival of patients with advanced prostate cancer. However, the efficacy of vaccine-elicited anticancer immune responses is heavily influenced by the physical, nutritional, and psychological status of the patient. Given their importance, these parameters should be carefully considered for the design of future clinical trials testing this immunotherapeutic paradigm in prostate cancer patients.

Structure-based energetics of protein interfaces guides foot-and-mouth disease virus vaccine design

Virus capsids are primed for disassembly, yet capsid integrity is key to generating a protective immune response. Foot-and-mouth disease virus (FMDV) capsids comprise identical pentameric protein subunits held together by tenuous noncovalent interactions and are often unstable. Chemically inactivated or recombinant empty capsids, which could form the basis of future vaccines, are even less stable than live virus. Here we devised a computational method to assess the relative stability of protein-protein interfaces and used it to design improved candidate vaccines for two poorly stable, but globally important, serotypes of FMDV: O and SAT2. We used a restrained molecular dynamics strategy to rank mutations predicted to strengthen the pentamer interfaces and applied the results to produce stabilized capsids. Structural analyses and stability assays confirmed the predictions, and vaccinated animals generated improved neutralizing-antibody responses to stabilized particles compared to parental viruses and wild-type capsids.