Inoculation of Scrapie with the Self-Assembling RADA-Peptide Disrupts Prion Accumulation and Extends Hamster Survival

Intracerebral inoculation of 263K Scrapie brain homogenate (PrPsc) with a self-assembling RADA-peptide (RADA) significantly delayed disease onset and increased hamster survival. Time of survival was dependent on the dose of RADA and pre-incubation with PrPsc prior to inoculation. RADA treatment resulted in the absence of detectable PrPsc at 40 d followed by an increased rate of PrPsc accumulation at 75 d up to sacrifice. In all PrPsc inoculated animals, clinical symptoms were observed ∼10 d prior to sacrifice and brains showed spongiform degeneration with Congo red positive plaques. A time-dependent increase in reactive gliosis was observed in both groups with more GFAP detected in RADA treated animals at all time points. The PrP protein showed dose-dependent binding to RADA and this binding was competitively inhibited by Congo Red. We conclude that RADA disrupts the efficacy of prion transmission by altering the rate of PrPsc accumulation. This is the first demonstration that a self-assembling biomolecular peptide can interact with PrPsc, disrupt the course of Scrapie disease process, and extend survival

Specific Binding of the Pathogenic Prion Isoform: Development and Characterization of a Humanized Single-Chain Variable Antibody Fragment

Murine monoclonal antibody V5B2 which specifically recognizes the pathogenic form of the prion protein represents a potentially valuable tool in diagnostics or therapy of prion diseases. As murine antibodies elicit immune response in human, only modified forms can be used for therapeutic applications. We humanized a single-chain V5B2 antibody using variable domain resurfacing approach guided by computer modelling. Design based on sequence alignments and computer modelling resulted in a humanized version bearing 13 mutations compared to initial murine scFv. The humanized scFv was expressed in a dedicated bacterial system and purified by metal-affinity chromatography. Unaltered binding affinity to the original antigen was demonstrated by ELISA and maintained binding specificity was proved by Western blotting and immunohistochemistry. Since monoclonal antibodies against prion protein can antagonize prion propagation, humanized scFv specific for the pathogenic form of the prion protein might become a potential therapeutic reagent

Effects of the Surrounding Matrix on Tree Recruitment in Amazonian Forest Fragments

Little is known about how the surrounding modified matrix affects tree recruitment in fragmented forests. We contrasted effects of two different matrix types, Vismia- and Cecropia-dominated regrowth, on recruitment of pioneer tree species in forest fragments in central Amazonia. Our analyses were based on 22, 1-ha plots in seven experimental forest fragments ranging in size from 1 to 100 ha. By 13 to 17 years after fragmentation, the population density of pioneer trees was significantly higher in plots surrounded by Vismia regrowth than in plots surrounded by Cecropia regrowth, and the species composition and dominance of pioneers differed markedly between the two matrix types. Cecropia sciadophylla was the most abundant pioneer in fragments surrounded by Cecropia regrowth (constituting nearly 50% of all pioneer trees), whereas densities of species in Vismia-surrounded fragments were distributed more evenly. Thus the surrounding matrix had a strong influence on patterns of tree recruitment in Amazonian forest fragments. ©2006 Society for Conservation Biology

Evolutionary social and biogeophysical changes in the Amazon, Ganges–Brahmaputra–Meghna and Mekong deltas

Policy-making in social-ecological systems increasingly looks to iterative, evolutionary approaches that can address the inherent complexity of interactions between human wellbeing, provision of goods, and the maintenance of ecosystem services. Here, we show how the analysis of available time-series in tropical delta regions over past decades can provide important insight into the social-ecological system dynamics in deltaic regions. The paper provides an exploratory analysis of the recent changes that have occurred in the major elements of three tropical deltaic social-ecological systems, such as demography, economy, health, climate, food, and water. Time-series data from official statistics, monitoring programmes, and Earth observation data are analysed to explore possible trends, slow and fast variables, and observed drivers of change in the Amazon, Ganges–Brahmaputra–Meghna and Mekong deltas. In the Ganges–Brahmaputra–Meghna delta zone, increasing gross domestic product and per capita income levels since the 1980s mirror rising levels of food and inland fish production. In contrast, non-food ecosystem services, such as water availability, water quality, and land stability appear to be deteriorating. In the Amazon delta, natural and anthropogenic perturbations are continuously degrading key ecosystem services, such as carbon storage in biomass and soils, the regulation of water balance, and the modulation of regional climate patterns. In the Mekong delta, rapid economic development, changing land-use practices, and salinity intrusion are progressively putting more pressure on the delivery of important provisioning services, such as rice and inland aquaculture production, which are key sources of staple food, farm incomes, and export revenue. Observed changes in many key indicators of ecosystem services point to a changing dynamic state and increased probability of systemic threshold transformations in the near future