Antibodies designed as effective cancer vaccines

Antigen/antibody complexes can efficiently target antigen presenting cells to allow stimulation of the cellular immune response. Due to the difficulty of manufacture and their inherent instability complexes have proved inefficient cancer vaccines. However, anti-idiotypic antibodies mimicking antigens have been shown to stimulate both antibody and T cell responses. The latter are due to T cell mimotopes expressed within the complementarity-determining regions (CDRs) of antibodies that are efficiently presented to dendritic cells in vivo. Based on this observation we have designed a DNA vaccine platform called ImmunoBody™, where cytotoxic T lymphocyte (CTL) and helper T cell epitopes replace CDR regions within the framework of a human IgG1 antibody. The ImmunoBody™ expression system has a number of design features which allow for rapid production of a wide range of vaccines. The CDR regions of the heavy and light chain have been engineered to contain unique restriction endonuclease sites, which can be easily opened, and oligonucleotides encoding the T cell epitopes inserted. The variable and constant regions of the ImmunoBody™ are also flanked by restriction sites, which permit easy exchange of other IgG subtypes. Here we show a range of T cell epitopes can be inserted into the ImmunoBody™ vector and upon immunization these T cell epitopes are efficiently processed and presented to stimulate high frequency helper and CTL responses capable of anti-tumor activity.Key words: DNA vaccines, cancer vaccines, melanoma, CTL, helper T cells     

出声阅读中语音通达的双通路模型

双通路模型理论认为语音的通达存在两条通路,即词典通路和非词典通路。该理论不仅可以解释大量正常人的阅读现象,比如频率效应、规则性效应等,而且得到了许多来自失语症病人资料的支持,比如表层失语、语音性失语等。双通路模型成功地实现了计算化,目前研究者们已经开始从脑加工机制方面对双通路模型进行检验。该文系统论述了双通路模型理论的发展过程及目前发展状况和趋势。     

Palatability of macrophytes to the invasive freshwater snail Pomacea canaliculata: differential effects of multiple plant traits

1. By selective grazing, invasive grazers can alter macrophyte‐herbivore relationships in shallow freshwater bodies. Evaluating the palatability of macrophytes and understanding the determinants of plant palatability can help predict grazing impact. In no‐choice feeding assays, we tested the palatability of 21 species of freshwater macrophytes to the invasive freshwater apple snail Pomacea canaliculata. 2. Daily feeding rate varied greatly with plant species, ranging from 1.1 to 22% of snail body mass. We assessed six plant properties and examined their correlation with feeding rate. Total nitrogen content was positively related, and C:N ratio and dry matter content (DMC) negatively related, to snail feeding rate. There was no significant correlation between snail feeding rate and plant phenolic content, but the feeding rate on Myriophyllum aquaticum (the plant with the highest phenolic content) was very low. 3. We repeated the feeding assays for 15 species that were not palatable as fresh leaves with reconstituted plant tissues formed by mixing ground up dried leaves with agar. The feeding rate still differed greatly among macrophyte species. Phragmites australis and Vallisneria natans (two species with the highest DMC) were eaten much more as reconstituted plant than as fresh leaves, indicating that structure (i.e. DMC) may be important in their defence against snail herbivory. For two plants (M. aquaticum and Alternanthera philoxeroides) that had moderate amounts of nitrogen/phosphorus but were consumed very little as fresh and reconstituted tissues, we incorporated their extracts into a palatable agar‐based food. The extracts from both species greatly reduced snail feeding rate, indicating the presence of chemical defences in these two species. 4. These results indicated that feeding was affected by several plant traits. The snail favoured plants with a high nitrogen content and avoided plants with a high DMC. Only a few plants possessed chemical feeding deterrents that were effective against this snail. Given the invasive spread of P. canaliculata in Asia, ecologists and managers should consider plant palatability when selecting plants for use in wetland restoration and when predicting the impact of further invasion by this species.     

Recovery of understorey vegetation after release from a long history of sheep grazing in a herb‐rich woodland

The effects of stock grazing on native grassy ecosystems in temperate southern Australia are well documented. However, less is known about the potential of ecosystems to recover after a long history of stock grazing and, in particular, whether the removal of stock will have positive, negative or neutral impacts on biodiversity. We examined the response of understorey vegetation to the removal of sheep grazing in a herb‐rich Eucalyptus camaldulensis (red gum) woodland in western Victoria. Using a space‐for‐time chronosequence, woodlands were stratified into groups based on their time‐since‐grazing removal; these were long‐ungrazed (>20 years), intermediate‐time‐since‐grazing (9–14 years), recently ungrazed (5 years) and continuously grazed. We found significantly higher species density in long‐ungrazed sites relative to sites with a more recent grazing history. No differences were found in species density between continuously grazed sites and those ungrazed in the previous 14 years. Species composition differed with time‐since‐grazing removal and indicator species analysis detected several native species (including tall native geophytes and herbs) associated with long‐ungrazed sites that were absent or in low abundance in the more recently grazed sites. Seven of the eight species significantly associated with continuously grazed sites were exotic. Removal of sheep grazing in red gum woodlands can have positive benefits for understorey diversity but it is likely that recovery of key indicators such as native species will be slow.