Assassins and apples: the environmental constraints of two snails that threaten Australian aquatic systems

Context: Alien freshwater snails pose a substantial risk to Australian native aquatic biota.Aims: This study aims to determine the thermal and salinity ranges of two introduced species within Australia, Pomacea sp. and Anentome sp., to facilitate predictions of their potential geographic range should they become widely established.Methods: Laboratory tests were conducted to assess behavioural responses of snails to altered temperature or salinity after different acclimation regimes.Key results: After acclimation at 25°C, Pomacea sp. had a median activity range of 13.5–38°C and Anentome sp. of 12–38.5°C. Higher acclimation temperatures produced observable effects, whereas lower acclimation temperatures did not. Salinity tolerances differed, with Pomacea sp. remaining active at up to 8 parts per thousand (ppt) (after acclimation at 25°C), with acclimation at 20°C resulting in a lower salinity tolerance. By contrast, Anentome sp. snails were active at up to 5 ppt after low salinity acclimation, demonstrating enhanced salinity tolerance compared with non-salinity acclimations.Conclusions: These results showed that both snails are capable of surviving temperatures and salinities that would allow invasion into subtropical and warm-temperate Australian aquatic systems.Implications: Free from the constraints of natural predators, competitors, and parasites, these snails should be of great concern to biosecurity agencies in Australia

Simulation of actively controlled spacecraft with flexible appendages

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76688/1/AIAA-25388-716.pd

Deletion Study of DNA Topoisomerase IB from Leishmania donovani: Searching for a Minimal Functional Heterodimer

The substantial differences between trypanosomal and leishmanial DNA topoisomerase IB concerning to their homologues in mammals have provided a new lead in the study of the structural determinants that can be effectively targeted. Leishmania donovani, the causative agent of visceral leishmaniasis, contains an unusual heterodimeric DNA topoisomerase IB. The catalytically active enzyme consists of a large subunit (LdTopIL), which contains the non-conserved N-terminal end and the phylogenetically conserved “core” domain, and of a small subunit (LdTopIS) which harbors the C-terminal region with the characteristic tyrosine residue in the active site. Heterologous co-expression of LdTopIL and LdTopIS genes in a topoisomerase I deficient yeast strain, reconstitutes a fully functional enzyme LdTopIL/S which can be used for structural studies. An approach by combinatorial cloning of deleted genes encoding for truncated versions of both subunits was used in order to find out structural insights involved in enzyme activity or protein-protein interaction. The role played by the non-conserved N-terminal extension of LdTopIL in both relaxation activity and CPT sensitivity has been examined co-expressing the full-length LdTopIS and a fully active LdTopIΔS deletion with several deletions of LdTopIL lacking growing sequences of the N-terminal end. The sequential deletion study shows that the first 26 amino acids placed at the N-terminal end and a variable region comprised between Ala548 to end of the C-terminal extension of LdTopIL were enzymatically dispensable. Altogether this combinatorial approach provides important structural insights of the regions involved in relaxation activity and for understanding the atypical structure of this heterodimeric enzyme

Anaesthesia of three young grey seals (Halichoerus grypus) for fracture repair

Three young grey seals (Halichoerus grypus) were presented separately for fracture repair to the veterinary teaching hospital of University College Dublin. The seals were premedicated with a combination of pethidine, midazolam and atropine; anaesthesia was induced with propofol via the front flipper vein and maintained with sevoflurane or isoflurane in oxygen. One of the seals did not breathe spontaneously after anaesthesia; a cardiac arrest, resulting in death, occurred after several hours of mechanical ventilation. Post-mortem examination revealed a severe lungworm infestation and parasitic pneumonia in this animal. The two other seals recovered uneventfully from anaesthesia

A novel form of constitutively active farnesylated Akt1 prevents mammary epithelial cells from anoikis and suppresses chemotherapy-induced apoptosis

Protein kinase B/Akt has been described as a central mediator of anti-apoptotic signals transduced by the PI3 kinase. Although the role of Akt in the suppression of apoptosis is well elucidated, a potential function of Akt in tumorigenesis and chemoresistance is less intensively documented. In this study, we describe the construction of a novel form of constitutively active Akt1, which relies on the deletion of its pleckstrin homology domain and the insertion of a C-terminal farnesylation sequence. Stable cell lines were generated with MCF10A mammary epithelial cells and A549 human NSCLC cells expressing constitutively active Akt1. Enigneered MCF10A cells were rendered resistant towards apoptosis resulting from loss of cellular substrate attachment (anoikis). We investigated the chemosensitivity of A549 cells expressing farnesylated Akt vs control cells. A profoundly decreased sensitivity towards Mitoxantrone and cisplatin was observed in cells expressing farnesylated Akt. No significant difference in sensitivity however was observed upon treatment with cell cycle specific chemotherapeutic agents like paclitaxel. Our data suggest, that Akt is a central mediator in the suppression of anoikis and modulation of chemotherapy-induced apoptosis. Therefore it represents a promising target for small molecule inhibitors to shift the apoptotic threshold in cancer cells after treatment with standard chemotherapy

Identification of a Novel Topoisomerase Inhibitor Effective in Cells Overexpressing Drug Efflux Transporters

BACKGROUND:Natural product structures have high chemical diversity and are attractive as lead structures for discovery of new drugs. One of the disease areas where natural products are most frequently used as therapeutics is oncology. METHOD AND FINDINGS:A library of natural products (NCI Natural Product set) was screened for compounds that induce apoptosis of HCT116 colon carcinoma cells using an assay that measures an endogenous caspase-cleavage product. One of the apoptosis-inducing compounds identified in the screen was thaspine (taspine), an alkaloid from the South American tree Croton lechleri. The cortex of this tree is used for medicinal purposes by tribes in the Amazonas basin. Thaspine was found to induce conformational activation of the pro-apoptotic proteins Bak and Bax, mitochondrial cytochrome c release and mitochondrial membrane permeabilization in HCT116 cells. Analysis of the gene expression signature of thaspine-treated cells suggested that thaspine is a topoisomerase inhibitor. Inhibition of both topoisomerase I and II was observed using in vitro assays, and thaspine was found to have a reduced cytotoxic effect on a cell line with a mutated topoisomerase II enzyme. Interestingly, in contrast to the topoisomerase II inhibitors doxorubicin, etoposide and mitoxantrone, thaspine was cytotoxic to cell lines overexpressing the PgP or MRP drug efflux transporters. We finally show that thaspine induces wide-spread apoptosis in colon carcinoma multicellular spheroids and that apoptosis is induced in two xenograft mouse models in vivo. CONCLUSIONS:The alkaloid thaspine from the cortex of Croton lechleri is a dual topoisomerase inhibitor effective in cells overexpressing drug efflux transporters and induces wide-spread apoptosis in multicellular spheroids