Tripeptides as selective inhibitors of src-SH2 phosphoprotein interactions

Summary This paper describes the synthesis of phosphorylated peptides of the general structural Ac-Tyr(PO₃H₂)-Glu-Xaa_NH₂, where Xaa represents a hydrophobic -amino acid of d-configuration. These peptides displayed activities in the micromolar range in inhibiting src-SH2 domain/epidermal growth factor receptor interactions.     

Bridging the Gap Between Salmon Spawner Abundance and Marine Nutrient Assimilation by Juvenile Salmon: Seasonal Cycles and Landscape Effects at the Watershed Scale

Ecosystems - Anadromous Pacific salmon are semelparous, and resource subsidies from spawning adults (marine-derived nutrients, or MDN) benefit juvenile salmonids rearing in freshwater. However, it...     

Amino Acid Transporters and Exchangers from the SLC1A Family: Structure,Mechanism and Roles in Physiology and Cancer

The Solute Carrier 1A (SLC1A) family includes two major mammalian transport systems—the alanine serine cysteine transporters (ASCT1-2) and the human glutamate transporters otherwise known as the excitatory amino acid transporters (EAAT1-5). The EAATs play a critical role in maintaining low synaptic concentrations of the major excitatory neurotransmitter glutamate, and hence they have been widely researched over a number of years. More recently, the neutral amino acid exchanger, ASCT2 has garnered attention for its important role in cancer biology and potential as a molecular target for cancer therapy. The nature of this role is still being explored, and several classes of ASCT2 inhibitors have been developed. However none have reached sufficient potency or selectivity for clinical use. Despite their distinct functions in biology, the members of the SLC1A family display structural and functional similarity. Since 2004, available structures of the archaeal homologues Glt_Ph and Glt_Tk have elucidated mechanisms of transport and inhibition common to the family. The recent determination of EAAT1 and ASCT2 structures may be of assistance in future efforts to design efficacious ASCT2 inhibitors. This review will focus on ASCT2, the present state of knowledge on its roles in tumour biology, and how structural biology is being used to progress the development of inhibitors.

     

Future Scenarios as a Research Tool: Investigating Climate Change Impacts, Adaptation Options and Outcomes for the Great Barrier Reef, Australia

Climate change is a significant future driver of change in coastal social-ecological systems. Our knowledge of impacts, adaptation options, and possible outcomes for marine environments and coastal industries is expanding, but remains limited and uncertain. Alternative scenarios are a way to explore potential futures under a range of conditions. We developed four alternative future scenarios for the Great Barrier Reef and its fishing and tourism industries positing moderate and more extreme (2–3 °C above pre-industrial temperatures) warming for 2050 and contrasting ‘limited’ and ‘ideal’ ecological and social adaptation. We presented these scenarios to representatives of key stakeholder groups to assess the perceived viability of different social adaptation options to deliver desirable outcomes under varied contexts.     

Generation and characterization of neuregulin-2-deficient mice

The neuregulins (NRGs) are a family of four structurally related growth factors that are expressed in the developing and adult brain. NRG-1 is essential for normal heart formation and has been implicated in the development and maintenance of both neurons and glia. NRG-2 was identified on the basis of its homology to NRG-1 and, like NRG-1, is expressed predominantly by neurons in the central nervous system. We have generated mice with the active domain of NRG-2 deleted in an effort to characterize the biological function of NRG-2 in vivo. In contrast to the NRG-1 knockout animals, NRG-2 knockouts have no apparent heart defects and survive embryogenesis. Mutant mice display early growth retardation and reduced reproductive capacity. No obvious histological differences were observed in the major sites of NRG-2 expression. Our results indicate that in vivo NRG-2 activity differs substantially from that of NRG-1 and that it is not essential for normal development in utero.     

Silicones containing pendant biocides for antifouling coatings

The preparation of biocide-incorporated silicone coatings for antifouling/fouling release applications is described. The biocide Triclosan (5-chloro-2-(2, 4-dichlorophenoxy) phenol) was modified with alkenyl moieties and incorporated into a silicone backbone through covalent bonds. The presence of the biocide on the coating surface was expected to deter fouling organisms from attaching to the surface of the coating. Allyl glycidyl ether was used to provide crosslink functionalities. Resins were cured using vinyl-terminated polydimethylsiloxane for hydrosilyl functionality and 1, 3-cyclohexane-bis (methylamine) for epoxy crosslinking functionality. Coatings were characterized by static water contact angle measurements and dynamic mechanical thermal analysis. Synthetic control over the incorporation of crosslink functionalities within the polymer resin allowed tuning of the surface of the coating and of mechanical properties. Resistance to macrofouling was tested by static immersion tests in the Indian River Lagoon at the Florida Institute of Technology from 15 October 2003 to 13 November 2003. Preliminary results showed that the coatings prepared from biocide-incorporated silicones with the appropriate bulk modulus significantly reduced macrofouling.