Examining the Drinking Motives Questionnaire-Revised Short Form among university students in Australia, New Zealand and Argentina

CAUL read and publish agreement 2023fals

The Role of Agriculture in the UN Climate Talks

Agriculture, and consequently food security and livelihoods, is already being affected by climate change, according to latest science from the IPCC. The various strands of work already underway on agriculture within the UNFCCC process can be strengthened and made more coherent. A 2015 climate agreement should reference food production and provide the financial, technical and capacity building support for countries to devise ambitious actions for the agricultural sector. A new climate agreement should be consistent with the Sustainable Development Goal (SDG) proces

Progress on agriculture in the UN climate talks: How COP21 can ensure a food-secure future

Agriculture, and consequently food security and livelihoods, is already being affected by climate change, according to latest science from the IPCC (Porter et al. 2014). The IPCC agrees that the world needs to produce at least 50% more food than we do today in order to meet the goal of feeding a projected 9 billion people by 2050. This must be achieved in the face of climatic variability and change, growing constraints on water and land for crops and livestock, and declining wild capture fishery stocks. Although the protection of food security lies within the core objective of the United Nations Framework Convention on Climate Change (UNFCCC) (Article 2), formal arrangements for addressing agriculture within COP21 are unlikely. CGIAR would welcome the strengthening of aspirations for food security through action on mitigation and adaptation within a new agreement. We recognise that the new climate agreement is unlikely to be prescriptive about how adaptation in agriculture is supported and how agriculture might contribute to emission cuts. These issues are addressed within countries’ INDCs and determined at national level

Specific Binding and Mineralization of Calcified Surfaces by Small Peptides

Several small (<25aa) peptides have been designed based on the sequence of the dentin phosphoprotein, one of the major noncollagenous proteins thought to be involved in the mineralization of the dentin extracellular matrix during tooth development. These peptides, consisting of multiple repeats of the tripeptide aspartate-serine-serine (DSS), bind with high affinity to calcium phosphate compounds and, when immobilized, can recruit calcium phosphate to peptide-derivatized polystyrene beads or to demineralized human dentin surfaces. The affinity of binding to hydroxyapatite surfaces increases with the number of (DSS)n repeats, and though similar repeated sequences—(NTT)n, (DTT)n, (ETT)n, (NSS)n, (ESS)n, (DAA)n, (ASS)n, and (NAA)n—also showed HA binding activity, it was generally not at the same level as the natural sequence. Binding of the (DSS)n peptides to sectioned human teeth was shown to be tissue-specific, with high levels of binding to the mantle dentin, lower levels of binding to the circumpulpal dentin, and little or no binding to healthy enamel. Phosphorylation of the serines of these peptides was found to affect the avidity, but not the affinity, of binding. The potential utility of these peptides in the detection of carious lesions, the delivery of therapeutic compounds to mineralized tissues, and the modulation of remineralization is discussed

Structural basis of TIR-domain-assembly formation in MAL- and MyD88-dependent TLR4 signaling

Toll-like receptor (TLR) signaling is a key innate immunity response to pathogens. Recruitment of signaling adapters such as MAL (TIRAP) and MyD88 to the TLRs requires Toll/interleukin-1 receptor (TIR)-domain interactions, which remain structurally elusive. Here we show that MAL TIR domains spontaneously and reversibly form filaments in vitro. They also form cofilaments with TLR4 TIR domains and induce formation of MyD88 assemblies. A 7-Å-resolution cryo-EM structure reveals a stable MAL protofilament consisting of two parallel strands of TIR-domain subunits in a BB-loop-mediated head-to-tail arrangement. Interface residues that are important for the interaction are conserved among different TIR domains. Although large filaments of TLR4, MAL or MyD88 are unlikely to form during cellular signaling, structure-guided mutagenesis, combined with in vivo interaction assays, demonstrated that the MAL interactions defined within the filament represent a template for a conserved mode of TIR-domain interaction involved in both TLR and interleukin-1 receptor signaling

Characterisation of lipid-protein interactions through computational modelling

Parallel advances in lipidomics and the structural biology of membrane proteins over the past decade have revealed the highly diverse and complex nature of cell membrane composition. These compositional complexities influence the behaviour of embedded proteins, and a number of biomedically important membrane proteins are now known to be modulated via interactions with their lipid environment. This project aims to apply an array of computational tools to probe and characterize the molecular level detail of these interactions, and obtain information to complement experimental studies. In particular the interactions of modulatory lipid species with the transmembrane domain of the epidermal growth factor (EGF) receptor were addressed using coarse-grained potential of mean force (PMF) calculations. The results suggest this approach, widely applied in other areas of computational biology, may be successfully adapted to probe the strength and selectivity of lipid-protein interactions, and the effects of protein mutation. Subsequently these calculations were applied in tandem with equilibrium simulations to explore cardiolipin interactions with a key mitochondrial transporter, the ADP/ATP Translocase. The data show the coarse-grained model employed is capable of accurately identifying three specific cardiolipin binding sites on the protein, in agreement with prior crystallographic and NMR data. These sites were shown to be specific to cardiolipin, rather than general phospholipid interaction sites. In the third project, prospective predictions were made as to the location of PIP2 lipid binding sites on the membrane-exposed surface of a class A GPCR, the Neurotensin Receptor 1 (NTS1). A protein known to specifically bind these lipids from native mass spectrometry (MS) measurements at hitherto unknown regions. The results suggest PIP2 binds to defined loop regions on the intracellular portion of the protein. Finally, atomistic simulations are applied to examine the effect of a crystallographically resolved cholesterol molecule on the dynamics of a class F GPCR, Smoothened. The data suggest a marked influence of bound cholesterol on intra-domain dynamics of the extracellular region of Smoothened