Responses of marine benthic microalgae to elevated CO<inf>2</inf>

Increasing anthropogenic CO2 emissions to the atmosphere are causing a rise in pCO2 concentrations in the ocean surface and lowering pH. To predict the effects of these changes, we need to improve our understanding of the responses of marine primary producers since these drive biogeochemical cycles and profoundly affect the structure and function of benthic habitats. The effects of increasing CO2 levels on the colonisation of artificial substrata by microalgal assemblages (periphyton) were examined across a CO2 gradient off the volcanic island of Vulcano (NE Sicily). We show that periphyton communities altered significantly as CO2 concentrations increased. CO2 enrichment caused significant increases in chlorophyll a concentrations and in diatom abundance although we did not detect any changes in cyanobacteria. SEM analysis revealed major shifts in diatom assemblage composition as CO2 levels increased. The responses of benthic microalgae to rising anthropogenic CO2 emissions are likely to have significant ecological ramifications for coastal systems. © 2011 Springer-Verlag

Discovery of High-Affinity Protein Binding Ligands – Backwards

BACKGROUND: There is a pressing need for high-affinity protein binding ligands for all proteins in the human and other proteomes. Numerous groups are working to develop protein binding ligands but most approaches develop ligands using the same strategy in which a large library of structured ligands is screened against a protein target to identify a high-affinity ligand for the target. While this methodology generates high-affinity ligands for the target, it is generally an iterative process that can be difficult to adapt for the generation of ligands for large numbers of proteins. METHODOLOGY/PRINCIPAL FINDINGS: We have developed a class of peptide-based protein ligands, called synbodies, which allow this process to be run backwards--i.e. make a synbody and then screen it against a library of proteins to discover the target. By screening a synbody against an array of 8,000 human proteins, we can identify which protein in the library binds the synbody with high affinity. We used this method to develop a high-affinity synbody that specifically binds AKT1 with a K(d)<5 nM. It was found that the peptides that compose the synbody bind AKT1 with low micromolar affinity, implying that the affinity and specificity is a product of the bivalent interaction of the synbody with AKT1. We developed a synbody for another protein, ABL1 using the same method. CONCLUSIONS/SIGNIFICANCE: This method delivered a high-affinity ligand for a target protein in a single discovery step. This is in contrast to other techniques that require subsequent rounds of mutational improvement to yield nanomolar ligands. As this technique is easily scalable, we believe that it could be possible to develop ligands to all the proteins in any proteome using this approach

The role of P2 receptors in controlling infections by intracellular pathogens

A growing number of studies have demonstrated the importance of ATPe-signalling via P2 receptors as an important component of the inflammatory response to infection. More recent studies have shown that ATPe can also have a direct effect on infection by intracellular pathogens, by modulating membrane trafficking in cells that contain vacuoles that harbour intracellular pathogens, such as mycobacteria and chlamydiae. A conserved mechanism appears to be involved in controlling infection by both of these pathogens, as a role for phospholipase D in inducing fusion between lysosomes and the vacuoles has been demonstrated. Other P2-dependent mechanisms are most likely operative in the cases of pathogens, such as Leishmania, which survive in an acidic phagolysosomal-like compartment. ATPe may function as a ‘danger signal–that alerts the immune system to the presence of intracellular pathogens that damage the host cell, while different intracellular pathogens have evolved enzymes or other mechanisms to inhibit ATPe-mediated signalling, which should, thus, be viewed as virulence factors for these pathogens

Role of IKK/NF-κB Signaling in Extinction of Conditioned Place Aversion Memory in Rats

The inhibitor κB protein kinase/nuclear factor κB (IKK/NF-κB) signaling pathway is critical for synaptic plasticity. However, the role of IKK/NF-κB in drug withdrawal-associated conditioned place aversion (CPA) memory is unknown. Here, we showed that inhibition of IKK/NF-κB by sulphasalazine (SSZ; 10 mM, i.c.v.) selectively blocked the extinction but not acquisition or expression of morphine-induced CPA in rats. The blockade of CPA extinction induced by SSZ was abolished by sodium butyrate, an inhibitor of histone deacetylase. Thus, the IKK/NF-κB signaling pathway might play a critical role in the extinction of morphine-induced CPA in rats and might be a potential pharmacotherapy target for opiate addiction

Neighbourhood built environment associations with body size in adults:mediating effects of activity and sedentariness in a cross-sectional study of New Zealand adults

Background: The aim of this study was to determine the associations between body size and built environment walkability variables, as well as the mediating role of physical activity and sedentary behaviours with body size. Methods: Objective environment, body size (body mass index (BMI), waist circumference (WC)), and sedentary time and physical activity data were collected from a random selection of 2033 adults aged 20-65 years living in 48 neighbourhoods across four New Zealand cities. Multilevel regression models were calculated for each comparison between body size outcome and built environment exposure. Results and Discussion: Street connectivity and neighborhood destination accessibility were significant predictors of body size (1 SDchange predicted a 1.27 to 1.41 % reduction in BMI and a 1.76 to 2.29 % reduction in WC). Significantrelationships were also observed for streetscape (1 SD change predicted a 1.33 % reduction in BMI) anddwelling density (1 SD change predicted a 1.97 % reduction in BMI). Mediation analyses revealed asignificant mediating effect of physical activity on the relationships between body size and street connectivity and neighbourhood destination accessibility (explaining between 10.4 and 14.6 % of the total effect). No significant mediating effect of sedentary behaviour was found. Findings from this cross-sectional study of a random selection of New Zealand adults are consistent with international research. Findings are limited to individual environment features only; conclusions cannot be drawn about the cumulative and combined effect of individual features on outcomes. Conclusions: Built environment features were associated with body size in the expected directions. Objectively-assessed physical activity mediated observed built environment-body size relationships