65 research outputs found

    Climate emergencies do not justify engineering the climate

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    Current climate engineering proposals do not come close to addressing the complex and contested nature of conceivable ‘climate emergencies’ resulting from unabated greenhouse gas emissions

    The kinetics of antibody binding to Plasmodium falciparum VAR2CSA PfEMP1 antigen and modelling of PfEMP1 antigen packing on the membrane knobs

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    <p>Abstract</p> <p>Background</p> <p>Infected humans make protective antibody responses to the PfEMP1 adhesion antigens exported by <it>Plasmodium falciparum </it>parasites to the erythrocyte membrane, but little is known about the kinetics of this antibody-receptor binding reaction or how the topology of PfEMP1 on the parasitized erythrocyte membrane influences antibody association with, and dissociation from, its antigenic target.</p> <p>Methods</p> <p>A Quartz Crystal Microbalance biosensor was used to measure the association and dissociation kinetics of VAR2CSA PfEMP1 binding to human monoclonal antibodies. Immuno-fluorescence microscopy was used to visualize antibody-mediated adhesion between the surfaces of live infected erythrocytes and atomic force microscopy was used to obtain higher resolution images of the membrane knobs on the infected erythrocyte to estimate knob surface areas and model VAR2CSA packing density on the knob.</p> <p>Results</p> <p>Kinetic analysis indicates that antibody dissociation from the VAR2CSA PfEMP1 antigen is extremely slow when there is a high avidity interaction. High avidity binding to PfEMP1 antigens on the surface of <it>P. falciparum</it>-infected erythrocytes in turn requires bivalent cross-linking of epitopes positioned within the distance that can be bridged by antibody. Calculations of the surface area of the knobs and the possible densities of PfEMP1 packing on the knobs indicate that high-avidity cross-linking antibody reactions are constrained by the architecture of the knobs and the large size of PfEMP1 molecules.</p> <p>Conclusions</p> <p>High avidity is required to achieve the strongest binding to VAR2CSA PfEMP1, but the structures that display PfEMP1 also tend to inhibit cross-linking between PfEMP1 antigens, by holding many binding epitopes at distances beyond the 15-18 nm sweep radius of an antibody. The large size of PfEMP1 will also constrain intra-knob cross-linking interactions. This analysis indicates that effective vaccines targeting the parasite's vulnerable adhesion receptors should primarily induce strongly adhering, high avidity antibodies whose association rate constant is less important than their dissociation rate constant.</p

    A scientific critique of the two-degree climate change target

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    The world's governments agreed to limit global mean temperature change to below 2-derees C compared with pr-industrial levels in the years following the 2009 climate conference in Copenhagen. This 2-degrees C warming target is perceived by the pulic as a universally accepted goal, identified by scientists as a safe limit that avoids dangerous climate change. This perception is incorrect: no scientific assessment has clearly justified or defended the 2-degrees C target as a safe level of warming, and indeed, this is not a problem that science alone can address. We argue that global temperature is the best climate target quantity, but it is unclear what level can be consiered safe. The 2-degrees C target is useful for anchoring discussions, but has been ineffective in triggering the required emission reductions; debates on considering a lower target are strongly at odds with the current real-world level of action. These debates are moot, however, as the decisions that need to be taken now to limit warming to 1.5 or 2 degrees C are very similar. We need to agree how to start, not where to end mitigation

    Cell division: control of the chromosomal passenger complex in time and space

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