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

<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

Energetic eruptions leading to a peculiar hydrogen-rich explosion of a massive star

Every supernova so far observed has been considered to be the terminal explosion of a star. Moreover, all supernovae with absorption lines in their spectra show those lines decreasing in velocity over time, as the ejecta expand and thin, revealing slower-moving material that was previously hidden. In addition, every supernova that exhibits the absorption lines of hydrogen has one main light-curve peak, or a plateau in luminosity, lasting approximately 100 days before declining1. Here we report observations of iPTF14hls, an event that has spectra identical to a hydrogen-rich core-collapse supernova, but characteristics that differ extensively from those of known supernovae. The light curve has at least five peaks and remains bright for more than 600 days; the absorption lines show little to no decrease in velocity; and the radius of the line-forming region is more than an order of magnitude bigger than the radius of the photosphere derived from the continuum emission. These characteristics are consistent with a shell of several tens of solar masses ejected by the progenitor star at supernova-level energies a few hundred days before a terminal explosion. Another possible eruption was recorded at the same position in 1954. Multiple energetic pre-supernova eruptions are expected to occur in stars of 95 to 130 solar masses, which experience the pulsational pair instability2,3,4,5. That model, however, does not account for the continued presence of hydrogen, or the energetics observed here. Another mechanism for the violent ejection of mass in massive stars may be required

Características do óleo essencial de capim-citronela em função de espaçamento, altura e época de corte Essential oil characteristics from citronella grass depending on planting space, cutting height and harvesting time

A importância do capim-citronela (Cymbopogon winterianum Jowitt.) tem crescido nos últimos anos no mercado de produtos naturais, devido à grande procura pelo seu óleo essencial. Neste trabalho, objetivou-se avaliar a influência do espaçamento (50 x 50; 50 x 80 e 80 x 80 cm), altura (15 e 30 cm do solo) e época de corte (quatro, seis e oito meses após o plantio) na produção e qualidade do óleo essencial de capim-citronela. Desenvolveu-se um ensaio na Fazenda Experimental Vale do Curu (FEVC), pertencente ao Centro de Ciências Agrárias, da Universidade Federal do Ceará, em Pentecoste - CE, no período de setembro de 2002 a setembro de 2003. Os tratamentos foram arranjados como fatorial 3 x 3 x 2, dispostos em blocos casualizados, com três repetições. Plantas colhidas quatro meses após o plantio apresentaram significativamente maior produção de óleo essencial se cortadas a 30 cm de altura. Já plantas colhidas seis meses após o plantio apresentaram maior produção de óleo essencial se cortadas a 15 cm de altura. Para plantas colhidas oito meses após o plantio, a altura de corte não interferiu na produção de óleo essencial. Para espaçamentos mais largos (80 x 80 cm), a produção de óleo essencial foi significativamente mais alta para plantas cortadas a 15 cm, acontecendo o inverso no espaçamento menor (50 x 50 cm). Quando foram avaliados os constituintes citronelol + citronelal observou-se que seus teores foram significativamente mais elevados em plantas cultivadas no espaçamento intermediário, colhidas após os seis meses e a 30 cm de altura. Já o teor de geraniol foi superior em plantas colhidas quatro meses após o plantio, porém não houve influência do espaçamento e altura de corte sobre o seu teor.<br>Citronella grass (Cymbopogon winterianum Jowitt.) has grown in importance due to an increasing demand of the essential oil. The influence of spacing (50 x 50; 50 x 80 e 80 x 80 cm), cutting height (15 and 30 cm above ground) and harvesting season (four, six and eight months after planting) on productivity and essential oil quality was evaluated. The study. occurred in field, in Pentecoste, Ceará State, Brazil, from September 2002 to September 2003. The treatments were organized in a factorial 3 x 3 x 2 scheme, in randomized block design, with three replicates. Cutting plants four months after planting date resulted in significantly higher essential oil production when cut at 30 cm height. Six months after planting date, higher yield was obtained at 15 cm height. The cutting height did not influence essential oil production when plants were harvested after eight months. Using larger plant spacing (80 x 80 cm) resulted in significantly higher essential oil production when plants were cut at 15 cm, divergent to the result observed with minor spacing (50 x 50 cm). The citronellol + citronellal content was significantly higher in plants cultivated at intermediate spacing and cut after six months at a height of 30 cm. The geraniol content, however, was higher in plants harvested after four months, with no influence of spacing or cutting height