604 research outputs found

    Reticulocyte binding protein homologues are key adhesins during erythrocyte invasion by Plasmodium falciparum

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    The Apicomplexan parasite responsible for the most virulent form of malaria, Plasmodium falciparum, invades human erythrocytes through multiple ligand–receptor interactions. The P. falciparum reticulocyte-binding protein homologue (PfRh or PfRBL) family have been implicated in the invasion process but their exact role is unknown. PfRh1 and PfRh4, members of this protein family, bind to red blood cells and function in merozoite invasion during which they undergo a series of proteolytic cleavage events before and during entry into the host cell. The ectodomain of PfRh1 and PfRh4 are processed to produce fragments consistent with cleavage in the transmembrane domain and released into the supernatant, at about the time of invasion, in a manner consistent with rhomboid protease cleavage. Processing of both PfRh1 and PfRh4, and by extrapolation all membrane-bound members of this protein family, is important for function and release of these proteins on the merozoite surface and they along with EBA-175 are important components of the tight junction, the transient structure that links the erythrocyte via receptor–ligand interactions to the actin–myosin motor in the invading merozoite

    Assessing Visual Attention Using Eye Tracking Sensors in Intelligent Cognitive Therapies Based on Serious Games

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    This study examines the use of eye tracking sensors as a means to identify children's behavior in attention-enhancement therapies. For this purpose, a set of data collected from 32 children with different attention skills is analyzed during their interaction with a set of puzzle games. The authors of this study hypothesize that participants with better performance may have quantifiably different eye-movement patterns from users with poorer results. The use of eye trackers outside the research community may help to extend their potential with available intelligent therapies, bringing state-of-the-art technologies to users. The use of gaze data constitutes a new information source in intelligent therapies that may help to build new approaches that are fully-customized to final users' needs. This may be achieved by implementing machine learning algorithms for classification. The initial study of the dataset has proven a 0.88 (Β±0.11) classification accuracy with a random forest classifier, using cross-validation and hierarchical tree-based feature selection. Further approaches need to be examined in order to establish more detailed attention behaviors and patterns among children with and without attention problems

    ENSO and the recent warming of the Indian Ocean

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    The recent Indian Ocean (IO) warming and its relation with the El NiΓ±o Southern Oscillation (ENSO) is investigated using available ocean and atmospheric reanalyses. By comparing the events before and after 1976 (identified as a threshold separating earlier and recent decades with respect to global warming trends), our results indicate that the IO had experienced a distinct change in the warming pattern. After 1976, during the boreal summer season the cold anomalies in the IO were replaced by warm anomalies in both warm (El NiΓ±o) and cold (La NiΓ±a) ENSO events. Strong sinking by upper level winds and the associated anomalous equatorial easterly winds created favourable conditions for the IO warming from 90Β°E towards the western IO. Our study highlights that after 1976, atmospheric and oceanic fields changed mostly during La NiΓ±a, with both ENSO phases contributing to the warming of the IO. Warm anomalies of 0.2 °C are seen over large areas of the IO in the post-1976 La NiΓ±a composites. Our analysis suggests that the IO warming during La NiΓ±a events after 1976 may have a relation to the warm anomalies persisting from the preceding strong El NiΓ±o events

    Plasmodium falciparum Reticulocyte Binding-Like Homologue Protein 2 (PfRH2) Is a Key Adhesive Molecule Involved in Erythrocyte Invasion

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    Erythrocyte invasion by Plasmodium merozoites is a complex, multistep process that is mediated by a number of parasite ligand-erythrocyte receptor interactions. One such family of parasite ligands includes the P. falciparum reticulocyte binding homologue (PfRH) proteins that are homologous with the P. vivax reticulocyte binding proteins and have been shown to play a role in erythrocyte invasion. There are five functional PfRH proteins of which only PfRH2a/2b have not yet been demonstrated to bind erythrocytes. In this study, we demonstrated that native PfRH2a/2b is processed near the N-terminus yielding fragments of 220 kDa and 80 kDa that exhibit differential erythrocyte binding specificities. The erythrocyte binding specificity of the 220 kDa processed fragment of native PfRH2a/2b was sialic acid-independent, trypsin resistant and chymotrypsin sensitive. This specific binding phenotype is consistent with previous studies that disrupted the PfRH2a/2b genes and demonstrated that PfRH2b is involved in a sialic acid independent, trypsin resistant, chymotrypsin sensitive invasion pathway. Interestingly, we found that the smaller 80 kDa PfRH2a/2b fragment is processed from the larger 220 kDa fragment and binds erythrocytes in a sialic acid dependent, trypsin resistant and chymotrypsin sensitive manner. Thus, the two processed fragments of PfRH2a/2b differed with respect to their dependence on sialic acids for erythrocyte binding. Further, we mapped the erythrocyte binding domain of PfRH2a/2b to a conserved 40 kDa N-terminal region (rPfRH240) in the ectodomain that is common to both PfRH2a and PfRH2b. We demonstrated that recombinant rPfRH240 bound human erythrocytes with the same specificity as the native 220 kDa processed protein. Moreover, antibodies generated against rPfRH240 blocked erythrocyte invasion by P. falciparum through a sialic acid independent pathway. PfRH2a/2b thus plays a key role in erythrocyte invasion and its conserved receptor-binding domain deserves attention as a promising candidate for inclusion in a blood-stage malaria vaccine

    Are happy drivers safer drivers? Evidence from hazard response times and eye tracking data

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    Previous research shows that negative emotions have a detrimental effect on cognitive processes in general and on driving safety in particular. However to date, there has been no empirical investigation of the impact that positive emotions might have on driving safety. This research examined the influence of mood on driving safety using hazard perception videos and an eye tracker. Participants’ mood was manipulated (Sad, Neutral, Happy) after which they observed videos containing a number of potential hazards. Hazard response times and eye fixations were measured. The Sad mood affected drivers the most, with the longest response times and fixation durations. The effects of the Happy mood were less clear, suggesting that apart from emotional valence, emotional arousal should be considered. In addition, hazard response times differed as a function of hazard onset (i.e. unexpected or developing hazard) and type of hazard (i.e. human, car). The results are interpreted in terms of theories of positive emotions and psychological arousal

    Plasmodium falciparum Merozoite Invasion Is Inhibited by Antibodies that Target the PfRh2a and b Binding Domains

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    Plasmodium falciparum, the causative agent of the most severe form of malaria in humans invades erythrocytes using multiple ligand-receptor interactions. The P. falciparum reticulocyte binding-like homologue proteins (PfRh or PfRBL) are important for entry of the invasive merozoite form of the parasite into red blood cells. We have analysed two members of this protein family, PfRh2a and PfRh2b, and show they undergo a complex series of proteolytic cleavage events before and during merozoite invasion. We show that PfRh2a undergoes a cleavage event in the transmembrane region during invasion consistent with activity of the membrane associated PfROM4 protease that would result in release of the ectodomain into the supernatant. We also show that PfRh2a and PfRh2b bind to red blood cells and have defined the erythrocyte-binding domain to a 15 kDa region at the N-terminus of each protein. Antibodies to this receptor-binding region block merozoite invasion demonstrating the important function of this domain. This region of PfRh2a and PfRh2b has potential in a combination vaccine with other erythrocyte binding ligands for induction of antibodies that would block a broad range of invasion pathways for P. falciparum into human erythrocytes
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