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The monkey malaria parasite Plasmodium knowlesi also infect humans. There is a lack of information on the molecular mechanisms that take place between this simian parasite and its heterologous human host erythrocytes leading to this zoonotic disease. Therefore, we investigated here the binding ability of P. knowlesi tryptophan-rich antigens (PkTRAgs) to the human erythrocytes and sharing of the erythrocyte receptors between them as well as with other commonly occurring human malaria parasites.Six PkTRAgs were cloned and expressed in E.coli as well as in mammalian CHO-K1 cell to determine their human erythrocyte binding activity by cell-ELISA, and in-vitro rosetting assay, respectively.Three of six PkTRAgs (PkTRAg38.3, PkTRAg40.1, and PkTRAg67.1) showed binding to human erythrocytes. Two of them (PkTRAg40.1 and PkTRAg38.3) showed cross-competition with each other as well as with the previously described P.vivax tryptophan-rich antigens (PvTRAgs) for human erythrocyte receptors. However, the third protein (PkTRAg67.1) utilized the additional but different human erythrocyte receptor(s) as it did not cross-compete for erythrocyte binding with either of these two PkTRAgs as well as with any of the PvTRAgs. These three PkTRAgs also inhibited the P.falciparum parasite growth in in-vitro culture, further indicating the sharing of human erythrocyte receptors by these parasite species and the biological significance of this receptor-ligand interaction between heterologous host and simian parasite.Recognition and sharing of human erythrocyte receptor(s) by PkTRAgs with human parasite ligands could be part of the strategy adopted by the monkey malaria parasite to establish inside the heterologous human host.

Tryptophan-rich proteins from several malarial parasites have been identified where they play an important role in host-parasite interaction. Structural characterization of these proteins is needed to develop them as therapeutic targets. Here, we describe a novel Plasmodium vivax tryptophan-rich protein named PvTRAg33.5. It is expressed by blood stage(s) of the parasite and its gene contains two exons. The exon 1 encodes for a 23 amino acids long putative signal peptide which is likely to be cleaved off whereas the exon 2 encodes for the mature protein of 252 amino acids. The mature protein contains B-cell epitopes which were recognized by the human immune system during P.vivax infection. The PvTRAg33.5 contains 24 (9.5%) tryptophan residues and six motifs whose patterns were similar among tryptophan-rich proteins. The modeled structure of the PvTRAg33.5 consists of a multidomain architecture which is stabilized by the presence of large number of tryptophan residues. The recombinant PvTRAg33.5 showed predominantly α helical structure and alpha helix to beta sheet transition at pH below 4.5. Protein acquires an irreversible non-native state at temperature more than 50°C at neutral pH. Its secondary and tertiary structures remain stable in the presence of 35% alcohol but these structures are destabilized at higher alcohol concentrations due to the disturbance of hydrophobic interactions between tryptophanyl residues. These structural changes in the protein might occur during its translocation to interact with other proteins at its final destination for biological function such as erythrocyte invasion.

In this paper, we report a successful realization and integration of a gold two-dimensional hole array (2DHA) structure with semiconductor InAs quantum dot (QD). We show experimentally that a properly designed 2DHA-QD photodetector can facilitate a strong plasmonic−QD interaction, leading to a 130% absolute enhancement of infrared photoresponse at the plasmonic resonance. Our study indicates two key mechanisms for the performance improvement. One is an optimized 2DHA design that permits an efficient coupling of light from the far-field to a localized plasmonic mode. The other is the close spatial matching of the QD layers to the wave function extent of the plasmonic mode. Furthermore, the processing of our 2DHA is amenable to large scale fabrication and, more importantly, does not degrade the noise current characteristics of the photodetector. We believe that this demonstration would bring the performance of QD-based infrared detectors to a level suitable for emerging surveillance and medical diagnostic applications. [ABSTRACT FROM AUTHOR]

The nonmevalonate pathway of isoprenoid biosynthesis in the apicoplast of the human malaria parasite Plasmodium falciparumis distinct from the mevalonate-dependent pathway of humans and thus a good drug target. We describe here the hammerhead ribozyme based cleavage of the ispH(lytB) gene transcript involved in the last step of this nonmevalonate pathway. Using RNA folding program, three hammerhead ribozymes named as RZ876, RZ1260, and RZ1331were predicted against ispH(lytB) mRNA. Messenger walk screening (RNaseH) assay confirmed the target accessibility for these ribozymes. All three ribozymes cleaved the target RNA in vitrobut RZ876exhibited the highest catalytic potential (62.92). Therefore, RZ876was chemically synthesized with appropriate chemical modifications to protect it from nuclease attack while using it for in vitroparasite growth inhibition assay. This ribozyme RZ876was able to inhibit 87.36 parasite growth at 30 μM concentration compared to the untreated culture. However, an absolute inhibition of 29.41 was achieved compared to the control ribozyme (RZctrl). Nonetheless, the growth inhibition effect was found to be sequence-specific as indicated by the decreased level of ispH(lytB) transcript after ribozyme treatment. In conclusion, we have identified the ispH(lytB) as a potential target whose transcript can be cleaved by a ribozyme RZ876. [ABSTRACT FROM AUTHOR]