Plasmodium cynomolgi: serum-mediated blocking and enhancement of infectivity to mosquitoes during infections in the natural host, Macaca sinica

The infectivity of Plasmodium cynomolgi in its natural host, the toque monkey, Macaca sinica, to Anopheles tessellatus mosquitoes was studied in relation to the evolution of anti-sexual-stage immunity in the host during the course of a blood-induced infection. The effects of serum on the infectivity of gametocytes and the intrinsic infectivity of gametocytes to mosquitoes on each day were assessed in membrane feeding experiments. Mosquitoes were also directly fed on the animal on each day. Our results demonstrate that during the very early patent period, before the peak of gametocytemia, the infection serum enhanced the infectivity of gametocytes up to two to three times above their infectivity in normal monkey serum. Subsequently, serum drawn post-peak of parasitemia ceased to enhance, and began to suppress, infectivity. After 2-3 months, long after parasitemias ceased patency, the serum no longer suppressed and between 3 and 4 months the serum again tended to enhance gamete infectivity before losing any significant effect. Serum infectivity enhancing effects were consistent with low indirect immunofluorescence test antibody titers against blood stage parasites first during the very early days of a blood infection before reaching blocking levels, and again during convalescence when antibodies were declining. The serum infectivity blocking effects on gametocytes were seen at the peak of antibody titers from about Days 9 to 23 of an infection. From 78 to 95% of the total infectivity of the parasite to mosquitoes during an infection occurred when infectivity enhancing activity was present in the serum. Hence, the infectivity of the parasite to mosquitoes was largely dependent on infectivity enhancing antibodies in host serum.     

The leukocidin pore: evidence for an octamer with four LukF subunits and four LukS subunits alternating around a central axis

The staphylococcal alpha-hemolysin (alphaHL) and leukocidin (Luk) polypeptides are members of a family of related beta-barrel pore-forming toxins. Upon binding to susceptible cells, alphaHL forms water-filled homoheptameric transmembrane pores. By contrast, Luk pores are formed by two classes of subunit, F and S, rendering a heptameric structure displeasing on symmetry grounds at least. Both the subunit stoichiometry and arrangement within the Luk pore have been contentious issues. Here we use chemical and genetic approaches to show that (1) the predominant, or perhaps the only, form of the Luk pore is an octamer; (2) the subunit stoichiometry is 1:1; and (3) the subunits are arranged in an alternating fashion about a central axis of symmetry, at least when a fused LukS-LukF construct is used. The experimental approaches we have used also open up new avenues for engineering the arrangement of the subunits of beta-barrel pore-forming toxins.     

True Molecular Scale Visualization of Variable Clustering Properties of Ryanodine Receptors

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Colletotrichum acutatum is the main cause of Colletotrichum leaf disease of rubber in Sri Lanka

Colletotrichum gloeosporoides has been described as the causal agent of Colletotrichum leaf disease of rubber in Sri Lanka and other parts of the world since 1905. A study carried out on vegetative and reproductive characteristics of 52 isolates from Colletotrichum leaf disease lesions on Hevea brasiliensis in Sri Lanka revealed that only 18 isolates belong to Colletotrichum gloeosporioides. The remaining 34 isolates represented C. aculatum indicating that C. acutatum is the main cause of Colletotrichum leaf disease in Sri Lanka.This revised version was published online in October 2005 with corrections to the Cover Date.     

Trophic Classification of Non‐Perennial Reservoirs Utilized for the Development of Culture‐Based Fisheries,Sri Lanka

The aim of this study was to check the suitability of some trophic models developed for temperate regions to classify the non‐perennial reservoirs of Sri Lanka in order to manage culture‐based fisheries of those reservoirs. A limnological study was carried out in 45 non‐perennial reservoirs, which have been randomly selected for stocking of fish fingerlings for the development of culture‐based fisheries. High total phosphorous (TP) content in relation to algal biomass indicates high non‐algal turbidity in all reservoirs. Carlson's trophic state indices (TSI) measured on the basis of Secchi disc depth [TSI (SDD)], TP [TSI (TP)] and chlorophyll a [TSI (Chl‐a)] show that the 45 reservoirs studied are characterized by TSI (TP) = TSI (SDD) > TSI (Chl‐a), indicating that non‐algal particulate matter or colour dominates underwater light attenuation. As TSI (Chl‐a) is positively correlated to culture‐based fisheries yield, it is useful for planning culture‐based fisheries development strategies in non‐perennial reservoirs of Sri Lanka, and has the potential to be used elsewhere in the tropics for comparable developments. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Structure of alpha-helical membrane-bound human islet amyloid polypeptide and its implications for membrane-mediated misfolding

Human islet amyloid polypeptide (hIAPP) misfolding is thought to play an important role in the pathogenesis of type II diabetes mellitus. It has recently been shown that membranes can catalyze the misfolding of hIAPP via an alpha-helical intermediate of unknown structure. To better understand the mechanism of membrane-mediated misfolding, we used site-directed spin labeling and EPR spectroscopy to generate a three-dimensional structural model of this membrane-bound form. We find that hIAPP forms a single alpha-helix encompassing residues 9-22. The helix is flanked by N- and C-terminal regions that do not take up a clearly detectable secondary structure and are less ordered. Residues 21 and 22 are located in a transitional region between the alpha-helical structure and C terminus and exhibit significant mobility. The alpha-helical structure presented here has important implications for membrane-mediated aggregation. Anchoring hIAPP to the membrane not only increases the local concentration but also reduces the encounter between peptides to essentially a two-dimensional process. It is significant to note that the alpha-helical membrane-bound form leaves much of an important amyloidogenic region of hIAPP (residues 20-29) exposed for misfolding. Misfolding of this and other regions is likely further aided by the low dielectric environment near the membrane that is known to promote secondary structure formation. Based upon these considerations, a structural model for membrane-mediated aggregation is discussed.     

MPEx: A tool for exploring membrane proteins

Hydropathy plot methods form a cornerstone of membrane protein research, especially in the early stages of biochemical and structural characterization. Membrane Protein Explorer (MPEx), described in this article, is a refined and versatile hydropathy‐plot software tool for analyzing membrane protein sequences. MPEx is highly interactive and facilitates the characterization and identification of favorable protein transmembrane regions using experiment‐based physical and biological hydrophobicity scales. Besides allowing the consequences of sequence mutations to be examined, it provides tools for aiding the design of membrane‐active peptides. MPEx is freely available as a Java Web Start application from our web site at http://blanco.biomol.uci.edu/mpex .