Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum

Background The ability of T cells, acting independently of antibodies, to control malaria parasite growth in people has not been defined. If such cell-mediated immunity was shown to be effective, an additional vaccine strategy could be pursued. Our aim was to ascertain whether or not development of cell-mediated immunity to Plasmodium falciparum blood-stage infection could be induced in human beings by exposure to malaria parasites in very low density. Methods We enrolled five volunteers from the staff at our research institute who had never had malaria. We used a cryopreserved inoculum of red cells infected with P falciparum strain 3D7 to give them repeated subclinical infections of malaria that we then cured early with drugs, to induce cell-mediated immune responses. We tested for development of immunity by measurement of parasite concentrations in the blood of volunteers by PCR of the multicopy gene STEVOR and by following up the volunteers clinically, and by measuring antibody and cellular immune responses to the parasite. Findings After challenge and a extended period without drug cure, volunteers were protected against malaria as indicated by absence of parasites or parasite DNA in the blood, and absence of clinical symptoms. Immunity was characterised by absence of detectable antibodies that bind the parasite or infected red cells, but by the presence of a proliferative T-cell response, involving CD4+ and CD8+ T cells, a cytokine response, consisting of interferon gamma but not interleukin 4 or interleukin 10, induction of high concentrations of nitric oxide synthase activity in peripheral blood mononuclear cells, and a drop in the number of peripheral natural killer T cells. Interpretation People can be protected against the erythrocytic stage of malaria by a strong cell-mediated immune response, in the absence of detectable parasite-specific antibodies, suggesting an additional strategy for development of a malaria vaccine.

Effect of soil composition and dissolved organic matter on pesticide sorption

The effect of the solid and dissolved organic matter fractions, mineral composition and ionic strength of the soil solution on the sorption behaviour of pesticides were studied. A number of soils, chosen so as to have different clay mineral and organic carbon content, were used to study the sorption of the pesticides atrazine (6-chloro-N-2-ethyl-N-4-isopropyl-1,3,5-triazine-2,4-diamine), 2,4-D ((2,4-dichlorophenoxy) acetic acid), isoproturon (3-(4-isopropylphenyl)1,1-dimethylurea) and paraquat (1,1'-dimethyl-4,4'-bipyridinium) in the presence of low and high levels of dissolved organic carbon and different background electrolytes. The sorption behaviour of atrazine, isoproturon and paraquat was dominated by the solid state soil components and the presence of dissolved organic matter had little effect. The sorption of 2,4-D was slightly affected by the soluble organic matter in the soil. However, this effect may be due to competition for adsorption sites between the pesticide and the soluble organic matter rather than due to a positive interaction between the pesticide and the soluble fraction of soil organic matter. It is concluded that the major factor governing the sorption of these pesticides is the solid state organic fraction with the clay mineral content also making a significant contribution. The dissolved organic carbon fraction of the total organic carbon in the soil and the ionic strength of the soil solution appear to have little or no effect on the sorption/transport characteristics of these pesticides over the range of concentrations studied. (C) 2002 Elsevier Science B.V. All rights reserved.

Cuticular hydrocarbons of Drosophila birchii and D-serrata: Identification and role in mate choice in D-serrata

The cuticular hydrocarbon compositions of two sympatric species of Australian Drosophila in the montium subgroup of the melanogaster group that use cuticular hydrocarbons in mate recognition have been characterized. Drosophila birchii has 34 components in greater than trace amounts, with a carbon number range of C-20 to C-33. Drosophila serrata has 21 components above trace level and a carbon number range of C-24 to C-31. These two species share eight hydrocarbon components, with all but two of them being monoenes. For both species, the (Z)-9-monoenes are the predominant positional isomer. The hydrocarbons of D. birchii are n-alkanes, n-alkenes (Z)-5-, (Z)-7-, (Z)-9-, and (Z)-11-), low to trace levels of homologous (Z,Z)-7,11- and (Z,Z)-9,13-dienes; and trace amounts of (Z,Z)-5,9- C-25:2, a major component of D. serrata. Only one methyl branched hydrocarbon was detected (2-methyl C-28), and it occurred at very low levels. The hydrocarbons of D. serrata are dominated by a homologous series of (Z,Z)-5,9-dienes, and notably, are characterized by the apparent absence of n-alkanes. Homologous series of (Z)-5-, (Z)-7-, and (Z)-9- alkenes are also present in D. serrata as well as 2-methyl alkanes. Drosophila serrata females display strong directional mate choice based on male cuticular hydrocarbons and prefer D. serrata males with higher relative abundances of the 2-methyl alkanes, but lower relative abundances of (Z,Z)-5,9- C-24:2 and (Z)-9-C-25:1.

Fitting genetic models to twin data with binary and ordered categorical responses: A comparison of structural equation modelling and Bayesian hierarchical models

We compare Bayesian methodology utilizing free-ware BUGS (Bayesian Inference Using Gibbs Sampling) with the traditional structural equation modelling approach based on another free-ware package, Mx. Dichotomous and ordinal (three category) twin data were simulated according to different additive genetic and common environment models for phenotypic variation. Practical issues are discussed in using Gibbs sampling as implemented by BUGS to fit subject-specific Bayesian generalized linear models, where the components of variation may be estimated directly. The simulation study (based on 2000 twin pairs) indicated that there is a consistent advantage in using the Bayesian method to detect a correct model under certain specifications of additive genetics and common environmental effects. For binary data, both methods had difficulty in detecting the correct model when the additive genetic effect was low (between 10 and 20%) or of moderate range (between 20 and 40%). Furthermore, neither method could adequately detect a correct model that included a modest common environmental effect (20%) even when the additive genetic effect was large (50%). Power was significantly improved with ordinal data for most scenarios, except for the case of low heritability under a true ACE model. We illustrate and compare both methods using data from 1239 twin pairs over the age of 50 years, who were registered with the Australian National Health and Medical Research Council Twin Registry (ATR) and presented symptoms associated with osteoarthritis occurring in joints of the hand.

Comparative genetic study confirms exceptionally low genetic variation in the ancient and endangered relictual conifer, Wollemia nobilis (Araucariaceae)

The Wollemi pine, Wollemia nobilis (Araucariaceae), was discovered in 1994 as the only extant member of the genus, previously known only from the fossil record. With fewer than 100 trees known from an inaccessible canyon in southeastern Australia, it is one of the most endangered tree species in the world. We conducted a comparative population genetic survey at allozyme, amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) loci in W. nobilis, Araucaria cunninghatnii and Agathis robusta - representatives of the two sister genera. No polymorphism was detected at 13 allozyme loci, more than 800 AFLP loci or the 20 SSR loci screened in W. nobilis. In Ag. robusta only one of 12 allozyme loci, five of 800 AFLP loci and none of the 15 SSR loci were variable. For A. cunninghamii, 10 of > 800 AFLP loci and five of 20 SSR loci were variable. Thus low genetic diversity characterizes all three species. While not ruling out the existence of genetic variation, we conclude that genetic diversity is exceptionally low in the Wollemi pine. To our knowledge this is the most extreme case known in plants. We conclude that the combination of small population effects, clonality and below-average genetic variation in the family are probable contributing factors to the low diversity. The exceptionally low genetic diversity of the Wollemi pine, combined with its known susceptibility to exotic fungal pathogens, reinforces current management policies of strict control of access to the pines and secrecy of the pine locations.

Effects of seawater components on immature Culicoides molestus (Skuse) (Diptera : Ceratopogonidae)

Following analysis of beach sites and an indication that seawater components might influence larval occurrence, we studied the impact of increasing salinity and seawater concentration on survival of fourth-instar larvae of the canal biting midge, Culicoides molestus . While NaCl had little effect on immature survival, increasing the concentration of seawater increased mortality prior to the adult stage. Seawater at three and four times the normal concentration killed all immatures. Artificial elevation of seawater concentration in the sandy substrate preferred by larvae, therefore, has the potential to reduce immature midge survival. Diet also affected survival, with higher mortality of immatures that were fed fish-food flakes compared with those that were fed live nematodes.

Occurrence of immature Culicoides molestus (Skuse) (Diptera : Ceratopogonidae) in relation to habitat characteristics

Analysis of beach sites on the Gold Coast, Australia, found that 14 physical and chemical habitat characteristics differed significantly between sites where numerous immatures of the canal biting midge, Culicoides molestus (Skuse), were found and sites where no midge immatures occurred. Five of the chemical factors found to reliably distinguish C. molestus habitat are major components of seawater, while another, electrical conductivity, is related to the concentration of seawater components. Calcium was the only one of the six primary components of seawater that was not a statistically significant correlate of C. molestus habitation by sand analysis. It is likely that a causative variable in occurrence of immatures is the concentration of seawater present in canals, because larvae are found where seawater component concentration is low in relation to uninhabited sites of similar appearance.

Relations between high and low power groups: The importance of legitimacy

Using a social identity perspective, two experiments examined the effects of power and the legitimacy of power differentials on intergroup bias. In Experiment 1, 125 math-science students were led to believe that they had high or low representation in a university decision-making body relative to social-science students and that this power position was either legitimate or illegitimate. Power did not have an independent effect on bias; rather, members of both high and low power groups showed more bias when the power hierarchy was illegitimate than when it was legitimate. This effect was replicated in Experiment 2 (N =105). In addition, Experiment 2 showed that groups located within an unfair power hierarchy expected the superordinate power body to be more discriminatory than did those who had legitimately high or low power. The results are discussed in terms of their implications for group relations.

Fas ligand and tumour counter-attack in colorectal cancer stratified according to microsatellite instability status

Expression of membrane-bound Fas ligand (FasL) by colorectal cancer cells may allow the development of an immune-privileged site by eliminating incoming tumour-infiltrating lymphocytes (TILs) in a Fas-mediated counter-attack. Sporadic colorectal cancer can be subdivided into three groups based on the level of DNA microsatellite instability (NISI). High-level NISI (NISI-High) is characterized by the presence of TILs and a favourable prognosis, while microsatellite-stable (MSS) cancers are TIL-deficient and low-level MSI (MSI-Low) is associated with an intermediate TIL density. The purpose of this study was to establish the relationship between MSI status and FasL expression in primary colorectal adenocarcinoma. Using immunohistochemistry and a selected series of 101 cancers previously classified as 31 MSI-High, 30 NISI-Low, and 40 MISS, the present study sought to confirm the hypothesis that increased TIL density in MSI-High cancers is associated with low or absent membrane-bound FasL expression, while increased FasL in MSS cancers allows the killing of host TILs. TUNEL/CD3 double staining was also used to determine whether MSS cancers contain higher numbers of apoptotic TILs in vivo than MSI-High or MSI-Low cancers. Contrary to the initial hypothesis, it was found that MSI-High cancers were associated with higher FasL expression (p = 0.04) and a stronger intensity of FasL staining (p = 0.007). In addition, mucinous carcinomas were independently characterized by increased FasL expression (p = 0.03) and staining intensity (p = 0.0005). Higher FasL expression and staining intensity did not correlate with reduced TIL density or increased numbers of apoptotic TILs. However, consistent with the hypothesis that curtailment of the host anti-tumour immune response contributes to the poor prognosis in MSS cancers, it was found that apoptotic TILs were most abundant in MSS carcinomas and metastatic Dukes' stage C or D tumours (p = 0.004; p = 0.046 respectively). This study therefore suggests that MSS colorectal cancers are killing incoming TILs in an effective tumour counter-attack, but apparently not via membrane-bound FasL. Copyright (C) 2003 John Wiley Sons, Ltd.

Low-density koala (Phascolarctos cinereus) populations in the mulgalands of south-west Queensland. III. Broad-scale patterns of habitat use

To date there have been few quantitative studies of the distribution of, and relative habitat utilisation by, koalas in the mulgalands of Queensland. To examine these parameters we applied habitat-accessibility and relative habitat-utilisation indices to estimates of faecal pellet density sampled at 149 sites across the region. Modelling the presence of pellets using logistic regression showed that the potential range of accessible habitats and relative habitat use varied greatly across the region, with rainfall being probably the most important determinant of distribution. Within that distribution, landform and rainfall were both important factors affecting habitat preference. Modelling revealed vastly different probabilities of finding a pellet under trees depending on the tree species, canopy size, and location within the region.

Low-density koala (Phascolarctos cinereus) populations in the mulgalands of south-west Queensland. II. Distribution and diet

This study used faecal pellets to investigate the broadscale distribution and diet of koalas in the mulgalands biogeographic region of south-west Queensland. Koala distribution was determined by conducting faecal pellet searches within a 30-cm radius of the base of eucalypts on 149 belt transects, located using a multi-scaled stratified sampling design. Cuticular analysis of pellets collected from 22 of these sites was conducted to identify the dietary composition of koalas within the region. Our data suggest that koala distribution is concentrated in the northern and more easterly regions of the study area, and appears to be strongly linked with annual rainfall. Over 50% of our koala records were obtained from non-riverine communities, indicating that koalas in the study area are not primarily restricted to riverine communities, as has frequently been suggested. Cuticular analysis indicates that more than 90% of koala diet within the region consists of five eucalypt species. Our data highlights the importance of residual Tertiary landforms to koala conservation in the region.

Stratigraphy, facies architecture and tectonic implications of the Upper Devonian to Lower Carboniferous Campwyn Volcanics of the northern New England Fold Belt

Upper Devonian to Lower Carboniferous strata of the Campwyn Volcanics of east central Queensland preserve a substantial sequence of first-cycle volcaniclastic sedimentary and coeval volcanic rocks that record prolonged volcanic activity along the northern New England Fold Belt. The style and scale of volcanism varied with time, producing an Upper Devonian sequence of mafic volcano-sedimentary rocks overlain by a rhyolitic ignimbrite-dominated sequence that passes upward into a Lower Carboniferous limestone-bearing sedimentary sequence. We define two facies associations for the Campwyn Volcanics. A lower facies association is dominated by mafic volcanic-derived sedimentary breccias with subordinate primary mafic volcanic rocks comprising predominantly hyaloclastite and peperite. Sedimentary breccias record episodic and high energy, subaqueous depositional events with clastic material sourced from a mafic lava-dominated terrain. Some breccias contain a high proportion of attenuated dense, glassy mafic juvenile clasts, suggesting a syn-eruptive origin. The lower facies association coarsens upwards from a lithic sand-dominated sequence through a thick interval of pebble- to boulder-grade polymict volcaniclastic breccias, culminating in facies that demonstrate subaerial exposure. The silicic upper facies association marks a significant change in eruptive style, magma composition and the nature of eruptive sources, as well as the widespread development of subaerial depositional conditions. Crystal-rich, high-grade, low- to high-silica rhyolite ignimbrites dominate the base of this facies association. Biostratigraphic age controls indicate that the ignimbrite-bearing sequences are Famennian to lower-mid Tournaisian in age. The ignimbrites represent extra-caldera facies with individual units up to 40 m thick and mostly lacking coarse lithic breccias. Thick deposits of pyroclastic material interbedded with fine-grained siliceous sandstone and mudstone (locally radiolarian-bearing) were deposited from pyroclastic flows that crossed palaeoshorelines or represent syn-eruptive, resedimented pyroclastic material. Some block-bearing lithic-pumice-crystal breccias may also reflect more proximal subaqueous silicic explosive eruptions. Crystal-lithic sandstones interbedded with, and overlying the ignimbrites, contain abundant detrital volcanic quartz and feldspar derived from the pyroclastic deposits. Limestone is common in the upper part of the upper facies association, and several beds are oolitic (cf. Rockhampton Group of the Yarrol terrane). Overall, the upper facies association fines upward and is transgressive, recording a return to shallow-marine conditions. Palaeocurrent data from all stratigraphic levels in the Campwyn Volcanics indicate that the regional sediment-dispersal direction was to the northwest, and opposed to the generally accepted notion of easterly sediment dispersal from a volcanic arc source. The silicic upper facies association correlates in age and lithology to Early Carboniferous silicic volcanism in the Drummond (Cycle 1) and Burdekin Basins, Connors Arch, and in the Yarrol terranes of eastern Queensland. The widespread development of silicic volcanism in the Early Carboniferous indicates that silicic (rift-related) magmatism was not restricted to the Drummond Basin, but was part of a more substantial silicic igneous province.