Lineage-specific positive selection at the merozoite surface protein 1 (msp1) locus of Plasmodium vivax and related simian malaria parasites

<p>Abstract</p> <p>Background</p> <p>The 200 kDa merozoite surface protein 1 (MSP-1) of malaria parasites, a strong vaccine candidate, plays a key role during erythrocyte invasion and is a target of host protective immune response. <it>Plasmodium vivax</it>, the most widespread human malaria parasite, is closely related to parasites that infect Asian Old World monkeys, and has been considered to have become a parasite of man by host switch from a macaque malaria parasite. Several Asian monkey parasites have a range of natural hosts. The same parasite species shows different disease manifestations among host species. This suggests that host immune responses to <it>P. vivax</it>-related malaria parasites greatly differ among host species (albeit other factors). It is thus tempting to invoke that a major immune target parasite protein such as MSP-1 underwent unique evolution, depending on parasite species that exhibit difference in host range and host specificity.</p> <p>Results</p> <p>We performed comparative phylogenetic and population genetic analyses of the gene encoding MSP-1 (<it>msp1</it>) from <it>P. vivax </it>and nine <it>P. vivax</it>-related simian malaria parasites. The inferred phylogenetic tree of <it>msp1 </it>significantly differed from that of the mitochondrial genome, with a striking displacement of <it>P. vivax </it>from a position close to <it>P. cynomolgi </it>in the mitochondrial genome tree to an outlier of Asian monkey parasites. Importantly, positive selection was inferred for two ancestral branches, one leading to <it>P. inui </it>and <it>P. hylobati </it>and the other leading to <it>P. vivax</it>, <it>P. fieldi </it>and <it>P. cynomolgi</it>. This ancestral positive selection was estimated to have occurred three to six million years ago, coinciding with the period of radiation of Asian macaques. Comparisons of <it>msp1 </it>polymorphisms between <it>P. vivax</it>, <it>P. inui </it>and <it>P. cynomolgi </it>revealed that while some positively selected amino acid sites or regions are shared by these parasites, amino acid changes greatly differ, suggesting that diversifying selection is acting species-specifically on <it>msp1</it>.</p> <p>Conclusions</p> <p>The present results indicate that the <it>msp1 </it>locus of <it>P. vivax </it>and related parasite species has lineage-specific unique evolutionary history with positive selection. <it>P. vivax </it>and related simian malaria parasites offer an interesting system toward understanding host species-dependent adaptive evolution of immune-target surface antigen genes such as <it>msp1</it>.</p

The influence of topographic variation on forest structure in two woody plant communities: A remote sensing approach

Aim of study:  The study aimed to characterise variation in structural attributes of vegetation in relation to variations in topographic position using LIDAR data over landscapes.Area of study: The study was conducted in open canopy eucalypt-dominated forest (Richmond Range National Park-RRNP) and closed canopy subtropical rainforest (Border Ranges National Park-BRNP) in north-eastern New South Wales, Australia.Material and Methods: one metre resolution digital canopy height model (CHM) was extracted from the LIDAR data and used to estimate maximum overstorey height and crown area. LIDAR fractional cover representing the photosynthetic and non-photosynthetic component of canopy was calculated using LIDAR points aggregated into 50 m spatial bins. Potential solar insolation, Topographic Wetness Index (TWI), slope and the elevation were processed using LIDAR derived digital elevation models.Main results: No relationship was found between maximum overstorey height and insolation gradient in the BRNP. Maximum overstorey height decreased with increasing insolation in the RRNP (R2 0.45). Maximum overstorey height increased with increasing TWI in the RRNP. Average crown area decreased with increasing insolation in both study areas. LIDAR fractional cover decreased with increasing insolation (R2 0.54), and increased with increasing TWI (R2 0.57) in the RRNP.Research highlights: The characterization of structural parameters of vegetation in relation to the variation of the topography was possible in eucalyptus dominated open canopy forest.  No reportable difference in variation of structural elements of vegetation was detected with topographic variation of subtropical rainforest. 

The influence of topographic variation on forest structure in two woody plant communities: A remote sensing approach

<p><em>Aim of study</em>:  The study aimed to characterise variation in structural attributes of vegetation in relation to variations in topographic position using LIDAR data over landscapes.</p><p><em>Area of study</em>: The study was conducted in open canopy eucalypt-dominated forest (Richmond Range National Park-RRNP) and closed canopy subtropical rainforest (Border Ranges National Park-BRNP) in north-eastern New South Wales, Australia.</p><p><em>Material and Methods</em>: one metre resolution digital canopy height model (CHM) was extracted from the LIDAR data and used to estimate maximum overstorey height and crown area. LIDAR fractional cover representing the photosynthetic and non-photosynthetic component of canopy was calculated using LIDAR points aggregated into 50 m spatial bins. Potential solar insolation, Topographic Wetness Index (TWI), slope and the elevation were processed using LIDAR derived digital elevation models.<em></em></p><p><em>Main results</em>:<em> </em>No relationship was found between maximum overstorey height and insolation gradient in the BRNP. Maximum overstorey height decreased with increasing insolation in the RRNP (R² 0.45). Maximum overstorey height increased with increasing TWI in the RRNP. Average crown area decreased with increasing insolation in both study areas. LIDAR fractional cover decreased with increasing insolation (R² 0.54), and increased with increasing TWI (R² 0.57) in the RRNP.</p><p><em>Research highlights</em>: The characterization of structural parameters of vegetation in relation to the variation of the topography was possible in eucalyptus dominated open canopy forest.  No reportable difference in variation of structural elements of vegetation was detected with topographic variation of subtropical rainforest. </p><p> </p

Estimating above-ground biomass by fusion of LiDAR and multispectral data in subtropical woody plant communities in topographically complex terrain in North-eastern Australia

We investigated a strategy to improve predicting capacity of plot-scale above-ground biomass (AGB) by fusion of LiDAR and Landsat5 TM derived biophysical variables for subtropical rainforest and eucalypts dominated forest in topographically complex landscapes in North-eastern Australia. Investigation was carried out in two study areas separately and in combination. From each plot of both study areas, LiDAR derived structural parameters of vegetation and reflectance of all Landsat bands, vegetation indices were employed. The regression analysis was carried out separately for LiDAR and Landsat derived variables individually and in combination. Strong relationships were found with LiDAR alone for eucalypts dominated forest and combined sites compared to the accuracy of AGB estimates by Landsat data. Fusing LiDAR with Landsat5 TM derived variables increased overall performance for the eucalypt forest and combined sites data by describing extra variation (3% for eucalypt forest and 2% combined sites) of field estimated plot-scale above-ground biomass. In contrast, separate LiDAR and imagery data, and fusion of LiDAR and Landsat data performed poorly across structurally complex closed canopy subtropical rainforest. These findings reinforced that obtaining accurate estimates of above ground biomass using remotely sensed data is a function of the complexity of horizontal and vertical structural diversity of vegetation

Evaluation of Different Topographic Corrections for Landsat TM Data by Prediction of Foliage Projective Cover (FPC) in Topographically Complex Landscapes

The reflected radiance in topographically complex areas is severely affected by variations in topography; thus, topographic correction is considered a necessary pre-processing step when retrieving biophysical variables from these images. We assessed the performance of five topographic corrections: (i) C correction (C), (ii) Minnaert, (iii) Sun Canopy Sensor (SCS), (iv) SCS + C and (v) the Processing Scheme for Standardised Surface Reflectance (PSSSR) on the Landsat-5 Thematic Mapper (TM) reflectance in the context of prediction of Foliage Projective Cover (FPC) in hilly landscapes in north-eastern Australia. The performance of topographic corrections on the TM reflectance was assessed by (i) visual comparison and (ii) statistically comparing TM predicted FPC with ground measured FPC and LiDAR (Light Detection and Ranging)-derived FPC estimates. In the majority of cases, the PSSSR method performed best in terms of eliminating topographic effects, providing the best relationship and lowest residual error when comparing ground measured FPC and LiDAR FPC with TM predicted FPC. The Minnaert, C and SCS + C showed the poorest performance. Finally, the use of TM surface reflectance, which includes atmospheric correction and broad Bidirectional Reflectance Distribution Function (BRDF) effects, seemed to account for most topographic variation when predicting biophysical variables, such as FPC

Strain-specific protective effect of the immunity induced by live malarial sporozoites under chloroquine cover.

The efficacy of a whole-sporozoite malaria vaccine would partly be determined by the strain-specificity of the protective responses against malarial sporozoites and liver-stage parasites. Evidence from previous reports were inconsistent, where some studies have shown that the protective immunity induced by irradiated or live sporozoites in rodents or humans were cross-protective and in others strain-specific. In the present work, we have studied the strain-specificity of live sporozoite-induced immunity using two genetically and immunologically different strains of Plasmodium cynomolgi, Pc746 and PcCeylon, in toque monkeys. Two groups of monkeys were immunized against live sporozoites of either the Pc746 (n = 5), or the PcCeylon (n = 4) strain, by the bites of 2-4 sporozoite-infected Anopheles tessellates mosquitoes per monkey under concurrent treatments with chloroquine and primaquine to abrogate detectable blood infections. Subsequently, a group of non-immunized monkeys (n = 4), and the two groups of immunized monkeys were challenged with a mixture of sporozoites of the two strains by the bites of 2-5 infective mosquitoes from each strain per monkey. In order to determine the strain-specificity of the protective immunity, the proportions of parasites of the two strains in the challenge infections were quantified using an allele quantification assay, Pyrosequencing™, based on a single nucleotide polymorphism (SNP) in the parasites' circumsporozoite protein gene. The Pyrosequencing™ data showed that a significant reduction of parasites of the immunizing strain in each group of strain-specifically immunized monkeys had occurred, indicating a stronger killing effect on parasites of the immunizing strain. Thus, the protective immunity developed following a single, live sporozoite/chloroquine immunization, acted specifically against the immunizing strain and was, therefore, strain-specific. As our experiment does not allow us to determine the parasite stage at which the strain-specific protective immunity is directed, it is possible that the target of this immunity could be either the pre-erythrocytic stage, or the blood-stage, or both

Assessment of environmental variability on malaria transmission in a malaria-endemic rural dry zone locality of Sri Lanka: The wavelet approach.

Malaria is a global public health concern and its dynamic transmission is still a complex process. Malaria transmission largely depends on various factors, including demography, geography, vector dynamics, parasite reservoir, and climate. The dynamic behaviour of malaria transmission has been explained using various statistical and mathematical methods. Of them, wavelet analysis is a powerful mathematical technique used in analysing rapidly changing time-series to understand disease processes in a more holistic way. The current study is aimed at identifying the pattern of malaria transmission and its variability with environmental factors in Kataragama, a malaria-endemic dry zone locality of Sri Lanka, using a wavelet approach. Monthly environmental data including total rainfall and mean water flow of the "Menik Ganga" river; mean temperature, mean minimum and maximum temperatures and mean relative humidity; and malaria cases in the Kataragama Medical Officer of Health (MOH) area were obtained from the Department of Irrigation, Department of Meteorology and Malaria Research Unit (MRU) of University of Colombo, respectively, for the period 1990 to 2005. Wavelet theory was applied to analyze these monthly time series data. There were two significant periodicities in malaria cases during the period of 1992-1995 and 1999-2000. The cross-wavelet power spectrums revealed an anti-phase correlation of malaria cases with mean temperature, minimum temperature, and water flow of "Menik Ganga" river during the period 1991-1995, while the in-phase correlation with rainfall is noticeable only during 1991-1992. Relative humidity was similarly associated with malaria cases between 1991-1992. It appears that environmental variables have contributed to a higher incidence of malaria cases in Kataragama in different time periods between 1990 and 2005

Ion Transport Modulators as Antimycobacterial Agents

There is an urgent need for better and safer therapeutic interventions for tuberculosis (TB). We assessed the effects of FDA-approved ion transport modulators, namely, ambroxol HCl, amiloride HCl, diazoxide, digoxin, furosemide, hydrochlorothiazide (HCTZ), metformin, omeprazole, pantoprazole, phenytoin, verapamil, and drug X and Y on the growth of free and intracellular Mycobacterium bovis BCG. Free and intracellular M. bovis BCG were cultured in the presence or absence of the test drugs for 3 to 9 days and then quantified. For both free and intracellular bacteria, cultures that were exposed to furosemide, phenytoin, or drug Y yielded lower bacteria counts compared to drug-free controls (p<0.05). The same was observed with diazoxide, HCTZ, verapamil, and drug X, but only for intracellular M. bovis BCG (p<0.05). To assess the effects of the drugs on bactericidal activity of rifampicin, free and intracellular M. bovis BCG were treated with rifampicin alone or in combination with each of the thirteen test drugs for 3 to 9 days. For extracellular bacteria, higher bacteria clearance rates were observed in cultures exposed to rifampicin in combination with amiloride HCl, diazoxide, digoxin, furosemide, HCTZ, metformin, pantoprazole, phenytoin, drug X, or drug Y than those exposed to rifampicin alone, indicating that rifampicin had a synergistic effect with these test drugs. Rifampicin was also synergistic with ambroxol HCl, diazoxide, digoxin, furosemide, HCTZ, omeprazole, pantoprazole, phenytoin, verapamil, and drug X against intracellular M. bovis BCG. The antimycobacterial properties exhibited by the ion transport modulators in this study make them viable candidates as adjuncts to the current anti-TB regimens