Bayesian geostatistics in health cartography: the perspective of malaria

Maps of parasite prevalences and other aspects of infectious diseases that vary in space are widely used in parasitology. However, spatial parasitological datasets rarely, if ever, have sufficient coverage to allow exact determination of such maps. Bayesian geostatistics (BG) is a method for finding a large sample of maps that can explain a dataset, in which maps that do a better job of explaining the data are more likely to be represented. This sample represents the knowledge that the analyst has gained from the data about the unknown true map. BG provides a conceptually simple way to convert these samples to predictions of features of the unknown map, for example regional averages. These predictions account for each map in the sample, yielding an appropriate level of predictive precision.     

Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry

The genome sequencing of H37Rv strain of Mycobacterium tuberculosis was completed in 1998 followed by the whole genome sequencing of a clinical isolate, CDC1551 in 2002. Since then, the genomic sequences of a number of other strains have become available making it one of the better studied pathogenic bacterial species at the genomic level. However, annotation of its genome remains challenging because of high GC content and dissimilarity to other model prokaryotes. To this end, we carried out an in-depth proteogenomic analysis of the M. tuberculosis H37Rv strain using Fourier transform mass spectrometry with high resolution at both MS and tandem MS levels. In all, we identified 3176 proteins from Mycobacterium tuberculosis representing ~80% of its total predicted gene count. In addition to protein database search, we carried out a genome database search, which led to identification of ~250 novel peptides. Based on these novel genome search-specific peptides, we discovered 41 novel protein coding genes in the H37Rv genome. Using peptide evidence and alternative gene prediction tools, we also corrected 79 gene models. Finally, mass spectrometric data from N terminus-derived peptides confirmed 727 existing annotations for translational start sites while correcting those for 33 proteins. We report creation of a high confidence set of protein coding regions in Mycobacterium tuberculosis genome obtained by high resolution tandem mass-spectrometry at both precursor and fragment detection steps for the first time. This proteogenomic approach should be generally applicable to other organisms whose genomes have already been sequenced for obtaining a more accurate catalogue of protein-coding genes.     

Theoretical studies on nitrogen rich energetic azoles

Different nitro azole isomers based on five membered heterocyclics were designed and investigated using computational techniques in order to find out the comprehensive relationships between structure and performances of these high nitrogen compounds. Electronic structure of the molecules have been calculated using density functional theory (DFT) and the heat of formation has been calculated using the isodesmic reaction approach at B3LYP/6-31G* level. All designed compounds show high positive heat of formation due to the high nitrogen content and energetic nitro groups. The crystal densities of these energetic azoles have been predicted with different force fields. All the energetic azoles show densities higher than 1.87 g/cm³. Detonation properties of energetic azoles are evaluated by using Kamlet-Jacobs equation based on the calculated densities and heat of formations. It is found that energetic azoles show detonation velocity about 9.0 km/s, and detonation pressure of 40GPa. Stability of the designed compounds has been predicted by evaluating the bond dissociation energy of the weakest C-NO₂ bond. The aromaticity using nucleus independent chemical shift (NICS) is also explored to predict the stability via delocalization of the π-electrons. Charge on the nitro group is used to assess the impact sensitivity in the present study. Overall, the study implies that all energetic azoles are found to be stable and expected to be the novel candidates of high energy density materials (HEDMs).     

Computational design and structure–property relationship studies on heptazines

This study aimed to design novel nitrogen-rich heptazine derivatives as high energy density materials (HEDM) by exploiting systematic structure–property relationships. Molecular structures with diverse energetic substituents at varying positions in the basic heptazine ring were designed. Density functional techniques were used for prediction of gas phase heat of formation by employing an isodesmic approach, while crystal density was assessed by packing calculations. The results reveal that nitro derivatives of heptazine possess a high heat of formation and further enhancement was achieved by the substitution of nitro heterocycles. The crystal packing density of the designed compounds varied from 1.8 to 2 g cm⁻³, and hence, of all the designed molecules, nitro derivatives of heptazine exhibit better energetic performance characteristics in terms of detonation velocity and pressure. The calculated band gap of the designed molecules was analyzed to establish sensitivity correlations, and the results reveal that, in general, amino derivatives possess better insensitivity characteristics. The overall performance of the designed compounds was moderate, and such compounds may find potential applications in gas generators and smoke-free pyrotechnic fuels as they are rich in nitrogen content.     

Mechanisms of Araucaria (Atlantic) Forest Expansion into Southern Brazilian Grasslands

Recent studies have shown that tropical and subtropical forests expanded during the late Holocene, but rates and mechanisms of expansion are still unknown. Here, we investigate how a forest–grassland mosaic changed over the past 10,000 years at the southernmost limit of the Brazilian Atlantic forest. We used soil organic matter carbon isotopes (δ¹³C and ¹⁴C) to quantify and date changes in vegetation, examining soil properties and leaf traits of tree species (nutrient content, δ¹³C, δ¹⁵N, and specific leaf area—SLA) to describe potential mechanisms of expansion. Our results show that after several millennia of stability, forests have been expanding over grasslands through continuous, but very slow, border dynamics and patch formation (<100 m since ~4,000 YBP). This process of expansion coincided with past changes in climate, but biotic feedback mechanisms also appear to be important for the long-term persistence and expansion of forests. Soil fertility and microbial biomass match current rather than past vegetation distribution, increasing progressively across the gradient: grasslands < isolated trees < forest patches < forests. Foliar δ¹⁵N values of trees that are able to colonize the grassland are consistently lower across this vegetation gradient, suggesting an increasingly greater reliance on symbiotic nutrient uptake from grasslands to forests. No significant relationships were found between soil and leaf nutrients, but SLA explained variation in leaf N, P, and K (positive relationships) and in leaf δ¹³C (negative relationship). These findings suggest that a tradeoff between tree growth and water use efficiency is an important regulator of forest–grassland dynamics in the study region.     

Assessing the Use of Functional Diversity as a Measure of Ecological Resilience in Arid Rangelands

It is becoming more apparent that species richness alone many not be sufficient to fully understand ecosystem resilience but that functional diversity (diversity of species having similar effects on an ecosystem process) may be more relevant. In particular, response diversity (diversity of species that respond differently to disturbance) within functional groups (FG) is suggested to be critical for resilience. We assess for the first time the use of response diversity as a measure of resilience in an empirical study. Our experimental design consisted of sites with three disturbance intensities during a grazing exclosure period and the same sites, 1 year later, after grazing. Plant FGs were identified based on effect traits related to nutrient cycling and soil retention, and species richness within groups was assessed during exclosure and after grazing. To assess if response diversity could predict loss of species richness (resilience analysis), response diversity was calculated only during the exclosure period, based on traits related to grazing tolerance. We also assessed the contribution of richness to response diversity during exclosure (redundancy analysis). Response diversity was significantly and highly correlated with species richness within FGs during disturbance. That is, FGs with the lowest response diversity were the most affected, disappearing when disturbance appeared. Richness within FGs during exclosure was not significantly correlated with response diversity, showing that higher richness does not ensure resilience. We conclude that response diversity can be used to predict which FGs are more resilient, and hence, less vulnerable to future disturbance.     

The importance of phase information for human genomics

Contemporary sequencing studies often ignore the diploid nature of the human genome because they do not routinely separate or 'phase' maternally and paternally derived sequence information. However, many findings - both from recent studies and in the more established medical genetics literature - indicate that relationships between human DNA sequence and phenotype, including disease, can be more fully understood with phase information. Thus, the existing technological impediments to obtaining phase information must be overcome if human genomics is to reach its full potential.