Mortality burden and socioeconomic status in India

Background

The dimensions along which mortality is patterned in India remains unclear. We examined the specific contribution of social castes, household income, assets, and monthly per capita consumption to mortality differentials in India.

Methods and Findings

Cross-sectional data on 217 363 individuals from 41 554 households from the 2004–2005 India Human Development Survey was analyzed using multiple logistic regressions. Mortality differentials across social castes were attenuated after adjusting for household economic factors such as income and assets. Individuals living in the lowest income and assets quintiles had an increased risk of mortality with odds ratio (OR) of 1.66 (95% CI  = 1.23–2.24) in the bottom income quintile and OR of 2.94 (95% CI  = 1.66–5.22) in the bottom asset quintile. Counter-intuitively, individuals living in households with lowest monthly consumption per capita had significantly lower probability of death (OR  = 0.27, 95% CI  = 0.20–0.38).

Conclusions

Mortality burden in India is largely patterned on economic dimensions as opposed to caste dimensions, though caste may play an important role in predicting economic opportunities.     

RTL551 treatment of EAE reduces CD226 and T-bet+ CD4 T cells in periphery and prevents infiltration of T-bet+ IL-17, IFN-γ producing T cells into CNS

Recombinant T cell receptor ligands (RTLs) that target encephalitogenic T-cells can reverse clinical and histological signs of EAE, and are currently in clinical trials for treatment of multiple sclerosis. To evaluate possible regulatory mechanisms, we tested effects of RTL therapy on expression of pathogenic and effector T-cell maturation markers, CD226, T-bet and CD44, by CD4+ Th1 cells early after treatment of MOG-35-55 peptide-induced EAE in C57BL/6 mice. We showed that 1-5 daily injections of RTL551 (two-domain I-A(b) covalently linked to MOG-35-55 peptide), but not the control RTL550 ("empty" two-domain I-A(b) without a bound peptide) or Vehicle, reduced clinical signs of EAE, prevented trafficking of cells outside the spleen, significantly reduced the frequency of CD226 and T-bet expressing CD4+ T-cells in blood and inhibited expansion of CD44 expressing CD4+ T-cells in blood and spleen. Concomitantly, RTL551 selectively reduced CNS inflammatory lesions, absolute numbers of CNS infiltrating T-bet expressing CD4+ T-cells and IL-17 and IFN-γ secretion by CNS derived MOG-35-55 reactive cells cultured ex vivo. These novel results demonstrate that a major effect of RTL therapy is to attenuate Th1 specific changes in CD4+ T-cells during EAE and prevent expansion of effector T-cells that mediate clinical signs and CNS inflammation in EAE.     

Rapid genotyping of soybean cultivars using high throughput sequencing

Soybean (Glycine max) breeding involves improving commercially grown varieties by introgressing important agronomic traits from poor yielding accessions and/or wild relatives of soybean while minimizing the associated yield drag. Molecular markers associated with these traits are instrumental in increasing the efficiency of producing such crosses and Single Nucleotide Polymorphisms (SNPs) are particularly well suited for this task, owing to high density in the non-genic regions and thus increased likelihood of finding a tightly linked marker to a given trait. A rapid method to develop SNP markers that can differentiate specific loci between any two parents in soybean is thus highly desirable. In this study we investigate such a protocol for developing SNP markers between multiple soybean accessions and the reference Williams 82 genome. To restrict sampling frequency reduced representation libraries (RRLs) of genomic DNA were generated by restriction digestion followed by library construction. We chose to sequence four accessions Dowling (PI 548663), Dwight (PI 597386), Komata (PI200492) and PI 594538A for their agronomic importance as well as Williams 82 as a control.MseI was chosen to digest genomic DNA based on predictions that it will cut sparingly in the mathematically defined high-copy-number regions of the genome. All RRLs were sequenced on the Illumina genome analyzer. Reads were aligned to the Glyma1 reference assembly and SNP calls made from the alignments. We identified from 4294 to 14550 SNPs between the four accessions and the Williams 82 reference. In addition a small number of SNPs (1142) were found by aligning Williams 82 reads to the reference assembly (Glyma1) suggesting limited genetic variation within the Williams 82 line. The SNP data allowed us to estimate genetic diversity between the four lines and Williams 82. Restriction digestion of soybean genomic DNA with MseI followed by high throughput sequencing provides a rapid and reproducible method for generating SNP markers.     

Crystal structure of the PAC1R extracellular domain unifies a consensus fold for hormone recognition by class B G-protein coupled receptors

Pituitary adenylate cyclase activating polypeptide (PACAP) is a member of the PACAP/glucagon family of peptide hormones, which controls many physiological functions in the immune, nervous, endocrine, and muscular systems. It activates adenylate cyclase by binding to its receptor, PAC1R, a member of class B G-protein coupled receptors (GPCR). Crystal structures of a number of Class B GPCR extracellular domains (ECD) bound to their respective peptide hormones have revealed a consensus mechanism of hormone binding. However, the mechanism of how PACAP binds to its receptor remains controversial as an NMR structure of the PAC1R ECD/PACAP complex reveals a different topology of the ECD and a distinct mode of ligand recognition. Here we report a 1.9 Å crystal structure of the PAC1R ECD, which adopts the same fold as commonly observed for other members of Class B GPCR. Binding studies and cell-based assays with alanine-scanned peptides and mutated receptor support a model that PAC1R uses the same conserved fold of Class B GPCR ECD for PACAP binding, thus unifying the consensus mechanism of hormone binding for this family of receptors.     

A bioinformatics approach for determining sample identity from different lanes of high-throughput sequencing data

The ability to generate whole genome data is rapidly becoming commoditized. For example, a mammalian sized genome (～3Gb) can now be sequenced using approximately ten lanes on an Illumina HiSeq 2000. Since lanes from different runs are often combined, verifying that each lane in a genome's build is from the same sample is an important quality control. We sought to address this issue in a post hoc bioinformatic manner, instead of using upstream sample or "barcode" modifications. We rely on the inherent small differences between any two individuals to show that genotype concordance rates can be effectively used to test if any two lanes of HiSeq 2000 data are from the same sample. As proof of principle, we use recent data from three different human samples generated on this platform. We show that the distributions of concordance rates are non-overlapping when comparing lanes from the same sample versus lanes from different samples. Our method proves to be robust even when different numbers of reads are analyzed. Finally, we provide a straightforward method for determining the gender of any given sample. Our results suggest that examining the concordance of detected genotypes from lanes purported to be from the same sample is a relatively simple approach for confirming that combined lanes of data are of the same identity and quality.     

Structural and biophysical characterization of Mycobacterium tuberculosis dodecin Rv1498A

Dodecins (assembly of twelve monomers) are the smallest known flavoprotein with only 65-73 amino acids and are involved in binding and storage of flavins in archaea. Here we report the crystal structure of Rv1498A, a Mycobacterium tuberculosis dodecin. This bacterial dodecin structure is similar to that of other reported dodecins. Each monomer has a 3 stranded β-sheet and an α-helix perpendicular to it. This protein has polyextreme (halophilic and thermophilic) properties. Interestingly, positively and negatively charged residues aggregate separately and do not seem to contribute to thermophilic and halophilic stability. We have examined the interactions that stabilize the Rv1498A dodecamer by preparing selected point mutants that break salt bridges and hydrophobic contacts, thereby leading to collapse of the assembly.     

Environmental Profile of a Community's Health (EPOCH): An Ecometric Assessment of Measures of the Community Environment Based on Individual Perception

BACKGROUND: Public health research has turned towards examining upstream, community-level determinants of cardiovascular disease risk factors. Objective measures of the environment, such as those derived from direct observation, and perception-based measures by residents have both been associated with health behaviours. However, current methods are generally limited to objective measures, often derived from administrative data, and few instruments have been evaluated for use in rural areas or in low-income countries. We evaluate the reliability of a quantitative tool designed to capture perceptions of community tobacco, nutrition, and social environments obtained from interviews with residents in communities in 5 countries. METHODOLOGY/ PRINCIPAL FINDINGS: Thirteen measures of the community environment were developed from responses to questionnaire items from 2,360 individuals residing in 84 urban and rural communities in 5 countries (China, India, Brazil, Colombia, and Canada) in the Environmental Profile of a Community's Health (EPOCH) study. Reliability and other properties of the community-level measures were assessed using multilevel models. High reliability (>0.80) was demonstrated for all community-level measures at the mean number of survey respondents per community (n?=?28 respondents). Questionnaire items included in each scale were found to represent a common latent factor at the community level in multilevel factor analysis models. CONCLUSIONS/ SIGNIFICANCE: Reliable measures which represent aspects of communities potentially related to cardiovascular disease (CVD)/risk factors can be obtained using feasible sample sizes. The EPOCH instrument is suitable for use in different settings to explore upstream determinants of CVD/risk factors.     

Poverty in the Midst of Plenty: Unmet Needs and Distribution of Health Care Resources in South Korea

Background

The unmet needs for health care have been used as an alternative measurement to monitor equity in health services. We sought to examine contextual influences on unmet needs for health care whereas precedent studies have been focused on individual characteristics on them.

Methods and Findings

The current study conducted multilevel logistic regression analysis to assess the effects of individual- and contextual-level predictors in meeting individual health care needs in South Korea. We sampled 7,200 individuals over the age of 19 in the Fourth Korea National Health and Nutrition Examination Survey in 2009. Included in the regression model were individual predictors such as demographic variables, socio-economic status, and self-rated health; the density of beds and physicians in public and private sectors within different regions were used as contextual-level predictors. This study showed the inverse association between unmet needs and regional resources in private sectors after controlling for the effects of individual-level predictors.

Conclusion

Our findings suggest that increasing regional resources in private sectors might produce inefficiency in the health care system and inequity in access to health services, particularly where the competition in private health care sectors was highly stimulated under the fee-for-service reimbursement scheme. Policies for the reallocation of health care resources and for reduction of individual health care costs are needed in Korea.