Infant and Child Mortality in India in the Last Two Decades: A Geospatial Analysis

Studies examining the intricate interplay between poverty, female literacy, child malnutrition, and child mortality are rare in demographic literature. Given the recent focus on Millennium Development Goals 4 (child survival) and 5 (maternal health), we explored whether the geographic regions that were underprivileged in terms of wealth, female literacy, child nutrition, or safe delivery were also grappling with the elevated risk of child mortality; whether there were any spatial outliers; whether these relationships have undergone any significant change over historical time periods.The present paper attempted to investigate these critical questions using data from household surveys like NFHS 1992-1993, NFHS 1998-1999 and DLHS 2002-2004. For the first time, we employed geo-spatial techniques like Moran's-I, univariate LISA, bivariate LISA, spatial error regression, and spatiotemporal regression to address the research problem. For carrying out the geospatial analysis, we classified India into 76 natural regions based on the agro-climatic scheme proposed by Bhat and Zavier (1999) following the Census of India Study and all estimates were generated for each of the geographic regions.This study brings out the stark intra-state and inter-regional disparities in infant and under-five mortality in India over the past two decades. It further reveals, for the first time, that geographic regions that were underprivileged in child nutrition or wealth or female literacy were also likely to be disadvantaged in terms of infant and child survival irrespective of the state to which they belong. While the role of economic status in explaining child malnutrition and child survival has weakened, the effect of mother's education has actually become stronger over time

The Influence of cis-Regulatory Elements on DNA Methylation Fidelity

It is now established that, as compared to normal cells, the cancer cell genome has an overall inverse distribution of DNA methylation (“methylome”), i.e., predominant hypomethylation and localized hypermethylation, within “CpG islands” (CGIs). Moreover, although cancer cells have reduced methylation “fidelity” and genomic instability, accurate maintenance of aberrant methylomes that underlie malignant phenotypes remains necessary. However, the mechanism(s) of cancer methylome maintenance remains largely unknown. Here, we assessed CGI methylation patterns propagated over 1, 3, and 5 divisions of A2780 ovarian cancer cells, concurrent with exposure to the DNA cross-linking chemotherapeutic cisplatin, and observed cell generation-successive increases in total hyper- and hypo-methylated CGIs. Empirical Bayesian modeling revealed five distinct modes of methylation propagation: (1) heritable (i.e., unchanged) high- methylation (1186 probe loci in CGI microarray); (2) heritable (i.e., unchanged) low-methylation (286 loci); (3) stochastic hypermethylation (i.e., progressively increased, 243 loci); (4) stochastic hypomethylation (i.e., progressively decreased, 247 loci); and (5) considerable “random” methylation (582 loci). These results support a “stochastic model” of DNA methylation equilibrium deriving from the efficiency of two distinct processes, methylation maintenance and de novo methylation. A role for cis-regulatory elements in methylation fidelity was also demonstrated by highly significant (p<2.2×10−5) enrichment of transcription factor binding sites in CGI probe loci showing heritably high (118 elements) and low (47 elements) methylation, and also in loci demonstrating stochastic hyper-(30 elements) and hypo-(31 elements) methylation. Notably, loci having “random” methylation heritability displayed nearly no enrichment. These results demonstrate an influence of cis-regulatory elements on the nonrandom propagation of both strictly heritable and stochastically heritable CGIs

Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies

The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only) in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-κB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway