Socioeconomic Inequalities in Childhood Undernutrition in India: Analyzing Trends between 1992 and 2005

Background

India experienced a rapid economic boom between 1991 and 2007. However, this economic growth has not translated into improved nutritional status among young Indian children. Additionally, no study has assessed the trends in social disparities in childhood undernutrition in the Indian context. We examined the trends in social disparities in underweight and stunting among Indian children aged less than three years using nationally representative data.

Methods

We analyzed data from the three cross-sectional rounds of National Family Health Survey of India from 1992, 1998 and 2005. The social factors of interest were: household wealth, maternal education, caste, and urban residence. Using multilevel modeling to account for the nested structure and clustering of data, we fit multivariable logistic regression models to quantify the association between the social factors and the binary outcome variables. The final models additionally included age, gender, birth order of child, religion, and age of mother. We analyzed the trend by testing for interaction of the social factor and survey year in a dataset pooled from all three surveys.

Results

While the overall prevalence rates of undernutrition among Indian children less than three decreased over the 1992–2005 period, social disparities in undernutrition over these 14 years either widened or stayed the same. The absolute rates of undernutrition decreased for everyone regardless of their social status. The disparities by household wealth were greater than the disparities by maternal education. There were no disparities in undernutrition by caste, gender or rural residence.

Conclusions

There was a steady decrease in the rates of stunting in the 1992–2005 period, while the decline in underweight was greater between 1992 and 1998 than between 1998 and 2005. Social disparities in childhood undernutrition in India either widened or stayed the same during a time of major economic growth. While the advantages of economic growth might be reaching everyone, children from better-off households, with better educated mothers appear to have benefited to a greater extent than less privileged children. The high rates of undernutrition (even among the socially advantaged groups) and the persistent social disparities need to be addressed in an urgent and comprehensive manner.     

Formation of transient amorphous calcium carbonate precursor in quail eggshell mineralization: an in vitro study

To understand the mechanism of quail eggshell biomineralization, we have performed two CaCO(3) precipitation experiments. In the reprecipitation experiments, supersaturated Ca(HCO(3))(2) was prepared by bubbling CO(2) through a slurry of biogenic CaCO(3) obtained from bleach-treated eggshell followed by filtration to obtain a clear solution for crystallization experiments. The nucleated crystals were collected at various time intervals and analyzed. In the second experiment, the extracted SOM from the bleach-treated eggshell was added to the supersaturated clear solution of Ca(HCO(3))(2) solution obtained by bubbling CO(2) gas through a slurry of synthetic CaCO(3) followed by filtration. The crystals/precipitates collected at various time intervals were analyzed. Both experiments showed that amorphous CaCO(3) (ACC) was precipitated in the early stages, which then transformed to the most stable crystalline calcite phase. Amino acid analysis of the soluble organic matrixes (SOM) indicated the presence of high amounts of Glx and Asx amino acids. Ovomucoid--an acidic glycoprotein, and lysozyme--a basic protein, are the two major components along with a few low molecular weight peptides present in the SOM of quail eggshell matrix. Both ovomucoid and lysozyme did not induce precipitation of the ACC phase in in vitro conditions, while the fraction containing low molecular weight peptides induced the precipitation of ACC, suggesting that the latter play an important role in the eggshell biomineralization. Thus, organisms can produce inorganic minerals which assume nonequilibrium morphologies and intricate architecture by precipitating transient ACC, which then transformed into the crystalline phase. Altogether, these observations further demonstrate that this strategy may be common in both vertebrate and invertebrate mineralized structures.     

Characterization of calcineurin-dependent response element binding protein and its involvement in copper-metallothionein gene expression in Neurospora

In continuation of our recent observations indicating the presence of a lone calcineurin-dependent response element (CDRE) in the -3730bp upstream region of copper-induced metallothionein (CuMT) gene of Neurospora [K.S. Kumar, S. Dayananda, C. Subramanyam, Copper alone, but not oxidative stress, induces copper-metallothionein gene in Neurospora crassa, FEMS Microbiol. Lett. 242 (2005) 45-50], we isolated and characterized the CDRE-binding protein. The cloned upstream region of CuMT gene was used as the template to specifically amplify CDRE element, which was immobilized on CNBr-activated Sepharose 4B for use as the affinity matrix to purify the CDRE binding protein from nuclear extracts obtained from Neurospora cultures grown in presence of copper. Two-dimensional gel electrophoresis of the affinity purified protein revealed the presence of a single 17kDa protein, which was identified and characterized by MALDI-TOF. Peptide mass finger printing of tryptic digests and analysis of the 17kDa protein matched with the regulatory beta-subunit of calcineurin (Ca(2+)-calmodulin dependent protein phosphatase). Parallel identification of nuclear localization signals in this protein by in silico analysis suggests a putative role for calcineurin in the regulation of CuMT gene expression.     

Susceptibility of Plodia interpunctella (Lepidoptera: Pyralidae) developmental stages to high temperatures used during structural heat treatments

Heating the ambient air of a whole, or a portion of a food-processing facility to 50 to 60 degrees C and maintaining these elevated temperatures for 24 to 36 h, is an old technology, referred to as heat treatment. There is renewed interest in adopting heat treatments around the world as a viable insect control alternative to fumigation with methyl bromide. There is limited published information on responses of the Indian meal moth, Plodia interpunctella (Hübner), exposed to elevated temperatures typically used during heat treatments. Time-mortality relationships were determined for eggs, fifth-instars (wandering-phase larvae), pupae, and adults of P. interpunctella exposed to five constant temperatures between 44 and 52 degrees C. Mortality of each stage increased with increasing temperature and exposure time. In general, fifth-instars were the most heat-tolerant stage at all temperatures tested. Exposure for a minimum of 34 min at 50 degrees C was required to kill 99% of the fifth-instars. It is proposed that heat treatments aimed at controlling fifth-instars should be able to control all other stages of P. interpunctella.     

Crystal structure of phosphatidylglycerophosphatase (PGPase), a putative membrane-bound lipid phosphatase, reveals a novel binuclear metal binding site and two "proton wires"

Phosphatidylglycerophosphatase (PGPase), an enzyme involved in lipid metabolism, catalyzes formation of phosphatidylglycerol from phosphatidylglycerophosphate. Phosphatidylglycerol is a multifunctional phospholipid, found in the biological membranes of many organisms. Here, we report the crystal structure of Listeria monocytogenes PGPase at 1.8 A resolution. PGPase, an all-helical molecule, forms a homotetramer. Each protomer contains an independent active site with two metal ions, Ca(2+) and Mg(2+), forming a hetero-binuclear center located in a hydrophilic cavity near the surface of the molecule. The binuclear center, conserved ligands, metal-bound water molecules, and an Asp-His dyad form the active site. The catalytic mechanism of this enzyme is likely to proceed via binuclear metal activated nucleophilic water. The binuclear metal-binding active-site environment of this structure should provide insights into substrate binding and metal-dependent catalysis. A long channel with inter-linked linear water chains, termed "proton wires," is observed at the tetramer interface. Comparison of similar water chain structures in photosynthetic reaction centers (RCs), Cytochrome f, gramicidin, and bacteriorhodopsin, suggests that PGPase may conduct protons via proton wires.     

Biochemical analysis of oxidative stress in the production of aflatoxin and its precursor intermediates

The relevance of oxidative stress in the production of aflatoxin and its precursors was examined in different mutants of Aspergillus parasiticus, which produce aflatoxin or its precursor intermediates, and compared with results obtained from a non-toxigenic strain. In comparison to the non-toxigenic strain (SRRC 255), an aflatoxin producing strain (NRRL 2999) or mutants that accumulate aflatoxin precursors such as norsolorinic acid (by SRRC 162) or versicolorin (by NRRL 6196) or O-methyl sterigmatocystin (by SRRC 2043) had greater oxygen requirements and higher contents of reactive oxygen species. These changes were in the graded order of NRRL 2999 > SRRC 2043 > NRRL 6196 > SRRC 162 > SRRC 255, indicating incremental accumulation of reactive oxygen species, being least in the non-toxigenic strain and increasing progressively during the ternary steps of aflatoxin formation. Oxidative stress in these strains was evident by increased activities of xanthine oxidase and free radical scavenging enzymes (superoxide dismutase and glutathione peroxidase) as compared to the non-toxigenic strain (SRRC 255). Culturing the toxigenic strain in presence of 0.1–10 μM H₂O₂ in the medium resulted in enhanced aflatoxin production, which could be related to dose-dependent increase in [¹⁴C]-acetate incorporation into aflatoxin B₁ and increased acetyl CoA carboxylase activity. The combined results suggest that formation of secondary metabolites such as aflatoxin and its precursors by A. parasiticus may occur as a compensatory response to reactive oxygen species accumulation.     

Structure- and substrate-based inhibitor design for Clostridium botulinum neurotoxin serotype A

The seven antigenically distinct serotypes of Clostridium botulinum neurotoxins cleave specific soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex proteins and block the release of neurotransmitters that cause flaccid paralysis and are considered potential bioweapons. Botulinum neurotoxin type A is the most potent among the clostridial neurotoxins, and to date there is no post-exposure therapeutic intervention available. To develop inhibitors leading to drug design, it is imperative that critical interactions between the enzyme and the substrate near the active site are known. Although enzyme-substrate interactions at exosites away from the active site are mapped in detail for botulinum neurotoxin type A, information about the active site interactions is lacking. Here, we present the crystal structures of botulinum neurotoxin type A catalytic domain in complex with four inhibitory substrate analog tetrapeptides, viz. RRGC, RRGL, RRGI, and RRGM at resolutions of 1.6-1.8 A. These structures show for the first time the interactions between the substrate and enzyme at the active site and delineate residues important for substrate stabilization and catalytic activity. We show that OH of Tyr(366) and NH(2) of Arg(363) are hydrogen-bonded to carbonyl oxygens of P1 and P1' of the substrate analog and position it for catalytic activity. Most importantly, the nucleophilic water is replaced by the amino group of the N-terminal residue of the tetrapeptide. Furthermore, the S1' site is formed by Phe(194), Thr(215), Thr(220), Asp(370), and Arg(363). The K(i) of the best inhibitory tetrapeptide is 157 nm.