Gender discrimination in undernutrition with mediating factors among Bengalee school children from Eastern India

This study was undertaken to determine age and sex variations in the prevalence of underweight and stunting, and to assess the impact of some socio-economic variables on undernutrition among 6–16 year old school children of Bengalee ethnicity in Chapra, West Bengal, India. The subjects were selected randomly from various schools and madrassas of the Chapra Block. A total of 725 children (342 boys and 383 girls) aged 6–16 years were measured and data on their socio-economic status were collected. Age and sex combined rates of underweight and stunting were 44.40% and 37.20%, respectively. Weight-for-age Z-score (WAZ) showed significant association with per-capita income (PCI) among boys (F = 5.45) and girls (F = 8.14). Height-for-age Z-score (HAZ) has also shown the association with per-capita income among boys (F = 4.43) and girls (F = 9.69). The WAZ was significantly associated with fathers’ educational status (FOS) (t = ?2.95) and the number of living rooms (NLR) (t = ?2.91) among girls. The HAZ showed significant association with number of siblings (NS) among girls (F = 4.25). Linear regression analyses revealed that NLR (t = 2.04) and NS (t = 1.95) had a significant impact on HAZ among boys. Among girls, PCI (t = 3.38), FOS (t = 2.87) and NLR (t = 2.81) had a significant impact on WAZ and also PCI (t = 3.28) and FOS (t = 2.90) had a significant impact on HAZ. NLR had significant associations with underweight (χ² = 3.59) and stunting (χ² = 4.20) among boys. Among girls, PCI had significant associations with underweight (χ² = 11.15) and stunting (χ² = 11.64). FOS also showed significant associations with underweight (χ² = 8.10) as well as stunting (χ² = 8.28) among girls. NLR showed a significant association with underweight (χ² = 7.75). Logistics regression analyses revealed that FOS (Wald = 8.00) and NLR (Wald = 4.09) were significant predictors of stunting among boys. Among girls, PCI was a significant predictor of underweight (Wald = 10.95) as well as stunting (Wald = 10.45). FOS, NLR and NS were also significant predictors of stunting (Wald = 8.16), underweight (Wald = 7.68) and stunting (Wald = 6.97) respectively. The present study revealed that the nutritional status of the children was unsatisfactory and it is of paramount importance not only to increase the amount of food supplementation given but also to promote gender equality.     

Conserved Ser/Arg-rich motif in PPZ orthologs from fungi is important for its role in cation tolerance

PPZ1 orthologs, novel members of a phosphoprotein phosphatase family of phosphatases, are found only in fungi. They regulate diverse physiological processes in fungi e.g. ion homeostasis, cell size, cell integrity, etc. Although they are an important determinant of salt tolerance in fungi, their physiological role remained unexplored in any halotolerant species. In this context we report here molecular and functional characterization of DhPPZ1 from Debaryomyces hansenii, which is one of the most halotolerant and osmotolerant species of yeast. Our results showed that DhPPZ1 knock-out strain displayed higher tolerance to toxic cations, and unlike in Saccharomyces cerevisiae, Na(+)/H(+) antiporter appeared to have an important role in this process. Besides salt tolerance, DhPPZ1 also had role in cell wall integrity and growth in D. hansenii. We have also identified a short, serine-arginine-rich sequence motif in DhPpz1p that is essential for its role in salt tolerance but not in other physiological processes. Taken together, these results underscore a distinct role of DhPpz1p in D. hansenii and illustrate an example of how organisms utilize the same molecular tool box differently to garner adaptive fitness for their respective ecological niches.     

Molecular tagging of a rust resistance gene in cultivated groundnut (Arachis hypogaea L.) introgressed from Arachis cardenasii

Rust is a serious and the most prevalent groundnut disease in tropical and subtropical growing regions of the world. A total of 164 recombinant inbred lines derived from resistant (VG 9514) and susceptible (TAG 24) cultivated groundnut parents were screened for rust resistance in five environments. Subsequent genotyping of these lines with 109 simple sequence repeat (SSR) markers generated a genetic linkage map with 24 linkage groups. The total length of the linkage map was 882.9 cM with an average of 9.0 cM between neighbouring markers. The markers pPGPseq4A05 and gi56931710 flanked the rust resistance gene at map distances of 4.7 cM and 4.3 cM, respectively, in linkage group 2. The significant association of these two markers with the rust reaction was also confirmed by discriminant analysis. The informative SSR markers classified rust-resistant and susceptible groups with 99.97% correctness. The SSR markers pPGPseq4A05 and gi56931710 were able to identify all the susceptible genotypes from a set of 20 cultivated genotypes differing in rust reaction. Tagging of the rust resistance locus with linked SSR markers will be useful in selecting the rust resistant genotypes from segregating populations and in introgressing the rust resistance genes from diploid wild species.     

Tex14, a Plk1-regulated protein, is required for kinetochore-microtubule attachment and regulation of the spindle assembly checkpoint

Proper assembly of kinetochores (KTs) during mitosis is required for bipolar attachment of spindle microtubules (MTs) and the accumulation of spindle assembly checkpoint (SAC) components. Here we show that testis-expressed protein 14 (Tex14), which has been implicated in midbody function, is recruited to KTs by Plk1 in a Cdk1-dependent manner during early mitosis. Exclusion of Tex14 from kinetochores results in an inability to efficiently localize outer KT components, impaired KT-MT attachment, chromosome congression defects, and whole-chromosome instability. In addition, we demonstrate that phosphorylation of Tex14 by Plk1 during metaphase promotes APC(Cdc20)-mediated Tex14 degradation. Inhibition of this phosphorylation event causes retention of Tex14 at KTs and results in delayed metaphase-to-anaphase transition and chromosome segregation defects. Our findings identify Tex14 as an important mediator of KT structure and function and the fidelity of chromosome separation.     

Uncertainties in Measuring Populations Potentially Impacted by Sea Level Rise and Coastal Flooding

A better understanding of the impact of global climate change requires information on the locations and characteristics of populations affected. For instance, with global sea level predicted to rise and coastal flooding set to become more frequent and intense, high-resolution spatial population datasets are increasingly being used to estimate the size of vulnerable coastal populations. Many previous studies have undertaken this by quantifying the size of populations residing in low elevation coastal zones using one of two global spatial population datasets available – LandScan and the Global Rural Urban Mapping Project (GRUMP). This has been undertaken without consideration of the effects of this choice, which are a function of the quality of input datasets and differences in methods used to construct each spatial population dataset. Here we calculate estimated low elevation coastal zone resident population sizes from LandScan and GRUMP using previously adopted approaches, and quantify the absolute and relative differences achieved through switching datasets. Our findings suggest that the choice of one particular dataset over another can translate to a difference of more than 7.5 million vulnerable people for countries with extensive coastal populations, such as Indonesia and Japan. Our findings also show variations in estimates of proportions of national populations at risk range from <0.1% to 45% differences when switching between datasets, with large differences predominantly for countries where coarse and outdated input data were used in the construction of the spatial population datasets. The results highlight the need for the construction of spatial population datasets built on accurate, contemporary and detailed census data for use in climate change impact studies and the importance of acknowledging uncertainties inherent in existing spatial population datasets when estimating the demographic impacts of climate change.     

Co-Factor Binding Confers Substrate Specificity to Xylose Reductase from Debaryomyces hansenii

Binding of substrates into the active site, often through complementarity of shapes and charges, is central to the specificity of an enzyme. In many cases, substrate binding induces conformational changes in the active site, promoting specific interactions between them. In contrast, non-substrates either fail to bind or do not induce the requisite conformational changes upon binding and thus no catalysis occurs. In principle, both lock and key and induced-fit binding can provide specific interactions between the substrate and the enzyme. In this study, we present an interesting case where cofactor binding pre-tunes the active site geometry to recognize only the cognate substrates. We illustrate this principle by studying the substrate binding and kinetic properties of Xylose Reductase from Debaryomyces hansenii (DhXR), an AKR family enzyme which catalyzes the reduction of carbonyl substrates using NADPH as co-factor. DhXR reduces D-xylose with increased specificity and shows no activity towards “non-substrate” sugars like L-rhamnose. Interestingly, apo-DhXR binds to D-xylose and L-rhamnose with similar affinity (K_d∼5.0–10.0 mM). Crystal structure of apo-DhXR-rhamnose complex shows that L-rhamnose is bound to the active site cavity. L-rhamnose does not bind to holo-DhXR complex and thus, it cannot competitively inhibit D-xylose binding and catalysis even at 4–5 fold molar excess. Comparison of K_d values with K_m values reveals that increased specificity for D-xylose is achieved at the cost of moderately reduced affinity. The present work reveals a latent regulatory role for cofactor binding which was previously unknown and suggests that cofactor induced conformational changes may increase the complimentarity between D-xylose and active site similar to specificity achieved through induced-fit mechanism.     

Characterization of Tannase Protein Sequences of Bacteria and Fungi: An In Silico Study

The tannase protein sequences of 149 bacteria and 36 fungi were retrieved from NCBI database. Among them only 77 bacterial and 31 fungal tannase sequences were taken which have different amino acid compositions. These sequences were analysed for different physical and chemical properties, superfamily search, multiple sequence alignment, phylogenetic tree construction and motif finding to find out the functional motif and the evolutionary relationship among them. The superfamily search for these tannase exposed the occurrence of proline iminopeptidase-like, biotin biosynthesis protein BioH, O-acetyltransferase, carboxylesterase/thioesterase 1, carbon–carbon bond hydrolase, haloperoxidase, prolyl oligopeptidase, C-terminal domain and mycobacterial antigens families and alpha/beta hydrolase superfamily. Some bacterial and fungal sequence showed similarity with different families individually. The multiple sequence alignment of these tannase protein sequences showed conserved regions at different stretches with maximum homology from amino acid residues 389–469 and 482–523 which could be used for designing degenerate primers or probes specific for tannase producing bacterial and fungal species. Phylogenetic tree showed two different clusters; one has only bacteria and another have both fungi and bacteria showing some relationship between these different genera. Although in second cluster near about all fungal species were found together in a corner which indicates the sequence level similarity among fungal genera. The distributions of fourteen motifs analysis revealed Motif 1 with a signature amino acid sequence of 29 amino acids, i.e. GCSTGGREALKQAQRWPHDYDGIIANNPA, was uniformly observed in 83.3 % of studied tannase sequences representing its participation with the structure and enzymatic function.     

Image-based modeling of hemodynamics in coronary artery aneurysms caused by Kawasaki disease

Kawasaki Disease (KD) is the leading cause of acquired pediatric heart disease. A subset of KD patients develops aneurysms in the coronary arteries, leading to increased risk of thrombosis and myocardial infarction. Currently, there are limited clinical data to guide the management of these patients, and the hemodynamic effects of these aneurysms are unknown. We applied patient-specific modeling to systematically quantify hemodynamics and wall shear stress in coronary arteries with aneurysms caused by KD. We modeled the hemodynamics in the aneurysms using anatomic data obtained by multi-detector computed tomography (CT) in a 10-year-old male subject who suffered KD at age 3?years. The altered hemodynamics were compared to that of a reconstructed normal coronary anatomy using our subject as the model. Computer simulations using a robust finite element framework were used to quantify time-varying shear stresses and particle trajectories in the coronary arteries. We accounted for the cardiac contractility and the microcirculation using physiologic downstream boundary conditions. The presence of aneurysms in the proximal coronary artery leads to flow recirculation, reduced wall shear stress within the aneurysm, and high wall shear stress gradients at the neck of the aneurysm. The wall shear stress in the KD subject (2.95-3.81 dynes/sq cm) was an order of magnitude lower than the normal control model (17.10-27.15 dynes/sq cm). Particle residence times were significantly higher, taking 5 cardiac cycles to fully clear from the aneurysmal regions in the KD subject compared to only 1.3 cardiac cycles from the corresponding regions of the normal model. In this novel quantitative study of hemodynamics in coronary aneurysms caused by KD, we documented markedly abnormal flow patterns that are associated with increased risk of thrombosis. This methodology has the potential to provide further insights into the effects of aneurysms in KD and to help risk stratify patients for appropriate medical and surgical interventions.     

Structural determinant of human La protein critical for internal initiation of translation of hepatitis C virus RNA

Human La protein has been implicated in facilitating internal ribosome entry site (IRES)-mediated translation of hepatitis C virus (HCV). Earlier, we demonstrated that the RNA recognition motif (RRM) encompassing residues 112 to 184 of La protein [La (112-184)] interacts with the HCV IRES near the initiator AUG codon. A synthetic peptide, LaR2C (24-mer), derived from La RRM (112-184), retains RNA binding ability, competes with La protein binding to the HCV IRES, and inhibits translation. The peptide interferes with the assembly of 48S complexes, resulting in the accumulation of preinitiation complexes that are incompetent for the 60S ribosomal subunit joining. Here, nuclear magnetic resonance spectroscopy of the HCV IRES-bound peptide complex revealed putative contact points, mutations that showed reduced RNA binding and translation inhibitory activity. The residues responsible for RNA recognition were found to form a turn in the RRM (112-184) structure. A 7-mer peptide comprising this turn showed significant translation inhibitory activity. The bound structure of the peptide inferred from transferred nuclear Overhauser effect experiments suggests that it is a β turn. This conformation is significantly different from that observed in the free RRM (112-184) NMR structure, suggesting paths toward a better-stabilized mimetic peptide. Interestingly, addition of hexa-arginine tag enabled the peptide to enter Huh7 cells and showed inhibition of HCV IRES function. More importantly, the peptide significantly inhibited replication of the HCV monocistronic replicon. Elucidation of the structural determinant of the peptide provides a basis for developing small peptidomimetic structures as potent anti-HCV therapeutics.     

Molecular identification and properties of a light-insensitive rice catalase-B expressed in E. coli

Catalase plays a central role in plant stress responses but is highly susceptible to photoinhibition. A rice catalase-B protein avoiding photoinhibition was developed by mutagenesis of specific amino acids: Leu-189 to Trp-189 and His-225 to Thr-225 and then recombinantly expressed in E. coli. In addition, the site specific mutation also induced 2–2.5-fold increase in enzyme velocity with high affinity for its substrate and showed nearly a 3-fold lower K _m than the wild protein. These characteristic of mutated rice catalase-B is highly promising in transgenic research to increase plant productivity under stress conditions.