Spectrum of large copy number variations in 26 diverse Indian populations: potential involvement in phenotypic diversity

Copy number variations (CNVs) have provided a dynamic aspect to the apparently static human genome. We have analyzed CNVs larger than 100 kb in 477 healthy individuals from 26 diverse Indian populations of different linguistic, ethnic and geographic backgrounds. These CNVRs were identified using the Affymetrix 50K Xba 240 Array. We observed 1,425 and 1,337 CNVRs in the deletion and amplification sets, respectively, after pooling data from all the populations. More than 50% of the genes encompassed entirely in CNVs had both deletions and amplifications. There was wide variability across populations not only with respect to CNV extent (ranging from 0.04–1.14% of genome under deletion and 0.11–0.86% under amplification) but also in terms of functional enrichments of processes like keratinization, serine proteases and their inhibitors, cadherins, homeobox, olfactory receptors etc. These did not correlate with linguistic, ethnic, geographic backgrounds and size of populations. Certain processes were near exclusive to deletion (serine proteases, keratinization, olfactory receptors, GPCRs) or duplication (homeobox, serine protease inhibitors, embryonic limb morphogenesis) datasets. Populations having same enriched processes were observed to contain genes from different genomic loci. Comparison of polymorphic CNVRs (5% or more) with those cataloged in Database of Genomic Variants revealed that 78% (2473) of the genes in CNVRs in Indian populations are novel. Validation of CNVs using Sequenom MassARRAY revealed extensive heterogeneity in CNV boundaries. Exploration of CNV profiles in such diverse populations would provide a widely valuable resource for understanding diversity in phenotypes and disease.     

Cockroach wings-promoted safe and greener synthesis of silver nanoparticles and their insecticidal activity

Bioprocess and Biosystems Engineering - Simpler and biocompatible greener approaches for the assembly of nanoparticles (NPs) have been the focus lately which have minimum environmental damage and...     

Development and characterization of lipidic cochleate containing recombinant factor VIII

Hemophilia A, a life-threatening bleeding disorder, is caused by deficiency of factor VIII (FVIII). Replacement therapy using rFVIII is the first line therapy for hemophilia A. However, 15-30% of patients develop neutralizing antibody, mainly against the C2, A3 and A2 domains. It has been reported that PS-FVIII complex reduced total and neutralizing anti-rFVIII antibody titers in hemophilia A murine models. Here, we developed FVIII-containing cochleate cylinders, utilizing PS-Ca(2+) interactions and characterized these particles for optimal in vivo properties using biophysical and biochemical techniques. Approximately 75% of the protein was associated with cochleate cylinders. Sandwich ELISA, acrylamide quenching and enzymatic digestion studies established that rFVIII was shielded from the bulk aqueous phase by the lipidic structures, possibly leading to improved in vivo stability. Freeze-thawing and rate-limiting diffusion studies revealed that small cochleate cylinders with a particle size of 500 nm or less could be generated. The release kinetics and in vivo experiments suggested that there is slow and sustained release of FVIII from the complex upon systemic exposure. In vivo studies using tail clip method indicated that FVIII-cochleate complex is effective and protects hemophilic mice from bleeding. Based on these studies, we speculate that the molecular interaction between FVIII and PS may provide a basis for the design of novel FVIII lipidic structures for delivery applications.     

Phytofabricated zinc oxide nanoparticles as a nanofungicide for management of Alternaria blight of Brassica

BioMetals - Plant pathogens resistant to the commercially available fungicides and bactericides even at higher concentrations are the biggest challenge for the farmers to control the losses due to...     

Broadband Reflection Minimization Using Silver Ultra Thin Film Sandwiched Between Silicon Nitride Layers for c-Si Solar Cell Application

Wafer thickness reduction is the main trend for cost reduction of crystalline silicon (c-Si) solar cells. For better light trapping in lower thickness wafers where traditional texturization method may not be promising, alternative techniques are being explored. Here, reflection minimization using silver ultra thin film sandwiched between silicon nitride (SiN_x) antireflection coating (ARC) layers on c-Si substrate is reported. SiN_x ARC layers were deposited by plasma-enhanced chemical vapor deposition (PECVD) and silver ultra thin film by e-beam evaporation; 41 % reflection reduction for silver ultra thin film sandwiched in SiN_x ARC layers as compared to standard 80 nm thin SiN_x ARC on c-Si substrate is shown. The sandwiched structure gives 8.1 % weighted total reflectance for wavelength range of 300–1,200 nm as compared to standard 80-nm SiN_x-based ARC which gives 13.8 %. Also, comparison of this Ag ultra thin film-based sandwiched geometry is done with randomly distributed nanoparticle (NP)-based ARC geometry. It is shown that optically, the sandwiched Ag ultra thin film-based device geometry is more promising than Ag NP-based device geometry and standard 80-nm SiN_x-based geometry for broad wavelength range of 300–1,200 nm.     

Longevity and Plasticity of CFTR Provide an Argument for Noncanonical SNP Organization in Hominid DNA

Like many other ancient genes, the cystic fibrosis transmembrane conductance regulator (CFTR) has survived for hundreds of millions of years. In this report, we consider whether such prodigious longevity of an individual gene – as opposed to an entire genome or species – should be considered surprising in the face of eons of relentless DNA replication errors, mutagenesis, and other causes of sequence polymorphism. The conventions that modern human SNP patterns result either from purifying selection or random (neutral) drift were not well supported, since extant models account rather poorly for the known plasticity and function (or the established SNP distributions) found in a multitude of genes such as CFTR. Instead, our analysis can be taken as a polemic indicating that SNPs in CFTR and many other mammalian genes may have been generated—and continue to accrue—in a fundamentally more organized manner than would otherwise have been expected. The resulting viewpoint contradicts earlier claims of ‘directional’ or ‘intelligent design-type’ SNP formation, and has important implications regarding the pace of DNA adaptation, the genesis of conserved non-coding DNA, and the extent to which eukaryotic SNP formation should be viewed as adaptive.