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.     

Water-soluble formulation of Coenzyme Q10 inhibits Bax-induced destabilization of mitochondria in mammalian cells

Oxidative stress leads to mitochondrial dysfunction, which triggers the opening of the permeability transition pores (PTP) and the release of pro-apoptotic factors causing apoptotic cell death. In a limited number of cell systems, anti-oxidants and free-radical scavengers have been shown to block this response. We have previously reported that coenzyme Q₁₀ (CoQ₁₀), an electron carrier in the mitochondrial respiratory chain, is involved in the reactive oxygen species (ROS) removal and prevention of oxidative stress-induced apoptosis in neuronal cells. However, the mechanism of this protection has not been fully elucidated. In the present study we investigated the effects of CoQ₁₀ on the mitochondrial events characteristic to apoptosis, especially on the function of pro-apoptotic protein Bax. Our results demonstrated that following a brief exposure of two human cell lines (fibroblasts and HEK293 cells) to H₂O₂ the intracellular levels of ROS and the association of Bax with the mitochondria significantly increased and the cells underwent apoptosis. Both of these events, as well as the release of cytochrome c from the mitochondria, were blocked by a 24 h pre-treatment with CoQ₁₀. It is therefore believed that CoQ₁₀ prevented the collapse of the mitochondrial membrane potential in response to the H₂O₂ treatment. Recombinant Bax protein alone caused the ROS generation and release of cytochrome c from isolated mitochondria and, again, CoQ₁₀ inhibited these Bax-induced mitochondrial dysfunctions.     

A UV resonance Raman investigation of poly(rI): Evidence for cation-dependent structural perturbations

Poly(rI) stabilized by either Na⁺ or K⁺ was investigated using uv resonance Raman (UVRR) spectroscopy. Raman excitation profiles of inosine 5′-monophosphate demonstrated the 250 nm excitation selectively enhances base stacking interactions, while ribose and carbonyl stretching vibrations are preferentially enhanced with 210 nm excitation. These wavelengths were used to examine the structure of poly(rI) in the presence of either K⁺ or Na⁺ as a function of temperature. UVRR studies revealed that the K⁺ stabilized form is more thermally stable, yielding a T_m of ∼ 47°C compared to a T_m of ∼ 30°C for the Na⁺ stabilized form. We observed that both the ribosyl conformation and the coordination of the carbonyl groups depend on the nature of the cation. The C₆O stretching frequency indicates that Na⁺ coordinates much more strongly to the carbonyl groups than K⁺ (1672 cm⁻¹ Na⁺ vs 1684 cm⁻¹ K⁺ at 4°C). Conformationally sensitive modes of the phosphate backbone and the ribosyl ring indicate that Na⁺ stabilized poly(rI) predominantly exists in a C_3′-endo ribose conformation, whereas K⁺ stabilized poly(rI) adopts a C_2′-endo conformation possibly as a consequence of the larger ionic radius of the K⁺ ion. © 1998 John Wiley & Sons, Inc. Biopoly 46: 475–487, 1998     

Pyridine nucleotides and redox state regulation of aflatoxin biosynthesis in Aspergillus parasiticus NRRL 3240

In vivo regulation of lipid and aflatoxin biosynthesis by pyridine nucleotides and their derived functions was studied in Aspergillus parasiticus NRRL 3240. Aflatoxins, total lipids and pyridine nucleotide content were estimated under different growth conditions. Aflatoxin formation was highest in cultures grown in sucroselow salts medium followed by asparagine- and zinc-deficient media. The lipid content of the cultures followed an inverse pattern. The levels of oxidized nucleotides decreased with age under all culture conditions employed. Concentrations of NADPH peaked before the onset of aflatoxin biosynthesis. For each medium used, the estimated catabolite reduction charge was constant at all stages of growth whereas the anabolic reduction charge varied. A direct relationship between the level of extracellular ammonium ions and anabolic reduction charge was established. A high anabolic reduction charge was associated with increased lipid biosynthesis rather than aflatoxin biosynthesis.     

Fungi of Delhi: III. Some interesting ascomycetes

Three coprophilous ascomycetes have been reported for the first time from India. They arePreussia isomera Cain,Gelasinospora tetraspora Dowding andPodospora absimilis Cain.     

Studies on indian laboulbeniales III. Three unrecorded dioecious genera

Three dioecious Laboulbeniomycetes are reported for the first time from India. These areAporomyces uniflagellatus on limnichid beetle,Dimeromyces anisolabis onLabiduara riparia (Dermaptera) andDioicomyces anthici on anthicid beetles.     

Production of cleistothecia in a sterile strain of Thielavia setosa Dade

Summary A sterile strain ofThielavia setosa Dade was isolated which produced cleistothecia in association withA. nidulans, A. variecolor, T. sepedonium andT. terricola.Portion of a thesis presented at the University of Lucknow for the degree of Doctor of Philosophy.