Department of Bioscience & Bioengineering

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IIT Jodhpur

The microRNAs, also known as miRNAs are, the class of small non-coding RNAs that repress the expression of a gene post-transcriptionally. In effect, they regulate expression of a gene or protein. It has been observed that they play an important role in various cellular processes and thus help in carrying out normal functioning of a cell. However, dysregulation of miRNAs is found to be a major cause of a disease. Various studies have also shown the role of miRNAs in cancer and utility of miRNAs for the diagnosis of cancer and other diseases. A large number of works have been conducted to identify differentially expressed miRNAs as unlike with mRNA expression, a modest number of miRNAs might be sufficient to classify human cancers. In this regard, this paper presents a rough set based feature selection algorithm to select miRNAs from expression data that can classify tissue samples into their respective category with minimal error rate. It selects a set of miRNAs by maximizing both the relevance and significance of miRNAs. The effectiveness of the rough set based algorithm, along with a comparison with other related algorithms, is demonstrated on three miRNA microarray expression data sets using the B.632+ bootstrap error rate of support vector machine. © 2012 IEEE.

World University root node

Proceedings - 2012 IEEE International Conference on Bioinformatics and Biomedicine Workshops, BIBMW 2012

Rough sets and support vector machine for selecting differentially expressed miRNAs

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. © 2011 Springer-Verlag.

Human Genetics

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

Virstatin is a small molecule that inhibits Vibrio cholerae virulence regulation, the causative agent for cholera. Here we report the interaction of virstatin with human serum albumin (HSA) using various biophysical methods. The drug binding was monitored using different isomeric forms of HSA (N form $\sim$pH 7.2, B form $\sim$pH 9.0 and F form $\sim$pH 3.5) by absorption and fluorescence spectroscopy. There is a considerable quenching of the intrinsic fluorescence of HSA on binding the drug. The distance (r) between donor (Trp214 in HSA) and acceptor (virstatin), obtained from Forster-type fluorescence resonance energy transfer (FRET), was found to be 3.05 nm. The ITC data revealed that the binding was an enthalpy-driven process and the binding constants Ka for N and B isomers were found to be 6.09×105M-1 and 4.47×105 M-1, respectively. The conformational changes of HSA due to the interaction with the drug were investigated from circular dichroism (CD) and Fourier Transform Infrared (FTIR) spectroscopy. For 1:1 molar ratio of the protein and the drug the far-UV CD spectra showed an increase in $\alpha$- helicity for all the conformers of HSA and the protein is stabilized against urea and thermal unfolding. Molecular docking studies revealed possible residues involved in the protein-drug interaction and indicated that virstatin binds to Site I (subdomain IIA), also known as the warfarin binding site. {\textcopyright} 2012 Chatterjee et al.

Fulltext

PLoS ONE

Interaction of virstatin with human serum albumin: Spectroscopic analysis and molecular modeling

In this work we have reported the controlled synthesis of gold nanoparticles into the surface cavities of P123 micellar assemblies together with the fluorescent dye molecules and investigated nanometal surface energy transfer (NSET) from confined donor dye to metal nanoparticles. The formation of hybrid spherical assemblies of P123 combined with fluorescent dyes and gold nanoparticles has been confirmed from HR-TEM, DLS, UV-vis, and fluorescence spectroscopic studies. The observed steady state as well as time-resolved fluorescence quenching of the confined micellar dyes present in the close proximity of gold nanoparticles which are attached to the surface of micellar assemblies, indicates efficient surface energy transfer from dye to gold (Au) nanoparticles. Since the NSET process is strongly dependent on the distance between donor dye and acceptor nanoparticles, successful applications of NSET require the perfect control over their relative location. Herein, we investigate the utilization of nanoparticles embedded self-assemblies of P123 for controlled NSET by tuning the precise location of donor dyes. Through the nanoencapsulation of the different fluorophore having different location inside P123 micelles, we have shown the corona region of P123 micelles as a perfect place for NSET and the core region as a barrier for NSET. Additionally, we have investigated the microenvironment of the confined micellar probe molecules in presence and absence of nanoparticles. This study further reveals that when the system changes from normal micelles to nanoparticles loaded hybrid micelles, unlike the probes C480 and C153, the anionic probe C343 undergoes a change in its location indicating the modulation of the properties of micelles in presence of nanoparticles. © 2012 American Chemical Society.

Journal of Physical Chemistry C

Pluronic micellar aggregates loaded with gold nanoparticles (Au NPs) and fluorescent dyes: A study of controlled nanometal surface energy transfer

We have investigated the effect of protic ionic liquid, N,N-Dimethylethanolammonium formate (DAF) addition on Triton X-100-cetyltrimethylammonium bromide (CTAB) mixed micellar solution. We have shown the effect of DAF addition on the size and zeta potential of the mixed micellar aggregates using dynamic light scattering measurements. The steady-state and time-resolved fluorescence spectroscopy have been used to investigate the effect of increasing CTAB/Triton X-100 ratio and DAF addition on the solvent and rotational relaxation of Coumarin-153 in CTAB-Triton X-100 mixed micellar solutions. The average solvation time decreases with increasing CTAB/Triton X-100 ratio and increases with the addition of DAF. © 2012 Elsevier B.V. All rights reserved.

Chemical Physics Letters

Protic ionic liquid-induced changes in the properties of aqueous triton X-100-CTAB surfactant solution: Solvent and rotational relaxation studies

In this paper, we propose a randomized scheduling algorithm on a fully connected homogeneous multiprocessor environment. This is a randomized version of our earlier algorithm in which we used priority of modules that was dependent on the computation and the communication times associated with the modules. First we propose a generalization of our earlier scheduling algorithm with restricted number of clusters to reduce the time complexity. Then we apply randomization to the generalized algorithm and demonstrate its superiority over our previous work. We show the complexity of our proposed algorithm as O(ab vertical bar V vertical bar(vertical bar V vertical bar+vertical bar E vertical bar)log(vertical bar V vertical bar + vertical bar E vertical bar). Here a is the number of randomization steps, and b is a limit on the number of clusters formed. If we use a and b as constants, then this gives a better complexity in comparison with the complexity of our previous algorithm that was O(vertical bar V vertical bar (2)(vertical bar V vertical bar + vertical bar E vertical bar)log(vertical bar V vertical bar+vertical bar E vertical bar)). In comparison with our previous work we get a performance improvement of up to 6.63\%; and a performance improvement of up to 12.56\% when compared with Sarkar's Edge Zeroing algorithm.

PARALLEL PROCESSING LETTERS

A RANDOMIZED SCHEDULING ALGORITHM FOR MULTIPROCESSOR ENVIRONMENTS

Fluorescent pseudomonads produce a characteristic fluorescent pigment, pyoverdines as their primary siderophore for iron acquisition under iron-limiting conditions. Here, we report the identification of a random transposon mutant IST3 of Pseudomonas putida S11 showing tolerance to iron starvation stress condition and increased pyoverdine production. The insertion of the Tn5 transposon was found to be in pstS gene of pstSR operon encoding sensor histidine kinase protein of the two-component signal transduction system. A pyoverdine negative derivative of IST3 mutant constructed was sensitive to iron stress condition. It indicated that increased survival of IST3 under iron-limiting condition was due to higher pyoverdine production. The iron starvation tolerant mutant (IST3) exhibited enhanced pyoverdine-mediated iron uptake in minimal medium which significantly improved its biofilm formation, seed adhesion and competitive root colonization. Copyright © Springer Science+Business Media, LLC. 2012.

BioMetals

Influence of siderophore pyoverdine synthesis and ironuptake on abiotic and biotic surface colonization of Pseudomonas putida S11

Kinetic energy fluctuations of a non-dissipative 1D granular chain held between perfectly reflecting walls with various precompressions are numerically investigated. The dynamics of the system is explored for three cases, i) for a weakly precompressed chain which admits only solitary waves that break down into secondary waves under wall collisions, which is consistent with other findings in the literature; ii) for a strongly precompressed chain which exhibits mostly acoustic waves; and iii) for a chain with intermediate precompression. Case iii) accommodates a nearly stable solitary wave that travels unaffected through the acoustic waves and bounces back and forth between the walls for extremely long times. © Copyright EPLA, 2012.

Long-lived solitary wave in a precompressed granular chain

APOBEC3B, a gene involved in innate response, exhibits insertion-deletion polymorphism across world populations. We observed the insertion allele to be nearly fixed in malaria endemic regions of sub-Saharan Africa as well as populations with high malaria incidence in the past. This prompted us to investigate the possible association of the polymorphism with falciparum malaria. We studied the distribution of APOBEC3B, in 25 diverse Indian populations comprising of 500 samples and 176 severe or non-severe Plasmodium falciparum patients and 174 ethnically-matched uninfected individuals from a P. falciparum endemic and a non-endemic region of India. The deletion frequencies ranged from 0% to 43% in the Indian populations. The frequency of the insertion allele strikingly correlated with the endemicity map of P. falciparum malaria in India. A strong association of the deletion allele with susceptibility to falciparum malaria in the endemic region (non-severe vs. control, Odds ratio=4.96, P value=9.5E -06; severe vs. control, OR=4.36, P value=5.76E -05) was observed. Although the frequency of deletion allele was higher in the non-endemic region, there was a significant association of the homozygous deletion genotype with malaria (OR=3.17, 95% CI=1.10-10.32, P value=0.0177). Our study also presents a case for malaria as a positive selection force for the APOBEC3B insertion and suggests a major role for this gene in innate immunity against malaria. © 2011 Elsevier B.V.

Infection, Genetics and Evolution

Deletion of the APOBEC3B gene strongly impacts susceptibility to falciparum malaria

The present study reveals the modulation of photophysical properties of curcumin, an important drug for numerous reasons, inside a micellar environment formed by a surfactant-like ionic liquid (IL-micelle) in aqueous solution. Higher stability of the drug inside IL-micelle in the absence and presence of a simple salt (sodium chloride) as well as considerably large partition coefficient (Kp = 8.59 × 103) to the micellar phase from water make this system a well behaved drug loading vehicle. Remarkable change in fluorescence intensity with a strong blue-shift implies the gradual perturbation of intramolecular hydrogen bond (H-bond) present within the keto-enol group of curcumin along with considerable formation of intermolecular H-bond between curcumin and the headgroup of surfactant-like IL. Very fast nonradiative decay channels in curcumin mainly caused by the excited state intramolecular proton transfer (ESIPT) are thus depleted remarkably in the presence of IL-micelle of reduced polarity and as a result of restricted rotational and vibrational degrees of freedom when bound to the micelle. Moreover, time-resolved results confirm that not only the keto-enol group of curcumin is playing here but also the phenolic hydroxyl groups are also responsible for such modulation in photophysical properties. From a thermodynamic point of view, our system shows good correlation with its stability parameters (higher binding constant with very less hydrolytic degradation rate ∼1%) and higher negative value of binding enthalpy of interaction (-ΔH) than total free energy change (-ΔG) implies that the nature of binding interaction is enthalpy driven not entropy alone. Summarizing all the above observations, we have concluded that the modulation of the intramolecular proton transfer is due to the presence of both intermolecular proton transfer as well as strong hydrophobic interaction between curcumin and the IL-micelle. © 2012 American Chemical Society.

Journal of Physical Chemistry B

An understanding of the modulation of photophysical properties of curcumin inside a micelle formed by an ionic liquid: A new possibility of tunable drug delivery system