Sanghamitra Sengupta

Separating the post-Glacial coancestry of European and Asian Y chromosomes within haplogroup R1a

Human Y-chromosome haplogroup structure is largely circumscribed by continental boundaries. One notable exception to this general pattern is the young haplogroup R1a that exhibits post-Glacial coalescent times and relates the paternal ancestry of more than 10% of men in a wide geographic area extending from South Asia to Central East Europe and South Siberia. Its origin and dispersal patterns are poorly understood as no marker has yet been described that would distinguish European R1a chromosomes from Asian. Here we present frequency and haplotype diversity estimates for more than 2000 R1a chromosomes assessed for several newly discovered SNP markers that introduce the onset of informative R1a subdivisions by geography. Marker M434 has a low frequency and a late origin in West Asia bearing witness to recent gene flow over the Arabian Sea. Conversely, marker M458 has a significant frequency in Europe, exceeding 30% in its core area in Eastern Europe and comprising up to 70% of all M17 chromosomes present there. The diversity and frequency profiles of M458 suggest its origin during the early Holocene and a subsequent expansion likely related to a number of prehistoric cultural developments in the region. Its primary frequency and diversity distribution correlates well with some of the major Central and East European river basins where settled farming was established before its spread further eastward. Importantly, the virtual absence of M458 chromosomes outside Europe speaks against substantial patrilineal gene flow from East Europe to Asia, including to India, at least since the mid-Holocene.

Cancer Classification from Gene Expression Data by NPPC Ensemble

The most important application of microarray in gene expression analysis is to classify the unknown tissue samples according to their gene expression levels with the help of known sample expression levels. In this paper, we present a nonparallel plane proximal classifier (NPPC) ensemble that ensures high classification accuracy of test samples in a computer-aided diagnosis (CAD) framework than that of a single NPPC model. For each data set only, a few genes are selected by using a mutual information criterion. Then a genetic algorithm-based simultaneous feature and model selection scheme is used to train a number of NPPC expert models in multiple subspaces by maximizing cross-validation accuracy. The members of the ensemble are selected by the performance of the trained models on a validation set. Besides the usual majority voting method, we have introduced minimum average proximity-based decision combiner for NPPC ensemble. The effectiveness of the NPPC ensemble and the proposed new approach of combining decisions for cancer diagnosis are studied and compared with support vector machine (SVM) classifier in a similar framework. Experimental results on cancer data sets show that the NPPC ensemble offers comparable testing accuracy to that of SVM ensemble with reduced training time on average.

Genetic association of Toll-like-receptor 4 and tumor necrosis factor-α polymorphisms with Plasmodium falciparum blood infection levels

Dysregulated innate immune responses due to inappropriate signaling by Toll-like receptors (TLRs) and aberrant production of pro-inflammatory cytokines are implicated in the immunopathology and disease outcome in Plasmodium falciparum malaria. This study investigates the relationship between polymorphic variability of candidate genes including TLR-2, -4, -9, tumor necrosis factor-alpha and lymphotoxin-alpha and blood infection level in Indian mild malaria patients. Genotyping was carried out by PCR-RFLP and sequencing. Association of parasite load with genotypes was examined using model based and model free approaches. Allele and haplotype based risk assessment for disease severity was performed by stratifying the patients into high and low parasitemic groups on the basis of a threshold value derived by employing a two-component mixture model and expectation-maximization algorithm. The mean parasitemia was significantly increased for variant homozygous genotype (C/C) at TNF-alpha promoter -1031 and major homozygous genotypes encoding Asp/Asp and Thr/Thr at codons 299 and 399, respectively, on TLR4 polypeptide. Individuals harboring combined genotype C/C-Asp/Asp-Thr/Thr on TNF-alpha and TLR4 presented the highest parasite load. The frequencies of variant allele C in TNF-1031 (OR=1.91 with 95% CI=1.24-2.94) and TNF-alpha promoter haplotypes C-C-G-G (OR=1.99 with 95% CI=1.21-3.27) and C-C-G-A (OR=2.96 with 95% CI=1.19-7.37) pertaining to loci TNF-1031/-857/-308/-238 were significantly elevated in the high parasitemic group. On the contrary, the frequencies of variant allele encoding Ile at 399 (OR=0.55 with 95% CI=0.32-0.94) and haplotype corresponding to Gly-Ile (299-399) (OR=0.51 with 95% CI=0.28-0.9) in TLR4 were higher in low parasitemic group. In silico analysis indicate differential binding of transcription factors to TNF-alpha promoter haplotypes and alteration in the surface charge distribution of the TLR4 variant proteins. Our results support a genetic role of TLR4 and TNF-alpha in controlling the blood infection level in mild malaria.

Assessment of malignant potential of oral submucous fibrosis through evaluation of p63, E-cadherin and CD105 expression

Background The assessment of malignant potential of oral submucous fibrosis grades vis-à-vis their progression towards malignancy is associated with expression of possible multiple molecular markers. Aims To analyse p63, E-cadherin and CD105 expression in this premalignant pathosis with a view to unravel and understand the expression of these molecules as markers. Methods The oral mucosal biopsies (normal, oral submucous fibrosis with and without dysplasia) were studied with routine H&E, and by immunohistochemistry for p63, E-cadherin and CD105 expression. p63 was assessed as percentage of positive nuclei. E-cadherin expression was estimated through (i) distance between basement membrane and E-cadherin expression initiation point, (ii) ratio between epithelial thickness and epithelial thickness displaying E-cadherin, and (iii) E-cadherin intensity variation along the expression path. CD105 expression was assessed qualitatively. Results The p63+ cells were highest in severely dysplastic tissues followed by other dysplastic grades, normal oral mucosa and non-dysplastic conditions. However, the p63+ cells displayed the feature of progressive maturation only in normal mucosa. There was a loss of membranous E-cadherin in basal layers of all diseased conditions; it was highest in severe dysplasia. There was significant variation (p<0.0001) in E-cadherin intensity within and between the tissues (normal and diseased). CD105 expression increased abruptly in dysplasia. Conclusions The malignant potential of this pre-cancerous condition is likely to be correlated with an increase in p63 and CD105 expression and a concomitant loss of membranous E-cadherin. This may lead to marker identification through greater validation.

Plant-microbe Cross-talk in the Rhizosphere: Insight and Biotechnological Potential

Rhizosphere, the interface between soil and plant roots, is a chemically complex environment which supports the development and growth of diverse microbial communities. The composition of the rhizosphere microbiome is dynamic and controlled by multiple biotic and abiotic factors that include environmental parameters, physiochemical properties of the soil, biological activities of the plants and chemical signals from the plants and bacteria which inhabit the soil adherent to root-system. Recent advancement in molecular and microbiological techniques has unravelled the interactions among rhizosphere residents at different levels. In this review, we elaborate on various factors that determine plant-microbe and microbe-microbe interactions in the rhizosphere, with an emphasis on the impact of host genotype and developmental stages which together play pivotal role in shaping the nature and diversity of root exudations. We also discuss about the coherent functional groups of microorganisms that colonize rhizosphere and enhance plant growth and development by several direct and indirect mechanisms. Insights into the underlying structural principles of indigenous microbial population and the key determinants governing rhizosphere ecology will provide directions for developing techniques for profitable applicability of beneficial microorganisms in sustainable agriculture and nature restoration.

Epithelio-mesenchymal transitional attributes in oral sub-mucous fibrosis.

Evaluating molecular attributes in association with its epithelial and sub-epithelial changes of oral sub-mucous fibrosis is meaningful in exploring the plausibility of an epithelio-mesenchymal transition (EMT) and malignant potentiality of this pathosis. In this study histopathological and histochemical attributes for basement membrane and connective tissue in biopsies of oral sub-mucous fibrosis (n = 55) and normal oral mucosa (n = 16) were assessed and expressions of p63, E-cadherin, β-catenin, N-cadherin and TWIST were analyzed immunohistochemically. The p63 and its isoforms (TA and ∆N), PARD3, E-cadherin and β-catenin were also assessed transcriptomically by q-PCR and EMT players like TWIST1, ZEB1, MMP9 and micro-RNA 205 were searched in gene expression microarrays. Oral epithelium demonstrating impairment in progressive maturation in oral sub-mucous fibrosis concomitantly experienced an increase in basement membrane thickness and collagen deposition along with alteration in target molecular expressions. In comparison to non-dysplastic conditions dysplastic stages exhibited significant increase in p63 and p63∆N expressions whereas, E-cadherin and β-catenin exhibited loss from the membrane with concurrent increase in cytoplasm. Further the N-cadherin and TWIST were gained remarkably along with the appearance of nuclear accumulation features of β-catenin. The microarray search had noticed the up-regulation of TWIST1, ZEB1 and MMP9 along with down regulation of micro-RNA 205. The simultaneous increase in basement membrane thickness and sub-epithelial collagen deposition were the plausible indicators for increased matrix stiffness with expected impact on oral epithelial functional homoeostasis. This was corroborated with the increase in expressions of epithelial master regulator p63 and its oncogenic isoform (∆N) along with membranous loss of E-cadherin (EMT hallmark) and its associate β-catein and gain of mesenchymal markers like N-cadherin and TWIST. These also became indicative for the induction of epithelial to mesenchymal transitional mechanism in oral sub-mucous fibrosis when connoted here with the relevant modulation in expressions of EMT regulators.

Co-existence of risk and protective haplotypes of Calpain 10 gene to type 2 diabetes in the eastern Indian population

Linkage and association studies have detected a role for Calpain-10 (CAPN10) polymorphisms in susceptibility to T2DM in many populations. This study aimed to evaluate possible associations between three SNPs in the CAPN10 (UCSNPs -43, -19 and -63) gene and T2DM in the east Indian population. The distribution of genotype frequency of UCSNP-63 varied significantly between T2DM patients and controls under a dominant model. The uncommon (T) allele (OR = 3.74, 95% CI: 1.44-9.7) of the UCSNP-63 and haplotype 112 (OR = 3.4, 95% CI: 1.17-9.9) were associated with increased risk of T2DM. On the contrary, the most common haplotype 121 (OR = 0.70 95% CI: 0.50-0.99) was associated with a reduced risk for T2DM. In our population a novel 111/112-haplotype combination created by the CAPN10 UCSNP-43, -19 and —63 was associated with risk of T2DM. Haplotypes 112 and 121 with opposite genetic influences also co-exist in our population.

A novel instantaneous power factor measurement method based on wavelet transform

Power factor monitoring is an important challenge in deregulated environment to maintain quality in delivered power as well as tariff assessment. In this paper, a unique power factor measurement method has been proposed that can measure the instantaneous power factor of a non-sinusoidal single-phase system accurately at every sample instant. The wavelet transform (WT) has been utilized for multiresolution analysis (MRA) of current waveform. The scheme has been implemented in real time with a Texas Instruments (TI) TMS320VC5416 digital signal processor (DSP) along with data acquisition system card PCI-02. The result has been found to be satisfactory

Genetic and functional diversities of bacterial communities in the rhizosphere of Arachis hypogaea

Bioinoculants are environmentally friendly, energy efficient and economically viable resources in sustainable agriculture. Knowledge of the structure and activities of microbial population in the rhizosphere of a plant is essential to formulate an effective bioinoculant. In this study, the bacterial community present in the rhizosphere of an important oilseed legume, Arachis hypogaea (L.) was described with respect to adjoining bulk soil as a baseline control using a 16S rDNA based metagenomic approach. Significantly higher abundance of Gamma-proteobacteria, a prevalence of Bacillus and the Cytophaga-Flavobacteria group of Bacteroidetes and absence of the Rhizobiaceae family of Alpha-proteobacteria were the major features observed in the matured Arachis-rhizosphere. The functional characterization of the rhizosphere-competent bacteria was performed using culture-dependent determination of phenotypes. Most bacterial isolates from the groundnut-rhizosphere exhibited multiple biochemical activities associated with plant growth and disease control. Validation of the beneficial traits in candidate bioinoculants in pot-cultures and field trials is necessary before their targeted application in the groundnut production system.

Multicategory cancer classification from gene expression data by multiclass NPPC ensemble

The discovery of DNA microarray technologies have given immense opportunity to make gene expression profiles for different cancer types. Besides binary classification such as normal versus tumor samples the discrimination of multiple tumor types is also important. In this work, we have first extended the recently developed binary nonparallel plane proximal classifier (NPPC) to multiclass NPPC by decomposition techniques. The multiclass NPPC is then used in a computer aided diagnosis framework to classify multicategory cancer from gene expression data by selecting very few genes by using mutual information criterion. The idea of binary NPPC ensemble is extended to form multiclass NPPC ensemble. Besides usual majority voting method, we have introduced minimum average proximity based decision combiner for multiclass NPPC ensemble. The effectiveness of the proposed method are demonstrated on four benchmark microarray data sets and compared with support vector machine (SVM) classifier in a similar framework.