Global gene expression profiling data analysis reveals key gene families and biological processes inhibited by Mithramycin in sarcoma cell lines

AbstractThe role of Mithramycin as an anticancer drug has been well studied. Sarcoma is a type of cancer arising from cells of mesenchymal origin. Though incidence of sarcoma is not of significant percentage, it becomes vital to understand the role of Mithramycin in controlling tumor progression of sarcoma. In this article, we have analyzed the global gene expression profile changes induced by Mithramycin in two different sarcoma lines from whole genome gene expression profiling microarray data. We have found that the primary mode of action of Mithramycin is by global repression of key cellular processes and gene families like phosphoproteins, kinases, alternative splicing, regulation of transcription, DNA binding, regulation of histone acetylation, negative regulation of gene expression, chromosome organization or chromatin assembly and cytoskeleton

Deep Rooting In-Situ Expansion of mtDNA Haplogroup R8 in South Asia

The phylogeny of the indigenous Indian-specific mitochondrial DNA (mtDNA) haplogroups have been determined and refined in previous reports. Similar to mtDNA superhaplogroups M and N, a profusion of reports are also available for superhaplogroup R. However, there is a dearth of information on South Asian subhaplogroups in particular, including R8. Therefore, we ought to access the genealogy and pre-historic expansion of haplogroup R8 which is considered one of the autochthonous lineages of South Asia.Upon screening the mtDNA of 5,836 individuals belonging to 104 distinct ethnic populations of the Indian subcontinent, we found 54 individuals with the HVS-I motif that defines the R8 haplogroup. Complete mtDNA sequencing of these 54 individuals revealed two deep-rooted subclades: R8a and R8b. Furthermore, these subclades split into several fine subclades. An isofrequency contour map detected the highest frequency of R8 in the state of Orissa. Spearman's rank correlation analysis suggests significant correlation of R8 occurrence with geography.The coalescent age of newly-characterized subclades of R8, R8a (15.4+/-7.2 Kya) and R8b (25.7+/-10.2 Kya) indicates that the initial maternal colonization of this haplogroup occurred during the middle and upper Paleolithic period, roughly around 40 to 45 Kya. These results signify that the southern part of Orissa currently inhabited by Munda speakers is likely the origin of these autochthonous maternal deep-rooted haplogroups. Our high-resolution study on the genesis of R8 haplogroup provides ample evidence of its deep-rooted ancestry among the Orissa (Austro-Asiatic) tribes

Phylogenetic analysis, based on EPIYA repeats in the cagA gene of Indian Helicobacter pylori, and the implications of sequence variation in tyrosine phosphorylation motifs on determining the clinical outcome

The population of India harbors one of the world’s most highly diverse gene pools, owing to the influx of successive waves of immigrants over regular periods in time. Several phylogenetic studies involving mitochondrial DNA and Y chromosomal variation have demonstrated Europeans to have been the first settlers in India. Nevertheless, certain controversy exists, due to the support given to the thesis that colonization was by the Austro-Asiatic group, prior to the Europeans. Thus, the aim was to investigate pre-historic colonization of India by anatomically modern humans, using conserved stretches of five amino acid (EPIYA) sequences in the cagA gene of Helicobacter pylori. Simultaneously, the existence of a pathogenic relationship of tyrosine phosphorylation motifs (TPMs), in 32 H. pylori strains isolated from subjects with several forms of gastric diseases, was also explored. High resolution sequence analysis of the above described genes was performed. The nucleotide sequences obtained were translated into amino acids using MEGA (version 4.0) software for EPIYA. An MJ-Network was constructed for obtaining TPM haplotypes by using NETWORK (version 4.5) software. The findings of the study suggest that Indian H. pylori strains share a common ancestry with Europeans. No specific association of haplotypes with the outcome of disease was revealed through additional network analysis of TPMs

Reconstructing the demographic history of the Himalayan and adjoining populations

The rugged topography of the Himalayan region has hindered large-scale human migrations, population admixture and assimilation. Such complexity in geographical structure might have facilitated the existence of several small isolated communities in this region. We have genotyped about 850,000 autosomal markers among 35 individuals belonging to the four major populations inhabiting the Himalaya and adjoining regions. In addition, we have genotyped 794 individuals belonging to 16 ethnic groups from the same region, for uniparental (mitochondrial and Y chromosomal DNA) markers. Our results in the light of various statistical analyses suggest a closer link of the Himalayan and adjoining populations to East Asia than their immediate geographical neighbours in South Asia. Allele frequency-based analyses likely support the existence of a specific ancestry component in the Himalayan and adjoining populations. The admixture time estimate suggests a recent westward migration of populations living to the East of the Himalaya. Furthermore, the uniparental marker analysis among the Himalayan and adjoining populations reveal the presence of East, Southeast and South Asian genetic signatures. Interestingly, we observed an antagonistic association of Y chromosomal haplogroups O3 and D clines with the longitudinal distance. Thus, we summarise that studying the Himalayan and adjoining populations is essential for a comprehensive reconstruction of the human evolutionary and ethnolinguistic history of eastern Eurasia

Biochemical profiling of areca nut product Dohra

Introduction Dohra is a locally produced areca nut preparations used with or without tobacco in Allahabad, Jaunpur and Pratapgarh districts of Uttar Pradesh (UP), India. Different varieties of Dohra exist such as Sukha Dohra, Geela Dohra, etc. Evidence suggests that it causes Oral Potentially Malignant Disorders and Oral Cancer. It contains arecoline which is a well-known carcinogen. In order to understand the potential role of Dohra in causing cancer biochemical profiling of different varieties of Dohra is needed. Aim To describe the biochemical profile of different varieties of Dohra. Methods Different varieties of Dohra were collected from Allahabad, Jaunpur and Pratapgarh districts of UP. All the varieties of Dohra were analyzed for biochemical profiling through Continuous Flow Autoanalyzer (CFA) using Flow View Solution 3700 Analyzer (version 1.2.2) software. Results The biochemical changes at arecoline levels were observed in different varieties of Dohra. The detailed chemical profiling will be furnished in the meeting. Conclusions Different varieties of Dohra preparations are produced and each of them have a different biochemical profile. The Dohra is rich is arecoline and hence its use should be banned/avoided

Biochemical profiling of smokeless tobacco product Kiwam at different processing steps

Introduction Kiwam (Qiwam) is a partially fermented tobacco product consumed with Betal Quid (Paan). The major constituents of this product are tobacco, saffron (Zaffrani) and some additives. It contains Tobacco-Specific Nitrosamines (TSNA) which is considered as a cancer-causing agent. To elucidate the carcinogenic property of Kiwam, biochemical profiling of its constituents at different stages of processing is needed. The major processing steps involved in the formation of Kiwam and biochemical profiling/changes at each processing step is still unknown. Aim To describe the major processing steps and biochemical changes that occurs at each processing step during the preparation of Kiwam. Method Tobacco leaves and stems were boiled in water followed by filtering of the constituents to remove the leaves and stem residues. The filtrate is again boiled to form a thick paste residue. The resultant paste was partially fermented through sun curing, and lastly saffron along with some additives were added. The samples from each step were analyzed for biochemical profiling through Continuous Flow Autoanalyzer (CFA) using Flow View Solution 3700 Analyzer (version 1.2.2) software. Results The biochemical changes at TSNA levels were observed at each processing steps. The detailed chemical profiling will be presented during the meeting. Conclusions Processing of Kiwam involves four major steps i.e. (i) boiling of tobacco leaves and stem (ii) filtration of product (iii) re-boiling of the filtrate till the paste is formed (iv) partial fermentation through sun curing. Kiwam is rich in TSNA and hence its use should be avoided

Dohra- a mixture of potent carcinogens

Background & objectives: Dohra is a areca nut preparation used with or without tobacco in a few of the areas of Uttar Pradesh (UP), India. There is evidence that it causes potentially malignant disorders and oral cancer. This study was undertaken to provide information on dohra by searching through literature and also through a survey in three areas of Uttar Pradesh (UP), India. Methods: The information on dohra was collected through literature search, study tour to different areas of UP, where group discussions with dohra vendors and with community members of different age group were done to obtain information. Results: Dohra was prepared by the users for their personal use or prepared by small-scale industry for sale. It was available mostly in betel shops or any other store/kiosks and was also available in special dohra shops. Dohra was available in both dry and wet form. Its common constituents were areca nut, catechu (Acacia catechu), edible lime, peppermint (Mentha piperita), cardamom (Elettaria cardamomum) and some flavoring agents. Dohra was consumed as such or with tobacco. Interpretation & conclusions: Different varieties of Dohra were available such as sukha dohra, sukha mulethi dohra and geela dohra. Different processing methods for producing dohra existed. As dohra increases the risk of cancer, it needs to be banned or it should be sold in packets with the details of its constituents and also statutory warning about its adverse health effects

Dopamine transporter (DAT1) VNTR polymorphism in 12 Indian populations

The dopamine transporter (DAT1) is a membrane spanning protein that binds the neurotransmitter dopamine and performs re-uptake of dopamine from the synapse into a neuron. The gene encoding DAT1 consists of 15 exons spanning 60 kb on chromosome 5p15.32. Several studies have investigated the possible associations between variants in DAT1 gene and psychiatric disorders. The present study aimed to determine the distribution of the variable number of tandem repeat (VNTR) polymorphism in the 3' untranslated region of DAT1 in 12 Indian populations. A total of 471 healthy unrelated individuals in 12 Indian populations from 3 linguistic groups were included in the present study. The analysis was carried out using PCR and electrophoresis. Overall, 4 alleles of the DAT1 40-bp VNTR, ranging from 7 to 11 repeats were detected. Heterozygosity indices were low and varied from 0.114 to 0.406. The results demonstrate the variability of the DAT1 40-bp VNTR polymorphism in Indian populations and revealed a high similarity with East Asian populations