Anticancer activity for 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) analogues and their abilities to interact with lymphoendothelial cell surface markers

The structure of the anticancer agent 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) has been modified through SAR and by incorporating barbituric acid, pyridine, quinoline, and alkylcarboxylic acids into A-007's moieties. Analogue anticancer activity and interacting with CD surface markers on a T-cell leukemia cell line were evaluated and the correlation between SAR and biological properties are discussed.     

Genetic affinities of the central Indian tribal populations

Background

The central Indian state Madhya Pradesh is often called as ‘heart of India’ and has always been an important region functioning as a trinexus belt for three major language families (Indo-European, Dravidian and Austroasiatic). There are less detailed genetic studies on the populations inhabited in this region. Therefore, this study is an attempt for extensive characterization of genetic ancestries of three tribal populations, namely; Bharia, Bhil and Sahariya, inhabiting this region using haploid and diploid DNA markers.

Methodology/Principal Findings

Mitochondrial DNA analysis showed high diversity, including some of the older sublineages of M haplogroup and prominent R lineages in all the three tribes. Y-chromosomal biallelic markers revealed high frequency of Austroasiatic-specific M95-O2a haplogroup in Bharia and Sahariya, M82-H1a in Bhil and M17-R1a in Bhil and Sahariya. The results obtained by haploid as well as diploid genetic markers revealed strong genetic affinity of Bharia (a Dravidian speaking tribe) with the Austroasiatic (Munda) group. The gene flow from Austroasiatic group is further confirmed by their Y-STRs haplotype sharing analysis, where we determined their founder haplotype from the North Munda speaking tribe, while, autosomal analysis was largely in concordant with the haploid DNA results.

Conclusions/Significance

Bhil exhibited largely Indo-European specific ancestry, while Sahariya and Bharia showed admixed genetic package of Indo-European and Austroasiatic populations. Hence, in a landscape like India, linguistic label doesn''t unequivocally follow the genetic footprints.     

Analysis of mitochondrial genome revealed a rare 50 bp deletion and substitutions in a family with hypertension

We have sequenced the complete mtDNA of a family with hypertension (HT), type 2 diabetes (T2D) and coronary artery disease (CAD). Our analysis revealed two novel mutations (C3519T, G13204A); of which G13204A replaces valine to isoleucine. In silico analysis of a rare missense mutation (T8597C) showed a deleterious effect. We also observed a 50 bp deletion (m.298_347del50) in the hypervariable region II (HVSII) of all the individuals, who had a common maternal lineage. This (50 bp) deletion was not found in 17,785 individuals from different ethnic populations of India or in a variety of different disease phenotypes. We predict that the mtDNA mutations might be responsible for the HT. Analysis of POLG (polymerase gamma) gene revealed 14 variants which might be responsible for some of the mtDNA mutations seen in this family.     

Quinoxalin-2-carboxamides: synthesis and pharmacological evaluation as serotonin type-3 (5-HT3) receptor antagonists

A series of quinoxalin-2-carboxamides were designed as per the pharmacophoric requirements of 5-HT(3) receptor antagonists and synthesized by condensing the carboxylic group of quinoxalin-2-carboxylic acid with various amines in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 1-hydroxybenzotriazole. The structures of the synthesized compounds were confirmed by physical and spectroscopic data. The carboxamides were evaluated for their 5-HT(3) receptor antagonisms in longitudinal muscle-myenteric plexus preparation from guinea pig ileum against 5-HT(3) agonist, 2-methy-5-HT. All the synthesized compounds showed 5-HT(3) receptor antagonism, (4-benzylpiperazin-1-yl)(quinoxalin-2-yl)methanone was the most potent compound among this series.     

Microsatellite diversity in Andhra Pradesh, India: genetic stratification versus social stratification

DNA samples of 948 individuals belonging to 27 populations from southern Andhra Pradesh were analyzed for nine AmpFlSTR Profiler Plus loci. The nature and extent of genomic diversity within and between these populations have been examined with reference to socioeconomic and geographic affiliations. The results suggest that the average heterozygosity is uniformly high in these populations (> 0.80) and that the patterns of allele distributions are similar across the populations. The value of the coefficient of gene differentiation and the AMOVA and structure analysis results suggest that these populations are highly homogeneous. The neighbor-joining tree constructed using either D(A) or F(ST) distances suggests no intelligible pattern of population clusters based on ethnohistoric or geographic affiliations. All these observations suggest either a common recent origin of these populations or extensive gene flow across the populations that erased the original genetic differences. Given strict endogamy, the latter explanation can hold only if there has been unauthorized or unrecognized gene flow transecting the social boundaries. Nevertheless, the regression plot of average heterozygosity versus distance from the centroid (Rii), based on Harpending and Ward's (1982) model, and the genetic distances computed between different hierarchical groups within Andhra Pradesh tend to support this conjecture. Overall, the results suggest lack of a significant degree of genetic stratification that is consistent with social stratification in Andhra Pradesh. Furthermore, the neighbor-joining tree based on comparative data from other Indian and continental populations brings out a single and compact cluster of all the Andhra populations that is clearly separated from the rest.     

Performance optimization of polysulfone ultrafiltration membranes for riboflavin separation using design experiments

Polysulfone membranes containing different concentrations of polyethylene glycol (M.Wt: 600 Da) as additive was prepared using N,N-dimethyl formamide as solvent. The parameters chosen for the study of separation of vitamin B₂ were concentrations of additive and feed and solvent evaporation time. Box-Behnken design methods and analysis of variance have been applied to the experimental separation of vitamin B₂ by polysulfone membranes. Box-Behnken design with three levels of additive concentration (2.5, 6.25 and 10 wt%), feed concentration (0.002, 0.005 and 0.008%) and solvent evaporation time (10, 20 and 30 s) is used for the identification of significant effects and interaction for the batch studied. Second order polynomial regression model which was used for analysis of the experiment made significant effect. The experimental values are in good correlation with predicted values, and the correlation coefficient was found to be 0.9194.     

Lipophorin transport of hydrocarbon during early vitellogenesis in the silkworm,Bombyx mori

Lipophorin transports the hydrophobic molecule from origin to destination in time specific manner. Here, we investigate the hydrocarbon composition in the lipophorin during day 2 of pupal silkworm, Bombyx mori. Lipophorin was isolated from hemolymph by immunoprecipitation; lipid extracted and analyzed in GC-MS, resulting in seventeen compounds including eight hydrocarbons. Which were searched with the Pherobase (Pheromone database) and functional roles analysed. All hydrocarbons denoted as a pheromone except pentatriacontane in lepidopteron insects. Other hand, hydrocarbons such as hexadecane, nonadecane, undecane and hexacosane specifically refer as an attractant, additionally heptacosane, octacosane and docosane indicate as an allomone in non-lepidopteron insects. As well as, docosane and undecane perform as kairomone. Identified pheromone interaction with lipophorin was analysed by molecular docking and shows the best binding score. All hydrocarbons bound in a lipid binding pocket, most of these sharing the same binding sites for hydrophobic interaction and hydrogen bonding. Overall findings elucidated that lipophorin associated with different hydrocarbons by hydrogen bonds and hydrophobic interactions, and each of the hydrocarbon having various functional roles.     

Breast Tumors with Elevated Expression of 1q Candidate Genes Confer Poor Clinical Outcome and Sensitivity to Ras/PI3K Inhibition

Genomic aberrations are common in cancers and the long arm of chromosome 1 is known for its frequent amplifications in breast cancer. However, the key candidate genes of 1q, and their contribution in breast cancer pathogenesis remain unexplored. We have analyzed the gene expression profiles of 1635 breast tumor samples using meta-analysis based approach and identified clinically significant candidates from chromosome 1q. Seven candidate genes including exonuclease 1 (EXO1) are consistently over expressed in breast tumors, specifically in high grade and aggressive breast tumors with poor clinical outcome. We derived a EXO1 co-expression module from the mRNA profiles of breast tumors which comprises 1q candidate genes and their co-expressed genes. By integrative functional genomics investigation, we identified the involvement of EGFR, RAS, PI3K / AKT, MYC, E2F signaling in the regulation of these selected 1q genes in breast tumors and breast cancer cell lines. Expression of EXO1 module was found as indicative of elevated cell proliferation, genomic instability, activated RAS/AKT/MYC/E2F1 signaling pathways and loss of p53 activity in breast tumors. mRNA–drug connectivity analysis indicates inhibition of RAS/PI3K as a possible targeted therapeutic approach for the patients with activated EXO1 module in breast tumors. Thus, we identified seven 1q candidate genes strongly associated with the poor survival of breast cancer patients and identified the possibility of targeting them with EGFR/RAS/PI3K inhibitors.     

Relationship between plasmid occurrence and antibiotic resistance in Myroides odoratimimus SKS05-GRD isolated from raw chicken meat

Fifteen flavobacterium strains were isolated from raw chicken meat, raw goat meat and poultry soil in Coimbatore, Tamil Nadu. Most of the isolates developed yellow pigmented colonies with mucoid-spreading edges on food flavobacterium medium. The flavobacteria were Gram-negative rods and failed to produce indole and were non-fermentative. Moreover, they produced a rich array of enzymes such as amylase, lipase, catalase, urease, gelatinase, DNase, and oxidase. Phylogenetic analyses of the strain SKS05-GRD based on 16S rRNA gene sequences revealed the bacterium as Myroides odoratimimus (nucleotide sequence accession number JQ178355). Antimicrobial susceptibility test for M. odoratimimus SKS05-GRD and other strains were assessed by disc diffusion method. M. odoratimimus SKS05-GRD showed wide resistance to the antibiotics such as amikacin, ampicillin, cefadroxil, cefoperazone, ceftazidine, ceftriaxone, netillin and gentamicin. M. odoratimimus was subjected to plasmid isolation and plasmid curing to seek the relationship between plasmid and antibiotic resistance. Plasmid curing was done by using ethidium bromide and was found to be effective at 300 and 500 μg/ml. Assessment of antibiotic sensitivity of M. odoratimimus SKS05-GRD showed sensitivity to amikacin, gentamicin and kanamycin confirming that resistance to these three antibiotics is plasmid mediated and other antibiotic resistance are chromosomal mediated.