1-Arylmethyl-2,3-dioxo-2,3-dihydroindole thiosemicarbazones as leads for developing cytotoxins and anticonvulsants

Various substituted 1-arylmethyl-2,3-dioxo-2,3-dihydroindole thiosemicarbazones 3a-h, 1-benzyl-2,3-dioxo-2,3-dihydroindole N⁴-aryl thiosemicarbazones 4a-i and 1-benzyl-2,3-dioxy-2,3-dihydroindole N⁴-cyclohexylthiocarbazone 5 were synthesized. All of these compounds were evaluated against human Molt 4/C8 and CEM T-lymphocytes as well as murine L1210 leukemia cells. Nearly 40% of these compounds possess low micromolar IC₅₀ values and some are either more potent than, or equipotent with, melphalan. Various correlations between the structures of these compounds and cytotoxic potencies were obtained which included the use of QSAR and molecular modeling techniques. Representative compounds displayed anticonvulsant properties in rats and were well tolerated by these animals. The encouraging biodata noted affords adequate rationale for outlining guidelines for further development of these molecular scaffolds.     

Cloning,expression and characterization of glucokinase gene involved in the glucose-6- phosphate formation in Staphylococcus aureus

Glucose-6-phosphate (G-6-P) formation in Staphylococcus aureus is catalysed by glucokinase (glkA) gene under high glucose concentration leading to upregulation of various pathogenic factors; therefore the present study is aimed in the cloning and characterization of glk A gene from S. aureus ATCC12600. The glk A gene was cloned in the Sma I site of pQE 30, sequenced (Accession number: {"type":"entrez-nucleotide","attrs":{"text":"JN645812","term_id":"374095279"}}JN645812) and expressed in E. coli DH5α. The recombinant glk A expressed from the resultant glk A 1 clone was purified using nickel metal chelate chromatography, the pure enzyme gave single band in SDS-PAGE with molecular weight of 33kDa. The rglk A showed very high affinity to glucose K_m 5.1±0.06mM with Hill coefficient of 1.66±0.032mM. Analysis of glucokinase sequence of S. aureus showed presence of typical ATP binding site and ROK motif CNCGRSGCIE. Sequentially and phylogenetically S. aureus glk A exhibited low identity with other bacterial glk A and 21% homology with human glucokinase (GCK). Functionally, S. aureus glk A showed higher rate of G-6-P formation compared to human GCK which may have profound role in the pathogenesis.     

Feature Selection for high Dimensional DNA Microarray data using hybrid approaches

Feature selection from DNA microarray data is a major challenge due to high dimensionality in expression data. The number of samples in the microarray data set is much smaller compared to the number of genes. Hence the data is improper to be used as the training set of a classifier. Therefore it is important to select features prior to training the classifier. It should be noted that only a small subset of genes from the data set exhibits a strong correlation with the class. This is because finding the relevant genes from the data set is often non-trivial. Thus there is a need to develop robust yet reliable methods for gene finding in expression data. We describe the use of several hybrid feature selection approaches for gene finding in expression data. These approaches include filtering (filter out the best genes from the data set) and wrapper (best subset of genes from the data set) phases. The methods use information gain (IG) and Pearson Product Moment Correlation (PPMC) as the filtering parameters and biogeography based optimization (BBO) as the wrapper approach. K nearest neighbour algorithm (KNN) and back propagation neural network are used for evaluating the fitness of gene subsets during feature selection. Our analysis shows that an impressive performance is provided by the IG-BBO-KNN combination in different data sets with high accuracy (>90%) and low error rate.     

Sexual dimorphism in digital dermatoglyphic traits among Sinhalese people in Sri Lanka

Background

The purpose of this study was to evaluate gender-wise diversity of digital dermatoglyphic traits in a sample of Sinhalese people in Sri Lanka.

Findings

Four thousand and thirty-four digital prints of 434 Sinhalese individuals (217 males and 217 females) were examined for their digital dermatoglyphic pattern distribution. The mean age for the entire group was 23.66 years (standard deviation = 4.93 years). The loop pattern is observed more frequently (n = 2,592, 59.72%) compared to whorl (n = 1,542, 35.53%) and arch (n = 206, 4.75%) in the Sinhalese population. Females (n = 1,274, 58.71%) have a more ulnar loop pattern than males (n = 1,231, 56.73%). The plain whorl pattern is observed more frequently in males (n = 560, 25.81%) compared to females (n = 514, 23.69%).The double loop pattern is observed more frequently on the right and left thumb (digit 1) of both males and females. Pattern intensity index, Dankmeijer index and Furuhata index are higher in males.

Conclusions

Ulnar loop is the most frequently occurring digital dermatoglyphic pattern among the Sinhalese. All pattern indices are higher in males. To some extent, dermatoglyphic patterns of Sinhalese are similar to North Indians and other Caucasoid populations. Further studies with larger sample sizes are recommended to confirm our findings.     

Simian immunodeficiency virus infection induces severe loss of intestinal central memory T cells which impairs CD4+ T-cell restoration during antiretroviral therapy

BACKGROUND: Simian immunodeficiency virus (SIV) infection leads to severe loss of intestinal CD4(+) T cells and, as compared to peripheral blood, restoration of these cells is slow during antiretroviral therapy (ART). Mechanisms for this delay have not been examined in context of which specific CD4(+) memory subsets or lost and fail to regenerate during ART. METHODS: Fifteen rhesus macaques were infected with SIV, five of which received ART (FTC/PMPA) for 30 weeks. Viral loads were measured by real-time PCR. Flow cytometric analysis determined changes in T-cell subsets and their proliferative state. RESULTS: Changes in proliferative CD4(+) memory subsets during infection accelerated their depletion. This reduced the central memory CD4(+) T-cell pool and contributed to slow CD4(+) T-cell restoration during ART. CONCLUSION: There was a lack of restoration of the CD4(+) central memory and effector memory T-cell subsets in gut-associated lymphoid tissue during ART, which may contribute to the altered intestinal T-cell homeostasis in SIV infection.     

Radio-frequency ablation in a realistic reconstructed hepatic tissue

This study uses a reconstructed vascular geometry to evaluate the thermal response of tissue during a three-dimensional radiofrequency (rf) tumor ablation. MRI images of a sectioned liver tissue containing arterial vessels are processed and converted into a finite-element mesh. A rf heat source in the form of a spherically symmetric Gaussian distribution, fit from a previously computed profile, is employed. Convective cooling within large blood vessels is treated using direct physical modeling of the heat and momentum transfer within the vessel. Calculations of temperature rise and thermal dose are performed for transient rf procedures in cases where the tumor is located at three different locations near the bifurcation point of a reconstructed artery. Results demonstrate a significant dependence of tissue temperature profile on the reconstructed vasculature and the tumor location. Heat convection through the arteries reduced the steady-state temperature rise, relative to the no-flow case, by up to 70% in the targeted volume. Blood flow also reduced the thermal dose value, which quantifies the extent of cell damage, from approximately 3600 min, for the no-flow condition, to 10 min for basal flow (13.8 cms). Reduction of thermal dose below the threshold value of 240 min indicates ablation procedures that may inadequately elevate the temperature in some regions, thereby permitting possible tumor recursion. These variations are caused by vasculature tortuosity that are patient specific and can be captured only by the reconstruction of the realistic geometry.     

Analysis of Genetic Diversity in the North Eastern Himalayan Maize Landraces using Microsatellite Markers

Population DNA fingerprinting of 48 selected North Eastern Himalayan (NEH) landrace accessions was undertaken using 41 polymorphic fluorescent dye-labelled microsatellite/Simple Sequence Repeat (SSR) markers, using a DNA Sequencer. The analysis revealed a large number of SSR alleles (576), with high mean number of alleles per locus (13.8), and Polymorphism Information Content (PIC) of 0.63, reflecting the level of diversity in the NEH accessions and the informativeness of the SSR markers. The study also led to identification of 135 unique alleles, differentiating 44 out of the 48 accessions. Five highly frequent (major) SSR alleles (umc1545 _80bp, phi062 _162bp, umc1367 _159bp, umc2250 _152bp and phi112 _152bp) were detected indicating that chromosomal regions harbouring these S SR alleles might not be selectively neutral. Analysis of population genetic parameters, including Wright’s F statistics, revealed high level of genetic differentiation, very low levels of inbreeding, and restricted gene flow between the NEH landraces. AMOVA (Analysis of Molecular Variance) showed that 67 per cent of the total variation in the accessions could be attributed to within-population diversity, and the rest between the accessions. Cluster analysis of SSR data using Rogers’ genetic distance and UPGMA, showed significant genetic diversity among the landraces from Sikkim. This is the first detailed study of SSR allele frequency-based analysis of genetic diversity in the NEH maize landraces of India.