Synthesis of a novel quinoline derivative, 2-(2-methylquinolin-4-ylamino)-N-phenylacetamide--a potential antileishmanial agent

Some novel quinoline derivatives were prepared and tested for antileishmanial activity. 2-(2-Methylquinolin-4-ylamino)-N-phenylacetamide (2) was found to be significantly more active than the standard antileishmanial drug sodium antimony gluconate (SAG) in reducing the parasite load both in the spleen and liver at a much lower concentration in hamster models. The results suggest that the compound could be exploited as an antileishmanial drug.     

Ion conductors derived from biogenic amines,bile acids,and amino acids

A family of conjugates has been synthesized from spermine, putrescine, lysine, gamma-aminobutyric acid, sarcosine, cholic acid, glycocholic acid, 3alpha,7alpha-dihydroxycholic acid, and 3alpha,12alpha-dihydroxycholic acid, based on a design principle previously reported (Bandyopadhyay, P., Janout, V., Zhang, L., Regen, S. L. (2001) J. Am. Chem. Soc. 123, 7691). Each of these conjugates was found to exhibit significant activity in promoting the transport of Na(+) across liposomal membranes derived from 1,2-dimyristoleoyl-sn-glycero-3-phosphocholine, and also from 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine. In all cases, plots of pseudo first-order rate constants, k(obsd) vs (mol % of ion conductor)(2) were found to be linear, indicating that transport-active dimers are involved and that only a small fraction of the conjugates are in an aggregated form. An operational comparison that has been made within this series of conjugates indicates that Na(+) transport activity and membrane selectivity have a moderate dependency on the composition and the structure of the ion conductor.     

Maneuvering hydrodynamics of fish and small underwater vehicles

The understanding of fish maneuvering and its application tounderwater rigid bodies are considered. The goal is to gaininsight into stealth. The recent progress made in NUWC is reviewed.Fish morphology suggests that control fins for maneuverabilityhave unique scalar relationships irrespective of their speedtype. Maneuvering experiments are carried out with fish thatare fast yet maneuverable. The gap in maneuverability betweenfish and small underwater vehicles is quantified. The hydrodynamicsof a dorsal fin based brisk maneuvering device and a dual flappingfoil device, as applied to rigid cylindrical bodies, are described.The role of pectoral wings in maneuvering and station keepingnear surface waves is discussed. A pendulum model of dolphinswimming is presented to show that body length and tail flappingfrequency are related. For nearly neutrally buoyant bodies,Froude number and maneuverability are related. Analysis of measurementsindicates that the Strouhal number of dolphins is a constant.The mechanism of discrete and deterministic vortex sheddingfrom oscillating control surfaces has the property of largeamplitude unsteady forcing and an exquisite phase dependence,which makes it inherently amenable to active control for precisionmaneuvering. Theoretical control studies are carried out todemonstrate the feasibility of maneuverability of biologicallyinspired bodies under surface waves. The application of fishhydrodynamics to the silencing of propulsors is considered.Two strategies for the reduction of radiated noise are developed.The effects of a reduction of rotational rate are modeled. Theactive cambering of blades made of digitally programmable artificialmuscles, and their thrust enhancement, are demonstrated. Next,wake momentum filling is carried out by artificial muscles atthe trailing edge of a stator blade of an upstream stator propulsor,and articulating them like a fish tail. A reduction of radiatednoise, called blade tonals, is demonstrated theoretically.     

Sequence analysis of VP7 gene of Indian bluetongue virus serotype-23 shows its close phylogenetic relationship to Australian and Chinese serotypes.

Bluetongue, an arthropod borne viral disease of wild and domestic ruminants, causes heavy economic losses throughout the world. In the present study, full-length VP7 gene of Indian bluetongue virus (BTV) serotype 23 was sequenced and compared with prototype strains of BTV reported from different countries. Nucleotide sequence analysis of VP7 gene revealed Indian BTV serotype 23 to have 1154 nucleotides with the deletion of two nucleotides at 3' non-coding region and a unique amino acid change 211S-N. The Indian virus also demonstrated a maximum similarity of 94.2% with Australian serotype 1 and a minimum similarity of 67.4% with Australian serotype 15. However, at deduced amino acid level, it had maximum similarity of 99.7% and a minimum of 82.5% with Chinese serotypes 1, 2 and 4 and Australian serotype 15, respectively. Deduced amino acid sequence analysis of putative receptor binding domain (121-249) revealed all the nine hydrophilic domains to be conserved across the serotypes. Functional motifs present in VP7 protein were also conserved in almost all the BTV serotypes including Indian serotype 23. Phylogenetic analysis based on VP7 gene sequence revealed Indian BTV serotype 23 segregating into a monophyletic group along with Australian serotype 1 and Chinese serotypes 1, 2 and 4, indicating its close evolutionary relationship with these Australian and Chinese serotypes.     

A parental combination analysis for ABO-HP interaction in a Bengali population

Blood samples from 577 couples and their 657 offspring of Bengali caste group derivation were used to study interactions between ABO blood groups and haptoglobin (HP) systems. There was no significant sex difference in HP distribution among the parents. Significantly higher incidences of HP^*1 allele were noted in the offspring of ABO-incompatible parental combinations in comparison with those in the offspring of ABO-compatible parents.     

A three-nucleotide insertion in the H stem-loop of the 5' untranslated region of Theiler's virus attenuates neurovirulence.

The highly structured 5' untranslated region (5' UTR) of Theiler's murine encephalomyelitis virus is involved in cap-independent translation of the viral RNA. Previously, we reported that the bicistronic mRNA chloramphenicol acetyltransferase-5' UTR-luciferase (Luc) efficiently expressed Luc both in a rabbit reticulocyte lysate and when transfected into BHK-21 cells. Insertion of 3 nucleotides at position 665 in the 5' UTR of this bicistronic mRNA resulted in greatly reduced Luc expression in BHK-21 cells but had little effect on expression of Luc in rabbit reticulocyte lysate. This mutation was also introduced into a virulent Theiler's murine encephalomyelitis virus chimera, Chi-VL. The kinetics of viral RNA and protein synthesis and virus production in BHK-21 cells were slower for the mutant chimera [Chi-VL(IN668)] than for Chi-VL; however, the final virus yields were comparable. Intracerebral inoculation of mice with the chimeras revealed that Chi-VL(IN668) was completely attenuated in neurovirulence. The reduced neurovirulence of Chi-VL(IN668) may be ascribed to its reduced growth in the central nervous system, most likely due to an impaired ability to synthesize viral proteins.     

ω-3 and ω-6 fatty acids and PGE2 stimulate the growth of normal but not tumor mouse mammary epithelial cells: Evidence for alterations in the signaling pathways in tumor cells

The direct effect of ω-3 and ω-6 fatty acids on the proliferation of mouse mammary tumor cells (MTC) was examined in a serum-free cell culture system. While the EGF-induced proliferation of normal mammary epithelial cells was shown to be enhanced by ω-3 and ω-6 fatty acids and prostaglandins (PGs), a majority (75–80%) of primary mammary tumors were not stimulated by these agents. Compared to normal cells, some MTC cultures showed a higher susceptibility to inhibition by ω-3 fatty acids. The general lack of response of MTC cultures to PGE₂ and cyclic adenosine monophosphate (cAMP) suggests some alterations in the cAMP-mediated pathway. However, the PGE₂-induced cAMP levels and cAMP-dependent protein kinase (PKA) activities in the tumor cells were comparable to normal cells. We conclude that the proliferation of mammary tumor cells either follow a cAMP-PKA-independent pathway or have some alterations in the serine/threonine kinase mediated signaling pathway.     

Expression of complete chicken thymidine kinase gene inserted in a retrovirus vector.

The chicken thymidine kinase (tk) gene was inserted into spleen necrosis virus. Thymidine kinase activity was expressed even when the promoter and terminator sequences for tk RNA synthesis were retained. When the promoter was present in the same orientation as the promoter in the long terminal repeat of the virus, deletions occurred both in the virus and in the tk gene, and the thymidine kinase-transforming activity of the recovered virus was low. Splicing of apparent intervening sequences in the tk gene was also observed. When the orientation of the tk promoter was opposite to the promoter in the long terminal repeat, virus synthesis was diminished, whereas thymidine kinase activity was expressed at an elevated level compared with virus in which the promoter was in the same orientation. However, when the apparent tk promoter was deleted from virus with the tk gene in the opposite orientation, a high level of virus synthesis was observed, probably as a result of absence of interference of RNA synthesis from converging promoters. The intervening sequences in the virus in which the promoters were in opposite orientation were not spliced.     

Studies on immobilized Saccharomyces cerevisiae. II. Effect of temperature distribution on continuous rapid ethanol formation in molasses fermentation

Recently, considerable interest has been shown in the study and analysis of immobilized cell reactors. One of the major uses of such a reactor system is expected to be in ethanol production from carbohydrates. One distinct disadvantage of this system is carbon dioxide gas holdup associated with unsteady-state temperature distribution across the reactor. Taking into account the earlier published data and assuming steady-state-substrate balance, and unsteady-state energy balance, and an average gas holdup of 20% with the heat retained by the gas neglected, the average reaction rate in the differential element was computed. Finally, a mathematical model to predict steady-state temperature profile along the reactor was developed. It was verified with experimental data obtained from an immobilized yeast reactor column (1 m x 14.5 cm). The experimental data fit well those computed from the model within an accuracy of 5%.