New series of 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazine thione (THTT) derivatives: Synthesis and potent antileishmanial activity

Four series of heterocyclic compounds, namely, tetrahydro-2H-1,3,5-thiadiazine thione derivatives were synthesized in good to excellent yields and were screened for their in vitro antileishmanial activities against Leishmania major (promastigotes). Most of the compounds showed significant antileishmanial activity within the range of IC₅₀?=?15.48–39.36?μM when compared with standard pentamidine (IC₅₀?=?14.95?μM). The structure-activity relationship showed that N-3 and N-5 substituents have a key role against leishmanicidal activity. The ester analogues (series B) were found to have a 1.5 to 5-fold reduced activity compared to their acidic counterparts. Cytotoxicity against mammalian mouse fibroblast 3?T3 cells was also evaluated and compared between the acid and its ester analogue. The reduction of antileishmanial activity and loss of toxicity in the newly developed THTT ester derivative indicates that these compounds can be used as a template study for the production of effective antileishmanial ester prodrugs.     

Studies on the expression of marker genes in chickpea

Conditions were established for the optimum transient expression of beta-glucuronidase and neomycin phosphotransferase II genes introduced into zygotic embryos of chickpea (Cicer arietinum L. 6153 and CM72) by accelerated tungsten particles. Plasmid DNA at a concentration of 12 microgram per milligram of tungsten particles when accelerated with an inflow of helium gas at 60 kilogram per square centimeter through a distance of 24 centimeter in a chamber maintained at a negative pressure of 71.12 centimeter of mercury, resulted in optimal transient expression of the beta-glucuronidase gene in chickpea embryos. However, the expression of the marker genes was 20-40% higher under a cauliflower mosaic virus promoter in comparison to the Win6 and actin promoters. When Agrobacterium tumefaciens was used to transfer marker genes into zygotic embryos and the resultant plants were analysed for activity of the beta-glucuronidase and neomycin phosphotransferase II genes, both of these genes were expressed in tumorous tissues. When a disarmed strain of Agrobacterium was used, normal shoots were regenerated in which the lower parts showed expression of both genes at a frequency of 20%. This revised version was published online in June 2006 with corrections to the Cover Date.     

Effects of quinine on K+ transport in heart mitochondria

Quinine inhibits the respiration-dependent extrusion of K⁺ from Mg²⁺-depleted heart mitochondria and the passive osmotic swelling of these mitochondria in K⁺ and Na⁺ acetate at alkaline pH. These observations concur with those of Nakashima and Garlid (J. Biol. Chem. 257, 9252, 1982) using rat liver mitochondria. Quinine also inhibits the respiration-dependent contraction of heart mitochondria swollen passively in Na⁺ or K⁺ nitrate and the increment of elevated respiration associated with the extrusion of ions from these mitochondria. Quinine, at concentrations up to 0.5 mM, inhibits the respiration-dependent⁴²K⁺/K⁺ exchange seen in the presence of mersalyl, but higher levels of the drug produce increased membrane permeability and net K⁺ loss from the matrix. These results are all consistent with an inhibition of the putative mitochondrial K⁺/H⁺ antiport by quinine. However, quinine has other effects on the mitochondrial membrane, and possible alternatives to this interpretation are discussed.     

Molecular cloning of cDNA for the catalytic subunit of rat liver type 2A protein phosphatase, and detection of high levels of expression of the gene in normal and cancer cells

A cloned cDNA encoding a catalytic subunit of type 2A protein phosphatase from a rat liver cDNA library was obtained by use of a synthetic oligonucleotide corresponding to the tryptic peptide sequence of the purified enzyme. There was only a single amino acid difference between the deduced amino acid sequence of the clone obtained and those of the catalytic subunits, 2A alpha, of the rabbit skeletal muscle, porcine kidney and human liver enzymes, suggesting that this clone was a rat 2A alpha cDNA. On Northern blot analysis using a cDNA fragment as a probe, three mRNA species were detected in rat liver: a major mRNA of 2.0 kb and a minor one of 2.7 kb under high stringency conditions, and also a 1.1 kb mRNA under low stringency conditions. The 2A alpha gene was found to be highly expressed in various tissues of rat, especially the brain. High levels of expression of the gene were also detected in mouse NIH3T3 cells and their transformants, and in human cancer cell lines as well as a human immortalized cell line.     

An analysis of the flow of a power law fluid due to ciliary motion in an infinite channel

The propulsion mechanics of cilia-induced flow is studied through a mathematical model. The problem of two-dimensional motion of a power law fluid inside a channel with ciliated walls is considered. The characteristics of ciliary systems are determined by the dominance of viscous effects over inertial effects using the long-wavelength approximation. Solutions for the longitudinal, transverse, and resultant velocities are obtained. The pressure gradient and volume flow rate for different values of the power law index are also calculated. The flow properties for the power law fluid are determined as a function of the cilia and metachronal wave velocity. The viscous and power law fluid are compared and discussed graphically.     

Exploration of Genetic Pattern of Phenological Traits in Wheat (<i>Triticum aestivum</i> L.) under Drought Stress

Drought is the major detrimental environmental factor for wheat (Triticum aestivum L.) production. The exploration of genetic patterns underlying drought tolerance is of great significance. Here we report the gene actions controlling the phenological traits using the line × tester model studying 27 crosses and 12 parents under normal irrigation and drought conditions. The results interpreted via multiple analysis (mean performance, correlations, principal component, genetic analysis, heterotic and heterobeltiotic potential) disclosed highly significant differences among germplasm. The phenological waxiness traits (glume, boom, and sheath) were strongly interlinked. Flag leaf area exhibits a positive association with peduncle and spike length under drought. The growing degree days (heat-units) greatly influence spikelets and grains per spike, however, the grain yield/plant was significantly reduced (17.44 g to 13.25 g) under drought. The principal components based on eigenvalue indicated significant PCs (first-seven) accounted for 79.9% and 73.9% of total variability under normal irrigation and drought, respectively. The investigated yield traits showed complex genetic behaviour. The genetic advance confronted a moderate to high heritability for spikelets/spike and grain yield/plant. The traits conditioned by dominant genetic effects in normal irrigation were inversely controlled by additive genetic effects under drought and vice versa. The magnitude of dominance effects for phenological and yield traits, i.e., leaf twist, auricle hairiness, grain yield/plant, spikelets, and grains/spike suggests that selection by the pedigree method is appropriate for improving these traits under normal irrigation conditions and could serve as an indirect selection index for improving yield-oriented traits in wheat populations for drought tolerance. However, the phenotypic selection could be more than effective for traits conditioned by additive genetic effects under drought. We suggest five significant cross combinations based on heterotic and heterobeltiotic potential of wheat genotypes for improved yield and enhanced biological production of wheat in advanced generations under drought.     

The acyl composition of mammalian phospholipids: an allometric analysis

Data concerning the acyl composition of tissue phospholipids from mammal species, ranging in size from the shrew (7 g) to cattle (370 kg), has been collated from the literature and analysed allometrically. Phospholipids from heart, skeletal muscle, liver and kidney exhibited similar allometric trends whereby phospholipids had a significant decrease in unsaturation index (number of double bonds per 100 acyl chains) as species body size increased whilst there was no change in the percent of unsaturated acyl chains. Whilst total polyunsaturate content did not change with body mass, both heart and skeletal muscle phospholipids showed a significant allometric decrease in the omega-3 polyunsaturate content. The content of the highly polyunsaturated docosahexaenoic acid (22:6 n-3) in phospholipids showed significant and substantial allometric decline with increasing body mass in all four tissues (exponents ranged from -0.19 in liver to -0.40 in skeletal muscle). Brain phospholipids showed no allometric trends in acyl composition and were highly polyunsaturated in all species. These trends are discussed in light of the hypothesis that the relative content of polyunsaturated acyl chains in membranes, and especially docosahexaenoate (22:6 n-3), can act as a membrane pacemaker for metabolic activity.