Synthesis and biological evaluation of trans 6-methoxy-1,1-dimethyl-2-phenyl-3-aryl-2,3-dihydro-1H-inden-4-yloxyalkylamine derivatives against drug susceptible,non-replicating M. tuberculosis H37Rv and clinical multidrug resistant strains

Synthesis of a library of novel trans 6-methoxy-1,1-dimethyl-2-phenyl-3-aryl-2,3-dihydro-1H-inden-4-yloxy alkyl amines and their antimycobacterial activity against drug sensitive and multidrug resistant strains of Mycobacterium tuberculosis have been reported. All the new compounds in the series exhibited MIC between 1.56 and 6.25 μg/ml. Two compounds 1i and 1j with low MIC and low cytotoxicity showed significant reduction in CFU in infected mouse macrophages at 1× MIC concentration. The compound 1i inhibited the growth of M. tuberculosis in mice at 100 mg/kg dose with 1.35 log₁₀ reduction of CFU in lungs tissue and was active against non-replicating Mycobacterium tuberculosis under anaerobic condition.     

Space use and genetic structure do not maintain color polymorphism in a species with alternative behavioral strategies

Space use including territoriality and spatial arrangement within a population can reveal important information on the nature, dynamics, and evolutionary maintenance of alternative strategies in color polymorphic species. Despite the prevalence of color polymorphic species as model systems in evolutionary biology, the interaction between space use and genetic structuring of morphs within populations has rarely been examined. Here, we assess the spatial and genetic structure of male throat color morphs within a population of the tawny dragon lizard, Ctenophorus decresii. Male color morphs do not differ in morphology but differ in aggressive and antipredator behaviors as well as androgen levels. Despite these behavioral and endocrine differences, we find that color morphs do not differ in territory size, with their spatial arrangement being essentially random with respect to each other. There were no differences in genetic diversity or relatedness between morphs; however, there was significant, albeit weak, genetic differentiation between morphs, which was unrelated to geographic distance between individuals. Our results indicate potential weak barriers to gene flow between some morphs, potentially due to nonrandom pre‐ or postcopulatory mate choice or postzygotic genetic incompatibilities. However, space use, spatial structure, and nonrandom mating do not appear to be primary mechanisms maintaining color polymorphism in this system, highlighting the complexity and variation in alternative strategies associated with color polymorphism.     

Lipid peroxidation in plumbagin administered rats

Plumbagin was administered to rats at a concentration of 1,2,4,8 and 16 mg per kg body weight. After 24 h lipid peroxide levels were found to decrease in subcellular fractions of liver. Plumbagin inhibited ascorbate and nicotinafde adenine dinucleotide phosphate (reduced) dependent lipid peroxidation but was without any effect on cumene hydroperoxide dependent lipid peroxidation. Injection of 16 mg of plumbagin per kg body weight was found to decrease liver total reduced glutathione and also fcrosomal glucose-6-phosphatase. The results are discussed with reference to the anti- and prooxidant properties of plumbagin.     

Taste systems of the petrosal ganglion of the rat glossopharyngeal nerve

Single unit recordings were taken from sensory ganglion cellsin the petrosal ganglion (PG) of the glossopharyngeal nerveof the rat. These taste units were examined with respect tospontaneous and evoked discharge patterns and responsivenessto a wide variety of chemical compounds, most of natural occurrence.Spontaneous activity patterns, with few exceptions, tended tobe extremely irregular with both bursting (clusters of 2–3spikes) and grouping (large groups of spikes as in evoked discharges).Most interspike interval histograms of spontaneous activitywere multimodal, similar to rat geniculate ganglion (GG) units.Evoked discharges usually displayed grouping of spikes, andlong latencies of onset and persistence of discharge after rinsewere sometimes seen. Little response was shown to nucleotidesor salts. Units responsive to amino acids tended to show largedischarge to only one or two amino acids; and the most responsiveamino acid usually varied from cell to cell. Units responsiveto alkaloids only responded to a few alkaloids with atropineand quinine being the most stimulatory. Units responsive toacids only discharged to a few of the acids tested and oftenacids of low pH elicited no discharge. Saccharin activated unitsresponsive to both sugar and alkaloids. A few units highly responsiveto both sugar and alkaloids were seen. The units were placedinto four clusters on the basis of chemicals activating themand certain neurophysiological characteristics: PG salt units,PG acid units and, tentatively, amino acid (sugar) units andX (alkaloid and alkaloid plus) units. The PG salt units didnot show the exclusive sensitivity to sodium and lithium compoundsas did the GG salt units. The PG acid units could also be differentiatedfrom the GG acid units. The petrosal amino acid and X units,on the other hand, could not be differentiated from similarunits in the rat GG.     

Glycosaminoglycan (GAG) level and activities of certain enzymes of GAG metabolism in Culex quinquefasciatus and Setaria digitata

Significant differences were observed in GAG metabolism of S. digitata and one of its intermediate vectors, C. quinquefasciatus. Distribution of different components such as hyaluronic acid, heparin-sulphate, chondroitin-4-sulphate, chondroitin-6-sulphate, dermatan sulphate and heparin was comparable in both. However, there were quantitative differences; the difference was marked in the activity of enzymes of GAG metabolism in presence and absence of diethylcarbamazine (DEC) a known antifilarial drug. While the activities of beta-galactosidase and beta-N-acetyl glucosaminidase of S. digitata systems showed an inhibition of 96.5 and 92.6% respectively, in the Culex systems they showed an inhibition of 93.3% and an activation of 18% respectively. The differences clearly indicate the existence of basic differences in GAG metabolism of vector and parasite.     

Influence of trace elements on biogas production from mango processing waste in 1.5 m3 KVIC digesters

Summary The influence of trace elements (Co²⁺, Ni²⁺ and Fe³⁺) in varying concentrations and combination, was studied in 1.5 m³ Khadi & Village Industries Commission (KVIC) digesters for biogas generation from mangopeel. Addition of these trace metals enhanced the biogas yield and methane content moderately, the maximum being with the iron fed digester. The digesters were always found to be stable without much variation in total volatile fatty acids (VFA), pH, total alkalinity and other parameters. A methane content of 62% and biogas yield of 0.49 m³/kg VS added was obtained with 4000 mg/L FeCl₃ supplemented mangopeel fed digester as compared to control having biogas yield of 0.22 m³/kg VS added with a methane content of about 48–50%.     

Stereochemical effects of non-ionic methylphosphonates on nucleotide conformations.

The preferred conformations of deoxyribo and ribonucleoside 3'-methylphosphonates are analysed by minimizing the conformational energy as a function of all the major parameters including the sugar ring for both the S- and R-isomers. The results show that neither the substitution nor the nature of the diastereomer affects significantly the preferred conformations compared to the naturally occurring nucleoside 3'-phosphates. The preferred range of C3'-O3' bond torsions or the phase angles of pseudorotation (P) of the sugar are unaffected. The chiral substitution on the phosphate always adopts a conformation distal to the secondary C3' carbon atom in the minimum energy conformational state. Further, it introduces certain restrictions on the preferred range of P-O3' torsions depending on the methylphosphonate configuration. Methylphosphonate, especially the S-isomer, renders the normal gauche- range of P-O3' bond torsions responsible for the stacked helical duplexes to be energetically unfavourable besides introducing a high energy barrier between trans and gauche conformations. Therefore it is suggested that duplexes with S-methylphosphonate may favour extended phosphodiester conformations. These factors explain the observed lower melting temperature as well as the downfield shifts in the 31P signals in duplexes containing the S-isomer.     

Neurophysiology of geniculate ganglion (facial nerve) taste systems: species comparisons

On the basis of various measures taken from geniculate gangliontaste neurons in four species, it was concluded that withineach species the neurons could be subdivided into distinct functionalgroups. In this report, the neural groups of different specieswere directly compared. Units from all four species were studiedwith a common test series of solutions in addition to otherstimuli. Since these stimuli were presented at the same concentrationsto all species, direct quantitative comparisons across specieswere possible for a wide range of chemical compounds. In addition,the neural groups were compared with respect to spontaneousand evoked activity measures, latency to electrical stimulation,and receptive field characteristics. These neurophysiologicaldata suggest a basic model of four distinct subgroups: acidunits, salt units, amino acid units, and X units.     

Expression and posttranslational processing of preprodynorphin complementary DNA in the mouse anterior pituitary cell line AtT-20

A recombinant plasmid containing the rat prodynorphin cDNA was introduced into the mouse anterior pituitary corticotroph cell line AtT-20. These cells normally express and posttranslationally process proopiomelanocortin, but not prodynorphin. Stable transformants were isolated and analyzed for the expression and processing of prodynorphin. The stably transformed AtT-20 cells that expressed a 1.3-kilobase prodynorphin mRNA also expressed prodynorphin protein and processed it to dynorphin peptides. The peptides included leucine-enkephalin, beta-neoendorphin, dynorphin-A8, and dynorphin-B, as identified by gel filtration and reverse phase HPLC followed by RIA using peptide-specific antisera. These results demonstrate that AtT-20 cells efficiently and accurately process prodynorphin at both dibasic sites and monobasic cleavage sites, indicating that the AtT-20 cells contain enzymes capable of cleaving the precursor not only at dibasic residues but also at monobasic residues. The release of prodynorphin-derived peptides paralleled secretion of endogenous proopiomelanocortin-derived peptides when stimulated by CRF, a natural secretagogue for ACTH.     

A study on large radial motion of arteries in vivo

This study analyses the radial periodic motion of an artery which is modelled as a thin cylinder of uniform cross-section subjected to dynamic inner pressure using the theory of finite deformation of elastic materials. The arterial tissue properties (anisotropy, homogeneity and incompressibility) are taken into account in an analysis based on the use of the strain energy function. The validity of the mathematical analysis is illustrated through numerical computation applying the available in vivo data for elastic constants of the canine middle descending thoracic aorta to the expressions for the intramural pressure and circumferential stresses obtained by solving the necessary equation of motion together with the boundary conditions. Results obtained in this study indicate very low stresses which suggest that the arteriosclerosis resulting from high stress gradients is effectively ruled out in this model.