Mutagenesis studies of the major benzo[a]pyrene N2-dG adduct in a 5'-TG versus a 5'-UG sequence: removal of the methyl group causes a modest decrease in the [G->T/G->A] mutational ratio

The potent mutagen/carcinogen benzo[a]pyrene (B[a]P) is metabolically activated to (+)-anti-B[a]PDE, which induces a full spectrum of mutations primarily at the G:C base pairs (e.g. GC-->TA, GC-->AT, etc.). Each of these mutations can be induced by its major adduct [+ta]-B[a]P-N(2)-dG, where DNA sequence context appears to influence both the quantitative and qualitative pattern of mutagenesis. We noted previously that 5'-TG sequences tend to have a higher fraction of G-->T mutations for both [+ta]-B[a]P-N(2)-dG and (+)-anti-B[a]PDE in comparison with 5'-CG, 5'-GG or 5'-AG sequences. To investigate a possible structural element for this trend, the role (if any) of the methyl group on the 5'-T is considered. Using adduct site-specific means, the [G-->T/G-->A] mutational ratio for [+ta]-B[a]P-N(2)-dG is determined to be approximately 1.08 in a 5'-TGT sequence, and approximately 0.60 in a 5'-UGT sequence. (G-->C mutations are minor.) Although this modest approximately 1.8-fold decrease in [G-->T/G-->A] ratio is statistically significant (P = 0.03), it suggests that the methyl group on the 5'-T is not the main reason why a 5'-T tends to enhance G-->T mutations. This study was prompted by an adduct conformational hypothesis, which predicted that the removal of the methyl group in a 5'-TG sequence would lower the fraction of G-->T mutations; however, the approximately 1.8-fold decrease is too small to do additional experiments to assess whether this conformational hypothesis, or other hypotheses, are the true cause of the decrease, which is discussed in this paper.     

Mutagenesis studies with four stereoisomeric N2-dG benzo[a]pyrene adducts in the identical 5'-CGC sequence used in NMR studies: G->T mutations dominate in each case

Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon (PAH) and a potent mutagen/carcinogen found ubiquitously in the environment. B[a]P is primarily metabolized to diol epoxides, which react principally at N2-dG in DNA. B[a]P-N2-dG adducts have been shown to induce a variety of mutations, notably G-->T, G-->A, G-->C and -1 frameshifts. Four stereoisomers of B[a]P-N2-dG (designated: [+ta]-;, [+ca]-, [-ta] and [-ca]) were studied by NMR in duplex 11mers in a 5'-CGC sequence context, and each adopted a different adduct conformation (Geacintov, et al. (1997) Chem. Res. Toxicol., 10, 111). Herein these four identical B[a]P-containing 11mers are built into duplex plasmid genomes and mutagenesis studied in Escherichia coli following SOS-induction. In nucleotide excision repair (NER) proficient E.coli, no adduct-derived mutants are detected. In NER deficient E.coli, G-->T mutations dominate for all four stereoisomers [+ta]-, [+ca]-, [-ta] and [-ca]-B[a]P-N(2)-dG, and mutation frequency is similar. Thus, the mutagenic pattern for these four B[a]P-N2-dG stereoisomers is the same, in spite of the fact that they adopt dramatically different conformations in ds-oligonucleotides as determined by NMR. These findings suggest that adduct conformation must be fluid enough in the 5'-CGC sequence that the duplex DNA conformation can interconvert to mutagenic and non-mutagenic conformations during lesion-bypass. A comparison of all published studies with these four B[a]P-N2-dG stereoisomers in E.coli reveals that B[a]P-N2-dG adduct stereochemistry tends to have a lesser impact on mutagenic pattern (e.g. G-->T versus G-->A mutations) than does DNA sequence context, which is discussed.     

Eco-friendly microbial route to synthesize cobalt nanoparticles using Bacillus thuringiensis against malaria and dengue vectors

The developments of resistance and persistence to chemical insecticides and concerns about the non-target effects have prompted the development of eco-friendly mosquito control agents. The aim of this study was to investigate the larvicidal activities of synthesized cobalt nanoparticles (Co NPs) using bio control agent, Bacillus thuringiensis against malaria vector, Anopheles subpictus and dengue vector, Aedes aegypti (Diptera: Culicidae). The synthesized Co NPs were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR), Field-emission scanning electron microscopy (FESEM) with energy dispersive X-ray spectroscopy, and Transmission electron microscopy (TEM). XRD analysis showed three distinct diffraction peaks at 27.03°, 31.00°, and 45.58° indexed to the planes 102, 122, and 024, respectively on the face-centered cubic cobalt acetate with an average size of 85.3 nm. FTIR spectra implicated role of the peak at 3,436 cm^?1 for O–H hydroxyl group, 2924 cm^?1 for methylene C–H stretch in the formation of Co NPs. FESEM analysis showed the topological and morphological appearance of NPs which were found to be spherical and oval in shape. TEM analysis showed polydispersed and clustered NPs with an average size of 84.81 nm. The maximum larvicidal mortality was observed in the cobalt acetate solution, B. thuringiensis formulation, and synthesized Co NPs against fourth instar larvae of A. subpictus and A. aegypti with LC₅₀ values of 29.16, 8.12, 3.59 mg/L; 34.61, 6.94, and 2.87 mg/L; r ² values of 0.986, 0.933, 0.942; 0.962, 0.957, and 0.922, respectively.     

Green synthesis of titanium dioxide nanoparticles using Psidium guajava extract and its antibacterial and antioxidant properties

Objective:To determine the efficacies of antibacterial and antioxidant activities of aqueous leaf extract of Psidium guajava mediated biosynthesis of titanium dioxide nanoparticles(TiO_2,NPs).Methods:Synthesized TiO_2 NPs were tested by disc diffusion method against against human pathogenic bacteria.The total antioxidant activity and phenolic content(Folin—Ciocalteau method) of synthesized TiO_2 NTs and aqueous plant extract were determined.The scavenging radicals were estimated hv DPPH method.The synthesized TiO_2 NPs were characterized by XRD,FTIR.FESEM and EDX,Results:FTIR spectra of synthesized TiO_2 NPs exhibited prominent peaks at 3410 cm~(-1)(alkynes),1 578 cm~(-1).1 451 cm~(-1)(alkanes),and 1 123 cm~(-1)(C-O absorption).The morphological characterization of synthesized TiO_2 NPs was analysed by FESEM which showed spherical shape and clusters with an average size of 32.58 nm.The maximum zone of inhibition was observed in the synthesized TiO_2 NPs(20 μg/mL) against Staphylococcus aureus(25 mm) and Escherichia coli(23 mm).The synthesized TiO_2 NPs showed more antibacterial activity than the standard antibiotic disk,tetracycline which drastically reduces the chances for the development of antibiotics resistance of bacterial species.The plant aqueous extract and synthesized TiO_2NPs were found to possess maximum antioxidant activity when compared with ascorbic acid.The content of phenolic compounds(mg/g) in Leaf aqueous extract and synthesized TiO_2 NPs were found to be 85.4 and 18.3 mgTA/g,respectively.Conclusions:Green synthesized TiO_2 NPs provides a promising approach can satisfy the requirement of large-scale industrial production hearing the advantage of low—cost,eco—friendly and reproducible.     

Effects of subthalamic nucleus lesions in a putative model of tardive dyskinesia in the rat

The effects of bilateral excitotoxic lesions of the subthalamic nucleus on vacuous chewing movements induced by chronic neuroleptic therapy were examined in the rat. Fluphenazine decanoate (25 mg/kg i.m. q 3 weeks × 24 weeks) induced vacuous chewing movements, as previously described. This response was suppressed to control levels in animals tested 1–3 weeks following bilateral infusion of quinolinic acid (100 nmol/1 μl per side) into the subthalamic nucleus. Subthalamic nucleus lesions resulted in increased locomotion and sniffing in neuroleptic-naive animals, but these responses were suppressed by concomitant neuroleptic treatment. As vacuous chewing movements induced by chronic neuroleptics are considered to be analogous to tardive dyskinesia in humans, our findings lend further support to the importance of the subthalamic nucleus in the regulation of orofacial movements and suggest that tardive dyskinesia may, in part, be related to altered activity in this structure. This, in turn, suggests that current models of basal ganglia function are inadequate to account for certain pathological states and require re-examination. © 1996 Wiley-Liss, Inc.     

Detection and mapping of hippocampal abnormalities in autism

Brain imaging studies of the hippocampus in autism have yielded inconsistent results. In this study, a computational mapping strategy was used to examine the three-dimensional profile of hippocampal abnormalities in autism. Twenty-one males with autism (age: 9.5+/-3.3 years) and 24 male controls (age: 10.3+/-2.4 years) underwent a volumetric magnetic resonance imaging scan at 3 Tesla. The hippocampus was delineated, using an anatomical protocol, and hippocampal volumes were compared between the two groups. Hippocampal traces were also converted into three-dimensional parametric surface meshes, and statistical brain maps were created to visualize morphological differences in the shape and thickness of the hippocampus between groups. Parametric surface meshes and shape analysis revealed subtle differences between patients and controls, particularly in the right posterior hippocampus. These deficits were significant even though the groups did not differ significantly with traditional measures of hippocampal volume. These results suggest that autism may be associated with subtle regional reductions in the size of the hippocampus. The increased statistical and spatial power of computational mapping methods provided the ability to detect these differences, which were not found with traditional volumetric methods.     

Influence of lattice strain on Fe3O4@carbon catalyst for the destruction of organic dye in polluted water using a combined adsorption and Fenton process

In this study, 8, 25 and 50 wt% Fe₃O₄@activated carbon (AC) catalysts were prepared by simple coprecipitation method. The efficiency of the catalysts for the advanced Fenton''s oxidation process using methylene blue (MB) as a model substrate was tested. Both modified and unmodified activated carbon catalysts exhibited similar activity towards the Fenton''s oxidation process. Therefore, it is difficult to identify the role of the catalyst in this dye removal process. Hence, we proposed a new methodology to remove the MB by adopting the adsorption process initially, followed by the Fenton''s oxidation process. The proposed process significantly improved the methylene blue decomposition reaction over the 25 wt% Fe₃O₄@AC catalyst. However, this trend was not seen in pure activated carbon and Fe₃O₄@AC (8 and 50 wt%) catalysts due to the instability of the material in the oxidizing medium. The possible reason for the deactivation of the catalysts was evaluated from lattice strain calculations, as derived from the modified W–H models (Uniform Deformational Model (UDM), Uniform Stress Deformation Model (USDM) and Uniform Deformation Energy Density Model (UDEDM)). These results provided a quantitative relationship between the experimentally calculated lattice strain values and Fenton''s catalytic activity. Furthermore, the optimized strain value and crystalite size of Fe₃O₄ on the activated carbon matrix are responsible for the high catalytic activity.

The activity of the catalyst was directly correlated using lattice strain calculations, as derived from the W–H model.     

Larvicidal, repellent, and ovicidal activity of marine actinobacteria extracts against Culex tritaeniorhynchus and Culex gelidus

The purpose of the present study was to assess the effect of crude extracts of marine actinobacteria on larvicidal, repellent, and ovicidal activities against Culex tritaeniorhynchus and Culex gelidus (Diptera: Culicidae). The early fourth instar larvae of C. tritaeniorhynchus and C. gelidus, reared in the laboratory, were used for larvicidal, ovicidal, and repellent assay with crude extracts of actinobacteria. Saccharomonospora spp. (LK-1), Streptomyces roseiscleroticus (LK-2), and Streptomyces gedanensis (LK-3) were identified as potential biocide producers. Based on the antimicrobial activity, three strains were chosen for larvicidal activity. The marine actinobacterial extracts showed moderate to high larvicidal effects after 24 h of exposure at 1,000 ppm and the highest larval mortality was found in extract of LK-3 (LC₅₀ = 108.08 ppm and LC₉₀ = 609.15 ppm) against the larvae of C. gelidus and (LC₅₀ = 146.24 ppm and LC₉₀ = 762.69 ppm) against the larvae of C. tritaeniorhynchus. Complete protections for 240 min were found in crude extract of LK-2 and LK-3 at 1,000 ppm, against mosquito bites of C. tritaeniorhynchus and C. gelidus, respectively. After 24-h treatment, mean percent hatchability of the ovicidal activity was observed. The percent hatchability was inversely proportional to the concentration of extract and directly proportional to the eggs. Crude extracts of LK-1 and LK-3 showed no hatchability at 1,000 ppm against C. tritaeniorhynchus and C. gelidus, respectively. This is an ideal ecofriendly approach for the control of Japanese encephalitis vectors, C. tritaeniorhynchus and C. gelidus.