Chemical weed management in wheat at higher altitudes

To evaluate the effect of different herbicides for controlling weeds in wheat (variety Fakhr-i-Sarhad),at higher attitude, an experiment was conducted at Agriculture Research Station, Chitral during Rabi season 2003-04, using Randomized Complete Block Design, keeping four replications. The experiment, sown in November comprised of eight treatments, viz; seven herbicides and a weedy check. Each treatment consisted of 5 rows each 30 cm apart and 5 m long thus giving a total size of 5 m x 1.5 m. The herbicides used included; terbutryn + triasulfuron at 0.16 kg, 2,4-D at 0.7 kg, fenoxaprop-P-ethyl at 0.93 kg, clodinafop at 0.05 kg, bromoxynil + MCPA at 0.49 kg, carfentrazon-ethyl at 0.02 kg and isoproturon at 1.0 kg a.i ha(-1). The data were recorded on weed kill efficiency (%), fresh weed biomass (kg ha(-1)), plant height (cm), spike length (cm), number of tillers m(-2), number of grains spike(-1), thousand grains weight (g), biological yield (kg ha(-1)), grain yield (kg ha(-1)) and harvest index (%). The data recorded on weed kill efficiency, weed biomass (kg ha1), grains yield (kg ha(-1)) and harvest index (%) were significantly affected by the different herbicidal treatments. Statistically isoproturon treatment exhibited the best performance, with maximum weed kill efficiency (48.26%) and minimum fresh weed biomass (433.3 kg ha(-1)) as compared to weedy check (6 %) and (1102 kg ha(-1)), respectively. Similarly, the spike length (8.34 cm), number of tillers (427 m(-2)), number of grains spike(-1) (38.0), thousand grains weight (39.85 g), biological yield (8475 kg ha(-1)), grain yield (2530 kg ha(-1)) and harvest index (31.3%) were the highest in isoproturon treatments as compared to weedy check having (7.64 cm), (356 m(-2)), (34.1), (37.12 g), (6858 kg), (1913 kg ha(-1)) and (27%), respectively.     

Molecular docking analysis of known flavonoids as duel COX-2 inhibitors in the context of cancer

Cyclooxygenase-2 (COX-2) catalyzed synthesis of prostaglandin E2 and it associates with tumor growth, infiltration, and metastasis in preclinical experiments. Known inhibitors against COX-2 exhibit toxicity. Therefore, it is of interest to screen natural compounds like flavanoids against COX-2. Molecular docking using 12 known flavanoids against COX-2 by FlexX and of ArgusLab were performed. All compounds showed a favourable binding energy of >-10 KJ/mol in FlexX and > -8 kcal/mol in ArgusLab. However, this data requires in vitro and in vivo verification for further consideration.     

Formation of dopamine quinone-DNA adducts and their potential role in the etiology of Parkinson's disease

The neurotransmitter dopamine is oxidized to its quinone (DA-Q), which at neutral pH undergoes intramolecular cyclization by 1,4-Michael addition, followed by oxidation to form leukochrome, then aminochrome, and finally neuromelanin. At lower pH, the amino group of DA is partially protonated, allowing the competitive intermolecular 1,4-Michael addition with nucleophiles in DNA to form the depurinating adducts, DA-6-N3Ade and DA-6-N7Gua. Catechol estrogen-3,4-quinones react by 1,4-Michael addition to form the depurinating 4-hydroxyestrone(estradiol)-1-N3Ade [4-OHE1(E2)-1-N3Ade] and 4-OHE1(E2)-1-N7Gua adducts, which are implicated in the initiation of breast and other human cancers. The effect of pH was studied by reacting tyrosinase-activated DA with DNA and measuring the formation of depurinating adducts. The most adducts were formed at pH 4, 5, and 6, and their level was nominal at pH 7 and 8. The N3Ade adduct depurinated instantaneously, but N7Gua had a half-life of 3 H. The slow loss of the N7Gua adduct is analogous to that observed in previous studies of natural and synthetic estrogens. The antioxidants N-acetylcysteine and resveratrol efficiently blocked formation of the DA-DNA adducts. Thus, slightly acidic conditions render competitive the reaction of DA-Q with DNA to form depurinating adducts. We hypothesize that formation of these adducts could lead to mutations that initiate Parkinson's disease. If so, use of N-acetylcysteine and resveratrol as dietary supplements may prevent initiation of this disease.     

EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy

Hepatitis C virus (HCV) is a major cause of liver disease, but therapeutic options are limited and there are no prevention strategies. Viral entry is the first step of infection and requires the cooperative interaction of several host cell factors. Using a functional RNAi kinase screen, we identified epidermal growth factor receptor and ephrin receptor A2 as host cofactors for HCV entry. Blocking receptor kinase activity by approved inhibitors broadly impaired infection by all major HCV genotypes and viral escape variants in cell culture and in a human liver chimeric mouse model in vivo. The identified receptor tyrosine kinases (RTKs) mediate HCV entry by regulating CD81-claudin-1 co-receptor associations and viral glycoprotein-dependent membrane fusion. These results identify RTKs as previously unknown HCV entry cofactors and show that tyrosine kinase inhibitors have substantial antiviral activity. Inhibition of RTK function may constitute a new approach for prevention and treatment of HCV infection.     

Organization of the CTX prophage in environmental isolates of Vibrio mimicus

The organization of the CTX prophage in environmental strains of Vibrio mimicus was investigated. Sixteen hundred non-sucrose fermenting vibrios were examined for ctx gene by hybridization. Out of 1,600 isolates, 6 V. mimicus isolates contained ctxA gene. The organization of CTX prophage was determined by RFLP using ctxA probe. The CTX prophage integrated at a single site in V. mimicus genome which was present as a single copy flanked by at least a single RS element. Ribotype pattern revealed that a particular clone of V. mimicus acquired the CTXPhi in the aquatic environment. This study demonstrated that V. mimicus could act as a reservoir of CTXPhi in the aquatic environment.     

Model platinum nucleobase and nucleoside complexes and antitumor activity: X-ray crystal structure of [PtIV(trans-1R,2R-diaminocyclohexane)trans-(acetate)2(9-ethylguanine)Cl]NO3.H2O

A series of platinum(II) and (IV) monoadducts of the type [Pt(II)(DACH)LCl]NO3 and [Pt(IV)(DACH)trans-(X)2LCl]NO3 (where DACH=trans-1R,2R-diaminocyclohexane, L=adenine, guanine, hypoxanthine, cytosine, adenosine, guanosine, inosine, cytidine, 9-ethylguanine (9-EtGua), or 1-methylcytosine and X=hydroxo or acetato ligand) have been synthesized and characterized by elemental analysis and by 1H and 195Pt nuclear magnetic resonance (NMR) spectroscopy. The crystal structure of the model nucleobase complex [Pt(IV)(trans-1R,2R-diaminocyclohexane)trans-(acetate)2(9-EtGua)Cl]NO3.H2O was determined using a single crystal X-ray diffraction method. The compound crystallized in the monoclinic space group P2(1), with a=10.446(2) A, b=22.906(5) A, c=10.978(2) A, Z=4, and R=0.0718, based upon the total of 11,724 collected reflections. In this complex, platinum had a slightly distorted octahedron geometry owing to the presence of a geometrically strained five-member ring. The two adjacent corners of the platinum plane were occupied by the two amino nitrogen of DACH, whereas, the other two equatorial positions occupied by chloride ion and 9-ethylguanine. The remaining two axial positions were occupied by the oxygen atoms of acetato ligands. The DACH ring was in a chair configuration. An intricate network of intermolecular hydrogen bonds held the crystal lattice together. Some of these synthesized models of DACH-Pt-DNA adducts have good in vitro cytotoxic activity against the cisplatin-sensitive human cancer ovarian A2780 cell line (IC50=1-8 microM). Interestingly, a substituted nucleobase (9-ethylguanine) adduct was over 6-fold more potent than regular adducts. The cross-resistance factor against the 44-fold cisplatin-resistant 2780CP/clone 16 cells was about 3-9; thus, the cytotoxicity of adducts was indicative of low potency, but the resistance factors were also substantially low. These results suggest that DNA adducts of DACH-Pt are cytotoxic with low cross-resistance.     

Metal binding and antibacterial activity of ciprofloxacin complexes

Four novel cobalt(II), copper(II), nickel(II) and zinc(II) complexes of the fluoroquinolone antibiotic ciprofloxacin have been prepared. The compounds were characterized by IR, UV-Visible, molar conductivity and elemental analyses. In all of the complexes, the drug ligand, ciprofloxacin (CFL) was coordinated through two carbonyl oxygen atoms. Octahedral and square-planar geometries have been proposed for the cobalt(II), nickel(II) and zinc(II), and copper(II) complexes, respectively. In vitro tests of susceptibility to these metal complexes showed stronger activity than that of ciprofloxacin against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Bacillus dysenteriae.     

Pandemic strains of O3:K6 Vibrio parahaemolyticus in the aquatic environment of Bangladesh

A total of 1500 environmental strains of Vibrio parahaemolyticus, isolated from the aquatic environment of Bangladesh, were screened for the presence of a major V. parahaemolyticus virulence factor, the thermostable direct haemolysin (tdh) gene, by the colony blot hybridization method using a digoxigenin-labeled tdh gene probe. Of 1500 strains, 5 carried the tdh sequence, which was further confirmed by PCR using primers specific for the tdh gene. Examination by PCR confirmed that the 5 strains were V. parahaemolyticus and lacked the thermostable direct haemolysin-related haemolysin (trh) gene, the alternative major virulence gene known to be absent in pandemic strains. All 5 strains gave positive Kanagawa phenomenon reaction with characteristic beta-haemolysis on Wagatsuma agar medium. Southern blot analysis of the HindIII-digested chromosomal DNA demonstrated, in all 5 strains, the presence of 2 tdh genes common to strains positive for Kanagawa phenomenon. However, the 5 strains were found to belong to 3 different serotypes (O3:K29, O4:K37, and O3:K6). The 2 with pandemic serotype O3:K6 gave positive results in group-specific PCR and ORF8 PCR assays, characteristics unique to the pandemic clone. Clonal variations among the 5 isolates were analyzed by comparing RAPD and ribotyping patterns. Results showed different patterns for the 3 serotypes, but the pattern was identical among the O3:K6 strains. This is the first report on the isolation of pandemic O3:K6 strains of V. parahaemolyticus from the aquatic environment of Bangladesh.     

Isolation and molecular characterization of toxigenic Vibrio parahaemolyticus from the Kii Channel, Japan

Studies were conducted on the ecology of potentially pathogenic Vibrio parahaemolyticus in three coastal areas of Kii Channel, Tokushima, Japan. Seawater and seaweed samples were collected seasonally between June 2003 and May 2004. Total and toxigenic strains of V. parahaemolyticus were isolated using most probable number culture and colony blot hybridization. Toxigenic strains were serotyped and further characterized by random amplified polymorphic DNA (RAPD) and ribotyping. Six thousand strains of V. parahaemolyticus were isolated and 18 were found positive for tdh. V. parahaemolyticus were detected in all samples during summer and autumn, and from some samples during winter and spring. Among the toxigenic strains seven serotypes, five ribotypes and RAPD patterns were observed. Seven strains belonged to O3:K6 clone with identical ribotypes and RAPD patterns to that of a pandemic reference strain. The presence of toxigenic V. parahaemolyticus with pandemic potential might indicate a human health risk due to consumption of marine food sources.