7,8-dihydropyrido[2,3-d]pyrimidin-2-one; a bicyclic cytosine analogue capable of enhanced stabilisation of DNA duplexes

Incorporation of a bicyclic cytosine analogue, 3-beta-D-(2'-deoxyribofuranosyl)7,8- dihydropyrido[ 2,3-d] pyrimidine, into synthetic DNA duplexes results in a greatly enhanced thermal stability ( 3 - 4 degrees C per modification) compared to the corresponding unmodified duplex.

Single versus multiple occupancy - Effects on toxicity parameters measured on Eisenia fetida in lead nitrate-treated soil

The mortality (7 and 14 d), weight change (7 and 14 d), and metal uptake of Eisenia fetida (Savigny, 1826) kept in Pb(NO3)(2)-treated Kettering loam soil in single- and multiple-occupancy (10 earthworms) test containers were determined. The number of earthworms to dry mass (g) ratio of soil was 1:50 in both sets of test containers. Lead concentrations were in the nominal range of 0 to 10,000 mg Pb/kg soil (mg/kg hereafter). Levels of mortality at a given concentration were statistically identical between the single- and multiple-occupancy tests, except at 1,800 mg/kg, at which significantly (p less than or equal to 0.05) more mortality occurred in the multiple-occupancy tests. Death of individual earthworms in the multiple-occupancy tests did not trigger death of the other earthworms in that soil. The LC50 values (concentration statistically likely to kill 50% of the population) were identical between the multiple- and single-occupancy soils: 2,662 mg/kg (2,598-2,984, 7 d) and 2,589 mg/kg (2,251-3,013, 14 d) for the multiple-occupancy soils and 2,827 mg/kg (2,443-3,168, both 7 and 14 d) for the single-occupancy soils (values in brackets represent the 95% confidence intervals). Data were insufficient to calculate the concentration statistically likely to reduce individual earthworm mass by 50% (EC50), but after 14 d, the decrease in earthworm weight in the 1,800 and 3,000 mg/kg tests was significantly greater in the multiple- than in the single-occupancy soils. At 1,000, 1,800, and 3,000 mg/kg tests, earthworm Pb tissue concentration was significantly (p less than or equal to 0.05) greater in earthworms from the multiple-occupancy soils. The presence of earthworms increased the NH3 content of the soil; earthworm mortality increased NH3 concentrations further but not to toxic levels.

Preparation and properties of gallaborane, GaBH6: structure of the gaseous molecule H2Ga(μ-H)2BH2 as determined by vibrational, electron diffraction, and ab initio studies, and structure of the crystalline solid at 110 K as determined by x-ray diffraction``

Gallaborane (GaBH6, 1), synthesized by the metathesis of LiBH4 with [H2GaCl]n at ca. 250 K, has been characterized by chemical analysis and by its IR and 1H and 11B NMR spectra. The IR spectrum of the vapor at low pressure implies the presence of only one species, viz. H2Ga(μ-H)2BH2, with a diborane-like structure conforming to C2v symmetry. The structure of this molecule has been determined by gas-phase electron diffraction (GED) measurements afforced by the results of ab initio molecular orbital calculations. Hence the principal distances (rα in Å) and angles ( α in deg) are as follows: r(Ga•••B), 2.197(3); r(Ga−Ht), 1.555(6); r(Ga−Hb), 1.800(6); r(B−Ht), 1.189(7); r(B−Hb), 1.286(7); Hb−Ga−Hb, 71.6(4); and Hb−B−Hb, 110.0(5) (t = terminal, b = bridging). Aggregation of the molecules occurs in the condensed phases. X-ray crystallographic studies of a single crystal at 110 K reveal a polymeric network with helical chains made up of alternating pseudotetrahedral GaH4 and BH4 units linked through single hydrogen bridges; the average Ga•••B distance is now 2.473(7) Å. The compound decomposes in the condensed phases at temperatures exceeding ca. 240 K with the formation of elemental Ga and H2 and B2H6. The reactions with NH3, Me3N, and Me3P are also described.

Atmospheric chemistry of C4F9OC2H5 (HFE-7200), C4F9OCH3 (HFE-7100), C3F7OCH3 (HFE-7000) and C3F7CH2OH: temperature dependence of the kinetics of their reactions with OH radicals, atmospheric lifetimes and global warming potentials

The atmospheric chemistry of several gases used in industrial applications, C4F9OC2H5 (HFE-7200), C4F9OCH3 (HFE-7100), C3F7OCH3 (HFE-7000) and C3F7CH2OH, has been studied. The discharge flow technique coupled with mass-spectrometric detection has been used to study the kinetics of their reactions with OH radicals as a function of temperature. The infrared spectra of the compounds have also been measured. The following Arrhenius expressions for the reactions were determined (in units of cm3 molecule-1 s-1): k(OH + HFE-7200) = (6.9+2.3-1.7) × 10-11 exp(-(2030 ± 190)/T); k(OH + HFE-7100) = (2.8+3.2-1.5) × 10-11 exp(-(2200 ± 490)/T); k(OH + HFE-7000) = (2.0+1.2-0.7) × 10-11 exp(-(2130 ± 290)/T); and k(OH + C3F7CH2OH) = (1.4+0.3-0.2) × 10-11 exp(-(1460 ± 120)/T). From the infrared spectra, radiative forcing efficiencies were determined and compared with earlier estimates in the literature. These were combined with the kinetic data to estimate 100-year time horizon global warming potentials relative to CO2 of 69, 337, 499 and 36 for HFE-7200, HFE-7100, HFE-7000 and CF3CF2CF2CH2OH, respectively.

Detection and enumeration of sulphate-reducing bacteria in estuarine sediments by competitive PCR

The distribution of sulphate-reducing bacteria (SRB) in the sediments of the Colne River estuary, Essex, UK covering different saline concentrations of sediment porewater was investigated by the use of quantitative competitive PCR. Here, we show that a new PCR primer set and a new quantitative method using PCR are useful tools for the detection and the enumeration of SRB in natural environments. A PCR primer set selective for the dissimilatory sulphite reductase gene (dsr) of SRB was designed. PCR amplification using the single set of dsr-specific primers resulted in PCR products of the expected size from all 27 SRB strains tested, including Gram-negative and positive species. Sixty clones derived from sediment DNA using the primers were sequenced and all were closely related with the predicted dsr of SRB. These results indicate that PCR using the newly designed primer set are useful for the selective detection of SRB from a natural sample. This primer set was used to estimate cell numbers by dsr selective competitive PCR using a competitor, which was about 20% shorter than the targeted region of dsr. This procedure was applied to sediment samples from the River Colne estuary, Essex, UK together with simultaneous measurement of in situ rates of sulphate reduction. High densities of SRB ranging from 0.2 - 5.7 × 108 cells ml-1 wet sediment were estimated by the competitive PCR assuming that all SRB have a single copy of dsr. Using these estimates cell specific sulphate reduction rates of 10-17 to 10-15 mol of SO42- cell-1 day-1 were calculated, which is within the range of, or lower than, those previously reported for pure cultures of SRB. Our results show that the newly developed competitive PCR technique targeted to dsr is a powerful tool for rapid and reproducible estimation of SRB numbers in situ and is superior to the use of culture-dependent techniques.

Stability of plasmid profile of highly virulent races of Xanthomonas campestris pv. malvacearum during storage and subculturing

Four races of Xanthomonas campestris pv. mal-vacearum (Xcm) viz. races 23, 27 and 32 (isolated from Gossypium hirsutum) and race 23b (from Gossypium barbadense) were studied. The plasmid profile of the natural isolates showed four plasmids in races 23 and 23b (ca. 60, 40, 23, 8.2 kb), five in race 27 (ca. 60, 40, 23, 8.2 and 3.7 kb) and six in race 32 (ca. 60, 40, 23, 8.2, 3.7 and 1.6 kb). Continuously sub-cultured laboratory isolates of the Xcm races resulted in the loss of all but two plasmids, ca. 60 and 40 kb in size. When the laboratory isolates were passed through cotton (Gossypium hirsutum), they regained certain plasmids so that four plasmids were found in race 23 and 23b (ca. 60, 40, 23 and 8.2 kb), five in race 27 (ca. 60, 40, 23, 8.2 and 3.7 kb) and six in race 32 (ca. 60, 40, 23, 8.2, 3.7 and 1.6 kb), which was more or less similar to the original isolates. The isolates recovered from cotton maintained their plasmid profile (except for minor changes in the miniplasmids) after storage for six months at -70degreesC in 50% glycerol. It is suggested that plasmid profiles among highly virulent races of Xcm are unstable during repeated sub-culturing at room temperature, resulting in rapid loss of some plasmids. However, when the cultures were sub-cultured and stored at -70degreesC the plasmid profile was fairly stable except for the miniplasmids (ca. 3.7 and 1.6 kb).

Neurokinin-B transcription in erythroid cells - Direct activation by the hematopoietic transcription factor GATA-1

The GATA family of transcription factors establishes genetic networks that control developmental processes including hematopoiesis, vasculogenesis, and cardiogenesis. We found that GATA-1 strongly activates transcription of the Tac-2 gene, which encodes proneurokinin-B, a precursor of neurokinin-B (NK-B). Neurokinins function through G protein-coupled transmembrane receptors to mediate diverse physiological responses including pain perception and the control of vascular tone. Whereas an elevated level of NK-B was implicated in pregnancy-associated pre-eclampsia ( Page, N. M., Woods, R. J., Gardiner, S. M., Lomthaisong, K., Gladwell, R. T., Butlin, D. J., Manyonda, I. T., and Lowry, P. J. ( 2000) Nature 405, 797 - 800), the regulation of NK-B synthesis and function are poorly understood. Tac-2 was expressed in normal murine erythroid cells and was induced upon ex vivo erythropoiesis. An estrogen receptor fusion to GATA-1 (ER-GATA-1) and endogenous GATA-1 both occupied a region of Tac-2 intron-7, which contains two conserved GATA motifs. Genetic complementation analysis in GATA-1-null G1E cells revealed that endogenous GATA-2 occupied the same region of intron-7, and expression of ER-GATA-1 displaced GATA-2 and activated Tac-2 transcription. Erythroid cells did not express neurokinin receptors, whereas aortic and yolk sac endothelial cells differentially expressed neurokinin receptor subtypes. Since NK-B induced cAMP accumulation in yolk sac endothelial cells, these results suggest a new mode of vascular regulation in which GATA-1 controls NK-B synthesis in erythroid cells.

Dicopper(II) complexes of a new di-para-xylyldioxatetraazamacrocycle and cascade species with dicarboxylate anions: thermodynamics and structural properties

The new dioxatetraazamacrocycle (L-1) was synthesized by a 2 + 2 condensation and characterized. Stability constants of its copper(II) complexes were determined by spectrophotometry in DMSO at 298.2 K in 0. 10 mol dm(-3) KClO4. Mainly dinuclear complexes are formed and the presence of mononuclear species is dependent on the counterion (Cl- or ClO4-). The association constants of the dinuclear copper(II) complexes with dicarboxylate anions [oxalate (oxa(2-)), malonate (mal(2-)), succinate (suc(2-)), and glutarate (glu(2-))] were also determined by spectrophotometry at 298.2 K in DMSO, and it was found that values decrease with an increase of the alkyl chain between the carboxylate groups. X-Band EPR spectra of the dicopper(II) complexes and of their cascade species in frozen DMSO exhibit dipole-dipole coupling, and their simulation, together with their UV-vis spectra, showed that the copper centres of the complexes in solution had square pyramidal geometries though with different distortions. From the experimental data, it was also possible to predict the Cu...Cu distances, the minimum being found at 6.4 angstrom for the (Cu2LCl4)-Cl-1 complex and then successively this distance slightly increases when the chloride anions are replaced by dicarboxylate anions, from 6.6 angstrom for oxa(2-) to 7.8 for glu(2-). The crystal structures of the dinuclear copper cascade species with oxa(2-) and suc(2-) were determined and showed one anion bridging both copper centres and Cu...Cu distances of 5.485(7) angstrom and 6.442(8) angstrom, respectively.

Bidentates versus monodentates in asymmetric hydrogenation catalysis: synergic effects on rate and allosteric effects on enantioselectivity

C-1-Symmetric phosphino/phosphonite ligands are prepared by the reactions of Ph2P(CH2)(2)P(NMe2)(2) with (S)-1,11'-bi-2-naphthol (to give L-A) or (S)-10,10'-bi-9-phenanthrol (to give L-B). Racemic 10,10'-bi-9-phenanthrol is synthesized in three steps from phenanthrene in 44% overall yield. The complexes [PdCl2(L-A,L-B)] (1a,b), [PtCl2(L-A,L-B)] (2a,b), [Rh(cod)(L-A,L-B)]BF4 (3a,b) and [Rh(L-A,L-B)(2)]BF4 (4a,b) are reported and the crystal structure of la has been determined. A P-31 NMR study shows that M, a 1:1 mixture of the monodentates, PMePh2 and methyl monophosphonite L-1a (based on (S)-1,11'-bi-2-naphthol), reacts with 1 equiv of [Rh(cod)(2)]BF4 to give the heteroligand complex [Rh(cod)(PMePh2)(L-1a)]BF4 (5) and homoligand complexes [Rh(cod)(PMePh2)(2)]BF4 (6) and [Rh(cod)(L-1a)(2)]BF4 (7) in the ratio 2:1:1. The same mixture of 5-7 is obtained upon mixing the isolated homoligand complexes 6 and 7 although the equilibrium is only established rapidly in the presence of an excess of PMePh2. The predominant species 5 is a monodentate ligand complex analogue of the chelate 3a. When the mixture of 5-7 is exposed to 5 atm H-2 for 1 h (the conditions used for catalyst preactivation in the asymmetric hydrogenation studies), the products are identified as the solvento species [Rh(PMePh2)(L-1a)(S)(2)]BF4 (5'), [Rh(S)(2)(PMePh2)(2)]BF4 (6') and [Rh(S)(2)(L-1a)(2)]BF4 (7') and are formed in the same 2:1:1 ratio. The reaction of M with 0.5 equiv of [Rh(cod)(2)]BF4 gives exclusively the heteroligand complex cis-[Rh(PMePh2)(2)(L-1a)(2)]BF4 (8), an analogue of 4a. The asymmetric hydrogenation of dehydroamino acid derivatives catalyzed by 3a,b is reported, and the enantioselectivities are compared with those obtained with (a) chelate catalysts derived from analogous diphosphonite ligands L-2a and L-2b, (b) catalysts based on methyl monophosphonites L-1a and L-1b, and (c) catalysts derived from mixture M. For the cinnamate and acrylate substrates studied, the catalysts derived from the phosphino/phosphonite bidentates L-A,L-B generally give superior enantioselectivities to the analogous diphosphonites L-2a and L-2b; these results are rationalized in terms of delta/lambda-chelate conformations and allosteric effects of the substrates. The rate of hydrogenation of acrylate substrate A with heterochelate 3a is significantly faster than with the homochelate analogues [Rh(L-2a)(cod)]BF4 and [Rh(dppe)(cod)]BF4. A synergic effect on the rate is also observed with the monodentate analogues: the rate of hydrogenation with the mixture containing predominantly heteroligand complex 5 is faster than with the monophosphine complex 6 or monophosphonite complex 7. Thus the hydrogenation catalysis carried out with M and [Rh(cod)(2)]BF4 is controlled by the dominant and most efficient heteroligand complex 5. In this study, the heterodiphos chelate 3a is shown to be more efficient and gives the opposite sense of optical induction t the heteromonophos analogue

Supramolecular hydrogen-bond structures and magnetic interactions in basal-apical, dinuclear, azide-bridged copper(II) complexes

The synthesis, characterisation, X-ray single crystal structures and magnetic properties of three new basal-apical mu(2)-1,1-azide-bridged complexes [(CuLN3)-N-1](2) (1), [(CuLN3)-N-2](2) (2) and [(CuLN3)-N-3](2) (3) with very similar tridentate Schiff-base blocking ligands {HL1 = N-[2-(ethylamino) ethyl] salicylaldimine; HL2 = 7-(ethylamino)-4-methyl-5-azahept-3-en-2-one; HL3 = 7-amino-4-methyl-5-azaoct-3-en-2-one} have been reported [complex 1: monoclinic, P2(1)/c, a = 8.390(2), b = 7.512(2), c = 19.822(6) Angstrom, beta = 91.45(5)degrees; complex 2: monoclinic, P2(1)/c, a = 8.070(9), b = 9.787(12), c = 15.743(17) A, beta = 98.467(10)degrees; complex 3: monoclinic, P2(1)/n, a = 5.884(7), b = 16.147(18), c = 11.901(12) Angstrom, beta = 90.050(10)degrees]. The structures consist of neutral dinuclear entities resulting from the pairing of two mononuclear units through end-on azide bridges connecting an equatorial position of one copper centre to an axial position of the other, The copper ions adopt a (4+1) square-based geometry in all the complexes. In complex 2, there is no inter-dimer hydrogen-bonding. However, complexes 1 and 3 form two different supramolecular structures in which the dinuclear entities are linked by H-bonds giving one-dimensional systems. Variable temperature (300-2 K) magnetic-susceptibility measurements and magnetisation measurements at 2 K reveal that all three complexes have antiferromagnetic coupling. Magneto-structural correlations have been made taking into consideration both the azido bridging ligands and the existence of intermolecular hydrogen bonds. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).

Artichoke leaf extract (Cynara scolymus) reduces plasma cholesterol in otherwise healthy hypercholesterolemic adults: A randomized, double blind placebo controlled trial

Cardiovascular diseases are the chief causes of death in the UK, and are associated with high circulating levels of total cholesterol in the plasma. Artichoke leaf extracts (ALEs) have been reported to reduce plasma lipids levels, including total cholesterol, although high quality data is lacking. The objective of this trial was to assess the effect of ALE on plasma lipid levels and general well-being in otherwise healthy adults with mild to moderate hypercholesterolemia. 131 adults were screened for total plasma cholesterol in the range 6.0-8.0 mmol/l, with 75 suitable volunteers randomised onto the trial. Volunteers consumed 1280 mg of a standardised ALE, or matched placebo, daily for 12 weeks. Plasma total cholesterol decreased in the treatment group by an average of 4.2% (from 7.16 (SD 0.62) mmol/l to 6.86 (SD 0.68) mmol/l) and increased in the control group by an average of 1.9% (6.90 (SD 0.49) mmol/l to 7.03 (0.61) mmol/l), the difference between groups being statistically significant (p = 0.025). No significant differences between groups were observed for LDL cholesterol, HDL cholesterol or triglyceride levels. General well-being improved significantly in both the treatment (11%) and control groups (9%) with no significant differences between groups. In conclusion, ALE consumption resulted in a modest but favourable statistically significant difference in total cholesterol after 12 weeks. In comparison with a previous trial, it is suggested that the apparent positive health status of the study population may have contributed to the modesty of the observed response. (C) 2008 Elsevier GmbH. All rights reserved.

Synergistic effect of BSA on antioxidant activities in model food emulsions

Sunflower oil-in-water emulsions containing TBHQ, caffeic acid, epigallocatechin gallate (EGCG), or 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), both with and without BSA, were stored at 50 and 30degreesC. Oxidation of the oil was monitored by determination of the PV, conjugated diene content, and hexanal formation. Emulsions containing EGCG, caffeic acid, and, to a lesser extent, Trolox were much more stable during storage in the presence of BSA than in its absence even though BSA itself did not provide an antioxidant effect. BSA did not have a synergistic effect on the antioxidant activity of TBHQ. The BSA structure changed, with a considerable loss of fluorescent tryptophan groups during storage of solutions containing BSA and antioxidants, and a BSA-antioxidant adduct with radical-scavenging activity was formed. The highest radical-scavenging activity observed was for the isolated protein from a sample containing EGCG and BSA incubated at 30degreesC for 10 d. This fraction contained unchanged BSA as well as BSA-antioxidant adduct, but 95.7% of the initial fluorescence had been lost, showing that most of the BSA had been altered. It can be concluded that BSA exerts its synergistic effect with antioxidants because of formation of a protein-antioxidant adduct during storage, which is concentrated at the oil-water interface owing to the surface-active nature of the protein.

The effects of pre- and postnatal depression in fathers: a natural experiment comparing the effects of exposure to depression on offspring

Background: Depression in fathers in the postnatal period is associated with an increased risk of behavioural problems in their offspring, particularly for boys. The aim of this study was to examine for differential effects of depression in fathers on children's subsequent psychological functioning via a natural experiment comparing prenatal and postnatal exposure. Methods:In a longitudinal population cohort study (the Avon Longitudinal Study of Parents and Children (ALSPAC)) we examined the associations between depression in fathers measured in the prenatal and postnatal period (measured using the Edinburgh Postnatal Depression Scale), and later behavioural/emotional and psychiatric problems in their children, assessed at ages 31/2 and 7 years. Results: Children whose fathers were depressed in both the prenatal and postnatal periods had the highest risks of subsequent psychopathology, measured by total problems at age 31/2 years (Odds Ratio 3.55; 95% confidence interval 2.07, 6.08) and psychiatric diagnosis at age 7 years (OR 2.54; 1.19, 5.41). Few differences emerged when prenatal and postnatal depression exposure were directly compared, but when compared to fathers who were not depressed, boys whose fathers had postnatal depression only had higher rates of conduct problems aged 31/2 years (OR 2.14; 1.22, 3.72) whereas sons of the prenatal group did not (OR 1.41; .75, 2.65). These associations changed little when controlling for maternal depression and other potential confounding factors. Conclusions: The findings of this study suggest that the increased risk of later conduct problems, seen particularly in the sons of depressed fathers, maybe partly mediated through environmental means. In addition, children whose fathers are more chronically depressed appear to be at a higher risk of emotional and behavioural problems. Efforts to identify the precise mechanisms by which transmission of risk may occur should be encouraged to enable the development of focused interventions to mitigate risks for young children.

Gender differences in early accommodation and vergence development

A remote haploscopic photorefractor was used to assess objective binocular vergence and accommodation responses in 157 full-term healthy infants aged 1-6 months while fixating a brightly coloured target moving between fixation distances at 2, 1, 0.5 and 0.33 m. Vergence and accommodation response gain matured rapidly from 'flat' neonatal responses at an intercept of approximately 2 dioptres (D) for accommodation and 2.5 metre angles(MA) for vergence, reaching adult-like values at 4 months. Vergence gain was marginally higher in females (p = 0.064), but accommodation gain (p = 0.034) was higher and accommodative intercept closer to zero (p = 0.004) in males in the first 3 months as they relaxed accommodation more appropriately for distant targets. More females showed flat accommodation responses (p = 0.029). More males behaved hypermetropically in the first two months of life, but when these hypermetropic infants were excluded from the analysis, the gender difference remained. Gender differences disappeared after three months. Data showed variable responses and infants could behave appropriately and simultaneously on both, neither or only one measure at all ages. If accommodation was appropriate (gain between 0.7 and 1.3; r(2) > 0.7) but vergence was not, males over- and under-converged equally, while the females who accommodated appropriately were more likely to overconverge (p = 0.008). The apparent earlier maturity of the male accommodative responses may be due to refractive error differences but could also reflect gender-specific male preference for blur cues while females show earlier preference for disparity, which may underpin the earlier emerging, disparity dependent, stereopsis and full vergence found in females in other studies.