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71.
Mayoral EP García-Amo M López P Soriano E Cerdán S Ballesteros P 《Bioorganic & medicinal chemistry》2003,11(24):5555-5567
We describe the syntheses, physicochemical properties and biological evaluation of a novel series of complexones containing bis- or biazoles moieties and two iminodiacetic acid units as novel ligands for paramagnetic lanthanides. The complexones were prepared by reaction of the corresponding 1,1′-bishaloethylbi- or bispyrazoles with methyl iminodiacetate and subsequent NaOH hydrolysis. 1,1′-Bisbromoethyl precursors were obtained by direct alkylation with an excess of 1,2-dibromoethane, or by heating the corresponding alcohol in HCl. Sigmoidal binding isotherms and MO calculations supported as most stable structures in solution, those containing two Gd(III) atoms bound per molecule of complexone with half saturation values S0.5 (M−1, 22 °C, pH 7.2) in the range 6.5 10−60.5<36.1 10−6. Relaxivity properties [r1, r2, s−1 mM−1 Gd(III)] determined at 1.5 Tesla gave values (12.0<r1<17.7, 12.2<r2<20), improving significantly the relaxivities of reference compounds such as Gd(III)EDTA (5.2, 5.6) or Gd(III)DTPA (4.30, 4.30). These improvements involve mainly increased hydration and slower rotational motions. In vitro toxicity experiments are reported. 相似文献
72.
Lodowski DT Salom D Le Trong I Teller DC Ballesteros JA Palczewski K Stenkamp RE 《Journal of structural biology》2007,158(3):455-462
Oligomerization has been proposed as one of several mechanisms to regulate the activity of G protein-coupled receptors (GPCRs), but little is known about the structure of GPCR oligomers. Crystallographic analyses of two new crystal forms of rhodopsin reveal an interaction surface which may be involved in the formation of functional dimers or oligomers. New crystallization conditions lead to the formation of two crystal forms with similar rhodopsin-rhodopsin interactions, but changes in the crystal lattice are induced by the addition of different surfactant additives. However, the intermolecular interactions between rhodopsin molecules in these crystal structures may reflect the contacts necessary for the maintenance of dimers or oligomers in rod outer segment membranes. Similar contacts may assist in the formation of dimers or oligomers in other GPCRs as well. These new dimers are compared with other models proposed by crystallography or EM and AFM studies. The inter-monomer surface contacts are different for each model, but several of these models coincide in implicating helix I, II, and H-8 as contributors to the main contact surface stabilizing the dimers. 相似文献
73.
Cristina Ballesteros Joaquín Vicente Ricardo Carrasco-García Rafael Mateo José de la Fuente Christian Gortázar 《European Journal of Wildlife Research》2011,57(4):749-757
Eurasian wild boar (Sus scrofa) is an important reservoir host for pathogens affecting humans and domestic animals. The eradication of these diseases may
require the development of control strategies that reduce pathogen transmission between wildlife and domestic animals. Baiting
for oral vaccine delivery is often considered for wildlife disease control. The effective and efficient field vaccination
of wildlife requires species-specific baits as delivery vehicles for oral vaccines and designing appropriate baiting strategies.
The objective of this study was to determine the proportion of young and adult wild boar and non-target animals that consumed
baits containing a chemical marker, iophenoxic acid (IPA), in delivery trials conducted in summer in four different sites
in the Mediterranean region of Spain where wild boar are abundant. The proportion of wild boar showing IPA markers in serum
in autumn ranged from 11.5% to 56.4%. When attending to age classes, 12.6% to 72.7% of young individuals presented IPA. The
results evidenced that the percent of wild boar that ingested the baits varied among study sites and age classes. Placing
baits inside selective cages (for juveniles) and under heavy pavel stones (for adults) contributed to improve age specificity
in bait consumption. We suggest ways for improving the age specificity of bait delivery systems used for young and adult wild
boar. 相似文献
74.
75.
The marine biodiversity of Gabon, West Africa has not been well studied and is largely unknown. Our examination of marine communities associated with oil platforms in Gabon is the first scientific investigation of these structures and highlights the unique ecosystems associated with them. A number of species previously unknown to Gabonese waters were recorded during our surveys on these platforms. Clear distinctions in benthic communities were observed between older, larger platforms in the north and newer platforms to the south or closer to shore. The former were dominated by a solitary cup coral, Tubastraea sp., whereas the latter were dominated by the barnacle Megabalanus tintinnabulum, but with more diverse benthic assemblages compared to the northerly platforms. Previous work documented the presence of limited zooxanthellated scleractinian corals on natural rocky substrate in Gabon but none were recorded on platforms. Total estimated fish biomass on these platforms exceeded one ton at some locations and was dominated by barracuda (Sphyraena spp.), jacks (Carangids), and rainbow runner (Elagatis bipinnulata). Thirty-four percent of fish species observed on these platforms are new records for Gabon and 6% are new to tropical West Africa. Fish assemblages closely associated with platforms had distinct amphi-Atlantic affinities and platforms likely extend the distribution of these species into coastal West Africa. At least one potential invasive species, the snowflake coral (Carijoa riisei), was observed on the platforms. Oil platforms may act as stepping stones, increasing regional biodiversity and production but they may also be vectors for invasive species. Gabon is a world leader in terrestrial conservation with a network of protected areas covering >10% of the country. Oil exploration and biodiversity conservation currently co-exist in terrestrial and freshwater ecosystems in Gabon. Efforts to increase marine protection in Gabon may benefit by including oil platforms in the marine protected area design process. 相似文献
76.
Raymond J Owens Simon Lumb Karen Rees-Milton Annette Russell Darren Baldock Volker Lang Tom Crabbe Mercedes Ballesteros Martin J Perry 《Cellular signalling》1997,9(8):575-585
A cDNA coding for a human phosphodiesterase 4C (PDE4C2) was isolated from the mRNA prepared from the glioblastoma cell line, U87. The cDNA contained an ORF of 1818 bp corresponding to a 605 amino acid polypeptide. The sequence differed at the 5′ end from the human PDE4C previously reported (Engels, P. et al, 1995 FEBs Letters 358, 305-310) indicating that it represents a novel splice variant of the human PDE4C gene. Evidence was also obtained for a third 5′ splice variant. The PDE4C2 cDNA was transfected into both COS 1 cells and yeast cells, and shown to direct the expression of an 80 kD polypeptide by Western blotting using a PDE4C specific antiserum. The activity of cell lysates was typical of PDE4 being specific for cAMP and inhibitable by the selective inhibitor, rolipram. However, the Km for cAMP of the enzyme produced in COS cells was 0.6 μM compared to 2.6 μM for the yeast 4C activity. In addition the COS cell PDE4 activity was much more sensitive to R rolipram than the yeast PDE4 enzyme (IC50 of 23 nM compared to 1648 nM). This difference in rolipram sensitivity was associated with the detection of a high affinity [3H] R rolipram binding site on the COS cell 4C enzyme but not on the yeast expressed enzyme. The results indicate that the enzyme can adopt more than one active conformation, which are distinguished by their interaction with rolipram. 相似文献
77.
Hassouan MK Ballesteros O Taoufiki J Vílchez JL Cabrera-Aguilera M Navalón A 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,852(1-2):625-630
An analytical method for the simultaneous determination of seven quinolones (ciprofloxacin, enrofloxacin, danofloxacin, difloxacin, flumequine, oxolinic acid and sarafloxacin) in egg samples of laying hens was developed. Their use is totally prohibited in animals from which eggs are produced for human consumption. Protein precipitation was achieved by addition of acetonitrile and ammonia, removal of acetonitrile with dichloromethane, the quinolones remaining in the basic aqueous extract. The aqueous extract was analysed by liquid chromatography with fluorescence detection (LC-FD). The mobile phase was composed of acetonitrile and 10 mM citrate buffer solution of pH 4.5, with an initial composition of acetonitrile-water (12:88, v/v) and using linear gradient elution. Norfloxacin was used as an internal standard. The limits of detection found were 4-12 ng g(-1). These values were lower than the maximum residue limits (MRLs) established by the European Union for these compounds in different tissues of eggs-producing animals. 相似文献
78.
Mami AG Ballesteros JR Fritz KI Kubin J Mishra OP Delivoria-Papadopoulos M 《Neurochemical research》2006,31(1):57-62
The present study tested the hypothesis that magnesium sulfate administration prior to hypoxia prevents hypoxia-induced increase
in Ca2+/Calmodulin-dependent-kinase (CaM Kinase) IV and Protein Tyrosine Kinase (PTK ) activities. Animals were randomly divided
into normoxic (Nx), hypoxic (Hx) and magnesium-pretreated hypoxic (Mg2+-Hx) groups. Cerebral hypoxia was confirmed biochemically by measuring ATP and phosphocreatine (PCr) levels. CaM Kinase IV
and PTK activities were determined in Nx, Hx and Mg2+-Hx newborn piglets. There was a significant difference between CaM kinase IV activity (pmoles/mg protein/min) in Nx (270 ± 49),
Mg2+-Hx (317 ± 82) and Hx (574 ± 41, P < 0.05 vs. Nx and Mg2+-Hx) groups. Similarly, there was a significant difference between Protein Tyrosine Kinase activity (pmoles/mg protein/h)
in normoxic (378 ± 68), Mg2+-Hx (455 ± 67) and Hx (922 ± 66, P < 0.05 vs. Nx and Mg2+-Hx ) groups. We conclude that magnesium sulfate administration prior to hypoxia prevents hypoxia-induced increase in CaM
Kinase IV and Protein Tyrosine Kinase activities. We propose that by blocking the NMDA receptor ion-channel mediated Ca2+-flux, magnesium sulfate administration inhibits the Ca2+/calmodulin-dependent activation of CaMKIV and prevents the generation of nitric oxide free radicals and the subsequent increase
in PTK activity. As a result, phosphorylation of CREB and Bcl-2 family of proteins is prevented leading to prevention of programmed
cell death. 相似文献
79.
The role of a conserved proline residue in mediating conformational changes associated with voltage gating of Cx32 gap junctions. 下载免费PDF全文
Y Ri J A Ballesteros C K Abrams S Oh V K Verselis H Weinstein T A Bargiello 《Biophysical journal》1999,76(6):2887-2898
We have explored the role of a proline residue located at position 87 in the second transmembrane segment (TM2) of gap junctions in the mechanism of voltage-dependent gating of connexin32 (Cx32). Substitution of this proline (denoted Cx32P87) with residues G, A, or V affects channel function in a progressive manner consistent with the expectation that a proline kink (PK) motif exists in the second transmembrane segment (TM2) of this connexin. Mutations of the preceding threonine residue T86 to S, A, C, V, N, or L shift the conductance-voltage relation of wild-type Cx32, such that the mutated channels close at smaller transjunctional voltages. The observed shift in voltage dependence is consistent with a reduction in the open probability of the mutant hemichannels at a transjunctional voltage (Vj) of 0 mV. In both cases in which kinetics were examined, the time constants for reaching steady state were faster for T86N and T86A than for wild type at comparable voltages, suggesting that the T86 mutations cause the energetic destabilization of the open state relative to the other states of the channel protein. The structural underpinnings of the observed effects were explored with Monte Carlo simulations. The conformational space of TM2 helices was found to differ for the T86A, V, N, and L mutants, which produce a less bent helix ( approximately 20 degrees bend angle) compared to the wild type, which has a approximately 37 degrees bend angle. The greater bend angle of the wild-type helix reflects the propensity of the T86 residue to hydrogen bond with the backbone carbonyl of amino acid residue I82. The relative differences in propensity for hydrogen bonding of the mutants relative to the wild-type threonine residue in the constructs we studied (T86A, V, N, L, S, and C) correlate with the shift in the conductance-voltage relation observed for T86 mutations. The data are consistent with a structural model in which the open conformation of the Cx32 channel corresponds to a more bent TM2 helix, and the closed conformation corresponds to a less bent helix. We propose that the modulation of the hydrogen-bonding potential of the T86 residue alters the bend angle of the PK motif and mediates conformational changes between open and closed channel states. 相似文献
80.
Linkage at 12q24 with systemic lupus erythematosus (SLE) is established and confirmed in Hispanic and European American families 下载免费PDF全文
Nath SK Quintero-Del-Rio AI Kilpatrick J Feo L Ballesteros M Harley JB 《American journal of human genetics》2004,74(1):73-82
Systemic lupus erythematosus (SLE) is a chronic, complex, and systemic human autoimmune disease, with both an environmental component and a heritable predisposition. Clinical studies, reinforced by epidemiology and genetics, show impressive variation in disease severity, expression, prevalence, and incidence by ethnicity and sex. To identify the novel SLE susceptibility loci, we performed a genomewide scan with 318 markers on 37 multiplex Hispanic families, using a nonparametric penetrance-independent affected-only allele-sharing method. Three chromosomal regions (12q24, 16p13, and 16q12-21) exceeded our predetermined threshold (Zlr>2.32; nominal P<.01) for further evaluation. Suspected linkages at 12q24, 16p13, and 16q12-21 were tested in an independent data set consisting of 92 European American (EA-1) and 55 African American (AA) families. The linkage at 12q24 was replicated in EA-1 (Zlr=3.06; P=.001) but not in AA (Zlr=0.37; P=.35). Although neither the 16p13 nor the 16q12-21 was confirmed in EA-1 or AA, the suggestive linkage (Zlr=3.06; P=.001) at 16q12-21 is sufficient to confirm the significant linkage, reported elsewhere, at this location. The evidence for linkage at 12q24 in the 129 combined (Hispanic and EA-1) families exceeded the threshold for genomewide significance (Zlr=4.39; P=5.7x10-6; nonparametric LOD=4.19). Parametric linkage analyses suggested a low-penetrance, dominant model (LOD=3.72). To confirm the linkage effect at 12q24, we performed linkage analysis in another set of 82 independent European American families (EA-2). The evidence for linkage was confirmed (Zlr=2.11; P=.017). Therefore, our results have detected, established, and confirmed the existence of a novel SLE susceptibility locus at 12q24 (designated "SLEB4") that may cause lupus, especially in Hispanic and European American families. 相似文献