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951.
Park JY Farrance IK Fenty NM Hagberg JM Roth SM Mosser DM Wang MQ Jo H Okazaki T Brant SR Brown MD 《American journal of physiology. Heart and circulatory physiology》2007,293(4):H2320-H2327
In endothelial cells, NF-kappaB is an important intracellular signaling molecule by which changes in wall shear stress are transduced into the nucleus to initiate downstream endothelial nitric oxide synthase (NOS3) gene expression. We investigated whether NF-kappa light-chain gene enhancer in B cells 1 (NFKB1) promoter polymorphism ((-94)NFKB1 I/D, where I is the insertion allele and D is the deletion allele) was associated with 1) NOS3 gene expression in endothelial cells under physiological levels of unidirectional laminar shear stress (LSS) and 2) endothelial function in prehypertensive and stage I hypertensive individuals before and after a 6-mo supervised endurance exercise intervention. Competitive EMSAs revealed that proteins present in the nuclei of endothelial cells preferentially bound to the I allele NFKB1 promoter compared with the D allele. Reporter gene assays showed that the I allele promoter had significantly higher activity than the D allele. In agreement with these observations, homozygous II genotype cells had higher p50 expression levels than homozygous DD genotype cells. Cells with the homozygous II genotype showed a greater increase in NOS3 protein expression than did homozygous DD genotype cells under LSS. Functional experiments on volunteers confirmed higher baseline reactive hyperemic forearm blood flow, and, furthermore, the subgroup analysis revealed that DD homozygotes were significantly less prevalent in the exercise responder group compared with II and ID genotypes. We conclude that the (-94)NFKB1 I/D promoter variation contributes to the modulation of vascular function and adaptability to exercise-induced flow shear stress, most likely due to differences in NFKB1 gene transactivity. 相似文献
952.
Gauthier JY Black WC Courchesne I Cromlish W Desmarais S Houle R Lamontagne S Li CS Massé F McKay DJ Ouellet M Robichaud J Truchon JF Truong VL Wang Q Percival MD 《Bioorganic & medicinal chemistry letters》2007,17(17):4929-4933
Highly potent, selective, and bioavailable inhibitors of human, mouse, or rat cathepsin S are described. The key structural features combine a sulfonyl moiety attached to a large group in P2 and a small substituent in P3. 相似文献
953.
Genetic and demographic estimates of dispersal are often thought to be inconsistent. In this study, we use the damselfly Coenagrion mercuriale (Odonata: Zygoptera) as a model to evaluate directly the relationship between estimates of dispersal rate measured during capture-mark-recapture fieldwork with those made from the spatial pattern of genetic markers in linear and two-dimensional habitats. We estimate the 'neighbourhood size' (Nb) - the product of the mean axial dispersal rate between parent and offspring and the population density - by a previously described technique, here called the regression method. Because C. mercuriale is less philopatric than species investigated previously by the regression method we evaluate a refined estimator that may be more applicable for relatively mobile species. Results from simulations and empirical data sets reveal that the new estimator performs better under most situations, except when dispersal is very localized relative to population density. Analysis of the C. mercuriale data extends previous results which demonstrated that demographic and genetic estimates of Nb by the regression method are equivalent to within a factor of two at local scales where genetic estimates are less affected by habitat heterogeneity, stochastic processes and/or differential selective regimes. The corollary is that with a little insight into a species' ecology the pattern of spatial genetic structure provides quantitative information on dispersal rates and/or population densities that has real value for conservation management. 相似文献
954.
High frequency of multiple paternity in the largest rookery of Mediterranean loggerhead sea turtles 总被引:2,自引:1,他引:1
Zbinden JA Largiadèr CR Leippert F Margaritoulis D Arlettaz R 《Molecular ecology》2007,16(17):3703-3711
Mating systems are a central component in the evolution of animal life histories and in conservation genetics. The patterns of male reproductive skew and of paternal shares in batches of offspring, for example, affect genetic effective population size. A prominent characteristic of mating systems of sea turtles seem to be a considerable intra- and interspecific variability in the degree of polyandry. Because of the difficulty of observing the mating behaviour of sea turtles directly in the open sea, genetic paternity analysis is particularly useful for gaining insights into this aspect of their reproductive behaviour. We investigated patterns of multiple paternity in clutches of loggerhead sea turtles in the largest Mediterranean rookery using four highly variable microsatellite loci. Furthermore, we tested for a relationship between the number of fathers detected in clutches and body size of females. More than one father was detected in the clutches of 14 out of 15 females, with two clutches revealing the contribution of at least five males. In more than half the cases, the contributions of different fathers to a clutch did not depart from equality. The number of detected fathers significantly increased with increasing female body size. This relationship indicates that males may prefer to mate with large, and therefore productive, females. Our results suggest that polyandry is likely to increase effective population size compared to a population in which females would mate with only one male; male reproductive contributions being equal. 相似文献
955.
Inter-individual differences in fitness in female vertebrates have often been related to phenotypic discrepancies, suggesting that bigger individuals exhibit greater fitness. However, the use of the temporally variable indices of quality, such as body mass/condition, may not represent the most reliable index over longer time intervals. Few studies have assessed the direct influence of body size (BS) on individual fitness. We addressed this knowledge gap using data from long-term monitoring of individually marked female subantarctic fur seals. The females of higher quality (i.e. higher lifetime reproductive success) were larger in BS than their counterparts, which correlated with their ability to provision their pup with greater and more regular energy supply, possibly through the maximization of foraging performance and body fat storage. We accordingly found that our study population could be divided into three contrasted categories of maternal quality, with 33% of the females producing over 71% of the viable offspring constituting the next generation. We suggest that a larger BS represents a crucial selective advantage for a central place forager, especially when exploiting remotely available resources. 相似文献
956.
Arlettaz R Patthey P Baltic M Leu T Schaub M Palme R Jenni-Eiermann S 《Proceedings. Biological sciences / The Royal Society》2007,274(1614):1219-1224
Stress generated by humans on wildlife by continuous development of outdoor recreational activities is of increasing concern for biodiversity conservation. Human disturbance often adds to other negative impact factors affecting the dynamics of vulnerable populations. It is not known to which extent the rapidly spreading free-riding snow sports actually elicit detrimental stress (allostatic overload) upon wildlife, nor what the potential associated fitness and survival costs are. Using a non-invasive technique, we evaluated the physiological stress response induced by free-riding snow sports on a declining bird species of Alpine ecosystems. The results of a field experiment in which radiomonitored black grouse (Tetrao tetrix) were actively flushed from their snow burrows once a day during four consecutive days showed an increase in the concentration of faecal stress hormone (corticosterone) metabolites after disturbance. A large-scale comparative analysis across the southwestern Swiss Alps indicated that birds had higher levels of these metabolites in human-disturbed versus undisturbed habitats. Disturbance by snow sport free-riders appears to elevate stress, which potentially represents a new serious threat for wildlife. The fitness and survival costs of allostatic adjustments have yet to be estimated. 相似文献
957.
Duarte CD Tributino JL Lacerda DI Martins MV Alexandre-Moreira MS Dutra F Bechara EJ De-Paula FS Goulart MO Ferreira J Calixto JB Nunes MP Bertho AL Miranda AL Barreiro EJ Fraga CA 《Bioorganic & medicinal chemistry》2007,15(6):2421-2433
We describe herein the discovery of LASSBio-881 (3c) as a novel in vivo antinociceptive, anti-inflammatory, and in vitro antiproliferative and antioxidant compound, with a cannabinoid ligand profile. We observed that LASSBio-881 (3c) was able to bind to CB1 receptors (71% at 100microM) and also to inhibit T-cell proliferation (66% at 10microM) probably by binding to CB2 receptors, in a non-proapoptotic manner, different from anandamide (1). It was also demonstrated that LASSBio-881 (3c) had an important antioxidant profile toward free radicals (DPPH and hydroxyl), probably due to its particular redox behavior, which reflects the presence of both nitro and 3,5-di-tert-butyl-4-hydroxyphenyl sub-units, as demonstrated by cyclic voltammetry studies. In addition, we showed that these structural sub-units are essential for the observed pharmacological activity. 相似文献
958.
Vidal A Sabatini M Rolland-Valognes G Renard P Madelmont JC Mounetou E 《Bioorganic & medicinal chemistry》2007,15(6):2368-2374
Among other non-antibiotic properties, tetracyclines inhibit matrix metalloproteinases and are currently under study for the treatment of osteoarthritis. Quaternary ammonium conjugates of tetracyclines were synthesized by direct alkylation of the amine function at the 4-position with methyl iodide. When tested in vitro, they inhibited cytokine-induced MMP expression to a lesser extent than parent tetracyclines. This was compensated by an improved inhibition of MMP catalytic activity. Since inhibition of collagen degradation was maintained these derivatives could be potent drug candidates for cartilage-targeted chondroprotective treatment. 相似文献
959.
Claudia M. Jacobi Flávio F. do Carmo Regina C. Vincent João R. Stehmann 《Biodiversity and Conservation》2007,16(7):2185-2200
Mountain areas are recognized centres of endemism and diversity on account of their isolation and altitudinal diversity. In
tropical regions, mountain tops usually stand as islands of xeric vegetation among mesophytic assemblages. Unlike the vegetation
growing on other rock outcrops lithologies, such as inselbergs (granite/gneiss) or campos rupestres (quartz/arenite), ironstone outcrop plant communities still lack systematic studies in Brazil. These outcrops (locally known
as canga) share most of the characteristics of other rock outcrops, such as isolation and edapho-climatic harshness, but differ in
that they are the object of opencast mining, and thus subjected to irrecoverable degradation. In addition, they are expected
to harbour metal-tolerant and hyperaccumulator plant species. A botanical survey of two ironstone outcrop locations in the
most important mining region of southeastern Brazil, the Iron Quadrangle, revealed a high within-site (138 and 160 species
per site), and between-site diversity (only 27% of common species), totaling 64 families and 234 species among basal families
and eudicots (154 species), monocots (68 species), and ferns (12 species). Canga crusts are rich in dicots, several of which play an important role in community structuring, together with the more usual
monocot aggregations. Distinct plant communities are found associated to different microhabitats within the iron crust, depending
primarily on the amount of soil and moisture retention in the different microtopographies. The environmental uniqueness, high
diversity, lack of studies and rapid destruction of these ecosystems pose an immediate challenge for their conservation. 相似文献