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Glucocorticoids (GCs) play a key role in skin homeostasis and stress responses acting through the GC receptor (GR), which modulates gene expression by DNA binding-dependent (transactivation) and -independent (transrepression) mechanisms. To delineate which mechanisms underlie the beneficial and adverse effects mediated by GR in epidermis and other epithelia, we have generated transgenic mice that express a mutant GR (P493R, A494S), which is defective for transactivation but retains transrepression activity, under control of the keratin 5 promoter (K5-GR-TR mice). K5-GR-TR embryos exhibited eyelid opening at birth and corneal defects that resulted in corneal opacity in the adulthood. Transgenic embryos developed normal skin, although epidermal atrophy and focal alopecia was detected in adult mice. GR-mediated transrepression was sufficient to inhibit keratinocyte proliferation induced by acute and chronic phorbol 12-myristate 13-acetate exposure, as demonstrated by morphometric analyses, bromodeoxyuridine incorporation, and repression of keratin 6, a marker of hyperproliferative epidermis. These antiproliferative effects were mediated through negative interference of GR with MAPK/activator protein-1 and nuclear factor-kappaB activities, although these interactions occurred with different kinetics. However, phorbol 12-myristate 13-acetate-induced inflammation was only partially inhibited by GR-TR, which efficiently repressed IL-1beta and MMP-3 genes while weakly repressing IL-6 and TNF-alpha. Our data highlight the relevance of deciphering the mechanisms underlying GR actions on epithelial morphogenesis as well as for its therapeutic use to identify more restricted targets of GC administration.  相似文献   
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The arrival of exotic pollinators to new habitats may introduce new patterns of floral preference and foraging behavior that modify the structure of the resident plant–pollinator community. The aim of this paper is to examine the potential impact of the exotic bumblebee Bombus terrestris on the pollination service provided by the native pollinator assemblage of the herb Mimulus luteus. The study was performed in a high-elevation locality in the Chilean Andes during the summer seasons of 2010, 2011, and 2012. We recorded visitation rate, and the number of pollen grains transported on the body of B. terrestris and native pollinators and the pollen deposition on the stigmas of M. luteus. Pollinator effectiveness (pollen deposited × visitation rate) was compared among species. Results revealed that B. terrestris was an inefficient pollinator, due to the low amount of pollen delivered on stigmas and the low and intermittent visitation rate across years. The parallel inter-annual variation in the visitation rate of B. terrestris and the native bumblebee Bombus dahlbomii suggests that the integration of B. terrestris had no important consequences for the congeneric species. In general, B. terrestris accounted for a low proportion of the pollen transfer in M. luteus, reaching 4.6 % in 2010, absence of effect in 2011, and 0.01 % in 2012. These results suggest that in spite of being a quickly spreading species in Chile, B. terrestris is still in the initial phase of invasion in this area.  相似文献   
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Plant mitochondrial genomes lack a number of tRNA genes and the corresponding tRNAs, which are nuclear-encoded, are imported from the cytosol. We show that specific import of tRNA(Gly) isoacceptors occurs in tobacco mitochondria: tRNA(Gly)(UCC) and tRNA(Gly)(CCC) are cytosolic and mitochondrial, while tRNA(Gly)(GCC) is found only in the cytosol. Exchange of sequences between tRNA(Gly)(UCC) and tRNA(Gly)(GCC) shows that the anticodon and D-domain are essential for tRNA(Gly)(UCC) import. However the reverse mutations in tRNA(Gly)(GCC) are not sufficient to promote its import into tobacco mitochondria.  相似文献   
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A new acidophilic, mineral sulphide oreoxidizing bacterium was isolated from a uranium mine near Salamanca, Spain. Cells were rod-shaped, motile and gram-negative. They were aerobes, could grow on pyrite and use sulphur or thiosulphate as sole energy source, suggesting this new isolate belongs to the genus Thiobacillus. It could grow neither with glucose nor with yeast extract as sole substrates. It could not grow on ferrous sulphate as the only energy source, although it grew in the same medium supplemented with glucose, yeast extract or thiosulphate. It was a mesophilic and extremely acidophilic Thiobacillus, with an optimal pH of 1.5 2. The G+C content of the DNA was 58%. The new isolate could grow in cultures on pyrite where electrophoretic pattern was clearly different from those of other thiobacilli, such as T. ferrooxidans.Abbreviations G+C Guanine + Cytosine  相似文献   
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CD40-CD154 interaction is an important mediator of inflammation and has been implicated in T helper type 1-mediated autoimmune diseases including rheumatoid arthritis (RA). Linkage studies have shown association of markers in the proximity of the CD154 gene. In the present work we investigated whether specific allele variants of the microsatellite in the 3' UTR of the CD154 gene might modulate the risk of RA. The study, in a case-control setting, included 189 patients and 150 healthy controls from the Canary Islands, Spain. The 24CAs allele was less represented in female patients than in controls (0.444 in controls versus 0.307 in patients, P = 0.006, odds ratio (OR) 0.556, 95% confidence interval (CI) 0.372 to 0.831) but not in males (0.414 versus 0.408), and only when homozygous (P = 0.012; OR 0.35, 95% CI 0.16 to 0.77). We also verified that CD154 association with RA was independent of human leukocyte antigen (HLA) phenotype. A further functional study showed that after stimulation anti-CD3, CD154 mRNA was more stable in CD4+ T lymphocytes from patients with RA bearing the 24CAs allele (mRNA half-life 208 minutes) than in patients without the 24CAs allele (109 minutes, P = 0.009). However, a lower percentage of CD154+CD4+ T lymphocytes was seen in freshly isolated peripheral blood mononuclear cells from patients carrying 24CAs alleles (mean 4.28 versus 8.12; P = 0.033), and also in CD4+ T lymphocytes stimulated with anti-CD3 (median 29.40 versus 47.60; P = 0.025). These results were concordant with the smaller amounts of CD154 mRNA isolated from stimulated T lymphocytes with 24CAs alleles. The CD154 microsatellite therefore seems to affect the expression of the gene in a complex manner that implies not only mRNA stability. These data suggest that the CD154 microsatellite contributes to the regulation of mRNA and protein expression, although further studies will be necessary to elucidate its role in disease predisposition.  相似文献   
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Sensory axons from dorsal root ganglia neurons are guided to spinal targets by molecules differentially expressed along the dorso-ventral axis of the neural tube. NT-3-responsive muscle afferents project ventrally, cease extending, and branch upon contact with motoneurons (MNs), their synaptic partners. We have identified WNT-3 as a candidate molecule that regulates this process. Wnt-3 is expressed by MNs of the lateral motor column at the time when MNs form synapses with sensory neurons. WNT-3 increases branching and growth cone size while inhibiting axonal extension in NT-3- but not NGF-responsive axons. Ventral spinal cord secretes factors with axonal remodeling activity for NT-3-responsive neurons. This activity is present at limb levels and is blocked by a WNT antagonist. We propose that WNT-3, expressed by MNs, acts as a retrograde signal that controls terminal arborization of muscle afferents.  相似文献   
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