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排序方式: 共有518条查询结果,搜索用时 31 毫秒
81.
Naetar N Korbei B Kozlov S Kerenyi MA Dorner D Kral R Gotic I Fuchs P Cohen TV Bittner R Stewart CL Foisner R 《Nature cell biology》2008,10(11):1341-1348
Lamina-associated polypeptide (LAP) 2alpha is a chromatin-associated protein that binds A-type lamins. Mutations in both LAP2alpha and A-type lamins are linked to human diseases called laminopathies, but the molecular mechanisms are poorly understood. The A-type lamin-LAP2alpha complex interacts with and regulates retinoblastoma protein (pRb), but the significance of this interaction in vivo is unknown. Here we address the function of the A-type lamin-LAP2alpha complex with the use of LAP2alpha-deficient mice. We show that LAP2alpha loss causes relocalization of nucleoplasmic A-type lamins to the nuclear envelope and impairs pRb function. This causes inefficient cell-cycle arrest in dense fibroblast cultures and hyperproliferation of epidermal and erythroid progenitor cells in vivo, leading to tissue hyperplasia. Our results support a disease-relevant model in which LAP2alpha defines A-type lamin localization in the nucleoplasm, which in turn affects pRb-mediated regulation of progenitor cell proliferation and differentiation in highly regenerative tissues. 相似文献
82.
Alvarez S Pazos-Randulfe Y Khanwalkar H Germain P Alvarez R Gronemeyer H de Lera AR 《Bioorganic & medicinal chemistry》2008,16(22):9719-9728
A series of 9-cis-retinoic acid analogs modified at the hydrophobic ring with a (bi)cyclohexenyl moiety derived from natural terpenes has been stereoselectively prepared using a Suzuki cross-coupling as key step. Transient transactivation studies indicate that modification of the hydrophobic ring impacts dramatically on RXR-binding and transactivation, with most retinoids being inactive on RXRbeta, while preserving their RAR pan-agonist profile. Furthermore, only the RARgamma subtype was capable of enantiomeric discrimination with some pairs of enantiomeric terpene-retinoids. 相似文献
83.
del Pozo Yauner L Ortiz E Sánchez R Sánchez-López R Güereca L Murphy CL Allen A Wall JS Fernández-Velasco DA Solomon A Becerril B 《Proteins》2008,72(2):684-692
Light chain-associated amyloidosis is a fatal disease characterized by the aggregation and pathologic deposition of monoclonal light chain-related fragments as amyloid fibrils in organs or tissues throughout the body. Notably, it has been observed that proteins encoded by the lambda variable light chain (V(L)) gene segment 6a are invariably associated with amyloid deposition; however, the contribution of the gene to this phenomenon has not been established. In this regard, we have determined the thermodynamic stability and kinetics of in vitro fibrillogenesis of a recombinant (r) V(L) protein, designated 6aJL2, which contains the predicted sequences encoded by the 6a and JL2 germline genes. Additionally, we studied a 6a mutant (6aJL2-Arg25Gly), that is present in approximately 25% of all amyloid-associated lambda6 light chains. Remarkably, the wild-type 6aJL2 protein was more stable than were all known amyloidogenic kappa and lambda light chains for which stability parameters are available; more importantly, it was even more so (and less fibrillogenic) than the only clinically proven nonamyloidogenic lambda6 protein, Jto. Conversely, the mutated 6aJL2-R25G molecule was considerably less stable and more fibrillogenic than was the native 6aJL2. Our data indicate that the propensity of lambda6 light chains to form amyloid can not be attributed to thermodynamic instability of the germline-encoded Vlambda6 domain, but rather, is dependent on sequence alterations that render such proteins amyloidogenic. 相似文献
84.
Vibrio parahaemolyticus ScrC modulates cyclic dimeric GMP regulation of gene expression relevant to growth on surfaces 总被引:1,自引:0,他引:1
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In Vibrio parahaemolyticus, scrC participates in controlling the decision to be a highly mobile swarmer cell or a more adhesive, biofilm-proficient cell type. scrC mutants display decreased swarming motility over surfaces and enhanced capsular polysaccharide production. ScrC is a cytoplasmic membrane protein that contains both GGDEF and EAL conserved protein domains. These domains have been shown in many organisms to respectively control the formation and degradation of the small signaling nucleotide cyclic dimeric GMP (c-di-GMP). The scrC gene is part of the three-gene scrABC operon. Here we report that this operon influences the cellular nucleotide pool and that c-di-GMP levels inversely modulate lateral flagellar and capsular polysaccharide gene expression. High concentrations of this nucleotide prevent swarming and promote adhesiveness. Further, we demonstrate that ScrC has intrinsic diguanylate cyclase and phosphodiesterase activities, and these activities are controlled by ScrAB. Specifically, ScrC acts to form c-di-GMP in the absence of ScrA and ScrB; whereas ScrC acts to degrade c-di-GMP in the presence of ScrA and ScrB. The scrABC operon is specifically induced by growth on a surface, and the analysis of mutant phenotypes supports a model in which the phosphodiesterase activity of ScrC plays a dominant role during surface translocation and in biofilms. 相似文献
85.
Osmundo B. Oliveira-Neto João A. N. Batista Daniel J. Rigden Octávio L. Franco Rosana Falcão Rodrigo R. Fragoso Luciane V. Mello Roseane C. dos Santos Maria F. Grossi-de-Sá 《The protein journal》2003,22(1):77-87
Anthonomus grandis, the cotton boll weevil, causes severe cotton crop losses in North and South America. Here we demonstrate the presence of starch in the cotton pollen grains and young ovules that are the main A. grandis food source. We further demonstrate the presence of α-amylase activity, an essential enzyme of carbohydrate metabolism for many crop pests, in A. grandis midgut. Two α-amylase cDNAs from A. grandis larvae were isolated using RT-PCR followed by 5′ and 3′ RACE techniques. These encode proteins with predicted molecular masses of 50.8 and 52.7 kDa, respectively, which share 58% amino acid identity. Expression of both genes is induced upon feeding and concentrated in the midgut of adult insects. Several α-amylase inhibitors from plants were assayed against A. grandis α-amylases but, unexpectedly, only the BIII inhibitor from rye kernels proved highly effective, with inhibitors generally active against other insect amylases lacking effect. Structural modeling of Amylag1 and Amylag2 showed that different factors seem to be responsible for the lack of effect of 0.19 and α-AI1 inhibitors on A. grandis α-amylase activity. This work suggests that genetic engineering of cotton to express α-amylase inhibitors may offer a novel route to A. grandis resistance. 相似文献
86.
Takayuki Onai Michael Schubert Peter W. Osborne Rosana Alvarez Linda Z. Holland 《Developmental biology》2009,332(2):223-4830
A role for Wnt/β-catenin signaling in axial patterning has been demonstrated in animals as basal as cnidarians, while roles in axial patterning for retinoic acid (RA) probably evolved in the deuterostomes and may be chordate-specific. In vertebrates, these two pathways interact both directly and indirectly. To investigate the evolutionary origins of interactions between these two pathways, we manipulated Wnt/β-catenin and RA signaling in the basal chordate amphioxus during the gastrula stage, which is the RA-sensitive period for anterior/posterior (A/P) patterning. The results show that Wnt/β-catenin and RA signaling have distinctly different roles in patterning the A/P axis of the amphioxus gastrula. Wnt/β-catenin specifies the identity of the ends of the embryo (high Wnt = posterior; low Wnt = anterior) but not intervening positions. Thus, upregulation of Wnt/β-catenin signaling induces ectopic expression of posterior markers at the anterior tip of the embryo. In contrast, RA specifies position along the A/P axis, but not the identity of the ends of the embryo—increased RA signaling strongly affects the domains of Hox expression along the A/P axis but has little or no effect on the expression of either anterior or posterior markers. Although the two pathways may both influence such things as specification of neuronal identity, interactions between them in A/P patterning appear to be minimal. 相似文献
87.
The use of luxABCDE (lux) offers certain advantages over other reporters, such as: lacZ and xylE. It is real time and its signal generation is produced without the requirement for any additional substrates. In some bacteria such as Staphylococcus spp, light production by luciferase is restricted because of a limited availability of endogenous substrates such as fatty acid aldehyde. We describe the construction of promoterless-lux cloning vectors, pGYlux and pAmilux. S. aureus carrying B. subtilis xyl/tetO promoter fused to the lux genes of pGYlux gave up to a 2.5-fold enhancement of luminescence over S. aureus carrying the xyl/tetO promoter fused to lux genes of the previously published parent vector pAL2. Furthermore, pAmilux showed a 6-fold enhancement of lux expression when compared to pGYlux in S. aureus. This was achieved by cloning the constitutive ami promoter upstream of the luxCDE genes to increase endogenous fatty acid aldehyde production while maintaining its reporter functionality by fusing promoters to the luxAB genes. 相似文献
88.
Tabebuia cassinoides (Lam.) DC (Bignoniaceae) is a tree species that occurs in swampy areas of the coastal “restinga” in SE Brazil (a coastal sandy plains scrub and forest formation). To elucidate possible adaptive strategies that enable this species to occupy areas subjected to seasonal or perennial waterlogging, metabolic, morphological and growth responses of plants under flooding conditions were studied. The root system of T. cassinoides plants presented elevated amounts of ethanol (10.6 μmol g−1 fresh wt) only in the first 5 d of soil water saturation. The two-fold increase in ethanol production under flooding was corroborated by an increase in ADH activity in the same period. Lactic acid concentrations did not change significantly during four months of flooding treatment. The decrease of alcoholic fermentation under hypoxia was associated with the appearing of new roots. The induction of aerenchyma formation in roots developed under flooding conditions, allowed oxygen transport from the shoot to these organs, thus maintaining an aerobic respiration. We conclude that this characteristic and the capacity to oxidize the rhizosphere are probably responsible for the survival and growth of plants while flooded and for their success in an environment, which restricts the presence of the majority of competing tree species. 相似文献
89.
To assess the potential of short-term screenings for drought resistance at the seedling stage to detect ecotypic variation
and predict field performance, we studied the responses to water deficit of seedlings of Pinus canariensis from five geographic origins under controlled conditions and compared these responses with the performance of provenances
in a multi-site field trial. Leaf water potential, the osmotic component, leaf chlorophyll fluorescence and growth and biomass
partitioning were measured as seedlings were subjected for 11 days to two levels of osmotic potential generated by polyethylene
glycol (PEG 6000), −1 MPa (slowly imposed water deficit; S) and −1.5 MPa (fast imposed water deficit; F), and a control treatment
(no PEG added to the nutrient solution; C). Leaf water potential declined to final mean values of −1.2, −2.7 and −4.7 MPa
in the C, S and F treatments, respectively. The ratio of variable to maximum chlorophyll fluorescence declined to final mean
values of 0.77, 0.66 and 0.40 in the C, S and F treatments, respectively, with no differences amongst provenances. All provenances
showed an active osmotic adjustment (OA) in response to water deficit which varied depending on the drying rate. A slow imposition
of water deficit favoured solute accumulation. Pooling all treatments, the index of OA ranged from 0.28 to 0.40, but rose
considerably when only C and S treatments were considered (0.56 to 0.70). There was a positive and significant correlation
between the overall index of OA (all treatments pooled) and the drought period in the site of origin, suggesting ecotypic
variation in OA as a result of drought duration. Seedlings allocated more dry matter to roots than shoots when subjected to
moderate and slowly imposed water deficit; only one provenance showed no increase in the root to shoot ratio at the end of
the treatment period compared with control seedlings. Responses to controlled water deficits were only qualitatively related
to performance (survival and growth) of provenances in several field sites, indicating the involvement of complex mechanisms
to cope with drought under natural conditions. However, the provenance with the highest overall index of OA outgrew and outsurvived
the other provenances in the most arid site, and the only provenance not modifying the root to shoot ratio in response to
water deficit survived the least in all field sites. Acclimation of root to shoot ratio and net solute accumulation to water
deficit could hence favour drought-tolerance beyond the seedling stage and be used as preliminary predictors of field performance. 相似文献
90.