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61.
D'Alessio A Cerchia L Amelio I Incoronato M Condorelli G de Franciscis V 《Cellular signalling》2007,19(6):1193-1200
The balance between specific signals from different growth factors dictates the biological response of mammalian cells including cell proliferation, differentiation and survival. PC12 cells represent a model of choice to compare the signalling of differentiative growth factors, as NGF, and of mitogenic growth factors, as EGF. In these cells the prolonged activity of the ERK kinase dictates the decision of cells to differentiate. Here we focused on the cytosolic tyrosine phosphatase Shp2 as an established regulator of the Ras-ERK cascade, to elucidate its involvement in determining the stimulation-dependent PC12 cell fate. To this end, we generated PC12 derived cell lines that express the interfering mutant of Shp2 under a tetracycline-inducible promoter. Our findings show that Shp2 participates to the opposite effects induced in PC12 cells by EGF and NGF and that the interactions with the multidocking Gab2 protein mediate such effects. 相似文献
62.
Di Giulio C Rapino M Zingariello M Antonucci A Cataldi A 《Histochemistry and cell biology》2007,127(3):327-333
Both hypoxia and aging affect the morphology and the function of rat myocardial tissue. Moreover the heart tries to counteract
the impaired function by activating specific signalling cascades. Here we report the involvement of CREB protein in “in vivo”
response to hypoxic challenge and during aging in rat hearts. CREB is activated in parallel to HIF-1α nuclear translocation
in the young after hypoxia exposure followed by reoxygenation, while this kind of response is not so dramatic in the old,
neither in terms of CREB activation, neither in terms of HIF-1α expression and translocation, suggesting in the old the existence
of an impaired oxygen-sensing mechanism or an adaptation of the cells to hypoxia. Moreover in the young a PKC α/Erk pathway
seems to be involved in the activation of HIF-1α along with CREB, suggesting an attempt of the young to counteract the damage
evoked by hypoxia, while in the old a PKC α/p38 MAPK/CREB pathway could determine the occurrence of both aging and aged cell
hypoxia response. 相似文献
63.
Marsupials, such as the tammar wallaby (Macropus eugenii), have adopted a reproductive strategy that is very different to eutherians. Both the rate of production and the composition of milk changes progressively during the lactation cycle to meet the nutritional demands of an altricial young. The tammar therefore provides a valuable model to study changes in milk composition, and in particular the genes that code for proteins secreted in the milk, to more accurately assess the role of gene products regulating either development of the young or mammary function. 相似文献
64.
The purpose of the present study was to develop and characterize an oral controlled release drug delivery system for concomitant administration of diclofenac sodium (DS) and chondroitin sulfate (CS). A hydrophilic matrix-based tablet using different concentrations of hydroxypropylmethylcellulose (HPMC) was developed using wet granulation technique to contain 100 mg of DS and 400 mg of CS. Formulations prepared were evaluated for the release of DS and CS over a period of 9 hours in pH 6.8 phosphate buffer using United States Pharmacopeia (USP) type II dissolution apparatus. Along with usual physical properties, the dynamics of water uptake and erosion degree of tablet were also investigated. The in vitro drug release study revealed that HPMC K100CR at a concentration of 40% of the dosage form weight was able to control the simultaneous release of both DS and CS for 9 hours. The release of DS matched with the marketed CR tablet of DS with similarity factor (f(2)) above 50. Water uptake and erosion study of tablets indicated that swelling followed by erosion could be the mechanism of drug release. The in vitro release data of CS and DS followed Korsmeyer-Peppas and zero-order kinetics, respectively. In conclusion, the in vitro release profile and the mathematical models indicate that release of CS and DS can be effectively controlled from a single tablet using HPMC matrix system. 相似文献
65.
Wei‐Hsiang Lin Mark J. Rocco Amelia Bertozzi‐Villa Edo Kussell 《Evolution; international journal of organic evolution》2015,69(6):1448-1460
Populations can adapt to changing environments by using allelic diversity, yet whether diversity is recently derived or ancestral is often debated. Although evolution could productively use both types of diversity in a changing environment, their relative frequency has not been quantified. We address this question experimentally using budding yeast strains that harbor a tandem repeat containing URA3 gene, which we expose to cyclical selection and counterselection. We characterize and quantify the dynamics of frameshift events in the URA3 gene in eight populations over 12 cycles of selection and find that ancestral alleles account for 10–20% of all adaptive events. Using a general model of fluctuating selection, we determine how these results depend on mutation rates, population sizes, and fluctuation timescales. We quantify the contribution of derived alleles to the adaptation process using the de novo mutation rate along the population's ancestral lineage, a novel measure that is applicable in a wide range of settings. We find that the adaptive dynamics undergoes a sharp transition from selection on ancestral alleles to selection on derived alleles as fluctuation timescales increase. Our results demonstrate that fluctuations can select between different modes of adaptation over evolutionary timescales. 相似文献
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68.
Serini S Donato V Piccioni E Trombino S Monego G Toesca A Innocenti I Missori M De Spirito M Celleno L Fasano E Ranelletti FO Calviello G 《The Journal of nutritional biochemistry》2011,22(9):874-885
The dramatic increase in the incidence of nonmelanoma skin cancer over the last decades has been related to the augmented exposure to ultraviolet (UV) radiation (UVR). It is known that apoptosis is induced as a protective mechanism after the acute irradiation of keratinocytes, whereas apoptotic resistance and carcinogenesis may follow the chronic exposure to UVR. We found that not all the human keratinocytes lines studied underwent apoptosis following acute exposure to UVR (10-60 mJ/cm2). Whereas UVR induced apoptosis in the HaCaT cells, NCTC 2544 and nr-HaCaT cells showed apoptosis resistance. The cytokeratin pattern of the apoptosis-resistant cells indicated that they possessed a degree of differentiation lower than that of HaCaT cells. They also showed an enhanced expression of cyclooxygenase-2 (COX-2), an early marker of carcinogenesis in various tissues, including skin. n-3 polyunsaturated fatty acids have drawn increasing interest as nutritional factors with the potential to reduce UVR carcinogenesis, and since they are apoptosis inducers and COX-2 inhibitors in cancer cells, we investigated the ability of n-3 polyunsaturated fatty acids to influence the resistance to UVR-induced apoptosis in keratinocytes. We observed that docosahexaenoic acid (DHA) reverted the resistance of nr-HaCaT cells to UVR-induced apoptosis, increasing the Bax/Bcl-2 ratio and caspase-3 activity, and reduced COX-2 levels by inhibiting the expression of the human antigen R (HuR), a known COX-2 mRNA stabilizer in keratinocytes. The transfection of nr-HaCaT cells with HuR siRNA mimicked the proapoptotic effect of DHA. Overall, our findings further support the role of DHA as a suitable anticarcinogenic factor against nonmelanoma skin cancers. 相似文献
69.
Common species can be major drivers of species richness patterns and make major contributions to biomass and ecosystem function,
and thus should be important targets for conservation efforts. However, it is unclear how common species respond to disturbance,
because the underlying reasons for their commonness may buffer or amplify their responses to disturbance. To assess how well
common species reflect changes in their community (and thus function as indicator species), we studied 58 bird species in
19 mixed conifer patches in northern British Columbia, Canada, between 1998 and 2010. During this time period two disturbance
events occurred, stand level timber harvest and a regional-scale bark beetle outbreak. We examined relationships among densities
of individual species, total bird density and overall species richness, correlations in abundance among species, and responses
to disturbance events. We found three broad patterns. First, densities of common species corresponded more strongly with changes
in total bird density and overall species richness than rare species. These patterns were non-linear and species with intermediate-high
commonness showed similar or better correspondence than the most common species. Second, common species tended to be more
strongly correlated with abundances of all other species in the community than less-common species, although on average correlations
among species were weak. Third, ecological traits (foraging guild, migratory status) were better predictors of responses to
disturbance than species commonness. These results suggest that common species can collectively be used to reflect changes
in the overall community, but that whenever possible monitoring programs should be extended to include species of intermediate-high
commonness and representatives from different ecological guilds. 相似文献
70.
Christina Greenaway Amelia Sandoe Bilkis Vissandjee Ian Kitai Doug Gruner Wendy Wobeser Kevin Pottie Erin Ueffing Dick Menzies Kevin Schwartzman 《CMAJ》2011,183(12):E939-E951