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Structural requirements for diacylglycerols to mimic tumor-promoting phobol diester action on the epidermal growth factor receptor 总被引:8,自引:0,他引:8
The structural requirements for diacylglycerols to mimic the action of tumor-promoting phorbol diesters on the epidermal growth factor (EGF) receptor of A431 human epidermoid carcinoma cells were investigated. Five biological effects were considered: inhibition of high affinity 125I-EGF binding, change in the phosphorylation state of the EGF receptor, inhibition of the EGF-dependent tyrosine phosphorylation of the EGF receptor, inhibition of [3H]phorbol 12 beta, 13 alpha-dibutyrate binding, and stimulation of calcium- and phospholipid-dependent protein kinase (C-kinase) in vitro. A marked effect of the acyl chain length, 3-10 carbons, of symmetric sn-1,2-diacylglycerols was observed on their ability to mimic the effect of 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA). sn-1,2-Dipropanoylglycerol did not mimic the effects of PMA, but sn-1,2-didecanoylglycerol potently mimicked PMA action. A correlation was found between the ability of these diacylglycerols to stimulate the activity of C-kinase in vitro and to mimic the effects of PMA on the EGF receptor in intact cells. Analogues of sn-1,2-dioctanoylglycerol in which the 3' hydroxyl group was substituted with hydrogen, thio or chloro moieties were inactive when assayed for their ability to stimulate C-kinase in vitro and mimic PMA action in intact cells. We conclude that the hydroxyl group of a diacylglycerol is vital for the interaction with the phorbol diester receptor. The stringent correlation between the potency of the 11 diacylglycerol analogues tested to modulate C-kinase in vitro and to mimic PMA action in vivo provides strong evidence for the hypothesis that C-kinase plays a central role in the regulation of A431 cell EGF receptors by tumor-promoting phorbol diesters. 相似文献
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We used self‐reported data from United Methodist clergy to assess the prevalence of obesity and having ever been told certain chronic disease diagnoses. Of all actively serving United Methodist clergy in North Carolina (NC) 95% (n = 1726) completed self‐report height and weight items and diagnosis questions from the Behavioral Risk Factor Surveillance Survey (BRFSS). We calculated BMI categories and diagnosis prevalence rates for the clergy and compared them to the NC population using BRFSS data. The obesity rate among clergy aged 35–64 years was 39.7%, 10.3% (95% CI = 8.5%, 12.1%) higher than their NC counterparts. Clergy also reported significantly higher rates of having ever been given diagnoses of diabetes, arthritis, high blood pressure, angina, and asthma compared to their NC peers. Health interventions that address obesity and chronic disease among clergy are urgently needed. 相似文献
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- Urban areas are often considered to be a hostile environment for wildlife as they are highly fragmented and frequently disturbed. However, these same habitats can contain abundant resources, while lacking many common competitors and predators. The urban environment can have a direct impact on the species living there but can also have indirect effects on their parasites and pathogens. To date, relatively few studies have measured how fine‐scale spatial heterogeneity within urban landscapes can affect parasite transmission and persistence.
- Here, we surveyed 237 greenspaces across the urban environment of Edinburgh (UK) to investigate how fine‐scale variation in socio‐economic and ecological variables can affect red fox (Vulpes vulpes) marking behavior, gastrointestinal (GI) parasite prevalence, and parasite community diversity.
- We found that the presence and abundance of red fox fecal markings were nonuniformly distributed across greenspaces and instead were dependent on the ecological characteristics of a site. Specifically, common foraging areas were left largely unmarked, which indicates that suitable resting and denning sites may be limiting factor in urban environments. In addition, the amount of greenspace around each site was positively correlated with overall GI parasite prevalence, species richness, and diversity, highlighting the importance of greenspace (a commonly used measure of landscape connectivity) in determining the composition of the parasite community in urban areas.
- Our results suggest that fine‐scale variation within urban environments can be important for understanding the ecology of infectious diseases in urban wildlife and could have wider implication for the management of urban carnivores.
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Interactions between two catalytically distinct MCM subgroups are essential for coordinated ATP hydrolysis and DNA replication. 总被引:9,自引:0,他引:9
The six MCM (minichromosome maintenance) proteins are essential DNA replication factors that each contain a putative ATP binding motif and together form a heterohexameric complex. We show that these motifs are required for viability in vivo and coordinated ATP hydrolysis in vitro. Mutational analysis discriminates between two functionally distinct MCM protein subgroups: Mcm4p, 6p, and 7p contribute canonical ATP binding motifs essential for catalysis, whereas the related motifs in Mcm2p, 3p, and 5p serve a regulatory function. Reconstitution experiments indicate that specific functional interactions between these two subgroups are required for robust ATP hydrolysis. Our observations show parallels between the MCM complex and the F1-ATPase, and we discuss how ATP hydrolysis by the MCM complex might be coupled to DNA strand separation. 相似文献
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Interactions between water availability and elevated atmosphericCO2 concentrations have the potential to be important factorsin determining future forage supply from temperate pastures.Using large turves from an established pasture, the responseof these communities at 350 or 700 l l1 CO2 to a soilmoisture deficit and to recovery from the deficit in comparisonto turves that were well-watered throughout was measured. Priorto this experiment the turves had been exposed to the CO2 treatmentsfor 324 d. Net CO2 exchange continued at elevated CO2 even when the volumetricsoil moisture content was less than 0.10 m3 m3 soil;at the same moisture deficit gas exchange at ambient CO2 waszero. The additional carbon fixed by the elevated CO2 turveswas primarily allocated below-ground as shown by the maintenanceof root length density at the same level as in well-wateredturves. When the dry turves were rewatered there was compensatorygrowth at ambient CO2 so that the above-ground growth rate exceededthat of turves that had not experienced a moisture deficit.At the start of this experiment, the turves that were growingat 700 l I1 CO2 had a greater proportion of legume (principallywhite clover, Trifolium repens L.) in the harvested herbage.There was a trend for the legume content at elevated CO2 tobe reduced under a soil moisture deficit. The results indicate different strategies in response to soilmoisture deficits depending on the CO2 concentration. At ambientCO2, growth stopped, but plants were able to respond stronglyon rewatering; while at elevated CO2 growth continued (particularlybelow-ground), but no additional growth was evident on rewatering.Ecosystem gas exchange measurements taken at the end of theexperiment (after 429 d of exposure to CO2) showed 33% moreCO2 was fixed at elevated CO2 with only a small (12%) and nonsignificantdownward regulation. Key words: Carbon dioxide, climate change, grassland, gas exchange, soil moisture deficit 相似文献