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971.
972.
ADP regulates SNF1, the Saccharomyces cerevisiae homolog of AMP-activated protein kinase 总被引:1,自引:0,他引:1
Mayer FV Heath R Underwood E Sanders MJ Carmena D McCartney RR Leiper FC Xiao B Jing C Walker PA Haire LF Ogrodowicz R Martin SR Schmidt MC Gamblin SJ Carling D 《Cell metabolism》2011,14(5):707-714
The SNF1 protein kinase complex plays an essential role in regulating gene expression in response to the level of extracellular glucose in budding yeast. SNF1 shares structural and functional similarities with mammalian AMP-activated protein kinase. Both kinases are activated by phosphorylation on a threonine residue within the activation loop segment of the catalytic subunit. Here we show that ADP is the long-sought metabolite that activates SNF1 in response to glucose limitation by protecting the enzyme against dephosphorylation by Glc7, its physiologically relevant protein phosphatase. We also show that the regulatory subunit of SNF1 has two ADP binding sites. The tighter site binds AMP, ADP, and ATP competitively with NADH, whereas the weaker site does not bind NADH, but is responsible for mediating the protective effect of ADP on dephosphorylation. Mutagenesis experiments suggest that the general mechanism by which ADP protects against dephosphorylation is strongly conserved between SNF1 and AMPK. 相似文献
973.
974.
Lena Scheubert Rainer Schmidt Dirk Repsilber Mitja Lu?trek Georg Fuellen 《DNA research》2011,18(4):233-251
Pluripotent stem cells are able to self-renew, and to differentiate into all adult cell types. Many studies report data describing these cells, and characterize them in molecular terms. Machine learning yields classifiers that can accurately identify pluripotent stem cells, but there is a lack of studies yielding minimal sets of best biomarkers (genes/features). We assembled gene expression data of pluripotent stem cells and non-pluripotent cells from the mouse. After normalization and filtering, we applied machine learning, classifying samples into pluripotent and non-pluripotent with high cross-validated accuracy. Furthermore, to identify minimal sets of best biomarkers, we used three methods: information gain, random forests and a wrapper of genetic algorithm and support vector machine (GA/SVM). We demonstrate that the GA/SVM biomarkers work best in combination with each other; pathway and enrichment analyses show that they cover the widest variety of processes implicated in pluripotency. The GA/SVM wrapper yields best biomarkers, no matter which classification method is used. The consensus best biomarker based on the three methods is Tet1, implicated in pluripotency just recently. The best biomarker based on the GA/SVM wrapper approach alone is Fam134b, possibly a missing link between pluripotency and some standard surface markers of unknown function processed by the Golgi apparatus. 相似文献
975.
Haen SP Gouttefangeas C Schmidt D Boss A Clasen S von Herbay A Kosan B Aebert H Pereira PL Rammensee HG 《Cell stress & chaperones》2011,16(5):495-504
Due to their adjuvant effect and their ability to chaperone tumor-associated peptides, heat shock proteins constitute a potent
alarm signal for the immune system and can lead to activation of anti-tumor T-cell immunity. Radiofrequency ablation has been
reported to induce heat shock protein expression especially that of heat shock protein 70 in sublethally damaged tumor cells.
In this study, we evaluated the release of heat shock protein 70 into the serum of cancer-bearing patients directly after
radiofrequency ablation. Sera of 22 patients undergoing radiofrequency ablation for the treatment of primary and secondary
malignancies of the liver, kidney, and lung, as well as control sera of 20 patients undergoing diagnostic liver biopsy were
analyzed using a manufactured heat shock protein 70 ELISA. A significant increase in serum levels of heat shock protein 70
was detectable in the patient cohort 1 day after radiofrequency ablation. More than a twofold increase was observed in nine
out of 22 patients, which tended to correlate with favorable clinical outcome. No patient of the control group revealed a
comparable increase. Radiofrequency ablation can lead to a release of heat shock protein 70 into the serum, which is transiently
detectable 1 day after treatment. Elevated heat shock protein 70 serum levels may constitute a biomarker for favorable clinical
outcome. 相似文献
976.
977.
Jackson B Peyrollier K Pedersen E Basse A Karlsson R Wang Z Lefever T Ochsenbein AM Schmidt G Aktories K Stanley A Quondamatteo F Ladwein M Rottner K van Hengel J Brakebusch C 《Molecular biology of the cell》2011,22(5):593-605
RhoA is a small guanosine-5'-triphosphatase (GTPase) suggested to be essential for cytokinesis, stress fiber formation, and epithelial cell-cell contacts. In skin, loss of RhoA was suggested to underlie pemphigus skin blistering. To analyze RhoA function in vivo, we generated mice with a keratinocyte-restricted deletion of the RhoA gene. Despite a severe reduction of cofilin and myosin light chain (MLC) phosphorylation, these mice showed normal skin development. Primary RhoA-null keratinocytes, however, displayed an increased percentage of multinucleated cells, defective maturation of cell-cell contacts. Furthermore we observed increased cell spreading due to impaired RhoA-ROCK (Rho-associated protein kinase)-MLC phosphatase-MLC-mediated cell contraction, independent of Rac1. Rho-inhibiting toxins further increased multinucleation of RhoA-null cells but had no significant effect on spreading, suggesting that RhoB and RhoC have partially overlapping functions with RhoA. Loss of RhoA decreased directed cell migration in vitro caused by reduced migration speed and directional persistence. These defects were not related to the decreased cell contraction and were independent of ROCK, as ROCK inhibition by Y27632 increased directed migration of both control and RhoA-null keratinocytes. Our data indicate a crucial role for RhoA and contraction in regulating cell spreading and a contraction-independent function of RhoA in keratinocyte migration. In addition, our data show that RhoA is dispensable for skin development. 相似文献
978.
Extreme climatic events change the dynamics and invasibility of semi-arid annual plant communities 总被引:1,自引:0,他引:1
Jiménez MA Jaksic FM Armesto JJ Gaxiola A Meserve PL Kelt DA Gutiérrez JR 《Ecology letters》2011,14(12):1227-1235
Extreme climatic events represent disturbances that change the availability of resources. We studied their effects on annual plant assemblages in a semi-arid ecosystem in north-central Chile. We analysed 130 years of precipitation data using generalised extreme-value distribution to determine extreme events, and multivariate techniques to analyse 20 years of plant cover data of 34 native and 11 exotic species. Extreme drought resets the dynamics of the system and renders it susceptible to invasion. On the other hand, by favouring native annuals, moderately wet events change species composition and allow the community to be resilient to extreme drought. The probability of extreme drought has doubled over the last 50 years. Therefore, investigations on the interaction of climate change and biological invasions are relevant to determine the potential for future effects on the dynamics of semi-arid annual plant communities. 相似文献
979.
Members of the kingdom fungi comprise numerous plant pathogens, including the causal agents of many agriculturally relevant plant diseases such as rust, powdery mildew, rice blast and cereal head blight. Data from recent sequencing projects provide deep insight into the genomes of a range of fungi that infect different organs of monocotyledonous or dicotyledonous hosts and that have diverse pathogenic lifestyles. These studies have revealed that, similar to sequenced phytopathogenic oomycetes, these plant parasites possess very plastic and dynamic genomes, which typically encode several hundred candidate secreted effector proteins that can be highly divergent even among related species. A new insight is the presence of lineage-specific genes on mobile and partly dispensable chromosomes that are transferred intraspecifically and possibly interspecifically, thereby constituting pathogenicity and host range determinants. Convergent lifestyle-specific adaptations have shaped the parasite genomes to maximize pathogenic success according to the different infection strategies employed. 相似文献
980.
Mammals are infected by a wide array of gastrointestinal parasites, including parasites that also infect humans and domesticated animals. Many of these parasites are acquired through contact with infectious stages present in soil, feces or vegetation, suggesting that ranging behavior will have a major impact on their spread. We developed an individual-based spatial simulation model to investigate how range use intensity, home range overlap, and defecation rate impact the spread of fecally transmitted parasites in a population composed of social groups (i.e., a socially structured population). We also investigated the effects of epidemiological parameters involving host and parasite mortality rates, transmissibility, disease-related mortality, and group size. The model was spatially explicit and involved the spillover of a gastrointestinal parasite from a reservoir population along the edge of a simulated reserve, which was designed to mimic the introduction pathogens into protected areas. Animals ranged randomly within a "core" area, with biased movement toward the range center when outside the core. We systematically varied model parameters using a Latin hypercube sampling design. Analyses of simulation output revealed a strong positive association between range use intensity and the prevalence of infection. Moreover, the effects of range use intensity were similar in magnitude to effects of group size, mortality rates, and the per-contact probability of transmission. Defecation rate covaried positively with gastrointestinal parasite prevalence. Greater home range overlap had no positive effects on prevalence, with a smaller core resulting in less range overlap yet more intensive use of the home range and higher prevalence. Collectively, our results reveal that parasites with fecal-oral transmission spread effectively in socially structured populations. Future application should focus on parameterizing the model with empirically derived ranging behavior for different species or populations and data on transmission characteristics of different infectious organisms. 相似文献