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961.
Trivedi CM Luo Y Yin Z Zhang M Zhu W Wang T Floss T Goettlicher M Noppinger PR Wurst W Ferrari VA Abrams CS Gruber PJ Epstein JA 《Nature medicine》2007,13(3):324-331
In the adult heart, a variety of stresses induce re-expression of a fetal gene program in association with myocyte hypertrophy and heart failure. Here we show that histone deacetylase-2 (Hdac2) regulates expression of many fetal cardiac isoforms. Hdac2 deficiency or chemical histone deacetylase (HDAC) inhibition prevented the re-expression of fetal genes and attenuated cardiac hypertrophy in hearts exposed to hypertrophic stimuli. Resistance to hypertrophy was associated with increased expression of the gene encoding inositol polyphosphate-5-phosphatase f (Inpp5f) resulting in constitutive activation of glycogen synthase kinase 3beta (Gsk3beta) via inactivation of thymoma viral proto-oncogene (Akt) and 3-phosphoinositide-dependent protein kinase-1 (Pdk1). In contrast, Hdac2 transgenic mice had augmented hypertrophy associated with inactivated Gsk3beta. Chemical inhibition of activated Gsk3beta allowed Hdac2-deficient adults to become sensitive to hypertrophic stimulation. These results suggest that Hdac2 is an important molecular target of HDAC inhibitors in the heart and that Hdac2 and Gsk3beta are components of a regulatory pathway providing an attractive therapeutic target for the treatment of cardiac hypertrophy and heart failure. 相似文献
962.
Fluxomics: mass spectrometry versus quantitative imaging 总被引:1,自引:0,他引:1
963.
964.
Fusiogenic endogenous-retroviral syncytin-1 exerts anti-apoptotic functions in staurosporine-challenged CHO cells 总被引:1,自引:0,他引:1
Knerr I Schnare M Hermann K Kausler S Lehner M Vogler T Rascher W Meissner U 《Apoptosis : an international journal on programmed cell death》2007,12(1):37-43
Fusiogenic glycoprotein syncytin-1, expressed in human placenta, is a promising candidate for acquiring a basic knowledge
of placental syncytialization. However, its cellular mode of action is unidentified. We investigated whether syncytin-1 may
exert influence on apoptotic processes. Therefore, we incubated CHO cells after stable transfection with syncytin-1 (CHO-52)
in the presence or absence of staurosporine (STS), a kinase inhibitor well characterized to induce apoptosis. When testing
the phenotype of CHO-52 cells, we could demonstrate that the induction of apoptosis by STS was delayed over a period of up
to 24 h. Furthermore, the cell death rate was decreased by approx 75% following transfection of syncytin-1 in CHO-52 compared
to mock-treated cells. In detail, after 18h of incubation with 500 nM STS, 64 ± 2% of CHO-52 cells were viable compared to
16 ± 1% of CHO-mocks, after 24 h 43 ± 3% vs 5 ± 2%, respectively. CHO-52 cells exhibited a lower expression of active caspase
3 and anti-apoptotic Bcl-2 was found to be increased in CHO-52 cells at baseline and following STS treatment.
Our study provides first evidence that syncytin-1 serves anti-apoptotic function under certain conditions. A lessened activation
of caspase 3 and an increased expression of Bcl-2 are possible mechanisms. 相似文献
965.
Rieping W Habeck M Bardiaux B Bernard A Malliavin TE Nilges M 《Bioinformatics (Oxford, England)》2007,23(3):381-382
Modern structural genomics projects demand for integrated methods for the interpretation and storage of nuclear magnetic resonance (NMR) data. Here we present version 2.1 of our program ARIA (Ambiguous Restraints for Iterative Assignment) for automated assignment of nuclear Overhauser enhancement (NOE) data and NMR structure calculation. We report on recent developments, most notably a graphical user interface, and the incorporation of the object-oriented data model of the Collaborative Computing Project for NMR (CCPN). The CCPN data model defines a storage model for NMR data, which greatly facilitates the transfer of data between different NMR software packages. Availability: A distribution with the source code of ARIA 2.1 is freely available at http://www.pasteur.fr/recherche/unites/Binfs/aria2. 相似文献
966.
967.
968.
969.
Effects of AiiA-mediated quorum quenching in Sinorhizobium meliloti on quorum-sensing signals, proteome patterns, and symbiotic interactions 总被引:1,自引:0,他引:1
970.
Cerebellar LTD and pattern recognition by Purkinje cells 总被引:2,自引:0,他引:2
Steuber V Mittmann W Hoebeek FE Silver RA De Zeeuw CI Häusser M De Schutter E 《Neuron》2007,54(1):121-136
Many theories of cerebellar function assume that long-term depression (LTD) of parallel fiber (PF) synapses enables Purkinje cells to learn to recognize PF activity patterns. We have studied the LTD-based recognition of PF patterns in a biophysically realistic Purkinje-cell model. With simple-spike firing as observed in vivo, the presentation of a pattern resulted in a burst of spikes followed by a pause. Surprisingly, the best criterion to distinguish learned patterns was the duration of this pause. Moreover, our simulations predicted that learned patterns elicited shorter pauses, thus increasing Purkinje-cell output. We tested this prediction in Purkinje-cell recordings both in vitro and in vivo. In vitro, we found a shortening of pauses when decreasing the number of active PFs or after inducing LTD. In vivo, we observed longer pauses in LTD-deficient mice. Our results suggest a novel form of neural coding in the cerebellar cortex. 相似文献