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81.
Yamaoka I Doi M Nakayama M Ozeki A Mochizuki S Sugahara K Yoshizawa F 《American journal of physiology. Endocrinology and metabolism》2006,290(5):E882-E888
The present study was conducted to determine the contribution of muscle protein synthesis to the prevention of anesthesia-induced hypothermia by intravenous administration of an amino acid (AA) mixture. We examined the changes of intraperitoneal temperature (Tcore) and the rates of protein synthesis (K(s)) and the phosphorylation states of translation initiation regulators and their upstream signaling components in skeletal muscle in conscious (Nor) or propofol-anesthetized (Ane) rats after a 3-h intravenous administration of a balanced AA mixture or saline (Sal). Compared with Sal administration, the AA mixture administration markedly attenuated the decrease in Tcore in rats during anesthesia, whereas Tcore in the Nor-AA group became slightly elevated during treatment. Stimulation of muscle protein synthesis resulting from AA administration was observed in each case, although K(s) remained lower in the Ane-AA group than in the Nor-Sal group. AA administration during anesthesia significantly increased insulin concentrations to levels approximately 6-fold greater than in the Nor-AA group and enhanced phosphorylation of eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) and ribosomal protein S6 protein kinase relative to all other groups and treatments. The alterations in the Ane-AA group were accompanied by hyperphosphorylation of protein kinase B and the mammalian target of rapamycin (mTOR). These results suggest that administration of an AA mixture during anesthesia stimulates muscle protein synthesis via insulin-mTOR-dependent activation of translation initiation regulators caused by markedly elevated insulin and, thereby, facilitates thermal accumulation in the body. 相似文献
82.
Bethke G Pecher P Eschen-Lippold L Tsuda K Katagiri F Glazebrook J Scheel D Lee J 《Molecular plant-microbe interactions : MPMI》2012,25(4):471-480
Mitogen-activated protein kinases (MAPK) mediate cellular signal transduction during stress responses, as well as diverse growth and developmental processes in eukaryotes. Pathogen infection or treatments with conserved pathogen-associated molecular patterns (PAMPs) such as the bacterial flagellin-derived flg22 peptide are known to activate three Arabidopsis thaliana MAPK: MPK3, MPK4, and MPK6. Several stresses, including flg22 treatment, are known to increase MPK11 expression but activation of MPK11 has not been shown. Here, we show that MPK11 activity can, indeed, be increased through flg22 elicitation. A small-scale microarray for profiling defense-related genes revealed that cinnamyl alcohol dehyrogenase 5 requires MPK11 for full flg22-induced expression. An mpk11 mutant showed increased flg22-mediated growth inhibition but no altered susceptibility to Pseudomonas syringae, Botrytis cinerea, or Alternaria brassicicola. In mpk3, mpk6, or mpk4 backgrounds, MPK11 is required for embryo or seed development or general viability. Although this developmental deficiency in double mutants and the lack of or only subtle mpk11 phenotypes suggest functional MAPK redundancies, comparison with the paralogous MPK4 reveals distinct functions. Taken together, future investigations of MAPK roles in stress signaling should include MPK11 as a fourth PAMP-activated MAPK. 相似文献
83.
Embryonic stem (ES) cells have been successfully used over the past decade to generate specific types of neuronal cells. In addition to its value for regenerative medicine, ES cell culture also provides versatile experimental systems for analyzing early neural development. These systems are complimentary to conventional animal models, particularly because they allow unique constructive (synthetic) approaches, for example, step-wise addition of components. Here we review the ability of ES cells to generate not only specific neuronal populations but also functional neural tissues by recapitulating microenvironments in early mammalian development. In particular, we focus on cerebellar neurogenesis from mouse ES cells, and explain the basic ideas for positional information and self-formation of polarized neuroepithelium. Basic research on developmental signals has fundamentally contributed to substantial progress in stem cell technology. We also discuss how in vitro model systems using ES cells can shed new light on the mechanistic understanding of organogenesis, taking an example of recent progress in self-organizing histogenesis. 相似文献
84.
85.
Ito S Fujiyama-Nakamura S Kimura S Lim J Kamoshida Y Shiozaki-Sato Y Sawatsubashi S Suzuki E Tanabe M Ueda T Murata T Kato H Ohtake F Fujiki R Miki T Kouzmenko A Takeyama K Kato S 《Molecular cell》2012,45(4):494-504
Cell cycle-dependent expression of canonical histone proteins enables newly synthesized DNA to be integrated into chromatin in replicating cells. However, the molecular basis of cell cycle-dependency in the switching of histone gene regulation remains to be uncovered. Here, we report the identification and biochemical characterization of a molecular switcher, HERS (histone gene-specific epigenetic repressor in late S phase), for nucleosomal core histone gene inactivation in Drosophila. HERS protein is phosphorylated by a cyclin-dependent kinase (Cdk) at the end of S-phase. Phosphorylated HERS binds to histone gene regulatory regions and anchors HP1 and Su(var)3-9 to induce chromatin inactivation through histone H3 lysine 9 methylation. These findings illustrate a salient molecular switch linking epigenetic gene silencing to cell cycle-dependent histone production. 相似文献
86.
Abhinav Kumar Sabine M?cklinghoff Fumiaki Yumoto Lukasz Jaroszewski Carol L. Farr Anna Grzechnik Phuong Nguyen Christian X. Weichenberger Hsiu-Ju Chiu Heath E. Klock Marc-André Elsliger Ashley M. Deacon Adam Godzik Scott A. Lesley Bruce R. Conklin Robert J. Fletterick Ian A. Wilson 《PloS one》2012,7(9)
87.
Tange Y Kurabayashi A Goto B Hoe KL Kim DU Park HO Hayles J Chikashige Y Tsutumi C Hiraoka Y Yamao F Nurse P Niwa O 《PLoS genetics》2012,8(6):e1002776
To identify the genes required to sustain aneuploid viability, we screened a deletion library of non-essential genes in the fission yeast Schizosaccharomyces pombe, in which most types of aneuploidy are eventually lethal to the cell. Aneuploids remain viable for a period of time and can form colonies by reducing the extent of the aneuploidy. We hypothesized that a reduction in colony formation efficiency could be used to screen for gene deletions that compromise aneuploid viability. Deletion mutants were used to measure the effects on the viability of spores derived from triploid meiosis and from a chromosome instability mutant. We found that the CCR4-NOT complex, an evolutionarily conserved general regulator of mRNA turnover, and other related factors, including poly(A)-specific nuclease for mRNA decay, are involved in aneuploid viability. Defective mutations in CCR4-NOT complex components in the distantly related yeast Saccharomyces cerevisiae also affected the viability of spores produced from triploid cells, suggesting that this complex has a conserved role in aneuploids. In addition, our findings suggest that the genes required for homologous recombination repair are important for aneuploid viability. 相似文献
88.
89.
Natsume T Tsutsui Y Sutani T Dunleavy EM Pidoux AL Iwasaki H Shirahige K Allshire RC Yamao F 《PloS one》2008,3(5):e2221
Specialized chromatin exists at centromeres and must be precisely transmitted during DNA replication. The mechanisms involved in the propagation of these structures remain elusive. Fission yeast centromeres are composed of two chromatin domains: the central CENP-A(Cnp1) kinetochore domain and flanking heterochromatin domains. Here we show that fission yeast Mcl1, a DNA polymerase alpha (Pol alpha) accessory protein, is critical for maintenance of centromeric chromatin. In a screen for mutants that alleviate both central domain and outer repeat silencing, we isolated several cos mutants, of which cos1 is allelic to mcl1. The mcl1-101 mutation causes reduced CENP-A(Cnp1) in the central domain and an aberrant increase in histone acetylation in both domains. These phenotypes are also observed in a mutant of swi7(+), which encodes a catalytic subunit of Pol alpha. Mcl1 forms S-phase-specific nuclear foci, which colocalize with those of PCNA and Pol alpha. These results suggest that Mcl1 and Pol alpha are required for propagation of centromere chromatin structures during DNA replication. 相似文献
90.
Motomura K Hagiwara A Komi-Kuramochi A Hanyu Y Honda E Suzuki M Kimura M Oki J Asada M Sakaguchi N Nakayama F Akashi M Imamura T 《Biochimica et biophysica acta》2008,1780(12):1432-1440
Structural instability of wild-type fibroblast growth factor (FGF)-1 and its dependence on exogenous heparin for optimal activity diminishes its potential utility as a therapeutic agent. Here we evaluated FGFC, an FGF1:FGF2 chimeric protein, for its receptor affinity, absolute heparin-dependence, stability and potential clinical applicability. Using BaF3 transfectants overexpressing each FGF receptor (FGFR) subtype, we found that, like FGF1, FGFC activates all of the FGFR subtypes (i.e., FGFR1c, FGFR1b, FGFR2c, FGFR2b, FGFR3c, FGFR3b and FGFR4) in the presence of heparin. Moreover, FGFC activates FGFRs even in the absence of heparin. FGFC stimulated keratinocytes proliferation much more strongly than FGF2, as would be expected from its ability to activate FGFR2b. FGFC showed greater structural stability, biological activity and resistance to trypsinization, and less loss in solution than FGF1 or FGF2. When FGFC was intraperitoneally administered to BALB/c mice prior to whole body gamma-irradiation, survival of small intestine crypts was significantly enhanced, as compared to control mice. These results suggest that FGFC could be useful in a variety of clinical applications, including promotion of wound healing and protection against radiation-induced damage. 相似文献