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91.
Mithieux G Bady I Gautier A Croset M Rajas F Zitoun C 《American journal of physiology. Endocrinology and metabolism》2004,286(3):E370-E375
We studied in rats the expression of genes involved in gluconeogenesis from glutamine and glycerol in the small intestine (SI) during fasting and diabetes. From Northern blot and enzymatic studies, we report that only phosphoenolpyruvate carboxykinase (PEPCK) activity is induced at 24 h of fasting, whereas glucose-6-phosphatase (G-6-Pase) activity is induced only from 48 h. Both genes then plateau, whereas glutaminase and glycerokinase strikingly rebound between 48 and 72 h. The two latter genes are fully expressed in streptozotocin-diabetic rats. From arteriovenous balance and isotopic techniques, we show that the SI does not release glucose at 24 h of fasting and that SI gluconeogenesis contributes to 35% of total glucose production in 72-h-fasted rats. The new findings are that 1) the SI can quantitatively account for up to one-third of glucose production in prolonged fasting; 2) the induction of PEPCK is not sufficient by itself to trigger SI gluconeogenesis; 3) G-6-Pase likely plays a crucial role in this process; and 4) glutaminase and glycerokinase may play a key potentiating role in the latest times of fasting and in diabetes. 相似文献
92.
The nuclear protein kinase ATR controls S-phase progression in response to DNA damage and replication fork stalling, including damage caused by ultraviolet irradiation, hyperoxia, and replication inhibitors like aphidicolin and hydroxyurea. ATR activation and substrate specificity require the presence of adapter and mediator molecules, ultimately resulting in the downstream inhibition of the S-phase kinases that function to initiate DNA replication at origins of replication. The data reviewed strongly support the hypothesis that ATR is activated in response to persistent RPA-bound single-stranded DNA, a common intermediate of unstressed and damaged DNA replication and metabolism. 相似文献
93.
Duc R Leong-Morgenthaler PM 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,802(1):183-187
Heterocyclic amines, found ubiquitously in our diet, are carcinogenic and mutagenic. Among this class of compounds, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) is the most abundant. To further understand the carcinogenesis of this compound, we studied the effects of PhIP on the progression of human lymphoblastoid cells through the cell-cycle. Cells differing in p53 or mismatch repair status were used to evaluate the role of those proteins. Following PhIP-treatment, a dose and time-dependent accumulation of p53 was found in cells containing functional p53. The augmentation of the p53 protein, accompanied by increases in p21-WAF1, confirms that the p53 is activated. The increase in p53 was independent of the mismatch repair status of the cells. Perturbations in the cell-cycle were also observed. Twenty-four hours after PhIP treatment, the activation of the G2-M checkpoint was evident. Functional p53 and mismatch repair were not required for the PhIP-induced G2-M arrest. The G2-M arrests were reversible and are interpreted as necessary for the repair of the PhIP-DNA lesions. Under treatment conditions where less than 5% of the cells survived, the G2-M arrests were absent. 相似文献
94.
Comparative RFLP mapping has revealed extensive conservation of marker order in different grass genomes. However, microcolinearity studies at the sequence level have shown rapid genome evolution and many exceptions to colinearity. Most of these studies have focused on a limited size of genomic fragment and the extent of microcolinearity over large distances or across entire genomes remains poorly characterized in grasses. Here, we have investigated the microcolinearity between the rice genome and a total of 1,500 kb from physical BAC contigs on wheat chromosome 1AS. Using ESTs mapped in wheat chromosome bins as an additional source of physical data, we have identified 27 conserved orthologous sequences between wheat chromosome 1AS and a region of 1,210 kb located on rice chromosome 5S. Our results extend the orthology described earlier between wheat chromosome group 1S and rice chromosome 5S. Microcolinearity was found to be frequently disrupted by rearrangements which must have occurred after the divergence of wheat and rice. At the Lr10 orthologous loci, microrearrangements were due to the insertion of mobile elements, but also originated from gene movement, amplification, deletion and inversion. These mechanisms of genome evolution are at the origin of the mosaic conservation observed between the orthologous regions. Finally, in silico mapping of wheat genes identified an intragenomic colinearity between fragments from rice chromosome 1L and 5S, suggesting an ancestral segmental duplication in rice.Electronic Supplementary Material Supplementary material is available in the online version of this article at 相似文献
95.
Large-scale exploration of growth inhibition caused by overexpression of genomic fragments in Saccharomyces cerevisiae
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Boyer J Badis G Fairhead C Talla E Hantraye F Fabre E Fischer G Hennequin C Koszul R Lafontaine I Ozier-Kalogeropoulos O Ricchetti M Richard GF Thierry A Dujon B 《Genome biology》2004,5(9):R72-19
We have screened the genome of Saccharomyces cerevisiae for fragments that confer a growth-retardation phenotype when overexpressed in a multicopy plasmid with a tetracycline-regulatable (Tet-off) promoter. We selected 714 such fragments with a mean size of 700 base-pairs out of around 84,000 clones tested. These include 493 in-frame open reading frame fragments corresponding to 454 distinct genes (of which 91 are of unknown function), and 162 out-of-frame, antisense and intergenic genomic fragments, representing the largest collection of toxic inserts published so far in yeast. 相似文献
96.
Rapid genome divergence at orthologous low molecular weight glutenin loci of the A and Am genomes of wheat 总被引:19,自引:0,他引:19
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Wicker T Yahiaoui N Guyot R Schlagenhauf E Liu ZD Dubcovsky J Keller B 《The Plant cell》2003,15(5):1186-1197
To study genome evolution in wheat, we have sequenced and compared two large physical contigs of 285 and 142 kb covering orthologous low molecular weight (LMW) glutenin loci on chromosome 1AS of a diploid wheat species (Triticum monococcum subsp monococcum) and a tetraploid wheat species (Triticum turgidum subsp durum). Sequence conservation between the two species was restricted to small regions containing the orthologous LMW glutenin genes, whereas >90% of the compared sequences were not conserved. Dramatic sequence rearrangements occurred in the regions rich in repetitive elements. Dating of long terminal repeat retrotransposon insertions revealed different insertion events occurring during the last 5.5 million years in both species. These insertions are partially responsible for the lack of homology between the intergenic regions. In addition, the gene space was conserved only partially, because different predicted genes were identified on both contigs. Duplications and deletions of large fragments that might be attributable to illegitimate recombination also have contributed to the differentiation of this region in both species. The striking differences in the intergenic landscape between the A and A(m) genomes that diverged 1 to 3 million years ago provide evidence for a dynamic and rapid genome evolution in wheat species. 相似文献
97.
Chazaud B Sonnet C Lafuste P Bassez G Rimaniol AC Poron F Authier FJ Dreyfus PA Gherardi RK 《The Journal of cell biology》2003,163(5):1133-1143
Once escaped from the quiescence niche, precursor cells interact with stromal components that support their survival, proliferation, and differentiation. We examined interplays between human myogenic precursor cells (mpc) and monocyte/macrophages (MP), the main stromal cell type observed at site of muscle regeneration. mpc selectively and specifically attracted monocytes in vitro after their release from quiescence, chemotaxis declining with differentiation. A DNA macroarray-based strategy identified five chemotactic factors accounting for 77% of chemotaxis: MP-derived chemokine, monocyte chemoattractant protein-1, fractalkine, VEGF, and the urokinase system. MP showed lower constitutive chemotactic activity than mpc, but attracted monocytes much strongly than mpc upon cross-stimulation, suggesting mpc-induced and predominantly MP-supported amplification of monocyte recruitment. Determination of [3H]thymidine incorporation, oligosomal DNA levels and annexin-V binding showed that MP stimulate mpc proliferation by soluble factors, and rescue mpc from apoptosis by direct contacts. We conclude that once activated, mpc, which are located close by capillaries, initiate monocyte recruitment and interplay with MP to amplify chemotaxis and enhance muscle growth. 相似文献
98.
Capillary malformation-arteriovenous malformation, a new clinical and genetic disorder caused by RASA1 mutations 总被引:6,自引:0,他引:6
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Eerola I Boon LM Mulliken JB Burrows PE Dompmartin A Watanabe S Vanwijck R Vikkula M 《American journal of human genetics》2003,73(6):1240-1249
Capillary malformation (CM), or "port-wine stain," is a common cutaneous vascular anomaly that initially appears as a red macular stain that darkens over years. CM also occurs in several combined vascular anomalies that exhibit hypertrophy, such as Sturge-Weber syndrome, Klippel-Trenaunay syndrome, and Parkes Weber syndrome. Occasional familial segregation of CM suggests that there is genetic susceptibility, underscored by the identification of a large locus, CMC1, on chromosome 5q. We used genetic fine mapping with polymorphic markers to reduce the size of the CMC1 locus. A positional candidate gene, RASA1, encoding p120-RasGAP, was screened for mutations in 17 families. Heterozygous inactivating RASA1 mutations were detected in six families manifesting atypical CMs that were multiple, small, round to oval in shape, and pinkish red in color. In addition to CM, either arteriovenous malformation, arteriovenous fistula, or Parkes Weber syndrome was documented in all the families with a mutation. We named this newly identified association caused by RASA1 mutations "CM-AVM," for capillary malformation-arteriovenous malformation. The phenotypic variability can be explained by the involvement of p120-RasGAP in signaling for various growth factor receptors that control proliferation, migration, and survival of several cell types, including vascular endothelial cells. 相似文献
99.
In vertebrates, little is known on the role of programmed cell death (PCD) occurring within the population of dividing neural precursors and newly formed neuroblasts during early neural development. During primary neurogenesis, PCD takes place within the neuroectoderm of Xenopus embryos in a reproducible stereotypic pattern, suggesting a role for PCD during the early development of the CNS. We find that the spatio-temporal pattern of PCD is unaffected in embryos in which cell proliferation has been blocked and whose neuroecotoderm contains half the normal number of cells. This shows that PCD is not dependent on cell division. It further suggests that PCD does not solely function to regulate absolute cell numbers within the neuroectoderm. We demonstrate that PCD can be reproducibly inhibited in vivo during primary neurogenesis by the overexpression of human Bcl-2. Following PCD inhibition, normal neurogenesis is disrupted, as seen by the expansion of the expression domains of XSox-2, XZicr-2, XNgnr-1, XMyT-1, and N-Tubulin, XNgnr-1 being the most affected. PCD inhibition, however, did not affect the outcome of lateral inhibition. We propose, then, that PCD regulates primary neurogenesis at the level of neuronal determination. 相似文献
100.
Early events of apoptosis following HSV-1 infection were investigated at the single-cell level using intensified fluorescence digital-imaging microscopy. The results provide evidence that infection of differentiated ND7 neuronlike cells by HSV-1 triggers detectable alterations indicative of physiological changes associated with the early stages of apoptosis. Less than 1 h after infection with HSV-1 (KOS strain) or K26GFP (GFP being fused to HSV-1 capsid protein VP26) we observed (i) moderate decrease in mitochondrial membrane potential (about 20%), (ii) exposure of phosphatidyl serine, (iii) morphological change in the mitochondria that became spherical instead of filamentous, and (iv) activation of caspase-8. Within 3 h changes reverted to normal, which indicated that apoptosis was counteracted very early following HSV-1 infection. Similar results were obtained with KOS-TK27GFP, lacking TK and UL24 proteins, suggesting that TK and UL24 play no role in apoptosis. In Vero cells mitochondrial changes characteristic of the apoptotic process were not observed following HSV-1 infection. The UV-inactivated K26GFP had the capacity to induce apoptosis in neuronlike cells. This real-time multiparametric analysis, in combination with relevant viral mutants, could be a useful approach for dissecting the roles of various viral genes in modulating apoptotic pathways during infection. 相似文献