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31.
Direct intracranial, FMRI, and lesion evidence for the causal role of left inferotemporal cortex in reading 总被引:8,自引:0,他引:8
Gaillard R Naccache L Pinel P Clémenceau S Volle E Hasboun D Dupont S Baulac M Dehaene S Adam C Cohen L 《Neuron》2006,50(2):191-204
Models of the "visual word form system" postulate that a left occipitotemporal region implements the automatic visual word recognition required for efficient reading. This theory was assessed in a patient in whom reading was explored with behavioral measures, fMRI, and intracranial local field potentials. Prior to surgery, when reading was normal, fMRI revealed a normal mosaic of ventral visual selectivity for words, faces, houses, and tools. Intracranial recordings demonstrated that the left occipitotemporal cortex responded with a short latency to conscious but also to subliminal words. Surgery removed a small portion of word-responsive occipitotemporal cortex overlapping with the word-specific fMRI activation. The patient developed a marked reading deficit, while recognition of other visual categories remained intact. Furthermore, in the post-surgery fMRI map of visual cortex, only word-specific activations disappeared. Altogether, these results provide direct evidence for the causal role of the left occipitotemporal cortex in the recognition of visual words. 相似文献
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Mostoslavsky R Chua KF Lombard DB Pang WW Fischer MR Gellon L Liu P Mostoslavsky G Franco S Murphy MM Mills KD Patel P Hsu JT Hong AL Ford E Cheng HL Kennedy C Nunez N Bronson R Frendewey D Auerbach W Valenzuela D Karow M Hottiger MO Hursting S Barrett JC Guarente L Mulligan R Demple B Yancopoulos GD Alt FW 《Cell》2006,124(2):315-329
The Sir2 histone deacetylase functions as a chromatin silencer to regulate recombination, genomic stability, and aging in budding yeast. Seven mammalian Sir2 homologs have been identified (SIRT1-SIRT7), and it has been speculated that some may have similar functions to Sir2. Here, we demonstrate that SIRT6 is a nuclear, chromatin-associated protein that promotes resistance to DNA damage and suppresses genomic instability in mouse cells, in association with a role in base excision repair (BER). SIRT6-deficient mice are small and at 2-3 weeks of age develop abnormalities that include profound lymphopenia, loss of subcutaneous fat, lordokyphosis, and severe metabolic defects, eventually dying at about 4 weeks. We conclude that one function of SIRT6 is to promote normal DNA repair, and that SIRT6 loss leads to abnormalities in mice that overlap with aging-associated degenerative processes. 相似文献
34.
Protein Kinase C Activation Upregulates Intercellular Adhesion of α-Catenin–negative Human Colon Cancer Cell Variants via Induction of Desmosomes 下载免费PDF全文
Jolanda van Hengel Lionel Gohon Erik Bruyneel Stefan Vermeulen Maria Cornelissen Marc Mareel Frans van Roy 《The Journal of cell biology》1997,137(5):1103-1116
The α-catenin molecule links E-cadherin/ β-catenin or E-cadherin/plakoglobin complexes to the actin cytoskeleton. We studied several invasive human colon carcinoma cell lines lacking α-catenin. They showed a solitary and rounded morphotype that correlated with increased invasiveness. These round cell variants acquired a more normal epithelial phenotype upon transfection with an α-catenin expression plasmid, but also upon treatment with the protein kinase C (PKC) activator 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Video registrations showed that the cells started to establish elaborated intercellular junctions within 30 min after addition of TPA. Interestingly, this normalizing TPA effect was not associated with α-catenin induction. Classical and confocal immunofluorescence showed only minor TPA-induced changes in E-cadherin staining. In contrast, desmosomal and tight junctional proteins were dramatically rearranged, with a conversion from cytoplasmic clusters to obvious concentration at cell–cell contacts and exposition at the exterior cell surface. Electron microscopical observations revealed the TPA-induced appearance of typical desmosomal plaques. TPA-restored cell–cell adhesion was E-cadherin dependent as demonstrated by a blocking antibody in a cell aggregation assay. Addition of an antibody against the extracellular part of desmoglein-2 blocked the TPA effect, too. Remarkably, the combination of anti–E-cadherin and anti-desmoglein antibodies synergistically inhibited the TPA effect.
Our studies show that it is possible to bypass the need for normal α-catenin expression to establish tight intercellular adhesion by epithelial cells. Apparently, the underlying mechanism comprises upregulation of desmosomes and tight junctions by activation of the PKC signaling pathway, whereas E-cadherin remains essential for basic cell–cell adhesion, even in the absence of α-catenin.
相似文献35.
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Bidet M Joubert O Lacombe B Ciantar M Nehmé R Mollat P Brétillon L Faure H Bittman R Ruat M Mus-Veteau I 《PloS one》2011,6(9):e23834
Background
Sonic hedgehog (Shh) signaling plays a crucial role in growth and patterning during embryonic development, and also in stem cell maintenance and tissue regeneration in adults. Aberrant Shh pathway activation is involved in the development of many tumors, and one of the most affected Shh signaling steps found in these tumors is the regulation of the signaling receptor Smoothened by the Shh receptor Patched. In the present work, we investigated Patched activity and the mechanism by which Patched inhibits Smoothened.Methodology/Principal Findings
Using the well-known Shh-responding cell line of mouse fibroblasts NIH 3T3, we first observed that enhancement of the intracellular cholesterol concentration induces Smoothened enrichment in the plasma membrane, which is a crucial step for the signaling activation. We found that binding of Shh protein to its receptor Patched, which involves Patched internalization, increases the intracellular concentration of cholesterol and decreases the efflux of a fluorescent cholesterol derivative (BODIPY-cholesterol) from these cells. Treatment of fibroblasts with cyclopamine, an antagonist of Shh signaling, inhibits Patched expression and reduces BODIPY-cholesterol efflux, while treatment with the Shh pathway agonist SAG enhances Patched protein expression and BODIPY-cholesterol efflux. We also show that over-expression of human Patched in the yeast S. cerevisiae results in a significant boost of BODIPY-cholesterol efflux. Furthermore, we demonstrate that purified Patched binds to cholesterol, and that the interaction of Shh with Patched inhibits the binding of Patched to cholesterol.Conclusion/Significance
Our results suggest that Patched may contribute to cholesterol efflux from cells, and to modulation of the intracellular cholesterol concentration. This activity is likely responsible for the inhibition of the enrichment of Smoothened in the plasma membrane, which is an important step in Shh pathway activation. 相似文献37.
Ola Palm W. Lionel Weerakoon M. Ananda P. de Silva Thomas Rosswall 《Plant and Soil》1988,108(2):201-209
Sesbania sesban was evaluated as green manure crop for lowland rice in the Dry Zone of Sri Lanka. The legume was grown during a fallow period
before lowland rice (Oryza sativa) and ploughed under just before transplanting. Weight loss and nitrogen content in litterbags containing leaves, stems and
roots of the legume were monitored. Comparisons were made between rice yields from 20 m2 plots after green manuring in combination with different nitrogen fertilizer levels (0, 2.4, 4.8 and 7.2 gm−2) and nitrogen fertilizer (9.6 gm−2) alone. Above-ground biomass ofS. sesban was 440 gm−2 (dry wt) when ploughed under after 84 days growth. N-content in leaves, stems and roots was 3.76%, 0.41% and 0.73%, respectively.
This gave a N-input fromS. sesban of 9.2 gm−2 (8.3 g from above-ground parts and 0.9 g from roots). The corresponding K and P inputs were 7.3 and 0.6 gm−2 respectively. The nitrogen rich leaves, which contained 88% of the nitrogen in the above-ground parts, decomposed and released
its nitrogen much more rapidly than the stems and roots. After only four days the leaves had released 5.3 g Nm−2 and after 14 days they had released 6.4 g Nm−2. The highest rice yield (505 gm−2) was obtained usingS. sesban and 4.8 gm−2 of N-fertilizer. The yields with only N-fertilizer or onlyS. sesban were 442 gm−2 and 396 gm−2, respectively. Due to the rapid decomposition of the nitrogen rich leaves,S. sesban did not behave as a slow release fertilizer. Thus, it is not necessary to apply nitrogen fertilizers as a basal dose. 相似文献
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André Dupont Lionel Cusan Marie Garon Gabriel Alvarado-Urbina Fernand Labrie 《Life sciences》1977,21(7):907-914
Thirty sec after the intrajugular injection of [3H] methionine-enkephalin (met-enkephalin) in the rat, the radioactivity was already distributed in an apparent volume of 53 ml and the metabolic clearance rate calculated from the characteristics of the plasma disappearance curve was 10 ml/min. As shown by partition chromatography plasma extracts obtained 15 sec after injection of [3H] met-enkephalin, only 5% of the total radioactivity migrated as the intact pentapeptide, while no detectable intact pentapeptide remained 2 min after injection, thus indicating a half-life of [3H] met-enkephalin of the order of 2 to 4 sec. Incubation of rat cerebral tissue with [3H] met-enkephalin indicates that the first step in the breakdown of met-enkephalin in both plasma and brain tissue is cleavage of the Tyr-Gly amide bond. These data offer an explanation for the low activity of met-enkephalin after intraventricular or intravenous administration. 相似文献
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