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91.
Synthesis of a C-terminal modified peptide with an -amido methylketone was efficiently carried out using a backbone-amide-type linker loading with a monofunctionalized diamine, provided that no base such as piperidine or diisopropylethylamine or a reducing agent such as triisopopylsilane was used for the synthetic pathway. The ketoxime-forming chemoselective ligation between a methylketone and an aminooxy was quantitative in 5 h at pH 2. 相似文献
92.
Audiovisual integration of speech falters under high attention demands 总被引:11,自引:0,他引:11
One of the most commonly cited examples of human multisensory integration occurs during exposure to natural speech, when the vocal and the visual aspects of the signal are integrated in a unitary percept. Audiovisual association of facial gestures and vocal sounds has been demonstrated in nonhuman primates and in prelinguistic children, arguing for a general basis for this capacity. One critical question, however, concerns the role of attention in such multisensory integration. Although both behavioral and neurophysiological studies have converged on a preattentive conceptualization of audiovisual speech integration, this mechanism has rarely been measured under conditions of high attentional load, when the observers' attention resources are depleted. We tested the extent to which audiovisual integration was modulated by the amount of available attentional resources by measuring the observers' susceptibility to the classic McGurk illusion in a dual-task paradigm. The proportion of visually influenced responses was severely, and selectively, reduced if participants were concurrently performing an unrelated visual or auditory task. In contrast with the assumption that crossmodal speech integration is automatic, our results suggest that these multisensory binding processes are subject to attentional demands. 相似文献
93.
Vignery A 《Médecine sciences : M/S》2005,21(12):1070-1075
The fusion of cells is a fundamental biological event that plays a central role in a variety of developmental and homeostatic processes. Macrophages are present in all tissues and can initiate interaction and fusion. The putative macrophage-fusion machinery is still poorly understood, but some of its components have been identified. Macrophages recognize each other as < self > in order to fuse but some essential questions remain: do macrophages fuse with somatic cells to repair tissues and organs? Do macrophages fuse with tumor cells to trigger metastasis? Agnès Vignery discusses these novel and challenging ideas in this review. 相似文献
94.
95.
Archer A Sauvaget D Chauffeton V Bouchet PE Chambaz J Pinçon-Raymond M Cardot P Ribeiro A Lacasa M 《Molecular endocrinology (Baltimore, Md.)》2005,19(9):2320-2334
In the small intestine, the expression of the apolipoprotein (apo) C-III and A-IV genes is restricted to the enterocytes of the villi. We have previously shown that, in transgenic mice, specific expression of the human apo C-III requires a hormone-responsive element (HRE) located in the distal region of the human apoA-IV promoter. This HRE binds the hepatic nuclear factors (HNF)-4alpha and gamma. Here, intraduodenal injections in mice and infections of human enterocytic Caco-2/TC7 cells with an adenovirus expressing a dominant-negative form of HNF-4alpha repress the expression of the apoA-IV gene, demonstrating that HNF-4 controls the apoA-IV gene expression in enterocytes. We show that HNF-4alpha and gamma functionally interact with a second HRE present in the proximal region of the human apoA-IV promoter. New sets of transgenic mice expressing mutated forms of the promoter, combined with the human apo C-III enhancer, demonstrate that, whereas a single HRE is sufficient to reproduce the physiological cephalo-caudal gradient of apoA-IV gene expression, both HREs are required for expression that is restricted to villi. The combination of multiple HREs may specifically recruit regulatory complexes associating HNF-4 and either coactivators in villi or corepressors in crypts. 相似文献
96.
G1 phase regulation, area-specific cell cycle control, and cytoarchitectonics in the primate cortex 总被引:1,自引:0,他引:1
Lukaszewicz A Savatier P Cortay V Giroud P Huissoud C Berland M Kennedy H Dehay C 《Neuron》2005,47(3):353-364
We have investigated the cell cycle-related mechanisms that lead to the emergence of primate areas 17 and 18. These areas are characterized by striking differences in cytoarchitectonics and neuron number. We show in vivo that (1) area 17 precursors of supragranular neurons exhibit a shorter cell cycle duration, a reduced G1 phase, and a higher rate of cell cycle reentry than area 18 precursors; (2) area 17 and area 18 precursors show contrasting and specific levels of expression of cyclin E (high in area 17, low in area 18) and p27Kip1 (low in area 17, high in area 18); (3) ex vivo up- and downmodulation of cyclin E and p27Kip1 show that both regulators influence cell cycle kinetics by modifying rates of cell cycle progression and cell cycle reentry; (4) modeling the areal differences in cell cycle parameters suggests that they contribute to areal differences in numbers of precursors and neuron production. 相似文献
97.
FADD (Fas Associated protein with Death Domain) is a key adaptor molecule transmitting the death signal mediated by death receptors. In addition, this multiple functional protein is implicated in survival/proliferation and cell cycle progression. FADD functions are regulated via cellular sublocalization, protein phosphorylation, and inhibitory molecules. In the present review, we focus on the role of the FADD adaptor in cancer. Increasing evidence shows that defects in FADD protein expression are associated with tumor progression both in mice and humans. Better knowledge of the mechanisms leading to regulation of FADD functions will improve understanding of tumor growth and the immune escape mechanisms, and could open a new field for therapeutic interventions. 相似文献
98.
Chevrier C Perret C Bahuau M Nelva A Herman C Francannet C Robert-Gnansia E Cordier S 《Birth defects research. Part A, Clinical and molecular teratology》2005,73(2):114-122
BACKGROUND: Maternal alcohol consumption has been associated with an increased risk of nonsyndromic oral clefts in some studies. Study of gene-environment interaction may provide insight into the reasons for their discrepancies observed. We focused on a polymorphism of the ADH1C gene (third gene of the class I alcohol dehydrogenase family), involved in the metabolism of ethanol and other alcohols. METHODS: Data come from a French case-control study (1998-2001), which tested the association between maternal alcohol consumption during the first trimester of pregnancy and the risk of nonsyndromic oral clefts (240 cases, 236 controls). A case-parent study design looked at the association with an ADH1C polymorphism (Ile349Val site) and potential gene-environment interaction effects. A log-linear model was used to distinguish the direct effect of the child's genotype from the maternally mediated effects. RESULTS: An increased risk of nonsyndromic oral clefts was observed for women who reported drinking alcohol during the first trimester, compared with women who did not. The mutated ADH1C allele carried by the child seemed to have a protective effect against the risk of oral clefts (RRone copy, 0.71; 95% confidence interval [CI], 0.50-1.02; RRtwo copies, 0.63; 95% CI, 0.3-1.3). The maternal genotype played a less important role than the child's, and its action remains unclear. No significant evidence of interaction effects between the ADH1C genotype and maternal alcohol consumption was observed. CONCLUSIONS: Because the ADH1C gene is involved in the metabolic pathways of many alcohols, we propose several hypotheses about the causal pathway, including ethanol oxidation activity and, more probably, retinol oxidation. 相似文献
99.
Acquisition of insertion sequences and the GBSi1 intron by Streptococcus agalactiae isolates correlates with the evolution of the species 总被引:2,自引:0,他引:2 下载免费PDF全文
Héry-Arnaud G Bruant G Lanotte P Brun S Rosenau A van der Mee-Marquet N Quentin R Mereghetti L 《Journal of bacteriology》2005,187(17):6248-6252
The prevalence of insertion sequences IS1548, IS861, IS1381, and ISSa4 and of the group II intron GBSi1 within Streptococcus agalactiae human isolates strongly correlates with the genetic lineages obtained by multilocus sequence typing. Our results yielded an evolutionary scheme for the acquisition of these genetic elements linked to the ecosystems from which the isolates were obtained. 相似文献
100.
Birtley JR Knox SR Jaulent AM Brick P Leatherbarrow RJ Curry S 《The Journal of biological chemistry》2005,280(12):11520-11527
Foot-and-mouth disease virus (FMDV) causes a widespread and economically devastating disease of domestic livestock. Although FMDV vaccines are available, political and technical problems associated with their use are driving a renewed search for alternative methods of disease control. The viral RNA genome is translated as a single polypeptide precursor that must be cleaved into functional proteins by virally encoded proteases. 10 of the 13 cleavages are performed by the highly conserved 3C protease (3C(pro)), making the enzyme an attractive target for antiviral drugs. We have developed a soluble, recombinant form of FMDV 3C(pro), determined the crystal structure to 1.9-angstroms resolution, and analyzed the cleavage specificity of the enzyme. The structure indicates that FMDV 3C(pro) adopts a chymotrypsin-like fold and possesses a Cys-His-Asp catalytic triad in a similar conformation to the Ser-His-Asp triad conserved in almost all serine proteases. This observation suggests that the dyad-based mechanisms proposed for this class of cysteine proteases need to be reassessed. Peptide cleavage assays revealed that the recognition sequence spans at least four residues either side of the scissile bond (P4-P4') and that FMDV 3C(pro) discriminates only weakly in favor of P1-Gln over P1-Glu, in contrast to other 3C(pro) enzymes that strongly favor P1-Gln. The relaxed specificity may be due to the unexpected absence in FMDV 3C(pro) of an extended beta-ribbon that folds over the substrate binding cleft in other picornavirus 3C(pro) structures. Collectively, these results establish a valuable framework for the development of FMDV 3C(pro) inhibitors. 相似文献