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111.
Genotype-phenotype correlations in families with deletions in the von Hippel-Lindau (VHL) gene 总被引:4,自引:0,他引:4
Hes F Zewald R Peeters T Sijmons R Links T Verheij J Matthijs G Leguis E Mortier G van der Torren K Rosman M Lips C Pearson P van der Luijt R 《Human genetics》2000,106(4):425-431
Von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome characterized by predisposition for bilateral and multi-centric hemangioblastoma in the retina and central nervous system, pheochromocytoma, renal cell carcinoma, and cysts in the kidney, pancreas, and epididymis. We describe five families for which direct sequencing of the coding region of the VHL gene had failed to identify the family-specific mutation. Further molecular analysis revealed deletions involving the VHL gene in each of these families. In four families, partial deletions of one or more exons were detected by Southern blot analysis. In the fifth family, FISH analysis demonstrated the deletion of the entire VHL gene. Our results show that (quantitative) Southern blot analysis is a sensitive method for detecting germline deletions of the VHL gene and should be implemented in routine DNA diagnosis for VHL disease. Our data support the previously established observation that families with a germline deletion have a low risk for pheochromocytoma. Further unraveling of genotype-phenotype correlations in VHL disease has revealed that families with a full or partial deletion of the VHL gene exhibit a phenotype with a preponderance of central nervous system hemangioblastoma. 相似文献
112.
Perdreau H Mortier E Bouchaud G Solé V Boublik Y Plet A Jacques Y 《European cytokine network》2010,21(4):297-307
Interleukin (IL)-15 is a cytokine critical for the homeostasis and the function of NK cells, NK-T cells, and memory CD8+ T cells. IL-15 signals are delivered through the IL-15Rβ and the common γ (γ(c)) receptor chains. The third receptor chain, IL-15Rα, confers specificity and high affinity for the cytokine. While IL-15 can activate with high affinity the trimeric receptor expressed by a target cell (cis-presentation), IL-15Rα is also known to trans-present IL-15 with high affinity to target cells expressing the IL-15Rβ/γ(c) complex. In order to compare the IL-15 cis- and trans-presentation processes, and using a T cell line expressing both IL-15Rα/β/γ(c) and IL-15Rβ/γ(c), we analyzed cell surface receptor chain down-modulation, cytokine internalization and signaling responses induced either with IL-15 (cis-presentation) or with RLI, a protein resulting from fusion between IL-15 and an extended IL-15Rα sushi domain, that mimics trans-presentation. Whereas IL-15 bound with high affinity to IL-15Rα/β/γ(c), RLI bound with a similar high affinity to IL-15Rβ/γ(c). The kinetics of cell surface IL-15R down-modulation were slower following RLI treatment than after IL-15 treatment, as were the kinetics of RLI internalization, which was slower than that of IL-15. IL-15 and RLI dose-dependently induced the activation of similar signaling pathways. However, the kinetics and duration of these activations were markedly different, RLI-induced signaling, being slower, but more prolonged than that induced by IL-15, although the final proliferative responses at 48?h were similar. These findings collectively indicate that IL-15 cis- and trans-presentation mechanisms lead to different dynamics of receptor activation and signal transduction, with cis-presentation inducing fast and transient responses, and trans-presentation inducing slower, more persistent ones. They provide clues for a better understanding of how IL-15 action is controlled, and how it plays a key role in the coordination between innate and adaptative immunity. 相似文献
113.
A structural model of the sushi domain of IL-15Ralpha was first obtained by homology modeling to study its interactions with IL-15 by means of molecular modeling, peptide scanning, and site-directed mutagenesis. From these experimental data, a putative interacting surface of IL-15Ralpha with a previously published IL-15 model was inferred: Leu25, Leu44, and Glu46 of IL-15 and Arg35 of IL-15Ralpha were found to be key interfacial residues and were subsequently used as filters for the construction of docking solutions. Human IL-15/IL-15Ralpha complexes were constructed in two stages, with a preliminary docking procedure, treating the two partners as rigid bodies and using these filters. In this first stage, two classes of docking solutions were characterized. From a topological point of view, each solution could be derived from the other by reverse orientation of one partner in relation to the other. In a second stage, several further energy refinements clearly favored one solution. Moreover, this unique docking solution was confirmed by molecular modeling of IL-15 mutants previously built and tested in our laboratory. Finally, this complex model, which is a useful tool to study the IL-15/IL-15Ralpha interface, was topologically compared to IL-2/IL-2Ralpha complexes (previous model in the literature and recent crystal structure). 相似文献
114.
AIMS: To examine the role of the nutrients on the onset of flocculation in an ale-brewing strain, Saccharomyces cerevisiae NCYC 1195. METHODS AND RESULTS: Flocculation was evaluated using the method of Soares, E.V. and Vroman, A. [Journal of Applied Microbiology (2003) 95, 325]. For cells grown in chemically defined medium (yeast nitrogen base with glucose) or in rich medium (containing yeast extract, peptone and fermentable sugars: fructose or maltose), the onset of flocculation occurred after the end of exponential respiro-fermentative phase of growth being coincident with the attainment of the lower level of carbon source in the culture medium. Cells, in exponential respiro-fermentative phase of growth, transferred to a glucose-containing medium without nitrogen source, developed a flocculent phenotype, while these carbon source starved cells, in the presence of all other nutrients that support growth, did not flocculate. In addition, cells in exponential phase of growth, under catabolite repression, when transferred to a medium containing 0.2% (w/v) of fermentable sugar (fructose or maltose) or 2% (v/v) ethanol, showed a rapid triggering of flocculation, while when incubated in 2% (v/v) glycerol did not develop a flocculent phenotype. CONCLUSIONS: The onset of flocculation occurs when a low sugar and/or nitrogen concentration is reached in culture media. The triggering of flocculation is an energetic dependent process influenced by the carbon source metabolism. The presence of external nitrogen source is not necessary for developing a flocculent phenotype. SIGNIFICANCE AND IMPACT OF THE STUDY: This work contributes to the elucidation of the role of nutrients on the onset of flocculation in NewFlo phenotype yeast strains. This information might be useful to the brewing industry, in the control of yeast flocculation, as the time when the onset of flocculation occurs can determine the fermentation performance and the beer quality. 相似文献
115.
Mutations in STRA6 cause a broad spectrum of malformations including anophthalmia, congenital heart defects, diaphragmatic hernia, alveolar capillary dysplasia, lung hypoplasia, and mental retardation 下载免费PDF全文
Pasutto F Sticht H Hammersen G Gillessen-Kaesbach G Fitzpatrick DR Nürnberg G Brasch F Schirmer-Zimmermann H Tolmie JL Chitayat D Houge G Fernández-Martínez L Keating S Mortier G Hennekam RC von der Wense A Slavotinek A Meinecke P Bitoun P Becker C Nürnberg P Reis A Rauch A 《American journal of human genetics》2007,80(3):550-560
116.
Phylogenetic relationships among prokaryotic and eukaryotic catalases 总被引:13,自引:1,他引:12
Seventy-four catalase protein sequences, including 29 bacterial, 8 fungal,
7 animal, and 30 plant sequences, were compiled, and 70 were used for
phylogenetic reconstruction. The core of the resulting tree revealed
unique, separate groups of plant and animal catalases, two groups of fungal
catalases, and three groups of bacterial catalases. The only overlap of
kingdoms occurred within one branch and involved fungal and bacterial
large-subunit enzymes. The other fungal branch was closely linked to the
group of animal enzymes. Group I bacterial catalases were more closely
related to the plant enzymes and contained such diverse taxa as the
Gram-positive Listeria seeligeri, Deinocococcus radiodurans, and
gamma-proteobacteria. Group III bacterial sequences were more closely
related to fungal and animal sequences and included enzymes from a broad
range of bacteria including high- and low-GC Gram positives,
proteobacteria, and a bacteroides species. Group II was composed of
large-subunit catalases from diverse sources including Gram positives
(low-GC Bacilli and high-GC Mycobacteria), proteobacteria, and species of
the filamentous fungus Aspergillus. These data can be interpreted in terms
of two gene duplication events that produced a minimum of three catalase
gene family members that subsequently evolved in response to environmental
demands. Horizontal gene transfer may have been responsible for the group
II mixture of bacterial and fungal large-subunit catalases.
相似文献
117.
118.
Macia E Partisani M Favard C Mortier E Zimmermann P Carlier MF Gounon P Luton F Franco M 《The Journal of biological chemistry》2008,283(28):19836-19844
The Arf6-specific exchange factor EFA6 coordinates membrane trafficking with actin cytoskeleton remodeling. It localizes to the plasma membrane where it catalyzes Arf6 activation and induces the formation of actin-based membrane ruffles. We have shown previously that the pleckstrin homology (PH) domain of EFA6 was responsible for its membrane localization. In this study we looked for the partners of the PH domain at the plasma membrane. Mutations of the conserved basic residues suspected to be involved in the binding to phosphoinositides redistribute EFA6-PH to the cytosol. In addition, phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) breakdown also leads to the solubilization of EFA6-PH. Direct binding measured by surface plasmon resonance gives an apparent affinity of approximately 0.5 microm EFA6-PH for PI(4,5)P2. Moreover, we observed in vitro that the catalytic activity of EFA6 is strongly increased by PI(4,5)P2. These results indicate that the plasma membrane localization of EFA6-PH is based on its interaction with PI(4,5)P2, and this interaction is necessary for an optimal catalytic activity of EFA6. Furthermore, we demonstrated by fluorescence recovery after photobleaching and Triton X-100 detergent solubility experiments that in addition to the phophoinositides, EFA6-PH is linked to the actin cytoskeleton. We observed both in vivo and in vitro that EFA6-PH interacts directly with F-actin. Finally, we demonstrated that EFA6 could bind simultaneously filamentous actin and phospholipids vesicles. Our results explain how the exchange factor EFA6 via its PH domain could coordinate at the plasma membrane actin cytoskeleton organization with membrane trafficking. 相似文献
119.
Andreas Zankl Emma?L. Duncan Paul?J. Leo Graeme?R. Clark Evgeny?A. Glazov Marie-Claude Addor Troels Herlin Chong?Ae Kim Bruno?P. Leheup Jim McGill Steven McTaggart Stephen Mittas Anna?L. Mitchell Geert?R. Mortier Stephen?P. Robertson Marie Schroeder Paulien Terhal Matthew?A. Brown 《American journal of human genetics》2014,94(4):643
120.
Bart I. Roman Laurens M. De Coen Séverine Thérèse F.C. Mortier Tine De Ryck Barbara W.A. Vanhoecke Alan R. Katritzky Marc E. Bracke Christian V. Stevens 《Bioorganic & medicinal chemistry》2013,21(17):5054-5063
In our ongoing exploration of the structure–activity landscape of anti-invasive chalcones, we have prepared and evaluated a number of structurally related (E)- and (Z)-stilbenes. These molecules exhibited an extraordinary high in vitro potency in the chick heart invasion assay, being active up to 10 nmol L?1, a concentration level a 100-fold lower than the lowest effective doses that have been reported for natural analogues. Furthermore, they possess an interesting pharmacological profile in silico. 相似文献