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排序方式: 共有111条查询结果,搜索用时 31 毫秒
31.
Yu L Mohamed AJ Vargas L Berglöf A Finn G Lu KP Smith CI 《The Journal of biological chemistry》2006,281(26):18201-18207
Bruton tyrosine kinase (Btk) is expressed in B-lymphocytes. Mutations in Btk cause X-linked agammaglobulinemia in humans. However, the mechanism of activation and signaling of this enzyme has not been fully investigated. We have here shown that the peptidylprolyl cis/trans isomerase (PPIase) Pin1 is a negative regulator of Btk, controlling its expression level by reducing its half-life, whereas the catalytic activity of Btk was unaffected. The negative regulatory effect of Pin1 was observed both in cell lines and in Pin(-/-) mice and was found to be dependent on a functionally intact Btk. This may constitute a feedback loop for the regulation of Btk. The target region in Btk was localized to the pleckstrin homology domain suggesting that interphase phosphorylation of serine 115 (Ser-115) in Btk is required, whereas mitosis phosphorylation of serine 21 (Ser-21) is critical. Accordingly, Pin 1 was shown to associate with Btk through binding to Ser-21 and -115, respectively, both of which lie in a classical Pin1-binding pocket. Using a phosphomitotic antibody, it was found that Btk harbors a bona fide MPM2 epitope corresponding to a phosphorylated serine or threonine residue followed by a proline. Our results indicate that the peptidylprolyl isomerase Pin1 interacts with Btk in a cell cycle-dependent manner, regulating the Btk expression level. 相似文献
32.
The didelphid marsupial, Didelphis aurita, is suggested as an intraguild predator and as key‐species in small mammal assemblages of the Atlantic Forest of Brazil. The field experiments required to test this hypothesis are complex to implement, but the recent revival of regression methods offers a viable alternative. Here we use the dynamic and static regression methods to determine the importance of D. aurita as a competitor and intraguild predator. Capture–recapture data from two localities in the Rio de Janeiro State were used, Garrafão (municipality of Guapimirim), a coastal forest of the Serra do Mar, and Barra de Maricá, a costal sand dune vegetation. Population and microhabitat variables were monitored from April 1997 to April 2003 in Garrafão, and from January 1986 to July 1990 in Barra de Maricá. Microhabitat variables were related to Canopy, Plant, Litter and Rock covers, Obstruction from 0 to 1.5 m, and Number of logs. Exploitation competition was tested by the dynamic method, which models the effects of D. aurita on the per capita growth rate of a species. Interference by predation or competition was tested by the static method, where the abundance of D. aurita at trap stations was regressed against the abundance of other small mammals, after removal of any variation associated with microhabitat factors. Exploitation competition was not detected, but the interference of D. aurita was pervasive, affecting all small mammals studied in the two localities. The clear avoidance of D. aurita by all small mammals tested in two localities of different physiognomies indicates that it functions as an intraguild predator, even if actual predation by D. aurita is an occasional event. 相似文献
33.
We are currently in an interesting phase of plant biotechnology releases, both for the scientists responsible for these innovations who are beginning to see their ideas realized, and for the biotechnology companies that are starting to see a return on their investment. One of the most notable examples, is the introduction of transgenic crops that are engineered to express a Bacillus thuringiensis toxin that confers resistance to insect predation. However, the picture is not altogether positive - there is concern that the introduction of this technology was premature or should not have happened at all, and that the valuable insecticidal properties of Bacillus thuringiensis will be lost. 相似文献
34.
35.
Amoresano A; Andolfo A; Siciliano RA; Mele A; Coscarella A; De Santis R; Mauro S; Pucci P; Marino G 《Glycobiology》1998,8(8):779-790
MEN 11300 is a hybrid glycoprotein of 297 amino acids obtained by fusion of
the cDNA encoding GM-CSF with the cDNA encoding EPO followed by
transfection of the hybrid gene into CHO cells. The oligonucleotide
construct incorporated a spacing sequence between the two individual cDNAs
which encodes eight amino acids constituting a linker peptide intended to
separate the GM-CSF and EPO moieties. The recombinant MEN 11300 protein was
submitted to a detailed structural characterization including the
verification of the entire amino acid sequence, the assignment of the
disulfide bridges pattern, the identification of the glycosylation sites
and the definition of the glycosidic moiety, including site-specificity.
Partial processing of the C-terminal Arg residue and the occurrence of
N-glycosylation sites at Asn27, Asn155, Asn169, Asn214 were established.
Moreover, O-glycosylation at Ser257 and at the N-terminal region was also
detected. A large heterogeneity was observed in the N-glycans due to the
presence of differently sialylated and fucosylated branched complex type
oligosaccharides whereas O-linked glycans were constituted by GalGalNAc
chains with a different number of sialic acids. The disulfide bridges
pattern was established by direct FABMS analysis of the proteolytic digests
or by ESMS analysis of HPLC purified fractions. Pairing of the eight
cysteine residues resulted in Cys54-Cys96, Cys88-Cys121, Cys138-Cys292, and
Cys160-Cys164. This S-S bridges pattern is identical to that occurring in
the individual natural GM-CSF and EPO, thus showing that the two protein
moieties in MEN 11300 can independently acquire their native
three-dimensional structure.
相似文献
36.
Unusual pattern of bacterial ice nucleation gene evolution 总被引:5,自引:0,他引:5
Edwards AR; Van den Bussche RA; Wichman HA; Orser CS 《Molecular biology and evolution》1994,11(6):911-920
Bacterial ice nucleation activity (INA+ phenotype) can be traced to the
product of a single gene, ina. A remarkably sparse distribution of this
phenotype within three bacterial genera indicates that the ina gene may
have followed an unusual evolutionary path. Southern blot analyses, coupled
with assays for ice-nucleating ability, revealed that within four bacterial
species an ina gene is present in some strains but absent from others.
Results of hybridization experiments using DNA fragments that flank the ina
gene suggested that the genotypic dimorphism of ina may be anomalous. A
phylogenetic analysis of 16S ribosomal RNA gene sequences from a total of
14 ina+ and ina- bacterial strains indicated that the ina+ bacteria are not
monophyletic but instead phylogenetically interspersed among ina- bacteria.
The relationships of ina+ bacteria inferred from ina sequence did not
coincide with those inferred from the 16S data. These results suggest the
possibility of horizontal transfer in the evolution of bacterial ina genes.
相似文献
37.
38.
Syed RA Gardezi 《Archives Of Phytopathology And Plant Protection》2013,46(2):113-122
Six species of mushrooms allied to the Family Sclerodermataceae, Lycoperdaceae and Geastraceae have been described for the first time from Azad Jammu and Kashmir. These are Scleroderma aurantium, Calvatia verrucosia sp. nov., Lycoperdon pedicellaton sp. nov. L. sphaericon sp. nov., L. echinulaton sp. nov., and Geastrum heptaplex sp. nov. 相似文献
39.
Amy L Roberts Ellen RA Thomas Shriram Bhosle Laurence Game Olga Obraztsova Timothy J Aitman Timothy J Vyse Benjamin Rhodes 《Arthritis research & therapy》2014,16(3):R114
Introduction
The majority of the genetic variance of systemic lupus erythematosus (SLE) remains unexplained by the common disease-common variant hypothesis. Rare variants, which are not detectable by genome-wide association studies because of their low frequencies, are predicted to explain part of this ”missing heritability.” However, recent studies identifying rare variants within known disease-susceptibility loci have failed to show genetic associations because of their extremely low frequencies, leading to the questioning of the contribution of rare variants to disease susceptibility. A common (minor allele frequency = 17.4% in cases) nonsynonymous coding variant rs1143679 (R77H) in ITGAM (CD11b), which forms half of the heterodimeric integrin receptor, complement receptor 3 (CR3), is robustly associated with SLE and has been shown to impair CR3-mediated phagocytosis.Methods
We resequenced ITGAM in 73 SLE cases and identified two previously unidentified, case-specific nonsynonymous variants, F941V and G1145S. Both variants were genotyped in 2,107 and 949 additional SLE cases, respectively, to estimate their frequencies in a disease population. An in vitro model was used to assess the impact of F941V and G1145S, together with two nonsynonymous ITGAM polymorphisms, A858V (rs1143683) and M441T (rs11861251), on CR3-mediated phagocytosis. A paired two-tailed t test was used to compare the phagocytic capabilities of each variant with that of wild-type CR3.Results
Both rare variants, F941V and G1145S, significantly impair CR3-mediated phagocytosis in an in vitro model (61% reduction, P = 0.006; 26% reduction, P = 0.0232). However, neither of the common variants, M441T and A858V, had an effect on phagocytosis. Neither rare variant was observed again in the genotyping of additional SLE cases, suggesting that there frequencies are extremely low.Conclusions
Our results add further evidence to the functional importance of ITGAM in SLE pathogenesis through impaired phagocytosis. Additionally, this study provides a new example of the identification of rare variants in common-allele-associated loci, which, because of their extremely low frequencies, are not statistically associated. However, the demonstration of their functional effects adds support to their contribution to disease risk, and questions the current notion of dismissing the contribution of very rare variants on purely statistical analyses. 相似文献40.
Teng E Leong KP Li HH Thong B Koh ET Loi PL Zhao Y Tan EK;TTSH RA Study Group 《DNA and cell biology》2012,31(4):607-610
A genome-wide association study in Japan identified the C-C chemokine receptor type 6 gene (CCR6) as associated with rheumatoid arthritis (RA). This finding has not been validated in other Asian populations. A case-control study involving 996 subjects, comprising 440 controls and 556 RA patients, was done to determine their anticyclic citrullinated peptide (anti-CCP) antibody status and CCR6 polymorphism (rs3093024) genotype. Three hundred eighty-seven patients were anti-CCP positive and 153 anti-CCP negative. Logistic regression showed that allele A was likely to increase the risk of developing RA among females via a recessive model (odds ratio [OR]=1.55, 95% confidence interval [CI]=1.01, 2.39), whereas the risk effect appeared to be reduced among males via an additive model (OR=0.60, 95% CI=0.42, 0.85). Considering only subjects who are anti-CCP positive, allele A increased RA risk among females via a recessive model (OR=1.68, 95% CI=1.07, 2.64) but decreased the risk among males via an additive model (OR=0.59, 95% CI=0.39, 0.89). We showed that CCR6 polymorphism was a risk factor among females but a protective factor among males. Functional studies are warranted to unravel the pathophysiological relevance of the gene variant and other linked variants with RA. 相似文献