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排序方式: 共有212条查询结果,搜索用时 15 毫秒
71.
Prendergast L van Vuuren C Kaczmarczyk A Doering V Hellwig D Quinn N Hoischen C Diekmann S Sullivan KF 《PLoS biology》2011,9(6):e1001082
Centromeres are differentiated chromatin domains, present once per chromosome, that direct segregation of the genome in mitosis and meiosis by specifying assembly of the kinetochore. They are distinct genetic loci in that their identity in most organisms is determined not by the DNA sequences they are associated with, but through specific chromatin composition and context. The core nucleosomal protein CENP-A/cenH3 plays a primary role in centromere determination in all species and directs assembly of a large complex of associated proteins in vertebrates. While CENP-A itself is stably transmitted from one generation to the next, the nature of the template for centromere replication and its relationship to kinetochore function are as yet poorly understood. Here, we investigate the assembly and inheritance of a histone fold complex of the centromere, the CENP-T/W complex, which is integrated with centromeric chromatin in association with canonical histone H3 nucleosomes. We have investigated the cell cycle regulation, timing of assembly, generational persistence, and requirement for function of CENPs -T and -W in the cell cycle in human cells. The CENP-T/W complex assembles through a dynamic exchange mechanism in late S-phase and G2, is required for mitosis in each cell cycle and does not persist across cell generations, properties reciprocal to those measured for CENP-A. We propose that the CENP-A and H3-CENP-T/W nucleosome components of the centromere are specialized for centromeric and kinetochore activities, respectively. Segregation of the assembly mechanisms for the two allows the cell to switch between chromatin configurations that reciprocally support the replication of the centromere and its conversion to a mitotic state on postreplicative chromatin. 相似文献
72.
Cryptococcus neoformans is an opportunistic fungal pathogen characterized by a prominent polysaccharide capsule that envelops the cell. Although this capsule is dispensable for in vitro growth, its presence is essential for virulence. The capsule is primarily made of two xylose-containing polysaccharides, glucuronoxylomannan and galactoxylomannan. There are likely to be multiple xylosyltransferases (XTs) involved in capsule synthesis, and the activities of these enzymes are potentially important for cryptococcal virulence. A beta-1,2-xylosyltransferase with specificity appropriate for capsule synthesis was purified approximately 3000-fold from C. neoformans, and the corresponding gene was identified and cloned. This sequence conferred XT activity when expressed in Saccharomyces cerevisiae, which lacks endogenous XT activity. The gene, termed CXT1 for cryptococcal xylosyltransferase 1, encodes a 79-kDa type II membrane protein with an N-linked glycosylation site and two DXD motifs. These latter motifs are believed to coordinate divalent cation binding in the activity of glycosyltransferases. Site-directed mutagenesis of one DXD motif abolished Cxt1p activity, even though this activity does not depend on the addition of a divalent cation. This may indicate a novel catalytic mechanism for glycosyl transfer. Five homologs of Cxt1p were found in the genome sequence of C. neoformans and 34 within the sequences of other fungi, although none were found in other organisms. Many of the homologous proteins are similar in size to Cxt1p, and all are conserved with respect to the essential DXD motif. These proteins represent a new family of glycosyltransferases, found exclusively within the fungal kingdom. 相似文献
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76.
Stephan Doering Bj?rn Enzi Cornelius Faber Jens Hinrichs Judith Bahmer Georg Northoff 《PloS one》2012,7(11)
Objective
Recent neuroscience studies explored the neuronal mechanisms underlying our sense of self. Thereby the cortical midline structures and their anterior and posterior regions have been shown to be central. What remains unclear though is how both, self and cortical midline structures, are related to the identity of the self which is of central importance in especially personality disorders.Methods
Conducting an exploratory study with a dimensional approach, we here compared subjects with high and low level of personality functioning and identity integration as measured in a standardized way in fMRI during both, emotion- and reward-related tasks.Results
Low levels of personality functioning and identity integration were predicted by significantly decreased degrees of deactivation in the anterior and posterior cortical midline structures.Conclusions
Though exploratory our results show for the first time direct relationship between cortical midline structures and personality functioning in terms of identity integration. This does not only contribute to our understanding of the neuronal mechanism underlying self and identity but carries also major implications for the treatment of patients with personality disorders. 相似文献77.
Eric AF Sim?es Xavier Carbonell-Estrany John R Fullarton Johannes G Liese Jose Figueras-Aloy Gunther Doering Juana Guzman European RSV Risk Factor Study Group 《Respiratory research》2008,9(1):78
Background
The aim of this study, conducted in Europe, was to develop a validated risk factor based model to predict RSV-related hospitalisation in premature infants born 33–35 weeks'' gestational age (GA).Methods
The predictive model was developed using risk factors captured in the Spanish FLIP dataset, a case-control study of 183 premature infants born between 33–35 weeks'' GA who were hospitalised with RSV, and 371 age-matched controls. The model was validated internally by 100-fold bootstrapping. Discriminant function analysis was used to analyse combinations of risk factors to predict RSV hospitalisation. Successive models were chosen that had the highest probability for discriminating between hospitalised and non-hospitalised infants. Receiver operating characteristic (ROC) curves were plotted.Results
An initial 15 variable model was produced with a discriminant function of 72% and an area under the ROC curve of 0.795. A step-wise reduction exercise, alongside recalculations of some variables, produced a final model consisting of 7 variables: birth ± 10 weeks of start of season, birth weight, breast feeding for ≤ 2 months, siblings ≥ 2 years, family members with atopy, family members with wheeze, and gender. The discrimination of this model was 71% and the area under the ROC curve was 0.791. At the 0.75 sensitivity intercept, the false positive fraction was 0.33. The 100-fold bootstrapping resulted in a mean discriminant function of 72% (standard deviation: 2.18) and a median area under the ROC curve of 0.785 (range: 0.768–0.790), indicating a good internal validation. The calculated NNT for intervention to treat all at risk patients with a 75% level of protection was 11.7 (95% confidence interval: 9.5–13.6).Conclusion
A robust model based on seven risk factors was developed, which is able to predict which premature infants born between 33–35 weeks'' GA are at highest risk of hospitalisation from RSV. The model could be used to optimise prophylaxis with palivizumab across Europe. 相似文献78.
The pathogenic yeast Cryptococcus neoformans is distinguished by an extensive polysaccharide capsule, which impedes host defences and is absolutely required for fungal virulence. Despite the biological importance of the capsule, nothing is known about how it is assembled. Substantial capsule growth occurs in two distinct situations relevant to cryptococcal pathogenesis: formation of new buds and induction of capsule on mature cells. We developed pulse-chase protocols to examine these events in a dynamic way using a variety of microscopy techniques. We show that the capsule overlying buds is newly synthesized and differs physically from the corresponding parental material. New capsule formed by mature cells upon induction of synthesis is added at the inner aspect of the existing structure, displacing pre-existing material outwards. Surprisingly, new polysaccharide material is also deposited throughout the capsule, yielding a progressively denser structure. These results yield the first model of capsule synthesis and open new lines of investigation into the underlying mechanisms. 相似文献
79.
The early adaptive evolution of calmodulin 总被引:7,自引:0,他引:7
Baba ML; Goodman M; Berger-Cohn J; Demaille JG; Matsuda G 《Molecular biology and evolution》1984,1(6):442-455
Interaction between gene duplication and natural selection in molecular
evolution was investigated utilizing a phylogenetic tree constructed by the
parsimony procedure from amino acid sequences of 50 calmodulin- family
protein members. The 50 sequences, belonging to seven protein lineages
related by gene duplication (calmodulin itself, troponin-C, alkali and
regulatory light chains of myosin, parvalbumin, intestinal calcium-binding
protein, and glial S-100 phenylalanine-rich protein), came from a wide
range of eukaryotic taxa and yielded a denser tree (more branch points
within each lineage) than in earlier studies. Evidence obtained from the
reconstructed pattern of base substitutions and deletions in these
ancestral loci suggests that, during the early history of the family,
selection acted as a transforming force on expressed genes among the
duplicates to encode molecular sites with new or modified functions. In
later stages of descent, however, selection was a conserving force that
preserved the structures of many coadapted functional sites. Each branch of
the family was found to have a unique average tempo of evolutionary change,
apparently regulated through functional constraints. Proteins whose
functions dictate multiple interaction with several other macromolecules
evolved more slowly than those which display fewer protein-protein and
protein-ion interactions, e.g., calmodulin and next troponin-C evolved at
the slowest average rates, whereas parvalbumin evolved at the fastest. The
history of all lineages, however, appears to be characterized by rapid
rates of evolutionary change in earlier periods, followed by slower rates
in more recent periods. A particularly sharp contrast between such fast and
slow rates is found in the evolution of calmodulin, whose rate of change in
earlier eukaryotes was manyfold faster than the average rate over the past
1 billion years. In fact, the amino acid replacements in the nascent
calmodulin lineage occurred at residue positions that in extant metazoans
are largely invariable, lending further support to the Darwinian hypothesis
that natural selection is both a creative and a conserving force in
molecular evolution.
相似文献
80.
A novel pathway for glycan assembly: biosynthesis of the glycosyl-phosphatidylinositol anchor of the trypanosome variant surface glycoprotein 总被引:38,自引:0,他引:38
The trypanosome variant surface glycoprotein (VSG), like many other eukaryotic cell surface proteins, is anchored to the plasma membrane by a glycosyl-phosphatidylinositol (GPI) moiety. This glycolipid is assembled first as a precursor (glycolipid A) that is then covalently attached to the newly synthesized polypeptide. We have developed a trypanosome cell-free system capable of performing all of the steps in the biosynthesis of the glycan portion of glycolipid A. Using [3H]sugar nucleotides as substrates, several biosynthetic intermediates have been identified. From structural analyses of these intermediates, we propose a pathway for GPI biosynthesis. Based on comparisons between the VSG GPI anchor and similar structures in other cells, we believe that this same pathway will apply to the GPI anchors, and the related insulin-mediator compound, of higher eukaryotes. 相似文献