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排序方式: 共有350条查询结果,搜索用时 15 毫秒
41.
John Westbrook Zukang Feng Shri Jain T. N. Bhat Narmada Thanki Veerasamy Ravichandran Gary L. Gilliland Wolfgang F. Bluhm Helge Weissig Douglas S. Greer Philip E. Bourne Helen M. Berman 《Nucleic acids research》2002,30(1):245-248
The Protein Data Bank (PDB; http://www.pdb.org/) is the single worldwide archive of structural data of biological macromolecules. This paper describes the progress that has been made in validating all data in the PDB archive and in releasing a uniform archive for the community. We have now produced a collection of mmCIF data files for the PDB archive (ftp://beta.rcsb.org/pub/pdb/uniformity/data/mmCIF/). A utility application that converts the mmCIF data files to the PDB format (called CIFTr) has also been released to provide support for existing software. 相似文献
42.
Ravichandran Yesuvadian Janarthanan Krishnamoorthy Ayyalusamy Ramamoorthy Anirban Bhunia 《Biochemical and biophysical research communications》2014
Recently, γ-secretase modulators (GSM) have been shown to interact directly with the amyloid precursor protein (APP) and simultaneously inhibit the activity of the Presenilin domain of γ-secretase. A clear understanding of the molecular recognition pathways by which GSM can target both γ-secretase and Aβ precursor protein can lead to the development of more effective inhibitors. To examine whether this direct interaction with APP affects the downstream Aβ fibril formation, we chose to investigate three different molecules in this study: Sulindac sulfide, Semagacestat and E2012 from the class of generation I GSMs, γ-secretase inhibitors (GSI), and generation II GSM molecules, respectively. Firstly, through NMR based ligand titration, we identified that Sulindac sulfide and Semagacestat interact strongly with Aβ40 monomers, whereas E2012 does not. Secondly, using saturation transfer difference (STD) NMR experiments, we found that all three molecules bind equally well with Aβ40 fibrils. To determine if these interactions with the monomer/fibril lead to a viable inhibition of the fibrillation process, we designed an NMR based time-dependent assay and accurately distinguished the inhibitors from the non-inhibitors within a short period of 12 h. Based on this pre-seeded fibril assay, we conclude that none of these molecules inhibit the ongoing fibrillation, rather ligands such as Semagacestat and E2012 accelerated the rate of aggregation. 相似文献
43.
Nowadays, quality of service (QoS) is very popular in various research areas like distributed systems, multimedia real-time applications and networking. The requirements of these systems are to satisfy reliability, uptime, security constraints and throughput as well as application specific requirements. The real-time multimedia applications are commonly distributed over the network and meet various time constraints across networks without creating any intervention over control flows. In particular, video compressors make variable bit-rate streams that mismatch the constant-bit-rate channels typically provided by classical real-time protocols, severely reducing the efficiency of network utilization. Thus, it is necessary to enlarge the communication bandwidth to transfer the compressed multimedia streams using Flexible Time Triggered- Enhanced Switched Ethernet (FTT-ESE) protocol. FTT-ESE provides automation to calculate the compression level and change the bandwidth of the stream. This paper focuses on low-latency multimedia transmission over Ethernet with dynamic quality-of-service (QoS) management. This proposed framework deals with a dynamic QoS for multimedia transmission over Ethernet with FTT-ESE protocol. This paper also presents distinct QoS metrics based both on the image quality and network features. Some experiments with recorded and live video streams show the advantages of the proposed framework. To validate the solution we have designed and implemented a simulator based on the Matlab/Simulink, which is a tool to evaluate different network architecture using Simulink blocks. 相似文献
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J C Pratt M R van den Brink V E Igras S F Walk K S Ravichandran S J Burakoff 《Journal of immunology (Baltimore, Md. : 1950)》1999,163(5):2586-2591
Engagement of the TCR determines the fate of T cells to activate their functional programs, proliferate, or undergo apoptosis. The intracellular signal transduction pathways that dictate the specific outcome of receptor engagement have only been partially elucidated. The adapter protein, Shc, is involved in cytokine production, mitogenesis, transformation, and apoptosis in different cell systems. We found that Shc becomes phosphorylated on tyrosine residues upon stimulation of the TCR in DO11.10 hybridoma T cells; therefore, we investigated the role of Shc in activation-induced cell death in these cells by creating a series of stably transfected cell lines. Expression of Shc-SH2 (the SH2 domain of Shc) or Shc-Y239/240F (full-length Shc in which tyrosines 239 and 240 have been mutated to phenylalanine) resulted in the inhibition of activation-induced cell death and Fas ligand up-regulation after TCR cross-linking. Expression of wild-type Shc or Shc-Y317F had no significant effect. In addition, we found that Shc-SH2 and Shc-Y239/240F, but not Shc-Y317F, inhibited phosphorylation of extracellular signal-regulated protein kinase and production of IL-2 after TCR cross-linking. These results indicate an important role for Shc in the early signaling events that lead to activation-induced cell death and IL-2 production after TCR activation. 相似文献
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Neurodegeneration in diseases caused by altered metabolism of mammalian prion protein (PrP) can be averted by reducing PrP expression. To identify novel pathways for PrP down-regulation, we analyzed cells that had adapted to the negative selection pressure of stable overexpression of a disease-causing PrP mutant. A mutant cell line was isolated that selectively and quantitatively routes wild-type and various mutant PrPs for ER retrotranslocation and proteasomal degradation. Biochemical analyses of the mutant cells revealed that a defect in glycosylphosphatidylinositol (GPI) anchor synthesis leads to an unprocessed GPI-anchoring signal sequence that directs both ER retention and efficient retrotranslocation of PrP. An unprocessed GPI signal was sufficient to impart ER retention, but not retrotranslocation, to a heterologous protein, revealing an unexpected role for the mature domain in the metabolism of misprocessed GPI-anchored proteins. Our results provide new insights into the quality control pathways for unprocessed GPI-anchored proteins and identify transamidation of the GPI signal sequence as a step in PrP biosynthesis that is absolutely required for its surface expression. As each GPI signal sequence is unique, these results also identify signal recognition by the GPI-transamidase as a potential step for selective small molecule perturbation of PrP expression. 相似文献
49.
Kirk C. Hansen Lauren Kiemele Ori Maller Jenean O'Brien Aarthi Shankar Jaime Fornetti Pepper Schedin 《Molecular & cellular proteomics : MCP》2009,8(7):1648-1657
Epithelial cell behavior is coordinated by the composition of the surrounding
extracellular matrix (ECM); thus ECM protein identification is critical for
understanding normal biology and disease states. Proteomic analyses of ECM
proteins have been hindered by the insoluble and digestion-resistant nature of
ECM. Here we explore the utility of combining rapid ultrasonication- and
surfactant-assisted digestion for the detailed proteomics analysis of ECM
samples. When compared with traditional overnight digestion, this optimized
method dramatically improved the sequence coverage for collagen I, revealed the
presence of hundreds of previously unidentified proteins in Matrigel, and
identified a protein profile for ECM isolated from rat mammary glands that was
substantially different from that found in Matrigel. In a three-dimensional
culture assay to investigate epithelial cell-ECM interactions, mammary
epithelial cells were found to undergo extensive branching morphogenesis when
plated with mammary gland-derived matrix in comparison with Matrigel.
Cumulatively these data highlight the tissue-specific nature of ECM composition
and function and underscore the need for optimized techniques, such as those
described here, for the proteomics characterization of ECM samples.Extracellular matrix (ECM)1 is a critical component of the tissue microenvironment. ECM plays a pivotal role
in embryonic stem cell development and differentiation (1, 2) as well as many physiological (3) and pathological processes, including cancer
progression (4, 5). Cell regulation by ECM has been studied with high frequency in recent years
(7, 8).
However, our ability to globally characterize ECM composition both in
vitro and in vivo has been severely limited because of several
unique attributes of ECM proteins such as high molecular weight glycans and the presence
of covalent protein cross-links (6, 9, 10).
Traditional proteomics approaches have proven to be ineffective for the identification
of ECM proteins as demonstrated by the fact that collagens, despite being the most
abundant protein in mammals, are significantly underrepresented in tissue-based
proteomics data sets.Ultrasonication has long been used for the digestion of bioorganic materials to allow for
maximal and reproducible extraction and hence the accurate identification of small
molecule and inorganic analytes (11). More
recently, Capelo et al. (12)
have used ultrasonic energy to catalyze tryptic digestion of proteins for subsequent
mass spectrometry-based identification. Here we sought to determine whether this method
could be optimized to prepare ECM samples for mass spectrometry-based analysis. For
method development, we used rat tail collagen as a representative ECM protein for which
current proteomics approaches have proven relatively unsuccessful. Type I collagen is
defined as a right-handed triple helix heterotrimer comprising two identical
α1 chains and one α2 chain that form a fibrillar network (6). The physical properties of the triple helical
structure render the protein resistant to proteasch as trypsin (9). In this work, we focused our efforts on developing a digestion
approach that improves our ability to perform proteomics analysis on a type I collagen
preparation and then used this method to identify the protein composition of EHS murine
chondrosarcoma matrix (10), herein referred to as
Matrigel, and a matrix preparation from rat mammary tissue.In this study, we developed a digestion approach suitable for a two-dimensional liquid
chromatography-tandem mass spectrometry-based analysis of ECM proteins. Our digestion
approach involves three cycles of ultrasonication for rapid initial trypsin digestion
followed by overnight digestion using an acid-labile surfactant. This approach resulted
in significant improvement in collagen peptide identification and the identification of
numerous ECM proteins previously uncharacterized in Matrigel and in mammary tissue. The
application of our ECM-optimized ultrasonic assisted trypsin digestion method is
anticipated to significantly advance the identification of tissue- and disease
state-specific ECM proteins. 相似文献
50.