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排序方式: 共有94条查询结果,搜索用时 15 毫秒
1.
V Muresan M P Sarras J D Jamieson 《The journal of histochemistry and cytochemistry》1982,30(9):947-955
Using the sialic acid-specific lectin, limulin (LPA; from Limulus polyphemus hemolymph), the distribution and nature of sialoglycoconjugates on the surface of rat pancreatic cells has been investigated. Binding of rhodaminated LPA (Rh-LPA) or horseradish peroxidase-conjugated LPA (HRP-LPA) to fixed-frozen sections of adult rat pancreas resulted in intense linear staining of the apical surface of acinar cells with fainter staining on the basal but not the lateral cell surfaces. LPA binding was specific in that it could be abolished by 1) pretreatment of tissue sections with neuraminidase or periodic acid; 2) competition with sialic acid; and 3) incubation in Ca2+ -free buffers. Pretreatment of sections with proteases abolished LPA binding to the apical surfaces of acinar cells and also enhanced LPA binding to the lateral cell surface. Lipid extraction of sections following protease treatment markedly reduced LPA binding to the acinar cell periphery. These results suggest that LPA binding sites on the acinar cell apical surface may be primarily sialoglycoproteins, while those on the basolateral surfaces may consist in part of gangliosides. Electron microscopy of collagenase-dispersed acini exposed to HRP-LPA confirmed binding of LPA to the basal plasmalemma and, in addition, revealed staining of basal lamina when present. LPA binding to the acinar cell surface was not affected by digestion of tissue sections with hyaluronidase, heparinase, collagenase, or 6 M guanidine-HCl. Control experiments indicated that rat pancreatic secretory proteins contain undetectable amounts of sialoglycoproteins and thus that the apical localization of LPA is not due to adherent secretory proteins. Islets of Langerhans were always uniformly and heavily stained with LPA conjugates; this staining was protease insensitive. Appearance of LPA binding sites was examined on embryonic pancreatic epithelia. At day 15 of gestation, Rh-LPA stained the entire periphery of the epithelial cells, including the lateral cell surface, although more intense staining was already noted on the apical surface. This pattern persisted through day 17 of gestation, but by day 19 an adult staining pattern was observed with loss of staining of the lateral cell surfaces. 相似文献
2.
R.H.A. Sorel C. Snelleman A. Hulshoff 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1981,222(2):241-248
A high-performance liquid chromatographic method has been developed for the determination of nitroxoline in 50-μl plasma and urine samples.A structural analogue of nitroxoline, 8-hydroxyquinoline, was added to the eluent in order to suppress peak asymmetry. Several parameters of the eluent were studied for the optimisation of the chromatographic system.Plasma concentration—time curves were constructed for three volunteers after they had received an oral dose of 100 mg of nitroxoline. Plasma half-life was about 1 h. Within 12 h, about 1% of the dose was excreted in the urine as free nitroxoline and about 30% as conjugated metabolite of the parent compound. 相似文献
3.
R.H.A. Sorel A. Hulshoff C. Snelleman 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1980,221(1):129-137
A rapid high-performance liquid chromatographic method has been developed for monitoring plasma levels of patients treated intravenously with nalidixic acid. The major metabolite (in vitro also active) can be determined as well; 50-μl plasma samples are sufficient. Use is made of a dynamic anion-exchange system. Different parameters such as adsorption of the surfactant cetrimide onto the column; pH and ionic strength of the eluent, and the critical micelle concentration of the surfactant in the eluent have been studied. 相似文献
4.
Christopher Southan Peter Varkonyi Kiran Boppana Sarma A.R.P. Jagarlapudi Sorel Muresan 《PloS one》2013,8(10)
The statistics of drug development output and declining yield of approved medicines has been the subject of many recent reviews. However, assessing research productivity that feeds development is more difficult. Here we utilise an extensive database of structure-activity relationships extracted from papers and patents. We have used this database to analyse published compounds cumulatively linked to nearly 4000 protein target identifiers from multiple species over the last 20 years. The compound output increases up to 2005 followed by a decline that parallels a fall in pharmaceutical patenting. Counts of protein targets have plateaued but not fallen. We extended these results by exploring compounds and targets for one large pharmaceutical company. In addition, we examined collective time course data for six individual protease targets, including average molecular weight of the compounds. We also tracked the PubMed profile of these targets to detect signals related to changes in compound output. Our results show that research compound output had decreased 35% by 2012. The major causative factor is likely to be a contraction in the global research base due to mergers and acquisitions across the pharmaceutical industry. However, this does not rule out an increasing stringency of compound quality filtration and/or patenting cost control. The number of proteins mapped to compounds on a yearly basis shows less decline, indicating the cumulative published target capacity of global research is being sustained in the region of 300 proteins for large companies. The tracking of six individual targets shows uniquely detailed patterns not discernible from cumulative snapshots. These are interpretable in terms of events related to validation and de-risking of targets that produce detectable follow-on surges in patenting. Further analysis of the type we present here can provide unique insights into the process of drug discovery based on the data it actually generates. 相似文献
5.
Mahbub Hasan Hophil Min Khandoker Asiqur Rahaman Anca Raluca Muresan Hyeyoon Kim Dohyun Han Oh‐Seung Kwon 《Proteomics》2019,19(5)
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS); its cause is unknown. To understand the pathogenesis of MS, researchers often use the experimental autoimmune encephalomyelitis (EAE) mouse model. Here, the aim is to build a proteome map of the biological changes that occur during MS at the major onset sites—the brain and the spinal cord. Quantitative proteome profiling is performed in five specific brain regions and the spinal cord of EAE and healthy mice with high‐resolution mass spectrometry based on tandem mass tags. On average, 7400 proteins per region are quantified, with the most differentially expressed proteins in the spinal cord (1691), hippocampus (104), frontal cortex (83), cerebellum (63), brainstem (50), and caudate nucleus (41). Moreover, region‐specific and commonly expressed proteins in each region are identified and bioinformatics analysis is performed. Pathway analysis reveals that protein clusters resemble their functions in disease pathogenesis (i.e., by inducing inflammatory responses, immune activation, and cell–cell adhesion). In conclusion, the study provides an understanding of the pathogenesis of MS in the EAE animal model. It is expected that the comprehensive proteome map of the brain and spinal cord can be used to identify biomarkers for the pathogenesis of MS. 相似文献
6.
Genomic trees have been constructed based on the presence and absence of families of protein-encoding genes observed in 27
complete genomes, including genomes of 15 free-living organisms. This method does not rely on the identification of suspected
orthologs in each genome, nor the specific alignment used to compare gene sequences because the protein-encoding gene families
are formed by grouping any protein with a pairwise similarity score greater than a preset value. Because of this all inclusive
grouping, this method is resilient to some effects of lateral gene transfer because transfers of genes are masked when the
recipient genome already has a homolog (not necessarily an ortholog) of the incoming gene. Of 71 genes suspected to have been
laterally transferred to the genome of Aeropyrum pernix, only approximately 7 to 15 represent genes where a lateral gene transfer appears to have generated homoplasy in our character
dataset. The genomic tree of the 15 free-living taxa includes six different bacterial orders, six different archaeal orders,
and two different eukaryotic kingdoms. The results are remarkably similar to results obtained by analysis of rRNA. Inclusion
of the other 12 genomes resulted in a tree only broadly similar to that suggested by rRNA with at least some of the differences
due to artifacts caused by the small genome size of many of these species. Very small genomes, such as those of the two Mycoplasma genomes included, fall to the base of the Bacterial domain, a result expected due to the substantial gene loss inherent to
these lineages. Finally, artificial ``partial genomes' were generated by randomly selecting ORFs from the complete genomes
in order to test our ability to recover the tree generated by the whole genome sequences when only partial data are available.
The results indicated that partial genomic data, when sampled randomly, could robustly recover the tree generated by the whole
genome sequences.
Received: 30 May 2001 / Accepted: 10 October 2001 相似文献
7.
Claude Guernet Francis LemeilleDenis Sorel Chantal BourdillonCatherine Berge-Thierry Maria Manakou 《Revue de Micropaléontologie》2003,46(2):73
The Upper Pleistocene and the Holocene of Aigion have delivered an abundant microfauna with 35 ostracode species. The Pleistocene from Aigion borehole generally provides Ostracodes from oligohaline environment with Cyprideis torosa, Candona angulata and Tyrrhenocythere amnicola while, in the Holocene, marine infralittoral species dominate with Cytheridea neapolitana, Carinocythereis whitei, Loxoconcha ovulata and Cytherois frequens. The marine sedimentation occurred at depth from some meters to some tens of meters. In the Aghios Constantinos section, the lagoonal marls are characterised by Euxinocythere schuldtae and a dwarf species of Xestoleberis. Then, a drastic environmental change occurs around the Pleistocene-Holocene boundary and presumably affected the whole Corinth gulf. 相似文献
8.
The amyloid-beta precursor protein is phosphorylated via distinct pathways during differentiation, mitosis, stress, and degeneration
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Phosphorylation of amyloid-beta precursor protein (APP) at Thr(668) is a normal process linked to neurite extension and anterograde transport of vesicular cargo. By contrast, increased phosphorylation of APP is a pathological trait of Alzheimer's disease. APP is overexpressed in Down's syndrome, a condition that occasionally leads to increased APP phosphorylation, in cultured cells. Whether phosphorylation of APP in normal versus high APP conditions occurs by similar or distinct signaling pathways is not known. Here, we addressed this problem using brainstem-derived neurons (CAD cells). CAD cells that ectopically overexpress APP frequently show features of degenerating neurons. We found that, in degenerating cells, APP is hyperphosphorylated and colocalizes with early endosomes. By contrast, in normal CAD cells, phosphorylated APP (pAPP) is excluded from endosomes, and localizes to the Golgi apparatus and to transport vesicles within the neurites. Whereas the neuritic APP is phosphorylated by c-Jun NH(2)-terminal kinase through a pathway that is modulated by glycogen synthase kinase 3beta, the endosomal pAPP in degenerated CAD cells results from activation of cyclin-dependent kinase 5. Additional signaling pathways, leading to APP phosphorylation, become active during stress and mitosis. We conclude that distinct pathways of APP phosphorylation operate in proliferating, differentiating, stressed, and degenerating neurons. 相似文献
9.
10.
Zhou CZ Meyer P Quevillon-Cheruel S Li De La Sierra-Gallay I Collinet B Graille M Blondeau K François JM Leulliot N Sorel I Poupon A Janin J Van Tilbeurgh H 《Protein science : a publication of the Protein Society》2005,14(1):209-215
We determined the three-dimensional crystal structure of the protein YML079wp, encoded by a hypothetical open reading frame from Saccharomyces cerevisiae to a resolution of 1.75 A. The protein has no close homologs and its molecular and cellular functions are unknown. The structure of the protein is a jelly-roll fold consisting of ten beta-strands organized in two parallel packed beta-sheets. The protein has strong structural resemblance to the plant storage and ligand binding proteins (canavalin, glycinin, auxin binding protein) but also to some plant and bacterial enzymes (epimerase, germin). The protein forms homodimers in the crystal, confirming measurements of its molecular mass in solution. Two monomers have their beta-sheet packed together to form the dimer. The presence of a hydrophobic ligand in a well conserved pocket inside the barrel and local sequence similarity with bacterial epimerases may suggest a biochemical function for this protein. 相似文献