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1.
Cecilia PC Soh Alastair SR Donald James Feeney Walter TJ Morgan Winifred M Watkins 《Glycoconjugate journal》1989,6(3):319-332
The tetrasaccharides GalNAcß1-4[NeuAc2-3]Galß1-4Glc and GalNAcß1-4[NeuAc2-3]Galß1-4GlcNAc were synthesised by enzymic transfer of GalNAc from UDP-GalNAc to 3-sialyllactose (NeuAc2-3Galß1-4Glc) and 3-sialyl-N-acetyllactosamine (NeuAc2-3Galß1-4GlcNAc). The structures of the products were established by methylation and1H-500 MHz NMR spectroscopy. In Sda serological tests the product formed with 3-sialyl-N-acetyllactosamine was highly active whereas that formed with 3-sialyllactose had only weak activity. 相似文献
2.
Accelerating the convergence of the back-propagation method 总被引:16,自引:0,他引:16
T. P. Vogl J. K. Mangis A. K. Rigler W. T. Zink D. L. Alkon 《Biological cybernetics》1988,59(4-5):257-263
The utility of the back-propagation method in establishing suitable weights in a distributed adaptive network has been demonstrated repeatedly. Unfortunately, in many applications, the number of iterations required before convergence can be large. Modifications to the back-propagation algorithm described by Rumelhart et al. (1986) can greatly accelerate convergence. The modifications consist of three changes:1) instead of updating the network weights after each pattern is presented to the network, the network is updated only after the entire repertoire of patterns to be learned has been presented to the network, at which time the algebraic sums of all the weight changes are applied:2) instead of keeping , the learning rate (i.e., the multiplier on the step size) constant, it is varied dynamically so that the algorithm utilizes a near-optimum , as determined by the local optimization topography; and3) the momentum factor is set to zero when, as signified by a failure of a step to reduce the total error, the information inherent in prior steps is more likely to be misleading than beneficial. Only after the network takes a useful step, i.e., one that reduces the total error, does again assume a non-zero value. Considering the selection of weights in neural nets as a problem in classical nonlinear optimization theory, the rationale for algorithms seeking only those weights that produce the globally minimum error is reviewed and rejected. 相似文献
3.
Arrangement and possible function of actin filament bundles in ectoplasmic specializations of ground squirrel Sertoli cells 总被引:2,自引:0,他引:2
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We have investigated the arrangement and function of actin filament bundles in Sertoli cell ectoplasmic specializations found adjacent to junctional networks and in areas of adhesion to spermatogenic cells. Tissue was collected, from ground squirrel (Spermophilus spp.) testes, in three ways: seminiferous tubules were fragmented mechanically; segments of intact epithelium and denuded tubule walls were isolated by using EDTA in a phosphate-buffered salt solution; and isolated epithelia and denuded tubule walls were extracted in glycerol. To determine the arrangement of actin bundles, the tissue was fixed, mounted on slides, treated with cold acetone (-20 degrees C), and then exposed to nitrobenzoxadiazole-phallacidin. Myosin was localized using immunofluorescence. To investigate the hypothesis that ectoplasmic specializations are contractile, glycerinated models were exposed to exogenous ATP and Ca++; then contraction was assessed qualitatively by using nitrobenzoxadiazole-phallacidin as a marker. Actin bundles in ectoplasmic specializations adjacent to junctional networks circumscribe the bases of Sertoli cells. When intact epithelia are viewed from an angle perpendicular to the epithelial base, honeycomb staining patterns are observed. Filament bundles in Sertoli cell regions adjacent to spermatogenic cells dramatically change organization during spermatogenesis. Initially, the bundles circle the region of contact between the developing acrosome and nucleus. They then expand to cover the entire head. As the spermatid flattens, filaments on one side of the now saucer-shaped head orient themselves parallel to the germ cell axis while those on the other align perpendicularly to it. Before sperm release, all filaments course parallel to the rim of the head. Contrary to the results we obtained with myoid cells, we could not convincingly demonstrate myosin in ectoplasmic specializations or induce contraction of glycerinated models. Our data are consistent with the hypothesis that actin in ectoplasmic specializations of Sertoli cells may be more skeletal than contractile. 相似文献
4.
Methyltransferase inhibitors block NGF-regulated survival and protein phosphorylation in sympathetic neurons. 总被引:2,自引:0,他引:2
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Nerve growth factor (NGF) and elevated K+ concentrations (35 mM) support the survival of the same population of chick embryonic sympathetic neurons. We have used methyltransferase inhibitors, which block protein methylation in intact cells, to investigate the mechanism(s) by which NGF and high K+ exert their effects. Methyltransferase inhibitors selectively blocked NGF-but not high K+-mediated survival of neurons. The ability of neurons, plated on laminin, to respond rapidly to NGF with neurite outgrowth was used to demonstrate that the blockade of the effects of NGF by methyltransferase inhibitors was reversible. At the molecular level, we studied the rapid decrease in phosphorylation of p70, a 70-kd phosphoprotein of sympathetic neurons regulated by both NGF and high K+. Methyltransferase inhibitors blocked the decrease in p70 phosphorylation induced by NGF but not that by high K+. We conclude that the early molecular events of NGF-mediated neuronal survival differ from those of high K+-mediated neuronal survival in that they involve protein methylation, whereas at a later step, possibly at the level of protein phosphorylation, the two pathways leading to survival of sympathetic neurons converge. 相似文献
5.
Ouabain-insensitive salt and water movements in duck red cells. II. Norepinephrine stimulation of sodium plus potassium cotransport 总被引:11,自引:9,他引:2
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Catecholamines induce net salt and water movements in duck red cells incubated in isotonic solutions. The rate of this response is approximately three times greater than a comparable effect observed in 400 mosmol hypertonic solutions in the absence of hormone (W.F. Schmidt and T. J. McManus. 1977 a.J. Gen. Physiol. 70:59-79. Otherwise, these two systems share a great many similarities. In both cases, net water and salt movements have a marked dependence on external cation concentrations, are sensitive to furosemide and insensitive to ouabain, and allow the substitution of rubidium for external potassium. In the presence of ouabain, but the absence of external potassium (or rubidium), a furosemide-sensitive net extrusion of sodium against a large electrochemical gradient can be demonstrated. When norepinephrine-treated cells are incubated with ouabain and sufficient external sodium, the furosemide-sensitive, unidirectional influxes of both sodium and rubidium are half- maximally saturated at similar rubidium concentrations; with saturating external rubidium, the same fluxes are half-maximal at comparable levels of external sodium. In the absence of sodium, a catecholamine-stimulated, furosemide-sensitive influx of rubidium persists. In the absence of rubidium, a similar but smaller component of sodium influx can be seen. We interpret these results in terms of a cotransport model for sodium plus potassium which is activated by hypertonicity or norepinephrine. When either ion is absent from the incubation medium, the system promotes an exchange-diffusion type of movement of the co-ion into the cells. In the absence of external potassium, net movement of potassium out of the cell leads to a coupled extrusion of sodium against its electrochemical gradient. 相似文献
6.
Kiran Nistala Hemlata Varsani Helmut Wittkowski Thomas Vogl Petra Krol Vanita Shah Kamel Mamchaoui Paul A Brogan Johannes Roth Lucy R Wedderburn 《Arthritis research & therapy》2013,15(5):R131
Introduction
The aetiopathogenesis of juvenile dermatomyositis (JDM) remains poorly understood. In particular the contribution of monocytes or macrophages, which are frequently observed to be an infiltrate within muscle tissue very early in the disease process, is unknown. We hypothesised that these cells secrete the pro-inflammatory myeloid related protein (MRP) 8/14 which may then contribute to muscle pathology in JDM.Methods
In this study of 56 JDM patients, serum MRP8/14 levels were compared with clinical measures of disease activity. Muscle biopsies taken early in disease were assessed by immunohistochemistry to determine the frequency and identity of MRP-expressing cells. The effects of MRP stimulation and endoplasmic reticulum (ER) stress on muscle were tested in vitro. Serum or supernatant levels of cytokines were analyzed by multiplex immunoassay.Results
Serum MRP8/14 correlated with physician’s global assessment of disease activity in JDM (R = 0.65, p = 0.0003) and muscle strength/endurance, childhood myositis assessment score (CMAS, R = −0.55, p = 0.004). MRP8/14 was widely expressed by CD68+ macrophages in JDM muscle tissue. When cultured with human myoblasts, MRP8 led to the secretion of MCP-1 and IL-6, which was enhanced by ER stress. Both inflammatory mediators were detected in significantly higher levels in the serum of JDM patients compared to healthy controls.Conclusions
This study is the first to identify serum MRP8/14 as a potential biomarker for disease activity in JDM. We propose that tissue infiltrating macrophages secreting MRP8/14 may contribute to myositis, by driving the local production of cytokines directly from muscle. 相似文献7.
Zhenfeng Liu Johannes Müller Tao Li Richard M Alvey Kajetan Vogl Niels-Ulrik Frigaard Nathan C Rockwell Eric S Boyd Lynn P Tomsho Stephan C Schuster Petra Henke Manfred Rohde J?rg Overmann Donald A Bryant 《Genome biology》2013,14(11):R127
Background
‘Chlorochromatium aggregatum’ is a phototrophic consortium, a symbiosis that may represent the highest degree of mutual interdependence between two unrelated bacteria not associated with a eukaryotic host. ‘Chlorochromatium aggregatum’ is a motile, barrel-shaped aggregate formed from a single cell of ‘Candidatus Symbiobacter mobilis”, a polarly flagellated, non-pigmented, heterotrophic bacterium, which is surrounded by approximately 15 epibiont cells of Chlorobium chlorochromatii, a non-motile photolithoautotrophic green sulfur bacterium.Results
We analyzed the complete genome sequences of both organisms to understand the basis for this symbiosis. Chl. chlorochromatii has acquired relatively few symbiosis-specific genes; most acquired genes are predicted to modify the cell wall or function in cell-cell adhesion. In striking contrast, ‘Ca. S. mobilis’ appears to have undergone massive gene loss, is probably no longer capable of independent growth, and thus may only reproduce when consortia divide. A detailed model for the energetic and metabolic bases of the dependency of ‘Ca. S. mobilis’ on Chl. chlorochromatii is described.Conclusions
Genomic analyses suggest that three types of interactions lead to a highly sophisticated relationship between these two organisms. Firstly, extensive metabolic exchange, involving carbon, nitrogen, and sulfur sources as well as vitamins, occurs from the epibiont to the central bacterium. Secondly, ‘Ca. S. mobilis’ can sense and move towards light and sulfide, resources that only directly benefit the epibiont. Thirdly, electron cycling mechanisms, particularly those mediated by quinones and potentially involving shared protonmotive force, could provide an important basis for energy exchange in this and other symbiotic relationships. 相似文献8.
9.
Sara Rosati Ewald TJ van den Bremer Janine Schuurman Paul WHI Parren Johannis P Kamerling Albert JR Heck 《MABS-AUSTIN》2013,5(6):917-924
Here, we describe a fast, easy-to-use, and sensitive method to profile in-depth structural micro-heterogeneity, including intricate N-glycosylation profiles, of monoclonal antibodies at the native intact protein level by means of mass spectrometry using a recently introduced modified Orbitrap Exactive Plus mass spectrometer. We demonstrate the versatility of our method to probe structural micro-heterogeneity by describing the analysis of three types of molecules: (1) a non-covalently bound IgG4 hinge deleted full-antibody in equilibrium with its half-antibody, (2) IgG4 mutants exhibiting highly complex glycosylation profiles, and (3) antibody-drug conjugates. Using the modified instrument, we obtain baseline separation and accurate mass determination of all different proteoforms that may be induced, for example, by glycosylation, drug loading and partial peptide backbone-truncation. We show that our method can handle highly complex glycosylation profiles, identifying more than 20 different glycoforms per monoclonal antibody preparation and more than 30 proteoforms on a single highly purified antibody. In analyzing antibody-drug conjugates, our method also easily identifies and quantifies more than 15 structurally different proteoforms that may result from the collective differences in drug loading and glycosylation. The method presented here will aid in the comprehensive analytical and functional characterization of protein micro-heterogeneity, which is crucial for successful development and manufacturing of therapeutic antibodies 相似文献
10.
Astrid Schmidt-Kloiber S. Jannicke Moe Bernard Dudley Jörg Strackbein Robert Vogl 《Hydrobiologia》2013,704(1):29-38
In ecological sciences, the role of metadata (i.e. key information about a dataset) to make existing datasets visible and discoverable has become increasingly important. Within the EU-funded WISER project (Water bodies in Europe: Integrative Systems to assess Ecological status and Recovery), we designed a metadatabase to allow scientists to find the optimal data for their analyses. An online questionnaire helped to collect metadata from the data providers and an online query tool (http://www.wiser.eu/results/meta-database/) facilitated data evaluation. The WISER metadatabase currently holds information on 114 datasets (22 river, 71 lake, 1 general freshwater and 20 coastal/transitional datasets), which also can be accessed by external scientists. We evaluate if generally used metadata standards (e.g. Darwin Core, ISO 19115, CSDGM, EML) are suitable for such specific purposes as WISER and suggest at least the linkage with standard metadata fields. Furthermore, we discuss whether the simple metadata documentation is enough for others to reuse a dataset and why there is still reluctance to publish both metadata and primary research data (i.e. time and financial constraints, misuse of data, abandoning intellectual property rights). We emphasise that metadata publication has major advantages as it makes datasets detectable by other scientists and generally makes a scientist’s work more visible. 相似文献