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141.
Background
The creation and modification of genome-scale metabolic models is a task that requires specialized software tools. While these are available, subsequently running or visualizing a model often relies on disjoint code, which adds additional actions to the analysis routine and, in our experience, renders these applications suboptimal for routine use by (systems) biologists.Results
The Flux Analysis and Modeling Environment (FAME) is the first web-based modeling tool that combines the tasks of creating, editing, running, and analyzing/visualizing stoichiometric models into a single program. Analysis results can be automatically superimposed on familiar KEGG-like maps. FAME is written in PHP and uses the Python-based PySCeS-CBM for its linear solving capabilities. It comes with a comprehensive manual and a quick-start tutorial, and can be accessed online at http://f-a-m-e.org/.Conclusions
With FAME, we present the community with an open source, user-friendly, web-based "one stop shop" for stoichiometric modeling. We expect the application will be of substantial use to investigators and educators alike. 相似文献142.
Wijnhoven TJ van de Westerlo EM Smits NC Lensen JF Rops AL van der Vlag J Berden JH van den Heuvel LP van Kuppevelt TH 《Glycoconjugate journal》2008,25(2):177-185
Heparinoids are used in the clinic as anticoagulants. A specific pentasaccharide in heparinoids activates antithrombin III,
resulting in inactivation of factor Xa and–when additional saccharides are present–inactivation of factor IIa. Structural
and functional analysis of the heterogeneous heparinoids generally requires advanced equipment, is time consuming, and needs
(extensive) sample preparation. In this study, a novel and fast method for the characterization of heparinoids is introduced
based on reactivity with nine unique anti-heparin antibodies. Eight heparinoids were biochemically analyzed by electrophoresis
and their reactivity with domain-specific anti-heparin antibodies was established by ELISA. Each heparinoid displayed a distinct
immunoprofile matching its structural characteristics. The immunoprofile could also be linked to biological characteristics,
such as the anti-Xa/anti-IIa ratio, which was reflected by reactivity of the heparinoids with antibodies HS4C3 (indicative
for 3-O-sulfates) and HS4E4 (indicative for domains allowing anti-factor IIa activity). In addition, the immunoprofile could be indicative
for heparinoid-induced side-effects, such as heparin-induced thrombocytopenia, as illustrated by reactivity with antibody
NS4F5, which defines a very high sulfated domain. In conclusion, immunoprofiling provides a novel, fast, and simple methodology
for the characterization of heparinoids, and allows high-throughput screening of (new) heparinoids for defined structural
and biological characteristics. 相似文献
143.
Lipids revert inert Abeta amyloid fibrils to neurotoxic protofibrils that affect learning in mice 总被引:1,自引:0,他引:1 下载免费PDF全文
Martins IC Kuperstein I Wilkinson H Maes E Vanbrabant M Jonckheere W Van Gelder P Hartmann D D'Hooge R De Strooper B Schymkowitz J Rousseau F 《The EMBO journal》2008,27(1):224-233
Although soluble oligomeric and protofibrillar assemblies of Abeta-amyloid peptide cause synaptotoxicity and potentially contribute to Alzheimer's disease (AD), the role of mature Abeta-fibrils in the amyloid plaques remains controversial. A widely held view in the field suggests that the fibrillization reaction proceeds 'forward' in a near-irreversible manner from the monomeric Abeta peptide through toxic protofibrillar intermediates, which subsequently mature into biologically inert amyloid fibrils that are found in plaques. Here, we show that natural lipids destabilize and rapidly resolubilize mature Abeta amyloid fibers. Interestingly, the equilibrium is not reversed toward monomeric Abeta but rather toward soluble amyloid protofibrils. We characterized these 'backward' Abeta protofibrils generated from mature Abeta fibers and compared them with previously identified 'forward' Abeta protofibrils obtained from the aggregation of fresh Abeta monomers. We find that backward protofibrils are biochemically and biophysically very similar to forward protofibrils: they consist of a wide range of molecular masses, are toxic to primary neurons and cause memory impairment and tau phosphorylation in mouse. In addition, they diffuse rapidly through the brain into areas relevant to AD. Our findings imply that amyloid plaques are potentially major sources of soluble toxic Abeta-aggregates that could readily be activated by exposure to biological lipids. 相似文献
144.
Hoehenwarter W van Dongen JT Wienkoop S Steinfath M Hummel J Erban A Sulpice R Regierer B Kopka J Geigenberger P Weckwerth W 《Proteomics》2008,8(20):4214-4225
The dynamics of a proteome can only be addressed with large-scale, high-throughput methods. To cope with the inherent complexity, techniques based on targeted quantification using proteotypic peptides are arising. This is an essential systems biology approach; however, for the exploratory discovery of unexpected markers, nontargeted detection of proteins, and protein modifications is indispensable. We present a rapid label-free shotgun proteomics approach that extracts relevant phenotype-specific peptide product ion spectra in an automated workflow without prior identification. These product ion spectra are subsequently sequenced with database search and de novo prediction algorithms. We analyzed six potato tuber cultivars grown on three plots of two geographically separated fields in Germany. For data mining about 1.5 million spectra from 107 analyses were aligned and statistically examined in approximately 1 day. Several cultivar-specific protein markers were detected. Based on de novo-sequencing a dominant protein polymorphism not detectable in the available EST-databases was assigned exclusively to a specific potato cultivar. The approach is applicable to organisms with unsequenced or incomplete genomes and to the automated extraction of relevant mass spectra that potentially cannot be identified by genome/EST-based search algorithms. 相似文献
145.
Comparative LC-MS is a powerful method for detailed quantitative comparison of complex protein mixtures. Dedicated software is required for detection, matching, and alignment of peaks in multiple LC-MS datasets. However, retention time shifts, saturation effects, limitations of experimental accuracy, and possible occurrence of split peaks make it difficult for software to perfectly match all chromatograms. We describe a procedure to assess the above problems and show that dataset quality can be enhanced with the aid of cluster analysis. 相似文献
146.
Welmoed Soepboer Joost M. Vervoort Shinya Sugita André F. Lotter 《Vegetation History and Archaeobotany》2008,17(5):497-506
We simulated pollen assemblages for 11 sites on the Swiss Plateau (Schweizer Mittelland) based on a low resolution land cover
map and pollen productivity estimates (PPE) from this region. A comparison between observed and simulated pollen data demonstrated
that the majority of the simulated pollen proportions were within a range of 5% of over- or underestimation, and that at eight
of the 11 sites the dominant taxon was correctly estimated. The modelled sum of arboreal pollen was correct within ±11% at
nine sites. Our results indicate that the PPE established for the Swiss Plateau can be used to simulate pollen assemblages
with reasonable accuracy. Moreover, our results justify the use of the POLLSCAPE simulation using the Prentice-Sugita model
and its variations of pollen dispersal and deposition in more complex topographic landscapes than those to which they have
hitherto been applied. 相似文献
147.
Nilsson M Wasylik S Mörgelin M Olin AI Meijers JC Derksen RH de Groot PG Herwald H 《Molecular microbiology》2008,67(3):482-492
During the last years, the importance of antibacterial peptides has attracted considerable attention. We report here that peptides derived from the fifth domain of beta-2 glycoprotein I (beta(2)GPI), a human heparin binding plasma protein, have antibacterial activities against Gram-positive and Gram-negative bacteria. Streptococcus pyogenes, an important human pathogen that can survive and grow in human blood, has developed mechanisms to escape the attack by these peptides. Thus, protein H and M1 protein, two surface proteins of the highly pathogenic S. pyogenes AP1 strain, bind full-length beta(2)GPI and thereby prevent the processing of beta(2)GPI by proteases from polymorphonuclear neutrophils (PMNs) into antibacterial peptides. In addition, protein H and M1 protein, released from the bacterial cell wall by PMN-derived proteases, bind to, and inhibit the activity of, beta(2)GPI-derived antibacterial peptides. Taken together, the data suggest that the interaction between the streptococcal proteins and beta(2)GPI or beta(2)GPI-derived peptides presents a novel mechanism to resist an antibacterial attack by beta(2)GPI-cleavage products. 相似文献
148.
Pentoxifylline reduces fibrin deposition and prolongs survival in neonatal hyperoxic lung injury. 总被引:4,自引:0,他引:4
Simone A J ter Horst Gerry T M Wagenaar Eveline de Boer Marg?t A van Gastelen Joost C M Meijers Bart J Biemond Ben J H M Poorthuis Frans J Walther 《Journal of applied physiology》2004,97(5):2014-2019
Bronchopulmonary dysplasia is a leading cause of mortality and morbidity in preterm infants despite improved treatment modalities. Pentoxifylline, a phosphodiesterase inhibitor, inhibits multiple processes that lead to neonatal hyperoxic lung injury, including inflammation, coagulation, and edema. Using a preterm rat model, we investigated the effects of pentoxifylline on hyperoxia-induced lung injury and survival. Preterm rat pups were exposed to 100% oxygen and injected subcutaneously with 0.9% saline or 75 mg/kg pentoxifylline twice a day. On day 10, lung tissue was harvested for histology, fibrin deposition, and mRNA expression, and bronchoalveolar lavage fluid was collected for total protein concentration. Pentoxifylline treatment increased mean survival by 3 days (P = 0.0018) and reduced fibrin deposition by 66% (P < 0.001) in lung homogenates compared with untreated hyperoxia-exposed controls. Monocyte chemoattractant protein-1 expression in lung homogenates was decreased, but the expressions of TNF-alpha, IL-6, matrix metalloproteinase-12, tissue factor, and plasminogen activator inhibitor-1 were similar in both groups. Total protein concentration in bronchoalveolar lavage fluid was decreased by 33% (P = 0.029) in the pentoxifylline group. Pentoxifylline treatment attenuates alveolar fibrin deposition and prolongs survival in preterm rat pups with neonatal hyperoxic lung injury, probably by reducing capillary-alveolar protein leakage. 相似文献
149.
Markus A Seeliger Joost W H Schymkowitz Frederic Rousseau Hannah R Wilkinson Laura S Itzhaki 《Biochemistry》2002,41(4):1202-1210
The two human proteins ckshs1 and ckshs2 are each 79 amino acids in length and consist of a four-stranded beta-sheet capped at one end by two alpha-helices. They are members of the cks family of essential cell cycle regulatory proteins that can adopt two native states, a monomer and a domain-swapped dimer formed by exchange of a C-terminal beta-strand. ckshs1 and ckshs2 both have marginal thermodynamic stability (the free energies of unfolding at 25 degrees C are 3.0 and 2.5 kcal/mol, respectively) and low kinetic stability (the rates of unfolding in water are approximately 1 s(-1)). Refolding of their denatured states to the monomeric forms of the proteins is slowed by transient oligomerization that is likely to occur via domain swapping. The folding behavior of ckshs1 and ckshs2 is markedly different from that of suc1, the cks protein from Schizosaccharomyces pombe, but the domain swapping propensities are similar. The greater thermodynamic and kinetic stability of suc1 and the population of a folding intermediate are most likely a consequence of its larger size (113 residues). The similarity in the domain swapping propensities, despite the contrast in other biophysical properties, may be attributable to the common double-proline motif in the hinge loop that connects the swapped domain to the rest of the protein. The motif was shown previously for suc1 to control the equilibrium between the monomer and the domain-swapped dimer. Finally, according to our model, the kinetic barrier separating the monomer and the domain-swapped dimer arises because the protein must unfold for beta-strand exchange to occur. Consistent with this, interconversion between the two states is much faster in the human proteins than it is for suc1, reflecting the faster unfolding rates of the former. 相似文献
150.