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排序方式: 共有234条查询结果,搜索用时 15 毫秒
21.
Lonardo E Hermann PC Mueller MT Huber S Balic A Miranda-Lorenzo I Zagorac S Alcala S Rodriguez-Arabaolaza I Ramirez JC Torres-Ruíz R Garcia E Hidalgo M Cebrián DÁ Heuchel R Löhr M Berger F Bartenstein P Aicher A Heeschen C 《Cell Stem Cell》2011,9(5):433-446
Nodal and Activin belong to the TGF-β superfamily and are important regulators of embryonic stem cell fate. Here we investigated whether Nodal and Activin regulate self-renewal of pancreatic cancer stem cells. Nodal and Activin were hardly detectable in more differentiated pancreatic cancer cells, while cancer stem cells and stroma-derived pancreatic stellate cells markedly overexpressed Nodal and Activin, but not TGF-β. Knockdown or pharmacological inhibition of the Nodal/Activin receptor Alk4/7 in cancer stem cells virtually abrogated their self-renewal capacity and in vivo tumorigenicity, and reversed the resistance of orthotopically engrafted cancer stem cells to gemcitabine. However, engrafted primary human pancreatic cancer tissue with a substantial stroma showed no response due to limited drug delivery. The addition of a stroma-targeting hedgehog pathway inhibitor enhanced delivery of the Nodal/Activin inhibitor and translated into long-term, progression-free survival. Therefore, inhibition of the Alk4/7 pathway, if combined with hedgehog pathway inhibition and gemcitabine, provides a therapeutic strategy for targeting cancer stem cells. 相似文献
22.
Torchetti EM Bonomi F Galluccio M Gianazza E Giancaspero TA Iametti S Indiveri C Barile M 《The FEBS journal》2011,278(22):4434-4449
A soluble form of human FAD synthase (isoform 2; hFADS2) was produced and purified to homogeneity as a recombinant His-tagged protein. The enzyme binds 1 mole of the FAD product very tightly, although noncovalently. Complete release of FAD from the 'as isolated' protein requires extensive denaturation. A 75 : 25 mixture of apo/holoprotein could be prepared by treatment with mild chaotropes, allowing estimatation of the contribution made by bound FAD to the protein stability and evaluatation of whether structural rearrangements may be required for FAD release. Under turnover conditions, the enzyme catalyzes FAD assembly from ATP and FMN and, at a much lower rate, the pyrophosphorolytic hydrolysis of FAD. Several mechanistic features of both reactions were investigated in detail, along with their dependence on environmental conditions (pH, temperature, dependence on metals). Our data indicate that FAD release may represent the rate-limiting step of the whole catalytic cycle and that the process leading to FAD synthesis, and delivery to client apoproteins may be tightly controlled. 相似文献
23.
Shu W Guttentag S Wang Z Andl T Ballard P Lu MM Piccolo S Birchmeier W Whitsett JA Millar SE Morrisey EE 《Developmental biology》2005,283(1):226-239
Branching morphogenesis in the lung serves as a model for the complex patterning that is reiterated in multiple organs throughout development. Beta-catenin and Wnt signaling mediate critical functions in cell fate specification and differentiation, but specific functions during branching morphogenesis have remained unclear. Here, we show that Wnt/beta-catenin signaling regulates proximal-distal differentiation of airway epithelium. Inhibition of Wnt/beta-catenin signaling, either by expression of Dkk1 or by tissue-specific deletion of beta-catenin, results in disruption of distal airway development and expansion of proximal airways. Wnt/beta-catenin functions upstream of BMP4, FGF signaling, and N-myc. Moreover, we show that beta-catenin and LEF/TCF activate the promoters of BMP4 and N-myc. Thus, Wnt/beta-catenin signaling is a critical upstream regulator of proximal-distal patterning in the lung, in part, through regulation of N-myc, BMP4, and FGF signaling. 相似文献
24.
Synthetic water-soluble meso-tetra(2,6-dichloro-3-sulfonatophenyl)porphyrinates of Mn(III) chloride [Mn-(TDCPPS)Cl] and iron(III) chloride [Fe-(TDCPPS)Cl] were employed as biomimetic catalysts in the photooxidative coupling of a terrestrial humic acid (HA). The changes in molecular dimension of HA induced by irradiation with UV light for different periods were followed by high-performance size-exclusion chromatography (HPSEC), with both spectrophotometric and refractive index (RI) detectors. Enhancement of apparent weight-average molecular weight (M(wa)) of sodium humate solutions at both pH 7 and 3.5, occurred after irradiation with UV light after 5.5 and 13 h by catalysis with either manganese or iron porphyrin. A significant increase in M(wa) values was also found when samples were kept in the dark for 8 and 11 days after the end of irradiation, thereby suggesting a progression of free-radicals coupling with time course after photoinduction. The enhancement of absorptivity of humic matter with catalyzed photooxidation was confirmed by the significant increase in apparent molecular mass as shown by the RI detector. The latter also indicated a slightly larger effect by iron-porphyrin than by manganese-porphyrin in the photooxidative coupling of humic molecules. These findings suggest that photooxidation may represent a valid alternative to oxidizing agents, such as H(2)O(2), in the polymerization of natural organic matter catalyzed by biomimetic metalporphyrins. 相似文献
25.
A synthetic water-soluble meso-tetra(2,6-dichloro-3-sulfonatophenyl)porphyrinate of iron(III) chloride, Fe(TDCPPS)Cl, was employed as a biomimetic catalyst in the oxidative coupling of terrestrial humic materials. High-performance size-exclusion chromatography (HPSEC), solid-state nuclear magnetic resonance (CPMAS-(13)C NMR), electron paramagnetic resonance (EPR), and diffuse reflectance infrared spectroscopy (DRIFT) were used to follow conformational and structural changes brought about in different humic materials by the oxidative coupling. Increase in apparent weight-average molecular weight (Mw(a)) occurred invariably for all humic substances with the oxidative polymerization catalyzed by Fe(TDCPPS)Cl. HPSEC further showed that the polymerization reaction turned the loosely bound humic supramolecular structures into more stable conformations which could no longer be disrupted by the disaggregating effect of acetic acid. DRIFT spectroscopy suggested the formation of new alkyl and aromatic ethers following the oxidative coupling with the biomimetic catalyst. CPMAS-(13)C NMR and EPR spectra suggested a reduced molecular mobility of humic components and enhanced stabilization of free radicals in larger oxidized fragments. All findings concur in indicating that the biomimetic catalysis by Fe(TDCPPS)Cl increased the molecular mass and chemical rigidity of humic materials by formation of intermolecular covalent bonds via a free-radical mechanism. The development of a technology based on oxidative polymerization by biomimetic catalysis may be of importance in controlling the properties and reactivity of humic matter for industrial and environmental applications. 相似文献
26.
Brizio C Galluccio M Wait R Torchetti EM Bafunno V Accardi R Gianazza E Indiveri C Barile M 《Biochemical and biophysical research communications》2006,344(3):1008-1016
FAD synthetase (FADS) (EC 2.7.7.2) is a key enzyme in the metabolic pathway that converts riboflavin into the redox cofactor FAD. Two hypothetical human FADSs, which are the products of FLAD1 gene, were over-expressed in Escherichia coli and identified by ESI-MS/MS. Isoform 1 was over-expressed as a T7-tagged protein which had a molecular mass of 63kDa on SDS-PAGE. Isoform 2 was over-expressed as a 6-His-tagged fusion protein, carrying an extra 84 amino acids at the N-terminal with an apparent molecular mass of 60kDa on SDS-PAGE. It was purified near to homogeneity from the soluble cell fraction by one-step affinity chromatography. Both isoforms possessed FADS activity and had a strict requirement for MgCl(2), as demonstrated using both spectrophotometric and chromatographic methods. The purified recombinant isoform 2 showed a specific activity of 6.8+/-1.3nmol of FAD synthesized/min/mg protein and exhibited a K(M) value for FMN of 1.5+/-0.3microM. This is the first report on characterization of human FADS, and the first cloning and over-expression of FADS from an organism higher than yeast. 相似文献
27.
Malavasi F Deaglio S Ferrero E Funaro A Sancho J Ausiello CM Ortolan E Vaisitti T Zubiaur M Fedele G Aydin S Tibaldi EV Durelli I Lusso R Cozno F Horenstein AL 《Molecular medicine (Cambridge, Mass.)》2006,12(11-12):334-341
This paper reviews some of the results and the speculations presented at the Torino CD38 Meeting in June, 2006 and focused on CD38 and CD157 seen as a family of molecules acting as surface receptors of immune cells. This partisan view was adopted in the attempt to combine the enzymatic functions with what the immunologists consider key functions in different cell models. At the moment, it is unclear whether the two functions are correlated, indifferent, or independent. Here we present conclusions inferred exclusively on human cell models, namely T and B lymphocytes, dendritic cells, and granulocytes. As an extra analytical tool, we try to follow in the history of life when the enzymatic and receptorial functions were generated, mixing ontogeny, membrane localization, and cell anchorage. 相似文献
28.
Prey capture success and foraging mode were studied in brown trout Salmo trutta at temperatures ranging from 5.7 to 14.0° C. At low temperatures, there was a positive correlation between prey capture success and the proportion of time that the fish spent holding feeding stations. This correlation was not found at temperatures >10° C. 相似文献
29.
Palomba S Cavella S Torrieri E Piccolo A Mazzei P Blaiotta G Ventorino V Pepe O 《Applied and environmental microbiology》2012,78(8):2737-2747
After isolation from different doughs and sourdoughs, 177 strains of lactic acid bacteria were screened at the phenotypic level for exopolysaccharide production on media containing different carbohydrate sources. Two exopolysaccharide-producing lactic acid bacteria (Lactobacillus curvatus 69B2 and Leuconostoc lactis 95A) were selected through quantitative analysis on solid media containing sucrose and yeast extract. The PCR detection of homopolysaccharide (gtf and lev) and heteropolysaccharide (epsA, epsB, epsD and epsE, and epsEFG) genes showed different distributions within species and strains of the lactic acid bacteria studied. Moreover, in some strains both homopolysaccharide and heteropolysaccharide genes were detected. Proton nuclear magnetic resonance spectra suggest that Lactobacillus curvatus 69B2 and Leuconostoc lactis 95A produced the same exopolysaccharide, which was constituted by a single repeating glucopyranosyl unit linked by an α-(1→6) glycosidic bond in a dextran-type carbohydrate. Microbial growth, acidification, and viscoelastic properties of sourdoughs obtained by exopolysaccharide-producing and nonproducing lactic acid bacterial strains were evaluated. Sourdough obtained after 15 h at 30°C with exopolysaccharide-producing lactic acid bacteria reached higher total titratable acidity as well as elastic and dissipative modulus curves with respect to the starter not producing exopolysaccharide, but they showed similar levels of pH and microbial growth. On increasing the fermentation time, no difference in the viscoelastic properties of exopolysaccharide-producing and nonproducing samples was observed. This study suggests that dextran-producing Leuconostoc lactis 95A and Lactobacillus curvatus 69B2 can be employed to prepare sourdough, and this would be particularly useful to improve the quality of baked goods while avoiding the use of commercially available hydrocolloids as texturizing additives. 相似文献
30.
Maureen Voigtlaender Jean-Paul Laclau José Leonardo de Moraes Gon?alves Marisa de Cássia Piccolo Marcelo Zacharias Moreira Yann Nouvellon Jacques Ranger Jean-Pierre Bouillet 《Plant and Soil》2012,352(1-2):99-111