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221.
Binz PA Müller M Hoogland C Zimmermann C Pasquarello C Corthals G Sanchez JC Hochstrasser DF Appel RD 《Current opinion in biotechnology》2004,15(1):17-23
Approaches aimed at deciphering the proteome have illustrated the need for relatively complex and highly sensitive methodologies. The major elements of proteome analysis, such as powerful protein separation and enzymatic processing, mass spectrometry and dedicated bioinformatics have been assembled in the development of the molecular scanner. This highly flexible and data-rich approach has combined the power of electrophoretic protein separation, the simultaneous digestion and transfer of proteins through an enzymatic membrane, the immediate use of the MALDI mass spectrometer to scan a collecting membrane, and the development of dedicated bioinformatics tools to perform protein identification and molecular imaging of the proteome. Clinical applications of the molecular scanner have also started to be developed for disease diagnosis in biological material. 相似文献
222.
Rouleau A Héron A Cochois V Pillot C Schwartz JC Arrang JM 《Journal of neurochemistry》2004,90(6):1331-1338
The existence of mouse H3-receptor isoforms was investigated by PCR analysis and cDNA cloning. Splicing mechanisms previously reported in various species are conserved in the mouse. The retention/deletion of a fragment in the third intracellular loop of the mouse receptor leads to the existence of three isoforms designated mH(3(445)), mH(3(413)) and mH(3(397)) according to the length of their deduced amino acid sequence. PCR analysis showed that mouse H3-receptor isoforms display different expression patterns in the brain. Following expression in Cos-1 cells, [125I]iodoproxyfan binding indicated similar pharmacological profiles of the mH(3(445)), mH(3(413)) and mH(3(397)) isoforms. The pharmacological profile of the mouse H3 receptor is more similar to the rat receptor than to the human receptor, although some differences were also observed between the mouse and rat receptors. For example, the potency of thioperamide and ciproxifan is slightly higher at the mouse receptor than at the rat receptor but 40-100-fold higher than at the human receptor. In situ hybridization histochemistry showed that the distribution of H3-receptor mRNAs in the mouse brain is rather similar to that previously reported in the rat brain. However, the autoradiographic and cellular expression patterns observed in several brain areas such as the thalamus or hippocampus reveal important differences between the two species. 相似文献
223.
Whole-genome sequence analysis of Pseudomonas syringae pv. phaseolicola 1448A reveals divergence among pathovars in genes involved in virulence and transposition
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Joardar V Lindeberg M Jackson RW Selengut J Dodson R Brinkac LM Daugherty SC Deboy R Durkin AS Giglio MG Madupu R Nelson WC Rosovitz MJ Sullivan S Crabtree J Creasy T Davidsen T Haft DH Zafar N Zhou L Halpin R Holley T Khouri H Feldblyum T White O Fraser CM Chatterjee AK Cartinhour S Schneider DJ Mansfield J Collmer A Buell CR 《Journal of bacteriology》2005,187(18):6488-6498
Pseudomonas syringae pv. phaseolicola, a gram-negative bacterial plant pathogen, is the causal agent of halo blight of bean. In this study, we report on the genome sequence of P. syringae pv. phaseolicola isolate 1448A, which encodes 5,353 open reading frames (ORFs) on one circular chromosome (5,928,787 bp) and two plasmids (131,950 bp and 51,711 bp). Comparative analyses with a phylogenetically divergent pathovar, P. syringae pv. tomato DC3000, revealed a strong degree of conservation at the gene and genome levels. In total, 4,133 ORFs were identified as putative orthologs in these two pathovars using a reciprocal best-hit method, with 3,941 ORFs present in conserved, syntenic blocks. Although these two pathovars are highly similar at the physiological level, they have distinct host ranges; 1448A causes disease in beans, and DC3000 is pathogenic on tomato and Arabidopsis. Examination of the complement of ORFs encoding virulence, fitness, and survival factors revealed a substantial, but not complete, overlap between these two pathovars. Another distinguishing feature between the two pathovars is their distinctive sets of transposable elements. With access to a fifth complete pseudomonad genome sequence, we were able to identify 3,567 ORFs that likely comprise the core Pseudomonas genome and 365 ORFs that are P. syringae specific. 相似文献
224.
Billiet L Furman C Larigauderie G Copin C Brand K Fruchart JC Rouis M 《The Journal of biological chemistry》2005,280(48):40310-40318
Oxidative stress plays an important role in atherosclerotic vascular disease, and several recent studies were focused on thioredoxin-1 (Trx-1) and its potential protective role against oxidative stress. Since human monocyte-derived macrophages (HMDM) are important cells in several inflammatory diseases including atherosclerosis, we conducted this study to evaluate the impact of extracellular recombinant human Trx-1 (rhTrx-1) on gene expression in lipopolysaccharide-activated HMDM. Our results showed that rhTrx-1 was capable of reducing interleukin (IL)-1beta mRNA and protein synthesis in a dose-dependent manner. This effect was partly mediated through a reduction of NF-kappaB activation as analyzed by transient transfection and gel shift assays. In addition, we showed that the attenuation of NF-kappaB activity was the result of the reduction of both p50 and p65 subunit mRNA and protein synthesis on one hand and of the induction of I-kappaBalpha mRNA and protein expression on the other hand. Moreover, inhibition of endogenous Trx-1 mRNA was also observed, suggesting a contribution to the diminution of NF-kappaB activity since endogenous Trx-1, in contrast to the exogenous Trx-1, activates the NF-kappaB system. Finally, H2O2-oxidized rhTrx-1 reduced IL-1beta mRNA synthesis in lipopolysaccharide-activated HMDM. This result highly suggested that the rhTrx-1 used in this study could be oxidized in the culture medium and, in turn, reduced IL-1beta mRNA and protein synthesis. Taken together, these data indicated a potential new mechanism through which extracellular rhTrx-1 exerts an anti-inflammatory function in HMDM. 相似文献
225.
The cytogenetic effect of a hormonal steroid, estradiol-17beta, was assessed in peripheral blood human lymphocyte culture. Sister chromatid exchanges (SCE) and chromosome aberrations (CA) were scored as genetic end points. Significant induction of CA was observed at 25 microg/ml and 50 microg/ml concentrations of estradiol-17beta in the absence of microsomal activation. The drug was effective in all treatments in the presence of rat liver S(9) microsomal fraction (S(9) mix) and exhibited increased frequency of chromosomal aberrations. The drug was effective in increasing the SCE frequency which was found to be maximum at the dose of 50 microg/ml concentration (i.e., 4.34+/-1.22) both with and without metabolic activation. It was found that estradiol-17beta itself and possibly its metabolites are potent mutagens beyond a particular dose in human lymphocytes. 相似文献
226.
Wang KS Komar AR Ma T Filiz F McLeroy J Hoda K Verkman AS Bastidas JA 《American journal of physiology. Gastrointestinal and liver physiology》2000,279(2):G448-G453
The aquaporin-4 (AQP4) water channel has been proposed to play a role in gastric acid secretion. Immunocytochemistry using anti-AQP4 antibodies showed strong AQP4 protein expression at the basolateral membrane of gastric parietal cells in wild-type (+/+) mice. AQP4 involvement in gastric acid secretion was studied using transgenic null (-/-) mice deficient in AQP4 protein. -/- Mice had grossly normal growth and appearance and showed no differences in gastric morphology by light microscopy. Gastric acid secretion was measured in anesthetized mice in which the stomach was luminally perfused (0. 3 ml/min) with 0.9% NaCl containing [(14)C]polyethylene glycol ([(14)C]PEG) as a volume marker. Collected effluent was assayed for titratable acid content and [(14)C]PEG radioactivity. After 45-min baseline perfusion, acid secretion was stimulated by pentagastrin (200 microg. kg(-1). h(-1) iv) for 1 h or histamine (0.23 mg/kg iv) + intraluminal carbachol (20 mg/l). Baseline gastric acid secretion (means +/- SE, n = 25) was 0.06 +/- 0.03 and 0.03 +/- 0.02 microeq/15 min in +/+ and -/- mice, respectively. Pentagastrin-stimulated acid secretion was 0.59 +/- 0.14 and 0.70 +/- 0.15 microeq/15 min in +/+ and -/- mice, respectively. Histamine plus carbachol-stimulated acid secretion was 7.0 +/- 1.9 and 8.0 +/- 1.8 microeq/15 min in +/+ and -/- mice, respectively. In addition, AQP4 deletion did not affect gastric fluid secretion, gastric pH, or fasting serum gastrin concentrations. These results provide direct evidence against a role of AQP4 in gastric acid secretion. 相似文献
227.
Le Maux Chansac B Moretta A Vergnon I Opolon P Lécluse Y Grunenwald D Kubin M Soria JC Chouaib S Mami-Chouaib F 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(9):5790-5798
NK cells are able to discriminate between normal cells and cells that have lost MHC class I (MHC-I) molecule expression as a result of tumor transformation. This function is the outcome of the capacity of inhibitory NK receptors to block cytotoxicity upon interaction with their MHC-I ligands expressed on target cells. To investigate the role of human NK cells and their various receptors in the control of MHC-I-deficient tumors, we have isolated several NK cell clones from lymphocytes infiltrating an adenocarcinoma lacking beta2-microglobulin expression. Unexpectedly, although these clones expressed NKG2D and mediated a strong cytolytic activity toward K562, Daudi and allogeneic MHC-class I+ carcinoma cells, they were unable to lyse the autologous MHC-I- tumor cell line. This defect was associated with alterations in the expression of natural cytotoxicity receptor (NCR) by NK cells and the NKG2D ligands, MHC-I-related chain A, MHC-I-related chain B, and UL16 binding protein 1, and the ICAM-1 by tumor cells. In contrast, the carcinoma cell line was partially sensitive to allogeneic healthy donor NK cells expressing high levels of NCR. Indeed, this lysis was inhibited by anti-NCR and anti-NKG2D mAbs, suggesting that both receptors are required for the induced killing. The present study indicates that the MHC-I-deficient lung adenocarcinoma had developed mechanisms of escape from the innate immune response based on down-regulation of NCR and ligands required for target cell recognition. 相似文献
228.
Khalil El Kadiri Francisco Serrano Rachid Hlila Hoda Liemlahi Ahmed Chalouan Angel Carlos López-Garrido Antonio Guerra-Merchán Carlos Sanz-de-Galdeano Karima Kerzazi Abdelaziz El Mrihi 《Facies》2005,50(3-4):477-503
The Tamezzakht succession (Maastrichtian–middle Burdigalian), situated at the fringe between the Internal and the External zones, displays contrasting lithologies with abrupt facies changes, discontinuities, and/or coarse-grained calciturbidite in between. These criteria allow the definition of seven main lithostratigraphic formations.Depositional environments (oxygenation levels, trophic conditions, omission histories, among others) and/or transgressive/regressive trends are inferred from integrated sedimentologic data including facies change, cyclicity pattern and the textural composition of the turbidite facies tracts. Special emphasis is given to the ichnological features.Taking into account the extended time-range, the position between the internal zones and the external ones, as well as the clear differentiation into several contrasting sedimentary formations, the Tamezzakht succession is expected to provide useful stratigraphic data for the regional correlations. 相似文献
229.
Ubiquitylation of a melanosomal protein by HECT-E3 ligases serves as sorting signal for lysosomal degradation 总被引:1,自引:0,他引:1
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Lévy F Muehlethaler K Salvi S Peitrequin AL Lindholm CK Cerottini JC Rimoldi D 《Molecular biology of the cell》2005,16(4):1777-1787
The production of pigment by melanocytic cells of the skin involves a series of enzymatic reactions that take place in specialized organelles called melanosomes. Melan-A/MART-1 is a melanocytic transmembrane protein with no enzymatic activity that accumulates in vesicles at the trans side of the Golgi and in melanosomes. We show here that, in melanoma cells, Melan-A associates with two homologous to E6-AP C-terminus (HECT)-E3 ubiquitin ligases, NEDD4 and Itch, and is ubiquitylated. Both NEDD4 and Itch participate in the degradation of Melan-A. A mutant Melan-A lacking ubiquitin-acceptor residues displays increased half-life and, in pigmented cells, accumulates in melanosomes. These results suggest that ubiquitylation regulates the lysosomal sorting and degradation of Melan-A/MART-1 from melanosomes in melanocytic cells. 相似文献
230.
Lentiviral-mediated silencing of SOD1 through RNA interference retards disease onset and progression in a mouse model of ALS 总被引:32,自引:0,他引:32
Raoul C Abbas-Terki T Bensadoun JC Guillot S Haase G Szulc J Henderson CE Aebischer P 《Nature medicine》2005,11(4):423-428
Mutations in Cu/Zn superoxide dismutase (encoded by SOD1), one of the causes of familial amyotrophic lateral sclerosis (ALS), lead to progressive death of motoneurons through a gain-of-function mechanism. RNA interference (RNAi) mediated by viral vectors allows for long-term reduction in gene expression and represents an attractive therapeutic approach for genetic diseases characterized by acquired toxic properties. We report that in SOD1(G93A) transgenic mice, a model for familial ALS, intraspinal injection of a lentiviral vector that produces RNAi-mediated silencing of SOD1 substantially retards both the onset and the progression rate of the disease. 相似文献