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121.
Infection with Helicobacter pylori induces various gastric diseases, including ulceration, gastritis and neoplasia. As H. pylori-induced cellular mechanisms leading to these disease states are widely unclear, we analysed the phosphoproteome of H. pylori-infected gastric epithelial cells. Phosphoproteins from infected cells were enriched using affinity columns and analysed by two-dimensional gel electrophoresis and mass spectrometry. Eleven novel phosphoproteins that showed differentially regulated phosphorylation levels during H. pylori infection were identified. Interestingly, the identified proteins were actin-binding, transport and folding, RNA/DNA-binding or cancer-associated proteins. We analysed functions of one identified H. pylori-regulated candidate, the vasodilator-stimulated phosphoprotein (VASP). H. pylori induced VASP phosphorylation at residues Ser157, Ser239 and Thr278, which was enhanced by the bacterial oncogene cytotoxin-associated gene A. Overexpression of a phosphorylation-resistant VASP mutant efficiently blocked host cell elongation. We identified cGMP-dependent protein kinase G-mediated Ser239 and Thr278 phosphorylation of VASP as a crucial event in H. pylori-dependent host cell elongation. These results suggest that phosphorylated VASP could be a novel target candidate for therapeutic intervention in H. pylori-related gastric diseases.  相似文献   
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Lactobacillus surface layers and their applications   总被引:6,自引:0,他引:6  
Surface (S-) layers are crystalline arrays of proteinaceous subunits present as the outermost component of cell wall in several species of the genus Lactobacillus, as well as in many other bacteria and Archaea. Despite the high similarity of the amino acid composition of all known S-layer proteins, the overall sequence similarity is, however, surprisingly small even between the Lactobacillus S-layer proteins. In addition, the typical characteristics of Lactobacillus S-layer proteins, distinguishing them from other S-layer proteins, are small size and high-predicted pI value. Several lactobacilli possess multiple S-layer protein genes, which can be differentially or simultaneously expressed. To date, the characterized functions of Lactobacillus S-layers are involved in mediating adhesion to different host tissues. A few applications for the S-layer proteins of lactobacilli already exist, including their use as antigen delivery vehicles.  相似文献   
124.
Mutations in the catalytic subunit of the mitochondrial DNA polymerase gamma (POLG) have been found to be an important cause of neurological disease. Recently, we and collaborators reported a new neurodegenerative disorder with autosomal recessive ataxia in four patients homozygous for two amino acid changes in POLG: W748S in cis with E1143G. Here, we studied the frequency of this allele and found it to be among the most common genetic causes of inherited ataxia in Finland. We identified 27 patients with mitochondrial recessive ataxia syndrome (MIRAS) from 15 Finnish families, with a carrier frequency in the general population of 1 : 125. Since the mutation pair W748S+E1143G has also been described in European patients, we examined the haplotypes of 13 non-Finnish, European patients with the W748S mutation. Haplotype analysis revealed that all the chromosomes carrying these two changes, in patients from Finland, Norway, the United Kingdom, and Belgium, originate from a common ancient founder. In Finland and Norway, long, common, northern haplotypes, outside the core haplotype, could be identified. Despite having identical homozygous mutations, the Finnish patients with this adult- or juvenile-onset disease had surprisingly heterogeneous phenotypes, albeit with a characteristic set of features, including ataxia, peripheral neuropathy, dysarthria, mild cognitive impairment, involuntary movements, psychiatric symptoms, and epileptic seizures. The high carrier frequency in Finland, the high number of patients in Norway, and the ancient European founder chromosome indicate that this newly identified ataxia should be considered in the first-line differential diagnosis of progressive ataxia syndromes.  相似文献   
125.
The icosahedral membrane-containing double-stranded DNA bacteriophage PRD1 has a labile receptor binding spike complex at the vertices. This complex, which is analogous to that of adenovirus, is formed of the penton protein P31, the spike protein P5, and the receptor binding protein P2. Upon infection, the internal phage membrane transforms into a tubular structure that protrudes through a vertex and penetrates the cell envelope for DNA injection. We describe here a new class of PRD1 mutants lacking virion-associated integral membrane protein P16. P16 links the spike complex to the viral membrane and is necessary for spike stability. We also show that the unique vertex used for DNA packaging is intact in the P16-deficient particle, indicating that the 11 adsorption vertices and the 1 portal vertex are functionally and structurally distinct.  相似文献   
126.
Mice double deficient in LAMP-1 and -2 were generated. The embryos died between embryonic days 14.5 and 16.5. An accumulation of autophagic vacuoles was detected in many tissues including endothelial cells and Schwann cells. Fibroblast cell lines derived from the double-deficient embryos accumulated autophagic vacuoles and the autophagy protein LC3II after amino acid starvation. Lysosomal vesicles were larger and more peripherally distributed and showed a lower specific density in Percoll gradients in double deficient when compared with control cells. Lysosomal enzyme activities, cathepsin D processing and mannose-6-phosphate receptor expression levels were not affected by the deficiency of both LAMPs. Surprisingly, LAMP-1 and -2 deficiencies did not affect long-lived protein degradation rates, including proteolysis due to chaperone-mediated autophagy. The LAMP-1/2 double-deficient cells and, to a lesser extent, LAMP-2 single-deficient cells showed an accumulation of unesterified cholesterol in endo/lysosomal, rab7, and NPC1 positive compartments as well as reduced amounts of lipid droplets. The cholesterol accumulation in LAMP-1/2 double-deficient cells could be rescued by overexpression of murine LAMP-2a, but not by LAMP-1, highlighting the more prominent role of LAMP-2. Taken together these findings indicate partially overlapping functions for LAMP-1 and -2 in lysosome biogenesis, autophagy, and cholesterol homeostasis.  相似文献   
127.
Vertical migration by diatoms is a well-known phenomenon, occurring in intertidal and subtidal benthic biofilms. It is partially endogenously driven, as cell movements can be observed in the absence of external stimuli such as light, temperature or water cover. Although vertical migration of diatoms under constant conditions has often been attributed to geotactic orientation, this hypothesis has never been experimentally demonstrated. Our study tested the gravitactic nature of the vertical migratory behaviour of benthic diatoms in sedimentary biofilms, using an experimental setup designed to distinguish gravitaxis from surface-oriented cell movements. The hourly variation of surface diatom biomass during migratory cycles was compared in homogenized sediment samples kept facing upwards (surface-oriented and gravity stimuli coinciding; controls) and facing sideways or downwards (surface-oriented and gravity stimuli not coinciding). During the experiments, sediment samples were kept in complete darkness in custom-made, sealed measuring chambers designed to avoid any contact with atmospheric air and the formation of physico-chemical gradients near the surface. Microalgal biomass was monitored non-intrusively using PAM fluorometry, by measuring dark-level fluorescence, Fo. The results showed a clear effect of sample orientation in relation to the gravitational stimulus. In the controls, a biphasic pattern in surface biomass was observed, with the formation of a clear biomass peak (three- to six-fold increase) followed by a slower decrease. In contrast, in samples facing sideways or downwards, surface biomass also varied but to a much lesser extent (typically < two-fold). These results strongly suggest that, in the absence of light, upward vertical migration of benthic diatoms is mostly guided by negative gravitaxis, supporting the often hypothesized capacity of these cells to sense and use gravity to move vertically within the sediment.  相似文献   
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129.
Silja Spitaels  Jean-Claude Fouron  André Davignon 《CMAJ》1972,107(11):1096-1103,1106
Experience in the pediatric age group with mechanography, an indirect method of cardiovascular investigation, is described with emphasis on the recording technique and on the analysis of the tracings. A few examples are presented with comments on the morphological aspects and the time characteristics of the pulse curves, showing how much information about cardiac disease and especially myocardial function in children may be obtained.  相似文献   
130.
Six mildly hypertensive subjects were exposed three times to −15 °C (wind 3.5 m/s) for 15 min. After an initial exposure for familiarisation, second and third exposures were arranged in a random double blind, crossover fashion after a week's ingestion of hydrochlorothiazide or placebo. Cold decreased skin temperatures, but not rectal temperature. Blood pressure increased 30/20 mmHg and heart rate decreased 12 beats/min by cold. Blood pressure seems to react in 3 min to changes in ambient temperature. The skin temperatures of uncovered body parts were apparently responsible for that. Hydrochlorothiazide did not affect either cardiovascular or thermal responses in cold.  相似文献   
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