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Anubha Sagar Carolin Klemm Lara Hartjes Stefanie Mauerer Ger van Zandbergen Barbara Spellerberg 《PloS one》2013,8(4)
S. agalactiae (group B streptococci, GBS) is a major microbial pathogen in human neonates and causes invasive infections in pregnant women and immunocompromised individuals. The S. agalactiae β-hemolysin is regarded as an important virulence factor for the development of invasive disease. To examine the role of β-hemolysin in the interaction with professional phagocytes, the THP-1 monocytic cell line and human granulocytes were infected with a serotype Ia S. agalactiae wild type strain and its isogenic nonhemolytic mutant. We could show that the nonhemolytic mutants were able to survive in significantly higher numbers than the hemolytic wild type strain, in THP-1 macrophage-like cells and in assays with human granulocytes. Intracellular bacterial multiplication, however, could not be observed. The hemolytic wild type strain stimulated a significantly higher release of Tumor Necrosis Factor-α than the nonhemolytic mutant in THP-1 cells, while similar levels of the chemokine Interleukin-8 were induced. In order to investigate bacterial mediators of IL-8 release in this setting, purified cell wall preparations from both strains were tested and found to exert a potent proinflammatory stimulus on THP-1 cells. In conclusion, our results indicate that the β-hemolysin has a strong influence on the intracellular survival of S. agalactiae and that a tightly controlled regulation of β-hemolysin expression is required for the successful establishment of S. agalactiae in different host niches. 相似文献
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Effect of valproate on lactate and glutamine metabolism by rat renal cortical tubules 总被引:3,自引:0,他引:3
M Doval M Culebras A Lopez-Farré M Rengel A Gougoux P Vinay J M Lopez-Novoa 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1989,190(4):357-364
The metabolic effects of sodium valproate (VPA) on rat renal cortical tubules have been examined. When 1 or 5 mM lactate was used as substrate in the incubation medium, VPA decreased markedly the lactate uptake by the tubules. When 1 or 5 mM glutamine was used, the addition of VPA accelerated glutamine uptake, ammoniagenesis, but also stimulated markedly the accumulation of lactate and pyruvate produced from glutamine. VPA had a dose-dependent inhibitory effect on gluconeogenesis from both glutamine and lactate. With 5 mM glutamine, VPA also induced a significant accumulation of glutamate in the medium. The oxygen consumption by the tubules was diminished by 40% following VPA addition. It is concluded that VPA modifies the metabolism of rat cortical tubules by interfering with the oxidation of natural substrates and stimulates in this fashion the production of ammonia by kidney tubules. 相似文献
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Man's influence on the greenhouse effect, the heating of the atmosphere due to increasing concentrations of tropospheric trace gases, is of much international concern. Among the climatic variables, elevated levels of carbon dioxide (CO2), ultraviolet-B (UV-B) radiation and ozone (O3) are known to have a direct effect on vegetation. Our current knowledge of these effects is mainly based on studies involving single stress mode. Thus, the joint effects of CO2, UV-B and O3 on vegetation are poorly understood. Nevertheless, based on the literature analysis of plant response to individual stress factors, it can be concluded that sorghum, pea, bean, potato, oat, lettuce, cucumber, rice and tomato are among the crop species potentially sensitive to the joint effects of the aforementioned three variables. Similar information for tree species is essentially lacking.At least with some climatic variables such as O3, present modeling efforts of cause-effect relationships have proven to be controversial. While at a regional geographic scale ambient CO2 concentrations appear to be relatively homogeneous, ambient concentrations of O3 exhibit significant temporal and spatial variability. Because of the protective action of O3 against UV-B, similar but inverse temporal and spatial variability is expected in the surface levels of UV-B. Thus, future experimental designs should consider these exposure dynamics and modeling cuase-effect relationships should be directed to stochastic processes. 相似文献
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OBJECTIVES--To examine the potential of lifelong patterns of increased physical activity to prevent stroke. DESIGN--Case-control study. SETTING--11 general practices in west Birmingham. SUBJECTS--125 men and women who had just had their first stroke and were aged 35-74 and 198 controls frequency matched for age and sex recruited over 24 months during 1988-90. Exclusion criteria were a previous history of stroke, mitral valvular heart disease combined with atrial fibrillation, primary or metastatic cerebral neoplasm, or coagulation disorder or myeloproliferative disease. MAIN OUTCOME MEASURES--Odds ratios for stroke related to lifetime history of exercise after 15 years of age. RESULTS--A history of vigorous exercise during the ages 15-25 appeared to protect from stroke: odds ratio adjusted for age and sex 0.33 (95% confidence interval 0.2 to 0.6). This effect was independent of other potential risk factors. Increasing years of participation in vigorous exercise between the ages of 15 and 55 produced an increasing protection from stroke (p < 0.001). In the 65 cases and 169 controls who were free of cardiac ischaemia, peripheral vascular disease, and poor health recent vigorous exercise and walking were protective against stroke: odds ratios of 0.41 (0.2 to 1.0) for recent vigorous exercise and 0.30 (0.1 to 0.7) for recent walking. CONCLUSIONS--Appreciable protection from stroke in later life is conferred by vigorous exercise in early adulthood. This increased level of physical activity should, if possible, be continued lifelong. 相似文献
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R. Ashton Lavoie Jeffrey T. Zugates Andrew T. Cheeseman Matt A. Teten Srivatsan Ramesh Julia M. Freeman Summer Swango Jeremy Fitzpatrick Amod Joshi Bradley Hollers Zufan Debebe Tyler K. Lindgren Amber N. Kozak Vinay K. Kondeti Mary K. Bright Eric J. Yearley Alexander Tracy Jacob A. Irwin Michael Guerrero 《Biotechnology and bioengineering》2023,120(10):2953-2968
Adeno-associated virus-based gene therapies have demonstrated substantial therapeutic benefit for the treatment of genetic disorders. In manufacturing processes, viral capsids are produced with and without the encapsidated gene of interest. Capsids devoid of the gene of interest, or “empty” capsids, represent a product-related impurity. As a result, a robust and scalable method to enrich full capsids is crucial to provide patients with as much potentially active product as possible. Anion exchange chromatography has emerged as a highly utilized method for full capsid enrichment across many serotypes due to its ease of use, robustness, and scalability. However, achieving sufficient resolution between the full and empty capsids is not trivial. In this work, anion exchange chromatography was used to achieve empty and full capsid resolution for adeno-associated virus serotype 5. A salt gradient screen of multiple salts with varied valency and Hofmeister series properties was performed to determine optimal peak resolution and aggregate reduction. Dual salt effects were evaluated on the same product and process attributes to identify any synergies with the use of mixed ion gradients. The modified process provided as high as ≥75% AAV5 full capsids (≥3-fold enrichment based on the percent full in the feed stream) with near baseline separation of empty capsids and achieved an overall vector genome step yield of >65%. 相似文献
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Schizopyrenus russelli, a free-living soil ameba, grows and encysts in the presence of bacteria. The encystment occurs with decline in the division rate. This is accompanied by incorporation of [U-14C] glucose into cyst cellulose. The degree of multiplication (but not of encystment) is a function of bacterial concentration. Berenil, a trypanocidal drug, while allowing excystment, completely inhibited multiplication of emerged amebae and their encystment. Addition of this drug after 24 hr, when amebae had gone into a phase of active division failed to check encystment, although it still inhibited further multiplication of the amebae. The findings suggest that a phase of cell division may be a prerequisite for encystment. 相似文献
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Land treatment of wastewater is an attractive alternative to conventional sewage treatment systems and is gaining widespread acceptance. Although land application systems prevent surface water pollution and augment the available water supplies, the potential dangers to human health should be evaluated. Since sewage may contain high amounts of bacterial endotoxin, the removal of endotoxin from sewage by percolation through soil was investigated. It was found that 90 to 99% of the endotoxin was removed after travel of sewage through 100 to 250 cm of loamy sand soil. When distilled water was allowed to infiltrate into the soil to simulate rainfall, the endotoxin was mobilized and moved in a concentrated band through the soil column. On testing samples from actual land treatment sites, as much as 480 ng of endotoxin per milliliter was found in some groundwater samples. The presence of endotoxin in potable water is known to be a potential problem under some circumstances, but the importance of endotoxin in water supplies has not been fully assessed. Therefore, the design, operation, and management of land application systems should take into account the fate of endotoxin in groundwater beneath the sites. 相似文献