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171.
Fitness trade‐offs explain low levels of persister cells in the opportunistic pathogen Pseudomonas aeruginosa 下载免费PDF全文
Edgar A. Duéñez‐Guzmán Frédéric Muratori Bram Van den Bergh Natalie Verstraeten Luc De Meester Kevin J. Verstrepen Jan Michiels 《Molecular ecology》2015,24(7):1572-1583
Microbial populations often contain a fraction of slow‐growing persister cells that withstand antibiotics and other stress factors. Current theoretical models predict that persistence levels should reflect a stable state in which the survival advantage of persisters under adverse conditions is balanced with the direct growth cost impaired under favourable growth conditions, caused by the nonreplication of persister cells. Based on this direct growth cost alone, however, it remains challenging to explain the observed low levels of persistence (<<1%) seen in the populations of many species. Here, we present data from the opportunistic human pathogen Pseudomonas aeruginosa that can explain this discrepancy by revealing various previously unknown costs of persistence. In particular, we show that in the absence of antibiotic stress, increased persistence is traded off against a lengthened lag phase as well as a reduced survival ability during stationary phase. We argue that these pleiotropic costs contribute to the very low proportions of persister cells observed among natural P. aeruginosa isolates (3 × 10?8–3 × 10?4) and that they can explain why strains with higher proportions of persister cells lose out very quickly in competition assays under favourable growth conditions, despite a negligible difference in maximal growth rate. We discuss how incorporating these trade‐offs could lead to models that can better explain the evolution of persistence in nature and facilitate the rational design of alternative therapeutic strategies for treating infectious diseases. 相似文献
172.
173.
Firdaus AA Mohamed Hoesein Pieter Zanen Pim A de Jong Bram van Ginneken H Marike Boezen Harry JM Groen Mathijs Oudkerk Harry J de Koning Dirkje S Postma Jan-Willem J Lammers 《Respiratory research》2013,14(1):55
Background
Little is known about the factors associated with CT-quantified emphysema progression in heavy smokers. The objective of this study was to investigate the effect of length of smoking cessation and clinical / demographical factors on the rate of emphysema progression and FEV1-decline in male heavy smokers.Methods
3,670 male smokers with mean (SD) 40.8 (17.9) packyears underwent chest CT scans and pulmonary function tests at baseline and after 1 and 3 years follow-up. Smoking status (quitted ≥5, ≥1-<5, <1 years or current smoker) was noted. Rate of progression of emphysema and FEV1-decline after follow-up were assessed by analysis of variance adjusting for age, height, baseline pulmonary function and emphysema severity, packyears, years in study and respiratory symptoms. The quitted ≥5 group was used as reference.Results
Median (Q1-Q3) emphysema severity,<-950 HU, was 8.8 (5.1 – 14.1) and mean (SD) FEV1 was 3.4 (0.73) L or 98.5 (18.5) % of predicted. The group quitted ‘>5 years’ showed significantly lower rates of progression of emphysema compared to current smokers, 1.07% and 1.12% per year, respectively (p<0.001). Current smokers had a yearly FEV1-decline of 69 ml, while subjects quit smoking >5 years had a yearly decline of 57.5 ml (p<0.001).Conclusion
Quit smoking >5 years significantly slows the rate of emphysema progression and lung function decline.Trial registration
Registered at http://www.trialregister.nl with trial number ISRCTN63545820. 相似文献174.
Akkelies E Dijkstra Dirkje S Postma Nick ten Hacken Judith M Vonk Matthijs Oudkerk Peter MA van Ooijen Pieter Zanen Firdaus A Mohamed Hoesein Bram van Ginneken Michael Schmidt Harry JM Groen 《Respiratory research》2013,14(1):11
Background
Increased airway wall thickness (AWT) and parenchymal lung destruction both contribute to airflow limitation. Advances in computed tomography (CT) post-processing imaging allow to quantify these features. The aim of this Dutch population study is to assess the relationships between AWT, lung function, emphysema and respiratory symptoms.Methods
AWT and emphysema were assessed by low-dose CT in 500 male heavy smokers, randomly selected from a lung cancer screening population. AWT was measured in each lung lobe in cross-sectionally reformatted images with an automated imaging program at locations with an internal diameter of 3.5 mm, and validated in smaller cohorts of patients. The 15th percentile method (Perc15) was used to assess the severity of emphysema. Information about respiratory symptoms and smoking behavior was collected by questionnaires and lung function by spirometry.Results
Median AWT in airways with an internal diameter of 3.5 mm (AWT3.5) was 0.57 (0.44 - 0.74) mm. Median AWT in subjects without symptoms was 0.52 (0.41-0.66) and in those with dyspnea and/or wheezing 0.65 (0.52-0.81) mm (p<0.001). In the multivariate analysis only AWT3.5 and emphysema independently explained 31.1%and 9.5%of the variance in FEV1%predicted, respectively, after adjustment for smoking behavior.Conclusions
Post processing standardization of airway wall measurements provides a reliable and useful method to assess airway wall thickness. Increased airway wall thickness contributes more to airflow limitation than emphysema in a smoking male population even after adjustment for smoking behavior. 相似文献175.
176.
Everaert N Willemsen H Kamers B Decuypere E Bruggeman V 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2011,158(2):215-220
It has been shown that during embryonic chicken (Gallus gallus) development, the metabolism of broiler embryos differs from that of layers in terms of embryonic growth, pCO2/pO2 blood levels, heat production, and heart rate. Therefore, these strains might adapt differently on extreme environmental factors such as exposure to high CO2. The aim of this study was to compare broiler and layer embryos in their adaptation to 4% CO2 from embryonic days (ED) 12 to 18. Due to hypercapnia, blood pCO2 increased in both strains. Blood bicarbonate concentration was ~10 mmol/L higher in embryos exposed to high CO2 of both strains, while the bicarbonates of broilers had ~5 mmol/L higher values than layer embryos. In addition, the pH increased when embryos of both strains were exposed to CO2. Moreover, under CO2 conditions, the blood potassium concentration increased in both strains significantly, reaching a plateau at ED14. At ED12, the layer strain had a higher increase in CAII protein in red blood cells due to incubation under high CO2 compared to the broiler strain, whereas at ED14, the broiler strain had the highest increase. In conclusion, the most striking observation was the similar mechanism of broiler and layer embryos to cope with high CO2 levels. 相似文献
177.
van den Berg L van Beekum O Heutink P Felius BA van de Heijning MP Strijbis S van Spaendonk R Piancatelli D Garner KM El Aouad R Sistermans E Adan RA Delemarre-van de Waal HA 《Obesity (Silver Spring, Md.)》2011,19(3):604-611
The most common monogenic form of obesity is caused by mutations in the gene encoding the melanocortin-4 receptor (MC4R). We have screened the MC4R coding sequence in 291 patients of a Dutch outpatient pediatric obesity clinic. We analyzed the minimal promoter region of the gene in a random subgroup of 217 children. Our aims were (i) to determine the frequency of MC4R mutations in a cohort of Dutch clinically obese children and (ii) to search for mutations in the promoter of the gene. Eleven MC4R coding variants were detected. Five children had mutations that have been shown to affect receptor function by other research groups (p.Y35X, p.I251fs, p.G231S). These children did not have earlier onset of obesity or higher BMI-SDS than the remainder of the cohort. One child had a novel nonsynonymous coding mutation (p.L304F). This variant showed a markedly decreased cell surface expression in in vitro experiments and is thus expected to be pathogenic. We detected 12 variants in the MC4R flanking regions. Five of these were not previously described (c.-1101C>T, c.-705A>T, c.-461A>G, c.-312T>C, c.-213A>G). We investigated these mutations by family studies and a bioinformatic approach. We conclude that rare heterozygous mutations in the coding sequence of MC4R account for some severe obesity cases in the Dutch population. These patients are difficult to recognize in a clinical setting. We generated a list of all MC4R variants that were described in the literature so far, which can aid the interpretation of mutations found in a diagnostic setting. 相似文献
178.
Bram C.J. van der Eerden Nadja Fratzl‐Zelman Tom Nijenhuis Paul Roschger Ulrich Zügel Andreas Steinmeyer Joost G.J. Hoenderop René J.M. Bindels Klaus Klaushofer Johannes P.T.M. van Leeuwen 《Journal of cellular physiology》2013,228(2):402-407
Mice lacking the renal epithelial Ca2+ channel TRPV5 (TRPV5?/?) display impaired renal Ca2+ reabsorption, hypercalciuria, and intestinal Ca2+ hyperabsorption, due to secondary hypervitaminosis D. Using these mice, we previously demonstrated that ZK191784 acts as an intestine‐specific 1,25(OH)2D3 antagonist without affecting serum calcium levels. On the other hand, it acted as an agonist in the kidney and the effects of ZK191784 on bone were ambiguous. The present study was undertaken to further evaluate the effect of the vitamin D receptor antagonist on murine bone in mice lacking TRPV5. Eight‐week‐old female Trpv5+/+ and Trpv5?/? mice were treated for 4 weeks with or without 50 µg/kg/day ZK191784. Quantitative backscattered electron imaging showed that the reduced bone matrix mineralization found in femoral bones of Trpv5?/? mice was partially but significantly restored upon ZK191784 treatment, just as we observed for trabecular bone thickness. This supports the significance of 1,25(OH)2D3 and optimal control of Ca2+ homeostasis for bone formation and matrix mineralization. Restoration also took place at the bone gene expression level, where 1α‐hydroxylase (Cyp27b1) mRNA in femurs from ZK‐treated Trpv5?/? mice was upregulated compared to control levels. The downregulated 24‐hydroxylase (Cyp24a1) gene expression in femoral bone indicated local vitamin D resistance in the mice treated with ZK191784. Phosphate homeostasis was unaffected between the groups as shown by unaltered serum and fibroblast growth factor (FGF) 23 as well as Fgf23 mRNA expression in bone. In conclusion, circulating 1,25(OH)2D3 is important for optimal control of Ca2+ homeostasis but also for controlled bone formation and matrix mineralization. J. Cell. Physiol. 228: 402–407, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
179.
Bram Sercu Antony D. G. Jones Cindy H. Wu Mauricio H. Escobar Carol L. Serlin Timothy A. Knapp Gary L. Andersen Patricia A. Holden 《Microbial ecology》2013,65(1):39-49
In situ chemical oxidation with permanganate has become an accepted remedial treatment for groundwater contaminated with chlorinated solvents. This study focuses on the immediate and short-term effects of sodium permanganate (NaMnO4) on the indigenous subsurface microbial community composition in groundwater impacted by trichloroethylene (TCE). Planktonic and biofilm microbial communities were studied using groundwater grab samples and reticulated vitreous carbon passive samplers, respectively. Microbial community composition was analyzed by terminal restriction fragment length polymorphism and a high-density phylogenetic microarray (PhyloChip). Significant reductions in microbial diversity and biomass were shown during NaMnO4 exposure, followed by recovery within several weeks after the oxidant concentrations decreased to <1 mg/L. Bray–Curtis similarities and nonmetric multidimensional scaling showed that microbial community composition before and after NaMnO4 was similar, when taking into account the natural variation of the microbial communities. Also, 16S rRNA genes of two reductive dechlorinators (Desulfuromonas spp. and Sulfurospirillum spp.) and diverse taxa capable of cometabolic TCE oxidation were detected in similar quantities by PhyloChip across all monitoring wells, irrespective of NaMnO4 exposure and TCE concentrations. However, minimal biodegradation of TCE was observed in this study, based on oxidized conditions, concentration patterns of chlorinated and nonchlorinated hydrocarbons, geochemistry, and spatiotemporal distribution of TCE-degrading bacteria. 相似文献
180.