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171.
Wouter de Jong Angel Manteca Jesus Sanchez Giselda Bucca Colin P. Smith Lubbert Dijkhuizen Dennis Claessen Han A. B. Wösten 《Molecular microbiology》2009,71(6):1591-1603
Streptomycetes have a complex morphogenetic programme culminating in the formation of aerial hyphae that develop into chains of spores. After spore dispersal, environmental signals trigger dormant spores to germinate to establish a new colony. We here compared whole genome expression of a wild-type colony of Streptomyces coelicolor forming aerial hyphae and spores with that of the chp null mutant that forms few aerial structures. This revealed that expression of 244 genes was significantly altered, among which genes known to be involved in development. One of the genes that was no longer expressed in the Δ chpABCDEFGH mutant was nepA , which was previously shown to be expressed in a compartment connecting the substrate mycelium with the sporulating parts of the aerial mycelium. We here show that expression is also detected in developing spore chains, where NepA is secreted to end up as a highly insoluble protein in the cell wall. Germination of spores of a nepA deletion mutant was faster and more synchronous, resulting in colonies with an accelerated morphogenetic programme. Crucially, spores of the Δ nepA mutant also germinated in water, unlike those of the wild-type strain. Taken together, NepA is the first bacterial structural cell wall protein that is important for maintenance of spore dormancy under unfavourable environmental conditions. 相似文献
172.
Wouter Van Hecke Clara Salaheddin Roland Ludwig Jo Dewulf Dietmar Haltrich Herman Van Langenhove 《Bioresource technology》2009,100(23):5566-5573
The interactions between two oxidoreductases coupled by an artificial redox mediator have been described quantitatively to increase both stability and productivity. In this cascade oxidation, pyranose 2-oxidase oxidizes several aldoses at the C-2 position to 2-ketoaldoses. A redox mediator is used as electron acceptor for pyranose 2-oxidase because it shows more favourable kinetics in comparison to oxygen. The reduced redox mediator is in turn re-oxidized by laccase, which uses oxygen as the terminal electron acceptor, reducing it fully to water. However, pyranose 2-oxidase is capable of using oxygen as an electron acceptor in a competing side reaction, leading to the formation of hydrogen peroxide, which is detrimental for both enzymes and seriously limits the operational stability of both enzymes.The experimental results showed full conversion of the aldose to the 2-ketoaldose and a good agreement with the simulations of the process. 相似文献
173.
Balancing Selection of a Frame-Shift Mutation in the MRC2 Gene Accounts for the Outbreak of the Crooked Tail Syndrome in Belgian Blue Cattle
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Corinne Fasquelle Arnaud Sartelet Wanbo Li Marc Dive Nico Tamma Charles Michaux Tom Druet Ivo J. Huijbers Clare M. Isacke Wouter Coppieters Michel Georges Carole Charlier 《PLoS genetics》2009,5(9)
We herein describe the positional identification of a 2-bp deletion in the open reading frame of the MRC2 receptor causing the recessive Crooked Tail Syndrome in cattle. The resulting frame-shift reveals a premature stop codon that causes nonsense-mediated decay of the mutant messenger RNA, and the virtual absence of functional Endo180 protein in affected animals. Cases exhibit skeletal anomalies thought to result from impaired extracellular matrix remodeling during ossification, and as of yet unexplained muscular symptoms. We demonstrate that carrier status is very significantly associated with desired characteristics in the general population, including enhanced muscular development, and that the resulting heterozygote advantage caused a selective sweep which explains the unexpectedly high frequency (25%) of carriers in the Belgian Blue Cattle Breed. 相似文献
174.
Ian Ford Vladimir Bezlyak David J Stott Naveed Sattar Chris J Packard Ivan Perry Brendan M Buckley J. Wouter Jukema Anton J. M de Craen Rudi G. J Westendorp James Shepherd 《PLoS medicine》2009,6(1)
Background
Reduced glomerular filtration rate (GFR) is associated with increased cardiovascular risk in young and middle aged individuals. Associations with cardiovascular disease and mortality in older people are less clearly established. We aimed to determine the predictive value of the GFR for mortality and morbidity using data from the 5,804 participants randomized in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).Methods and Findings
Glomerular filtration rate was estimated (eGFR) using the Modification of Diet in Renal Disease equation and was categorized in the ranges ([20–40], [40–50], [50–60]) ≥ 60 ml/min/1.73 m2. Baseline risk factors were analysed by category of eGFR, with and without adjustment for other risk factors. The associations between baseline eGFR and morbidity and mortality outcomes, accrued after an average of 3.2 y, were investigated using Cox proportional hazard models adjusting for traditional risk factors. We tested for evidence of an interaction between the benefit of statin treatment and baseline eGFR status. Age, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, C-reactive protein (CRP), body mass index, fasting glucose, female sex, histories of hypertension and vascular disease were associated with eGFR (p = 0.001 or less) after adjustment for other risk factors. Low eGFR was independently associated with risk of all cause mortality, vascular mortality, and other noncancer mortality and with fatal and nonfatal coronary and heart failure events (hazard ratios adjusted for CRP and other risk factors (95% confidence intervals [CIs]) for eGFR < 40 ml/min/1.73m2 relative to eGFR ≥ 60 ml/min/1.73m2 respectively 2.04 (1.48–2.80), 2.37 (1.53–3.67), 3.52 (1.78–6.96), 1.64 (1.18–2.27), 3.31 (2.03–5.41). There were no nominally statistically significant interactions (p < 0.05) between randomized treatment allocation and eGFR for clinical outcomes, with the exception of the outcome of coronary heart disease death or nonfatal myocardial infarction (p = 0.021), with the interaction suggesting increased benefit of statin treatment in subjects with impaired GFRs.Conclusions
We have established that, in an elderly population over the age of 70 y, impaired GFR is associated with female sex, with presence of vascular disease, and with levels of other risk factors that would be associated with increased risk of vascular disease. Further, impaired GFR is independently associated with significant levels of increased risk of all cause mortality and fatal vascular events and with composite fatal and nonfatal coronary and heart failure outcomes. Our analyses of the benefits of statin treatment in relation to baseline GFR suggest that there is no reason to exclude elderly patients with impaired renal function from treatment with a statin. 相似文献175.
Morreel K Goeminne G Storme V Sterck L Ralph J Coppieters W Breyne P Steenackers M Georges M Messens E Boerjan W 《The Plant journal : for cell and molecular biology》2006,47(2):224-237
Genetical metabolomics [metabolite profiling combined with quantitative trait locus (QTL) analysis] has been proposed as a new tool to identify loci that control metabolite abundances. This concept was evaluated in a case study with the model tree Populus. Using HPLC, the peak abundances were analyzed of 15 closely related flavonoids present in apical tissues of two full-sib poplar families, Populus deltoides cv. S9-2 x P. nigra cv. Ghoy and P. deltoides cv. S9-2 x P. trichocarpa cv. V24, and correlation and QTL analysis were used to detect flux control points in flavonoid biosynthesis. Four robust metabolite quantitative trait loci (mQTL), associated with rate-limiting steps in flavonoid biosynthesis, were mapped. Each mQTL was involved in the flux control to one or two flavonoids. Based on the identities of the affected metabolites and the flavonoid pathway structure, a tentative function was assigned to three of these mQTL, and the corresponding candidate genes were mapped. The data indicate that the combination of metabolite profiling with QTL analysis is a valuable tool to identify control points in a complex metabolic pathway of closely related compounds. 相似文献
176.
Sven R. Kantelhardt Wouter Caarls Anthony H. B. de Vries Guy M. Hagen Thomas M. Jovin Walter Schulz-Schaeffer Veit Rohde Alf Giese Donna J. Arndt-Jovin 《PloS one》2010,5(6)
Background
The current therapy of malignant gliomas is based on surgical resection, radio-chemotherapy and chemotherapy. Recent retrospective case-series have highlighted the significance of the extent of resection as a prognostic factor predicting the course of the disease. Complete resection in low-grade gliomas that show no MRI-enhanced images are especially difficult. The aim in this study was to develop a robust, specific, new fluorescent probe for glioma cells that is easy to apply to live tumor biopsies and could identify tumor cells from normal brain cells at all levels of magnification.Methodology/Principal Findings
In this investigation we employed brightly fluorescent, photostable quantum dots (QDs) to specifically target epidermal growth factor receptor (EGFR) that is upregulated in many gliomas. Living glioma and normal cells or tissue biopsies were incubated with QDs coupled to EGF and/or monoclonal antibodies against EGFR for 30 minutes, washed and imaged. The data include results from cell-culture, animal model and ex vivo human tumor biopsies of both low-grade and high-grade gliomas and show high probe specificity. Tumor cells could be visualized from the macroscopic to single cell level with contrast ratios as high as 1000: 1 compared to normal brain tissue.Conclusions/Significance
The ability of the targeted probes to clearly distinguish tumor cells in low-grade tumor biopsies, where no enhanced MRI image was obtained, demonstrates the great potential of the method. We propose that future application of specifically targeted fluorescent particles during surgery could allow intraoperative guidance for the removal of residual tumor cells from the resection cavity and thus increase patient survival. 相似文献177.
Tiago M. Malaquias Carolina Silveira Wouter Aerts Friedl De Groote Greta Dereymaeker Jos Vander Sloten 《Computer methods in biomechanics and biomedical engineering》2017,20(2):153-159
Multibody simulations of human motion require representative models of the anatomical structures. A model that captures the complexity of the foot is still lacking. In the present work, two detailed 3D multibody foot-ankle models generated based on CT scans using a semi-automatic tool are described. The proposed models consists of five rigid segments (talus, calcaneus, midfoot, forefoot and toes), connected by five joints (ankle, subtalar, midtarsal, tarsometatarsal and metatarsophalangeal), one with 15DOF and the other with 8DOF. The calculated kinematics of both models were evaluated using gait trials and compared against literature, both presenting realistic results. An inverse dynamic analysis was performed for the 8DOF model, again presenting feasible dynamic results. 相似文献
178.
Young-Lim Lee Haruko Takeda Gabriel Costa Monteiro Moreira Latifa Karim Erik Mullaart Wouter Coppieters The GplusE consortium Ruth Appeltant Roel F. Veerkamp Martien A. M. Groenen Michel Georges Mirte Bosse Tom Druet Aniek C. Bouwman Carole Charlier 《PLoS genetics》2021,17(7)
Clinical mastitis (CM) is an inflammatory disease occurring in the mammary glands of lactating cows. CM is under genetic control, and a prominent CM resistance QTL located on chromosome 6 was reported in various dairy cattle breeds. Nevertheless, the biological mechanism underpinning this QTL has been lacking. Herein, we mapped, fine-mapped, and discovered the putative causal variant underlying this CM resistance QTL in the Dutch dairy cattle population. We identified a ~12 kb multi-allelic copy number variant (CNV), that is in perfect linkage disequilibrium with a lead SNP, as a promising candidate variant. By implementing a fine-mapping and through expression QTL mapping, we showed that the group-specific component gene (GC), a gene encoding a vitamin D binding protein, is an excellent candidate causal gene for the QTL. The multiplicated alleles are associated with increased GC expression and low CM resistance. Ample evidence from functional genomics data supports the presence of an enhancer within this CNV, which would exert cis-regulatory effect on GC. We observed that strong positive selection swept the region near the CNV, and haplotypes associated with the multiplicated allele were strongly selected for. Moreover, the multiplicated allele showed pleiotropic effects for increased milk yield and reduced fertility, hinting that a shared underlying biology for these effects may revolve around the vitamin D pathway. These findings together suggest a putative causal variant of a CM resistance QTL, where a cis-regulatory element located within a CNV can alter gene expression and affect multiple economically important traits. 相似文献
179.
Wouter H. Südkamp 《Pal?ontologische Zeitschrift》2014,88(2):235-238
Südkamp (Paläontologische Zeitschrift 81:181–204, 2007: 198; Figs. 15A, B) described and figured the diplobathrid camerate crinoid Acanthocrinus spinosus n. sp. from the lower Devonian Hunsrück Slate of Karschheck quarry near Oberkirn, Rhineland-Palatinate, Germany. However, this name is preoccupied by Rhodocrinus (=Acanthocrinus Goldring 1926) spinosus Hall 1862 and therefore is invalid. A replacement name is proposed as Acanthocrinus multispina nom. nov. 相似文献
180.
A Single Oncogenic Enhancer Rearrangement Causes Concomitant EVI1 and GATA2 Deregulation in Leukemia
Stefan Gröschel Mathijs A. Sanders Remco Hoogenboezem Elzo de Wit Britta A.M. Bouwman Claudia Erpelinck Vincent H.J. van der Velden Marije Havermans Roberto Avellino Kirsten van Lom Elwin J. Rombouts Mark van Duin Konstanze Döhner H. Berna Beverloo James E. Bradner Hartmut Döhner Bob Löwenberg Peter J.M. Valk Eric M.J. Bindels Wouter de Laat Ruud Delwel 《Cell》2014