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121.
Christof J Majoor Marianne A van de Pol Pieter Willem Kamphuisen Joost CM Meijers Richard Molenkamp Katja C Wolthers Tom van der Poll Rienk Nieuwland Sebastian L Johnston Peter J Sterk Elisabeth HD Bel Rene Lutter Koenraad F van der Sluijs 《Respiratory research》2014,15(1):14
Background
Asthma exacerbations are frequently triggered by rhinovirus infections. Both asthma and respiratory tract infection can activate haemostasis. Therefore we hypothesized that experimental rhinovirus-16 infection and asthmatic airway inflammation act in synergy on the haemostatic balance.Methods
28 patients (14 patients with mild allergic asthma and 14 healthy non-allergic controls) were infected with low-dose rhinovirus type 16. Venous plasma and bronchoalveolar lavage fluid (BAL fluid) were obtained before and 6 days after infection to evaluate markers of coagulation activation, thrombin-antithrombin complexes, von Willebrand factor, plasmin-antiplasmin complexes, plasminogen activator inhibitor type-1, endogenous thrombin potential and tissue factor-exposing microparticles by fibrin generation test, in plasma and/or BAL fluid. Data were analysed by nonparametric tests (Wilcoxon, Mann Whitney and Spearman correlation).Results
13 patients with mild asthma (6 females, 19-29 y) and 11 healthy controls (10 females, 19-31 y) had a documented Rhinovirus-16 infection. Rhinovirus-16 challenge resulted in a shortening of the fibrin generation test in BAL fluid of asthma patients (t = -1: 706 s vs. t = 6: 498 s; p = 0.02), but not of controls (t = -1: 693 s vs. t = 6: 636 s; p = 0.65). The fold change in tissue factor-exposing microparticles in BAL fluid inversely correlated with the fold changes in eosinophil cationic protein and myeloperoxidase in BAL fluid after virus infection (r = -0.517 and -0.528 resp., both p = 0.01).Rhinovirus-16 challenge led to increased plasminogen activator inhibitor type-1 levels in plasma in patients with asthma (26.0 ng/mL vs. 11.5 ng/mL in healthy controls, p = 0.04). Rhinovirus-16 load in BAL showed a linear correlation with the fold change in endogenous thrombin potential, plasmin-antiplasmin complexes and plasminogen activator inhibitor type-1.Conclusions
Experimental rhinovirus infection induces procoagulant changes in the airways of patients with asthma through increased activity of tissue factor-exposing microparticles. These microparticle-associated procoagulant changes are associated with both neutrophilic and eosinophilic inflammation. Systemic activation of haemostasis increases with Rhinoviral load.Trial registration
This trial was registered at the Dutch trial registry (http://www.trialregister.nl): NTR1677. 相似文献122.
Realistically parameterized and dynamically simulated food-webs are useful tool to explore the importance of the functional diversity of ecosystems, and in particular relations between the dynamics of species and the whole community. We present a stochastic dynamical food web simulation for the Kelian River (Borneo). The food web was constructed for six different locations, arrayed along a gradient of increasing human perturbation (mostly resulting from gold mining activities) along the river. Along the river, the relative importance of grazers, filterers and shredders decreases with increasing disturbance downstream, while predators become more dominant in governing eco-dynamics. Human activity led to increased turbidity and sedimentation which adversely impacts primary productivity. Since the main difference between the study sites was not the composition of the food webs (structure is quite similar) but the strengths of interactions and the abundance of the trophic groups, a dynamical simulation approach seemed to be useful to better explain human influence. In the pristine river (study site 1), when comparing a structural version of our model with the dynamical model we found that structurally central groups such as omnivores and carnivores were not the most important ones dynamically. Instead, primary consumers such as invertebrate grazers and shredders generated a greater dynamical response. Based on the dynamically most important groups, bottom-up control is replaced by the predominant top-down control regime as distance downstream and human disturbance increased. An important finding, potentially explaining the poor structure to dynamics relationship, is that indirect effects are at least as important as direct ones during the simulations. We suggest that our approach and this simulation framework could serve systems-based conservation efforts. Quantitative indicators on the relative importance of trophic groups and the mechanistic modeling of eco-dynamics could greatly contribute to understanding various aspects of functional diversity. 相似文献
123.
Based upon an extensive single-channel data set, a Markov model for types I and II inositol trisphosphate receptors (IP(3)R) is developed. The model aims to represent accurately the kinetics of both receptor types of IP(3)R depending on the concentrations of inositol trisphosphate (IP(3)), adenosine trisphosphate (ATP), and intracellular calcium (Ca(2+)). In particular, the model takes into account that for some combinations of ligands the IP(3)R switches between extended periods of inactivity alternating with intervals of bursting activity (mode changes). In a first step, the inactive and active modes are modeled separately. It is found that, within modes, both receptor types are ligand-independent. In a second step, the submodels are connected by transition rates. Ligand-dependent regulation of the channel activity is achieved by modulating these transitions between active and inactive modes. As a result, a compact representation of the IP(3)R is obtained that accurately captures stochastic single-channel dynamics including mode changes in a model with six states and 10 rate constants, only two of which are ligand-dependent. 相似文献
124.
125.
Liviu R Totir Rohan L Fernando Jack CM Dekkers Soledad A Fernández Bernt Guldbrandtsen 《遗传、选种与进化》2004,36(1):29-48
Under additive inheritance, the Henderson mixed model equations (HMME) provide an efficient approach to obtaining genetic evaluations by marker assisted best linear unbiased prediction (MABLUP) given pedigree relationships, trait and marker data. For large pedigrees with many missing markers, however, it is not feasible to calculate the exact gametic variance covariance matrix required to construct HMME. The objective of this study was to investigate the consequences of using approximate gametic variance covariance matrices on response to selection by MABLUP. Two methods were used to generate approximate variance covariance matrices. The first method (Method A) completely discards the marker information for individuals with an unknown linkage phase between two flanking markers. The second method (Method B) makes use of the marker information at only the most polymorphic marker locus for individuals with an unknown linkage phase. Data sets were simulated with and without missing marker data for flanking markers with 2, 4, 6, 8 or 12 alleles. Several missing marker data patterns were considered. The genetic variability explained by marked quantitative trait loci (MQTL) was modeled with one or two MQTL of equal effect. Response to selection by MABLUP using Method A or Method B were compared with that obtained by MABLUP using the exact genetic variance covariance matrix, which was estimated using 15 000 samples from the conditional distribution of genotypic values given the observed marker data. For the simulated conditions, the superiority of MABLUP over BLUP based only on pedigree relationships and trait data varied between 0.1% and 13.5% for Method A, between 1.7% and 23.8% for Method B, and between 7.6% and 28.9% for the exact method. The relative performance of the methods under investigation was not affected by the number of MQTL in the model. 相似文献
126.
Gert Jan Boender Gonnie Nodelijk Thomas J Hagenaars Armin RW Elbers Mart CM de Jong 《BMC veterinary research》2008,4(1):9
Background
In the recent past, the introduction of Classical Swine Fever Virus (CSFV) followed by between-herd spread has given rise to a number of large epidemics in The Netherlands and Belgium. Both these countries are pork-exporting countries. Particularly important in these epidemics has been the occurrence of substantial "neighborhood transmission" from herd to herd in the presence of base-line control measures prescribed by EU legislation. Here we propose a calculation procedure to map out "high-risk areas" for local between-herd spread of CSFV as a tool to support decision making on prevention and control of CSFV outbreaks. In this procedure the identification of such areas is based on an estimated inter-herd distance dependent probability of neighborhood transmission or "local transmission". Using this distance-dependent probability, we derive a threshold value for the local density of herds. In areas with local herd density above threshold, local transmission alone can already lead to epidemic spread, whereas in below-threshold areas this is not the case. The first type of area is termed 'high-risk' for spread of CSFV, while the latter type is termed 'low-risk'.Results
As we show for the case of The Netherlands, once the distance-dependent probability of local transmission has been estimated from CSFV outbreak data, it is possible to produce a map of the country in which areas of high-risk herds and of low-risk herds are identified. We made these maps even more informative by estimating border zones between the two types of areas. In these border zones the risk of local transmission of infection to a nearby high-risk area exceeds a certain level.Conclusion
The risk maps provide an easily understandable visualization of the spatial heterogeneities in transmission risk. They serve as a tool for area-specific designs of control strategies, and possibly also for spatial planning of areas where livestock farming is allowed. Similar risk maps can in principle be constructed for other highly-transmissible livestock infections that spread via neighborhood transmission.127.
Shanshan Wang Ke Xie Guoyong Xu Huarui Zhou Qiang Guo Jingyi Wu Zengwei Liao Na Liu Yan Wang Yule Liu 《植物学报(英文版)》2018,60(7):541-561
Maintaining endoplasmic reticulum (ER) homeostasis is essential for the production of biomolecules. ER retrieval, i.e., the retrograde transport of compounds from the Golgi to the ER, is one of the pathways that ensures ER homeostasis. However, the mechanisms underlying the regulation of ER retrieval in plants remain largely unknown. Plant ERD2‐like proteins (ERD2s) were recently suggested to function as ER luminal protein receptors that mediate ER retrieval. Here, we demonstrate that heterotrimeric G protein signaling is involved in ERD2‐mediated ER retrieval. We show that ERD2s interact with the heterotrimeric G protein Gα and Gγ subunits at the Golgi. Silencing of Gα, Gβ, or Gγ increased the retention of ER luminal proteins. Furthermore, overexpression of Gα, Gβ, or Gγ caused ER luminal proteins to escape from the ER, as did the co‐silencing of ERD2a and ERD2b. These results suggest that G proteins interact with ER luminal protein receptors to regulate ER retrieval. 相似文献
128.
Since 1999, large-scale mortalities of fish-eating birds have been observed on the Great Lakes, and more specifically on Lake Erie. Type E botulism has been established as the primary cause of death. The mechanism of type E botulism exposure in fish-eating birds is unclear. Given that these birds are thought to eat live fish exclusively, it seems likely that their prey play a key role in the process, but the role of fish as potential transport vectors of botulinum neurotoxin type E (BoNT/E) to birds has not been adequately investigated. Between June 2003 and April 2004 a methodological model for exposing fish to Clostridium botulinum was developed and used to compare the sensitivity of rainbow trout (Oncorhynchus mykiss), round goby (Neogobius melanostomas), walleye (Stizostedion vitreum), and yellow perch (Perca flavescens) to four doses (0, 800, 1,500, and 4,000 Mouse Lethal Doses) of Clostridium botulinum type E neurotoxin. Each fish species expressed unique changes in both behavior and skin pigmentation prior to death. Yellow perch survived significantly longer (P < 0.05) than the three other species at all toxin treatments. Results of this study suggest that live fish can represent a significant vector for transfer of BoNT/E to birds. 相似文献
129.
Stimulant-evoked depolarization and increase in [Ca2+]
i
in insulin-secreting cells is dependent on external Na+ 总被引:1,自引:0,他引:1
M. J. Dunne D. I. Yule D. V. Gallacher O. H. Petersen 《The Journal of membrane biology》1990,113(2):131-138
Summary The patch-clamp technique and measurements of single cell [Ca2+]
i
have been used to investigate the importance of extracellular Na+ for carbohydrate-induced stimulation of RINm5F insulin-secreting cells. Using patch-clamp whole-cell (current-clamp) recordings the average cellular transmembrane potential was estimated to be –60±1 mV (n=83) and the average basal [Ca2+]
i
102±6nm (n=37). When challenged with either glucose (2.5–10mm) ord-glyceraldehyde (10mm) the cells depolarized, which led to the initiation of Ca2+ spike potentials and a sharp rise in [Ca2+]
i
. Similar effects were also observed with the sulphonylurea compound tolbutamide (0.01–0.1mm). Both the generation of the spike potentials and the increase in [Ca2+]
i
were abolished when Ca2+ was removed from the bathing media. When all external Na+ was replaced with N-methyl-d-glucamine, in the continued presence of either glucose,d-glyceraldehyde or tolbutamide, a membrane repolarization resulted, which terminated Ca2+ spike potentials and attenuated the rise in [Ca2+]
i
. Tetrodotoxin (TTX) (1–2 m) was also found to both repolarize the membrane and abolish secretagogue-induced rises in [Ca2+]
i
. 相似文献
130.
Tom?PMM?VluggenEmail author Jolanda?CM?van Haastregt Jeanine?A?Verbunt Elly?JM?Keijsers Jos?MGA?Schols 《BMC neurology》2012,12(1):164