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101.
Interactions of donor sources and media influence the histo‐morphological quality of full‐thickness skin models
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Julia Lange Frederik Weil Christoph Riegler Florian Groeber Silke Rebhan Szymon Kurdyn Miriam Alb Hermann Kneitz Götz Gelbrich Heike Walles Stephan Mielke 《Biotechnology journal》2016,11(10):1352-1361
Human artificial skin models are increasingly employed as non‐animal test platforms for research and medical purposes. However, the overall histopathological quality of such models may vary significantly. Therefore, the effects of manufacturing protocols and donor sources on the quality of skin models built‐up from fibroblasts and keratinocytes derived from juvenile foreskins is studied. Histo‐morphological parameters such as epidermal thickness, number of epidermal cell layers, dermal thickness, dermo‐epidermal adhesion and absence of cellular nuclei in the corneal layer are obtained and scored accordingly. In total, 144 full‐thickness skin models derived from 16 different donors, built‐up in triplicates using three different culture conditions were successfully generated. In univariate analysis both media and donor age affected the quality of skin models significantly. Both parameters remained statistically significant in multivariate analyses. Performing general linear model analyses we could show that individual medium‐donor‐interactions influence the quality. These observations suggest that the optimal choice of media may differ from donor to donor and coincides with findings where significant inter‐individual variations of growth rates in keratinocytes and fibroblasts have been described. Thus, the consideration of individual medium‐donor‐interactions may improve the overall quality of human organ models thereby forming a reproducible test platform for sophisticated clinical research. 相似文献
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This article discusses the historical perspective and the new findings of autophagy and ubiquitin-proteasome system cooperation during the post-fertilization sperm mitophagy, a process that eliminates potentially damaged paternal mitochondrial DNA from an early embryo. New insight into the mechanism that promotes clonal, maternal inheritance of mitochondrial genes may be helpful for managing mitochondrial disease and infertility in humans, as well as reproductive performance and production traits in agriculturally important domestic animals. 相似文献
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Kartik S. Bane Simone Lepper Jessica Kehrer Julia M. Sattler Mirko Singer Miriam Reinig Dennis Klug Kirsten Heiss Jake Baum Ann-Kristin Mueller Friedrich Frischknecht 《PLoS pathogens》2016,12(7)
Parasites causing malaria need to migrate in order to penetrate tissue barriers and enter host cells. Here we show that the actin filament-binding protein coronin regulates gliding motility in Plasmodium berghei sporozoites, the highly motile forms of a rodent malaria-causing parasite transmitted by mosquitoes. Parasites lacking coronin show motility defects that impair colonization of the mosquito salivary glands but not migration in the skin, yet result in decreased transmission efficiency. In non-motile sporozoites low calcium concentrations mediate actin-independent coronin localization to the periphery. Engagement of extracellular ligands triggers an intracellular calcium release followed by the actin-dependent relocalization of coronin to the rear and initiation of motility. Mutational analysis and imaging suggest that coronin organizes actin filaments for productive motility. Using coronin-mCherry as a marker for the presence of actin filaments we found that protein kinase A contributes to actin filament disassembly. We finally speculate that calcium and cAMP-mediated signaling regulate a switch from rapid parasite motility to host cell invasion by differentially influencing actin dynamics. 相似文献
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Qingling Zhang Michael Cox Zhike Liang Folke Brinkmann Paul A Cardenas Rachael Duff Pankaj Bhavsar William Cookson Miriam Moffatt Kian Fan Chung 《PloS one》2016,11(4)
BackgroundThe lower airways harbor a community of bacterial species which is altered in asthma.ObjectivesWe examined whether the lower airway microbiota were related to measures of asthma severity.MethodsWe prospectively recruited 26 severe asthma, 18 non-severe asthma and 12 healthy subjects. DNA was extracted from induced sputum and PCR amplification of the V3-V5 region of bacterial 16S rRNA gene was performed.ResultsWe obtained 138,218 high quality sequences which were rarefied at 133 sequences/sample. Twenty OTUs had sequences ≥1% of total. There were marked differences in the distribution of Phyla between groups (P = 2.8x10-118). Bacteroidetes and Fusobacteria were reduced in non-severe and severe asthmatic groups. Proteobacteria were more common in non-severe asthmatics compared to controls (OR = 2.26; 95% CI = 1.94–2.64) and Firmicutes were increased in severe asthmatics compared to controls (OR = 2.15; 95%CI = 1.89–2.45). Streptococcal OTUs amongst the Firmicutes were associated with recent onset asthma, rhinosinusitis and sputum eosinophilia.ConclusionsSputum microbiota in severe asthma differs from healthy controls and non-severe asthmatics, and is characterized by the presence of Streptococcus spp with eosinophilia. Whether these organisms are causative for the pathophysiology of asthma remains to be determined. 相似文献
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Catalina Perello Ernesto Llamas Vincent Burlat Miriam Ortiz-Alcaide Michael A. Phillips Pablo Pulido Manuel Rodriguez-Concepcion 《PloS one》2016,11(2)
Plastidial isoprenoids are a diverse group of metabolites with roles in photosynthesis, growth regulation, and interaction with the environment. The methylerythritol 4-phosphate (MEP) pathway produces the metabolic precursors of all types of plastidial isoprenoids. Proteomics studies in Arabidopsis thaliana have shown that all the enzymes of the MEP pathway are localized in the plastid stroma. However, immunoblot analysis of chloroplast subfractions showed that the first two enzymes of the pathway, deoxyxylulose 5-phosphate synthase (DXS) and reductoisomerase (DXR), can also be found in non-stromal fractions. Both transient and stable expression of GFP-tagged DXS and DXR proteins confirmed the presence of the fusion proteins in distinct subplastidial compartments. In particular, DXR-GFP was found to accumulate in relatively large vesicles that could eventually be released from chloroplasts, presumably to be degraded by an autophagy-independent process. Together, we propose that protein-specific mechanisms control the localization and turnover of the first two enzymes of the MEP pathway in Arabidopsis chloroplasts. 相似文献
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Andreas Entenmann Ronald Schmiedel Miriam Michel Friedemann Egender Vera He?ling Ingo D?hnert Roman Gebauer 《PloS one》2016,11(3)
Background
Postoperative junctional ectopic tachycardia (JET) occurs frequently after pediatric cardiac surgery. R-wave synchronized atrial (AVT) pacing is used to re-establish atrioventricular synchrony. AVT pacing is complex, with technical pitfalls. We sought to establish and to test a low-cost simulation model suitable for training and analysis in AVT pacing.Methods
A simulation model was developed based on a JET simulator, a simulation doll, a cardiac monitor, and a pacemaker. A computer program simulated electrocardiograms. Ten experienced pediatric cardiologists tested the model. Their performance was analyzed using a testing protocol with 10 working steps.Results
Four testers found the simulation model realistic; 6 found it very realistic. Nine claimed that the trial had improved their skills. All testers considered the model useful in teaching AVT pacing. The simulation test identified 5 working steps in which major mistakes in performance test may impede safe and effective AVT pacing and thus permitted specific training. The components of the model (exclusive monitor and pacemaker) cost less than $50. Assembly and training-session expenses were trivial.Conclusions
A realistic, low-cost simulation model of AVT pacing is described. The model is suitable for teaching and analyzing AVT pacing technique. 相似文献109.
Although serotonin is known to play an important role in pain processing, the relationship between the polymorphism in 5-HTTLPR and pain processing is not well understood. To examine the relationship more comprehensively, various factors of pain processing having putative associations with 5-HT functioning were studied, namely the subjective pain experience (pain threshold, rating of experimental pain), catastrophizing about pain (Pain Catastrophizing Scale = PCS) and motor responsiveness (facial expression of pain). In 60 female and 67 male participants, heat pain stimuli were applied by a contact thermode to assess pain thresholds, supra-threshold ratings and a composite score of pain-relevant facial responses. Participants also completed the PCS and were grouped based on their 5-HTTLPR genotype (bi-allelic evaluation) into a group with s-allele carriers (ss, sl) and a second group without (ll). S-allele carriers proved to have lower pain thresholds and higher PCS scores. These two positive findings were unrelated to each other. No other difference between genotype groups became significant. In all analyses, “age” and “gender” were controlled for. In s-allele carriers the subjective pain experience and the tendency to catastrophize about pain was enhanced, suggesting that the s-allele might be a risk factor for the development and maintenance of pain. This risk factor seems to act via two independent routes, namely via the sensory processes of subjective pain experiences and via the booster effects of pain catastrophizing. 相似文献
110.