1,720,961 research outputs found
Fluorescent fatty acid conjugates for live cell imaging of peroxisomes
No full textPeroxisomes are eukaryotic organelles that are essential for multiple metabolic pathways, including fatty acid oxidation, degradation of amino acids, and biosynthesis of ether lipids. Consequently, peroxisome dysfunction leads to pediatric-onset neurodegenerative conditions, including Peroxisome Biogenesis Disorders (PBD). Due to the dynamic, tissue-specific, and context-dependent nature of their biogenesis and function, live cell imaging of peroxisomes is essential for studying peroxisome regulation, as well as for the diagnosis of PBD-linked abnormalities. However, the peroxisomal imaging toolkit is lacking in many respects, with no reporters for substrate import, nor cell-permeable probes that could stain dysfunctional peroxisomes. Here we report that the BODIPY-C12 fluorescent fatty acid probe stains functional and dysfunctional peroxisomes in live mammalian cells. We then go on to improve BODIPY-C12, generating peroxisome-specific reagents, PeroxiSPY650 and PeroxiSPY555. These probes combine high peroxisome specificity, bright fluorescence in the red and far-red spectrum, and fast non-cytotoxic staining, making them ideal tools for live cell, whole organism, or tissue imaging of peroxisomes. Finally, we demonstrate that PeroxiSPY enables diagnosis of peroxisome abnormalities in the PBD CRISPR/Cas9 cell models and patient-derived cell lines.GR-SCHUHMACHERPTC
Quantification of stored red blood cell fluctuations by time-lapse holographic cell imaging
Full text linkWe propose methods to quantitatively calculate the fluctuation rate of red blood cells with nanometric axial and millisecond temporal sensitivity at the single-cell level by using time-lapse holographic cell imaging. For this quantitative analysis, cell membrane fluctuations (CMFs) were measured for RBCs stored at different storage times. Measurements were taken over the whole membrane for both the ring and dimple sections separately. The measurements show that healthy RBCs that maintain their discocyte shape become stiffer with storage time. The correlation analysis demonstrates a significant negative correlation between CMFs and the sphericity coefficient, which characterizes the morphological type of erythrocyte. In addition, we show the correlation results between CMFs and other morphological properties such as projected surface area, surface area, mean corpuscular volume, and mean corpuscular hemoglobin. (C) 2018 Optical Society of America under the terms of the OSA Open Access Publishing AgreementPTC
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
New routes in additive solution formulations to improve the quality of stored red blood cells
No full textBlood transfusion is a procedure that enables us to save lives every day. In Switzerland, 221'100 red cell concentrates, 38'947 platelet concentrates, and 30'552 units of fresh frozen plasma have been used in 2018 (Swiss Transfusion SRC). Red Blood Cells (RBCs), once separated from other blood components, can be stored for several weeks (generally between 6 and 7) at 4°C in gas-permeable plastic bags. To this end, an additive solution containing all necessary elements for cell survival is routinely added. Such storage conditions, however, differ from the physiological environment in which cells naturally live, leading to metabolic, oxidative and functional changes called RBC "storage lesions" which can be irreversible and progressively accumulate after transfusion.
As of today, scientific consensus has not been reached concerning the clinical impact of these RBC storage lesions. In fact, some studies demonstrated that patients transfused with “old” blood, i.e. close to expiration date, have an increased risk of developing transfusion-related adverse effects, whereas others showed no such correlations. The only certainty is that such RBCs no longer have their original properties, potentially reducing their effectiveness. In this context, this thesis aims at proposing novel cheaper ways of improving RBC storage, thereby improving the quality of transfusions for patients.
The first part of this thesis provides a deeper understanding of the causes and mechanisms linked to storage lesions. Using a variety of measurement tools, key parameters of RBC metabolism, antioxidant defenses, and morphology, are reported. The analysis of this data demonstrates that RBCs are prematurely impacted by changes in their environment, including depletion of the uric acid naturally present in high concentration in blood plasma. Based on these results, improvements to storage solutions are proposed. In particular, the effect of adding uric acid with or without vitamin C is tested. Results show significant improvements at level of the cell metabolism, suggesting that proposed treatments are effective. However, limited changes are found for other parameters such as hemolysis, raising the question of dosage and efficacy. To address this issue, the second part of this thesis is devoted to the development of an assay compatible with high-throughput screening to quickly and easily evaluate antioxidant properties of a wide range of molecules. This test provides a way to better define the amount of chemical or natural compounds to add in blood bags to have a positive impact on the aging of RBCs in storage units to prolong the quality of transfusions for patients.
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La transfusion sanguine est une procédure qui permet de sauver des vies quotidiennement. En Suisse, 221'100 concentrés érythrocytaires, 38'947 concentrés thrombocytaires et 30'552 unités de plasma frais congelés ont ainsi été consommés en 2018 (Transfusion CRS Suisse). Les globules rouges (GR) une fois séparés des autres composants sanguins peuvent être conservés plusieurs semaines (généralement entre 6 et 7) à 4°C dans une poche plastique perméable aux gaz. Pour ce faire, une solution additive contenant les éléments nécessaires à leur survie est ajoutée. Ces conditions de stockage diffèrent de l’environnement physiologique dans lequel ces cellules évoluent normalement. Au cours du temps des lésions métaboliques, oxydatives et fonctionnelles, qui peuvent être réversibles ou irréversibles après transfusion, communément nommées « lésions de stockage des GR » s’accumulent.
La communauté scientifique n’est aujourd’hui pas unanime sur la question de l’impact clinique de ces lésions sur le patient traité. En effet, certaines études ont démontré que les receveurs du sang
« vieux », c’est-à-dire proche de la péremption, couraient un risque accru de développer des effets indésirables en lien avec la transfusion, alors que d’autres travaux n’ont montré aucune corrélation. La certitude qui demeure néanmoins est que ces GR n’ont plus les mêmes propriétés, réduisant ainsi potentiellement leur efficacité. C’est dans ce contexte que s’inscrit cette thèse de doctorat dont le but fût de proposer de nouvelles solutions simples et peu coûteuses permettant d’améliorer le stockage des GR, et ainsi la qualité du produit pour le patient.
La première partie de ce travail a consisté à acquérir une meilleure compréhension des causes et mécanismes liés à ces lésions. Les différents outils utilisés ont permis de suivre l’évolution de paramètres reflétant le métabolisme, les défenses antioxydantes et la morphologie cellulaire. Cette étude a notamment démontré que les GR étaient impactés précocement par le changement de leur milieu et notamment la déplétion de l’acide urique contenu dans le plasma. C’est sur la base de ces observations que diverses modifications de la composition de la solution de stockage furent ensuite proposées. L’effet de l’ajout d’acide urique avec ou sans vitamine C a ainsi été testé. Les résultats ont montré des modifications significatives au niveau du métabolisme cellulaire, suggérant un effet du traitement, mais des effets limités sur d’autres paramètres telle que l’hémolyse. Ces résultats ont soulevé la question de la dose et de l’efficacité. C’est pourquoi, la dernière partie de cette thèse fut consacrée au développement d’un test (compatible avec le criblage à haut débit) permettant d’évaluer rapidement et simplement les propriétés antioxydantes d’un large panel de composés. Ce test devrait également permettre de mieux définir la quantité de molécule à ajouter afin d’avoir un impact réel sur le vieillissement des GR dans les poches de stockage, et ainsi d’assurer un produit de qualité constante pour le patient transfusé
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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