1,720,957 research outputs found
Preserving vascular stability: FVIII's influence on endothelial cells
Full text linkHemophilia A (HA) is a genetic bleeding disorder caused by the deficiency of coagulation factor VIII (FVIII) and its severity is categorized based on FVIII residual activity: severe (< 1%), moderate (1-5%), and mild (5-40%). Current treatment primarily consists of frequent FVIII infusions, aiming to prevent spontaneous hemorrhages. These bleeding episodes are HA patients’ hallmarks, but they also manifest hemarthrosis and spontaneous intracranial hemorrhages (ICHs) whose exact cause remains unclear. Furthermore, HA patients exhibit endothelial dysfunction and a pro-inflammatory environment, suggesting the potential involvement of FVIII in maintaining endothelial cell (EC) homeostasis. To explore the role of FVIII in endothelial stability, we investigated the functionality of blood outgrowth endothelial cells obtained from both healthy (C-BOECs) and severe HA individuals (HA-BOECs). HA-BOECs showed a reduced tubulogenic capacity, decreased migratory ability, and a higher permeability than C-BOECs. Interestingly, when HA-BOECs were transduced with a lentiviral vector (LV) carrying FVIII or when treated with recombinant FVIII, they displayed rescued functions. To corroborate these data, we also performed CRISPR/Cas9 knockout of F8 in C-BOECs showing a significantly decreased in vitro functionality. For the first time, we found that FVIII binds to integrin βeta1 (ITGB1) activating focal adhesion kinase (FAK) and its downstream effectors in ECs. Moreover, both transcriptomic and proteomic analysis demonstrate that BOECs expressing FVIII result in a higher expression of genes and proteins related to angiogenesis, and extracellular matrix organization. Specifically, we focused on nidogen 2, involved in the endothelial basement membrane stability, whose expression was dependent to FVIII-ITGB1-FAK pathway. Subsequently, we found a drastic reduction in vascular density in HA brains compared to WT ones, and, importantly, long-term LV-FVIII injected HA mice significantly improved brain vessel formation. These preliminary data indicate that FVIII plays a critical role in the brainvasculature development. In conclusion, we explored the intricate effects of FVIII on ECs demonstrating its direct role in preserving the physiological functions of these cells. In HA, where FVIII levels are reduced or absent, disruptions in endothelial signaling occur, potentially leading to vessel fragility. This study is central to formulating precise therapeutic strategies for HA patients
Hemostasis and endothelial functionality: the double face of coagulation factors
Full text link: Hemostasis is a sophisticated sequence of events aimed to repair vessel injury. This process occurs in combination with angiogenesis, which leads to new blood vessel formation helping in the wound repair and facilitating tissue healing. The fine mechanisms that regulate hemostasis and angiogenesis are well described, but for long time, coagulation factors (CFs) have been considered merely players in the coagulation cascade. However, several experimental evidences highlight the crucial functions of these CFs in regulating endothelial functionality, especially in the angiogenic process. Some of these CFs (e.g. thrombin and tissue factor) have been widely investigated and have been described to trigger intracellular signaling related to endothelial cell (EC) functionality. For others (e.g. factor VIII and thrombomodulin), potential receptors and molecular mechanisms have not been fully elucidated but some data show their potential to induce EC response. This review focuses on the emerging roles of selected CFs in regulating EC functions, especially highlighting their ability to activate signaling pathways involved in the angiogenesis, migration, proliferation and endothelial barrier stability
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
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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