1,721,028 research outputs found

    Analysis of HIF-1 alpha and HIF-2 alpha in dendritic cells stimulated under hypoxic conditions

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    Analysis of HIF-1 alpha and HIF-2 alpha in dendritic cells stimulated under hypoxic conditions Barroeta Seijas AB.1, Filippi I.2, Vitale S. 1, Simonetti S. 3, Naldini A.2, Di Rosa F.1 1 Institute of Biology and Molecular Pathology (IBPM)- National Research Council (CNR), Rome, Italy 2 Department of Physiology, University of Siena, Siena, Italy. 3 Department of Molecular Medicine, University of Rome “Sapienza”, Rome, Italy Dendritic cells (DCs) are professional antigen-presenting cells that have a pivotal role in linking innate and acquired immunity, and in the maintenance of selftolerance. DCs can activate resting T cells in spleen and lymph nodes, stimulate effector T cells in inflamed tissues and contribute to maintenance of memory T cells in different organs, including the bone marrow (BM). Alternatively activated DCs have been involved in regulation of angiogenesis during chronic inflammation. Inflamed tissues and BM share a common feature: a low oxygen tension. Under hypoxic conditions, different levels of hypoxia inducible factors HIF-1 alpha and HIF-2 alpha modulate the expression of a variety of genes related to apoptosis, cell migration, metabolic changes necessaries for adaptation to the hypoxic environment. Although it is generally believed that hypoxic conditions are inhibitory for protective immune responses, a clear picture of the hypoxia-induced pathways in DCs has not emerged yet. We aim to investigate the molecular and functional changes induced by hypoxia in mouse BM-derived DCs. Specifically, we will evaluate the regulation of the transcription factors HIF-1 alpha and HIF-2 alpha in DCs stimulated with classical (e.g. LPS) and alternative stimuli (e.g. IL-10), under either normoxic or hypoxic conditions. We will investigate the production by stimulated DCs of molecular mediators affecting both angiogenesis and T cell responses. We expect to gain more information on the cross-talk between angiogenic molecules and cytokines involved in immune regulation, occurring both in hypoxic lymphoid organs and inflamed tissues

    Persisting viruses and autoimmunity

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    Viral infections can be responsible for the onset and sustaining of autoimmune processes. We discuss how chronic inflammation associated with viral persistence is the prerequisite for initiation of a multi-step process leading to autoimmunity. Firstly, chronic inflammation may favor the priming of autoreactive T cells that have escaped thymic selection and are specific for self-mimicking viral peptides in the periphery. In addition, viral persistence and inflammation can act synergistically to induce and sustain autoimmunity either unveiling cryptic self-epitopes, or favoring determinant spreading, or activating dendritic cells, or promoting constant priming of new autoreactive T cells, or contributing to the efficient generation of effector cells, or, finally, restimulating memory T lymphocytes

    Corrigendum: To Ki or Not to Ki: Re-Evaluating the Use and Potentials of Ki-67 for T Cell Analysis (Front. Immunol., (2021), 12, (653974), 10.3389/fimmu.2021.653974)

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    In the original article, there was a mistake in the legend for Figure 1 as published. On the Viable cells, no “dump” gate, “CD16” was written instead of “CD19”. The correct legend appears below. “HD PBMCs were stained with the viability dye eFluor 780 (eF780), the DNA dye Hoechst-33342, and fluorochrome conjugated mAbs against surface markers and Ki-67, as described (16). An example of flow cytometry analysis is shown. (A) Gating of viable single CD8 T cells in 6 steps: 1) DNA-A/-W singlets. Single cells having 2n≤ DNA content ≤4n were selected on the DNA-area (A) versus (vs) DNA-width (W) plot; 2) Time exclusion. Stable acquisition over time (seconds) was monitored on the time vs DNA-A plot and any events collected in case of pressure fluctuations were excluded; 3) Viable cells, no “dump”. Cells expressing CD4, CD14 and CD19, and dead cells were excluded; 4) FSC-A/SSC-A “relaxed” gate. A “relaxed” gate was used on the FSC-A vs SSC-A plot, to include highly activated and cycling lymphocytes (15); 5) CD8 T cells. CD8 T cells were gated on the CD3 versus CD8 plot; 6) Refined singlets. A few remaining doublets composed by one cell sitting on top of another (so called “shadow” doublets) were excluded as Ki-67int/- events having > 2n DNA content (16). This gating strategy was used as a base for the subsequent gates. (B) The following naïve/memory subsets of CD8 T cells were identified: CD45RA+ CCR7+ Naïve, CD45RA- CCR7+ central memory (CM), CD45RA- CCR7- effector memory (EM), and CD45RA+ CCR7- (EMRA). (C) Cell cycle phases of each naïve/memory CD8 T cell subset were defined on DNA-A vs Ki67-A plot as follows: cells in G0 were identified as DNA 2n/Ki67- (bottom left quadrant); cells in G1 as DNA 2n/Ki67+ (upper left quadrant); cells in S-G2/M (or TDS cells) as DNA>2n/Ki67+ (top right quadrant). Unpublished data in relation to (16).” In the original article, there was also amistake in the legend for SupplementaryTable 1 as published. The peptide- HLA-A*02 tetramer list was incorrectly formatted, there was missing information about numbers in the table (they represent average percentages); missing information about the number of mice (panel A) and number of human donors (panel B and C); and a missing citation of original references at the end. The corrected Supplementary Material File is linked below. In the original article, there was also a mistake in Figure 1 as published. There was an incorrect y-axis label in panel A, third graph from left. The corrected Figure 1 appears below. (Figure presented.) The authors apologize for these errors and state that they do not change the scientific conclusions of the article in any way. The original article has been updated

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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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