1,720,984 research outputs found
Polyphosphates interfere with the host immunity in Legionella infection
Full text link2026Legionnaire’s disease, caused by Legionella bacteria, is uncommon but serious cause of community-acquired pneumonia. Legionella resides within alveolar macrophages of infected hosts, where it releases effector molecules to evade phagocytic clearance. One of these molecules is predicted to be polyphosphates, which are produced by bacteria to help prolong their survival in hosts. Previous work has reported that long-chain polyphosphates derived from Escherichia coli interfere with the host innate response against infection. Here, I hypothesize that a similar mechanism occurs during Legionella infection. Macrophages derived from bone marrow of C57BL/6J mice were infected in vitro with Legionella pneumophila in the presence of purified polyphosphates. Additionally, polyphosphate levels were found to be elevated in human Legionellosis, murine Legionellosis, and in bone marrow-derived macrophage infection. In bulk RNA sequencing, the expression patterns of inflammatory response genes were mostly downregulated by long-chain polyphosphates (Pi 700). Specifically, interleukin-12 (IL-12) family cytokines and their signaling pathways (including signal transducer and activator of transcription (STAT) 1, STAT2 and STAT3) were suppressed by polyphosphates during Legionella pneumophila infection. IL-12 is a proinflammatory cytokine promoting type 1 T helper cell (Th1) polarization and, together with interleukin-18 (IL-18), induces interferon-γ production by natural killer (NK) and T cells, which are essential for the clearance of Legionella. The inhibition of IL-12 expression and release was confirmed by semi quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Polyphosphates cause a durable antagonism of IL-12 by 70% after 48 hours of infection in a chain-length-dependent manner.
A potential signaling pathway involving toll-like receptor 4 (TLR4) with myeloid differentiation primary response 88 (MyD88) and activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) cascade by polyphosphates was investigated. It was also confirmed that IL-18 and interleukin-1β (IL-1β) release, both cytokines produced by inflammasome activation and important for host defense against Legionella, were not affected by polyphosphates.
In conclusion, the presented studies provide novel evidence that long-chain polyphosphates specifically interfere with the IL-12-mediated immune response of macrophages against Legionella infection
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
Elucidating the role of CCDC9 in RNA-signaling through the stimulation of pattern recognition receptors
Full text linkCoiled-Coil Domain Containing 9 is a novel gene located beside C5aR1/R2 on murine chromosome 7. This proximal relationship is mirrored on human chromosome 19, making this research translational and relevant to the medical field. CCDC9-/- mice were created through a contract research organization utilizing CRISPR/Cas9 gene editing. Necropsy, gross examination, hematology, and clinical chemistry analysis were conducted to ensure that the global knockout of the CCDC9 gene did not induce any abnormalities in the development of the mice. Bone Marrow Derived Macrophages and Thioglycolate Elicited Peritoneal Macrophages were utilized from wild type and CCDC9-/- mice to explore the cytokine response from these macrophages when stimulated with various pattern recognition receptor agonists. Poly (I:C) and LPS were the two agonists that led to the most significant difference in cytokine release. Interactions with Poly (I:C), a synthetic double-stranded RNA that activates anti-viral RNA sensing immune responses, were targeted to elucidate how CCDC9 may be interacting with RNA. Meanwhile, interactions with LPS demonstrated that the role of CCDC9 is not specific to RNA-sensing but plays a modulatory role in the TLR4 and LPS pathway. These agonists were then paired with complement anaphylatoxin, C5a, and stimulated TEPM to explore the proximal relationship between CCDC9 and C5aR1/R2. The pairing with Poly (I:C) did not reveal any significant changes, but the pairing with LPS lead to a cytokine decrease that was not mirrored in CCDC9-/- macrophages. In-vivo applications were established in which wild type and CCDC9 -/- mice were injected intraperitoneally with LPS and Poly (I:C) to investigate the cytokine release. CCDC9-/- mice and cells consistently displayed a greater inflammatory cytokine induction when encountering stimulators of viral and bacterial pathogen sensing, suggesting that CCDC9 plays a role in immune function.2025-03-07T00:00:00
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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