1,720,980 research outputs found
The G2A receptor controls polarization of macrophage by determining their localization within the inflamed tissue
Full text linkMacrophages are highly versatile cells, which acquire, depending on their microenvironment, pro- (M1-like), or antiinflammatory (M2-like) phenotypes. Here, we studied the role of the G-protein coupled receptor G2A (GPR132), in chemotactic migration and polarization of macrophages, using the zymosan-model of acute inflammation. G2A-deficient mice showed a reduced zymosan-induced thermal hyperalgesia, which was reversed after macrophage depletion. Fittingly, the number of M1-like macrophages was reduced in the inflamed tissue in G2A-deficient mice. However, G2A activation was not sufficient to promote M1-polarization in bone marrow-derived macrophages. While the number of monocyte-derived macrophages in the inflamed paw was not altered, G2A-deficient mice had less macrophages in the direct vicinity of the origin of inflammation, an area marked by the presence of zymosan, neutrophil accumulation and proinflammatory cytokines. Fittingly neutrophil efferocytosis was decreased in G2A-deficient mice and several lipids, which are released by neutrophils and promote G2A-mediated chemotaxis, were increased in the inflamed tissue. Taken together, G2A is necessary to position macrophages in the proinflammatory microenvironment surrounding the center of inflammation. In absence of G2A the macrophages are localized in an antiinflammatory microenvironment and macrophage polarization is shifted toward M2-like macrophages
Polarization of human macrophages by interleukin-4 does not require ATP-citrate lyase
Full text linkMacrophages exposed to the Th2 cytokines interleukin (IL) IL-4 and IL-13 exhibit a distinct transcriptional response, commonly referred to as M2 polarization. Recently, IL-4-induced polarization of murine bone marrow-derived macrophages (BMDMs) has been linked to acetyl-CoA levels through the activity of the cytosolic acetyl-CoA-generating enzyme ATP-citrate lyase (ACLY). Here, we studied how ACLY regulated IL-4-stimulated gene expression in human monocyte-derived macrophages (MDMs). Although multiple ACLY inhibitors attenuated IL-4-induced target gene expression, this effect could not be recapitulated by silencing ACLY expression. Furthermore, ACLY inhibition failed to alter cellular acetyl-CoA levels and histone acetylation. We generated ACLY knockout human THP-1 macrophages using CRISPR/Cas9 technology. While these cells exhibited reduced histone acetylation levels, IL-4-induced gene expression remained intact. Strikingly, ACLY inhibitors still suppressed induction of target genes by IL-4 in ACLY knockout cells, suggesting off-target effects of these drugs. Our findings suggest that ACLY may not be the major regulator of nucleocytoplasmic acetyl-CoA and IL-4-induced polarization in human macrophages. Furthermore, caution should be warranted in interpreting the impact of pharmacological inhibition of ACLY on gene expression
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
Development of alphaviral vectors for macrophage activation in cancer immunotherapy
No full textAudzēju-iefiltrējošiem makrofāgiem piemīt gan spēja veicināt audzēja attīstību, gan inhibēt, attiecībā no to aktivācijas stāvokļa. In vitro pētījumos ir ticis parādīts, ka, iedarbojoties ar interferonu-g (IFN-γ) kopā ar Toll-like receptora (TLR) ligandu, tika ierosināts M1 makrofāgu fenotips, kas tiek asociēts ar audzēja iznīcināšanu. Audzēja imūnterapiju varētu nodrošināt M1 makrofāgu fenotipa inducēšana audzēju-iefiltrējošos makrofāgos. Šajā darbā mēs izvērtējām Semliki meža vīrusa (SFV) vektoru potenciālu makrofāgu aktivācijā pret vēzi. SFV tika izmantots, lai konstruētu replikācijas defektīvus konstruktus ar ieklonētiem peļu audzēja nekrozes faktora (mTNFα), peļu IFNγ un cilvēka IFNγ gēniem. Lai noteiktu SFV-mIFNγ vektora ekspresēta mIFNγ (vd-IFNγ) efektus in vitro, no peļu kaula smadzenēm izdalīti makrofāgi (BMDM) tika aktivēti ar vd-mIFNγ, un ietekme uz Lewis plaušu karcinomas (LLC) šūnu proliferāciju tika izmērīta. Mēs parādījām, ka vd-mIFNγ sinerģē ar TLR2 un TLR7 ligandiem, lai aktivētu makrofāgus un inhibētu LLC šūnu augšanu koncentrācijas atkarīgā manierē. Kā arī tika parādīts, ka vd-mIFNγ varētu tikt izmantots paaugstinātai makrofāgu aktivācijai uz vēža supresīvu fenotipu caur TLRs. Tika izvērtēts SFV-mIFNγ vektora efekts atsevišķi vai kopā ar TLR2 uz peļu dzīvildzi un audzēja attīstību pēc i.t. injekcijas LLC audzēja modelī NSG pelēs. Vislabākos dzīvildzes rādītājus uzrādīja SFV-mIFNγ kopā ar TLR2, bet audzēja inhibīcija tika novērota gan SFV-mIFNγ, gan SFV-mIFNγ + TLR2 liganda grupai. Šie rezultāti parādīja, ka SFV-mIFNγ var tikt izmantots kā terapeitisks līdzeklis vēža imūnoterapijā.Tumor-infiltrating macrophages may either promote or inhibit tumor growth depending on their activation status. In vitro studies have shown that treatment of macrophages with interferon-γ (IFN-γ) together with a Toll-like receptor (TLR) ligand induced an M1 phenotype associated with killing of cancer cells. Cancer immunotherapy may potentially be achieved by induction of such an M1 phenotype in tumor-infiltrating macrophages. Here, we investigated the potential of Semliki Forest virus (SFV) based vectors for macrophage activation against cancer. SFV based, replication deficient constructs incorporating mouse tumour necrosis factor-α (TNFα), mouse IFN-γ (mIFN and human IFN-γ (hIFN genes were developed. To study SFV-mIFN vector derived IFN (vd-mIFN) effects in vitro, murine bone marrow derived macrophages (BMDM) were challenged with vd-mIFN and impact on Lewis Lung Carcinoma (LLC) cell growth was measured. We showed that vd-mIFN synergised with TLR2 and TLR7 ligands to activate macrophages and inhibit LLC cell growth in concentration dependant manner. We demonstrated that vd-mIFN could be used for enhanced activation of macrophages to cancer suppressive phenotype through TLRs. The effect of SFV-mIFN vector alone or together with TLR2 ligand on animal survival and tumour growth inhibition was measured after intra-tumoural injections in LLC based tumor model in NSG mice. Therapy with SFV-mIFN together with TLR2 ligand showed the best survival rates, whereas tumour growth inhibition was observed for both, SFV-mIFN and SFV-mIFN together with TLR2 ligand groups. These results demonstrated that SFV-IFN could be used as a potential therapeutic agent in cancer immunotherapy
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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