36 research outputs found

    Focusing Knowledge-based Graph Argument Mining via Topic Modeling

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    Decision-making usually takes five steps: identifying the problem, collecting data, extracting evidence, identifying pro and con arguments, and making decisions. Focusing on extracting evidence, this paper presents a hybrid model that combines latent Dirichlet allocation and word embeddings to obtain external knowledge from structured and unstructured data. We study the task of sentence-level argument mining, as arguments mostly require some degree of world knowledge to be identified and understood. Given a topic and a sentence, the goal is to classify whether a sentence represents an argument in regard to the topic. We use a topic model to extract topic- and sentence-specific evidence from the structured knowledge base Wikidata, building a graph based on the cosine similarity between the entity word vectors of Wikidata and the vector of the given sentence. Also, we build a second graph based on topic-specific articles found via Google to tackle the general incompleteness of structured knowledge bases. Combining these graphs, we obtain a graph-based model which, as our evaluation shows, successfully capitalizes on both structured and unstructured data

    Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells

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    Self-renewing tissue-resident macrophages are thought to be exclusively derived from embryonic progenitors. However, whether circulating monocytes can also give rise to such macrophages has not been formally investigated. Here we use a new model of diphtheria toxin-mediated depletion of liver-resident Kupffer cells to generate niche availability and show that circulating monocytes engraft in the liver, gradually adopt the transcriptional profile of their depleted counterparts and become long-lived self-renewing cells. Underlining the physiological relevance of our findings, circulating monocytes also contribute to the expanding pool of macrophages in the liver shortly after birth, when macrophage niches become available during normal organ growth. Thus, like embryonic precursors, monocytes can and do give rise to self-renewing tissue-resident macrophages if the niche is available to them

    A Universal Cognitive Bias in Word Order:Evidence From Speakers Whose Language Goes Against It

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    There is a long-standing debate in cognitive science surrounding the source of commonalities among languages of the world. Indeed, there are many potential explanations for such commonalities—accidents of history, common processes of language change, memory limitations, constraints on linguistic representations, and so on. Recent research has used psycholinguistic experiments to provide empirical evidence linking common linguistic patterns to specific features of human cognition, but these experiments tend to use English speakers, who in many cases have direct experience with the common patterns of interest. Here we highlight the importance of testing populations whose languages go against cross-linguistic trends. We investigate whether adult monolingual speakers of Kîîtharaka, which has an unusual way of ordering words, mirror the word-order preferences of English speakers. We find that they do, supporting the hypothesis that universal cognitive representations play a role in shaping word order.</p

    Longitudinal changes in telomere length in PCB-exposed individuals: interaction with CMV infection

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    We recently demonstrated a significant shortening of age-adapted telomere length (TL) in lymphocytes of polychlorinated biphenyls (PCB)-exposed individuals. Here, we analyzed TL in individuals of the same PCB-exposed cohort during a 6-year follow-up period, investigating the change in TL between the first and second measurement as a function of time, concentration of PCBs and cytomegalovirus (CMV) infection. The age-adjusted TL of lymphocytes within the cohort of PCB-exposed individuals recovered from a first assessment in 2011 to a second assessment in 2017. Remarkably, if the concentration of lower chlorinated PCBs (LC PCBs) in 2011 was high (≥ 0.055 µg/L), the TL of CMV seropositive individuals remained significantly shortened both compared to age-adjusted controls as well as intra individually. This was confirmed by analysis of covariance as well as by multivariate linear mixed effects models. Since telomeres are responsive to various stress response pathways, including viral infection, we conclude that PCBs could contribute to immune senescence-like phenotypes associated with CMV infections and exacerbate negative aspects associated with the aging of the immune system

    Ly6C- Monocytes Regulate Parasite-Induced Liver Inflammation by Inducing the Differentiation of Pathogenic Ly6C+ Monocytes into Macrophages

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    Monocytes consist of two well-defined subsets, the Ly6C(+) and Ly6C(-) monocytes. Both CD11b(+) myeloid cells populations have been proposed to infiltrate tissues during inflammation. While infiltration of Ly6C(+) monocytes is an established pathogenic factor during hepatic inflammation, the role of Ly6C(-) monocytes remains elusive. Mice suffering experimental African trypanosome infection die from systemic inflammatory response syndrome (SIRS) that is initiated by phagocytosis of parasites by liver myeloid cells and culminates in apoptosis/necrosis of liver myeloid and parenchymal cells that reduces host survival. C57BL/6 mice are considered as trypanotolerant to Trypanosoma congolense infection. We have reported that in these animals, IL-10, produced among others by myeloid cells, limits the liver damage caused by pathogenic TNF-producing Ly6C(+) monocytes, ensuring prolonged survival. Here, the heterogeneity and dynamics of liver myeloid cells in T. congolense-infected C57/BL6 mice was further dissected. Moreover, the contribution of Ly6C(-) monocytes to try-panotolerance was investigated. By using FACS analysis and adoptive transfer experiments, we found that the accumulation of Ly6C(-) monocytes and macrophages in the liver of infected mice coincided with a drop in the pool of Ly6C(+) monocytes. Pathogenic TNF mainly originated from Ly6C(+) monocytes while Ly6C(-) monocytes and macrophages were major and equipotent sources of IL-10 within myeloid cells. Moreover, Nr4a1 (Nur77) transcription factor-dependent Ly6C(-) monocytes exhibited IL-10-dependent and cell contact-dependent regulatory properties contributing to trypanotolerance by suppressing the production of TNF by Ly6C(+) monocytes and by promoting the differentiation of the latter cells into macrophages. Thus, Ly6C(-) monocytes can dampen liver damage caused by an extensive Ly6C(+) monocyte-associated inflammatory immune response in T. congolense trypanotolerant animals. In a more general context, Ly6C(-) or Ly6C(+) monocyte targeting may represent a therapeutic approach in liver pathogenicity induced by chronic infection

    Ly6C<sup>-</sup> monocytes induce differentiation of Ly6C<sup>+</sup> monocytes into macrophages in <i>T</i>. <i>congolense</i>-infected WT mice.

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    <p><b>(A)</b> Liver MHC-II<sup>- to lo</sup> Ly6C<sup>-</sup> monocytes (Ly6C<sup>-</sup> Mo) purified from CX<sub>3</sub>CR1-GFP<sup>+/-</sup> mice at day 21 pi were transferred in CD45.1 WT mice at day 4 and day 6 pi. Control mice received HBSS. At day 7 pi, percentages of Ly6C<sup>+</sup> monocytes (Ly6C<sup>+</sup> Mo), Ly6C<sup>-</sup> monocytes (Ly6C<sup>-</sup> Mo) and macrophages (MF) within liver non-parenchymal cells were determined in recipient mice. Data are shown as mean + SD of 3 individual mice of one representative out of three independent experiments. *p<0.05 compared to control mice. <b>(B)</b> GFP<sup>+</sup> Ly6C<sup>+</sup> monocytes purified from CD45.2 LysM-GFP mice at day 7 pi were transferred in CD45.1 WT mice at day 12 pi with or without MHC-II<sup>-to lo</sup> Ly6C<sup>-</sup> monocytes gated as described in S5A Fig in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004873#ppat.1004873.s001" target="_blank">S1 Text</a> and purified from CD45.2 WT mice at day 21 pi. After 48 h, liver CD45.2<sup>+</sup> GFP<sup>+</sup> cells in recipient mice were analyzed for CD11b and Ly6C expression. MHC-II expression was then investigated in Ly6C<sup>-</sup> CD11b<sup>+</sup> cells. FACS profiles are representative of 1 out of 9 mice tested in three independent experiments. Percentages of cells in indicated gates are shown as mean ± SD of 3 individual mice of one representative out of three independent experiments. <b>(C)</b> TNF and <b>(D)</b> IL-10 concentration in supernatants of liver non-parenchymal cell cultures from recipient mice. <b>(E)</b> ALT levels in blood serum from recipient mice. Data are shown as mean + SD of 3 individual mice of one representative out of three independent experiments. *p<0.05 compared to recipient mice receiving only Ly6C<sup>+</sup> monocytes.</p

    Differentiation of Ly6C<sup>+</sup> monocytes into macrophages requires a physical contact with Ly6C<sup>-</sup> monocytes.

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    <p><b>(A)</b> Ly6C<sup>+</sup> monocytes (Ly6C<sup>+</sup> Mo) purified from <i>T</i>. <i>congolense</i>-infected CD45.2 WT mice at day 6 pi were cultured alone or with MHC-II<sup>- to lo</sup> Ly6C- monocytes (Ly6C<sup>-</sup> Mo) purified from infected CD45.2 LysM-GFP mice at day 21 pi (1: 1 ratio). Similar cultures were performed in transwell plates. Expression of Ly6C, F4/80, Mertk, CD64 or MHC-II (white line) was investigated 7 days later on GFP<sup>-</sup> Ly6C<sup>+</sup> monocyte-derived cells gated as in S5A Fig in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004873#ppat.1004873.s001" target="_blank">S1 Text</a> (grey line: isotype control). Results are representative of 1 out of 9 mice tested in 3 independent experiments. <b>(B)</b> TNF concentration in cell culture supernatants was measured. Data are shown as mean + SD of 1 representative out of three independent experiments. * p<0.05 compared to Ly6C<sup>+</sup> monocytes cultured alone; § p<0.05 comparing populations linked by horizontal bar.</p
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