4 research outputs found

    miR-155 overexpressing monocytes resemble HLA highISG15 + synovial tissue macrophages from patients with rheumatoid arthritis and induce polyfunctional CD4+ T cell activation

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    MicroRNAs (miRs) are known to regulate pro-inflammatory effector functions of myeloid cells, and miR dysregulation is implicated in rheumatoid arthritis (RA), a condition characterized by inflammation and destruction of the joints. We showed previously that miR-155 is increased in myeloid cells in RA and induces pro-inflammatory activation of monocytes and macrophages; however, its role at the interface between innate and adaptive immunity was not defined. Here, RNA-sequencing revealed that overexpression of miR-155 in healthy donor monocytes conferred a specific gene profile which bears similarities to that of RA synovial fluid-derived CD14+ cells and HLAhighISG15+ synovial tissue macrophages, both of which are characterized by antigen-presenting pathways. In line with this, monocytes in which miR-155 was overexpressed, displayed increased expression of HLA-DR and both co-stimulatory and co-inhibitory molecules, and induced activation of polyfunctional T cells. Together, these data underpin the notion that miR-155-driven myeloid cell activation in the synovium contributes not only to inflammation but may also influence the adaptive immune response

    Heritage Speakers as Part of the Native Language Continuum

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    We argue for a perspective on bilingual heritage speakers as native speakers of both their languages and present results from a large-scale, cross-linguistic study that took such a perspective and approached bilinguals and monolinguals on equal grounds. We targeted comparable language use in bilingual and monolingual speakers, crucially covering broader repertoires than just formal language. A main database was the open-access RUEG corpus, which covers comparable informal vs. formal and spoken vs. written productions by adolescent and adult bilinguals with heritage-Greek, -Russian, and -Turkish in Germany and the United States and with heritage-German in the United States, and matching data from monolinguals in Germany, the United States, Greece, Russia, and Turkey. Our main results lie in three areas. (1) We found non-canonical patterns not only in bilingual, but also in monolingual speakers, including patterns that have so far been considered absent from native grammars, in domains of morphology, syntax, intonation, and pragmatics. (2) We found a degree of lexical and morphosyntactic inter-speaker variability in monolinguals that was sometimes higher than that of bilinguals, further challenging the model of the streamlined native speaker. (3) In majority language use, non-canonical patterns were dominant in spoken and/or informal registers, and this was true for monolinguals and bilinguals. In some cases, bilingual speakers were leading quantitatively. In heritage settings where the language was not part of formal schooling, we found tendencies of register leveling, presumably due to the fact that speakers had limited access to formal registers of the heritage language. Our findings thus indicate possible quantitative differences and different register distributions rather than distinct grammatical patterns in bilingual and monolingual speakers. This supports the integration of heritage speakers into the native-speaker continuum. Approaching heritage speakers from this perspective helps us to better understand the empirical data and can shed light on language variation and change in native grammars. Furthermore, our findings for monolinguals lead us to reconsider the state-of-the art on majority languages, given recurring evidence for non-canonical patterns that deviate from what has been assumed in the literature so far, and might have been attributed to bilingualism had we not included informal and spoken registers in monolinguals and bilinguals alike

    Cell-specific Bioorthogonal Tagging of Glycoproteins

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    Altered glycoprotein expression is an undisputed corollary of cancer development. Understanding these alterations is paramount but hampered by limitations underlying cellular model systems. For instance, the intricate interactions between tumour and host cannot be adequately recapitulated in monoculture of tumour-derived cell lines. More complex co-culture models usually rely on sorting procedures for proteome analyses and rarely capture the details of protein glycosylation. Here, we report a strategy termed Bio-Orthogonal Cell line-specific Tagging of Glycoproteins (BOCTAG). Cells are equipped by transfection with an artificial biosynthetic pathway that transforms bioorthogonally tagged sugars into the corresponding nucleotide-sugars. Only transfected cells incorporate bioorthogonal tags into glycoproteins in the presence of non-transfected cells. We employ BOCTAG as an imaging technique and to annotate cell-specific glycosylation sites in mass spectrometry-glycoproteomics. We demonstrate application in co-culture and mouse models, allowing for profiling of the glycoproteome as an important modulator of cellular function

    ΜΕΛΕΤΗ ΤΩΝ ΙΣΟΜΟΡΦΩΝ ΤΟΥ ΚΟΛΛΑΓΟΝΟΥ XI (Α1) ΣΕ ΑΝΕΥΡΙΣΜΑΤΑ ΑΝΙΟΥΣΗΣ ΑΟΡΤΗΣ ΚΑΙ ΣΤΟΝ ΚΑΡΚΙΝΟ ΤΩΝ ΠΝΕΥΜΟΝΩΝ

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    Έχει αποδειχθεί ότι η έκφραση των κολλαγόνων αλλάζει στις κακοήθειες, ιδίως εκείνη του κολλαγόνου XI. Αυτό θα μπορούσε να επηρεάσει την ικανότητα των καρκινικών κυττάρων να εισβάλλουν στο στρώμα και να δημιουργούν μεταστάσεις. Η α1 αλυσίδα του κολλαγόνου XI (COL11A1 γονίδιο), μεταγράφεται μέσω εναλλακτικού ματίσματος σε τουλάχιστον τέσσερις διαφορετικές ισομορφές (Α, Β, C και Ε) που διαφέρουν ως προς την πρωτεόλυση του Ν-τελικού άκρου και δυνητικά, στον τρόπο που διευθετούν την εξωκυττάρια μήτρα. Οι ισομορφές δεν έχουν προηγουμένων μελετηθεί στον καρκίνο του πνεύμονα. Σκοπός της μελέτης ήταν αφού αναπτυχθούν νέες μεθοδολογίες για το γενικό COL11A1 μετάγραφο και την C ισομορφή στη συνέχεια να ποσοτικοποιηθούν όλα τα μετάγραφα και να διερευνηθεί η πιθανή συσχέτιση μεταξύ της διαφορικής έκφρασης τους και προγνωστικών παραμέτρων στον καρκίνο του πνεύμονα.It has been shown that the expression of collagen changes in malignancies, especially that of collagen XI. This would affect the ability of cancer cells to invade the stroma and metastasize. The a1 chain of collagen XI is transcribed from COL11A1 gene by alternative splicing in at least four different transcripts (A, B, C, and E). The corresponding protein isoforms differ in the proteolysis of the N- terminus and potentially, in the way that mediates extracellular matrix. Collagen isoforms have not previously been studied in lung cancer. The purpose of the study was the development of new methodologies for the general (total) COL11A1 transcript and C isoform (A and E were developed previously by our group), the quantification of all transcripts and the investigation of their potential association with histopathological prognostic factors in lung cancer
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