| 1. |
- Aguilar, Helena, et al.
(author)
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VAV3 mediates resistance to breast cancer endocrine therapy
- 2014
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In: Breast Cancer Research. - : BioMed Central. - 1465-5411 .- 1465-542X. ; 16:3, s. R53-
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor alpha (ERalpha) are among the most effective systemic treatments for ERalpha-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through mechanisms that involve ERalpha transcriptional regulatory plasticity. Here, we identify VAV3 as a critical component in this process.METHODS: A cell-based chemical compound screen was carried out to identify therapeutic strategies against resistance to endocrine therapy. Binding to ERalpha was evaluated by molecular docking analyses, an agonist fluoligand assay, and short-hairpin (sh) RNA-mediated protein depletion. Microarray analyses were performed to identify altered gene expression. Western blot of signaling and proliferation markers and shRNA-mediated protein depletion in viability and clonogenic assays were performed to delineate the role of VAV3. Genetic variation in VAV3 was assessed for association with the response to tamoxifen. Immunohistochemical analyses of VAV3 were carried out to determine the association with therapy response and different tumor markers. An analysis of gene expression association with drug sensitivity was carried out to identify a potential therapeutic approach based on differential VAV3 expression.RESULTS: The compound YC-1 was found to comparatively reduce the viability of cell models of acquired resistance. This effect was probably not due to activation of its canonical target (soluble guanylyl cyclase) but instead a result of binding to ERalpha. VAV3 was selectively reduced upon exposure to YC-1 or ERalpha depletion and, accordingly, VAV3 depletion comparatively reduced the viability of cell models of acquired resistance. In the clinical scenario, germline variation in VAV3 was associated with response to tamoxifen in Japanese breast cancer patients (rs10494071 combined P value = 8.4 x 10-4). The allele association combined with gene expression analyses indicated that low VAV3 expression predicts better clinical outcome. Conversely, high nuclear VAV3 expression in tumor cells was associated with poorer endocrine therapy response. Based on VAV3 expression levels and the response to erlotinib in cancer cell lines, targeting EGFR signaling may be a promising therapeutic strategy.CONCLUSIONS: This study proposes VAV3 as a biomarker and rationale signaling target to prevent and/or overcome resistance to endocrine therapy in breast cancer.
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| 2. |
- Arévalo-Soler, Josep, et al.
(author)
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Dynamic Converter Control Role Configuration in Grid of Grids
- 2023
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In: 2023 25th European Conference on Power Electronics and Applications, EPE 2023 ECCE Europe. - : Institute of Electrical and Electronics Engineers (IEEE).
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Conference paper (peer-reviewed)abstract
- The control role of power converters conforming an HVDC link is generally static, i.e. changing the control role of the power converters is not considered in the power system operation. In this paper a lab-scaled demonstration on the control role reconfiguration while an AC/DC/AC link is in operation is presented.
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| 3. |
- Benaiges-Fernandez, Robert, et al.
(author)
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Dissimilatory bioreduction of iron(III) oxides by Shewanella loihica under marine sediment conditions
- 2019
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In: Marine Environmental Research. - : Elsevier. - 0141-1136 .- 1879-0291. ; 151
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Journal article (peer-reviewed)abstract
- Shewanella is a genus of marine bacteria capable of dissimilatory iron reduction (DIR). In the context of deep-sea mining activities or submarine mine tailings disposal, dissimilatory iron reducing bacteria may play an important role in biogeochemical reactions concerning iron oxides placed on the sea bed. In this study, batch experiments were performed to evaluate the capacity of Shewanella loihica PV-4 to bioreduce different iron oxides (ferrihydrite, magnetite, goethite and hematite) under conditions similar to those in anaerobic sea sediments. Results showed that bioreduction of structural Fe(III) via oxidation of labile organic matter occurred in all these iron oxides. Based on the aqueous Fe (II) released, derived Fe(II)/acetate ratios and bioreduction coefficients seem to be only up to about 4% of the theoretical ones, considering the ideal stoichiometry of the reaction. A loss of aqueous Fe (II) was caused by adsorption and mineral transformation processes. Scanning electron microscope images showed that Shewanella lohica was attached to the Fe(III)-oxide surfaces during bioreduction. Our findings suggest that DIR of Fe(III) oxides from mine waste placed in marine environments could result in adverse ecological impacts such as liberation of trace metals in the environment.
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| 4. |
- Darquennes, Jeroen, et al.
(author)
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Language diversity management in higher education : towards an analytical framework
- 2020
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In: Sociolinguistica. - : Walter de Gruyter GmbH. - 0933-1883 .- 1865-939X. ; 34:1, s. 7-29
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Journal article (peer-reviewed)abstract
- Linguistic diversity and its management have become increasingly significant for higher education institutions around the world. Indeed, in the context of a growing student and staff mobility, information exchange, and networked multilateral interactions, the multiplicity of languages used by university stakeholders in more and more contexts has steadily grown over the past decades. A wide range of scholars (from applied and sociolinguists to higher education researchers) have responded with an equal growing attention to this phenomenon. In this paper, we funnel some of the relevant recent scholarship on the language-planning dimension of the internationalization of higher education, providing as a result an analytical framework that attempts to capture the complex sociolinguistic nature of present-day universities. To date, with only a handful of exceptions, few attempts have been made to provide a comprehensive overview of the different levels, stakeholders, and contexts of language use in higher education. Given the rapid changing nature of language matters in such context, the framework we present in this paper should be useful to both sociolinguists interested in language issues in higher education and to on-the-ground university administrators actively engaged in language planning initiatives in their institutions. The framework, however, is not conceived of as a closed-end solution to language problems at universities today, but rather as a guiding roadmap to think productively about such issues.
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| 5. |
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| 6. |
- Darquennes, Jeroen, et al.
(author)
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‘New speakers’ and language policy research : thematic and theoretical contributions to the field
- 2019
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In: Language Policy. - : Springer Science and Business Media LLC. - 1568-4555 .- 1573-1863. ; 18:4, s. 475-491
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Journal article (peer-reviewed)abstract
- In this article, we reflect on the extent to which ‘new speaker’ research feeds into recent theoretical discussions in language policy scholarship, especially in connection to the discursive and ethnographically oriented perspectives which of late have become increasingly prominent. We begin with a brief overview of the ‘new speaker’ concept, its theoretical and empirical origins, and then we situate the discussions on ‘new speakers’ against the background of traditional language policy research. Thereafter the bulk of the article is dedicated to developing two main arguments: first, we provide an overview of the language policy themes that are already present in ‘new speaker’ research; and secondly, we elaborate on how ‘new speaker’ studies can contribute to current discussions in the field of language policy. We conclude with a short overview of future research directions that, in our view, can strengthen the link and the mutual benefits of the connection between ‘new speaker’ and language policy scholarship.
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| 7. |
- Docherty, Anna R, et al.
(author)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Journal article (peer-reviewed)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 8. |
- Erdocia, Iker, et al.
(author)
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English language and the career progression of academics in Anglophone universities
- 2023
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In: Higher Education. - 0018-1560 .- 1573-174X.
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Journal article (peer-reviewed)abstract
- This study aims to contribute to the ongoing scholarly debate about linguistic privilege in academia. The article pushes this debate forward by considering the role of English in the career development of academics in Anglophone universities. More concretely, our study empirically explores the career trajectories of multilingual scholars in Ireland who speak English as an additional language (EAL). Adopting a Bourdieusian lens, the article conceptualises academia as a locus of competitive struggle over authority, recognition, and prestige, in which scholars avail themselves of different kinds of capital, including linguistic capital, and deploy strategies to flourish. Through a qualitative approach, the article examines data from university documents and procedures, from interviews with EAL scholars in different disciplines and at different stages of their career, and from interviews with academics holding senior management positions in three universities in Dublin. We analyse the language-related challenges that EAL scholars encounter and the affordances with which Anglophone universities provide them, as well as the ways in which language impacts on their career progression. The empirical data reveals a complex and nuanced interplay between language and other academic factors. Our findings suggest the need to go beyond simple hierarchies of academic privilege or disadvantage based on a scholar’s first or additional language alone.
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| 9. |
- Erdocia, Iker, et al.
(author)
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In pursuit of epistemic authority in public intellectual engagement : the case of language and gender
- 2024
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In: Multilingua - Journal of Cross-cultural and Interlanguage Communication. - 0167-8507 .- 1613-3684. ; 43:1, s. 91-118
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Journal article (peer-reviewed)abstract
- Public intellectual life is an area of inquiry that has not received a great deal of attention within the field of sociolinguistics. This article investigates the performative dimension of public intellectual engagement in the area of language and gender and, more specifically, how epistemic authority about gender-neutral language is constructed in public intellectual contributions in Catalonia, Spain. Adopting Arendt’s notion of truth claim and the Foucauldian concepts of regimes of truth and epistemic sovereignty, we empirically examine the mechanisms of reception and validation of the public engagements of one highly visible linguistic scholar. Our study shows the ways in which this intellectual figure strives to be recognised as having exclusive scientific authority about language. We argue that pursuing the allegedly impartial standpoint of epistemic authority about gender and language inevitably advances the interests of specific political actors and large media corporations of a conservative strand that fervently oppose gender-neutral language.
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| 10. |
- Erdocia, Iker, et al.
(author)
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Sociolinguists and their publics : Epistemologicaltension and disciplinary contestation over languagein Catalonia
- 2022
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In: Journal of Sociolinguistics. - : Wiley. - 1360-6441 .- 1467-9841. ; 26:1, s. 45-64
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Journal article (peer-reviewed)abstract
- This article aims to investigate the relationship of sociolinguists with the publics in Catalonia and to disentangle the complex interrelationships among academics within the discipline. By examining material from mainstream media outlets and data from interviews with a selected number of sociolinguist scholars, we show how the public sphere is a site in which competing epistemological and disciplinary visions contest for discursive dominance in language-in-society matters, institutional authorization, and resources. Rather than seeing the engagement of sociolinguists with publics as a disinterested activity of knowledge dissemination and the provision of facts, we argue that the publics are better conceived as a terrain toward which sociolinguists direct institutional, disciplinary, and professional interests. Ultimately, our article contributes to a more encompassing understanding of ourselves as sociolinguists.
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