2,723 research outputs found

    A balancing act: Agency and constraints in university students’ understanding of and responses to sexual violence in the night-time economy

    Get PDF
    The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Open Access articleThis paper extends our understanding of how university students make sense of, and respond to, sexual violence in the night-time economy (NTE). Based on semi-structured interviews with 26 students in a city in England, we examine students’ constructions of their experiences of sexual violence within the NTE, exploring their negotiations with, and resistance to, this violence. Building upon theories of postfeminism, we interrogate the possibilities for resistance within the gendered spaces of the NTE and propose a disaggregated conceptualisation of agency to understand responses to sexual violence, thereby offering useful insights for challenging sexual violence in the NTE and in universities

    Masculinizing Care? Gender, Ethics of Care, and Fathers' Rights Groups

    Get PDF
    This article contributes to theoretical debates around caring masculinity, especially attempts to integrate feminist ethics of care with masculinities scholarship. I apply ethics of care and masculinities theories to an illustrative case study of fathers’ rights group (FRG), (Real) Fathers 4 Justice, who, I argue, employ aspects of care perspectives framed as a “new man/new father” masculinity. Applying ethics of care to analyze caring masculinities demonstrates that men care and that caring masculinity can potentially destabilize dominant notions of masculinity. However, care is also coded masculine in complex, sometimes troubling, ways. The promise of masculinized care in the context of fathers’ rights is limited as, ultimately, gender binaries are reinforced more than they are rendered contingent. As well as contributing to analyses of the gender politics of FRGs, I argue that we should pay careful attention to the contexts within which caring masculinities may be strategically and problematically employed

    Crisis, what crisis? A feminist analysis of discourse on masculinities and suicide

    Get PDF
    High male suicide rates are often constructed as evidence for an apparent “crisis of masculinity”. Conversely, “crisis of masculinity” has been used to explain differential rates of male and female suicide in the UK (and elsewhere). We analyse three public cases where male suicide and “masculinity-crisis” discourse are employed together. Our feminist analysis demonstrates that “crisis talk” and male suicide are addressed in divergent ways. We therefore distinguish between “progressive” and “conservative” crisis narratives. Conservative narratives position high male suicide rates as a pernicious outcome of “threats” to traditional gender roles and norms, suggesting the solution is to return to them. Contrastingly, progressive crisis accounts use male suicide to demonstrate that existing gender norms harm men as well as women and argue they should be altered to address male suicide. Conservative narratives often map on to anti-feminist politics, whereas progressive accounts reflect aspects of feminism. There is no neat feminist/anti-feminist distinction, however, as postfeminist ideas are also evident. We argue that, overall, each of the articulations of a “crisis of masculinity” as evidenced by high rates of male suicide reinforces problematic gender politics. Further, in reifying simplistic, dualistic models of gender, they may ultimately constrain efforts to reduce suicide

    Treatment of Polarized Cystic Fibrosis Airway Cells With HGF Prevents VX-661-Rescued F508del-CFTR Destabilization Caused by Prolonged Co-exposure to VX-770

    Get PDF
    Cystic fibrosis (CF), the most common inherited disease in Caucasians, is caused by mutations in CFTR, the most frequent of which is F508del. F508del causes ER retention and degradation of the mutant CFTR protein, but also defective channel gating and decreased half-life at the plasma membrane. Despite the recent successes with small molecule CFTR modulator drugs, the folding-corrector/gating-potentiator drug combinations approved for CF individuals carrying F508del-CFTR have sometimes produced severe side effects. Previously, we showed that a prolonged, 15-days treatment of polarized bronchial epithelial monolayers with the VX-809+VX-770 combination resulted in epithelial dedifferentiation effects that we found were caused specifically by VX-809. Moreover, prolonged VX-770 exposure also led to the destabilization of VX-809-rescued F508del-CFTR. Notably, co-treatment with the physiological factor HGF prevented VX-809-mediated epithelial differentiation and reverted the destabilizing effect of VX-770 on VX-809-rescued CFTR. Here, we show that prolonged treatment with VX-661, a second-generation corrector developed based on VX-809 structure, does not perturb epithelial integrity of polarized bronchial epithelial monolayers. Yet, its efficacy is still affected by co-exposure to VX-770, the potentiator present in all VX-661-containing combination therapies approved in the United States and Europe for treatment of F508del-CFTR carriers. Importantly, we found that co-treatment with HGF still ameliorated the impact of VX-770 in F508del-CFTR functional rescue by VX-661, without increasing cell proliferation (Ki-67) or altering the overall expression of epithelial markers (ZO-1, E-cadherin, CK8, CK18). Our findings highlight the importance of evaluating the cellular effects of prolonged exposure to CFTR modulators and suggest that the benefits of adding HGF to current combination therapies should be further investigated.This work was supported by the Grant PTDC/BIA-CEL/28408/2017 (to PJ and PM) and Center Grant UID/MULTI/04046/2019 to BioISI, both from the Portuguese Fundação para a CiĂȘncia e a Tecnologia.info:eu-repo/semantics/publishedVersio

    The politics of LGBT+ suicide and suicide prevention in the UK:Risk, responsibility and rhetoric

    Get PDF
    Suicide is a major public health concern, patterned by systematic inequalities, with lesbian, gay, bisexual and trans (LGBT+) people being one example of a minoritised group that is more likely to think about and attempt suicide worldwide. To address this, UK national suicide prevention policies have suggested that LGBT+ people should be prioritised in prevention activities. However, there is little research seeking to understand how LGBT+ suicide is re/presented in political and policy spheres. In this article, we critically analyse all mentions of LGBT+ suicide in UK parliamentary debates between 2009-2019 and in the eight suicide prevention policies in use during this period. We argue that LGBT+ suicide is understood in two contrasting ways: firstly, as a pathological ‘problem’, positioning LGBT+ people either as risks or as at risk and in need of mental health support. Alternatively, suicide can be seen as externally attributable to perpetrators of homophobic, biphobic and transphobic hate, requiring anti-hate activities as part of suicide prevention. In response, we argue that although these explanations may appear oppositional; they both draw on reductive explanations of LGBT+ suicide, failing to consider the complexity of suicidal distress, thus constraining understandings of suicide and suicide prevention

    YES1 Kinase Mediates the Membrane Removal of Rescued F508del-CFTR in Airway Cells by Promoting MAPK Pathway Activation via SHC1

    Get PDF
    (This article belongs to the Section Molecular Biology)Recent developments in CFTR modulator drugs have had a significant transformational effect on the treatment of individuals with Cystic Fibrosis (CF) who carry the most frequent F508del- CFTR mutation in at least one allele. However, the clinical effects of these revolutionary drugs remain limited by their inability to fully restore the plasma membrane (PM) stability of the rescued mutant channels. Here, we shed new light on the molecular mechanisms behind the reduced half-life of rescued F508del-CFTR at the PM of airway cells. We describe that YES1 protein kinase is enriched in F508del-CFTR protein PM complexes, and that its interaction with rescued channels is mediated and dependent on the adaptor protein YAP1. Moreover, we show that interference with this complex, either by depletion of one of these components or inhibiting YES1 activity, is sufficient to significantly improve the abundance and stability of modulator-rescued F508del-CFTR at the surface of airway cells. In addition, we found that this effect was mediated by a decreased phosphorylation of the scaffold protein SHC1, a key regulator of MAPK pathway activity. In fact, we showed that depletion of SHC1 or inhibition of MAPK pathway signaling was sufficient to improve rescued F508del-CFTR surface levels, whereas an ectopic increase in pathway activation downstream of SHC1, through the use of a constitutively active H-RAS protein, abrogated the stabilizing effect of YES1 inhibition on rescued F508del-CFTR. Taken together, our findings not only provide new mechanistic insights into the regulation of modulator-rescued F508del-CFTR membrane stability, but also open exciting new avenues to be further explored in CF research and treatment.Funding: This work was supported by the Grant PTDC/BIA-CEL/28408/2017 (to PJ and PM) and Center Grant UID/MULTI/04046/2019 to BioISI from the Portuguese Fundação para a CiĂȘncia e a Tecnologia.info:eu-repo/semantics/publishedVersio

    Synonymous Codon Pair Recoding of the HIV-1 env Gene Affects Virus Replication Capacity

    Get PDF
    Synonymous codon pair deoptimization is an efficient strategy for virus attenuation; however, the underlying mechanism remains controversial. Here, we optimized and deoptimized the codon pair bias (CPB) of the human immunodeficiency virus type 1 (HIV-1) envelope (env) gene to investigate the influence of env synonymous CPB recoding on virus replication capacity, as well as the potential mechanism. We found that env CPB deoptimization did not always generate attenuation, whereas CPB optimization attenuated virus replication in MT-4 cells. Furthermore, virus attenuation correlated with reduced Env protein production but not with decreased viral RNA synthesis. Remarkably, in our model, increasing the number of CpG dinucleotides in the 5' end of env did not reduce the replication capacity of HIV-1. These results indicate that factors other than CPB or CpG content may have impacted the viral fitness of the synonymously recoded study variants. Our findings provide evidence that CPB recoding-associated attenuation can affect translation efficiency. Moreover, we demonstrated that an increased number of CpGs in the 5' end of HIV-1 env is not always associated with reduced virus replication capacity

    Tribute to the research of liturgical ambiences in church architecture from the Zadar area in the periods of Early Christianity and Early Middle Ages

    Get PDF
    U radu se donose nove spoznaje o liturgijskim ambijentima u crkvenoj arhitekturi sa zadarskog područja iz vremena kasne antike te ranog srednjeg vijeka. Daje se naglasak na one dodane ambijente koji su obiljeĆŸili ranokrơćansku arhitekturu te su tako utjecali na izvođenje liturgijskog obreda. Pritom se ukazuje na specifičnosti koje su zastupljene na razmatranom području. Posebno se analiziraju liturgijski ambijenti koji se crkvenim građevinama dodaju u razdoblju predromanike i romanike jer tada pod utjecajem Bizantske crkve nastaju promjene u liturgiji. Od 9. stoljeća razvija se kult zadarskih svetaca, ĆĄto je u razdoblju kasne antike bilo nepoznato. S vremenom nastaju posve novi sakralni prostori ili manji ambijenti namijenjeni za liturgiju posvećenu relikvijama. U tome kontekstu ukazuje se na značenje tih sakralnih prostora koji su utjecali na daljnji razvoj crkvene arhitekture tijekom romanike, ali i u kasnijim stoljećima.In this paper, the author presents new knowledge regarding liturgical ambiences in church architecture from the Zadar area in the periods of Late Antiquity and Early Middle Ages. In the first part of the paper, the author analyses those ambiences that were usually added to sacral objects during Early Christianity due to being needed in liturgical celebrations. A fact of major interest is that ambiences such as narthexes or pastophories had not been included from the earliest days of church building; they had not been introduced in church architecture before the 6th century. During this period, the number of newly erected baptisteries was almost doubled. New ambiences, such as cathecumenium and consignatorium, were introduced in the 6th century; this was an indication that the liturgical ritual was developed, and that the number of the baptised grew. The second part of the paper tackles liturgical ambiences added to sacral buildings in the Pre-Romanic and Romanic periods. The most comprehensive interventions were made in Zadar’s central basilica of St. Peter, extended in the Pre-Romanic period by pastophories and the crypt, which considerably enlarged the space of its presbytery. In the Pre-Romanic and Romanic periods, side apses often appeared as liturgical ambiences in sacral objects. Simple smaller niches, mainly incorporated into the mass of the sidewalls, occasionally replaced them. The added apses and niches were undoubtedly intended to serve as separate praying sites within the existing churches. Since such smaller ambiences mainly served for liturgy including relics, it may be concluded that their existence was registered following the development of the cult of Christian saints in the Zadar area, that is to say, from the 9th century onwards. Introducing additional praying sites within or next to the existing churches enabled celebrating multiple daily liturgies during the Middle Ages, which was not the case in Late Antiquity