1,859 research outputs found

    Use of computed tomography imaging during long-term follow-up of nine feline tuberculosis cases

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    Case series summary: Feline tuberculosis is an increasingly recognised potential zoonosis of cats. Treatment is challenging and prognosis can vary greatly between cases. Pulmonary infection requires extended courses of antibiotics, but methodologies for sensitively monitoring response to treatment are currently lacking. In this case series, we retrospectively examined the serial computed tomography (CT) findings in nine cats that had been diagnosed with tuberculosis. Changes in pathology (where applicable to tuberculosis) were correlated with the clinical presentation of each of the cats, the treatment protocol, and previous and contemporary diagnostic investigations. This study found that changes in CT findings during the medium- to long-term management of feline tuberculosis were highly variable between cats. The majority of cats had reduced pathology at re-examination during anti-tuberculous therapy, but pathology only resolved in a minority of cases. In some cases recurrence of pathology detected by CT imaging preceded clinical deterioration, allowing for rapid therapeutic intervention. Relevance and novel information: When considered in combination with clinical findings, CT studies can aid in decision making regarding tapering of antibiotic protocols, or reintroduction of therapy in cases of recurrence or reinfection. This series also highlights that, in some cases, persistent abnormalities can be detected by CT, so complete resolution of CT pathology should not always be a goal in the management of feline tuberculosis

    Protein proximity networks and functional evaluation of the casein kinase 1 gamma family reveal unique roles for CK1γ3 in WNT signaling

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    Aberrant activation or suppression of WNT/β-catenin signaling contributes to cancer initiation and progression, neurodegeneration, and bone disease. However, despite great need and more than 40 years of research, targeted therapies for the WNT pathway have yet to be fully realized. Kinases are considered exceptionally druggable and occupy key nodes within the WNT signaling network, but several pathway-relevant kinases remain understudied and dark. Here, we studied the function of the casein kinase 1γ (CSNK1γ) subfamily of human kinases and their roles in WNT signaling. miniTurbo-based proximity biotinylation and mass spectrometry analysis of CSNK1γ1, CSNK1γ2, and CSNK1γ3 revealed numerous components of the β-catenin-dependent and β-catenin-independent WNT pathways. In gain-of-function experiments, we found that CSNK1γ3 but not CSNK1γ1 or CSNK1γ2 activated β-catenin-dependent WNT signaling, with minimal effect on other signaling pathways. We also show that within the family, CSNK1γ3 expression uniquely induced low-density lipoprotein receptor-related protein 6 phosphorylation, which mediates downstream WNT signaling transduction. Conversely, siRNA-mediated silencing of CSNK1γ3 alone had no impact on WNT signaling, though cosilencing of all three family members decreased WNT pathway activity. Finally, we characterized two moderately selective and potent small-molecule inhibitors of the CSNK1γ family. We show that these inhibitors and a CSNK1γ3 kinase-dead mutant suppressed but did not eliminate WNT-driven low-density lipoprotein receptor-related protein 6 phosphorylation and β-catenin stabilization. Our data suggest that while CSNK1γ3 expression uniquely drives pathway activity, potential functional redundancy within the family necessitates loss of all three family members to suppress the WNT signaling pathway

    Staff and student perspectives of online teaching and learning : implications for belonging and engagement at university : a qualitative exploration

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    A sense of belonging within higher education (HE) enhances educational engagement and attainment. The rapid shift to online provision has implications for reducing students’ sense of belonging at university. We have previously shown that students consider belonging in HE to be important and that their personal sense of belonging was high. We also found that sense of belonging had elements of people and place: relationships with peers and staff were influential and the physical campus facilitated social relationships. In the first lockdown, we showed that sense of belonging in both staff and students at our large widening-participation London university was reduced. In this paper, we report on a continuing project to explore the impact of sustained provision of learning online, focusing on qualitative interviews carried out with forty-three students and twenty-three staff. Both groups identified advantages and disadvantages of online provision. Advantages included flexibility and accessibility, with savings – financial and time – owing to reduced commuting. However, both groups identified a negative impact on social relationships, student motivation and engagement. Future development of blended learning should be planned, supported and structured to optimise the benefits

    Sarah: historiografkinja prošlosti i sadašnjosti žene francuskog poručnika

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    The article argues that Sarah, the title character of Fowles’ novel The French Lieutenant’s Woman (1969), resists the oppressive ideology of her time by writing her own historiography. In the process, not only does she emplot a tragic past for herself but she also insists on being identified as a depraved woman in the present. The analysis attempts to highlight the fact that Sarah, like a historiographer, selects the referents for her historiography—Mrs. Poulteney and Charles—and imposes her emplotment and prefiguration on her historiography of both her past and present. Employing Hayden White’s theories of postmodern historiography and Linda Hutcheon’s concept of historiographic metafiction, the paper illustrates ways in which Sarah historicizes her own past through tragic emplotment and metaphoric prefiguration of her narrative in order to convey her anarchist ideology, at the same time portraying herself as the “Woman” who has been abandoned by the French Lieutenant. Furthermore, by means of her historiography of the present, she imposes her liberal ideology through satiric emplotment of her fictional construct and ironic prefiguration of the referents of textualized oppression in society. She ironically puts Mrs. Poulteney and Charles in the situations in which their oppressive ideology is unraveled; in this way, she satirizes the codes of behavior of her present time.U članku se tvrdi da se Sarah, naslovni lik Fowlesova romana Ženska francuskog poručnika (1969), opire opresivnoj ideologiji svojega vremena pišući vlastitu historiografiju. Na taj način ona fabulira tragičnu prošlost za sebe i inzistira na tome da ju se percipira kao izopačenu ženu u sadašnjosti. Analiza pokušava istaknuti činjenicu da Sarah, poput povjesničara, odabire referente za svoju historiografiju – gđu Poulteney i Charlesa – i nameće svoju fabulaciju i prefiguraciju historiografije vlastite prošlosti i sadašnjosti. Koristeći se teorijom postmoderne historiografije Haydena Whitea i konceptom historiografske metafikcije Linde Hutcheon, rad prikazuje načine na koje Sarah historizira vlastitu prošlost kroz tragičnu fabulaciju i metaforičku prefiguraciju svoje pripovijesti kako bi istaknula svoju anarhističku ideologiju i istodobno sebe prikazala kao „žensku“ koju je napustio francuski poručnik. Nadalje, pomoću svoje historiografije sadašnjosti ona nameće svoju liberalnu ideologiju satiričkom fabulacijom svog fikcionalnog konstrukta i ironičnom prefiguracijom referenata tekstualiziranog društvenog ugnjetavanja. Na ironičan način, ona gospođu Poulteney i Charlesa stavlja u situacije u kojima se njihova represivna ideologija razotkriva; na taj način satirizira kodove ponašanja u svojoj sadašnjosti
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