Thatcherism and Popular Culture

Editors' introduction to a special issue on Thatcherism and popular culture.</p

Viihdettä vai valistusta? Fasistiset ja äärikonservatiiviset vaihtoehtohistoriat 2010-luvun televisioviihteessä ja uuspopulistisessa ruohonjuuritason politiikassa

Alternative histories are part of today’s ‘alternative understanding’, in which expertise and facts are no longer necessarily central to the definitions of history. This article focuses in particular on four alternative historical prestige television series examining fascism in its various forms, The Man in the High Castle (2015–), SS-GB (2017), The Plot Against America (2020), and The Handmaid’s Tale (2017), and their appearance in the grassroots politics of the 2010s. In particular, the election of Donald Trump as president of the United States in November 2016 brought to life alternative historical depictions – novels and films – previously widely featured in US public and media life in the 1930s, in which the United States also slipped into fascism or authoritarianism. Movements such as #MeToo and Black Lives Matter also strongly coloured the contemporary experience attached to the traumatic memories of US history. The Brexit vote in June 2016, which led to Britain’s withdrawal from the European Union, sparked similar political and cultural activism in the UK. The article examines the effectual historical context of the series, their audio-visual aesthetics, public history dynamics, and alternative historical speculations in the activities of both the neo-populists and civil rights groups.Erityisesti Donald Trumpin valinta Yhdysvaltain presidentiksi marraskuussa 2016 herätti henkiin aiemmin 1930-luvulla yhdysvaltalaisessa julkisuudessa laajasti esillä olleet vaihtoehtohistorialliset esitykset – romaanit ja elokuvat – joissa Yhdysvallat liukui Euroopan vanavedessä erityisen amerikkalaisen fasismin tai autoritäärisyyden hallintaan. Myös #MeToo- ja Black Lives Matter -identiteettipolitiikkaan kytkeytynyt liikehdintä väritti vahvasti aikalaiskokemusta, joka kiinnittyi Yhdysvaltain historian traumaattisiin muistoihin. Kesäkuussa 2016 toteutunut Brexit-äänestys, joka johti Britannian eroamiseen Euroopan unionista, synnytti vastaavaa poliittista ja kulttuurista liikehdintää Yhdistyneessä kuningaskunnassa. Vaihtoehtohistorioista on kasvanut osa tämän päivän ”vaihtoehtoista ymmärrystä”, jossa asiantuntijuus ja faktat eivät enää välttämättä ole historiaa koskevien määrittelyjen keskiössä. Tämä artikkeli keskittyy erityisesti neljään fasismia sen eri muodoissa tarkastelevaan vaihtoehtohistorialliseen prestiisitelevisiosarjaan, The Man in the High Castle (2015–), SS-GB (2017), The Plot Against America (2020) ja The Handmaid’s Tale (2017–), joissa historiallisia tapahtumia muokataan eri suuntiin, sekä näiden sarjojen näkymiseen 2010-luvun ruohonjuuritason politiikassa. Artikkelissa tarkastellaan sarjojen vaikutushistoriallista kontekstia, audiovisuaalista estetiikkaa, historiakulttuurista dynamiikkaa sekä niiden vaihtoehtohistoriallisten spekulaatioiden näkymistä niin uuspopulististien kuin kansalaisoikeus- ja identiteettipolitiikkaan kiinnittyvien ryhmittymien toiminnassa.&nbsp

Analysis of BMP4 and BMP7 signaling in breast cancer cells unveils time-dependent transcription patterns and highlights a common synexpression group of genes

<p>Abstract</p> <p>Background</p> <p>Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily of growth factors. They are known for their roles in regulation of osteogenesis and developmental processes and, in recent years, evidence has accumulated of their crucial functions in tumor biology. BMP4 and BMP7, in particular, have been implicated in breast cancer. However, little is known about BMP target genes in the context of tumor. We explored the effects of BMP4 and BMP7 treatment on global gene transcription in seven breast cancer cell lines during a 6-point time series, using a whole-genome oligo microarray. Data analysis included hierarchical clustering of differentially expressed genes, gene ontology enrichment analyses and model based clustering of temporal data.</p> <p>Results</p> <p>Both ligands had a strong effect on gene expression, although the response to BMP4 treatment was more pronounced. The cellular functions most strongly affected by BMP signaling were regulation of transcription and development. The observed transcriptional response, as well as its functional outcome, followed a temporal sequence, with regulation of gene expression and signal transduction leading to changes in metabolism and cell proliferation. Hierarchical clustering revealed distinct differences in the response of individual cell lines to BMPs, but also highlighted a synexpression group of genes for both ligands. Interestingly, the majority of the genes within these synexpression groups were shared by the two ligands, probably representing the core molecular responses common to BMP4 and BMP7 signaling pathways.</p> <p>Conclusions</p> <p>All in all, we show that BMP signaling has a remarkable effect on gene transcription in breast cancer cells and that the functions affected follow a logical temporal pattern. Our results also uncover components of the common cellular transcriptional response to BMP4 and BMP7. Most importantly, this study provides a list of potential novel BMP target genes relevant in breast cancer.</p

Multiomics characterization implicates PTK7 in ovarian cancer EMT and cell plasticity and offers strategies for therapeutic intervention

Most patients with ovarian cancer (OC) are diagnosed at a late stage when there are very few therapeutic options and a poor prognosis. This is due to the lack of clearly defined underlying mechanisms or an oncogenic addiction that can be targeted pharmacologically, unlike other types of cancer. Here, we identified protein tyrosine kinase 7 (PTK7) as a potential new therapeutic target in OC following a multiomics approach using genetic and pharmacological interventions. We performed proteomics analyses upon PTK7 knockdown in OC cells and identified novel downstream effectors such as synuclein-gamma (SNCG), SALL2, and PP1 gamma, and these findings were corroborated in ex vivo primary samples using PTK7 monoclonal antibody cofetuzumab. Our phosphoproteomics analyses demonstrated that PTK7 modulates cell adhesion and Rho-GTPase signaling to sustain epithelial-mesenchymal transition (EMT) and cell plasticity, which was confirmed by high-content image analysis of 3D models. Furthermore, using high-throughput drug sensitivity testing (525 drugs) we show that targeting PTK7 exhibited synergistic activity with chemotherapeutic agent paclitaxel, CHK1/2 inhibitor prexasertib, and PLK1 inhibitor GSK461364, among others, in OC cells and ex vivo primary samples. Taken together, our study provides unique insight into the function of PTK7, which helps to define its role in mediating aberrant Wnt signaling in ovarian cancer.Peer reviewe

HOX gene expression predicts response to BCL-2 inhibition in acute myeloid leukemia

Peer reviewe