16 research outputs found
On the application of geophysics in the exploration for copper and chrome ores in Albania1
CRISPR-Cas9 screen reveals a MYCN-amplified neuroblastoma dependency on EZH2
Pharmacologically difficult targets, such as MYC transcription factors, represent a major challenge in cancer therapy. For the childhood cancer neuroblastoma, amplification of the oncogene MYCN is associated with high-risk disease and poor prognosis. Here, we deployed genome-scale CRISPR-Cas9 screening of MYCN-amplified neuroblastoma and found a preferential dependency on genes encoding the polycomb repressive complex 2 (PRC2) components EZH2, EED, and SUZ12. Genetic and pharmacological suppression of EZH2 inhibited neuroblastoma growth in vitro and in vivo. Moreover, compared with neuroblastomas without MYCN amplification, MYCN-amplified neuroblastomas expressed higher levels of EZH2. ChIP analysis showed that MYCN binds at the EZH2 promoter, thereby directly driving expression. Transcriptomic and epigenetic analysis, as well as genetic rescue experiments, revealed that EZH2 represses neuronal differentiation in neuroblastoma in a PRC2-dependent manner. Moreover, MYCN-amplified and high-risk primary tumors from patients with neuroblastoma exhibited strong repression of EZH2-regulated genes. Additionally, overexpression of IGFBP3, a direct EZH2 target, suppressed neuroblastoma growth in vitro and in vivo. We further observed strong synergy between histone deacetylase inhibitors and EZH2 inhibitors. Together, these observations demonstrate that MYCN upregulates EZH2, leading to inactivation of a tumor suppressor program in neuroblastoma, and support testing EZH2 inhibitors in patients with MYCN-amplified neuroblastoma
Polarization without radicalization: political radicalism in Albania in a comparative perspective
‘Women Here Are Like at the Time of Enver [Hoxha]…’: Socialist and Post-Socialist Gendered Mobilities in Albanian Society
“Women here are like at the time of Enver [Hoxha] …”: socialist and post-socialist gendered mobility in Albanian society
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Disaggregating Opportunities: Opportunity Structures and Organisational Resources in the Study of Armed Conflict
The intersection of gender and generation in Albanian migration, remittances and transnational care
The Albanian case represents the most dramatic instance of post-communist migration: about one million Albanians, a quarter of the country's total population, are now living abroad, most of them in Greece and Italy, with the UK becoming increasingly popular since the late 1990s. This paper draws on three research projects based on fieldwork in Italy, Greece, the UK and Albania. These projects have involved in-depth interviews with Albanian migrants in several cities, as well as with migrant-sending households in different parts of Albania. In this paper we draw out those findings which shed light on the intersections of gender and generations in three aspects of the migration process: the emigration itself, the sending and receiving of remittances, and the care of family members (mainly the migrants' elderly parents) who remain in Albania. Theoretically, we draw on the notion of `gendered geographies of power and on how spatial change and separation through migration reshapes gender and generational relations. We find that, at all stages of the migration, Albanian migrants are faced with conflicting and confusing models of gender, behavioural and generational norms, as well as unresolved questions about their legal status and the likely economic, social and political developments in Albania, which make their future life plans uncertain. Legal barriers often prevent migrants and their families from enjoying the kinds of transnational family lives they would like