A small supramolecular system which emulates the unidirectional, path-selective photoinduced electron transfer (PET) of the bacterial photosynthetic reaction centre (PRC)

The singlet excited state of the 4-aminonaphthalimide fluorophore in 1a and 1b directs electron transfer from intramolecular but external amine groups along only one of two available paths.

New Irish speakers and the ‘gaelicisation’ of Belfast

New Irish speakers in Belfast play a crucial, complex part in the revitalization and change of both the city and Irish within Northern Ireland. This paper examines the role of new Irish speakers in transforming Belfast, whose emergence from a post-conflict period involves a reassessment of communal cultural expressions. Markers of ethno-national identity are bitterly contentious locally, and yet increasingly celebrated, in line with international trends, as high status cultural forms and potentially profitable tourist attractions. Irish in Belfast currently occupies an ambiguous position: divisive enough for a sign reading ‘Happy Christmas’ in Irish to be experienced as an insult by some city councillors, yet a secure enough part of the establishment for a neighbourhood to be officially rebranded as the Gaeltacht Quarter.
When, how and where new Irish speakers use the language in Belfast has implications for the relationship of Irishness to the Northern Irish state and for the place of Belfast within regional frameworks across the UK, Ireland and Europe. Adult learners and young people exiting Irish medium education have an impact on life in Belfast beyond its small population of Irish speakers. Urbanisation fuelled by new speakers, which shifts the balance of Irish language resources and speakers away from traditional rural Gaeltacht areas and towards cities, also has implications for the language itself. Recent increase in new Irish speakers in Belfast is due to expansion in the Irish-medium sector as well as to adult learners, whose decisions contribute to the school expansion.
Urbanisation, multilingualism and intergenerational shift combine in Belfast to produce new linguistic norms. Moreover, in a minority language community where hierarchies of ‘authenticity’ are weighted towards the rural and the native speaker, where the rural and the native have traditionally been conflated, and where indigeneity is a central concept to contested nationalisms, the emergence of a self-confident, youthful Irish speaking community in Northern Ireland’s biggest city involves a recalibration of the qualities signifying ‘gaelicness’. As students, professionals, hobbyists and activists, new Irish speakers in Belfast occupy a vital position at the crux of changing ideas about place, language and identity.

Invasive alien species disrupt spatial and temporal ecology and threaten extinction in an insular, small mammal community

The impact of invasive bank vole (Myodes glareolus) and greater white-toothed shrew (Crocidura russula) on indigenous Irish small mammals, varies with season and habitat. We caught bank voles in deciduous woodland, young coniferous plantations and open habitats such as rank grass. The greater white-toothed shrew was absent from deciduous woods and plantations but did use open habitats with low level cover in addition to field margins. Numbers of both invasive species in field margins during summer were higher than in the previous spring. The indigenous wood mouse (Apodemus sylvaticus) and pygmy shrew (Sorex minutus), differed in degrees of negative response to invasive species. Wood mice with bank voles in hedgerows had reduced recruitment and lower peak abundance. This effect was less extreme where both invasive species were present. Wood mice numbers along field margins and open habitats were significantly depressed by the presence of the bank vole with no such effect in deciduous woodland or coniferous plantations. Summer recruitment in pygmy shrews was reduced in hedgerows with bank voles. Where greater white-toothed shrew was present, the pygmy shrew was entirely absent from field margins. Species replacement due to invasive small mammals is occurring in their major habitat i.e. field margins and open habitats where there is good ground cover. Pygmy shrew will probably disappear from these habitats throughout Ireland. Wood mice and possibly pygmy shrew may survive in deciduous woodland and conifer plantations. Mitigation of impacts of invasive species should include expansion of woodland in which native species can survive.

Expression of the NF-kappaB targets BCL2 and BIRC5/Survivin characterizes small B-cell and aggressive B-cell lymphomas, respectively

Nuclear factor kappa B (NF-kappaB) activation has been proposed as a cardinal feature of tumourigenesis, although the precise mechanism, frequency, relevance, and extent of NF-kappaB activation in lymphomas remain to be fully elucidated. In this study, expression profiling and tissue microarray studies of 209 and 323 non-Hodgkin's lymphomas (NHLs) respectively, including the most frequent sub-types of NHL, were employed to generate a hypothesis concerning the most common NF-kappaB targets in NHL. These analyses showed that NF-kappaB activation is a common phenomenon in NHL, resulting in the expression of distinct sets of NF-kappaB target genes, depending on the cell context. BCL2 and BIRC5/Survivin were identified as key NF-kappaB targets and their expression distinguished small and aggressive B-cell lymphomas, respectively. Interestingly, in the vast majority of B-cell lymphomas, the expression of these markers was mutually exclusive. A set of genes was identified whose expression correlates either with BIRC5/Survivin or with BCL2. BIRC5/Survivin expression, in contrast to BCL2, was associated with a signature of cell proliferation (overexpression of cell cycle control, DNA repair, and polymerase genes), which may contribute to the aggressive phenotype and poor prognosis of these lymphomas. Strikingly, mantle cell lymphoma and chronic lymphocytic leukaemia expressed highly elevated levels of BCL2 protein and mRNA, higher than that observed in reactive mantle zone cells or even in follicular lymphomas, where BCL2 expression is deregulated through the t(14;18) translocation. In parallel with this observation, BIRC5/Survivin expression was higher in Burkitt's lymphoma and diffuse large B-cell lymphoma than in non-tumoural germinal centre cells. In vitro studies confirmed that NF-kappaB activation contributes to the expression of both markers. In cell lines representing aggressive lymphomas, NF-kappaB inhibition resulted in a decrease in BIRC5/Survivin expression. Meanwhile, in chronic lymphocytic leukaemia (CLL)-derived lymphocytes, NF-kappaB inhibition resulted in a marked decrease in BCL2 expression.

Studying administrative reforms through textual analysis: the case of Italian central government accounting

This paper contributes to the literature on public-sector reforms by proposing textual analysis as a useful research strategy to explore how reform archetypes and related ideas are deployed in the parliamentary debate and regulations advancing reforms. Public Administration (PA) (Wilson 1887; Weber 1922), New Public Management (NPM) (Hood 1991, 1995; Dunleavy and Hood 1994; Ferlie et al. 1996) and Public Governance (GOV) (Osborne 2010; Rhodes 1997) can be depicted as three different archetypes providing characteristic administrative ideas and concepts (i.e. interpretive schemes) and related tools and practices (i.e. structures and systems) which lead reforms. We use textual analysis to look into more than twenty years of Italian central government accounting reforms and investigate how the three administrative archetypes have evolved, intertwined and replaced each other. Textual analysis proves a useful tool to investigate reform processes and allows highlighting that in neo-Weberian countries, such as Italy, NPM and GOV, far from being revolutionary paradigms, may represent fashionable trends that did not leave significant traces in the practice and rhetoric of reforms. These results also suggest interesting implications for practitioners and policy makers.

O-GlcNAc transferase integrates metabolic pathways to regulate the stability of c-MYC in human prostate cancer cells

Metabolic disruptions that occur widely in cancers offer an attractive focus for generalized treatment strategies. The hexosamine biosynthetic pathway (HBP) senses metabolic status and produces an essential substrate for O-linked β-N-acetylglucosamine transferase (OGT), which glycosylates and thereby modulates the function of its target proteins. Here, we report that the HBP is activated in prostate cancer cells and that OGT is a central regulator of c-Myc stability in this setting. HBP genes were overexpressed in human prostate cancers and androgen regulated in cultured human cancer cell lines. Immunohistochemical analysis of human specimens (n = 1987) established that OGT is upregulated at the protein level and that its expression correlates with high Gleason score, pT and pN stages, and biochemical recurrence. RNA interference-mediated siliencing or pharmacologic inhibition of OGT was sufficient to decrease prostate cancer cell growth. Microarray profiling showed that the principal effects of OGT inhibition in prostate cancer cells were related to cell-cycle progression and DNA replication. In particular, c-MYC was identified as a candidate upstream regulator of OGT target genes and OGT inhibition elicited a dose-dependent decrease in the levels of c-MYC protein but not c-MYC mRNA in cell lines. Supporting this relationship, expression of c-MYC and OGT was tightly correlated in human prostate cancer samples (n = 1306). Our findings identify HBP as a modulator of prostate cancer growth and c-MYC as a key target of OGT function in prostate cancer cells.

The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis

The androgen receptor (AR) is a key regulator of prostate growth and the principal drug target for the treatment of prostate cancer. Previous studies have mapped AR targets and identified some candidates which may contribute to cancer progression, but did not characterize AR biology in an integrated manner. In this study, we took an interdisciplinary approach, integrating detailed genomic studies with metabolomic profiling and identify an anabolic transcriptional network involving AR as the core regulator. Restricting flux through anabolic pathways is an attractive approach to deprive tumours of the building blocks needed to sustain tumour growth. Therefore, we searched for targets of the AR that may contribute to these anabolic processes and could be amenable to therapeutic intervention by virtue of differential expression in prostate tumours. This highlighted calcium/calmodulin-dependent protein kinase kinase 2, which we show is overexpressed in prostate cancer and regulates cancer cell growth via its unexpected role as a hormone-dependent modulator of anabolic metabolism. In conclusion, it is possible to progress from transcriptional studies to a promising therapeutic target by taking an unbiased interdisciplinary approach.