Molecular Genetics of T Cell Development

T cell development is guided by a complex set of transcription factors that act recursively, in different combinations, at each of the developmental choice points from T-lineage specification to peripheral T cell specialization. This review describes the modes of action of the major T-lineage-defining transcription factors and the signal pathways that activate them during intrathymic differentiation from pluripotent precursors. Roles of Notch and its effector RBPSuh (CSL), GATA-3, E2A/HEB and Id proteins, c-Myb, TCF-1, and members of the Runx, Ets, and Ikaros families are critical. Less known transcription factors that are newly recognized as being required for T cell development at particular checkpoints are also described. The transcriptional regulation of T cell development is contrasted with that of B cell development, in terms of their different degrees of overlap with the stem-cell program and the different roles of key transcription factors in gene regulatory networks leading to lineage commitment

Tightrope walkers and solidarity sisters: critical workplace educators in the garment industry

Abstract: This article focuses on the complex negotiations of critical workplace educators positioned amongst contradictory agendas and discourses in the workplace. While philosophically aligned with critical pedagogical agendas of transformation and collective action for workplace change, these educators perform an array of pedagogic articulations in everyday practice to secure their continued presence in the workplace. What becomes evident in these seemingly opposing articulations are various strategic political positionings of educators alongside their juggling of demands, attachments and inter-identifications with both learners and managers. The pedagogy that emerges challenges conventional binaries of ‘transformative’ and ‘reproductive’ learning. Dynamics of transformation and liberation as well as reproduction and subjugation appear to be interlinked, along with expanding nets of social relations that blur power hierarchies and spatial boundaries, in a pedagogy that ultimately appears to mobilise hope and agency among workers. The workplace educator works a delicate balance of these dynamics to survive. The argument is based on a case study of a garment factory in Canada in which an adult education programme managed to thrive for 17 years: both workers and educators were interviewed in depth

‘Where are we when we think?’ Space, time and emancipatory education in galleries

Adult education in art galleries sits on a fault line, at once an apparatus upholding the affirmative aspects of museum culture cultivated by global elites, a propellant in the whirring of an increasingly dislocated set of events on trendy and consumable political themes, and a site for ‘allyship’ and other kinds of radical and socially transformative work. Resurrecting Hannah Arendt’s question,‘where are we when we think?’ this paper explores how we might move from a moment in which the ‘space’ of the gallery is replaced by the ‘time’ of the event (Helguera) and towards embedded space-times that attempt to address contemporary urgencies through situated practices that collectively analyse and respond to conditions. Drawn from examples derived from the author’s practice, the paper argues for the use of popular education and anti-colonial pedagogies in the production of adult education in galleries, suggesting that such processes support groups in collectively naming and thinking through conflicts to re-shape both the galleries in which they have congregated and the worlds beyond their doors. This paper suggests that the re-construction and use of the often forgotten genealogies of emancipatory education are pivotal to doing social justice work in galleries

The Flip-Flop Trail and Fragile Globalisation

The flip-flop trail is an object biography. It follows the translocal journeys of a pair of plastic sandals, unpacking the lives and landscapes hidden in the plastic. An important shoe-infrastructure enabling human mobility, flip-flops work as an offbeat proxy for globalization too. They proffer empirical footings in translocally-connected worlds in which people and the social textures and terrains of their everyday lives come to the fore, in place of economic processes and commodity chains favoured in hegemonic versions of globalization. These reduce globalization’s complex social forms to the grand narratives of the logics of capital accumulation, implicitly naturalizing it, if critically, as inevitable, entrenched and robust. From the vantage point of the flip- flop trail, globalization looks rather different. It is more fragile and shifting, generating multiple forms of uncertainty in the lives and landscapes it simultaneously sustains and undermines

Allele-specific control of rodent and human lncRNA KMT2E-AS1 promotes hypoxic endothelial pathology in pulmonary hypertension

Hypoxic reprogramming of vasculature relies on genetic, epigenetic, and metabolic circuitry, but the control points are unknown. In pulmonary arterial hypertension (PAH), a disease driven by hypoxia inducible factor (HIF)–dependent vascular dysfunction, HIF-2α promoted expression of neighboring genes, long noncoding RNA (lncRNA) histone lysine N-methyltransferase 2E-antisense 1 (KMT2E-AS1) and histone lysine N-methyltransferase 2E (KMT2E). KMT2E-AS1 stabilized KMT2E protein to increase epigenetic histone 3 lysine 4 trimethylation (H3K4me3), driving HIF-2α–dependent metabolic and pathogenic endothelial activity. This lncRNA axis also increased HIF-2α expression across epigenetic, transcriptional, and posttranscriptional contexts, thus promoting a positive feedback loop to further augment HIF-2α activity. We identified a genetic association between rs73184087, a single-nucleotide variant (SNV) within a KMT2E intron, and disease risk in PAH discovery and replication patient cohorts and in a global meta-analysis. This SNV displayed allele (G)–specific association with HIF-2α, engaged in long-range chromatin interactions, and induced the lncRNA-KMT2E tandem in hypoxic (G/G) cells. In vivo, KMT2E-AS1 deficiency protected against PAH in mice, as did pharmacologic inhibition of histone methylation in rats. Conversely, forced lncRNA expression promoted more severe PH. Thus, the KMT2E-AS1/KMT2E pair orchestrates across convergent multi-ome landscapes to mediate HIF-2α pathobiology and represents a key clinical target in pulmonary hypertension

Women workers in the NAFTA food chain

In IDL-2279