Migration decision-making: a geographical imaginations approach

Within the past two decades, scholars of migration are beginning to understand the importance of incorporating cultural dimensions into research concerning migration decision‐making practices. While it is recognised that economic, social and political factors are central in the formation of the desire to migrate, these factors alone are unable to explain the migratory decisions of many. However, although cultures of migration has emerged as the dominant approach for incorporating cultural facets of migration decision‐making, I suggest this approach does not offer a holistic exploration into the impacts of ‘culture’ due to its reluctance to fully engage with the importance of place. This paper outlines a geographical imaginations approach that is able to account for the complexities of culture and place on migration decision‐making, based on insights developed from interviews undertaken with Filipino nurses in the UK and in the Philippines. The approach is able to account for the impacts of culture and place on migration decision‐making in four main, interlinking ways. It is sensitive to the influence of geographical scales, to ideas of culture and place, to understandings of both home and away, and is able to account for non‐migration

Molecular mechanisms of developmentally programmed crinophagy in Drosophila

At the onset of metamorphosis, Drosophila salivary gland cells undergo a burst of glue granule secretion to attach the forming pupa to a solid surface. Here, we show that excess granules evading exocytosis are degraded via direct fusion with lysosomes, a secretory granule-specific autophagic process known as crinophagy. We find that the tethering complex HOPS (homotypic fusion and protein sorting); the small GTPases Rab2, Rab7, and its effector, PLEKHM1; and a SNAP receptor complex consisting of Syntaxin 13, Snap29, and Vamp7 are all required for the fusion of secretory granules with lysosomes. Proper glue degradation within lysosomes also requires the Uvrag-containing Vps34 lipid kinase complex and the v-ATPase proton pump, whereas Atg genes involved in macroautophagy are dispensable for crinophagy. Our work establishes the molecular mechanism of developmentally programmed crinophagy in Drosophila and paves the way for analyzing this process in metazoans

A reversible phospho-switch mediated by ULK1 regulates the activity of autophagy protease ATG4B

Upon induction of autophagy, the ubiquitin-like protein LC3 is conjugated to phosphatidylethanolamine (PE) on the inner and outer membrane of autophagosomes to allow cargo selection and autophagosome formation. LC3 undergoes two processing steps, the proteolytic cleavage of pro-LC3 and the de-lipidation of LC3-PE from autophagosomes, both executed by the same cysteine protease ATG4. How ATG4 activity is regulated to co-ordinate these events is currently unknown. Here we find that ULK1, a protein kinase activated at the autophagosome formation site, phosphorylates human ATG4B on serine 316. Phosphorylation at this residue results in inhibition of its catalytic activity in vitro and in vivo. On the other hand, phosphatase PP2A-PP2R3B can remove this inhibitory phosphorylation. We propose that the opposing activities of ULK1-mediated phosphorylation and PP2A-mediated dephosphorylation provide a phospho-switch that regulates the cellular activity of ATG4B to control LC3 processing

Immersion education outcomes and the Gaelic community:Identities and language ideologies among Gaelic-medium educated adults in Scotland

Scholars have consistently theorised that language ideologies can influence the ways in which bilingual speakers in minority language settings identify and engage with the linguistic varieties available to them. Research conducted by the author examined the interplay of language use and ideologies among a purposive sample of adults who started in Gaelic medium education during the first years of its availability. Crucially, the majority of participants’ Gaelic use today is limited, although notable exceptions were found among individuals who were substantially socialised in the language at home during childhood, and a small number of new speakers. In this paper, I draw attention to some of the language ideologies that interviewees conveyed when describing their cultural identifications with Gaelic. I argue that the ideologies that informants express seem to militate against their more frequent use of the language and their association with the wider Gaelic community. In particular, I discuss interviewees’ negative perceptions of the traditionally defined, ethnolinguistic identity category ‘Gael(s)’ in their expression of language ideologies and identities, and the implications of this finding for other contexts of minority language revitalisation

TBP Binding-Induced Folding of the Glucocorticoid Receptor AF1 Domain Facilitates Its Interaction with Steroid Receptor Coactivator-1

The precise mechanism by which glucocorticoid receptor (GR) regulates the transcription of its target genes is largely unknown. This is, in part, due to the lack of structural and functional information about GR's N-terminal activation function domain, AF1. Like many steroid hormone receptors (SHRs), the GR AF1 exists in an intrinsically disordered (ID) conformation or an ensemble of conformers that collectively appears to be unstructured. The GR AF1 is known to recruit several coregulatory proteins, including those from the basal transcriptional machinery, e.g., TATA box binding protein (TBP) that forms the basis for the multiprotein transcription initiation complex. However, the precise mechanism of this process is unknown. We have earlier shown that conditional folding of the GR AF1 is the key for its interactions with critical coactivator proteins. We hypothesize that binding of TBP to AF1 results in the structural rearrangement of the ID AF1 domain such that its surfaces become easily accessible for interaction with other coactivators. To test this hypothesis, we determined whether TBP binding-induced structure formation in the GR AF1 facilitates its interaction with steroid receptor coactivator-1 (SRC-1), a critical coactivator that is important for GR-mediated transcriptional activity. Our data show that stoichiometric binding of TBP induces significantly higher helical content at the expense of random coil configuration in the GR AF1. Further, we found that this induced AF1 conformation facilitates its interaction with SRC-1, and subsequent AF1-mediated transcriptional activity. Our results may provide a potential mechanism through which GR and by large other SHRs may regulate the expression of the GR-target genes

The Intriguing Life of Autophagosomes

Autophagosomes are double-membrane vesicles characteristic of macroautophagy, a degradative pathway for cytoplasmic material and organelles terminating in the lysosomal or vacuole compartment for mammals and yeast, respectively. This highly dynamic, multi-step process requires significant membrane reorganization events at different stages of the macroautophagic process. Such events include exchange and flow of lipids and proteins between membranes and vesicles (e.g., during initiation and growth of the phagophore), vesicular positioning and trafficking within the cell (e.g., autophagosome location and movement) and fusion of autophagosomes with the boundary membranes of the degradative compartment. Here, we review current knowledge on the contribution of different organelles to the formation of autophagosomes, their trafficking and fate within the cell. We will consider some of the unresolved questions related to the molecular mechanisms that regulate the “life and death” of the autophagosome