Explaining immigration casework in federal Members of Parliament's district offices in Canada.

In Canada, a majority of federal constituency offices deal primarily with immigration files. The few qualitative studies on the subject show that the resources dedicated to these files and the type of work carried out on the immigration files handled vary between offices, thus contributing to disparities in service between federal electoral districts. How can such variation be explained? Based on the quantitative analysis of unpublished administrative data, this article first highlights the diversity of files handled by constituency offices, as well as the types of intervention carried out by constituency assistants. It then aims to explain the variations in case processing according to the type of case and the volume of requests handled. Studies of constituents' files received and processed at constituency office level have argued that the political ideology, gender and ethnicity of the deputy as well as the demographics of the constituency are explanatory factors. This analysis shows that in the case of immigration files, constituency demography is the most important factor, while the MP's political affiliation plays a very limited role. These results shed new light on the factors involved in the processing of immigration cases at constituency level, and add nuance to previous, mainly qualitative analyses. Our results also contribute to understanding the work of constituency offices for constituents, which appears to be far less partisan than in other countries where similar offices exist.

Au Canada, une majorité de bureaux de circonscription fédérale traite principalement des dossiers d'immigration. Les quelques études qualitatives portant sur le sujet montrent que les ressources dédiées à ces dossiers et le type de travail effectué sur les dossiers dʼimmigration traités varient entre les bureaux, contribuant ainsi à des disparités de services entre les circonscriptions électorales fédérales. Comment expliquer une telle variation? En sʼappuyant sur lʼanalyse quantitative de données administratives inédites, cet article met dʼabord en évidence la diversité des dossiers traités par les bureaux de circonscription ainsi que les types d'intervention effectués par les adjoints de circonscription. Ensuite, il vise à expliquer les variations du traitement des dossiers en fonction du type de dossier et du volume des demandes traité. Les études sur les dossiers de commettants reçus et traités au niveau des bureaux de circonscription ont soutenu que lʼidéologie politique, le genre et lʼethnicité du député ainsi que la démographie de la circonscription sont des facteurs explicatifs. Cette analyse montre que dans le cas des dossiers dʼimmigration, la démographie de la circonscription est le facteur le plus important, tandis que l'appartenance politique du député joue un rôle très limité. Ces résultats apportent un nouvel éclairage sur les facteurs du traitement des dossiers dʼimmigration au niveau des circonscriptions et nuancent les analyses antérieures, principalement qualitatives. Nos résultats contribuent également à la compréhension du travail des bureaux de circonscription pour les commettants, qui semble être bien moins partisan que dans dʼautres pays où des bureaux semblables existent.

Deciphering the genetic structure of the Quebec founder population using genealogies.

Using genealogy to study the demographic history of a population makes it possible to overcome the models and assumptions often used in population genetics. The Quebec founder population is one of the few populations in the world having access to the complete genealogy of the last 400 years. The goal of this study is to follow the evolution of the Quebec population structure over time from the beginning of European colonization until the present day. To do so, we calculated the kinship coefficients of all ancestors' pairs in the ascending genealogy of 665 subjects from eight regional and ethnocultural groups per 25-year period. We show that the Quebec population structure appeared progressively in the St. Lawrence valley as early as 1750 with the distinction of the Saguenay and Gaspesian groups. At that time, the ancestors of two groups, the Sagueneans and the Acadians from the Gaspé Peninsula, experienced a marked increase in kinship and inbreeding levels which have shaped the structure and led to the contemporary population structure. Interestingly, this structure arose before the colonization of the Saguenay region and at the very beginning of the Gaspé Peninsula settlement. The resulting regional founder effects in these groups led to differences in the present-day identity-by-descent sharing, the Gaspé and North Shore groups sharing more large segments and the Sagueneans more short segments. This is also reflected by the distribution of the number of most recent common ancestors at different generations and their genetic contribution to the studied subjects.

Angiotensin II type 1 receptor variants alter endosomal receptor-ß-arrestin complex stability and MAPK activation.

The angiotensin II (AngII) type 1 receptor (AT1R), a member of the G protein-coupled receptor (GPCR) family, signals through G proteins and ß-arrestins, which act as adaptors to regulate AT1R internalization and mitogen-activated protein kinase (MAPK) ERK1/2 activation. ß-arrestin-dependent ERK1/2 regulation is the subject of important studies because its spatiotemporal control remains poorly understood for many GPCRs, including AT1R. To study the link between ß-arrestin-dependent trafficking and ERK1/2 signaling, we investigated three naturally occurring AT1R variants that show distinct receptor-ß-arrestin interactions: A163T, T282M, and C289W. Using bioluminescence resonance energy transfer (BRET)-based and conformational fluorescein arsenical hairpin-BRET sensors coupled with high-resolution fluorescence microscopy, we show that all AT1R variants form complexes with ß-arrestin2 at the plasma membrane and efficiently internalize into endosomes upon AngII stimulation. However, mutant receptors imposed distinct conformations in ß-arrestin2 and differentially impacted endosomal trafficking and MAPK signaling. Notably, T282M accumulated in endosomes, but its ability to form stable complexes following internalization was reduced, markedly impairing its ability to co-traffic with ß-arrestin2. We also found that despite ß-arrestin2 overexpression, T282M's and C289W's residency with ß-arrestin2 in endosomes was greatly reduced, leading to decreased ß-arrestin-dependent ERK1/2 activation, faster recycling of receptors to the plasma membrane, and impaired AngII-mediated proliferation. Our findings reveal that naturally occurring AT1R variants alter the patterns of receptor/ß-arrestin2 trafficking and suggest conformationally dependent ß-arrestin-mediated MAPK activation as well as endosomal receptor-ß-arrestin complex stabilization in the mitogenic response of AT1R.

Genetic code expansion and photocross-linking identify different ß-arrestin binding modes to the angiotensin II type 1 receptor.

The angiotensin II (AngII) type 1 receptor (AT1R) is a member of the G protein-coupled receptor (GPCR) family and binds ß-arrestins (ß-arrs), which regulate AT1R signaling and trafficking. These processes can be biased by different ligands or mutations in the AGTR1 gene. As for many GPCRs, the exact details for AT1R-ß-arr interactions driven by AngII or ß-arr-biased ligands remain largely unknown. Here, we used the amber-suppression technology to site-specifically introduce the unnatural amino acid (UAA) p-azido-l-phenylalanine (azF) into the intracellular loops (ICLs) and the C-tail of AT1R. Our goal was to generate competent photoreactive receptors that can be cross-linked to ß-arrs in cells. We performed UV-mediated photolysis of 25 different azF-labeled AT1Rs to cross-link ß-arr1 to AngII-bound receptors, enabling us to map important contact sites in the C-tail and in the ICL2 and ICL3 of the receptor. The extent of AT1R-ß-arr1 cross-linking among azF-labeled receptors differed, revealing variability in ß-arr's contact mode with the different AT1R domains. Moreover, the signature of ligated AT1R-ß-arr complexes from a subset of azF-labeled receptors also differed between AngII and ß-arr-biased ligand stimulation of receptors and between azF-labeled AT1R bearing and that lacking a bias signaling mutation. These observations further implied distinct interaction modalities of the AT1R-ß-arr1 complex in biased signaling conditions. Our findings demonstrate that this photocross-linking approach is useful for understanding GPCR-ß-arr complexes in different activation states and could be extended to study other protein-protein interactions in cells.