122 research outputs found
La gouvernance autochtone en milieu urbain: le cas de Montréal
Au fil des annĂ©es, les Autochtones ont obtenu la reconnaissance par lâĂtat canadien de certains droits inhĂ©rents, soit le droit Ă lâautodĂ©termination et le droit Ă lâautonomie gouvernementale. Cependant, lors de la mise en places dâinitiatives de gouvernance autochtone, les diffĂ©rents niveaux de gouvernement ont prĂ©sumĂ© que les groupes revendicateurs disposaient dâune assise territoriale pour rĂ©aliser ces objectifs, telles les communautĂ©s dâorigine des PremiĂšres nations, Inuites ou mĂ©tisses. Or, ces modĂšles sont inadĂ©quats pour la majoritĂ© des Autochtones au pays qui vivent en milieu urbain, une population hĂ©tĂ©rogĂšne, disparate, trĂšs mobile et surtout sans assise territoriale. Pour tenter de concilier lâexercice de lâautonomie gouvernementale avec lâurbanitĂ©, certains modĂšles thĂ©oriques de gouvernance ont Ă©tĂ© Ă©laborĂ©s afin de permettre une meilleure reprĂ©sentation politique aux Autochtones en milieu urbain. En gardant Ă lâesprit la situation de MontrĂ©al, câest-Ă -dire le problĂšme de lâidentitĂ© du titulaire du droit Ă lâautodĂ©termination, le territoire et la nature des pouvoirs Ă exercer, nous tenterons au cours de ce mĂ©moire de dĂ©terminer quel modĂšle de gouvernance autochtone serait le plus appropriĂ© pour les Autochtones de MontrĂ©al.In recent years, Aboriginals have obtained from the Canadian State recognition of certain inherent rights, including the right to self-determination and the right to self-government. However, when implementing Aboriginal governance initiatives, the various levels of government have operated on the assumption that Aboriginal groups all have a land base on which they can achieve their objectives, such as First Nations, Inuit and MĂ©tis home communities. These models are inadequate for the majority of Aboriginals who live in urban areas and who form a diverse and extremely mobile population without a land base. In order to reconcile the exercise of self-government and urbanity, new theoretical models of governance were developed to provide for better political representation of urban Aboriginals. By taking into account the issue of identifying who holds the right to self-determination, the nature of powers to be exercised and the area over which they would be exercised, we will attempt to determine in this thesis which Aboriginal governance model is best suited for Montrealâs Aboriginal population
Pascal : La géométrie du hasard
Even if Pascal's works are often considered as the origin of the calculus of probabilities, Pascal discovered, strictly speaking, only the solution to the problem of departing the stakes, or division problem, and never called it a "calculus of probabilities". He never used it neither to solve problems due to epistemic uncertainty. He only used the departing of stakes in a decisional context. The most famous example of that use is the thought known as "Pascal's wager". This article is an attempt to examine in which context the Pascalian discovery must be replaced, what is the originality of Pascal's statement, and what are the reasons to explain why Pascal chose other methods to face the epistemic uncertainty, precisely where we would use the calculus of probabilities.Bien que l'on considĂšre souvent que les travaux de Pascal sont Ă l'origine du calcul des probabilitĂ©s, Pascal n'a dĂ©couvert Ă proprement parler que la "rĂšgle des partis", qu'il n'appelle jamais "calcul des probabilitĂ©s", et qu'il n'utilise jamais pour rĂ©soudre des problĂšmes liĂ©s Ă l'incertitude Ă©pistĂ©mique. Il n'utilise la rĂšgle des partis que dans un cadre dĂ©cisionnel dont l'exemple le plus connu est le fragment dit du pari. Cet article tente de montrer dans quel contexte se situe la dĂ©couverte pascalienne, quelle est son originalitĂ©, et quelles sont les raisons qui peuvent expliquer que Pascal choisisse d'autres mĂ©thodes face Ă l'incertitude Ă©pistĂ©mique, lĂ oĂč nous choisirions d'utiliser le calcul des probabilitĂ©s
A Ralstonia solanacearum type III effector directs the production of the plant signal metabolite trehalose-6-phosphate
The plant pathogen Ralstonia solanacearum possesses two genes encoding a trehalose-6-phosphate synthase (TPS), an enzyme of the trehalose biosynthetic pathway. One of these genes, named ripTPS, was found to encode a protein with an additional N-terminal domain which directs its translocation into host plant cells through the type 3 secretion system. RipTPS is a conserved effector in the R. solanacearum species complex, and homologues were also detected in other bacterial plant pathogens. Functional analysis of RipTPS demonstrated that this type 3 effector synthesizes trehalose-6-phosphate and identified residues essential for this enzymatic activity. Although trehalose-6-phosphate is a key signal molecule in plants that regulates sugar status and carbon assimilation, the disruption of ripTPS did not alter the virulence of R. solanacearum on plants. However, heterologous expression assays showed that this effector specifically elicits a hypersensitive-like response on tobacco that is independent of its enzymatic activity and is triggered by the C-terminal half of the protein. Recognition of this effector by the plant immune system is suggestive of a role during the infectious process.Ralstonia solanacearum, the causal agent of bacterial wilt disease, infects more than two hundred plant species, including economically important crops. The type III secretion system plays a major role in the pathogenicity of this bacterium, and approximately 70 effector proteins have been shown to be translocated into host plant cells. This study provides the first description of a type III effector endowed with a trehalose-6-phosphate synthase enzymatic activity and illustrates a new mechanism by which the bacteria may manipulate the plant metabolism upon infection. In recent years, trehalose-6-phosphate has emerged as an essential signal molecule in plants, connecting plant metabolism and development. The finding that a bacterial pathogen could induce the production of trehalose-6-phosphate in plant cells further highlights the importance of this metabolite in multiple aspects of the molecular physiology of plants
Differential Regulation of HIV-1 Clade-Specific B, C, and E Long Terminal Repeats by NF-ÎșB and the Tat Transactivator
AbstractThe major group of human immunodeficiency viruses (HIV-1) that comprise the current global pandemic have diversified during their worldwide spread and may be divided into at least 10 distinct subtypes or clades, A through J. Subtype B predominates in North America and Europe, subtype E predominates in Southeast Asia, and subtype C predominates in sub-Saharan Africa. Functional distinctions in long terminal repeat (LTR) architecture among HIV subtypes have been identified, thus raising the possibility that regulatory divergence among the subtypes of HIV-1 has occurred. In addition to the transcriptional specificity of the HIV-1 LTR, productive HIV-1 replication is also dependent upon the viral Tat protein. Therefore, we sought to investigate whether interactions between host signaling pathways and the NF-ÎșB regions of different HIV-1 subtypes, together with subtype-specific interactions between Tat, TAR, and cellular proteins, modulate the efficiency of HIV-1 clade-specific gene transcription. We demonstrate that the NF-ÎșB sites of subtypes B and E both bind NF-ÎșB-related complexes. However, the duplicated ÎșB sites of the C subtype do not compete for NF-ÎșB binding. Also, clade E Tat protein possesses the highest transactivation capacity, regardless of the LTR context. Furthermore, preliminary evidence suggests that the acetylation of subtype-specific Tat proteins may correlate with their transactivation efficiency
Identification of Germinal Center B Cells in Blood from HIV-infected Drug-naive Individuals in Central Africa
To better understand the pathophysiology of B cell populationsâthe precursors of antibody secreting
cellsâduring chronic human immunodeficiency virus (HIV) infection, we examined the phenotype of
circulating B cells in newly diagnosed Africans. We found that all African individuals displayed low
levels of naive B cells and of memory-type CD27+ B cells, and high levels of differentiated B cells. On
the other hand, HIV-infected African patients had a population of germinal center B cells (i.e. CD20+,
sIgM-, sIgD+, CD77+, CD138±), which are generally restricted to lymph nodes and do not circulate
unless the lymph node architecture is altered. The first observations could be linked to the tropical
environment whereas the presence of germinal center B cells may be attributable to chronic exposure to
HIV as it is not observed in HIV-negative African controls and HAART treated HIV-infected
Europeans. It may impact the management of HIV infection in countries with limited access to HIV
drugs and urges consideration for implementation of therapeutic vaccines
A mitochondrial origin for frontotemporal dementia and amyotrophic lateral sclerosis through CHCHD10 involvement.
Mitochondrial DNA instability disorders are responsible for a large clinical spectrum, among which amyotrophic lateral sclerosis-like symptoms and frontotemporal dementia are extremely rare. We report a large family with a late-onset phenotype including motor neuron disease, cognitive decline resembling frontotemporal dementia, cerebellar ataxia and myopathy. In all patients, muscle biopsy showed ragged-red and cytochrome c oxidase-negative fibres with combined respiratory chain deficiency and abnormal assembly of complex V. The multiple mitochondrial DNA deletions found in skeletal muscle revealed a mitochondrial DNA instability disorder. Patient fibroblasts present with respiratory chain deficiency, mitochondrial ultrastructural alterations and fragmentation of the mitochondrial network. Interestingly, expression of matrix-targeted photoactivatable GFP showed that mitochondrial fusion was not inhibited in patient fibroblasts. Using whole-exome sequencing we identified a missense mutation (c.176C>T; p.Ser59Leu) in the CHCHD10 gene that encodes a coiled-coil helix coiled-coil helix protein, whose function is unknown. We show that CHCHD10 is a mitochondrial protein located in the intermembrane space and enriched at cristae junctions. Overexpression of a CHCHD10 mutant allele in HeLa cells led to fragmentation of the mitochondrial network and ultrastructural major abnormalities including loss, disorganization and dilatation of cristae. The observation of a frontotemporal dementia-amyotrophic lateral sclerosis phenotype in a mitochondrial disease led us to analyse CHCHD10 in a cohort of 21 families with pathologically proven frontotemporal dementia-amyotrophic lateral sclerosis. We identified the same missense p.Ser59Leu mutation in one of these families. This work opens a novel field to explore the pathogenesis of the frontotemporal dementia-amyotrophic lateral sclerosis clinical spectrum by showing that mitochondrial disease may be at the origin of some of these phenotypes
Factors that influence the levels of cerebrospinal fluid biomarkers in memory clinic patients
Spatial navigation deficits â overlooked cognitive marker for preclinical Alzheimer disease?
Detection of incipient Alzheimer disease (AD) pathophysiology is critical to identify preclinical individuals and target potentially disease-modifying therapies towards them. Current neuroimaging and biomarker research is strongly focused in this direction, with the aim of establishing AD fingerprints to identify individuals at high risk of developing this disease. By contrast, cognitive fingerprints for incipient AD are virtually non-existent as diagnostics and outcomes measures are still focused on episodic memory deficits as the gold standard for AD, despite their low sensitivity and specificity for identifying at-risk individuals. This Review highlights a novel feature of cognitive evaluation for incipient AD by focusing on spatial navigation and orientation deficits, which are increasingly shown to be present in at-risk individuals. Importantly, the navigation system in the brain overlaps substantially with the regions affected by AD in both animal models and humans. Notably, spatial navigation has fewer verbal, cultural and educational biases than current cognitive tests and could enable a more uniform, global approach towards cognitive fingerprints of AD and better cognitive treatment outcome measures in future multicentre trials. The current Review appraises the available evidence for spatial navigation and/or orientation deficits in preclinical, prodromal and confirmed AD and identifies research gaps and future research priorities
Integrated monitoring of mola mola behaviour in space and time
Over the last decade, ocean sunfish movements have been monitored worldwide using various satellite tracking methods. This study reports the near-real time monitoring of finescale (< 10 m) behaviour of sunfish. The study was conducted in southern Portugal in May 2014 and involved satellite tags and underwater and surface robotic vehicles to measure both the movements and the contextual environment of the fish. A total of four individuals were tracked using custom-made GPS satellite tags providing geolocation estimates of fine-scale resolution. These accurate positions further informed sunfish areas of restricted search (ARS), which were directly correlated to steep thermal frontal zones. Simultaneously, and for two different occasions, an Autonomous Underwater Vehicle (AUV) videorecorded the path of the tracked fish and detected buoyant particles in the water column. Importantly, the densities of these particles were also directly correlated to steep thermal gradients. Thus, both sunfish foraging behaviour (ARS) and possibly prey densities, were found to be influenced by analogous environmental conditions. In addition, the dynamic structure of the water transited by the tracked individuals was described by a Lagrangian modelling approach. The model informed the distribution of zooplankton in the region, both horizontally and in the water column, and the resultant simulated densities positively correlated with sunfish ARS behaviour estimator (r(s) = 0.184, p < 0.001). The model also revealed that tracked fish opportunistically displace with respect to subsurface current flow. Thus, we show how physical forcing and current structure provide a rationale for a predator's finescale behaviour observed over a two weeks in May 2014
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