La sécurité alimentaire durable au Nunavik : les enjeux juridiques de la commercialisation de la viande de caribou et de ses sous-produits par les Inuits

Le régime alimentaire des Inuits du Nunavik s’est modifié considérablement au cours des dernières décennies. Leur alimentation traditionnelle, constituée de viande et de poisson, a évolué vers un régime composé majoritairement de produits alimentaires importés du Sud, bien que l’apport en protéines demeure largement basé sur la consommation de gibier et de poisson. En raison du coût important lié à cette nouvelle forme d’alimentation, la transformation des habitudes alimentaires des Inuits modifie l’état de la sécurité alimentaire au Nunavik. Parce qu’elle permettrait de générer des revenus supplémentaires aux Inuits, la commercialisation de la viande de caribou et de ses sous-produits pourrait contribuer à renforcer l’accessibilité économique des Inuits aux produits du Sud et ainsi participer à l’atteinte d’une sécurité alimentaire durable au Nunavik. La Convention de la Baie-James et du Nord québécois et ses conventions complémentaires, qui établissent le régime de chasse des Inuits, permettent effectivement à ces derniers de pratiquer la chasse commerciale du caribou tout en leur assurant un accès sécurisé à cette ressource faunique dans une perspective de développement durable. Toutefois, certaines dispositions de ces conventions posent problème, principalement en cas de diminution importante des populations de caribous. De plus, des difficultés sont prévisibles quant au respect des règles nationales et internationales liées au commerce des produits alimentaires, notamment en ce qui a trait aux règles d’innocuité et de salubrité.Over the past decades, the food patterns of the Inuit of Nunavik have undergone substantial changes. Their traditional diet, mainly of meat and fish, has evolved towards a regimen made up largely of food products imported from the south, despite the fact that their intake of proteins is mainly based on the consumption of game animals and fish. Owing to the high cost of their new eating habits, the change in diet among the Inuit has modified food security in Nunavik. Since this enables the Inuit to generate extra income, the marketing of caribou meat and its derivative products could contribute to reinforcing Inuit economic access to products from the south and thereby participate in the attainment of sustainable food security for Nunavik. The Agreement concerning James Bay and Northern Québec and its complementary agreements, which establish the Inuit hunting regime, do in effect allow them to practice commercial hunting while ensuring for themselves secure access to this wildlife resource with a view to sustainable development. Nonetheless, some provisions of these agreements are problematical, especially in the case of a significant decline in caribou populations. Moreover, difficulties are foreseen regarding compliance with national and international rules relevant to the marketing of food products, particularly with regard to rules of safety and health

Et si on normalisait la folie?: Démarche de conscientisation face à la stigmatisation par le biais d'une intervention de groupe avec des individus vivant avec le trouble de personnalité limite

Essai critique présenté à la Faculté des études supérieures en vue de l’obtention du grade de M.Sc. en service socialLe présent essai critique se veut une réflexion sur l’implantation et la réalisation d’un projet d’intervention de groupe, basé sur les principes de la conscientisation, s’adressant aux personnes présentant un trouble de la personnalité limite quant aux enjeux de la stigmatisation et ses conséquences en lien avec ce trouble. Ce projet d’intervention expérimenté au programme des troubles relationnels et de la personnalité de l’Institut universitaire en santé mentale de Montréal vise, chez les participants, le passage d’une lecture pessimiste de leur réalité à une lecture critique de celle-ci. De plus, grâce à la création d’un outil de sensibilisation en collaboration avec les participants, ce projet souhaite sensibiliser la population générale aux enjeux de la stigmatisation pour les personnes vivant avec un trouble de la personnalité limite ainsi que les professionnels de la santé rencontrant des personnes aux prises avec ce trouble dans leur pratique

Études Structurales par Résonance Magnétique Nucléaire (RMN) du Site Actif du Ribozyme VS de Neurospora

Nous étudions le ribozyme VS de Neurospora, en tant que système modèle, pour augmenter nos connaissances sur la relation entre la structure et la fonction chez les ARNs, ainsi que pour mieux comprendre le mécanisme de clivage de ce ribozyme. Il a été proposé précédemment que la boucle interne A730 dans la tige-boucle VI (SLVI) contient le site actif du ribozyme et lie un ou plusieurs ions métalliques qui pourraient participer au mécanisme réactionnel. Nous avons déterminé par spectroscopie RMN la structure de la tige-boucle SLVI contenant la boucle A730 afin d’éclaircir ce mécanisme. La structure obtenue est en accord avec les études biochimiques antérieures et présente un ou plusieurs sites de liaison au magnésium associé à la boucle interne. Suite à des études de cinétique et de mutagenèse, il a été proposé qu’une adénine localisée dans le site actif, A756, participe à la catalyse par acide/base générale. Des études de pH effectuées précédemment ont identifié un pKa catalytique (5.2-5.8) qui correspond probablement à l’équilibre de protonation du A756. À l’aide de méthodes utilisant le carbone-13, nous avons identifié un pKa modifié appartenant au A756, ce qui supporte le rôle de ce résidu dans la catalyse par acide/base générale. Les études structurales présentées ici aident donc à augmenter notre compréhension du mécanisme de clivage chez le ribozyme VS.We are studying the Neurospora VS ribozyme as a model system to increase our knowledge of the structure-function relationship in RNA and to better understand the mechanism of the cleavage reaction. It has been previously postulated that the A730 internal loop of stem-loop VI (SLVI) forms the active site of the VS ribozyme and binds magnesium ion(s) that may participate in catalysis. To get insights into the catalytic mechanism, we have determined by NMR spectroscopy the structure of a SLVI fragment containing the A730 loop. The structure we obtained is in agreement with previous biochemical studies and contains one or more magnesium-ion binding sites in the active site. Based on kinetic and mutagenesis studies, it has been proposed that an adenine in the A730 loop, A756, is important for catalysis and may participate in general acid/base catalysis. Previous pH-dependent enzymatic studies identified a catalytic pKa of 5.2-5.8, which likely corresponds to the protonation equilibrium of this A756 adenine in the A730 loop. Using 13C NMR methods, we have identified a shifted pKa for A756, which gives additional support to the role of this residue in the general acid/base mechanism. The NMR studies presented here therefore increase our understanding of the cleavage reaction in the VS ribozyme

Genetic Background of Escherichia coli and Extended-spectrum β-Lactamase Type

ESBL-producing E. coli may arise from interactions between ESBL type, strain genetic background, and selective pressures in various ecologic niches

GDF15 promotes weight loss by enhancing energy expenditure in muscle

Funding Information: We thank R. Seeley for sharing GFRAL-null mice; B. Lowell for sharing β-less mice; and J. Wu for shipping β-less mice to us. G.R.S. was supported by a Diabetes Canada Investigator Award (DI-5-17-5302-GS), a Canadian Institutes of Health Research Foundation Grant (201709FDN-CEBA-116200), a Tier 1 Canada Research Chair in Metabolic Diseases and a J. Bruce Duncan Endowed Chair in Metabolic Diseases; D.W. by Fellowship Grants from the McMaster Institute for Research on Aging (MIRA) at McMaster University; S.R. by a postdoctoral fellowship supported by MITACS and Novo Nordisk; L.K.T. by a CIHR Post-Doctoral Fellowship Award and Michael DeGroote Fellowship Award in Basic Biomedical Science; E.M.D. by a Vanier Canada Graduate Scholarship; G.P.H. by the Natural Sciences and Engineering Research Council of Canada (NSERC: 400362); G.J.D. and S.M.F. by NSERC-CGSM scholarships; L.D. by the Fonds de Recherche du Québec-Santé doctoral training award; D.P.B. by the GSK Chair in Diabetes of Université de Sherbrooke and a FRQS J1 salary award. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by the NCI, NHGRI, NHLBI, NIDA, NIMH and NINDS. Funding Information: S.B.J. and R.E.K. are employees of Novo Nordisk, a pharmaceutical company producing and selling medicine for the treatment of diabetes and obesity. G.R.S. is a co-founder and shareholder of Espervita Therapeutics. McMaster University has received funding from Espervita Therapeutics, Esperion Therapeutics, Poxel Pharmaceuticals and Nestle for research conducted in the laboratory of G.R.S. S.R. is supported by a MITACS postdoctoral fellowship sponsored by Novo Nordisk. H.C.G. holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. G.R.S., G.P. and H.C.G. are inventors listed on a patent for identifying GDF15 as a biomarker for metformin. G.R.S. has received consulting/speaking fees from Astra Zeneca, Eli Lilly, Esperion Therapeutics, Merck, Poxel Pharmaceuticals and Cambrian Biosciences. The other authors declare no competing interests. Publisher Copyright: © 2023, The Author(s).Peer reviewedPublisher PD

NMR structure of the A730 loop of the Neurospora VS ribozyme: insights into the formation of the active site

The Neurospora VS ribozyme is a small nucleolytic ribozyme with unique primary, secondary and global tertiary structures, which displays mechanistic similarities to the hairpin ribozyme. Here, we determined the high-resolution NMR structure of a stem–loop VI fragment containing the A730 internal loop, which forms part of the active site. In the presence of magnesium ions, the A730 loop adopts a structure that is consistent with existing biochemical data and most likely reflects its conformation in the VS ribozyme prior to docking with the cleavage site internal loop. Interestingly, the A730 loop adopts an S-turn motif that is also present in loop B within the hairpin ribozyme active site. The S-turn appears necessary to expose the Watson–Crick edge of a catalytically important residue (A756) so that it can fulfill its role in catalysis. The A730 loop and the cleavage site loop of the VS ribozyme display structural similarities to internal loops found in the active site of the hairpin ribozyme. These similarities provided a rationale to build a model of the VS ribozyme active site based on the crystal structure of the hairpin ribozyme

Variations in the NBN/NBS1 gene and the risk of breast cancer in non-BRCA1/2 French Canadian families with high risk of breast cancer

<p>Abstract</p> <p>Background</p> <p>The Nijmegen Breakage Syndrome is a chromosomal instability disorder characterized by microcephaly, growth retardation, immunodeficiency, and increased frequency of cancers. Familial studies on relatives of these patients indicated that they also appear to be at increased risk of cancer.</p> <p>Methods</p> <p>In a candidate gene study aiming at identifying genetic determinants of breast cancer susceptibility, we undertook the full sequencing of the <it>NBN </it>gene in our cohort of 97 high-risk non-<it>BRCA1 </it>and -<it>BRCA2 </it>breast cancer families, along with 74 healthy unrelated controls, also from the French Canadian population. <it>In silico </it>programs (ESEfinder, NNSplice, Splice Site Finder and MatInspector) were used to assess the putative impact of the variants identified. The effect of the promoter variant was further studied by luciferase gene reporter assay in MCF-7, HEK293, HeLa and LNCaP cell lines.</p> <p>Results</p> <p>Twenty-four variants were identified in our case series and their frequency was further evaluated in healthy controls. The potentially deleterious p.Ile171Val variant was observed in one case only. The p.Arg215Trp variant, suggested to impair NBN binding to histone γ-H2AX, was observed in one breast cancer case and one healthy control. A promoter variant c.-242-110delAGTA displayed a significant variation in frequency between both sample sets. Luciferase reporter gene assay of the promoter construct bearing this variant did not suggest a variation of expression in the MCF-7 breast cancer cell line, but indicated a reduction of luciferase expression in both the HEK293 and LNCaP cell lines.</p> <p>Conclusion</p> <p>Our analysis of <it>NBN </it>sequence variations indicated that potential <it>NBN </it>alterations are present, albeit at a low frequency, in our cohort of high-risk breast cancer cases. Further analyses will be needed to fully ascertain the exact impact of those variants on breast cancer susceptibility, in particular for variants located in <it>NBN </it>promoter region.</p

Structural characterization of DNA binding and autoinhibition by the Ets1 transcription factor

Ets1 belongs to the ETS transcription factor family and plays key roles in regulating eukaryotic gene expression. The affinity of the Ets1 for its cognate DNA sites is autoinhibited by an intrinsically disordered serine-rich region (SRR) and an appended helical inhibitory module (IM). Through transient interactions, the SRR both sterically blocks the ETS domain and allosterically stabilizes the IM to modulate DNA-binding affinity. Calmodulin-dependent kinase II phosphorylation of five serines within the SRR progressively reinforces autoinhibition in response to calcium signaling. Using mutagenesis and quantitative DNA-binding measurements, we demonstrate that phosphorylation-enhanced autoinhibition requires the presence of phenylalanine/tyrosine (ϕ) residues adjacent to the SRR phosphoacceptor serines. The introduction of additional phosphorylated Ser-ϕ-Asp, but not Ser-Ala-Asp, repeats within the SRR dramatically reinforces autoinhibition. NMR spectroscopic studies of phosphorylated and mutated SRR variants, both within their native context and as separate trans-acting peptides, confirmed that the aromatic residues and phosphoserines contribute to the formation of a dynamic complex with the ETS domain. Complementary NMR studies also identified the SRR-interacting surface of the ETS domain, which encompasses its positively-charged DNA recognition interface and an adjacent region of neutral polar and nonpolar residues. Collectively, these studies highlight the role of aromatic residues and their synergy with phosphoserines in an intrinsically disordered regulatory sequence that integrates cellular signaling and gene expression. We also investigated by NMR spectroscopy the interaction of Ets1 with specific and nonspecific oligonucleotides. Upon binding DNA, helices HI-1 and HI-2 of the IM unfold. Thus, autoinibition does not impart DNA-binding specificity. Using amide chemical shift perturbation mapping, we also show that Ets1 binds both specific and non-specific oligonucleotides through its canonical ETS domain interface. However, the non-specific complex is formed by weak and dynamic electrostatic interactions, whereas the specific complex involves well-ordered hydrogen bonds and salt bridges. In support of this conclusion, five lysine sidechains are protected from rapid hydrogen exchange upon binding of specific DNA, whereas only one is stabilized in the non-specific complex. Overall, these data are consistent with Ets1 rapidly finding specific DNA sites within the genome via facilitated diffusion (sliding and hopping) within a vast background of non-specific sequences.Medicine, Faculty ofBiochemistry and Molecular Biology, Department ofGraduat

Engagement paternel et mobilisation communautaire : étude de cas de deux initiatives communautaires

Lorsqu’un groupe de partenaires, hommes et femmes, décide de travailler ensemble à promouvoir l’engagement paternel dans sa communauté, il fait oeuvre de pionniers dans un domaine d’intervention encore peu développé. Le présent article se fonde sur une étude de cas de deux initiatives locales pour valoriser le rôle du père. Ces initiatives ont mis à l’essai dans deux milieux vulnérables un modèle communautaire inspiré de la promotion de la santé et de la démarche d’action intersectorielle locale. L’article rapporte les étapes d’implantation des initiatives, les actions réalisées par les partenaires des sites et les effets perçus par les acteurs en place. Il fait ressortir des facteurs de succès de l’intervention dans le champ de la paternité tels qu’opter pour une approche souple adaptée aux particularités individuelles des pères et privilégier une approche famille plutôt que centrée uniquement sur les pères. À la suite d’autres études sur les processus de mobilisation locale, il met en évidence la nécessité de tenir compte des caractéristiques des communautés et du temps d’existence des initiatives.When a group of partners, whether male or female, decide to work together in order to promote paternal involvement in their community, they are pioneers in a poorly-developed area of intervention. This article is based on the case of two local initiatives to increase awareness of the value of the role fathers play in the community. In two communities judged to be vulnerable, they ran a trial inspired by the community model of the promotion of health and local inter sector cooperation. The article relates the various stages of implementation of these initiatives, the actions of the sites' partners, and the effects perceived by the actors. It highlights the successful factors of intervention in the field of paternity such as opting for a more flexible approach adapted to the individual needs of fathers and to favour a family approach rather than one focused uniquely on fathers. After citing other studies on local mobilization, the article emphasizes the necessity of taking into account the individual characteristics of communities and the length of time the initiatives have been in place.Cuando un grupo de asociados, hombres y mujeres, deciden de trabajar juntos para promover el compromiso paternal en su comunidad, ellos hacen obra de pioneros en un campo de intervención todavía poco desarrollado. El presente articulo se basa en un estudio de caso de dos iniciativas locales inclinadas hacia la valorización del rol del padre. Esas iniciativas han puesto a prueba en dos medios vulnerables un modelo comunitario inspirado de la promoción de la salud y de la gestión de la acción intersectorial local. El articulo relata las etapas de implantación de las iniciativas, las acciones realizadas por los asociados de esos sitios y los efectos percibidos por los actores del lugar. También hace resaltar los factores de éxito de la intervención en el campo de la paternidad, optando por un enfoque flexible adaptado a las particularidades individuales de los padres y privilegiando un enfoque familiar que no sea solamente centrado sobre los padres. En continuación con otros estudios sobre los procesos de movilización local, el articulo pone en evidencia la necesidad de tener en cuenta las características de las comunidades y el tiempo de existencia de las iniciativas