75 research outputs found
La main prédominante des Alouatta palliata lors de la réalisation de leurs activités quotidiennes telles que la nutrition, le déplacement, l'agrippement, le grattage, le jeu et le toilettage
Affiche prĂ©sentĂ©e dans le cadre du Colloque de l'ARC, «La recherche collĂ©giale et son milieu : enracinement, dĂ©ploiement et interdĂ©pendance», dans le cadre du 83e CongrĂšs de lâAcfas, UniversitĂ© du QuĂ©bec Ă Rimouski (UQAR), Rimouski, le 27 mai 2015.Le troisiĂšme prix a Ă©tĂ© dĂ©cernĂ© Ă Ămilie Forget-Klein, Julie Piotte et Ămile Richer au concours des Prix Ă©tudiants 2014-2015 de l'ARC.Puisque l'ĂȘtre humain prĂ©sente une asymĂ©trie cĂ©rĂ©brale qui se traduit par un cĂŽtĂ© gauche de l'encĂ©phale plus dĂ©veloppĂ©, il est droitier dans 70 % Ă 90 % des cas. Comme certains primates ont des gĂ©nomes Ă 99,4 % identiques Ă ceux des humains, il est intĂ©ressant de savoir si cette particularitĂ© est Ă©galement observĂ©e chez les Alouatta palliata (singe hurleur), un primate d'AmĂ©rique centrale. Ainsi, l'Ă©tude cherche Ă dĂ©terminer si les Alouatta palliata prĂ©fĂšrent aussi l'utilisation d'une main lors de la rĂ©alisation d'activitĂ©s quotidiennes : la nutrition, le dĂ©placement, l'agrippement, le grattage, le jeu et le toilettage. La portĂ©e scientifique de cette Ă©tude comportementale est de dĂ©terminer si les Alouatta palliata font Ă©galement preuve d'une latĂ©ralisation au niveau de l'encĂ©phale gauche qui s'exprimerait par une prĂ©dominance dans l'usage de la main droite, ce qui renseignerait sur la progression cĂ©rĂ©brale de l'Homme dans l'Ă©volution. Ă la suite d'une Ă©tude rĂ©alisĂ©e Ă la station biologique El Zota, au nord-est du Costa Rica, et grĂące Ă la technique d'Ă©chantillonnage par individu, il a Ă©tĂ© possible de noter la main utilisĂ©e lorsque les Alouatta palliata rĂ©alisaient leurs activitĂ©s quotidiennes. L'Ă©tude dĂ©montre que ces primates d'El Zota utilisent Ă©galement leurs deux mains lors des activitĂ©s observĂ©es. Ils sont donc ambidextres, contrairement aux humains
Les métropoles sont-elles multipolaires ? Analyses multi-critÚres de l'autonomie des villes intermédiaires dans les régions métropolitaines par la mobilité du quotidien
International audienceQuelles sont les limites des mĂ©tropoles ? Cette question alimente beaucoup de dĂ©bats sans jamais trouver de rĂ©ponses dĂ©finitives. Les rĂ©formes territoriales cherchent Ă renforcer une gouvernance mĂ©tropolitaine Ă lâĂ©chelle des espaces de vie. Les dĂ©coupes politico-administratives renvoient Ă un contenu complexe de pratiques et de reprĂ©sentations dont les institutions sâefforcent de fonder en raison la dĂ©finition des limites [Pinson, Thomann, 2001]. Il apparaĂźt vite difficile de dĂ©terminer « lâidĂ©al scalaire », de mettre des bornes aux espaces mĂ©tropolitains ou de dessiner des bassins de vie : « qui, de nos jours, peut prĂ©tendre vivre et travailler dans un bassin ? » [Pelletier, Vanier, 1997]. Lâenjeu est de passer de la recherche dâune image figĂ©e des aires fonctionnelles des pratiques mĂ©tropolitaines au film animĂ© des territoires de la mobilitĂ©. Pour rĂ©pondre Ă la complexitĂ© des pratiques de dĂ©placements, il est nĂ©cessaire de disposer de mĂ©thodes proposant une vision multi-niveaux des bassins de mobilitĂ©. In fine, notre objectif est dâobserver le niveau dâautonomie ou de dĂ©pendance des pĂŽles relais des mĂ©tropoles pour apprĂ©hender leur caractĂšre multipolaire. Nous proposons de dessiner les espaces fĂ©dĂ©rĂ©s par les dĂ©placements quotidiens des habitants des rĂ©gions mĂ©tropolitaines pour mesurer le degrĂ© dâautonomie des villes intermĂ©diaires. Pour cela, nous utilisons la mĂ©thode et lâoutil de gĂ©ovisualisation appelĂ© « bassin de dĂ©placement » et dĂ©veloppĂ© par le Cerema [Hurez, Pelata, 2016]. Lâoutil « bassin de dĂ©placement » est basĂ© sur les dĂ©placements dĂ©crits dans les EnquĂȘtes-DĂ©placements (ED), hors retour au domicile, des habitants des territoires concernĂ©s. Il a pour objectif de reconstituer les bassins dedĂ©placements de maniĂšre itĂ©rative en partant de la matrice des dĂ©placements tous modes et tous motifs issus dâune ED
Choosing Wisely Canada: The Canadian College of Medical Geneticistsâ (CCMG) List of Five Items Physicians and Patients Should Question
Nonstop mRNAs generate a ground state of mitochondrial gene expression noise
Funding Information: This work was supported by the Academy of Finland (307431 and 314706 to B.J.B.), the Sigrid Juselius Foundation Senior Investigator Award to B.J.B., and United Mitochondrial Disease Foundation (PI-16-0598 to B.J.B.) and donations from the Hereditary Neuropathy Foundation, Lindsey Flynt, and Medtronic to B.J.B.; the Orion Research Foundation and the Finnish Cultural Foundation to K.Y.N.; the Academy of Finland (321961 to U.R.); the Sigrid Juselius Foundation, the Academy of Finland (331556), and the Jane and Aatos Erkko Foundation to C.D.D.; Action Medical Research (GN2494 to W.G.N.) and the Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007 to W.G.N.); the Wellcome Centre for Mitochondrial Research (203105/Z/16/Z to R.W.T.), the Mitochondrial Disease Patient Cohort (UK) (G0800674 to R.W.T.), the Medical Research Council International Centre for Genomic Medicine in Neuromuscular Disease (MR/S005021/1 to R.W.T.), the Lily Foundation, the UK NIHR Biomedical Research Centre for Ageing and Age-related disease award to the Newcastle upon Tyne Foundation Hospitals NHS Trust, the Pathological Society, and the UK NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children to R.W.T.; Medical Research Council (MR/W019027/1 to W.G.N. and R.W.T.); the Academy of Finland (338836 and 314672 to V.O.P.); and the Sigrid Juselius Foundation and the Jane and Aatos Erkko Foundation. Publisher Copyright: Copyright © 2022 The Authors, some rights reserved;A stop codon within the mRNA facilitates coordinated termination of protein synthesis, releasing the nascent polypeptide from the ribosome. This essential step in gene expression is impeded with transcripts lacking a stop codon, generating nonstop ribosome complexes. Here, we use deep sequencing to investigate sources of nonstop mRNAs generated from the human mitochondrial genome. We identify diverse types of nonstop mRNAs on mitochondrial ribosomes that are resistant to translation termination by canonical release factors. Failure to resolve these aberrations by the mitochondrial release factor in rescue (MTRFR) imparts a negative regulatory effect on protein synthesis that is associated with human disease. Our findings reveal a source of underlying noise in mitochondrial gene expression and the importance of responsive ribosome quality control mechanisms for cell fitness and human health.Peer reviewe
MMTV-PyMT and derived Met-1 mouse mammary tumor cells as models for studying the role of the androgen receptor in triple-negative breast cancer progression
Triple-negative breast cancer (TNBC) has a faster rate of metastasis compared to other breast cancer subtypes and no effective targeted therapies are currently FDA-approved. Recent data indicate that the androgen receptor (AR) promotes tumor survival and may serve as a potential therapeutic target in TNBC. Studies of AR in disease progression and the systemic effects of anti-androgens have been hindered by the lack of an AR-positive (AR+) immunocompetent preclinical model. In this study we identified the transgenic MMTV-PyMT (mouse mammary tumor virus-polyoma middle tumor antigen) mouse mammary gland carcinoma model of breast cancer and Met-1 cells derived from this model as tools to study the role of AR in breast cancer progression. AR protein expression was examined in late-stage primary tumors and lung metastases from MMTV-PyMT mice as well as in Met-1 cells by immunohistochemistry (IHC). Sensitivity of Met-1 cells to the AR agonist dihydrotestosterone (DHT) and anti-androgen therapy was examined using cell viability, migration/invasion, and anchorage-independent growth assays. Late-stage primary tumors and lung metastases from MMTV-PyMT mice and Met-1 cells expressed abundant nuclear AR protein, while negative for estrogen and progesterone receptors. Met-1 sensitivity to DHT and AR antagonists demonstrated a reliance on AR for survival, and AR antagonists inhibited invasion and anchorage-independent growth. These data suggest that the MMTV-PyMT model and Met-1 cells may serve as valuable tools for mechanistic studies of the role of AR in disease progression and how anti-androgens affect the tumor microenvironment
Opening the Woods: Towards a Quantification of Neolithic Clearance Around the Somerset Levels and Moors
Environmental reconstructions from pollen records collected within archaeological landscapes have traditionally taken a broadly narrative approach, with few attempts made at hypothesis testing or formal assessment of uncertainty. This disjuncture between the traditional interpretive approach to palynological data and the requirement for detailed, locally specific reconstructions of the landscapes in which people lived has arguably hindered closer integration of palaeoecological and archaeological datasets in recent decades. Here we implement a fundamentally different method for reconstructing past land cover from pollen records to the landscapes of and around the Somerset Levels and Moors â the Multiple Scenario Approach (MSA) â to reconstruct land cover for a series of 200-year timeslices covering the period 4200â2000 cal BC. Modelling of both archaeological and sediment chronologies enables integration of reconstructed changes in land cover with archaeological evidence of contemporary Neolithic human activity. The MSA reconstructions are presented as a series of land cover maps and as graphs of quantitative measures of woodland clearance tracked over time. Our reconstructions provide a more nuanced understanding of the scale and timing of Neolithic clearance than has previously been available from narrative based interpretations of pollen data. While the archaeological record tends to promote a view of long-term continuity in terms of the persistent building of wooden structures in the wetlands, our new interpretation of the palynological data contributes a more dynamic and varying narrative. Our case study demonstrates the potential for further integration of archaeological and palynological datasets, enabling us to get closer to the landscapes in which people lived
The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position statement of the Canadian College of medical geneticists
Purpose and scope: The aim of this Position Statement is to provide recommendations for Canadian medical geneticists, clinical laboratory geneticists, genetic counsellors and other physicians regarding the use of genome-wide sequencing of germline DNA in the context of clinical genetic diagnosis. This statement has been developed to facilitate the clinical translation and development of best practices for clinical genome-wide sequencing for genetic diagnosis of monogenic diseases in Canada; it does not address the clinical application of this technology in other fields such as molecular investigation of cancer or for population screening of healthy individuals. Methods of statement development: Two multidisciplinary groups consisting of medical geneticists, clinical laboratory geneticists, genetic counsellors, ethicists, lawyers and genetic researchers were assembled to review existing literature and guidelines on genome-wide sequencing for clinical genetic diagnosis in the context of monogenic diseases, and to make recommendations relevant to the Canadian context. The statement was circulated for comment to the Canadian College of Medical Geneticists (CCMG) membership-at-large and, following incorporation of feedback, approved by the CCMG Board of Directors. The CCMG is a Canadian organisation responsible for certifying medical geneticists and clinical laboratory geneticists, and for establishing professional and ethical standards for clinical genetics services in Canada. Results and conclusions: Recommendations include (1) clinical genome-wide sequencing is an appropriate approach in the diagnostic assessment of a patient for whom there is suspicion of a significant monogenic disease that is associated with a high degree of genetic heterogeneity, or where specific genetic tests have failed to provide a diagnosis; (2) until the benefits of reporting incidental findings are established, we do not endorse the intentional clinical analysis of disease-associated genes other than those linked to the primary indication; and (3) clinicians should provide genetic counselling and obtain informed consent prior to undertaking clinical genome-wide sequencing. Counselling should include discussion of the limitations of testing, likelihood and implications of diagnosis and incidental findings, and the potential need for further analysis to facilitate clinical interpretation, including studies performed in a research setting. These recommendations will be routinely reevaluated as knowledge of diagnostic and clinical utility of clinical genome-wide sequencing improves. While the document was developed to direct practice in Canada, the applicability of the statement is broader and will be of interest to clinicians and health jurisdictions internationally
Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations
Smooth muscle dysfunction syndrome (SMDS) due to heterozygous ACTA2 arginine 179 alterations is characterized by patent ductus arteriosus, vasculopathy (aneurysm and occlusive lesions), pulmonary arterial hypertension, and other complications in smooth muscle-dependent organs. We sought to define the clinical history of SMDS to develop recommendations for evaluation and management.
Medical records of 33 patients with SMDS (median age 12 years) were abstracted and analyzed.
All patients had congenital mydriasis and related pupillary abnormalities at birth and presented in infancy with a patent ductus arteriosus or aortopulmonary window. Patients had cerebrovascular disease characterized by small vessel disease (hyperintense periventricular white matter lesions; 95%), intracranial artery stenosis (77%), ischemic strokes (27%), and seizures (18%). Twelve (36%) patients had thoracic aortic aneurysm repair or dissection at median age of 14 years and aortic disease was fully penetrant by the age of 25 years. Three (9%) patients had axillary artery aneurysms complicated by thromboembolic episodes. Nine patients died between the ages of 0.5 and 32 years due to aortic, pulmonary, or stroke complications, or unknown causes.
Based on these data, recommendations are provided for the surveillance and management of SMDS to help prevent early-onset life-threatening complications
Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)
The Global Parkinson's Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia
Loss-of-function mutations in the X-linked biglycan gene cause a severe syndromic form of thoracic aortic aneurysms and dissections.
Thoracic aortic aneurysm and dissection (TAAD) is typically inherited in an autosomal dominant manner, but rare X-linked families have been described. So far, the only known X-linked gene is FLNA, which is associated with the periventricular nodular heterotopia type of Ehlers-Danlos syndrome. However, mutations in this gene explain only a small number of X-linked TAAD families.
We performed targeted resequencing of 368 candidate genes in a cohort of 11 molecularly unexplained Marfan probands. Subsequently, Sanger sequencing of BGN in 360 male and 155 female molecularly unexplained TAAD probands was performed.
We found five individuals with loss-of-function mutations in BGN encoding the small leucine-rich proteoglycan biglycan. The clinical phenotype is characterized by early-onset aortic aneurysm and dissection. Other recurrent findings include hypertelorism, pectus deformity, joint hypermobility, contractures, and mild skeletal dysplasia. Fluorescent staining revealed an increase in TGF-ÎČ signaling, evidenced by an increase in nuclear pSMAD2 in the aortic wall. Our results are in line with those of prior reports demonstrating that Bgn-deficient male BALB/cA mice die from aortic rupture.
In conclusion, BGN gene defects in humans cause an X-linked syndromic form of severe TAAD that is associated with preservation of elastic fibers and increased TGF-ÎČ signaling.Genet Med 19 4, 386-395
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