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1. Impact of multidomain preventive strategies on functional brain connectivity in older adults with cognitive complaint: Subset from the Montpellier center of the ancillary MAPT-MRI study

Author

Lisa Perus, Jean-François Mangin, Jérémy Deverdun, Laure-Anne Gutierrez, Emmanuelle Gourieux, Clara Fischer, Liesjet E. H. Van Dokkum, Clara Manesco, Germain Busto, Sophie Guyonnet, Bruno Vellas, Audrey Gabelle, Emmanuelle Le Bars, The MAPT/DSA group, Isabelle Carrié, Lauréne Brigitte, Catherine Faisant, Françoise Lala, Julien Delrieu, Hélène Villars, Emeline Combrouze, Carole Badufle, Audrey Zueras, Sandrine Andrieu, Christelle Cantet, Christophe Morin, Gabor Abellan Van Kan, Charlotte Dupuy, Yves Rolland, Céline Caillaud, Pierre-Jean Ousset, Sherry Willis, Sylvie Belleville, Brigitte Gilbert, Francine Fontaine, Jean-François Dartigues, Isabelle Marcet, Fleur Delva, Alexandra Foubert, Sandrine Cerda, Marie-Noëlle-Cuffi, Corinne Costes, Olivier Rouaud, Patrick Manckoundia, Valérie Quipourt, Sophie Marilier, Evelyne Franon, Lawrence Bories, Marie-Laure Pader, Marie-France Basset, Bruno Lapoujade, Valérie Faure, Michael Li Yung Tong, Christine Malick-Loiseau, Evelyne Cazaban-Campistron, Françoise Desclaux, Colette Blatge, Thierry Dantoine, Cécile Laubarie-Mouret, Isabelle Saulnier, Jean-Pierre Clément, Marie-Agnès Picat, Laurence Bernard-Bourzeix, Stéphanie Willebois, Iléana Désormais, Noëlle Cardinaud, Marc Bonnefoy, Pierre Livet, Pascale Rebaudet, Claire Gédéon, Catherine Burdet, Flavien Terracol, Alain Pesce, Stéphanie Roth, Sylvie Chaillou, Sandrine Louchart, Kristel Sudres, Nicolas Lebrun, Nadège Barro-Belaygues, Jacques Touchon, Karim Bennys, Aurélia Romano, Lynda Touati, Cécilia Marelli, Cécile Pays, Philippe Robert, Franck Le Duff, Claire Gervais, Sébastien Gonfrier, Yannick Gasnier, Serge Bordes, Danièle Begorre, Christian Carpuat, Khaled Khales, Jean-François Lefebvre, Samira Misbah El Idrissi, Pierre Skolil, Jean-Pierre Salles, Carole Dufouil, Stéphane Lehéricy, Marie Chupin, Ali Bouhayia, Michèle Allard, Frédéric Ricolfi, Dominique Dubois, Marie Paule Bonceour Martel, François Cotton, Alain Bonafé, Stéphane Chanalet, Françoise Hugon, Fabrice Bonneville, Christophe Cognard, François Chollet, Pierre Payoux, Thierry Voisin, Sophie Peiffer, Anne Hitzel, Michel Zanca, Jacques Monteil, Jacques Darcourt, Laurent Molinier, Hélène Derumeaux, Nadège Costa, Bertrand Perret, Claire Vinel, Sylvie Caspar-Bauguil, Pascale Olivier-Abbal, and Nicola Coley

Subjects
magnetic resonance imaging (MRI), resting-state functional MRI (rs-fMRI), multidomain intervention, exercise, cognitive training, omega-3 fatty acids, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

IntroductionThe impact of multi-domain preventive interventions on older adults, in particular on those with higher risk to develop Alzheimer's disease (AD), could be beneficial, as it may delay cognitive decline. However, the precise mechanism of such positive impact is not fully understood and may involve brain reserve and adaptability of brain functional connectivity (FC).MethodsTo determine the effect of multidomain interventions (involving physical activity, cognitive training, nutritional counseling alone or in combination with omega-3 fatty acid supplementation and vs. a placebo) on the brain, longitudinal FC changes were assessed after 36 months of intervention on 100 older adults (above 70 year-old) with subjective cognitive complaints.ResultsNo global change in FC was detected after uni or multidomain preventive interventions. However, an effect of omega-3 fatty acid supplementation dependent on cognitive decline status was underlined for frontoparietal, salience, visual and sensorimotor networks FC. These findings were independent of the cortical thickness and vascular burden.DiscussionThese results emphasize the importance of patient stratification, based on risk factors, for preventive interventions.

Published
2023
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2. Modeling gene-environment interactions in longitudinal family studies: a comparison of methods and their application to the association between the IGF pathway and childhood obesity

Author

Cheng Wang, Marie-Hélène Roy-Gagnon, Jean-François Lefebvre, Kelly M. Burkett, and Lise Dubois

Subjects
Childhood obesity, Insulin-like growth factors, Twin studies, Longitudinal family studies, Gene-environment interaction, Non-linear interaction, Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background The interactive effect of the IGF pathway genes with the environment may contribute to childhood obesity. Such gene-environment interactions can take on complex forms. Detecting those relationships using longitudinal family studies requires simultaneously accounting for correlations within individuals and families. Methods We studied three methods for detecting interaction effects in longitudinal family studies. The twin model and the nonparametric partition-based score test utilized individual outcome averages, whereas the linear mixed model used all available longitudinal data points. Simulation experiments were performed to evaluate the methods’ power to detect different gene-environment interaction relationships. These methods were applied to the Quebec Newborn Twin Study data to test for interaction effects between the IGF pathway genes (IGF-1, IGFALS) and environmental factors (physical activity, daycare attendance and sleep duration) on body mass index outcomes. Results For the simulated data, the twin model with the mean time summary statistic yielded good performance overall. Modelling an interaction as linear when the true model had a different relationship influenced power; for certain non-linear interactions, none of the three methods were effective. Our analysis of the IGF pathway genes showed suggestive association for the joint effect of IGF-1 variant at position 102,791,894 of chromosome 12 and physical activity. However, this association was not statistically significant after multiple testing correction. Conclusions The analytical approaches considered in this study were not robust to different gene-environment interactions. Methodological innovations are needed to improve the current methods’ performances for detecting non-linear interactions. More studies are needed in order to better understand the IGF pathway’s role in childhood obesity development.

Published
2019
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3. Investigating Gene–Gene and Gene–Environment Interactions in the Association Between Overnutrition and Obesity-Related Phenotypes

Author

François Tessier, Bénédicte Fontaine-Bisson, Jean-François Lefebvre, Ahmed El-Sohemy, and Marie-Hélène Roy-Gagnon

Subjects
genetic, gene–environment interactions, overnutrition, obesity, BMI, macronutrient, Genetics, QH426-470
Abstract

Introduction: Animal studies suggested that NFKB1, IKBKB, and SOCS3 genes could be involved in the association between overnutrition and obesity. This study aims to investigate interactions involving these genes and macronutrient intakes affecting obesity-related phenotypes.Methods: We used a traditional statistical method, logistic regression, and compared it to alternative statistical method, multifactor dimensionality reduction (MDR) and penalized logistic regression (PLR), to better detect genes/environment interactions in the Toronto Nutrigenomics and Health Study (n = 1639) using dichotomized body mass index (BMI) and waist circumference as obesity-related phenotypes. Exposure variables included genotype on 54 single nucleotide polymorphisms (NFKB1: 18, IKBKB: 9, SOCS3: 27), macronutrient (carbohydrates, protein, fat) and alcohol intakes and ethno-cultural background.Results: After correction for multiple testing, no interaction was found using logistic regression. MDR identified interactions between SOCS3 rs6501199 and rs4969172, and IKBKB rs3747811 affecting BMI in the Caucasian population; SOCS3 rs6501199 and NFKB1 rs1609798 affecting WC in the Caucasian population; and SOCS3 rs4436839 and IKBKB rs3747811 affecting WC in the South Asian population. PLR found a main effect of SOCS3 rs12944581 on BMI among the South Asian population.Conclusion: While MDR and PLR had discordant results, some models support results from previous studies. These results emphasize the need to use alternative statistical methods to investigate high-order interactions and suggest that variants in the nutrient-responsive hypothalamic IKKB/NF-kB signaling pathway may be involved in obesity pathogenesis.

Published
2019
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4. X-linked MTMR8 diversity and evolutionary history of sub-Saharan populations.

Author

Damian Labuda, Vania Yotova, Jean-François Lefebvre, Claudia Moreau, Gerd Utermann, and Scott M Williams

Subjects
Medicine, Science
Abstract

The genetic diversity within an 11 kb segment of the MTMR8 gene in a sample of 111 sub-Saharan and 49 non-African X chromosomes was investigated to assess the early evolutionary history of sub-Saharan Africans and the out-of-Africa expansion. The analyses revealed a complex genetic structure of the Africans that contributed to the emergence of modern humans. We observed partitioning of two thirds of old lineages among southern, west/central and east African populations indicating ancient population stratification predating the out of Africa migration. Age estimates of these lineages, older than coalescence times of uniparentally inherited markers, raise the question whether contemporary humans originated from a single population or as an amalgamation of different populations separated by years of independent evolution, thus suggesting a greater antiquity of our species than generally assumed. While the oldest sub-Saharan lineages, ~500 thousand years, are found among Khoe-San from southern-Africa, a distinct haplotype found among Biaka is likely due to admixture from an even older population. An East African population that gave rise to non-Africans underwent a selective sweep affecting the subcentromeric region where MTMR8 is located. This and similar sweeps in four other regions of the X chromosome, documented in the literature, effectively reduced genetic diversity of non-African chromosomes and therefore may have exacerbated the effect of the demographic bottleneck usually ascribed to the out of Africa migration. Our data is suggestive, however, that a bottleneck, occurred in Africa before range expansion.

Published
2013
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5. Native American admixture in the Quebec founder population.

Author

Claudia Moreau, Jean-François Lefebvre, Michèle Jomphe, Claude Bhérer, Andres Ruiz-Linares, Hélène Vézina, Marie-Hélène Roy-Gagnon, and Damian Labuda

Subjects
Medicine, Science
Abstract

For years, studies of founder populations and genetic isolates represented the mainstream of genetic mapping in the effort to target genetic defects causing Mendelian disorders. The genetic homogeneity of such populations as well as relatively homogeneous environmental exposures were also seen as primary advantages in studies of genetic susceptibility loci that underlie complex diseases. European colonization of the St-Lawrence Valley by a small number of settlers, mainly from France, resulted in a founder effect reflected by the appearance of a number of population-specific disease-causing mutations in Quebec. The purported genetic homogeneity of this population was recently challenged by genealogical and genetic analyses. We studied one of the contributing factors to genetic heterogeneity, early Native American admixture that was never investigated in this population before. Consistent admixture estimates, in the order of one per cent, were obtained from genome-wide autosomal data using the ADMIXTURE and HAPMIX software, as well as with the fastIBD software evaluating the degree of the identity-by-descent between Quebec individuals and Native American populations. These genomic results correlated well with the genealogical estimates. Correlations are imperfect most likely because of incomplete records of Native founders' origin in genealogical data. Although the overall degree of admixture is modest, it contributed to the enrichment of the population diversity and to its demographic stratification. Because admixture greatly varies among regions of Quebec and among individuals, it could have significantly affected the homogeneity of the population, which is of importance in mapping studies, especially when rare genetic susceptibility variants are in play.

Published
2013
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11. STRmix™ put to the test: 300 000 non-contributor profiles compared to four-contributor DNA mixtures and the impact of replicates

Author

Dominic Granger, Sarah Noël, Jean-François Lefebvre, Josée Noël, and Diane Séguin

Subjects
0301 basic medicine, Computational biology, Replicate, Pathology and Forensic Medicine, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, Genetics, 030216 legal & forensic medicine, Genotyping, DNA, Mathematics
Abstract

Probabilistic genotyping approaches are increasingly used for the interpretation of DNA mixtures. To explore the specificity of one of these systems (STRmix™), we conducted an extensive study using 24 complex mixtures: all were known or apparent 4-person mixtures with at least one contributor representing less than 20% of total DNA, and all mixtures had at least one contributor with suboptimal DNA quantity. Those mixtures were either generated in-house or from casework. All the mixtures were compared to 300,000 virtual non-contributors, resulting in a dataset of 7.2 million comparisons. The great majority of the non-contributor comparisons led to a LR lower than 1 for a specificity of 99.1%. The effect of using replicate amplifications to calculate the LR of non-contributors was also assessed as triplicates were used and led to an increased specificity of 99.8%. The very large extent of the analyzed data shows that STRmix™ has an excellent ability to discriminate non-contributors from complex DNA mixtures.

Published
2019
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12. Synthesis of Ruthenium Tris‐Diimine Photosensitizers Substituted by Four Methylphosphonate Anchoring Groups for Dye‐Sensitized Photoelectrochemical Cell Applications

Author

Nicolas Queyriaux, Emmanouil Giannoudis, Jean-François Lefebvre, Vincent Artero, Murielle Chavarot-Kerlidou, Solar fuels, hydrogen and catalysis (SolHyCat ), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), DPM, Département de pharmacochimie moléculaire (DPM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017)

Subjects
Tris, Photoelectrochemistry, chemistry.chemical_element, Anchoring, 02 engineering and technology, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, Photoelectrochemical cell, 010402 general chemistry, 021001 nanoscience & nanotechnology, Photochemistry, 01 natural sciences, Photosensitizers, Ruthenium, 0104 chemical sciences, Inorganic Chemistry, chemistry.chemical_compound, chemistry, Anchoring groups, 0210 nano-technology, Diimine
Abstract

International audience; The design and synthesis of ruthenium tris-diimine photosensitizers appropriately functionalized to be (i) anchored onto transparent conductive oxides (TCO) and (ii) covalently coupled with a water-splitting catalyst represents an important target for solar fuel production in dye-sensitized photoelectrochemical cells (DS-PECs). In this study, two different synthetic routes to prepare heteroleptic [Ru(4,4 '-(CH2PO3Et2)(2)-bpy)(2)((NN)-N-)](PF6)(2) complexes are evaluated, the scope and limitations of the organometallic pathway involving half-sandwich eta(6)-arene ruthenium complexes as synthetic intermediates being especially studied. The spectroscopic and electrochemical characterization of a series of novel structures varying by the nature of the third diimine (NN)-N- ligand is reported.

Published
2019
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13. Meal-related difficulties and weight loss in older people: Longitudinal data from MAPT study

Author

Gaëlle Soriano, Philippe De Souto Barreto, Kelly Virecoulon Giudici, Christelle Cantet, Sophie Guyonnet, Bruno Vellas, Yves Rolland, Sandrine Andrieu, Isabelle Carrié, Lauréane Brigitte, Catherine Faisant, Françoise Lala, Julien Delrieu, Hélène Villars, Emeline Combrouze, Carole Badufle, Audrey Zueras, Christophe Morin, Gabor Abellan Van Kan, Charlotte Dupuy, Céline Caillaud, Pierre-Jean Ousset, Bertrand Fougère, Sherry Willis, Sylvie Belleville, Brigitte Gilbert, Francine Fontaine, Jean-François Dartigues, Isabelle Marcet, Fleur Delva, Alexandra Foubert, Sandrine Cerda Marie-Noëlle-Cuffi, Corinne Costes, Olivier Rouaud, Patrick Manckoundia, Valérie Quipourt, Sophie Marilier, Evelyne Franon, Lawrence Bories, Marie-Laure Pader, Marie-France Basset, Bruno Lapoujade, Valérie Faure, Michael Li Yung Tong, Christine Malick-Loiseau, Evelyne Cazaban-Campistron, Françoise Desclaux, Colette Blatge, Thierry Dantoine, Cécile Laubarie-Mouret, Isabelle Saulnier, Jean-Pierre Clément, Marie-Agnès Picat, Laurence Bernard-Bourzeix, Stéphanie Willebois, Iléana Désormais, Noëlle Cardinaud, Marc Bonnefoy, Pierre Livet, Pascale Rebaudet, Claire Gédéon, Catherine Burdet, Flavien Terracol, Alain Pesce, Stéphanie Roth, Sylvie Chaillou, Sandrine Louchart, Kristelle Sudres, Nicolas Lebrun, Nadège Barro-Belaygues, Jacques Touchon, Karim Bennys, Audrey Gabelle, Aurélia Romano, Lynda Touati, Cécilia Marelli, Cécile Pays, Philippe Robert, Franck Le Duff, Claire Gervais, Sébastien Gonfrier, Yannick Gasnier, Serge Bordes, Danièle Begorre, Christian Carpuat, Khaled Khales, Jean-François Lefebvre, Samira Misbah El Idrissi, Pierre Skolil, Jean-Pierre Salles, Carole Dufouil, Stéphane Lehéricy, Marie Chupin, Jean-François Mangin, Ali Bouhayia, Michèle Allard, Frédéric Ricolfi, Dominique Dubois, Marie Paule Bonceour Martel, François Cotton, Alain Bonafé, Stéphane Chanalet, Françoise Hugon, Fabrice Bonneville, Christophe Cognard, François Chollet, Pierre Payoux, Thierry Voisin, Sophie Peiffer, Anne Hitzel, Michel Zanca, Jacques Monteil, Jacques Darcourt, Laurent Molinier, Hélène Derumeaux, Nadège Costa, Christian Vincent, Bertrand Perret, Claire Vinel, Pascale Olivier-Abbal, Nicola Coley, Laboratoire de Gérontechnologie [Hôpital La Grave-CHU de Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Gérontopôle, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut Jean Lamour (IJL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Vieillissement, MAPT DSA Study Group: Bruno Vellas, Sophie Guyonnet, Isabelle Carrié, Lauréane Brigitte, Catherine Faisant, Françoise Lala, Julien Delrieu, Hélène Villars, Emeline Combrouze, Carole Badufle, Audrey Zueras, Sandrine Andrieu, Christelle Cantet, Christophe Morin, Gabor Abellan Van Kan, Charlotte Dupuy, Yves Rolland, Céline Caillaud, Pierre-Jean Ousset, Bertrand Fougère, Sherry Willis, Sylvie Belleville, Brigitte Gilbert, Francine Fontaine, Jean-François Dartigues, Isabelle Marcet, Fleur Delva, Alexandra Foubert, Sandrine Cerda Marie-Noëlle-Cuffi, Corinne Costes, Olivier Rouaud, Patrick Manckoundia, Valérie Quipourt, Sophie Marilier, Evelyne Franon, Lawrence Bories, Marie-Laure Pader, Marie-France Basset, Bruno Lapoujade, Valérie Faure, Michael Li Yung Tong, Christine Malick-Loiseau, Evelyne Cazaban-Campistron, Françoise Desclaux, Colette Blatge, Thierry Dantoine, Cécile Laubarie-Mouret, Isabelle Saulnier, Jean-Pierre Clément, Marie-Agnès Picat, Laurence Bernard-Bourzeix, Stéphanie Willebois, Iléana Désormais, Noëlle Cardinaud, Marc Bonnefoy, Pierre Livet, Pascale Rebaudet, Claire Gédéon, Catherine Burdet, Flavien Terracol, Alain Pesce, Stéphanie Roth, Sylvie Chaillou, Sandrine Louchart, Kristelle Sudres, Nicolas Lebrun, Nadège Barro-Belaygues, Jacques Touchon, Karim Bennys, Audrey Gabelle, Aurélia Romano, Lynda Touati, Cécilia Marelli, Cécile Pays, Philippe Robert, Franck Le Duff, Claire Gervais, Sébastien Gonfrier, Yannick Gasnier, Serge Bordes, Danièle Begorre, Christian Carpuat, Khaled Khales, Jean-François Lefebvre, Samira Misbah El Idrissi, Pierre Skolil, Jean-Pierre Salles, Carole Dufouil, Stéphane Lehéricy, Marie Chupin, Jean-François Mangin, Ali Bouhayia, Michèle Allard, Frédéric Ricolfi, Dominique Dubois, Marie Paule Bonceour Martel, François Cotton, Alain Bonafé, Stéphane Chanalet, Françoise Hugon, Fabrice Bonneville, Christophe Cognard, François Chollet, Pierre Payoux, Thierry Voisin, Julien Delrieu, Sophie Peiffer, Anne Hitzel, Michel Zanca, Jacques Monteil, Jacques Darcourt, Laurent Molinier, Hélène Derumeaux, Nadège Costa, Christian Vincent, Bertrand Perret, Claire Vinel, Pascale Olivier-Abbal, Sandrine Andrieu, Christelle Cantet, Nicola Coley, and CCSD, Accord Elsevier

Subjects
0301 basic medicine, Gerontology, Male, Meal preparation, Weight loss, Activities of daily living, [SDV]Life Sciences [q-bio], Health Behavior, 030209 endocrinology & metabolism, (financial or non-financial) related to the study, Disease, Critical Care and Intensive Care Medicine, Body Mass Index, Preparing meals, 03 medical and health sciences, Eating, Food Preferences, 0302 clinical medicine, Cognition, Elderly, Shopping, medicine, Humans, Longitudinal Studies, Prospective Studies, Cooking, Meals, Aged, Randomized Controlled Trials as Topic, 2. Zero hunger, Aged, 80 and over, Meal, 030109 nutrition & dietetics, Nutrition and Dietetics, Proportional hazards model, business.industry, Depression, 3. Good health, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, Functional Status, Female, Independent Living, medicine.symptom, business
Abstract

International audience; BACKGROUND: Difficulties with meal-related activities (preparing meals and food shopping) may influence food intake, and contribute to nutritional risk among elderly people. All known studies on this topic had a cross-sectional design, thereby no causal relationships could be derived. We aim to investigate if difficulties with meal-related activities can contribute to subsequent weight loss in community-dwelling older people. METHODS: We used data of older subjects from the MAPT Study (n = 1531, median age = 74 years, 64% women), who provided prospective data on weight every 6 months and cognitive, physical condition, and functional capacities every year during a 3-year period. Difficulties preparing meals and shopping were evaluated each year with the Alzheimer's Disease Cooperative Study-Activities of Daily Living Prevention Instrument (ADCS ADL-PI) Scale. The risk of losing weight (≥5% or ≥ 3 kg in the following year) was estimated using a time-dependent Cox regression model. RESULTS: During the 3-year follow-up, a total of 851 subjects experienced at least a 5% or 3 kg weight loss. Two hundred thirty-seven subjects declared having difficulties with meal preparation at least once, and 133 declared having difficulties shopping. Subjects reporting any meal-related difficulties were older (p \textless 0.001), had more depressive symptoms (p \textless 0.001), and a lower physical function (p \textless 0.001) compared to those without difficulties. They also had a lower cognitive score (preparing meals: p \textless 0.001; shopping: p = 0.005) and a lower body mass index (preparing meals: p = 0.005; shopping: p = 0.023) at the end of the study. Meal-related activities were not associated with weight loss in unadjusted analysis and after adjustment for sex, age, depression, physical and cognitive status. CONCLUSION: Difficulties preparing meals and shopping had no effect on weight loss in community-dwelling older people, despite their association with advanced age, functional decline, and depressive symptoms.

Published
2020
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14. Associations Between Physical Activity, Blood-Based Biomarkers of Neurodegeneration, and Cognition in Healthy Older Adults: The MAPT Study

Author

Randall J. Bateman, Jean-Pierre Salles, Pascale Rebaudet, Jacques Touchon, Christian Carpuat, Claire Vinel, Dominique Dubois, Aurélia Romano, Flavien Terracol, Emeline Combrouze, Marc Bonnefoy, Philipe de Souto Barreto, Thierry Dantoine, Sylvie Caspar-Bauguil, Stéphane Chanalet, Marie-Laure Pader, Isabelle Saulnier, Sandrine Andrieu, Philippe Robert, Mapt, Céline Caillaud, Michèle Allard, Christelle Cantet, Pierre Payoux, Christine Malick-Loiseau, Sandrine Louchart, Nicola Coley, Lynda Touati, Françoise Hugon, Charlotte Dupuy, Alexandra Foubert, Olivier Rouaud, Kristel Sudres, Alain Bonafe, Geetika Aggarwal, Audrey Gabelle, Sophie Peiffer, Karim Bennys, Francine Fontaine, H. Villars, N. Costa, Evelyne Franon, Jean-François Dartigues, Jean-François Lefebvre, Carole Badufle, Sandrine Cerda, Catherine Burdet, Pierre Livet, Frédéric Ricolfi, Jean-François Mangin, Andrew D. Nguyen, Michael Li Yung Tong, Sylvie Chaillou, Lawrence Bories, Jérémy Raffin, Yan Li, Samira Misbah El Idrissi, Sophie Marilier, Nadège Barro-Belaygues, Bruno Vellas, Marie-Agnès Picat, Catherine Faisant, Françoise Desclaux, Bertrand Perret, Serge Bordes, Pierre-Jean Ousset, Laurent Molinier, Cécile Pays, Yves Rolland, Jean-Pierre Clément, Stéphanie Willebois, Patrick Manckoundia, Michel Zanca, Yannick Gasnier, Valérie Quipourt, Isabelle Carrié, Valérie Faure, Christophe Morin, Christophe Cognard, Claire Gédéon, Lauréane Brigitte, Colette Blatge, Julien Delrieu, Claire Gervais, Pascale Olivier-Abbal, Hélène Derumeaux, Carole Dufouil, Ali Bouhayia, Danièle Begorre, Alain Pesce, Marie Chupin, Françoise Lala, Fabrice Bonneville, Brigitte Gilbert, Franck Le Duff, Laurence Bernard-Bourzeix, Evelyne Cazaban-Campistron, Isabelle Marcet, Jacques Darcourt, François Cotton, Bruno Lapoujade, Gabor Abellan van Kan, John E. Morley, Sophie Guyonnet, Corinne Costes, Sebastien Gonfrier, Audrey Zueras, Anne Hitzel, Stéphanie Roth, Cecilia Marelli, Fleur Delva, Stéphane Lehéricy, Nicolas Lebrun, Pierre Skolil, Khaled Khales, Cécile Laubarie-Mouret, Jacques Monteil, Marie-France Basset, Thierry Voisin, François Chollet, Noëlle Cardinaud, Marie Paule Bonceour Martel, and Ileana Desormais

Subjects
0301 basic medicine, Oncology, Male, medicine.medical_specialty, Aging, Amyloid, Physical exercise, Neuropsychological Tests, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Cognition, Alzheimer Disease, Neurofilament Proteins, Internal medicine, Medicine, Humans, Cognitive Dysfunction, Cognitive decline, Correlation of Data, Exercise, Geriatric Assessment, Aged, Amyloid beta-Peptides, business.industry, Peptide Fragments, Cognitive test, 030104 developmental biology, Cross-Sectional Studies, Quartile, Concomitant, Female, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Biomarkers
Abstract

Physical activity (PA) demonstrated benefits on brain health, but its relationship with blood biomarkers of neurodegeneration remains poorly investigated. We explored the cross-sectional associations of PA with blood concentrations of neurofilament light chain (NFL) and beta amyloid (Aβ)42/40. We further examined whether the interaction between PA and these biomarkers was longitudinally related to cognition. Four-hundred and sixty-five nondemented older adults engaged in an interventional study and who had a concomitant assessment of PA levels and blood measurements of NFL (pg/mL) and Aβ 42/40 were analyzed. A composite Z-score combining 4 cognitive tests was used for cognitive assessment up to a 4-year follow-up. Multiple linear regressions demonstrated that people achieving 500–999 and 2000+ MET-min/week of PA had lower (ln)NFL concentrations than their inactive peers. Logistic regressions revealed that achieving at least 90 MET-min/week of PA was associated with a lower probability of having high NFL concentrations (ie, ≥91.961 pg/mL [third quartile]). PA was not associated with (Aβ)42/40. Mixed-model linear regressions demonstrated that the reverse relationship between PA and cognitive decline tended to be more pronounced as Aβ 42/40 increased, while it was dampened with increasing levels of (ln)NFL concentrations. This study demonstrates that PA is associated with blood NFL but not with Aβ 42/40. Furthermore, it suggests that PA may attenuate the negative association between amyloid load and cognition, while having high NFL levels mitigates the favorable relationship between PA and cognition. More investigations on non demented older adults are required for further validation of the present findings.

Published
2020

15. Determining the impact of unknown individuals in criminality using network analysis of DNA matches

Author

Léo Lavergne, Rémi Boivin, Simon Baechler, Patrick Jeuniaux, Karine Fiola, Diane Séguin, Jean-François Lefebvre, and Emmanuel Milot

Subjects
Criminal Behavior, Humans, DNA, Criminals, Forensic Medicine, Law, Police, Pathology and Forensic Medicine
Abstract

Criminal offenders missing from police files limit the capacity to reconstruct criminal networks for criminological research and operational purposes. Recent studies show that forensic DNA databanks offer potential to address this problem, through large-scale analysis of DNA matches, many of which involve unidentified offenders. Applying social network analysis (SNA) to 18 years of DNA match data from Québec, Canada, we found that 1400 unknowns do not occupy more marginal positions in the network than 13,000 known offenders, and explain up to 18% of SNA values (e.g., betweenness centrality) for the latter while supporting 46% of their clustering values. Our results contrast with previous studies, showing moreover that unknown individuals who are positioned centrally in a network may have a larger impact than previously expected on investigation policing with implications for forensic intelligence.

Published
2022
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16. Photophysics of a Ruthenium Complex with a π-Extended Dipyridophenazine Ligand for DNA Quadruplex Labeling

Author

Linda Zedler, Julian Schindler, Stephan Kupfer, Benjamin Dietzek, Jean-François Lefebvre, Stefanie Gräfe, Philipp Traber, Ying Zhang, Murielle Chavarot-Kerlidou, Martine Demeunynck, Institute of Physical Chemistry, Abbe Center of Photonics, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Leibniz Institute of Photonic Technology Jena, Department Functional Interfaces, Albert-Einstein-Straße 9, 07745 Jena, Germany, Département de pharmacochimie moléculaire (DPM ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
Light, Pyridines, Phenazine, chemistry.chemical_element, Ligands, Spectrum Analysis, Raman, 010402 general chemistry, Photochemistry, 01 natural sciences, Ruthenium, chemistry.chemical_compound, Coordination Complexes, Ultrafast laser spectroscopy, [CHIM]Chemical Sciences, Emission spectrum, Physical and Theoretical Chemistry, Luminescent Agents, 010405 organic chemistry, Ligand, Water, DNA, Electrochemical Techniques, 0104 chemical sciences, 3. Good health, G-Quadruplexes, Models, Chemical, chemistry, Spectrophotometry, Phenazines, Quantum Theory, [PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph], Oxidation-Reduction
Abstract

International audience; The light-switch mechanism of the complex [Ru(bpy)2(Br-dpqp)](PF6)2 (1, bpy = 2,2′-bipyridine, Br-dpqp = 12-bromo-14-ethoxydipyrido[3,2-a:2′,3′-c]quinolino[3,2-h]phenazine), i.e., a light-up probe for the selective labeling of G-quadruplexes, is investigated by time-resolved transient absorption and emission spectroscopy. We show that, in contrast to the prototypical light-switch complex [Ru(bpy)2(dppz)](PF6)2 (2, dppz = dipyrido[3,2-a:2′,3′-c]phenazine), a 3ππ* state localized on the π-extended ligand is the state determining the excited-state properties in both protic and aprotic environments. In aprotic environments, emission originates from a bright 3MLCTphen state, which is thermally accessible from the 3ππ* state at ambient temperature. In the presence of water, i.e., in environments resembling in cellulo situations, the thermally accessible 3MLCT state is altered and becomes close in energy to the 3ππ* state, which induces a rapid excited-state deactivation of the 3ππ* state and a comparably weak emission.

Published
2018
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17. Historical human remains identification through maternal and paternal genetic signatures in a founder population with extensive genealogical record

Author

Damian Labuda, Jean-François Lefebvre, Brad Loewen, Isabelle Ribot, Hélène Vézina, Claudia Moreau, Roger Anglada, Jean-Sébastien Bournival, Emmanuel Milot, Catherine Laprise, Ferran Casals, Tommy Harding, Carles Lalueza-Fox, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fonds de Recherche du Québec, and Natural Sciences and Engineering Research Council of Canada

Subjects
Adult, Genetic Markers, Male, 0106 biological sciences, Buried's identification, 010603 evolutionary biology, 01 natural sciences, Anthropology, Physical, Young Adult, Operating time, Humans, 0601 history and archaeology, Genotyping, Uniparental DNA markers, 060101 anthropology, Osteology, Ancient DNA, Haplotype, Quebec, 06 humanities and the arts, Middle Aged, Genealogy, Body Remains, Geography, Genetic marker, Anthropology, Paternal Inheritance, Identification (biology), Whole-population genealogy, Maternal Inheritance, Anatomy, Founder effect
Abstract

[Objectives] We describe a method to identify human remains excavated from unmarked graves in historical Québec cemeteries by combining parental‐lineage genetic markers with the whole‐population genealogy of Québec contained in the BALSAC database., [Materials and methods] The remains of six men were exhumed from four historical cemeteries in the province of Québec, Canada. DNA was extracted from the remains and genotyped to reveal their mitochondrial and Y‐chromosome haplotypes, which were compared to a collection of haplotypes of genealogically‐anchored modern volunteers. Maternal and paternal genealogies were searched in the BALSAC genealogical record for parental couples matching the mitochondrial and the Y‐chromosome haplotypic signatures, to identify candidate sons from whom the remains could have originated., [Results] Analysis of the matching genealogies identified the parents of one man inhumed in the cemetery of the investigated parish during its operating time. The candidate individual died in 1833 at the age of 58, a plausible age at death in light of osteological analysis of the remains., [Discussion] This study demonstrates the promising potential of coupling genetic information from living individuals to genealogical data in BALSAC to identify historical human remains. If genetic coverage is increased, the genealogical information in BALSAC could enable the identification of 87% of the men (n = 178,435) married in Québec before 1850, with high discriminatory power in most cases since >75% of the parental couples have unique biparental signatures in most regions. Genotyping and identifying Québec's historical human remains are a key to reconstructing the genomes of the founders of Québec and reinhuming archeological remains with a marked grave., European Regional Development Fund, Grant/Award Number: PGC2018‐095931‐B‐100; Fonds de Recherche du Québec ‐ Santé; Fonds de Recherche du Québec‐Société et Culture; Natural Sciences and Engineering Research Council of Canada.

Published
2020

18. Adherence to multidomain interventions for dementia prevention: Data from the FINGER and MAPT trials

Author

Noëlle Cardinaud, Francine Fontaine, Marie Paule Bonceour Martel, Danièle Begorre, Claire Vinel, Dominique Dubois, Serge Bordes, Charlotte Dupuy, Jean-François Dartigues, Lars Bäckman, Marie-Laure Pader, Colette Blatge, Jacques Touchon, Julien Delrieu, Karim Bennys, Miia Kivipelto, Pierre Payoux, Christian Vincent, Ileana Desormais, Françoise Hugon, Isabelle Saulnier, Michèle Allard, Pascale Olivier-Abbal, Patrick Manckoundia, Audrey Gabelle, Yannick Gasnier, Olivier Rouaud, Christine Malick-Loiseau, Carole Badufle, Christian Carpuat, Sophie Marilier, Sophie Peiffer, Stéphane Chanalet, Riitta Antikainen, Jean-Pierre Salles, Stéphanie Roth, Catherine Burdet, Pierre Livet, Nadège Barro-Belaygues, François Cotton, Tiia Ngandu, Pim van Gool, Alexandra Foubert, Eric P. Moll van Charante, Khaled Khales, Pierre-Jean Ousset, Hilkka Soininen, Valérie Faure, Sandrine Andrieu, Corinne Costes, Marie-Noelle-Cuffi, Frédéric Ricolfi, Pascale Rebaudet, Samira Misbah El Idrissi, Céline Caillaud, Marie Chupin, Alain Pesce, Françoise Lala, N. Costa, Emeline Combrouze, Carol Brayne, Bertrand Fougère, Michel Zanca, H. Villars, Sebastien Gonfrier, Fabrice Bonneville, Lynda Touati, Sandrine Cerda, Katri Hemio, Esko Levälahti, Jacques Darcourt, Philippe Robert, Christophe Morin, Brigitte Gilbert, Alain Bonafe, Catherine Faisant, Jacques Monteil, Lawrence Bories, Bram van de Groep, Edo Richard, Gabor Abellan van Kan, Valérie Quipourt, Marc Bonnefoy, Françoise Desclaux, Kristelle Sudres, Thierry Voisin, Timo E. Strandberg, Yves Rolland, Evelyne Franon, Susan Jongstra, Anna Stigsdotter-Neely, Marie-France Basset, Thierry Dantoine, Laurent Molinier, Tiina Laatikainen, Audrey Zueras, Jean-François Lefebvre, Claire Gédéon, Christelle Cantet, Jean-Pierre Clément, Jean-François Mangin, Aurélia Romano, François Chollet, Tuomo Hänninen, Yannick Meiller, Marie-Agnès Picat, Satu Havulinna, Tessa van Middelaar, Jenni Lehtisalo, Isabelle Marcet, Stéphanie Willebois, Christophe Cognard, Hélène Derumeaux, Cécile Pays, Laurence Bernard-Bourzeix, Sylvie Belleville, Anne Hitzel, Cathrien Beishuizen, Ali Bouhayia, Sylvie Chaillou, Bruno Lapoujade, Franck Le Duff, Bruno Vellas, Michael Li Yung Tong, Marieke P. Hoevenaar-Blom, Cecilia Marelli, Rainer Rauramaa, Flavien Terracol, Marko Gronholm, Fleur Delva, Mariagnese Barbera, Sandrine Louchart, Isabelle Carrié, Lauréane Brigitte, Alina Solomon, Bertrand Perret, Claire Gervais, Jaakko Tuomilehto, Carole Dufouil, Sherry L. Willis, Lennard L. van Wanrooij, Cécile Laubarie-Mouret, Nicolas Lebrun, Pierre Skolil, Francesca Mangiasche, Stéphane Lehéricy, Sophie Guyonnet, Jaana Lindström, Evelyne Cazaban-Campistron, Markku Peltonen, Antti Jula, Juliette Guillemont, Nicola Coley, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Karolinska Institutet [Stockholm], University of Helsinki, Faculty of Health Sciences [UEF, Kuopio, Finland], University of Eastern Finland, Vrije Universiteit Amsterdam [Amsterdam] (VU), Nijmegen Medical Centre [Nijmegen], Centre d'investigation clinique de Toulouse (CIC 1436), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), General practice, Public and occupational health, ACS - Diabetes & metabolism, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Aging & Later Life, Graduate School, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CCSD, Accord Elsevier, Department of Public Health, Oral and Maxillofacial Surgery, Department of Medicine, Timo Strandberg / Principal Investigator, and HUS Internal Medicine and Rehabilitation

Subjects
Epidemiology, LIFE-STYLE INTERVENTIONS, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Psychological intervention, 3124 Neurology and psychiatry, Trial, 0302 clinical medicine, Risk Factors, Outcome Assessment, Health Care, 030212 general & internal medicine, PREDICTORS, Cognitive impairment, Finland, Depression (differential diagnoses), Clinical Trials as Topic, Health Policy, DEPRESSION, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Cognitive training, Exercise Therapy, 3. Good health, ALZHEIMERS-DISEASE, Psychiatry and Mental health, Female, medicine.medical_specialty, DISABILITY FINGER, Physical activity, Intervention, Placebo, EXERCISE ADHERENCE, 03 medical and health sciences, Cellular and Molecular Neuroscience, Developmental Neuroscience, Intervention (counseling), Fatty Acids, Omega-3, medicine, Humans, Dementia, OLDER-ADULTS, Life Style, Aged, Cognitive Behavioral Therapy, business.industry, Prevention, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, 3112 Neurosciences, COGNITIVE IMPAIRMENT, medicine.disease, Multidomain, FINNISH GERIATRIC INTERVENTION, PHYSICAL-ACTIVITY, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Adherence, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Physical therapy, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Abstract

Introduction: Multidomain interventions, targeting multiple risk factors simultaneously, could be effective dementia prevention strategies, but may be burdensome and not universally acceptable. Methods: We studied adherence rates and predictors in the Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability and Multidomain Alzheimer Preventive Trial prevention trials, for all intervention components (separately and simultaneously). Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability participants received a 2-year multidomain lifestyle intervention (physical training, cognitive training, nutritional counseling, and cardiovascular monitoring). Multidomain Alzheimer Preventive Trial participants received a 3-year multidomain lifestyle intervention (cognitive training, physical activity counseling, and nutritional counseling) with either an omega-3 supplement or placebo. Results: Adherence decreased with increasing intervention complexity and intensity: it was highest for cardiovascular monitoring, nutritional counseling, and the omega-3 supplement, and lowest for unsupervised computer-based cognitive training. The most consistent baseline predictors of adherence were smoking and depressive symptoms. Discussion: Reducing participant burden, while ensuring that technological tools are suitable for older individuals, maintaining face-to-face contacts, and taking into account participant characteristics may increase adherence in future trials. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Published
2019
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21. Modeling gene-environment interactions in longitudinal family studies: a comparison of methods and their application to the association between the IGF pathway and childhood obesity

Author

Marie-Hélène Roy-Gagnon, Kelly M. Burkett, Lise Dubois, Jean-François Lefebvre, and Cheng Wang

Subjects
0301 basic medicine, Score test, Mixed model, Male, lcsh:Internal medicine, Pediatric Obesity, lcsh:QH426-470, Computational biology, 030105 genetics & heredity, Biology, Simulation studies, Interaction, Longitudinal family studies, Childhood obesity, Statistics, Nonparametric, Twin studies, Body Mass Index, 03 medical and health sciences, Insulin-like growth factors, Genetics, medicine, Humans, Longitudinal Studies, Gene–environment interaction, Non-linear interaction, Insulin-Like Growth Factor I, lcsh:RC31-1245, Child, Genetics (clinical), Glycoproteins, Chromosomes, Human, Pair 12, Nonparametric statistics, Infant, Newborn, Quebec, Infant, medicine.disease, Twin study, Gene-environment interaction, 3. Good health, lcsh:Genetics, 030104 developmental biology, Child, Preschool, Multiple comparisons problem, Linear Models, Female, Carrier Proteins, Research Article, Follow-Up Studies
Abstract

Background The interactive effect of the IGF pathway genes with the environment may contribute to childhood obesity. Such gene-environment interactions can take on complex forms. Detecting those relationships using longitudinal family studies requires simultaneously accounting for correlations within individuals and families. Methods We studied three methods for detecting interaction effects in longitudinal family studies. The twin model and the nonparametric partition-based score test utilized individual outcome averages, whereas the linear mixed model used all available longitudinal data points. Simulation experiments were performed to evaluate the methods’ power to detect different gene-environment interaction relationships. These methods were applied to the Quebec Newborn Twin Study data to test for interaction effects between the IGF pathway genes (IGF-1, IGFALS) and environmental factors (physical activity, daycare attendance and sleep duration) on body mass index outcomes. Results For the simulated data, the twin model with the mean time summary statistic yielded good performance overall. Modelling an interaction as linear when the true model had a different relationship influenced power; for certain non-linear interactions, none of the three methods were effective. Our analysis of the IGF pathway genes showed suggestive association for the joint effect of IGF-1 variant at position 102,791,894 of chromosome 12 and physical activity. However, this association was not statistically significant after multiple testing correction. Conclusions The analytical approaches considered in this study were not robust to different gene-environment interactions. Methodological innovations are needed to improve the current methods’ performances for detecting non-linear interactions. More studies are needed in order to better understand the IGF pathway’s role in childhood obesity development. Electronic supplementary material The online version of this article (10.1186/s12881-018-0739-x) contains supplementary material, which is available to authorized users.

Published
2019

22. STRmix

Author

Sarah, Noël, Josée, Noël, Dominic, Granger, Jean-François, Lefebvre, and Diane, Séguin

Subjects
Likelihood Functions, Genotype, Datasets as Topic, Humans, DNA, DNA Fingerprinting, Polymerase Chain Reaction, Sensitivity and Specificity, Software, Microsatellite Repeats
Abstract

Probabilistic genotyping approaches are increasingly used for the interpretation of DNA mixtures. To explore the specificity of one of these systems (STRmix

Published
2018

23. An artificial photosynthetic system for photoaccumulation of two electrons on a fused dipyridophenazine (dppz)-pyridoquinolinone ligand

Author

Isabelle Baussanne, Vincent Artero, Jean-Marie Mouesca, Jean-François Lefebvre, Martine Demeunynck, Ying Zhang, Serge Gambarelli, Philipp Traber, Stefanie Gräfe, Benjamin Dietzek, Stephan Kupfer, Julian Schindler, Murielle Chavarot-Kerlidou, Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Département de pharmacochimie moléculaire (DPM ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institute of Physical Chemistry, Abbe Center of Photonics, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Leibniz Institute of Photonic Technology Jena, Department Functional Interfaces, Albert-Einstein-Straße 9, 07745 Jena, Germany, Conception d’Architectures Moléculaires et Processus Electroniques (CAMPE), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institute for Physical Chemistry and Center for Energy and Environmental Chemistry, ANR-11-LABX-0003,ARCANE,Grenoble, une chimie bio-motivée(2011), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)

Subjects
Materials science, 010405 organic chemistry, chemistry.chemical_element, Electron donor, General Chemistry, Electron, [CHIM.CATA]Chemical Sciences/Catalysis, 010402 general chemistry, Photochemistry, Solar fuel, 01 natural sciences, 0104 chemical sciences, Catalysis, law.invention, Ruthenium, Electron transfer, symbols.namesake, chemistry.chemical_compound, Chemistry, chemistry, law, [SDE]Environmental Sciences, symbols, Electron paramagnetic resonance, Raman spectroscopy
Abstract

The π-extended ligand of a ruthenium complex stores two photo-generated electrons, mimicking a key step in photosynthesis., Increasing the efficiency of molecular artificial photosynthetic systems is mandatory for the construction of functional devices for solar fuel production. Decoupling the light-induced charge separation steps from the catalytic process is a promising strategy, which can be achieved thanks to the introduction of suitable electron relay units performing charge accumulation. We report here on a novel ruthenium tris-diimine complex able to temporarily store two electrons on a fused dipyridophenazine–pyridoquinolinone π-extended ligand upon visible-light irradiation in the presence of a sacrificial electron donor. Full characterization of this compound and of its singly and doubly reduced derivatives thanks to resonance Raman, EPR and (TD)DFT studies allowed us to localize the two electron-storage sites and to relate charge photoaccumulation with proton-coupled electron transfer processes.

Published
2018
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24. Design and characterisation of bodipy sensitizers for dye-sensitized NiO solar cells

Author

Karel Zidek, Tõnu Pullerits, E. Stephen Davies, Gareth H. Summers, Christopher J. Wood, Elizabeth A. Gibson, Fiona Black, and Jean-François Lefebvre

Subjects
Photocurrent, Non-blocking I/O, General Physics and Astronomy, 02 engineering and technology, Chromophore, 010402 general chemistry, 021001 nanoscience & nanotechnology, Photochemistry, Triphenylamine, 01 natural sciences, Acceptor, 0104 chemical sciences, law.invention, chemistry.chemical_compound, chemistry, law, Solar cell, Thiophene, Physical and Theoretical Chemistry, BODIPY, 0210 nano-technology
Abstract

A series of photosensitizers for NiO-based dye-sensitized solar cells is presented. Three model compounds containing a triphenylamine donor appended to a boron dipyrromethene (bodipy) chromophore have been successfully prepared and characterised using emission spectroscopy, electrochemistry and spectroelectrochemistry, to ultimately direct the design of dyes with more complex structures. Carboxylic acid anchoring groups and thiophene spacers were appended to the model compounds to provide five dyes which were adsorbed onto NiO and integrated into dye-sensitized solar cells. Solar cells incorporating the simple Bodipy-CO₂H dye were surprisingly promising relative to the more complex dye 4. Cell performances were improved with dyes which had increased electronic communication between the donor and acceptor, achieved by incorporating a less hindered bodipy moiety. Further increases in performances were obtained from dyes which contained a thiophene spacer. Thus, the best performance was obtained for 7 which generated a very promising photocurrent density of 5.87 mA cm(-2) and an IPCE of 53%. Spectroelectrochemistry combined with time-resolved transient absorption spectroscopy were used to determine the identity and lifetime of excited state species. Short-lived (ps) transients were recorded for 4, 5 and 7 which are consistent with previous studies. Despite a longer lived (25 ns) charge-separated state for 6/NiO, there was no increase in the photocurrent generated by the corresponding solar cell.

Published
2016
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25. Complexes de palladium de carbènes N-hétérocycliques fusionnés à des porphyrines comme pré-catalyseurs modulables de la réaction de Mizoroki–Heck : Comment la porphyrine peut-elle moduler l'activité catalytique apparente?

Author

Karine Molvinger, Jean-François Longevial, Jean-François Lefebvre, Sébastien Richeter, Sébastien Clément, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Agence Nationale de la Recherche, and ANR-09-JCJC-0089,PORPH-NHC,Ligands ' Porphyrine-Carbène N-Hétérocyclique ' Réglables et Réactifs à des Stimuli Externes pour la Catalyse(2009)

Subjects
Porphyrins, Chemistry(all), General Chemical Engineering, Iodobenzene, chemistry.chemical_element, 010402 general chemistry, Photochemistry, 01 natural sciences, Catalysis, Styrene, Metal, chemistry.chemical_compound, Heck reaction, Porphyrines, Polymer chemistry, Complexes de palladium, Palladium complexes, [CHIM.COOR]Chemical Sciences/Coordination chemistry, N-heterocyclic carbenes, 010405 organic chemistry, Nanoparticules, General Chemistry, [CHIM.CATA]Chemical Sciences/Catalysis, Réaction de Heck, Porphyrin, 0104 chemical sciences, chemistry, visual_art, Carbènes N-hétérocycliques, visual_art.visual_art_medium, Chemical Engineering(all), Nanoparticles, Carbene, Palladium
Abstract

International audience; Porphyrins fused to N-heterocyclic carbenes (NHCs) 1M, with inner metal M = Ni, Cu, Zn and H2, were used to synthesize palladium(II) complexes. These complexes behaved as precatalysts for high-temperature Mizoroki–Heck reactions between iodobenzene and styrene. Despite similar electronic properties between 1M ligands, catalytic activity was found to significantly depend on the presence, or not, of a central metal incorporated in the porphyrin core: a conversion of iodobenzene between 80–90% was observed with metalloporphyrins (M = Ni, Cu and Zn), whereas only 30% was observed with free-base porphyrins (M = H2) after 10 h. Palladium leaching and subsequent trapping of free palladium in the inner core of the free-base porphyrin modified the concentration of Pd(0) active species and may explain the lower catalytic activity observed.; Des porphyrines conjuguées à des carbènes N-hétérocycliques 1M avec M = Ni, Cu, Zn et H2 ont été utilisées pour synthétiser des complexes de palladium(II). Ces complexes sont des pré-catalyseurs de la réaction de couplage de Heck entre l’iodobenzène et le styrène à haute température. Malgré des propriétés électroniques similaires entre les ligands 1M, les activités catalytiques dépendent significativement de la présence, ou non, d’un métal central dans la porphyrine : une conversion de 80–90% de l’iodobenzène est observée avec les métalloporphyrines (M = Ni, Cu et Zn), tandis qu’une conversion de seulement 30% est observée avec des porphyrines bases libres (M = H2) après 10 heures de réaction. La libération de palladium et son piégeage dans la porphyrine base libre modifie la concentration d’espèces actives de Pd(0) et peut expliquer la plus faible activité catalytique observée.

Published
2016
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26. A ππ* State Enables Photoaccumulation of Charges on a π‑ExtendedDipyridophenazine Ligand in a Ru(II) Polypyridine Complex

Author

Philipp Traber, Martine Demeunynck, Jean-François Lefebvre, Stephan Kupfer, Ying Zhang, Julian Schindler, Benjamin Dietzek, Stefanie Gräfe, Murielle Chavarot-Kerlidou, Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Leibniz Institute of Photonic Technology Jena, Department Functional Interfaces, Albert-Einstein-Straße 9, 07745 Jena, Germany, Département de pharmacochimie moléculaire (DPM ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institute for Physical Chemistry and Center for Energy and Environmental Chemistry, Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
education.field_of_study, Polypyridine complex, 010405 organic chemistry, Ligand, Population, Phenazine, 010402 general chemistry, Resonance (chemistry), 01 natural sciences, 0104 chemical sciences, 3. Good health, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Crystallography, chemistry.chemical_compound, General Energy, chemistry, Moiety, [CHIM]Chemical Sciences, Density functional theory, [PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph], Physical and Theoretical Chemistry, education, Electronic density
Abstract

International audience; The pi-extended dipyrido[3,2-a:2',3'-c]phenazine (dppz) ligand of the Ru(II) complex [Ru(bpy)(2)(oxo-dppqp)](PF6)(2) (oxo-dppqp = dipyrido[3,2-a:2',3'-c]pyrido[2?,3?-4,5,6]quinolino[2,3-h]phenazin-15-one, bpy = 2,2'-bipyridine) enables the mononuclear complex for visible-light-driven accumulation of two electrons on a single ligand structure. Although this has been shown before, the excited-state physics underlying this promising feature are exploited in this work. The photophysics of the complex was investigated by excitation-wavelength-dependent resonance Raman and transient absorption spectroscopy in combination with time-dependent density functional theory. The results show that excitation with visible light leads to the population of the two excited-state branches: (i) the population of a short-lived (MLCT)-M-3 state in which the excess electronic density is localized on the pyridoquinolinone moiety of the extended ligand (t = 105 ps) and (ii) the population of a more long-lived (3)pi pi* state (iota = 9 ns). Notably, the long-lived (3)pi pi* state rather than a 3MLCT state is prone to reductive quenching by the sacrificial electron donor and, hence, presents the critical excited-state intermediate in the photochemical charge accumulation experiments

Published
2018
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27. Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial

Author

Sandrine Andrieu, Sophie Guyonnet, Nicola Coley, Christelle Cantet, Marc Bonnefoy, Serge Bordes, Lawrence Bories, Marie-Noëlle Cufi, Thierry Dantoine, Jean-François Dartigues, Françoise Desclaux, Audrey Gabelle, Yannick Gasnier, Alain Pesce, Kristel Sudres, Jacques Touchon, Philippe Robert, Olivier Rouaud, Philippe Legrand, Pierre Payoux, Jean-Paul Caubere, Michael Weiner, Isabelle Carrié, Pierre-Jean Ousset, Bruno Vellas, Lauréane Brigitte, Catherine Faisant, Françoise Lala, Julien Delrieu, Hélène Villars, Emeline Combrouze, Carole Badufle, Audrey Zueras, Christophe Morin, Gabor Abellan Van Kan, Charlotte Dupuy, Yves Rolland, Céline Caillaud, Bertrand Fougère, Sherry Willis, Sylvie Belleville, Brigitte Gilbert, Francine Fontaine, Isabelle Marcet, Fleur Delva, Alexandra Foubert, Sandrine Cerda, Marie Noëlle-Cuffi, Corinne Costes, Patrick Manckoundia, Valérie Quipourt, Sophie Marilier, Evelyne Franon, Marie-Laure Pader, Marie-France Basset, Bruno Lapoujade, Valérie Faure, Michael Li, Yung Tong, Christine Malick-Loiseau, Evelyne Cazaban-Campistron, Colette Blatge, Cécile Laubarie-Mouret, Isabelle Saulnier, Jean-Pierre Clément, Marie-Agnès Picat, Laurence Bernard-Bourzeix, Stéphanie Willebois, Iléana Désormais, Noëlle Cardinaud, Pierre Livet, Pascale Rebaudet, Claire Gédéon, Catherine Burdet, Flavien Terracol, Stéphanie Roth, Sylvie Chaillou, Sandrine Louchart, Nicolas Lebrun, Nadège Barro-Belaygues, Karim Bennys, Aurélia Romano, Lynda Touati, Cécilia Marelli, Cécile Pays, Franck Le Duff, Claire Gervais, Sébastien Gonfrier, Danièle Begorre, Christian Carpuat, Khaled Khales, Jean-François Lefebvre, Samira Misbah El Idrissi, Pierre Skolil, Jean-Pierre Salles, Carole Dufouil, Stéphane Lehéricy, Marie Chupin, Jean-François Mangin, Ali Bouhayia, Michèle Allard, Frédéric Ricolfi, Dominique Dubois, Marie Paule, Bonceour Martel, François Cotton, Alain Bonafé, Stéphane Chanalet, Françoise Hugon, Fabrice Bonneville, Christophe Cognard, François Chollet, Thierry Voisin, Sophie Peiffer, Anne Hitzel, Michel Zanca, Jacques Monteil, Jacques Darcourt, Laurent Molinier, Hélène Derumeaux, Nadège Costa, Christian Vincent, Bertrand Perret, Claire Vinel, Pascale Olivier-Abbal, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, CHU Toulouse [Toulouse], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital de Tarbes, Service de Gériatrie (CHARLES FOIX - Gériatrie), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hopital de castres, CHU Limoges, CHU Bordeaux [Bordeaux], Hopital Lavaur, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Princesse Grace [Monaco], Centre hospitalier de Montauban, Neuropsychiatrie : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Cognition Behaviour Technology (CobTek), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut Claude Pompidou [Nice] (ICP - Nice)-Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Mémoire Ressources et Recherche [Dijon] (CMRR Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut National de la Recherche Agronomique (INRA), Department of Nuclear Medicine, CHU de Toulouse (CHU), Centre de Recherche Pierre Fabre, University of California [San Francisco] (UCSF), University of California, Service d'Etudes du Comportement des Matériaux de Conditionnement (SECM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Interactions, transferts, ruptures artistiques et culturels - EA 6301 (InTRu), Université de Tours, École de sages-femmes Baudelocque (ESF Baudelocque), Université Paris Descartes - Paris 5 (UPD5), Gérontopôle, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Genetique medicale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine gériatrique (CHU de Dijon - Centre gériatrique de Champmaillot - EHPAD), Cabinet médical [Dijon], Cabinet médical, Handicap, Activité, Vieillissement, Autonomie, Environnement (HAVAE), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Sciences et Société, Historicité, Éducation et Pratiques (EA S2HEP), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre de Mémoire de Ressources et de Recherches [Limoges] (CMRR Limoges), CHU Limoges-CH Esquirol [Limoges] (CH Esquirol), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], Centre d'EPistémologie et d'ERgologie Comparatives - UMR 7304 (CEPERC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre de droit privé fondamental (CDPF), Université de Strasbourg (UNISTRA)-L'europe en mutation : histoire, droit, économie et identités culturelles, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Neurologie, Université Montpellier 1 (UM1)-Hôpital Guy de Chauliac-Centre Mémoire Ressources Recherche Languedoc - Roussillon, Laboratoire d'Informatique Médicale (LIM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), The Smithsonian Museum Conservation Institute, Chercheur indépendant, Centre Léon Bérard [Lyon], Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Service de neuroradiologie, imagerie des urgences [CHU de Dijon], Urgence et post-urgence psychiatrique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Pasteur [Nice] (CHU), Imagerie cérébrale et handicaps neurologiques, Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Service de Médecine Nucléaire [Toulouse], CHU Toulouse [Toulouse]-Hôpital Rangueil, Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Transporteurs en Imagerie et Radiothérapie en Oncologie (TIRO - UMR E4320), Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-UMR E4320 (TIRO-MATOs), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Service de l'Information Médicale, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Centre hospitalier de Montauban (CH Montauban), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Institut Claude Pompidou [Nice] (ICP - Nice)-Université Côte d'Azur (UCA), Service de Médecine Nucléaire - Rangueil [CHU Toulouse], Pôle imagerie médicale [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE, University of California [San Francisco] (UC San Francisco), University of California (UC), Université de Tours (UT), Université Paris Descartes - École de sages-femmes Baudelocque (UPD ESF Baudelocque), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre d'EPistémologie et d'ERgologie Comparatives (CEPERC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Mémoire Ressources Recherche Languedoc - Roussillon, Université de Rennes (UR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier (INM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine Nucléaire - Pierre-Paul Riquet [CHU Toulouse], Hôpital Gui de Chauliac [CHU Montpellier], Transporteurs et Imagerie, Radiothérapie en Oncologie et Mécanismes biologiques des Altérations du Tissu Osseux (TIRO-MATOs - UMR E4320), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-UMR E4320 (TIRO-MATOs), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA), Département d'Information Médicale [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), French Ministry of Health, Pierre Fabre Research Institute, Gerontopole, Exhonit Therapeutics, Avid Radiopharmaceuticals, Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute [Basel], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Gérontopôle, Department of Geriatrics, Centre Hospitalier Universitaire de Toulouse, Geriatrics Department, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), hopital de Foix, U897, Memory Research Resource Center for Alzheimer's Disease, Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Centre Hospitalier Princesse Grace, Hopital Montauban, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Institut Claude Pompidou [Nice] (ICP - Nice), Memory Research Resource Center, Neurology Department, Laboratoire de Biochimie et Nutrition Humaine, AGROCAMPUS OUEST, Department of Nuclear Medicine, National Institute of Neurosurgery, Toulouse NeuroImaging Centre, Centre Hospitalier Universitaire de Purpan (CHU Purpan), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UMR E4320 (TIRO-MATOs), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Service Hospitalier Frédéric Joliot (SHFJ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
Male, [SDV]Life Sciences [q-bio], Placebo-controlled study, Neuropsychological Tests, decline, law.invention, 0302 clinical medicine, Cognition, Randomized controlled trial, prevention, law, Medicine, 030212 general & internal medicine, Cognitive decline, alzheimers-disease, risk, chemistry.chemical_classification, Aged, 80 and over, education.field_of_study, Eicosapentaenoic acid, 3. Good health, Exercise Therapy, Treatment Outcome, Female, performance, Polyunsaturated fatty acid, medicine.medical_specialty, brain, Population, Placebo, 03 medical and health sciences, Double-Blind Method, Fatty Acids, Omega-3, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, education, plasma, Aged, clinical-trials, Memory Disorders, Cognitive Behavioral Therapy, business.industry, Clinical trial, chemistry, Dietary Supplements, Physical therapy, Neurology (clinical), business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, gait speed, 030217 neurology & neurosurgery, dementia
Abstract

Summary Background No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline. Methods The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco. Participants were non-demented, aged 70 years or older, and community-dwelling, and had either relayed a spontaneous memory complaint to their physician, limitations in one instrumental activity of daily living, or slow gait speed. They were randomly assigned (1:1:1:1) to either the multidomain intervention (43 group sessions integrating cognitive training, physical activity, and nutrition, and three preventive consultations) plus omega 3 polyunsaturated fatty acids (ie, two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid), the multidomain intervention plus placebo, omega 3 polyunsaturated fatty acids alone, or placebo alone. A computer-generated randomisation procedure was used to stratify patients by centre. All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment, but were unblinded to the multidomain intervention component. Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment. The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests (free and total recall of the Free and Cued Selective Reminding test, ten Mini-Mental State Examination orientation items, Digit Symbol Substitution Test, and Category Naming Test) in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT00672685). Findings 1680 participants were enrolled and randomly allocated between May 30, 2008, and Feb 24, 2011. In the modified intention-to-treat population (n=1525), there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group. Between-group differences compared with placebo were 0·093 (95% CI 0·001 to 0·184; adjusted p=0·142) for the combined intervention group, 0·079 (−0·012 to 0·170; 0·179) for the multidomain intervention plus placebo group, and 0·011 (−0·081 to 0·103; 0·812) for the omega 3 polyunsaturated fatty acids group. 146 (36%) participants in the multidomain plus polyunsaturated fatty acids group, 142 (34%) in the multidomain plus placebo group, 134 (33%) in the polyunsaturated fatty acids group, and 133 (32%) in the placebo group had at least one serious emerging adverse event. Four treatment-related deaths were recorded (two in the multidomain plus placebo group and two in the placebo group). The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events. Interpretation The multidomain intervention and polyunsaturated fatty acids, either alone or in combination, had no significant effects on cognitive decline over 3 years in elderly people with memory complaints. An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined, particularly in real-world settings. Funding French Ministry of Health, Pierre Fabre Research Institute, Gerontopole, Exhonit Therapeutics, Avid Radiopharmaceuticals.

Published
2017
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28. Unexpected Drastic Decrease in the Excited-State Electronic Communication between Porphyrin Chromophores Covalently Linked by a Palladium(II) Bridge

Author

Jean-François Lefebvre, Romain Ruppert, Sébastien Richeter, Paul-Ludovic Karsenti, Adam Langlois, Mohammed Abdelhameed, Pierre D. Harvey, Université de Sherbrooke (UdeS), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Institut de Chimie de Strasbourg, Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Financement ANR

Subjects
Models, Molecular, Metalloporphyrins, Electrons, 010402 general chemistry, Photochemistry, 01 natural sciences, Catalysis, chemistry.chemical_compound, Heterocyclic Compounds, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Molecular orbital, Singlet state, 010405 organic chemistry, Chemistry, Organic Chemistry, General Chemistry, Chromophore, Porphyrin, Acceptor, 0104 chemical sciences, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Zinc, Energy Transfer, Covalent bond, Excited state, Quantum Theory, Methane, Carbene, Palladium
Abstract

International audience; A dyad built up of a zinc(II) porphyrin and the corresponding free base, [Zn-Fb], fused to N-heterocyclic carbene (NHCs) ligands, respectively acting as singlet energy donor and acceptor, and a bridging trans-PdI2 unit, along with the corresponding [Zn-Zn] and [Fb-Fb] dimers were prepared and investigated by absorption and emission spectroscopy and density functional computations. Despite favorable structural and spectroscopic parameters, unexpectedly slow singlet energy transfer rates are measured in comparison with the predicted values by the Förster theory and those observed for other structurally related dyads. This observation is rationalized by the lack of large molecular orbital (MO) overlaps between the frontier MOs of the donor and acceptor, thus preventing a double electron exchange through the trans-PdI2 bridge, and by an electronic shielding induced by the presence of this same linker preventing the two chromophores to fully interact via their transition dipoles.

Published
2014
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29. The Catalytic Function of Hormone-Sensitive Lipase is Essential for Fertility in Male Mice

Author

Jiang Wei Wu, Blair R. Leavitt, Charles E. Smith, Jean François Lefebvre, Shu Pei Wang, Stéphanie Casavant, Grant A. Mitchell, Damian Labuda, Hugo Bourdages, Louis Hermo, and Jacquetta M. Trasler

Subjects
Male, Gene isoform, Transgene, food and beverages, Mice, Transgenic, Hormone-sensitive lipase, Sterol Esterase, Biology, Molecular biology, Peptide Fragments, Rats, Mice, Exon, Fertility, Endocrinology, Transcription (biology), Catalytic Domain, Testis, Animals, Humans, Peptide sequence, Gene, Transcription factor
Abstract

In male mice, deficiency of hormone sensitive lipase (HSL, Lipe gene, E.C.3.1.1.3) causes deficient spermatogenesis, azoospermia, and infertility. Postmeiotic germ cells express a specific HSL isoform that includes a 313 amino acid N-terminus encoded by a testis-specific exon (exon T1). The remainder of testicular HSL is identical to adipocyte HSL. The amino acid sequence of the testis-specific exon is poorly conserved, showing only a 46% amino acid identity with orthologous human and rat sequences, compared with 87% over the remainder of the HSL coding sequence, providing no evidence in favor of a vital functional role for the testis-specific N-terminus of HSL. However, exon T1 is important for Lipe transcription; in mouse testicular mRNA, we identified 3 major Lipe transcription start sites, finding numerous testicular transcription factor binding motifs upstream of the transcription start site. We directly explored two possible mechanisms for the infertility of HSL-deficient mice, using mice that expressed mutant HSL transgenes only in postmeiotic germ cells on a HSL-deficient background. One transgene expressed human HSL lacking enzyme activity but containing the testis-specific N-terminus (HSL−/−muttg mice). The other transgene expressed catalytically inactive HSL with the testis-specific N-terminal peptide (HSL−/−atg mice). HSL−/−muttg mice were infertile, with abnormal histology of the seminiferous epithelium and absence of spermatozoa in the epididymal lumen. In contrast, HSL−/−atg mice had normal fertility and normal testicular morphology. In conclusion, whereas the catalytic function of HSL is necessary for spermatogenesis in mice, the presence of the N-terminal testis-specific fragment is not essential.

Published
2014
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30. Porphyrins Fused to N-Heterocyclic Carbenes (NHCs): Modulation of the Electronic and Catalytic Properties of NHCs by the Central Metal of the Porphyrin

Author

Olivier Coulembier, Sébastien Clément, Sébastien Richeter, Jean-François Lefebvre, Mamadou Lo, Jean-Paul Gisselbrecht, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Institut de Chimie de Strasbourg, Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie des Matériaux et Polymères (SMPC), and Université de Mons-Hainaut

Subjects
ring-opening polymerization, Inorganic chemistry, porphyrinoids, 010402 general chemistry, 01 natural sciences, Ring-opening polymerization, Catalysis, Metal, chemistry.chemical_compound, Polymer chemistry, organocatalysis, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Reactivity (chemistry), UV/Vis spectroscopy, 010405 organic chemistry, Transition metal carbene complex, Organic Chemistry, [CHIM.CATA]Chemical Sciences/Catalysis, General Chemistry, Porphyrin, 0104 chemical sciences, carbenes, [CHIM.POLY]Chemical Sciences/Polymers, chemistry, Organocatalysis, visual_art, visual_art.visual_art_medium, Carbene
Abstract

We report herein a detailed study of the use of porphyrins fused to imidazolium salts as precursors of N- heterocyclic carbene ligands 1M. Rho- dium(I) complexes 6M - 9M were pre- pared by using 1M ligands with differ- ent metal cations in the inner core of the porphyrin (M = Ni II ,Z n II ,M n III , Al III , 2H). The electronic properties of the corresponding N-heterocyclic car- bene ligands were investigated by mon- itoring the spectroscopic changes oc- curring in the cod and CO ancillary ligands of (( 1M )RhA and (( 1M )Rh(CO)2Cl) complexes (cod = 1,5-cyclooctadiene). Porphyrin-NHC li- gands 1M with a trivalent metal cation such as Mn III and Al III are overall poorer electron donors than porphy- rin-NHC ligands with no metal cation or incorporating a divalent metal cation such as Ni II and Zn II . Imidazoli- um salts 3M (M = Ni, Zn, Mn, 2H) have also been used as NHC precur- sors to catalyze the ring-opening poly- merization of l-lactide. The results clearly show that the inner metal of the porphyrin has an important effect on the reactivity of the outer carbene.

Published
2013
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31. A resonance Raman study of new pyrrole-anchoring dyes for NiO-sensitized solar cells

Author

Grace Lowe, Simbarashe Ngwerume, Maximilian Bräutigam, Gareth H. Summers, Jean-François Lefebvre, Benjamin Dietzek, Elizabeth A. Gibson, Jason E. Camp, Summers, Gareth H, Lowe, Grace, Lefebvre, Jean-Francois, Ngwerume, Simbarashe, and Brautigam, Maximilian

Subjects
Chemistry, Resonance Raman spectroscopy, 02 engineering and technology, 010402 general chemistry, 021001 nanoscience & nanotechnology, Photochemistry, Triphenylamine, 01 natural sciences, Acceptor, Atomic and Molecular Physics, and Optics, 0104 chemical sciences, chemistry.chemical_compound, symbols.namesake, symbols, Moiety, QD, Physical and Theoretical Chemistry, BODIPY, 0210 nano-technology, Raman spectroscopy, Linker, Pyrrole
Abstract

Three dyes for p-type dye-sensitised solar cells containing a novel doubly anchored pyrrole donor group were synthesised and their solar cell performances were evaluated. Dye 1 was comprised of a phenyl-thiophene linker and a maleonitrile acceptor, which has been established as an effective motif in other push-pull dyes. Two boron dipyrromethane analogues, dyes 2 and 3, were made with different linker groups to compare their effect on the behaviour of these dyes adsorbed onto nickel oxide (dye|NiO) under illumination. The photo-excited states of dye|NiO were probed using resonance Raman spectroscopy and compared to dyes anchored using the conventional 4-aminobenzoic acid moiety (P1 and 4). All three components, the anchor, the linker and the acceptor group were found to alter both the electronic structure following excitation and the overall solar cell performance. The bodipy acceptor gave a better performance than the maleonitrile acceptor when the pyrrole anchor was used, which is the opposite of the triphenylamine push-pull dyes. The linker group was found to have a large influence on the short-circuit current and efficiency of the p-type cells constructed.

Published
2016

32. Measuring the sustainability of cities: An analysis of the use of local indicators

Author

Georges A. Tanguay, Juste Rajaonson, Jean-François Lefebvre, and Paul Lanoie

Subjects
Sustainable development, Ecology, Computer science, business.industry, media_common.quotation_subject, Selection strategy, Environmental resource management, General Decision Sciences, Ambiguity, Environmental economics, Local governance, Sustainability, The Conceptual Framework, Selection method, business, Ecology, Evolution, Behavior and Systematics, Selection (genetic algorithm), media_common
Abstract

We analyze 17 studies of the use of urban sustainable development indicators (SDI) in developed western countries. The analysis reveals a lack of consensus not only on the conceptual framework and the approach favored, but also on the selection and optimal number of indicators. First, by performing different classifications and categorizations of SDI we identify problems inherent in territorial practices that use SDI. Second, we argue that the lack of consensus in several steps of the creation of SDI stems notably from the ambiguity in the definitions of sustainable development, objectives for the use of such indicators, the selection method and the accessibility of qualitative and quantitative data. Third, based on the reviewed studies, we propose a selection strategy for SDI through which we demonstrate the need to adopt a parsimonious list of SDI covering the sustainable development components and their constituent categories as broadly as possible while minimizing the number of indicators retained.

Published
2010
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33. Female-to-Male Breeding Ratio in Modern Humans—an Analysis Based on Historical Recombinations

Author

Philippe Nadeau, Damian Labuda, Marie-Hélène Roy-Gagnon, and Jean-François Lefebvre

Subjects
Male, Mutation rate, Population, Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Databases, Genetic, Genetic variation, Genetics, Animals, Chromosomes, Human, Humans, Genetics(clinical), Sex Ratio, Marriage, International HapMap Project, Letters to the Editor, education, History, Ancient, Phylogeny, Genetics (clinical), X chromosome, 030304 developmental biology, Recombination, Genetic, Chromosomes, Human, X, 0303 health sciences, education.field_of_study, Genetic diversity, Autosome, Models, Genetic, Genetic Variation, Biological Evolution, Genetics, Population, Female, Erratum, 030217 neurology & neurosurgery, Sex ratio
Abstract

Was the past genetic contribution of women and men to the current human population equal? Was polygyny (excess of breeding women) present among hominid lineages? We addressed these questions by measuring the ratio of population recombination rates between the X chromosome and the autosomes, rho(X)/rho(A). The X chromosome recombines only in female meiosis, whereas autosomes undergo crossovers in both sexes; thus, rho(X)/rho(A) reflects the female-to-male breeding ratio, beta. We estimated beta from rho(X)/rho(A) inferred from genomic diversity data and calibrated with recombination rates derived from pedigree data. For the HapMap populations, we obtained beta of 1.4 in the Yoruba from West Africa, 1.3 in Europeans, and 1.1 in East Asian samples. These values are consistent with a high prevalence of monogamy and limited polygyny in human populations. More mutations occur during male meiosis as compared to female meiosis at the rate ratio referred to as alpha. We show that at alpha not equal 1, the divergence rates and genetic diversities of the X chromosome relative to the autosomes are complex functions of both alpha and beta, making their independent estimation difficult. Because our estimator of beta does not require any knowledge of the mutation rates, our approach should allow us to dissociate the effects of alpha and beta on the genetic diversity and divergence rate ratios of the sex chromosomes to the autosomes.

Published
2010
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34. Tracing genetic history of modern humans using X-chromosome lineages

Author

Roman Michalski, Jerzy Jurka, Vania Yotova, Oleksiy Kohany, David Modiano, Jean-François Lefebvre, Scott M. Williams, Damian Labuda, and Gerd Utermann

Subjects
Gene Flow, Male, Demographic history, Population, Biology, Gene flow, Dystrophin, Evolution, Molecular, Genetic variation, Genetics, Humans, Genetic variability, education, History, Ancient, Genetics (clinical), DNA Primers, Chromosomes, Human, X, education.field_of_study, Base Sequence, Models, Genetic, Haplotype, Genetic Variation, Introns, Genetics, Population, Haplotypes, Homo sapiens, Evolutionary biology, Africa, Mutation, Genetic structure, Microsatellite Repeats
Abstract

Genetic variability of the compound interrupted microsatellite DXS1238, in intron 44 of the dystrophin gene, provides evidence for a complex structure of the ancestral population that led to the emergence of modern humans. We sequenced DXS1238 in 600 X-chromosomes from all over the world. Forty four percent of African-specific chromosomes belong to the ancestral lineage that did not participate in the out-of-Africa expansion and subsequent colonization of other continents. Based on the coalescence analysis these lineages separated from those that contributed to the out-of-Africa expansion 366 +/- 136 thousands years ago (Kya). Independently, the analysis of the variance in the repeat length and of the decay of the ancestral alleles of the two DXS1238 repeats, GT and GA, dates this separation at more than 200 Kya. This suggests a complex demographic history and genetic structure of the African melting pot that led to the emergence of modern humans and their out-of-Africa migration. The subsequent subdivisions of human populations among different continents appear to be preceded by even more structured population history within Africa itself, which resulted from a restricted gene flow between lineages allowing for genetic differences to accumulate. If the transition to modern humans occurred during that time, it necessarily follows that genes associated with this transformation spread between subpopulations via gene flow. Otherwise, in spite of subsequent anatomical variation, Homo sapiens as a species could have emerged in Africa already between 300 and 200 Kya, i.e. before the mitochondrial DNA and well before the Y-chromosome most recent common ancestors.

Published
2007
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35. Patterns of variation in DNA segments upstream of transcription start sites

Author

Patrick Beaulieu, Catherine Labbé, Thomas J. Hudson, Virginie Freytag, Daniel Sinnett, Damian Labuda, Jean-François Lefebvre, Claudia Moreau, Jakub Sawicki, Sylvie Langlois, and Tomi Pastinen

Subjects
haplotypes, Genotype, Transcription, Genetic, Population, Biology, Fixation index, Coalescent theory, 03 medical and health sciences, Negative selection, selective sweeps, 0302 clinical medicine, Genetic variation, promoter regions, Genetics, Animals, Humans, Allele, Promoter Regions, Genetic, education, Alleles, Genetics (clinical), 030304 developmental biology, 0303 health sciences, education.field_of_study, Genetic diversity, Polymorphism, Genetic, human populations, Haplotype, DNA, 030217 neurology & neurosurgery, Research Article, DNA diversity
Abstract

It is likely that evolutionary differences among species are driven by sequence changes in regulatory regions. Likewise, polymorphisms in the promoter regions may be responsible for interindividual differences at the level of populations. We present an unbiased survey of genetic variation in 2-kb segments upstream of the transcription start sites of 28 protein-coding genes, characterized in five population groups of different geographic origin. On average, we found 9.1 polymorphisms and 8.8 haplotypes per segment with corresponding nucleotide and haplotype diversities of 0.082% and 58%, respectively. We characterized these segments through different summary statistics, Hardy-Weinberg equilibria fixation index (Fst) estimates, and neutrality tests, as well as by analyzing the distributions of haplotype allelic classes, introduced here to assess the departure from neutrality and examined by coalescent simulations under a simple population model, assuming recombinations or different demography. Our results suggest that genetic diversity in some of these regions could have been shaped by purifying selection and driven by adaptive changes in the other, thus explaining the relatively large variance in the corresponding genetic diversity indices loci. However, some of these effects could be also due to linkage with surrounding sequences, and the neutralists' explanations cannot be ruled out given uncertainty in the underlying demographic histories and the possibility of random effects due to the small size of the studied segments. Hum Mutat 28(5), 441–450, 2007. © 2007 Wiley-Liss, Inc.

Published
2007
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36. A Comparison of Statistical Methods for the Discovery of Genetic Risk Factors Using Longitudinal Family Study Designs

Author

Kelly M. Burkett, Marie-Hélène Roy-Gagnon, Bénédicte Fontaine-Bisson, Cheng Wang, Lise Dubois, and Jean-François Lefebvre

Subjects
lcsh:Immunologic diseases. Allergy, Longitudinal study, genetic association, Immunology, Bayesian probability, Population, Biology, family designs, computer.software_genre, Generalized linear mixed model, family design, Statistics, Immunology and Allergy, Longitudinal Studies, education, Generalized estimating equation, Genetic Association Studies, Original Research, Genetic association, education.field_of_study, Heritability, Twin study, linear mixed models, Generalized estimating equations, Data mining, lcsh:RC581-607, computer
Abstract

The etiology of immune-related diseases or traits is often complex, involving many genetic and environmental factors and their interactions. While methodological approaches focusing on an outcome measured at one time point have succeeded in identifying genetic factors involved in immune-related traits, they fail to capture complex disease mechanisms that fluctuate over time. It is increasingly recognized that longitudinal studies, where an outcome is measured at multiple time points, have great potential to shed light on complex disease mechanisms involving genetic factors. However, longitudinal data require specialized statistical methods, especially in family studies where multiple sources of correlation in the data must be modeled. Using simulated data with known genetic effects, we examined the performance of different analytical methods for investigating associations between genetic factors and longitudinal phenotypes in twin data. The simulations were modeled on data from the Québec Newborn Twin Study, an ongoing population-based longitudinal study of twin births with multiple phenotypes, such as cortisol levels and body mass index, collected multiple times in infancy and early childhood and with sequencing data on immune-related genes and pathways. We compared approaches that we classify as (1) family-based methods applied to summaries of the observations over time, (2) longitudinal-based methods with simplifications of the familial correlation, and (3) Bayesian family-based method with simplifications of the temporal correlation. We found that for estimation of the genetic main and interaction effects, all methods gave estimates close to the true values and had similar power. If heritability estimation is desired, approaches of type (1) also provide heritability estimates close to the true value. Our work shows that the simpler approaches are likely adequate to detect genetic effects; however, interpretation of these effects is more challenging.

Published
2015
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38. Inside Cover: Selective Luminescent Labeling of DNA and RNA Quadruplexes by π-Extended Ruthenium Light-Up Probes (Chem. Eur. J. 21/2017)

Author

Jean-François Lefebvre, Mehdi M. Bellakhal, Isabelle Baussanne, Cécile Moucheron, Dounia Saadallah, Souheila Amor, Martine Demeunynck, David Monchaud, Murielle Chavarot-Kerlidou, Chimie Organique et Photochimie, Université libre de Bruxelles (ULB), Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Solar fuels, hydrogen and catalysis (SolHyCat ), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Département de pharmacochimie moléculaire (DPM ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Libre de Bruxelles, Département de Chimie Moléculaire - Ingéniérie et Intéractions BioMoléculaires (DCM - I2BM), Département de Chimie Moléculaire (DCM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Conception, synthèse et vectorisation de biomolécules. (CSVB), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris], Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Libre de Bruxelles [Bruxelles] (ULB), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), CMOS, Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Solar fuels, hydrogen and catalysis (SolHyCat), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Département de pharmacochimie moléculaire (DPM), Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Institut Curie-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
010405 organic chemistry, Organic Chemistry, RNA, chemistry.chemical_element, General Chemistry, 010402 general chemistry, Photochemistry, 01 natural sciences, Catalysis, 0104 chemical sciences, Ruthenium, chemistry.chemical_compound, chemistry, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Cover (algebra), Light Up, Luminescence, ComputingMilieux_MISCELLANEOUS, DNA
Abstract

International audience

Published
2017
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39. Promoting charge-separation in p-type dye-sensitized solar cells using bodipy

Author

Michael W. George, Xue-Zhong Sun, Elizabeth A. Gibson, James A. Calladine, and Jean-François Lefebvre

Subjects
Materials science, Charge separation, Non-blocking I/O, Metals and Alloys, General Chemistry, Photochemistry, Triphenylamine, Acceptor, Catalysis, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Dye-sensitized solar cell, chemistry.chemical_compound, chemistry, Materials Chemistry, Ceramics and Composites, BODIPY
Abstract

The viability of applying bodipy sensitisers to NiO-based p-type dye-sensitised solar cells (p-DSCs) has been successfully demonstrated. The triphenylamine donor-bodipy acceptor design promotes a long-lived charge-separated state which is difficult to achieve with NiO-based devices. The current was above 3 mA cm(-2) and the IPCE was 28%.

Published
2013

40. Genome-wide patterns of identity-by-descent sharing in the French Canadian founder population

Author

Hélène Vézina, Catherine Laprise, Jean-François Lefebvre, Marie-Hélène Roy-Gagnon, Claudia Moreau, Héloïse Gauvin, and Damian Labuda

Subjects
relatedness, Canada, Genome-wide association study, Consanguinity, Genome, Identity by descent, Polymorphism, Single Nucleotide, Article, SNP data, 03 medical and health sciences, Genetics, Kinship, Humans, Genetics (clinical), 030304 developmental biology, Ancestor, 0303 health sciences, 030305 genetics & heredity, Haplotype, population structure, genealogical data, Founder Effect, Geography, Genetics, Population, Haplotypes, Evolutionary biology, identity-by-descent, France, founder population, Founder effect, Genealogy and Heraldry, Genome-Wide Association Study
Abstract

In genetics the ability to accurately describe the familial relationships among a group of individuals can be very useful. Recent statistical tools succeeded in assessing the degree of relatedness up to 6–7 generations with good power using dense genome-wide single-nucleotide polymorphism data to estimate the extent of identity-by-descent (IBD) sharing. It is therefore important to describe genome-wide patterns of IBD sharing for more remote and complex relatedness between individuals, such as that observed in a founder population like Quebec, Canada. Taking advantage of the extended genealogical records of the French Canadian founder population, we first compared different tools to identify regions of IBD in order to best describe genome-wide IBD sharing and its correlation with genealogical characteristics. Results showed that the extent of IBD sharing identified with FastIBD correlates best with relatedness measured using genealogical data. Total length of IBD sharing explained 85% of the genealogical kinship's variance. In addition, we observed significantly higher sharing in pairs of individuals with at least one inbred ancestor compared with those without any. Furthermore, patterns of IBD sharing and average sharing were different across regional populations, consistent with the settlement history of Quebec. Our results suggest that, as expected, the complex relatedness present in founder populations is reflected in patterns of IBD sharing. Using these patterns, it is thus possible to gain insight on the types of distant relationships in a sample from a founder population like Quebec.

Published
2013

41. Native American admixture in the Quebec founder population

Author

Marie-Hélène Roy-Gagnon, Claude Bhérer, Jean-François Lefebvre, Claudia Moreau, Andres Ruiz-Linares, Damian Labuda, Hélène Vézina, and Michèle Jomphe

Subjects
Gene Flow, Linkage disequilibrium, Epidemiology, Population, lcsh:Medicine, Population genetics, Genetic admixture, Ethnic Groups, HapMap Project, Biology, Social and Behavioral Sciences, Human Geography, Linkage Disequilibrium, White People, Cultural Anthropology, Genetic variation, Genetic predisposition, Humans, Geographic and National Differences, lcsh:Science, education, Historical Geography, Genetics, education.field_of_study, Evolutionary Biology, Multidisciplinary, Population Biology, Geography, Genetic heterogeneity, lcsh:R, Quebec, Genetic Variation, Gene Pool, Genomics, Comparative Genomics, Founder Effect, Regional Geography, Genetics, Population, Haplotypes, Evolutionary biology, Genetic Epidemiology, Anthropology, Settlement Patterns, Indians, North American, lcsh:Q, Population Genetics, Founder effect, Research Article
Abstract

For years, studies of founder populations and genetic isolates represented the mainstream of genetic mapping in the effort to target genetic defects causing Mendelian disorders. The genetic homogeneity of such populations as well as relatively homogeneous environmental exposures were also seen as primary advantages in studies of genetic susceptibility loci that underlie complex diseases. European colonization of the St-Lawrence Valley by a small number of settlers, mainly from France, resulted in a founder effect reflected by the appearance of a number of population-specific disease-causing mutations in Quebec. The purported genetic homogeneity of this population was recently challenged by genealogical and genetic analyses. We studied one of the contributing factors to genetic heterogeneity, early Native American admixture that was never investigated in this population before. Consistent admixture estimates, in the order of one per cent, were obtained from genome-wide autosomal data using the ADMIXTURE and HAPMIX software, as well as with the fastIBD software evaluating the degree of the identity-by-descent between Quebec individuals and Native American populations. These genomic results correlated well with the genealogical estimates. Correlations are imperfect most likely because of incomplete records of Native founders' origin in genealogical data. Although the overall degree of admixture is modest, it contributed to the enrichment of the population diversity and to its demographic stratification. Because admixture greatly varies among regions of Quebec and among individuals, it could have significantly affected the homogeneity of the population, which is of importance in mapping studies, especially when rare genetic susceptibility variants are in play.

Published
2013

42. X-linked MTMR8 diversity and evolutionary history of sub-Saharan populations

Author

Gerd Utermann, Scott M. Williams, Vania Yotova, Damian Labuda, Jean-François Lefebvre, and Claudia Moreau

Subjects
Genetic Linkage, Population, lcsh:Medicine, Biology, Population stratification, Polymerase Chain Reaction, Evolution, Molecular, 03 medical and health sciences, 0302 clinical medicine, Genetic linkage, Genetic variation, Humans, 10. No inequality, education, lcsh:Science, Africa South of the Sahara, 030304 developmental biology, 0303 health sciences, Genetic diversity, education.field_of_study, Chromosomes, Human, X, Multidisciplinary, Polymorphism, Genetic, Haplotype, lcsh:R, Genetic Variation, Genetics, Population, Haplotypes, Evolutionary biology, Genetic structure, lcsh:Q, Selective sweep, 030217 neurology & neurosurgery, Research Article
Abstract

The genetic diversity within an 11 kb segment of the MTMR8 gene in a sample of 111 sub-Saharan and 49 non-African X chromosomes was investigated to assess the early evolutionary history of sub-Saharan Africans and the out-of-Africa expansion. The analyses revealed a complex genetic structure of the Africans that contributed to the emergence of modern humans. We observed partitioning of two thirds of old lineages among southern, west/central and east African populations indicating ancient population stratification predating the out of Africa migration. Age estimates of these lineages, older than coalescence times of uniparentally inherited markers, raise the question whether contemporary humans originated from a single population or as an amalgamation of different populations separated by years of independent evolution, thus suggesting a greater antiquity of our species than generally assumed. While the oldest sub-Saharan lineages, ,500 thousand years, are found among Khoe-San from southern-Africa, a distinct haplotype found among Biaka is likely due to admixture from an even older population. An East African population that gave rise to non-Africans underwent a selective sweep affecting the subcentromeric region where MTMR8 is located. This and similar sweeps in four other regions of the X chromosome, documented in the literature, effectively reduced genetic diversity of non-African chromosomes and therefore may have exacerbated the effect of the demographic bottleneck usually ascribed to the out of Africa migration. Our data is suggestive, however, that a bottleneck, occurred in Africa before range expansion.

Published
2013

44. Stepwise Fusion of Porphyrin β,β'-Pyrrolic Positions to Imidazole Rings

Author

Arie van der Lee, Sébastien Richeter, Jean-François Lefebvre, Mamadou Lo, Dominique Leclercq, Chimie moléculaire et organisation du solide (CMOS), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), IEM, Institut Européen des membranes (IEM), and Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)

Subjects
Tris, Annulation, Fusion, Molecular Structure, Metalloporphyrins, 010405 organic chemistry, Chemistry, Stereochemistry, Organic Chemistry, Imidazoles, 010402 general chemistry, 01 natural sciences, Biochemistry, Medicinal chemistry, Porphyrin, 0104 chemical sciences, 3. Good health, chemistry.chemical_compound, Nickel, Imidazole, Pyrroles, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Janus, Physical and Theoretical Chemistry
Abstract

International audience; A strategy for the stepwise annulation of pyrrolic rings of a porphyrin to imidazole rings is presented. Mono(imidazole), Janus and corner bis(imidazole), T-shaped tris(imidazole), and tetrakis(imidazole) porphyrins have been synthesized and characterized.

Published
2011
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45. N-Heterocyclic Carbene (NHC) Ligands Annulated to Free–Base Porphyrins: Modulation of the Electronic Properties of the NHC Upon Protonation or Metallation of the Porphyrin

Author

Sébastien Richeter, Dominique Leclercq, Jean-François Lefebvre, Mamadou Lo, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Financement ANR JCJC09, PORPH-NHC, and ANR-09-JCJC-0089,PORPH-NHC,Ligands ' Porphyrine-Carbène N-Hétérocyclique ' Réglables et Réactifs à des Stimuli Externes pour la Catalyse(2009)

Subjects
chemistry.chemical_element, Protonation, 010402 general chemistry, Photochemistry, 01 natural sciences, Medicinal chemistry, Catalysis, Rhodium, chemistry.chemical_compound, Deprotonation, polycyclic compounds, Materials Chemistry, [CHIM.COOR]Chemical Sciences/Coordination chemistry, organometallic complexes, 010405 organic chemistry, Ligand, Metals and Alloys, Free base, General Chemistry, Porphyrin, 0104 chemical sciences, 3. Good health, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Nickel, chemistry, rhodium, Ceramics and Composites, Carbene, porphyrin, N-heterocyclic carbene
Abstract

International audience; NHC ligands annulated to free-base porphyrins can be reversibly switched between electron-poor and electron-rich states upon protonation and deprotonation of the inner nitrogen atoms of the porphyrin. Metallation of the macrocycle with nickel(II) locks the peripheral NHC ligand in its electron-rich state.

Published
2011
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46. Synthesis, Caharacterization, and Electronic Properties of Metalloporphyrins Annulated to Exocyclic Imidazole and Imidazolium Rings

Author

Jean-François Lefebvre, Dominique Leclercq, Jean-Paul Gisselbrecht, Sébastien Richeter, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Institut de Chimie de Strasbourg, Centre National de la Recherche Scientifique (CNRS)-Université Louis Pasteur - Strasbourg I-Institut de Chimie du CNRS (INC), and ANR-09-JCJC-0089,PORPH-NHC,Ligands ' Porphyrine-Carbène N-Hétérocyclique ' Réglables et Réactifs à des Stimuli Externes pour la Catalyse(2009)

Subjects
Annulation, Trimethyl orthoformate, Alkylation, 010405 organic chemistry, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Ammonium hexafluorophosphate, Porphyrinoids, 010402 general chemistry, Ring (chemistry), 01 natural sciences, Porphyrin, 0104 chemical sciences, chemistry.chemical_compound, Cyclization, Hexafluorophosphate, Polymer chemistry, Electrochemistry, Organic chemistry, Imidazole, Physical and Theoretical Chemistry, Fused-ring systems
Abstract

Full paper; International audience; meso-Tetraarylporphyrin complexes (M = Ni, Cu, Zn, H2) fused to an imidazole ring across two neighboring β-pyrrolic positions were synthesized through a cyclization reaction between β,β'-diaminoporphyrins and formic acid or trimethyl orthoformate under acidic conditions. Two synthetic procedures were used to obtain the corresponding porphyrin N,N'-dimethylimidazolium salts derivatives: alkylation of the imidazole nitrogen atoms with iodomethane and the cyclization reaction between the porphyrin bearing two neighboring β-N-methyl groups and trimethyl orthoformate in the presence of ammonium hexafluorophosphate. The electrochemical properties of these porphyrins annulated to an imidazole/imidazolium ring have been investigated by cyclic and rotating disk voltammetry.

Published
2010
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47. Measuring the Sustainability of Cities: A Survey-Based Analysis of the Use of Local Indicators

Author

Paul Lanoie, Juste Rajaonson, Jean-François Lefebvre, and Georges A. Tanguay

Subjects
Sustainable development, Geography, media_common.quotation_subject, Selection strategy, Sustainability, The Conceptual Framework, Ambiguity, Selection method, Environmental economics, Local governance, Cartography, Selection (genetic algorithm), media_common
Abstract

We analyze 17 studies of the use of sustainable development indicators (SDI) in an urban setting. The analysis reveals a lack of consensus not only on the conceptual framework and the approach favored, but also on the selection and optimal number of indicators. First, by performing different classifications and categorizations of SDI we identify problems inherent in territorial practices that use SDI. Second, we argue that the lack of consensus in several steps of the creation of SDI stems notably from the ambiguity in the definitions of sustainable development, objectives for the use of such indicators, the selection method and the accessibility of qualitative and quantitative data. Third, we propose a selection strategy for SDI through which we demonstrate the need to adopt a parsimonious list of SDI covering the sustainable development components and their constituent categories as broadly as possible while minimizing the number of indicators retained.

Published
2009
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48. Assessment of Chlamydia trachomatis infection by Cobas Amplicor PCR and in-house LightCycler assays using PreservCyt and 2-SP media in voluntary legal abortions

Author

François Eb, Jean François Lefebvre, Henri Sevestre, Farida Hamdad, and Jacques Mention

Subjects
Microbiology (medical), Adult, medicine.medical_specialty, Adolescent, Prevalence, Chlamydia trachomatis, Roche Diagnostics, medicine.disease_cause, Microbiology, Polymerase Chain Reaction, law.invention, Specimen Handling, Automation, law, Pregnancy, Pelvic inflammatory disease, Cobas amplicor, Medicine, Humans, Polymerase chain reaction, Chlamydia trachomatis infection, Gynecology, business.industry, General Medicine, Chlamydia Infections, Virology, Culture Media, Abortion, Legal, Legal abortion, Female, business, Bacterial Outer Membrane Proteins
Abstract

Chlamydial infection of the upper genital tract after abortion is well recognized, but routine screening for infection before termination is rare, and few centres are aware of the prevalence of post-abortion complications in their patient population. Knowledge of the patient population is the best guide for developing screening strategies. The aim of this study was to determine the prevalence of chlamydial infection in patients presenting for legal termination of pregnancy, and to assess the presence of Chlamydia trachomatis by PCR on specimens collected in either PreservCyt (ThinPrep) or 2-sucrose phosphate (2-SP) transport medium. Two hundred and eleven single, sexually active women, aged 15–26 years, attending the Gynaecology and Obstetric Hospital, Amiens, France, for surgical termination of pregnancy were enrolled in this study from June 2002 to June 2003. C. trachomatis detection using a Cobas Amplicor PCR test (Roche Diagnostics) targeting a 207 bp segment of the common cryptic plasmid and a quantitative LightCycler real-time PCR (LC-PCR) (Roche Diagnostics) targeting a 123 bp fragment within the highly conserved constant domain 3 of the single-chromosome-copy ompA gene were performed on endocervical swabs in 2-SP, and on specimens collected using a cytobrush and placed in PreservCyt medium. The in-house LC-PCR was used as a chromosomal diagnosis method and to determine the load of C. trachomatis. This method was able to detect the mutant Swedish variant with a deletion of 377 bp in the target area in the cryptic plasmid, which is the region targeted by the Cobas Amplicor PCR test. C. trachomatis was detected in 19/211 patients (9 %) by both PCR methods. Among the 19 infected women, C. trachomatis was detected by the Cobas Amplicor PCR in 16 specimens in PreservCyt (7.6 %) and in 12 endocervical swabs in 2-SP (5.7 %). Specimens from only nine women were PCR-positive in both PreservCyt and 2-SP media by this method. Cobas Amplicor PCR revealed that 10.9 and 2.3 % of the PreservCyt and 2-SP samples, respectively, contained inhibitors. The same 19 infected women were LC-PCR positive in both PreservCyt and 2-SP samples. No additional infected women were found by this last method; thus, it was concluded that none of the samples contained the new variant of C. trachomatis. The load in each sample varied from 102 to 107 copies ml−1.

Published
2008

49. The lack of a systematic validation of reference genes: a serious pitfall undervalued in reverse transcription-polymerase chain reaction (RT-PCR) analysis in plants

Author

Catherine Bellini, Thomas Moritz, Jérôme Pelloux, Christine Rusterucci, Olivier Van Wuytswinkel, Jean-François Lefebvre, Laurent Gutierrez, Stéphanie Guénin, François Guerineau, Romain Louvet, Mélanie Mauriat, Gutierrez, Laurent, Umea Plant Science Center (UPSC), Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences (SLU)-Swedish University of Agricultural Sciences (SLU), Biologie des Plantes et Innovation - UR UPJV 3900 (BIOPI), Université de Picardie Jules Verne (UPJV)-Transfrontalière BioEcoAgro - UMR 1158 (BioEcoAgro), Université d'Artois (UA)-Université de Liège-Université de Picardie Jules Verne (UPJV)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Université d'Artois (UA)-Université de Liège-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Université de Picardie Jules Verne (UPJV), Laboratoire de biologie cellulaire et moléculaire, and Institut National de la Recherche Agronomique (INRA)

Subjects
0106 biological sciences, [SDV]Life Sciences [q-bio], Arabidopsis, RT-PCR, reference genes, Plant Science, Biology, Genes, Plant, 01 natural sciences, Transcriptome, 03 medical and health sciences, transcript profiling, Reference genes, Gene expression, Gene, 030304 developmental biology, Genetics, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Reproducibility of Results, Housekeeping gene, Gene expression profiling, Reverse transcription polymerase chain reaction, gene expression, normalization, quantitative PCR, Populus, Real-time polymerase chain reaction, Agronomy and Crop Science, 010606 plant biology & botany, Biotechnology
Abstract

International audience; Reverse transcription-polymerase chain reaction (RT-PCR) approaches have been used in a large proportion of transcriptome analyses published to date. The accuracy of the results obtained by this method strongly depends on accurate transcript normalization using stably expressed genes, known as references. Statistical algorithms have been developed recently to help validate reference genes, and most studies of gene expression in mammals, yeast and bacteria now include such validation. Surprisingly, this important approach is under-utilized in plant studies, where putative housekeeping genes tend to be used as references without any appropriate validation. Using quantitative RT-PCR, the expression stability of several genes commonly used as references was tested in various tissues of Arabidopsis thaliana and hybrid aspen (Populus tremula x Populus tremuloides). It was found that the expression of most of these genes was unstable, indicating that their use as references is inappropriate. The major impact of the use of such inappropriate references on the results obtained by RT-PCR is demonstrated in this study. Using aspen as a model, evidence is presented indicating that no gene can act as a universal reference, implying the need for a systematic validation of reference genes. For the first time, the extent to which the lack of a systematic validation of reference genes is a stumbling block to the reliability of results obtained by RT-PCR in plants is clearly shown.

Published
2008
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50. Correction: Design and characterisation of bodipy sensitizers for dye-sensitized NiO solar cells

Author

Karel Zidek, Christopher Wood, Elizabeth A. Gibson, Fiona Black, Tõnu Pullerits, Gareth H. Summers, E. Stephen Davies, and Jean-François Lefebvre

Subjects
chemistry.chemical_compound, Chemistry, Non-blocking I/O, General Physics and Astronomy, 02 engineering and technology, Physical and Theoretical Chemistry, BODIPY, 010402 general chemistry, 021001 nanoscience & nanotechnology, 0210 nano-technology, Photochemistry, 01 natural sciences, 0104 chemical sciences
Abstract

Correction for 'Design and characterisation of bodipy sensitizers for dye-sensitized NiO solar cells' by Gareth H. Summers et al., Phys. Chem. Chem. Phys., 2016, DOI: 10.1039/c5cp05177k.

Published
2016
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