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11 results on '"AXA Research Fund"'

1. Inhibition of autophagy curtails visual loss in a model of autosomal dominant optic atrophy

Author

Bodossaki Foundation, AXA Research Fund, Hellenic Foundation for Research and Innovation, European Commission, Fondazione Umberto Veronesi, Japan Society for the Promotion of Science, Telethon Italia, Ministero della Salute, Ministero dell'Istruzione, dell'Università e della Ricerca, Fondation Leducq, European Research Council, General Secretariat of Research and Technology (Greece), International Foundation for Optic Nerve Disease, Palikaras, Konstantinos[0000-0001-6992-5560], Naon, Deborah [0000-0002-9726-4664], Quintana-Cabrera, Ruben [0000-0002-0601-349X], Tavernarakis, Nektarios [0000-0002-5253-1466], Scorrano, Luca [0000-0002-8515-8928], Zaninello, Marta, Palikaras, Konstantinos, Naon, Deborah, Iwata, keiko, Herkenne, Stephanie, Quintana-Cabrera, Ruben, Semenzato, Martina, Grespi, Francesca, Ross-Cisneros, Fred N., Carelli, Valerio, Sadun, Alfredo A., Tavernarakis, Nektarios, Scorrano, Luca, Bodossaki Foundation, AXA Research Fund, Hellenic Foundation for Research and Innovation, European Commission, Fondazione Umberto Veronesi, Japan Society for the Promotion of Science, Telethon Italia, Ministero della Salute, Ministero dell'Istruzione, dell'Università e della Ricerca, Fondation Leducq, European Research Council, General Secretariat of Research and Technology (Greece), International Foundation for Optic Nerve Disease, Palikaras, Konstantinos[0000-0001-6992-5560], Naon, Deborah [0000-0002-9726-4664], Quintana-Cabrera, Ruben [0000-0002-0601-349X], Tavernarakis, Nektarios [0000-0002-5253-1466], Scorrano, Luca [0000-0002-8515-8928], Zaninello, Marta, Palikaras, Konstantinos, Naon, Deborah, Iwata, keiko, Herkenne, Stephanie, Quintana-Cabrera, Ruben, Semenzato, Martina, Grespi, Francesca, Ross-Cisneros, Fred N., Carelli, Valerio, Sadun, Alfredo A., Tavernarakis, Nektarios, and Scorrano, Luca

Abstract

In autosomal dominant optic atrophy (ADOA), caused by mutations in the mitochondrial cristae biogenesis and fusion protein optic atrophy 1 (Opa1), retinal ganglion cell (RGC) dysfunction and visual loss occur by unknown mechanisms. Here, we show a role for autophagy in ADOA pathogenesis. In RGCs expressing mutated Opa1, active 5’ AMP-activated protein kinase (AMPK) and its autophagy effector ULK1 accumulate at axonal hillocks. This AMPK activation triggers localized hillock autophagosome accumulation and mitophagy, ultimately resulting in reduced axonal mitochondrial content that is restored by genetic inhibition of AMPK and autophagy. In C. elegans, deletion of AMPK or of key autophagy and mitophagy genes normalizes the axonal mitochondrial content that is reduced upon mitochondrial dysfunction. In conditional, RGC specific Opa1-deficient mice, depletion of the essential autophagy gene Atg7 normalizes the excess autophagy and corrects the visual defects caused by Opa1 ablation. Thus, our data identify AMPK and autophagy as targetable components of ADOA pathogenesis.

Published
2020

2. Reconstructing Mayaro virus circulation in French Guiana shows frequent spillovers

Author

Antoine Enfissi, Matthieu Najm, Sarah Bailly, Nathanaël Hozé, Dominique Rousset, Jessica Vanhomwegen, Jean-Claude Manuguerra, Camille Fritzell, Claude Flamand, Simon Cauchemez, Henrik Salje, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence pour les Arbovirus - Laboratoire associé de Virologie [Cayenne, Guyane] (CNR), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Unité d'Epidémiologie, Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris], This study was supported by the 'European Regional Development Fund' under EPI-ARBO grant agreement (GY0008695), the 'Regional Health Agency of French Guiana', the 'National Center of Spatial Studies'. C.Fl. and C. Fr. acknowledge funding from Calmette and Yersin allocated by the 'Pasteur Institut Department of International Affairs'. N.H. and S.C. acknowledge financial support from the AXA Research Fund, the Investissement d’Avenir program, the Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases program (Grant ANR-10-LABX-62-IBEID), the Models of Infectious Disease Agent Study of the National Institute of General Medical Sciences, the INCEPTION project (PIA/ANR-16-CONV-0005), the European Union’s Horizon 2020 research and innovation programme under ZIKAlliance grant agreement No. 734548., We wish to thank Mirdad Kazanji (Institut Pasteur in French Guiana), Félix Djossou (Cayenne hospital center), Sandrine Fernandes-Pellerin (Institut Pasteur - CRT), and Léna Berthelot, Séverine Matheus, Laetitia Bremand, Bhety Labeau, David Moua, and Marine Rangon from the Arbovirus National Reference Center for their valuable contribution in the laboratory analyses. We thank Juliette Paireau and Quirine ten Bosch for insightful discussions., ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l’étude de l’Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 734548,ZIKAlliance(2016), University of Cambridge [UK] (CAM), Centre National de Référence pour les Arbovirus - Laboratoire de Virologie [Cayenne, Guyane française] (CNR - laboratoire associé), Réseau International des Instituts Pasteur (RIIP), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Hozé, Nathanaël [0000-0002-3977-8966], Salje, Henrik [0000-0003-3626-4254], Rousset, Dominique [0000-0002-1473-3147], Manuguerra, Jean-Claude [0000-0002-5202-6531], Flamand, Claude [0000-0002-8064-445X], and Apollo - University of Cambridge Repository

Subjects
Male, 0301 basic medicine, Statistical methods, Epidemiology, [SDV]Life Sciences [q-bio], viruses, General Physics and Astronomy, Rural Health, Antibodies, Viral, medicine.disease_cause, Communicable Diseases, Emerging, Viral infection, MESH: Cross Reactions, 13/1, Seroepidemiologic Studies, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Arboviruses, MESH: Child, MESH: Communicable Diseases, Emerging, 692/308/174, Chikungunya, [MATH]Mathematics [math], Child, MESH: Alphavirus Infections, lcsh:Science, MESH: Immunoglobulin G, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Multidisciplinary, MESH: Middle Aged, article, virus diseases, Middle Aged, 631/114/2415, MESH: Infant, French Guiana, 3. Good health, [STAT]Statistics [stat], Geography, MESH: Young Adult, Child, Preschool, Epidemiological Monitoring, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Sylvatic cycle, Chikungunya virus, Adult, Adolescent, Science, 030106 microbiology, Cross Reactions, Arbovirus, General Biochemistry, Genetics and Molecular Biology, Virus, Young Adult, 03 medical and health sciences, MESH: Cross-Sectional Studies, 692/699/255/2514, Environmental health, MESH: French Guiana, medicine, Humans, Natural reservoir, Viral immunology, MESH: Adolescent, MESH: Seroepidemiologic Studies, MESH: Humans, Alphavirus Infections, MESH: Child, Preschool, Infant, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Adult, MESH: Chikungunya virus, General Chemistry, MESH: Rural Health, biochemical phenomena, metabolism, and nutrition, medicine.disease, MESH: Male, Cross-Sectional Studies, 030104 developmental biology, Immunoglobulin G, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, lcsh:Q, MESH: Epidemiological Monitoring, MESH: Female, Arboviruses, MESH: Antibodies, Viral
Abstract

Characterizing the circulation of Mayaro virus (MAYV), an emerging arbovirus threat, is essential for risk assessment but challenging due to cross-reactivity with other alphaviruses such as chikungunya virus (CHIKV). Here, we develop an analytical framework to jointly assess MAYV epidemiology and the extent of cross-reactivity with CHIKV from serological data collected throughout French Guiana (N = 2697). We find strong evidence of an important sylvatic cycle for MAYV with most infections occurring near the natural reservoir in rural areas and in individuals more likely to go to the forest (i.e., adult males) and with seroprevalences of up to 18% in some areas. These findings highlight the need to strengthen MAYV surveillance in the region and showcase how modeling can improve interpretation of cross-reacting assays., Mayaro virus (MAYV) is an emerging arbovirus, but cross-reactivity with other alphaviruses makes analysis of its epidemiology difficult. Here, the authors develop an analytical framework to assess MAYV epidemiology and find evidence for an important sylvatic cycle and seroprevalences of up to 18% in some areas of French Guiana.

Published
2020

3. Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus

Author

Donal Bisanzio, Thomas W. Scott, G. R. William Wint, T. Alex Perkins, Nicole Davis Weaver, Lucas Earl, Laurie B. Marczak, Erik Wetter, Hongjie Yu, Shengjie Lai, Dingdong Yi, Simon I. Hay, Wim Van Bortel, Cedric Marsboom, Francis Schaffner, Giovanini E. Coelho, David M. Pigott, Jane P. Messina, Xin Lu, Robert C. Reiner, Linus Bengtsson, Andrew J. Tatem, David L. Smith, Chester G. Moore, Shreya Shirude, Qiyong Liu, Peter A. Jones, Kimberly J. Johnson, Roberta G. Carvalho, John S. Brownstein, Moritz U. G. Kraemer, Oliver J. Brady, Nuno R. Faria, Louis Lambrechts, Nick Golding, Marius Gilbert, Heinrich H. Nax, Guy Hendrickx, Oliver G. Pybus, Simon Cauchemez, Catherine Linard, University of Oxford [Oxford], Boston Children's Hospital, Harvard Medical School [Boston] (HMS), University of Washington [Seattle], London School of Hygiene and Tropical Medicine (LSHTM), Université libre de Bruxelles (ULB), Fonds National de la Recherche Scientifique [Bruxelles] (FNRS), Harvard University [Cambridge], University of Nottingham, UK (UON), Eck Institute for Global Health, University of Notre Dame [Indiana] (UND), Fudan University [Shanghai], University of Southampton, Flowminder Foundation, Central South University [Changsha], National University of Defense Technology [China], Southwestern University of Finance and Economics [Chengdu, China], Waen Associates Ltd, Pan American Health Organization [Washington] (PAHO), Ministry of Health [Brasília, Brazil], European Centre for Disease Prevention and Control (ECDC), Institute of Tropical Medicine [Antwerp] (ITM), Egis Avia (FRANCE), Francis Schaffner Consultancy, Colorado State University [Fort Collins] (CSU), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Karolinska Institutet [Stockholm], Stockholm School of Economics (SSE), Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université de Namur [Namur] (UNamur), University of California [Davis] (UC Davis), University of California, Chinese Center for Disease Control and Prevention, Shandong University, University of Melbourne, The authors thank S. Ray for providing comments during the revision process. M.U.G.K. acknowledges funding from the Society in Science, The Branco Weiss Fellowship, administered by the ETH Zurich. M.U.G.K. also acknowledges funding from the Training Grant from the National Institute of Child Health and Human Development (T32HD040128). M.U.G.K., S.I.H., J.P.M., N.G., O.J.B. and G.R.W.W. acknowledge funding from the International Research Consortium on Dengue Risk Assessment Management and Surveillance (IDAMS, European Commission 7th Framework Programme no. 21893). O.B.J. was funded by a Sir Henry Wellcome Fellowship funded by the Wellcome Trust (grant number 206471/Z/17/Z) and a grant from the Bill and Melinda Gates Foundation (OP1183567). S.I.H. received a grant from the Research for Health in Humanitarian Crises (R2HC) Programme, managed by Enhancing Learning and Research for Humanitarian Assistance (ELRHA, no. 13468), which also supported M.U.G.K. and N.G. The R2HC programme aims to improve health outcomes by strengthening the evidence base for public health interventions in humanitarian crises. The £8 million R2HC programme is funded equally by the Wellcome Trust and Department of International Development (DFiD), with ELRHA overseeing the programme’s execution and management. S.I.H. was also funded by a Senior Research Fellowship from the Wellcome Trust (no. 95066) and grants from the Bill & Melinda Gates Foundation (OPP1106023, OPP1093011, OPP1132415 and OPP1159934). This study was made possible by the support of the American people through the US Agency for International Development Emerging Pandemic Threats Program-2 PREDICT-2 (Cooperative Agreement number AID-OAA-A-14-00102), which also supported M.U.G.K. J.S.B. is supported by the National Library of Medicine of the National Institutes of Health (R01LM010812 and R01LM011965), which also supports M.U.G.K. D.L.S. is funded by the National Institutes of Health and National Institute of Allergy and Infectious Diseases (no. U10AI089674). H.H.N. was funded by the European Commission through the European Research Council Advanced Investigator Grant ‘Momentum’ 324247. L.L. received funding from the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (grant ANR-10-LABX-62-IBEID), the French Agence Nationale de la Recherche (grant ANR-16-CE35-0004), the City of Paris Emergence(s) programme in Biomedical Research, and the European Union’s Horizon 2020 research and innovation programme under ZikaPLAN grant agreement No. 734584. S.C. received funding from the AXA Research Fund, the Investissement d’Avenir program, the Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases program (Grant ANR-10-LABX-62-IBEID), the Models of Infectious Disease Agent Study of the National Institute of General Medical Sciences, the INCEPTION project (PIA/ANR-16-CONV-0005), and the European Union’s Horizon 2020 research and innovation programme under ZIKAlliance grant agreement No 734548. N.G. is supported by a University of Melbourne McKenzie fellowship. W.V.B., G.H. and F.S. acknowledge funding from VBORNET and VectorNet, an ECDC and EFSA-funded project (no. ECDC/09/018 and OC/EFSA/AHAW/2013/02), and thank all contributing VBORNET and VectorNet experts for data sharing. T.W.S., R.C.R. and L.L. received funding from the National Institutes of Health Program Project grant (no. P01 AI098670). X.L. is supported by the Natural Science Foundation of China (71771213, 71522014, 71725001, 91846301 and 71790615). This work was also partially supported by the European Union’s Horizon 2020 Research and Innovation Programme under ZIKAlliance Grant Agreement no. 734548., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CE35-0004,MOSQUIBIOTA,Contribution de la diversité bactérienne intestinale à la capacité vectorielle d'Aedes aegypti(2016), European Project: 734548,ZIKAlliance(2016), European Project: 324247,EC:FP7:ERC,ERC-2012-ADG_20120411,MOMENTUM(2013), European Project: 281803,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,IDAMS(2011), University of Oxford, Harvard University, European Centre for Disease Prevention and Control [Stockholm, Sweden] (ECDC), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and University of California (UC)

Subjects
Microbiology (medical), Microbiologie et protistologie [parasitologie hum. et anim.], Aedes albopictus, Arbovirus Infections, Immunology, Aedes aegypti, medicine.disease_cause, Applied Microbiology and Biotechnology, Arbovirus, Microbiology, Article, Dengue fever, Zika virus, 03 medical and health sciences, Genetics, medicine, Chikungunya, 030304 developmental biology, Aedes, 0303 health sciences, biology, 030306 microbiology, Ecology, virus diseases, Cell Biology, biology.organism_classification, medicine.disease, 3. Good health, Microbiologie et protistologie [entomologie,phytoparasitolog.], Geography, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Infectious diseases
Abstract

The global population at risk from mosquito-borne diseases—including dengue, yellow fever, chikungunya and Zika—is expanding in concert with changes in the distribution of two key vectors: Aedes aegypti and Aedes albopictus. The distribution of these species is largely driven by both human movement and the presence of suitable climate. Using statistical mapping techniques, we show that human movement patterns explain the spread of both species in Europe and the United States following their introduction. We find that the spread of Ae. aegypti is characterized by long distance importations, while Ae. albopictus has expanded more along the fringes of its distribution. We describe these processes and predict the future distributions of both species in response to accelerating urbanization, connectivity and climate change. Global surveillance and control efforts that aim to mitigate the spread of chikungunya, dengue, yellow fever and Zika viruses must consider the so far unabated spread of these mosquitos. Our maps and predictions offer an opportunity to strategically target surveillance and control programmes and thereby augment efforts to reduce arbovirus burden in human populations globally., 0, SCOPUS: ar.j, SCOPUS: er.j, info:eu-repo/semantics/published

Published
2019

4. MiRNA-15b and miRNA-125b are associated with regional Aβ-PET and FDG-PET uptake in cognitively normal individuals with subjective memory complaints

Author

Vergallo, Andrea, Lista, Simone, group, INSIGHT-preAD study, Lucía, Alejandro, Mango, Dalila, Mapstone, Mark, Neri, Christian, Nisticò, Robert, O'Bryant, Sid E, Palermo, Giovanni, Perry, George, Ritchie, Craig, Rossi, Simone, Initiative, Alzheimer Precision Medicine, Saidi, Amira, Santarnecchi, Emiliano, Schneider, Lon S, Sporns, Olaf, Toschi, Nicola, Valenzuela, Pedro L, Vellas, Bruno, Verdooner, Steven R, Villain, Nicolas, Giudici, Kelly Virecoulon, Bakardjian, Hovagim, Watling, Mark, Welikovitch, Lindsay A, Woodcock, Janet, Younesi, Erfan, Zugaza, José L, Benali, Habib, Bertin, Hugo, Bonheur, Joel, Boukadida, Laurie, Boukerrou, Nadia, Cavedo, Enrica, Chiesa, Patrizia, Zhao, Yuhai, Colliot, Olivier, Dubois, Bruno, Dubois, Marion, Epelbaum, Stéphane, Gagliardi, Geoffroy, Genthon, Remy, Habert, Marie-Odile, Hampel, Harald, Houot, Marion, Kas, Aurélie, Lemercier, Pablo, Lamari, Foudil, Levy, Marcel, Metzinger, Christiane, Mochel, Fanny, Nyasse, Francis, Poisson, Catherine, Potier, Marie-Claude, Revillon, Marie, Santos, Antonio, Teipel, Stefan J, Andrade, Katia Santos, Sole, Marine, Surtee, Mohmed, de Schotten, Michel Thiebaut, Younsi, Nadjia, Afshar, Mohammad, Aguilar, Lisi Flores, Akman-Anderson, Leyla, Arenas, Joaquín, Ávila, Jesús, Babiloni, Claudio, Baldacci, Filippo, Batrla, Richard, Benda, Norbert, Black, Keith L, Bokde, Arun L W, Bonuccelli, Ubaldo, Broich, Karl, Cacciola, Francesco, Caraci, Filippo, Caruso, Giuseppe, Castrillo, Juan, Ceravolo, Roberto, Chiesa, Patrizia A, Corbo, Massimo, Corvol, Jean-Christophe, Cuello, Augusto Claudio, Cummings, Jeffrey L, Depypere, Herman, Duggento, Andrea, Emanuele, Enzo, Escott-Price, Valentina, Federoff, Howard, Ferretti, Maria Teresa, Fiandaca, Massimo, Frank, Richard A, Garaci, Francesco, Lukiw, Walter J, Geerts, Hugo, Giacobini, Ezio, Giorgi, Filippo S, Goetzl, Edward J, Graziani, Manuela, Haberkamp, Marion, Hänisch, Britta, Herholz, Karl, Hernandez, Felix, Imbimbo, Bruno P, Kapogiannis, Dimitrios, Karran, Eric, Kiddle, Steven J, Kim, Seung H, Koronyo, Yosef, Koronyo-Hamaoui, Maya, Langevin, Todd, Lehéricy, Stéphane, Llavero, Francisco, Lorenceau, Jean, Ministre de l'Enseignement Supérieur, de la Recherche et de l'Innovation (France), Sorbonne Université, AXA Research Fund, Fondation partenariale, Fondation pour la Recherche sur Alzheimer, Investissement d’Avenir French program, Vergallo, Andrea [0000-0002-0208-6384], Apollo - University of Cambridge Repository, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-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), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Louisiana State University (LSU), University of Rostock, Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CATI Multicenter Neuroimaging Platform (CATI), Service de médecine nucléaire [CHU Pitié-Salpétrière], Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), Department of Psychiatry, Psychosomatic Medicine and Psychotherapy [Goethe Universität], Goethe-Universität Frankfurt am Main, HAL-SU, Gestionnaire, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 APM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Service de Médecine nucléaire [CHU Pitié-Salpétrière], Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France, Groupe de recherche clinique Alzheimer Precision Medicine (GRC 21 - APM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
Apolipoprotein E, Aging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Disease, miRNAs plasma concentrations, Alzheimer's Disease, amyloid-β (Aβ)-positron emission tomography (Aβ-PET), Prognostic markers, 0302 clinical medicine, Medicine, Psychology, Aetiology, education.field_of_study, MicroARNs, Settore FIS/07, amyloid, Brain, Pathophysiology, ALZHEIMERS-DISEASE, Psychiatry and Mental health, Alzheimer's disease (AD), Public Health and Health Services, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MiRNA, medicine.medical_specialty, 18F-fluorodeoxyglucose-PET (18F-FDG-PET), BIOMARKERS, Neurociencias, Clinical Sciences, Molecular neuroscience, Predictive markers, Article, VESICLES, lcsh:RC321-571, 03 medical and health sciences, Memory, Clinical Research, Alzheimer Disease, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], microRNA, Genetics, Humans, education, Biological Psychiatry, Prevention, Memory, MiRNA, Alzheimer, biological markers, amyloid, 030104 developmental biology, Endocrinology, Cross-Sectional Studies, Positron-Emission Tomography, CELLS, Dementia, diagnostic imaging [Alzheimer Disease], INSIGHT-preAD study group, 030217 neurology & neurosurgery, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 0301 basic medicine, genetics [Alzheimer Disease], Pilot Projects, Neurodegenerative, Medicine and Health Sciences, 2.1 Biological and endogenous factors, genetics [MicroRNAs], MIR-125B, screening and diagnosis, PLASMA, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Detection, Real-time polymerase chain reaction, Neurological, medicine.symptom, biological markers, Biotechnology, EXPRESSION, Population, metabolism [Amyloid beta-Peptides], Asymptomatic, Salud mental, Cellular and Molecular Neuroscience, ADULT, Fluorodeoxyglucose F18, Internal medicine, Acquired Cognitive Impairment, ddc:610, Allele, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, diagnostic imaging [Brain], Psiquiatría, Amyloid beta-Peptides, Enfermedad de alzheimer, business.industry, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Neurosciences, Alzheimer Precision Medicine Initiative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, MicroRNAs, metabolism [Brain], Alzheimer, business, Psychiatric disorders
Abstract

There is substantial experimental evidence for dysregulation of several microRNA (miRNA) expression levels in Alzheimer’s disease (AD). MiRNAs modulate critical brain intracellular signaling pathways and are associated with AD core pathophysiological mechanisms. First, we conducted a real-time quantitative PCR-based pilot study to identify a set of brain-enriched miRNAs in a monocentric cohort of cognitively normal individuals with subjective memory complaints, a condition associated with increased risk of AD. Second, we investigated the impact of age, sex, and the Apolipoprotein E ε4 (APOE ε4) allele, on the identified miRNA plasma concentrations. In addition, we explored the cross-sectional and longitudinal association of the miRNAs plasma concentrations with regional brain metabolic uptake using amyloid-β (Aβ)-positron emission tomography (Aβ-PET) and F-fluorodeoxyglucose-PET (F-FDG-PET). We identified a set of six brain-enriched miRNAs—miRNA-125b, miRNA-146a, miRNA-15b, miRNA-148a, miRNA-26b, and miRNA-100. Age, sex, and APOE ε4 allele were not associated with individual miRNA abundance. MiRNA-15b concentrations were significantly lower in the Aβ-PET-positive compared to Aβ-PET-negative individuals. Furthermore, we found a positive effect of the miRNA-15b*time interaction on regional metabolic F-FDG-PET uptake in the left hippocampus. Plasma miRNA-125b concentrations, as well as the miRNA-125b*time interaction (over a 2-year follow-up), were negatively associated with regional Aβ-PET standard uptake value ratio in the right anterior cingulate cortex. At baseline, we found a significantly negative association between plasma miRNA-125b concentrations and F-FDG-PET uptake in specific brain regions. In an asymptomatic at-risk population for AD, we show significant associations between plasma concentrations of miRNA-125b and miRNA-15b with core neuroimaging biomarkers of AD pathophysiology. Our results, coupled with existing experimental evidence, suggest a potential protective anti-Aβ effect of miRNA-15b and a biological link between miRNA-125b and Aβ-independent neurotoxic pathways., “Investissement d’Avenir” (ANR-10-AIHU-06) French program. The study was promoted in collaboration with the “CHU de Bordeaux” (coordination CIC EC7), the promoter of Memento cohort, funded by the Foundation Plan-Alzheimer. The study was further supported by AVID/Lilly. CATI is a French neuroimaging platform funded by the French Plan Alzheimer (available at http://cati-neuroimaging.com). A.V. is an employee of Eisai Inc. This work has been performed during his previous position at Sorbonne University, Paris, France. H.H. is an employee of Eisai Inc. This work has been performed during his previous position at Sorbonne University, Paris, France. At Sorbonne University he was supported by the AXA Research Fund, the “Fondation partenariale Sorbonne Université” and the “Fondation pour la Recherche sur Alzheimer

Published
2021

5. p21Cip1 plays a critical role in the physiological adaptation to fasting through activation of PPARα

Author

Maribel Muñoz-Martin, Manuel Serrano, Elena Lopez-Guadamillas, Ángela M. Valverde, Pablo J. Fernandez-Marcos, Ramón Campos-Olivas, Cristina Pantoja, Dolores Martinez, Gonzalo Gómez-López, Ministerio de Ciencia e Innovación (España), Asociación Española Contra el Cáncer, European Research Council, Comunidad de Madrid (España), Botín Foundation, Banco Santander, Fundación Ramón Areces, Fundación AXA, Centro Nacional de Investigaciones Oncológicas (España), Ministerio de Educación (España), Ministerio de Economía y Competitividad (España), Comunidad de Madrid, Fundación Botín, AXA Research Fund, and European Commission

Subjects
0301 basic medicine, Cyclin-Dependent Kinase Inhibitor p21, Male, medicine.medical_specialty, Regulator, Peroxisome proliferator-activated receptor, Biology, Article, law.invention, Transcriptome, 03 medical and health sciences, Mice, 0302 clinical medicine, Downregulation and upregulation, law, Internal medicine, medicine, Animals, PPAR alpha, chemistry.chemical_classification, Messenger RNA, Multidisciplinary, Metabolism, Fasting, Adaptation, Physiological, Mice, Mutant Strains, 3. Good health, Protein catabolism, 030104 developmental biology, Endocrinology, chemistry, 030220 oncology & carcinogenesis, Suppressor, Tumor Suppressor Protein p53
Abstract

et al., Fasting is a physiological stress that elicits well-known metabolic adaptations, however, little is known about the role of stress-responsive tumor suppressors in fasting. Here, we have examined the expression of several tumor suppressors upon fasting in mice. Interestingly, p21 mRNA is uniquely induced in all the tissues tested, particularly in liver and muscle (>10 fold), and this upregulation is independent of p53. Remarkably, in contrast to wild-type mice, p21-null mice become severely morbid after prolonged fasting. The defective adaptation to fasting of p21-null mice is associated to elevated energy expenditure, accelerated depletion of fat stores, and premature activation of protein catabolism in the muscle. Analysis of the liver transcriptome and cell-based assays revealed that the absence of p21 partially impairs the transcriptional program of PPARα, a key regulator of fasting metabolism. Finally, treatment of p21-null mice with a PPARα agonist substantially protects them from their accelerated loss of fat upon fasting. We conclude that p21 plays a relevant role in fasting adaptation through the positive regulation of PPARα., E.L.-G. was recipient of a predoctoral contract from the Spanish Ministry of Education. P.J.F.-M. has been funded by the Spanish Association Against Cancer (aecc). Work in the laboratory of M.S. is funded by the CNIO and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (SAF project), the European Research Council (ERC Advanced Grant), the Regional Government of Madrid co-funded by the European Social Fund (ReCaRe project), the Botin Foundation and Banco Santander (Santander Universities Global Division), the Ramon Areces Foundation, and the AXA Foundation.

Published
2016

6. The global spectrum of plant form and function

Author

Stéphane Dray, Andrew N. Gillison, Jérôme Chave, Gerhard Bönisch, Miguel D. Mahecha, Angela Günther, Jens Kattge, Sandra Díaz, S. Joseph Wright, Michael Kleyer, Amy E. Zanne, Angela T. Moles, Hendrik Poorter, Eric Garnier, Bill Shipley, Hervé Jactel, Bruno Enrico Leone Cerabolini, Lucas D. Gorné, Mark Westoby, Björn Reu, Christian Wirth, Johannes H. C. Cornelissen, Don Kirkup, I. Colin Prentice, Simon Pierce, Peter B. Reich, Christopher Baraloto, Julia Joswig, Serge N. Sheremetev, Fernando Casanoves, Nadja Rüger, John B. Dickie, Ian J. Wright, Sandra Lavorel, Valeria Falczuk, AXA Research Fund, Systems Ecology, Amsterdam Global Change Institute, Ecologie quantitative et évolutive des communautés, Département écologie évolutive [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0106 biological sciences, Biodiversity, Databases, Factual, Genetic Variation, Internationality, Models, Biological, Nitrogen, Organ Size, Plant Development, Plant Leaves, Plant Stems, Plants, Reproduction, Seeds, Selection, Genetic, Species Specificity, Phenotype, Plant Physiological Phenomena, Multidisciplinary, [SDV]Life Sciences [q-bio], 01 natural sciences, EVOLUTIONARY ECOLOGY, Models, CLIMATE-CHANGE ECOLOGY, 2. Zero hunger, Spectrum (functional analysis), ECOSYSTEM ECOLOGY, Bioquímica y Biología Molecular, Multidisciplinary Sciences, SEED SIZE, KERNEL DENSITY-ESTIMATION, FOLIAR NITROGEN ISOTOPES, Science & Technology - Other Topics, RAIN-FOREST TREES, ECOPHYSIOLOGY, LEAF ECONOMICS SPECTRUM, Biological system, Ecosystem ecology, PHOTOSYNTHETIC CAPACITY, CIENCIAS NATURALES Y EXACTAS, Scale (ratio), General Science & Technology, Biology, Photosynthesis, 010603 evolutionary biology, Ciencias Biológicas, Databases, Genetic, Form and function, TRAIT-ENVIRONMENT RELATIONSHIPS, Botany, MD Multidisciplinary, Selection, Factual, DRY-MATTER CONTENT, Science & Technology, Plane (geometry), HAWAIIAN METROSIDEROS-POLYMORPHA, 15. Life on land, Biological, Photosynthetic capacity, BIODIVERSITY, RELATIVE GROWTH-RATE, 010606 plant biology & botany
Abstract

Earth is home to a remarkable diversity of plant forms and life histories, yet comparatively few essential trait combinationshave proved evolutionarily viable in today?s terrestrial biosphere. By analysing worldwide variation in six major traitscritical to growth, survival and reproduction within the largest sample of vascular plant species ever compiled, we foundthat occupancy of six-dimensional trait space is strongly concentrated, indicating coordination and trade-offs. Threequartersof trait variation is captured in a two-dimensional global spectrum of plant form and function. One majordimension within this plane reflects the size of whole plants and their parts; the other represents the leaf economicsspectrum, which balances leaf construction costs against growth potential. The global plant trait spectrum provides abackdrop for elucidating constraints on evolution, for functionally qualifying species and ecosystems, and for improvingmodels that predict future vegetation based on continuous variation in plant form and function. Fil: Díaz, Sandra Myrna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Kattge, Jens. Max Planck Institute for Biogeochemistry; Alemania Fil: Cornelissen, Johannes H. C.. Vrije Universiteit; Países Bajos Fil: Wright, Ian J.. Macquarie University; Australia Fil: Lavorel, Sandra. Université Grenoble Alpes; Francia Fil: Dray, Stéphane. Université Lyon; Francia Fil: Reu, Björn. University of Leipzig; Francia Fil: Kleyer, Michael. University of Oldenburg; Alemania Fil: Wirth, Christian. Max Planck Institute for Biogeochemistry; Alemania Fil: Prentice, I. Colin. Macquarie University; Australia Fil: Garnier, Eric. Université Paul-Valéry Montpellier; Francia Fil: Bönisch, Gerhard. Max Planck Institute for Biogeochemistry; Alemania Fil: Westoby, Mark. Macquarie University; Australia Fil: Poorter, Hendrik. Forschungszentrum Jülich GmbH; Alemania Fil: Reich, Peter B.. University of Minnesota; Estados Unidos. University of Western Sydney; Australia Fil: Moles, Angela T.. University of New South Wales; Australia Fil: Dickie, John. The Royal Botanic Gardens Kew; Reino Unido Fil: Gillison, Andrew N.. Center for Biodiversity Management; Australia Fil: Zanne, Amy E.. George Washington University; Estados Unidos. Missouri Botanical Garden; Estados Unidos Fil: Chave, Jérôme. Université Paul Sabatier; Francia Fil: Wright, S. Joseph. Smithsonian Tropical Research Institute; Estados Unidos Fil: Sheremetev, Serge N.. Komarov Botanical Institute; Rusia Fil: Jactel, Hervé. Université de Bordeaux; Francia Fil: Baraloto, Christopher. Florida International University; Estados Unidos. Ecologie des Forêts de Guyane; Guayana Francesa Fil: Cerabolini, Bruno. University of Insubria; Italia Fil: Pierce, Simon. University of Milan; Italia Fil: Shipley, Bill. Université de Sherbrooke; Canadá Fil: Kirkup, Donald. The Royal Botanic Gardens Kew; Reino Unido Fil: Casanoves, Fernando. Centro Agronómico Tropical de Investigación y Enseñanza; Costa Rica Fil: Joswig, Julia S.. Max Planck Institute for Biogeochemistry; Alemania Fil: Günther, Angela. Max Planck Institute for Biogeochemistry; Alemania Fil: Falczuk, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Rüger, Nadja. German Centre for Integrative Biodiversity Research; Alemania Fil: Mahecha, Miguel D.. Max Planck Institute for Biogeochemistry; Alemania Fil: Gorne, Lucas Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina

Published
2015

7. Using ecosystem experiments to improve vegetation models

Author

Belinda E. Medlyn, Shusen Wang, Peter E. Thornton, Paul J. Hanson, Martin G. De Kauwe, Anthony P. Walker, Atul K. Jain, Colleen M. Iversen, Richard J. Norby, William J. Parton, Heather R. McCarthy, Ram Oren, I. Colin Prentice, Ying-Ping Wang, Thomas Hickler, Yiqi Luo, Michael Dietze, Sönke Zaehle, Jeffrey M. Warren, Ensheng Weng, and AXA Research Fund

Subjects
ELEVATED ATMOSPHERIC CO2, Environmental Studies, STOMATAL CONDUCTANCE, AIR CO2 ENRICHMENT, Environmental Sciences & Ecology, Environmental Science (miscellaneous), Meteorology & Atmospheric Sciences, Ecosystem, FACE EXPERIMENTS, WATER-STRESS, Science & Technology, business.industry, Water stress, Environmental resource management, Vegetation, DECIDUOUS FOREST, CLIMATE, TEMPERATE FOREST, Physical Sciences, Environmental science, business, CARBON-NITROGEN INTERACTIONS, Life Sciences & Biomedicine, Social Sciences (miscellaneous), Environmental Sciences, CYCLE MODELS
Abstract

Ecosystem responses to rising CO2 concentrations are a major source of uncertainty in climate change projections. Data from ecosystem-scale Free-Air CO2 Enrichment (FACE) experiments provide a unique opportunity to reduce this uncertainty. The recent FACE Model–Data Synthesis project aimed to use the information gathered in two forest FACE experiments to assess and improve land ecosystem models. A new 'assumption-centred' model intercomparison approach was used, in which participating models were evaluated against experimental data based on the ways in which they represent key ecological processes. By identifying and evaluating the main assumptions causing differences among models, the assumption-centred approach produced a clear roadmap for reducing model uncertainty. Here, we explain this approach and summarize the resulting research agenda. We encourage the application of this approach in other model intercomparison projects to fundamentally improve predictive understanding of the Earth system.

Published
2015

8. Optimal stomatal behaviour around the world

Author

Pasi Kolari, Jesse B. Nippert, Norma Salinas, Derek Eamus, Oula Ghannoum, Johan Uddling, Qingmin Han, Belinda E. Medlyn, Wei Sun, Joana Zaragoza-Castells, Maj-Lena Linderson, Yusuke Onoda, Yan-Shih Lin, Teresa E. Gimeno, M. S. J. Broadmeadow, Sofia Baig, Sabine Tausz-Posch, Lindsay B. Hutley, Patrick Meir, John E. Drake, Göran Wallin, Markus Löw, Lasse Tarvainen, Lucy Rowland, Kouki Hikosaka, David S. Ellsworth, Samantha A. Setterfield, Antonio Carlos Lola da Costa, Han Wang, Craig V. M. Barton, Jonathan Bennie, Alexandre Bosc, Michael Freeman, Kohei Koyama, Troy W. Ocheltree, Teis Nørgaard Mikkelsen, Maarten Op de Beeck, Lisa Wingate, Ana Rey, I. Colin Prentice, Víctor Resco de Dios, Jeff W. G. Kelly, Remko A. Duursma, Cate Macinins-Ng, Jean-Marc Limousin, Damien Bonal, Lucas A. Cernusak, Patrick J. Mitchell, Paolo De Angelis, Nicolas Martin-StPaul, Alistair Rogers, Jeffrey M. Warren, David T. Tissue, Kihachiro Kikuzawa, Macquarie University, Hawkesbury Institute for the Environment [Richmond] (HIE), Western Sydney University (UWS), Imperial College London, University of Technology Sydney (UTS), Universitat de Lleida, Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Universiteit Antwerpen [Antwerpen], University of Gothenburg (GU), Swedish University of Agricultural Sciences (SLU), Lund University [Lund], James Cook University (JCU), Kansas State University, Colorado State University [Fort Collins] (CSU), Ecologie Systématique et Evolution (ESE), Université Paris-Sud - Paris 11 (UP11)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS), Brookhaven National Laboratory [Upton] (BNL), Stony Brook University [SUNY] (SBU), State University of New York (SUNY)-State University of New York (SUNY), Oak Ridge National Laboratory [Oak Ridge] (ORNL), UT-Battelle, LLC, Università degli studi della Tuscia [Viterbo], Tohoku University [Sendai], Forestry and Forest Products Research Institute (FFPRI), Kyoto University [Kyoto], College of Life and Environmental Sciences, University of Exeter, Ecologie et Ecophysiologie Forestières [devient SILVA en 2018] (EEF), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Interactions Sol Plante Atmosphère (ISPA), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine (Bordeaux Sciences Agro), INRA Villenave d'Ornon, Institut National de la Recherche Agronomique (INRA), University of Melbourne, University of Auckland [Auckland], Consejo Superior de Investigaciones Científicas [Spain] (CSIC), University of Edinburgh, Charles Darwin University, Forestry Commission, Ishikawa National College of Technology, University of Helsinki, Obihiro University of Agriculture and Veterinary Medicine, Federal University of Para - Universidade Federal do Para [Belem - Brésil], Technical University of Denmark [Lyngby] (DTU), Pontificia Universidad Católica del Perú (PUCP), School of Geography and the Environment [Oxford], University of Oxford [Oxford], Northeast Normal University, Western Sydney University, Brookhaven National Laboratory [Upton, NY] (BNL), U.S. Department of Energy [Washington] (DOE)-UT-Battelle, LLC-Stony Brook University [SUNY] (SBU), Interactions Sol Plante Atmosphère (UMR ISPA), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), School of Geography and the Environment [Oxford] (SoGE), and AXA Research Fund

Subjects
0106 biological sciences, Stomatal conductance, 010504 meteorology & atmospheric sciences, [SDV]Life Sciences [q-bio], Environmental Studies, Biome, Climate change, Environmental Sciences & Ecology, Environmental Science (miscellaneous), Atmospheric sciences, 01 natural sciences, Carbon cycle, LEAF, Evapotranspiration, CONVERGENCE, Meteorology & Atmospheric Sciences, Ecosystem, Biology, 0105 earth and related environmental sciences, Transpiration, Science & Technology, Ecology, Physics, Global change, MODEL, Chemistry, Physical Sciences, Environmental science, Life Sciences & Biomedicine, Environmental Sciences, Social Sciences (miscellaneous), 010606 plant biology & botany
Abstract

Yan-Shih Lin [et al.].- Received 16 August 2014, Accepted 16 January 2015, Published online 02 March 2015, Stomatal conductance (gs) is a key land-surface attribute as it links transpiration, the dominant component of global land evapotranspiration, and photosynthesis, the driving force of the global carbon cycle. Despite the pivotal role of gs in predictions of global water and carbon cycle changes, a global-scale database and an associated globally applicable model of gs that allow predictions of stomatal behaviour are lacking. Here, we present a database of globally distributed gs obtained in the field for a wide range of plant functional types (PFTs) and biomes. We find that stomatal behaviour differs among PFTs according to their marginal carbon cost of water use, as predicted by the theory underpinning the optimal stomatal model1 and the leaf and wood economics spectrum2, 3. We also demonstrate a global relationship with climate. These findings provide a robust theoretical framework for understanding and predicting the behaviour of gs across biomes and across PFTs that can be applied to regional, continental and global-scale modelling of ecosystem productivity, energy balance and ecohydrological processes in a future changing climate.

Published
2015

9. Identification of TERRA locus unveils a telomere protection role through association to nearly all chromosomes

Author

Isabel López de Silanes, Osvaldo Graña, Maria A. Blasco, David G. Pisano, Maria Luigia De Bonis, Orlando Domínguez, Ministerio de Economía y Competitividad (España), Comunidad de Madrid, European Research Council (ERC), Fundacion Lilly (Spain), Fundacion Botin (Spain), AXA Research Fund, Comunidad de Madrid (España), European Research Council, Fundación Lilly, Botín Foundation, and Fundación AXA

Subjects
Telomeric repeat-containing RNAs, Primary Cell Culture, General Physics and Astronomy, Gene Expression, Chromosome 9, Locus (genetics), Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Chromosome 18, Genes, Reporter, Animals, RNA, Messenger, Luciferases, Gene, In Situ Hybridization, Fluorescence, 030304 developmental biology, Repetitive Sequences, Nucleic Acid, Genetics, 0303 health sciences, Multidisciplinary, Genome, Cell Cycle, Chromosome, High-Throughput Nucleotide Sequencing, RNA-Binding Proteins, General Chemistry, Fibroblasts, Telomere, Subtelomere, Embryo, Mammalian, Chromosomes, Mammalian, Genetic Loci, 030217 neurology & neurosurgery, Protein Binding, Transcription Factors
Abstract

Telomeric RNAs (TERRAs) are UUAGGG repeat-containing RNAs that are transcribed from the subtelomere towards the telomere. The precise genomic origin of TERRA has remained elusive. Using a whole-genome RNA-sequencing approach, we identify novel mouse transcripts arising mainly from the subtelomere of chromosome 18, and to a lesser extend chromosome 9, that resemble TERRA in several key aspects. Those transcripts contain UUAGGG-repeats and are heterogeneous in size, fluctuate in abundance in a TERRA-like manner during the cell cycle, are bound by TERRA RNA-binding proteins and are regulated in a manner similar to TERRA in response to stress and the induction of pluripotency. These transcripts are also found to associate with nearly all chromosome ends and downregulation of the transcripts that originate from chromosome 18 causes a reduction in TERRA abundance. Interestingly, downregulation of either chromosome 18 transcripts or TERRA results in increased number of telomere dysfunction-induced foci, suggesting a protective role at telomeres., Telomeric RNAs (TERRAs) are known to be transcribed towards the telomere from subtelomeric regions, however, their precise genomic origins are unclear. Here López de Silanes et al. identify novel transcripts that originate from the subtelomeric region of mouse chromosome 18 and behave as bona fide TERRAs.

Published
2014

10. Reduced basal forebrain atrophy progression in a randomized Donepezil trial in prodromal Alzheimer's disease.

Author

Cavedo E, Grothe MJ, Colliot O, Lista S, Chupin M, Dormont D, Houot M, Lehéricy S, Teipel S, Dubois B, and Hampel H

Subjects
Aged, Alzheimer Disease pathology, Atrophy diagnostic imaging, Atrophy drug therapy, Atrophy prevention & control, Basal Forebrain diagnostic imaging, Basal Forebrain drug effects, Cholinergic Neurons drug effects, Cholinergic Neurons pathology, Cholinergic Neurons ultrastructure, Donepezil administration & dosage, Female, Gray Matter drug effects, Humans, Magnetic Resonance Imaging methods, Male, Alzheimer Disease drug therapy, Basal Forebrain pathology, Disease Progression, Donepezil therapeutic use, Prodromal Symptoms
Abstract

Acetylcholinesterase inhibitors are approved drugs currently used for the treatment of Alzheimer's disease (AD) dementia. Basal forebrain cholinergic system (BFCS) atrophy is reported to precede both entorhinal cortex atrophy and memory impairment in AD, challenging the traditional model of the temporal sequence of topographical pathology associated with AD. We studied the effect of one-year Donepezil treatment on the rate of BFCS atrophy in prodromal AD patients using a double-blind, randomized, placebo-controlled trial of Donepezil (10 mg/day). Reduced annual BFCS rates of atrophy were found in the Donepezil group compared to the Placebo treated arm. Secondary analyses on BFCS subregions demonstrated the largest treatment effects in the Nucleus Basalis of Meynert (NbM) and the medial septum/diagonal band (Ch1/2). Donepezil administered at a prodromal stage of AD seems to substantially reduce the rate of atrophy of the BFCS nuclei with highest concentration of cholinergic neurons projecting to the cortex (NbM), hippocampus and entorhinal cortex (Ch1/2).

Published
2017
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11. Excess of rare coding variants in PLD3 in late- but not early-onset Alzheimer's disease.

Author

Schulte EC, Kurz A, Alexopoulos P, Hampel H, Peters A, Gieger C, Rujescu D, Diehl-Schmid J, and Winkelmann J

Abstract

Recently, mutations in phospholipase D3 (PLD3) were reported in late-onset Alzheimer's disease (AD). By screening the coding regions of PLD3 for variants in a European cohort of 1,089 AD cases, 182 individuals with frontotemporal lobar degeneration and 1,456 controls, we identified 32 variants with a minor allele frequency <5% and observed an excess of rare variants in individuals with late- but not early-onset AD (P=0.034, χ (2)-test; odds ratio=1.46).

Published
2015
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