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Loss of canonical Wnt signaling is involved in the pathogenesis of Alzheimer's disease

Neural Regeneration Research 2018年第10期13卷 1705-1710页

作者： Cheril Tapia-Rojas Nibaldo C.Inestrosa Centro de Envejecimiento y Regeneración (CARE UC) Departamento de Biología Celular y MolecularFacultad de Ciencias BiológicasPontificia Universidad Católica de Chile Centre for Healthy Brain Ageing School of PsychiatryFaculty of MedicineUniversity of New South Wales Centro de Excelencia en Biomedicina de Magallanes (CEBIMA) Universidad de Magallanes

Alzheimer＇s disease（AD） is the most common form of dementia in the older population, however, the precise cause of the disease is unknown. The neuropathology is characterized by the presence of aggregates formed by amyloid-β（Aβ） peptide and phosphorylated tau; which is accompanied by progressive impairment of memory. Diverse signaling pathways are linked to AD, and among these the Wnt signaling pathway is becoming increasingly relevant, since it plays essential roles in the adult brain. Initially, Wnt signaling activation was proposed as a neuroprotective mechanism against Aβ toxicity. Later, it was reported that it participates in tau phosphorylation and processes of learning and memory. Interestingly, in the last years we demonstrated that Wnt signaling is fundamental in amyloid precursor protein（APP） processing and that Wnt dysfunction results in Aβ production and aggregation in vitro. Recent in vivo studies reported that loss of canonical Wnt signaling exacerbates amyloid deposition in a transgenic（Tg） mouse model of AD. Finally, we showed that inhibition of Wnt signaling in a Tg mouse previously at the appearance of AD signs, resulted in memory loss, tau phosphorylation and Aβ formation and aggregation; indicating that Wnt dysfunction accelerated the onset of AD. More importantly, Wnt signaling loss promoted cognitive impairment, tau phosphorylation and Aβ1–42 production in the hippocampus of wild-type（WT） mice, contributing to the development of an Alzheimer＇s-like neurophatology. Therefore, in this review we highlight the importance of Wnt/β-catenin signaling dysfunction in the onset of AD and propose that the loss of canonical Wnt signaling is a triggering factor of AD.

关键词： Wnt signaling Wnt target genes Wnt/β-catenin Alzheimer disease amyloid-β tau phosphorylation memory loss synaptic dysfunction

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Phosphorylated tau as a toxic agent in synaptic mitochondria: implications in aging and Alzheimer’s disease

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Neural Regeneration Research 2022年第8期17卷 1645-1651页

作者： Angie K.Torres Bastián I.Rivera Catalina M.Polanco Claudia Jara Cheril Tapia-Rojas Laboratory of Neurobiology of Aging Centro de Biología Celular y Biomedicina(CEBICEM)Facultad de Medicina y CienciaUniversidad San SebastiánSede Los LeonesSantiagoChile

During normal aging,there is a decline in all physiological functions in the organism.One of the most affected organs is the brain,where neurons lose their proper synaptic function leading to cognitive impairment.Aging is one of the main risk factors for the development of neurodegenerative diseases,such as Alzheimer’s disease.One of the main responsible factors for synaptic dysfunction in aging and neurodegenerative diseases is the accumulation of abnormal proteins forming aggregates.The most studied brain aggregates are the senile plaques,formed by Aβpeptide;however,the aggregates formed by phosphorylated tau protein have gained relevance in the last years by their toxicity.It is reported that neurons undergo severe mitochondrial dysfunction with age,with a decrease in adenosine 5′-triphosphate production,loss of the mitochondrial membrane potential,redox imbalance,impaired mitophagy,and loss of calcium buffer capacity.Interestingly,abnormal tau protein interacts with several mitochondrial proteins,suggesting that it could induce mitochondrial dysfunction.Nevertheless,whether tau-mediated mitochondrial dysfunction occurs indirectly or directly is still unknown.A recent study of our laboratory shows that phosphorylated tau at Ser396/404(known as PHF-1),an epitope commonly related to pathology,accumulates inside mitochondria during normal aging.This accumulation occurs preferentially in synaptic mitochondria,which suggests that it may contribute to the synaptic failure and cognitive impairment seen in aged individuals.Here,we review the main tau modifications promoting mitochondrial dysfunction,and the possible mechanism involved.Also,we discuss the evidence that supports the possibility that phosphorylated tau accumulation in synaptic mitochondria promotes synaptic and cognitive impairment in aging.Finally,we show evidence and argue about the presence of phosphorylated tau PHF-1 inside mitochondria in Alzheimer’s disease,which could be considered as an early event in the neurodegenerative process.Thus,phosphoryl

关键词： age pathology aging Alzheimer’s disease hippocampus memory mitochondria PHF-1 phosphorylated tau synaptic mitochondria tau

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Bioequivalence Study of Two Hydrochlorothiazide Formulations after Oral Administration in Healthy Chilean Volunteers

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Journal of Pharmacy and Pharmacology 2016年第12期4卷 679-685页

作者： Fierro Humberto rojas Romina Yanez Sebastian Acufia Paola Rosales Katherine Yevenes Paulina Yzoard Marcia tapia Claudia Rivas Violeta Caba Alvaro Copaja Miguel Jorge Fuentealba Center for Advanced Research on Biomedicine (CIAB-UdeC) University of Concepcion Concepcion 4070038 Chile Area Health and Safety AGQ Santiago 8590829 Chile Regional Hospital Guillermo Grant Benavente Concepcion 4070038 Chile Laboratory of Screening of Neuroactive Compounds Department of Physiology Faculty of Biological Sciences University ofConcepcion Concepcion 4070038 Chile

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Turbo-taxonomy to assemble a megadiverse lichen genus:seventy new species of Cora(Basidiomycota:Agaricales:Hygrophoraceae),honouring David Leslie Hawksworth’s seventieth birthday

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Fungal Diversity 2017年第3期84卷 139-207页

作者： Robert Lücking Manuela Dal Forno Bibiana Moncada Luis Fernando Coca Leidy Yasmín Vargas-Mendoza André Aptroot Laura Juliana Arias Betty Besal Frank Bungartz Diego Mauricio Cabrera-Amaya Marcela E.S.Cáceres José Luis Chaves Sionara Eliasaro Martha Cecilia Gutiérrez Jesús E.Hernández Marin María de los Ángeles Herrera-Campos María E.Holgado-rojas Harald Jonitz Martin Kukwa Fabiane Lucheta Santiago Madriñán Marcelo Pinto Marcelli Suzana Maria de Azevedo Martins Joel A.Mercado-Díaz Jorge Alberto Molina Eduardo A.Morales Peter R.Nelson Freddy Nugra Francisco Ortega Telma Paredes Ayda Lucía Patiño Rouchi Nadine Peláez-Pulido Rosa Emilia Pérez Pérez Gary B.Perlmutter Eimy Rivas-Plata Javier Robayo Camilo Rodríguez Diego Fernando Simijaca Edier Soto-Medina Adriano Afonso Spielmann Alejandra Suárez-Corredor Jean-Marc Torres Carlos Alberto Vargas Alba Yánez-Ayabaca Gothamie Weerakoon Karina Wilk Marcela Celis Pacheco Mauricio Diazgranados Grischa Brokamp Thomas Borsch Patrick M.Gillevet Masoumeh Sikaroodi James D.Lawrey Botanical Garden and Botanical Museum Berlin KöniginLuise-Straße 6-814195 BerlinGermany Science Education The Field Museum1400 South Lake ShoreChicagoIL 60605USA Department of Botany Smithsonian InstitutionNational Museum of Natural History10th St Constitution Ave NWWashingtonDC 20560USA Department of Environmental Science and Policy George Mason UniversityFairfaxVA 22030-4444USA Licenciatura en Biologı´a Universidad Distrital Francisco Jose´de CaldasCra.4 No.26D-54Torre de LaboratoriosHerbarioBogota´D.C.Colombia Herbario Universidad de Caldas(FAUC) Edificio BicentenarioCalle 65No.26-10ManizalesA.A.275CaldasColombia ABL Herbarium G.v.d.Veenstraat 1073762 XK SoestThe Netherlands Biologı´a Universidad del Quindı´oCarrera 15 Calle 12 NorteArmeniaQuindı´oColombia 120 Chavis Avenue LexingtonVA 24450USA Charles Darwin Foundation Puerto AyoraSanta Cruz IslandGala´pagosEcuador Schedestraße 8 53113 BonnGermany Jardı´n Bota´nico de Bogota´Jose´Celestino Mutis Avenida Calle 63 No.68-95Bogota´D.C.Colombia Departamento de Biocieˆncias Universidade Federal de SergipeAvenida Vereador Olı´mpio Grandes/n.ItabaianaCEP:49.500-000 SergipeBrazil Laboratorio de Hongos Instituto Nacional de Biodiversidad(INBio)Apdo.22-3100Santo Domingo de HerediaCosta Rica Departamento de Botaˆnica Universidade Federal do Parana´Campus Polite´cnicoSetor de Cieˆncias Biolo´gicasAv.Cel.Francisco H.dos Santoss/nJardim das Ame´ricas81531-980 CuritibaPRBrazil Ingenierı´a Ambiental Universidad Distrital Francisco Jose´de CaldasCarrera 5 Este No.15-82Av.CircumvalarBogota´D.C.Colombia Instituto Experimental Jardı´n Bota´nico Dr.Tobı´as Lasser Centro de Investigacio´n y DesarrolloUniversidad Central de VenezuelaAve.Salvador AllendeJardı´n Bota´nico de CaracasApartado#2156Caracas 1010-AVenezuela Departamento de Bota´nica Instituto de Biologı´aUniversidad Nacional Auto´noma de Me´xicoApartado Postal 70-36704510 Ciudad De Me´xicoMexico Facultad de Ciencias Escuela Profesional de Biologı´aUniv

Following a large-scale phylogenetic study of the lichenized genus Cora(Basidiomycota:Agaricales:Hygrophoraceae),we formally describe 70 new species,honouring the seventieth birthday of David Leslie Hawksworth,one of the preeminent figures in mycology and lichenology in the past 50 years.Based on an updated phylogeny using the ITS fungal barcoding locus,we now recognize 189 taxa in a genus that until recently was considered to represent a single species;including this contribution,92 of these are formally recognized,including five taxa based on historical names or collections that have not been sequenced.Species of Cora can be recognized by a combination of morphological(size,colour,lobe configuration,surface hairs,hymenophore size and shape),anatomical(thallus thickness,cortex structure,photobiont type,hyphal papillae),and ecogeographical features(substrate,habitat,distribution),and a keytable allowing the identification of all accepted taxa is provided.The new species are:Cora accipiter Moncada,Madrin˜a´n&Lücking spec.nov.,C.applanata Moncada,Soto-Medina&Lücking spec.nov.,C.arachnodavidea Moncada,Dal Forno&Lücking spec.nov.,C.arborescens Dal Forno,Chaves&Lücking spec.nov.,C.arcabucana Moncada,C.Rodrı´guez&Lücking spec.nov.,C.aturucoa Lücking,Moncada&C.Vargas spec.nov.,C.auriculeslia Moncada,Ya´nez-Ayabaca&Lücking spec.nov.,C.barbifera Moncada,Patin˜o&Lücking spec.nov.,C.boleslia Lücking,E.Morales&Dal Forno spec.nov.,C.caliginosa Holgado,Rivas Plata&Perlmutter spec.nov.,C.campestris Dal Forno,Eliasaro&Spielmann spec.nov.,C.canari Nugra,Dal Forno&Lücking spec.nov.,C.caraana Lücking,Martins&Lucheta spec.nov.,C.casasolana Moncada,R.-E.Pe´rez&Lücking spec.nov.,C.caucensis Moncada,M.Gut.&Lücking spec.nov.,C.celestinoa Moncada,CabreraAmaya&Lücking spec.nov.,C.comaltepeca Moncada,R.-E.Pe´rez&Herrera-Camp.***.nov.,C.corani Lücking,E.Morales&Dal Forno spec.nov.,C.corelleslia Moncada,A.Sua´rez-Corredor&Lücking spec.nov.,C.crispoleslia Moncada,J.Molina&Lücking spec.nov.,C.cuzcoensis Holgado,Rivas Plata&Perlmutter spec.nov

关键词： Bolivia Citizen science Chile Mexico Puerto Rico Sri Lanka

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Performance and calibration of quark/gluon-jet taggers using 140 fb^(-1) of pp collisions at √s=13 TeV with the ATLAS detector

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Chinese Physics C 2024年第2期48卷 1-25页

作者： G. Aad B. Abbott K. Abeling N.J. Abicht S.H. Abidi A. Aboulhorma H. Abramowicz H. Abreu Y. Abulaiti B.S. Acharya C. Adam Bourdarios L. Adamczyk S.V. Addepalli M.J. Addison J. Adelman A. Adiguzel T. Adye A.A. Affolder Y. Afik M.N. Agaras J. Agarwala A. Aggarwal C. Agheorghiesei A. Ahmad F. Ahmadov W.S. Ahmed S. Ahuja X. Ai G. Aielli A. Aikot M. Ait Tamlihat B. Aitbenchikh I. Aizenberg M. Akbiyik T.P.A. Åkesson A.V. Akimov D. Akiyama N.N. Akolkar K. Al Khoury G.L. Alberghi J. Albert P. Albicocco G.L. Albouy S. Alderweireldt M. Aleksa I.N. Aleksandrov C. Alexa T. Alexopoulos F. Alfonsi M. Algren M. Alhroob B. Ali H.M.J. Ali S. Ali S.W. Alibocus M. Aliev G. Alimonti W. Alkakhi C. Allaire B.M.M. Allbrooke J.F. Allen C.A. Allendes Flores P.P. Allport A. Aloisio F. Alonso C. Alpigiani M. Alvarez Estevez A. Alvarez Fernandez M. Alves Cardoso M.G. Alviggi M. Aly Y. Amaral Coutinho A. Ambler C. Amelung M. Amerl C.G. Ames D. Amidei S.P. Amor Dos Santos K.R. Amos V. Ananiev C. Anastopoulos T. Andeen J.K. Anders S.Y. Andrean A. Andreazza S. Angelidakis A. Angerami A.V. Anisenkov A. Annovi C. Antel M.T. Anthony E. Antipov M. Antonelli F. Anulli M. Aoki T. Aoki J.A. Aparisi Pozo M.A. Aparo L. Aperio Bella C. Appelt A. Apyan N. Aranzabal S.J. Arbiol Val C. Arcangeletti A.T.H. Arce E. Arena J-F. Arguin S. Argyropoulos J.-H. Arling O. Arnaez H. Arnold G. Artoni H. Asada K. Asai S. Asai N.A. Asbah J. Assahsah K. Assamagan R. Astalos S. Atashi R.J. Atkin M. Atkinson H. Atmani P.A. Atmasiddha K. Augsten S. Auricchio A.D. Auriol V.A. Austrup G. Avolio K. Axiotis G. Azuelos D. Babal H. Bachacou K. Bachas A. Bachiu F. Backman A. Badea P. Bagnaia M. Bahmani A.J. Bailey V.R. Bailey J.T. Baines L. Baines O.K. Baker E. Bakos D. Bakshi Gupta V. Balakrishnan R. Balasubramanian E.M. Baldin P. Balek E. Ballabene F. Balli L.M. Baltes W.K. Balunas J. Balz E. Banas M. Bandieramonte A. Bandyopadhyay S. Bansal L. Barak M. Barakat E.L. Barberio D. Barberis M. Barbero M.Z. Barel K.N. Barends T. Barillari M-S. Barisits T. Barklow P. Baron D.A. Baron Mo The ATLAS Collaboration

The identification of jets originating from quarks and gluons,often referred to as quark/gluon tagging,plays an important role in various analyses performed at the Large Hadron Collider,as Standard Model measurements and searches for new particles decaying to quarks often rely on suppressing a large gluon-induced background.This paper describes the measurement of the efficiencies of quark/gluon taggers developed within the ATLAS Collaboration,using √s=13 TeV proton–proton collision data with an integrated luminosity of 140 fb^(-1) collected by the ATLAS experiment.Two taggers with high performances in rejecting jets from gluon over jets from quarks are studied:one tagger is based on requirements on the number of inner-detector tracks associated with the jet,and the other combines several jet substructure observables using a boosted decision tree.A method is established to determine the quark/gluon fraction in data,by using quark/gluon-enriched subsamples defined by the jet pseudorapidity.Differences in tagging efficiency between data and simulation are provided for jets with transverse momentum between 500 GeV and 2 TeV and for multiple tagger working points.

关键词： ATLAS JET QUARK GLUON TAGGING

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