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Tau-mediated Neurodegeneration and Potential Implications in Diagnosis and Treatment of Alzheimer＇s Disease

Chinese Medical Journal 2017年第24期130卷 2978-2990页

作者： Xi-Lin Wu Juan Pina-crespo Yun-Wu Zhang Xiao-Chun Chen Hua-Xi Xu Neuroscience Initiative Neuroscience and Aging Research Center Sanford Burnham Prebys Medical Discovery Institute La Jolla CA 92037 USA Department of Neurology Fujian Institute of Geriatrics Fujian Medical University Union Hospital Fujian Key Laboratory of Molecular Neurology Fujian Medical University Fuzhou Fujian 350001 China Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research Institute of Neuroscience College of Medicine Xiamen University XiamenFujian 361102 China

Objective：To review recent research advances on tau,a major player in Alzheimer＇s disease （AD） pathogenesis,a biomarker for AD onset,and potential target for AD *** Sources：This review was based on a comprehensive search using online literature databases,including PubMed,Web of Science,and Google *** Selection：Literature search was based on the following keywords：Alzheimer＇s disease,tau protein,biomarker,cerebrospinal fluid （CSF）,therapeutics,plasma,imaging,propagation,spreading,seeding,prion,conformational templating,and posttranslational *** articles were carefully reviewed,with no exclusions applied to study design and publication ***：Amyloid plaques enriched with extracellular amyloid beta （Aβ） and intracellular neurofibrillary tangles comprised of hyperphosphorylated tau proteins are the two main pathological hallmarks *** the Aβ hypothesis has dominated AD research for many years,clinical Aβ-targeting strategies have consistently failed to effectively treat AD or prevent AD *** research focus in AD has recently shifted to the role oftau in *** addition to phosphorylation,tau is acetylated and proteolytically cleaved,which also contribute to its physiological and pathological *** evidence characterizing pathological tau propagation and spreading provides new avenues for research into the molecular and cellular mechanisms underlying AD *** to detect tau at minute levels in CSF and blood have been developed,and improved tracers have facilitated tau imaging in the *** advances have potential to accurately determine tau levels at early diagnostic stages in *** that tau is a potential therapeutic target,anti-tau immunotherapy may potentially be a viable treatment strategy in AD ***：Detecting changes in tau and targeting tau pathology represent a promising lead in the diagnosis and treatment of AD.

关键词： Alzheimer's Disease Biomarker lmmunotherapy Tau Imaging Tau Protein Transcellular Propagation

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Historical perspective of cell transplantation in Parkinson's disease

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World Journal of Transplantation 2017年第3期7卷 179-192页

作者： Alejandra Boronat-García Magdalena Guerra-crespo René Drucker-Colín Departamento de Neuropatología Molecular Instituto de Fisiología CelularUniversidad Nacional Autónoma de México

Cell grafting has been considered a therapeutic approach for Parkinson's disease(PD) since the 1980 s. The classical motor symptoms of PD are caused by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to a decrement in dopamine release in the striatum. Consequently, the therapy of celltransplantation for PD consists in grafting dopamineproducing cells directly into the brain to reestablish dopamine levels. Different cell sources have been shown to induce functional benefits on both animal models of PD and human patients. However, the observed motor improvements are highly variable between individual subjects, and the sources of this variability are not fully understood. The purpose of this review is to provide a general overview of the pioneering studies done in animal models of PD that established the basis for the first clinical trials in humans, and compare these with the latest findings to identify the most relevant aspects that remain unanswered to date. The main focus of the discussions presented here will be on the mechanisms associated with the survival and functionality of the transplants. These include the role of the dopamine released by the grafts and the capacity of the grafted cells to extend fibers and to integrate into the motor circuit. The complete understanding of these aspects will require extensive research on basic aspects of molecular and cellular physiology, together with neuronal network function, in order to uncover the real potential of cell grafting for treating PD.

关键词： Parkinson’s disease Cell replacement Animal models Nigrostriatal pathway Striatum Dopaminergic loss

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DuaISPHysics：A numerical tool to simulate real breakwaters

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Journal of Hydrodynamics 2018年第1期30卷 95-105页

作者：张峰 Alejandro crespo Corrado Altomare José Domínguez Andrea Marzeddu 商少平 Moncho Gómez-Gesteira College of Ocean and Earth Science Xiamen University Xiamen 361005 China Environmental Physics Laboratory Universidade de Vigo Ourense Spain Department of Mobility and Public Works Ghent University Ghent Belgium Flanders Hydraulics Research Antwerp Belgium Laboratory of Maritime Engineering Universitat Politkcnica de Catalunya Barcelona Spain

The open-source code DualSPHysics is used in this work to compute the wave run-up in an existing dike in the Chinese coast using realistic dimensions, bathymetry and wave conditions. The GPU computing power of the DualSPHysics allows simulating real-engineering problems that involve complex geometries with a high resolution in a reasonable computational time. The code is first validated by comparing the numerical free-surface elevation, the wave orbital velocities and the time series of the run-up with physical data in a wave flume. Those experiments include a smooth dike and an armored dike with two layers of cubic blocks. After validation,the code is applied to a real case to obtain the wave run-up under different incident wave conditions. In order to simulate the real open sea, the spurious reflections from the wavemaker are removed by using an active wave absorption technique.

关键词： SPH DualSPHysics wavemaker wave run-up

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The presence and outcome of biliary sphincter disorders in liver-transplant recipients according to the Rome IV classification

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Gastroenterology Report 2021年第4期9卷 299-305,I0001页

作者： Alejandro Fernandez-Simon Oriol Sendino Karina Chavez-Rivera Henry Córdova Jordi Colmenero gonzalo crespo Yilliam Fundora Franco Samaniego Pablo Ruiz Constantino Fondevila Miquel Navasa Andrés Cárdenas GI Unit Institut Clı´nic de Malalties Digestives i MetaboliquesHospital Clı´nicUniversity of BarcelonaBarcelonaSpain Institut d’Investigacions Biomèdiques August Pi-Sunyer(IDIBAPS)and Ciber de Enfermedades Hepáticas y Digestivas(CIBEREHD) BarcelonaSpain Liver Transplant Unit Institut Clínic de Malalties Digestives i MetabóliquesHospital ClínicUniversity of BarcelonaBarcelonaSpain

Background Biliary sphincter disorders after liver transplantation(LT)are poorly *** aim to describe the presence and outcome of patients with papillary stenosis(PS)and functional biliary sphincter disorders(FBSDs)after LT according to the updated Rome IV *** We reviewed all endoscopic retrograde cholangiopancreatographies(ERCPs)performed in LT recipients between January 2003 and December *** on clinical and endoscopic findings was obtained from electronic health records and endoscopy *** and clinical findings were collected at the time of ERCP and 1 month after *** Among the 1,307 LT recipients,336 underwent 849 ***(1.0%)patients met the updated Rome IV criteria for PS[former sphincter of Oddi dysfunction(SOD)type I]and 14 patients(1.0%)met the Rome IV criteria for FBSD(former SOD type II).Biliary sphincterotomy was performed in 13 PS and 10 FBSD *** month after sphincterotomy,bilirubin,gamma-glutamyl transferase and alkaline phosphatase levels decreased in 85%,61%,and 92%of those in the PS group(P¼0.019,0.087,and 0.003,respectively)and in 50%,70%,and 80%of those in the FBSD group(P¼0.721,0.013,and 0.093,respectively).All the 14 patients initially suspected of having a FBSD turned out to have a different diagnosis during the *** PS after LT is uncommon and occurs in only 1%of LT *** data do not support the presence of an FBSD after *** is a safe and effective procedure in LT recipients with PS.

关键词： sphincter of Oddi dysfunction liver transplantation biliary sphincterotomy papillary stenosis functional biliary sphincter disorder

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Lower serum expression of miR-181c-5p is associated with increased plasma levels of amyloid-beta 1-40 and cerebral vulnerability in normal aging

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Translational Neurodegeneration 2019年第1期8卷 423-432页

作者： Marta Manzano-crespo Mercedes Atienza Jose L.Cantero Laboratory of Functional Neuroscience Pablo de Olavide UniversityCtra.de Utrera Km 141013 SevilleSpain CIBERNED Network Center for Biomedical Research in Neurodegenerative Diseases28031MadridSpain

Background:Previous studies have shown that expression levels of miR-181c are downregulated by amyloid-β(Aβ)deposition and chronic cerebral hypoperfusion,both factors largely associated with the development of ***,reduced 2-[18F]fluoro-2-deoxy-D-glucose(FDG)-PET brain metabolism and volume loss of regions of the medial temporal lobe have been generally recognized as hallmarks of *** on this evidence,we have here investigated potential associations between serum levels of miR-181c-5p and these AD signatures in asymptomatic elderly ***:Ninety-five normal elderly subjects underwent clinical,cognitive,structural MRI,and FDG-PET *** expression levels of miR-181c-5p and plasma Aβ concentrations were further analyzed in this *** analyses were performed to assess associations between serum miR-181c-5p levels and cognitive functioning,plasma Aβ,structural and metabolic brain ***:Decreased serum expression of miR-181c-5p was associated with increased plasma levels of Aβ1–40,deficits in cortical glucose metabolism,and volume reduction of the entorhinal *** significant associations were found between lower miR-181c-5p levels and cognitive deficits or cortical ***:These findings suggest that deregulation of serum miR-181c-5p may indicate cerebral vulnerability in late life.

关键词： Aging Alzheimer’s disease Blood biomarkers microRNAs Amyloid-beta FDG-PET Entorhinal cortex

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Phylogenomic analysis of 2556 single-copy protein-coding genes resolves most evolutionary relationships for the major clades in the most diverse group of lichen-forming fungi

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Fungal Diversity 2018年第5期92卷 31-41页

作者： David Pizarro Pradeep K.Divakar Felix Grewe Steven D.Leavitt Jen-Pan Huang Francesco Dal Grande Imke Schmitt Mats Wedin Ana crespo H.Thorsten Lumbsch Departamento de Farmacologı́a Farmacognosia y BotánicaFacultad de FarmaciaUniversidad Complutense de Madrid28040 MadridSpain Science&Education The Field Museum1400 S.Lake Shore DriveChicagoILUSA Department of Biology and M.L.Bean Life Science Museum Brigham Young UniversityLife Science Building 4102ProvoUT 84602USA Senckenberg Biodiversity and Climate Research Centre(SBiK-F) Senckenberganlage 2560325 Frankfurt am MainGermany Institute of Ecology Evolution and DiversityGoethe UniversityFrankfurt am MainMax-von-Laue-Str.960438 Frankfurt am MainGermany Department of Botany Swedish Museum of Natural HistoryPO Box 5000710405 StockholmSweden

Phylogenomic datasets continue to enhance our understanding of evolutionary relationships in many lineages of ***,genome-scale data have not been widely implemented in reconstructing relationships in lichenized *** we generate a data set comprised of 2556 single-copy protein-coding genes to reconstruct previously unresolved rela-tionships in the most diverse family of lichen-forming fungi,*** sampling included 51 taxa,mainly from the subfamily Parmelioideae,and represented six of the seven previously identified major clades within the *** results provided strong support for the monophyly of each of these major clades and most backbone relationships in the topology were recovered with high nodal support based on concatenated dataset and species tree *** alectorioid clade was strongly supported as sister-group to all remaining clades,which were divided into two major *** the first major clade the anzioid and usneoid clades formed a strongly supported sister-group relationship with the cetrarioid?hypogymnioid *** sister-group relationship of Evernia with the cetrarioid clade was also strongly supported,whereas that between the anzioid and usneoid clades needs further *** the second major clade Oropogon and Platismatia were sister to the parmelioid group,while the position of Omphalora was not fully *** study demonstrates the power of genome-scale data sets to resolve long-standing,ambiguous phylogenetic rela-tionships of lichen-forming ***,the topology inferred in this study will provide a valuable framework for better understanding diversification in the most diverse lineage of lichen-forming fungi,Parmeliaceae.

关键词： Fungi Lecanorales Lichenized fungi Parmeliaceae Parmelioideae Phylogeny Systematics

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Global DNA methylation and transcriptional analyses of human ESC-derived cardiomyocytes

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Protein & Cell 2014年第1期5卷 59-68页

作者： Ying Gut Guang-Hui Liu Nongluk Plongthongkum' Christopher Benner Fei Yi Jing Qu Keiichiro Suzuki Jiping Yang Weiqi Zhang Mo Li Nuria Montserrat Isaac crespo Antonio del Sol Concepcion Rodriguez Esteban Kun Zhang Juan Carlos Izpisua Belmonte Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA National Laboratory of Biomacromolecules institute of Biophysics Chinese Academy of Sciences Beijing 100101 China ' State key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China Department of Bioengineering University of California at San Diego La Jolla CA 92093 USA center of Regenerative Medicine in Barcelona Dr. Aiguader 88 08003 Barcelona Spain Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine (CIBER-BBN) Poeta MarianoEsquillor s/n 50018 Sargossa Spain Luxembourg Centre for Systems Biomedicine (LCSB) University of Luxembourg Walferdange Luxembourg

With defined culture protocol, human embryonic stem cells （hESCs） are able to generate cardiomyocytes in vitro, therefore providing a great model for human heart development, and holding great potential for car- diac disease therapies. In this study, we successfully generated a highly pure population of human cardio- myocytes （hCMs）（〉95% cTnT＋） from hESC line, which enabled us to identify and characterize an hCM-specific signature, at both the gene expression and DNA meth- ylation levels. Gene functional association network and gene-disease network analyses of these hCM-enriched genes provide new insights into the mechanisms of hCM transcriptional regulation, and stand as an informative and rich resource for investigating cardiac gene func- tions and disease mechanisms. Moreover, we show that cardiac-structural genes and cardiac-transcription fac- tors have distinct epigenetic mechanisms to regulate their gene expression, providing a better understandingof how the epigenetic machinery coordinates to regulate gene expression in different cell types.

关键词： human cardiomyocyte DNA methylation,microarray heart development

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多功能Las Naves法院大楼

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世界建筑导报 2019年第2期34卷 18-23页

作者： Sebastián crespo arquitectura x Colectivo Arquitectura and Espinoza Carvajal for Hospiplan Cia.Ltda

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Suppression of FIP200 and autophagy by tumor derived lactate promotes nave T cell apoptosis and affects tumor immunity

Suppression of FIP200 and autophagy by tumor derived lactate...

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第十二届全国免疫学学术大会

作者：王巍 Houjun Xia Joel crespo Ilona Kryczek Weiping Zou 北京大学医学部 Departments of Surgery University of Michigan Schoolof Medicine

Naive T cells are poorly studied in cancer ***,we report that naive T cells are prone to undergo apoptosis due to a selective loss of FIP200 in ovarian cancer patients and tumor bearing *** results in poor anti-tumor ... 详细信息

关键词： FIP200 autophagy naive T cell apoptosis microRNA

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Structural and ferroelectric properties of Sr_(1-x)Ba_(x)Bi_(2)Nb_(2)O_(9)thin films obtained by dip-coating

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Journal of Advanced Dielectrics 2017年第5期7卷 57-61页

作者： Y.gonzalez-Abreu A.Pelaiz-Barranco P.Saint-Gregoire C.E.Moreno-crespo H.Limborço J.C.gonzalez Facultad de Fisica-IMRE Universidad de La Habana.San Lazaro y LVedado La Habana 10400Cuba MIPA Laboratory University of NîmesRue du Docteur Georges Salan CS 1301930021 NîmescedexFrance Departamento de Fisica-ICEX Universidade Federal de Minas Gerais Belo HorizonteMG 31270-901Brasil

The paper presents the structural and ferroelectric results for Sr_(1-x)Ba_(x)Bi_(2)Nb_(2)O_(9)(x=0.30;0.85)thin films,which were obtained by using *** solutions containing the desirable ions were prepared from the powders of the previous studied ceramic *** films were deposited at room temperature on Fluorine-doped Tin Oxide(FTO)substrates and submitted to a heat treatment for *** films were characterized by using scanning microscopy electronic,energy dispersive spectroscopy and *** ferroelectric loops were obtained,at room temperature,by using a Sawyer-Tower circuit at several frequencies.A well-defined grain structure was observed for both *** energy dispersive spectroscopy(EDS)measurements revealed the presence of the corresponding elements from the chemical composition of the ceramic *** band-gap energy was around 3.3 eV for both *** hysteresis loops for normal and relaxor ferroelectrics were obtained for x=0.30 and 0.85,respectively.

关键词： Ferroelectrics Aurivillius thin films relaxor

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