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Reciprocal effects of alpha-synuclein aggregation and lysosomal homeostasis in synucleinopathy models

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Translational Neurodegeneration 2023年第1期12卷 479-499页

作者： Alice Drobny Fanni Annamária Boros Denise Balta Susy prieto Huarcaya Deniz Caylioglu Niyeti Qazi Julia Vandrey Yanni Schneider Jan Philipp Dobert Caleb Pitcairn Joseph Robert mazzulli Friederike Zunke Department of Molecular Neurology University Hospital ErlangenFriedrich-Alexander University Erlangen-Nürnberg91054 ErlangenGermany Institute of Biochemistry Christian-Albrechts-University KielKielGermany The Ken and Ruth Davee Department of Neurology Northwestern University Feinberg School of MedicineChicagoIL 60611USA.

Background Lysosomal dysfunction has been implicated in a number of neurodegenerative diseases such as Parkinson’s disease(PD).Various molecular,clinical and genetic studies have highlighted a central role of lysosomal pathways and proteins in the pathogenesis of *** PD pathology the synaptic protein alpha-synuclein(αSyn)converts from a soluble monomer to oligomeric structures and insoluble amyloid *** aim of this study was to unravel the effect ofαSyn aggregates on lysosomal turnover,particularly focusing on lysosomal homeostasis and *** these enzymes have been shown to be directly involved in the lysosomal degradation ofαSyn,impairment of their enzymatic capacity has extensive *** We used patient-derived induced pluripotent stem cells and a transgenic mouse model of PD to examine the effect of intracellularαSyn conformers on cell homeostasis and lysosomal function in dopaminergic(DA)neurons by biochemical *** We found impaired lysosomal trafficking of cathepsins in patient-derived DA neurons and mouse models withαSyn aggregation,resulting in reduced proteolytic activity of cathepsins in the *** a farnesyltransferase inhibitor,which boosts hydrolase transport via activation of the SNARE protein ykt6,we enhanced the maturation and proteolytic activity of cathepsins and thereby decreasedαSyn protein *** Our findings demonstrate a strong interplay betweenαSyn aggregation pathways and function of lysosomal *** appears thatαSyn directly interferes with the enzymatic function of cathepsins,which might lead to a vicious cycle of impairedαSyn degradation.

关键词： Dopaminergic neurons iPSC-derived models Lysosome Parkinson’s disease Protein trafficking Synucleinopathy

Fagus sylvatica and Quercus pyrenaica:Two neighbors with few things in common

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Forest Ecosystems 2023年第2期10卷 162-175页

作者： Sergio de Tomás marín Jesús Rodríguez-Calcerrada Salvador Arenas-Castro Iván prieto Guillermo González Luis Gil Enrique G.de la Riva Department of Ecology Brandenburgische Technische Universität Cottbus-SenftenbergKonrad-Wachsmann-Allee 603046CottbusGermany Forest Genetics and Ecophysiology Research Group School of Forestry EngineeringUniversidad Politécnica de MadridMadridSpain Area of Ecology Botany DepartmentEcology and Plant PhysiologyFaculty of SciencesUniversidad de CórdobaCórdobaSpain Ecology Department Faculty of Biology and Environmental SciencesUniversidad de LeónLeónSpain

Background:The Iberian Peninsula comprises one of the largest boundaries between Mediterranean and Eurosiberian vegetation,known as sub-Mediterranean *** ecotone hosts many unique plant species and communities and constitutes the low-latitude(warm)margin of numerous central European species which co-occur with Mediterranean *** of the main species found in this region are the Eurosiberian European beech(Fagus sylvatica L.)and the Mediterranean Pyrenean oak(Quercus pyrenaica Willd.).It remains unclear how the different physiological and adaptive strategies of these two species reflect their niche partitioning within a subMediterranean community and to what extent phenotypic variation(intraspecific variability)is driving niche partitioning across Eurosiberian and Mediterranean ***:We quantified functional niche partitioning,based on the n-dimensional hypervolume to nine traits related to resource acquisition strategies(leaf,stem and root)plus relative growth rate as an additional wholeplant trait,and the environmental niche similarity between Pyrenean oak and European ***,we analyzed the degree of phenotypic variation of both target species and its relationship with relative growth rates(RGR)and environmental *** recruitment was measured for both target species as a proxy for the average ***:Species’functional space was highly segregated(13.09%overlap),mainly due to differences in niche breadth(59.7%)rather than niche replacement(25.6%),and beech showed higher trait variability,i.e.,had larger functional ***,both species shared the environmental space,i.e.,environmental niches were *** plant traits were not related to abiotic variables or RGR,neither did RGR to plant ***:Both target species share similar environmental space,however,show notably different functional resource-use strategies,promoting a high complementarity that contributes to maintaining a high functiona

关键词： Environmental niche European beech Forest dynamics Functional niche Hypervolume Pyrenean oak Species coexistence Sub-Mediterranean community

Newly self-administered two-step tool for screening cognitive function in an ageing Chinese population:an exploratory cross-sectional study

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General Psychiatry 2023年第1期36卷 28-35页

作者： Jing Nie Yang Yang Yining Gao Wenwen Jiang Aisikeer Aidina Fei Sun Lucas R prieto Jie Yu Kang Ju Lisheng Song Xia Li Department of Geriatric Psychiatry Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina School of Social Work Michigan State UniversityEast LansingMichiganUSA Department of Psychiatry Shanghai Changning Mental Health CenterShanghaiChina Department of Psychiatry Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina

Background Early screening of cognitive function is critical to dementia treatment and ***,traditional tests require face-to-face administration and are often limited by implementation costs and *** This study aimed to assess whether the Thoven Cognitive Self-Assessment(TCSA),a novel,innovative two-step touchscreen-based cognition assessment tool,could identify early cognitive impairment due to dementia in older *** The TCSA was administered to 61 healthy controls(HCs),46 participants with mild cognitive impairment(MCI)and 44 participants diagnosed with dementia recruited from *** outcome measures were generated from the TCSA test:the TCSA_(primary task)score and the TCSA_(secondary task)*** The total average scores in the control group for the TCSA_(primary task)and TCSA_(secondary task)were significantly higher than those in the MCI and dementia groups(TCSA_(primary task):HCs vs MCI group vs dementia group,8.58±1.76 vs 5.40±2.67 vs 2.74±2.11,F=75.40,pia group,23.02±3.31 vs 17.95±4.93 vs 11.93±5.50,F=76.46,pmary task)and a score below 22.5 for the TCSA_(secondary task)were indicators of *** The TCSA appears to be efficacious for the detection of cognitive impairment in older *** demonstrates the potential for large-scale cognition screening in community service settings.

关键词： function sectional cognitive

Review of incomplete macroscopic resections(R2)in rectal cancer:Treatment,prognosis and future perspectives

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World Journal of Gastrointestinal Oncology 2021年第9期13卷 1062-1072页

作者： Francisco Javier Pérez Lara maria Luisa Hebrero Jimenez Francisco Javier Moya Donoso Jose manuel Hernández Gonzalez maria Pitarch martinez Tatiana prieto-Puga Arjona Department of Surgery Antequera HospitalMálaga 29200Spain Department of Oncologic Radiotherapy Hopital Regional de MálagaMálaga 29010Spain

Colorectal cancer is one of the most prevalent tumours,but with improved treatment and early detection,its prognosis has greatly improved in recent ***,when the tumour is locally advanced at diagnosis or if there is local recurrence,it is more difficult to perform a complete tumour resection,and there may be a residual macroscopic *** this paper,we review the literature on residual macroscopic tumour resections,concerning both locally advanced primary tumours and recurrences,evaluating the main problems encountered,the treatments applied,the prognosis and future perspectives in this field.

关键词： Rectal cancer Surgery Treatment Incomplete resection Local recurrence

Neurological manifestations with jugular vein thrombosis linked to an inflammatory profile may be a sequela of long COVID

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Neuroprotection 2023年第2期1卷 170-175页

作者： Elizabeth Mendoza-Portillo Estefania Aleman-Navarro G.Aleph prieto Yvonne Rosenstein Jose J.Lozano-Nuevo Araceli Perez-Lopez Instituto Nacional de Neurología y Neurocirugía manuel Velasco Suarez Ciudad de MéxicoMéxico Instituto de Biotecnología Universidad Nacional Autónoma de México(UNAM)CuernavacaMorelosMéxico Instituto de Neurobiología UNAM-JuriquillaQuerétaroMéxico Institute for Memory Impairments and Neurological Disorders University of California-IrvineIrvineCaliforniaUSA Hospital General de Ticomán Secretaría de Salud de la Ciudad de MéxicoCiudad de MéxicoMéxico Unidad de Investigación en Biomedicina Facultad de Estudios Superiores IztacalaUNAMTlalneplantlaEstado de MéxicoMéxico

More than 670 million cases of coronavirus disease 2019(COVID-19)have been recorded worldwide in the 3 years since the start of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** 45%of survivors of COVID-19 develop a syndrome known as long-term COVID,in which symptoms persist even months after the acute *** 76%of patients with long COVID experience neurological ***,patients who have survived COVID-19 have an increased risk of cerebral venous *** case report describes a 41-year-old woman who developed neurological manifestations associated with jugular vein thrombosis 24 h after administration of the Oxford–AstraZeneca(ChAdOx1 nCoV-19)vaccine(AstraZeneca-Serum Institute of India).She had been infected with SARS-CoV-2 three months before *** initially suspected to be a case of vaccine-induced immune thrombotic thrombocytopenia(VITT)in view of her recent vaccination,the patient did not have any hallmarks of VITT,such as thrombocytopenia,an increased D-dimer level,or antibodies against platelet ***,the neurological manifestations were associated with a high concentration of inflammatory cytokines,including interleukin(IL)-6,IL-17A,and IL-21,and elevated neutrophil levels in cerebrospinal fluid,suggesting that inflammatory immune components had a role in the development of thrombotic events and pointing to an alternative *** this case,the laboratory results indicated that the neurological manifestations associated with jugular vein thrombosis were not associated with ***,we propose that the thrombosis of the left jugular vein was a sequela of SARS-CoV-2 infection.

关键词： cerebral venous thrombosis long COVID vaccine

Mechanical properties of the A356 aluminum alloy modified with La/Ce

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Journal of Rare Earths 2013年第8期31卷 811-816页

作者： E. Aguirre-De la Torre R. Pérez-Bustamante J. Camarillo-Cisneros C.D. Gómez-Esparza H.M. Medrano-prieto R. martínez-Sánchez Advanced materials Research Center (CImaV) National Laboratory of Nanotechnology

The research of rare earths for the synthesis of materials with improved mechanical performance is of great interest when they are considered for potential applications in the automotive industry. In this regard, the effect on the mechanical properties and microstmcture of the automotive A356 aluminum alloy reinforced with 0.2 （wt.%） AI-6Ce-3La （ACL） was investigated. The ACL was added to the melted A356 alloy in the as-received condition and processed by mechanical milling. In the second route, the effect of the ACL processed by mechanical milling and powder metallurgy techniques was investigated, and compared with the results ob- tained from the A356 alloy strengthened with ACL in the as-received condition. Microstmctural properties were evaluated by means of X-ray diffraction in order to observe the solubility of Ce/La in the A1 matrix. In addition, electron microscopy was employed in or- der to investigate the effect of milling time on the size and morphology of La/Ce phase under milling process. Mechanical properties of the A356 alloy modified with ACL were measured by hardness and tensile test. For comparison unmodified specimens of the A356 were characterized according to the previous procedure. The microstructural and mechanical characterization was carried out in specimens alter solution and artificial aging. Observations in scanning electron microscopy indicated a homogeneous dispersion of La/Ce phases by using both routes; however, mechanical results, in the modified A356 alloy with the ACL in the as-received condi- tion, showed an improvement in the mechanical performance of the A356 alloy over that reinforced with the ACL mechanically milled.

关键词： A356 rare earths mechanical milling mechanical properties

Biosensors for Pesticide Detection: New Trends

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American Journal of Analytical Chemistry 2012年第3期3卷 210-232页

作者： Audrey Sassolas Beatriz prieto-Simón Jean-Louis marty Laboratoire ImaGES EA 4218 Université de Perpignan via Domitia Perpignan France Nanobioengineering Group Institute for Bioengineering of Catalonia Barcelone Spain

Due to the large amounts of pesticides commonly used and their impact on health, prompt and accurate pesticide analysis is important. This review gives an overview of recent advances and new trends in biosensors for pesticide detection. Optical, electrochemical and piezoelectric biosensors have been reported based on the detection method. In this review biosensors have been classified according to the immobilized biorecognition element: enzymes, cells, antibodies and, more rarely, DNA. The use of tailor-designed biomolecules, such as aptamers and molecularly imprinted polymers, is reviewed. Artificial Neural Networks, that allow the analysis of pesticide mixtures are also presented. Recent advances in the field of nanomaterials merit special mention. The incorporation of nanomaterials provides highly sensitive sensing devices allowing the efficient detection of pesticides.

关键词： Biosensors Pesticides

Isothermal hydrogen absorption process of Pd-capped Mg films traced by ion beam techniques and optical methods

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Journal of magnesium and Alloys 2024年第9期12卷 3675-3684页

作者： D.Abejón P.prieto J.K.Kim A.Redondo-Cubero M.L.Crespillo F.Leardini I.J.Ferrer G.García J.R.Ares Departamento de Fisica de materiales Universidad Autónoma de MadridMadrid28049Spain Centro de Micro-Análisis de materiales(CmaM) Universidad Autónoma de MadridMadrid28049Spain Advanced Analysis Center KIST5 Hwarang-ro 14-gilSeoul 02792Republic of Korea Departamento de Física Aplicada Universidad Autónoma de MadridMadrid28049Spain Instituto Nicolás Cabrera Universidad Autónoma de MadridMadrid28049Spain

Pd-capped nanocrystalline Mg films were prepared by electron beam evaporation and hydrogenated under isothermal conditions to inves-tigate the hydrogen absorption process via ion beam techniques and in situ optical *** were characterized by different techniques such as X-ray diffraction(XRD)and scanning electron microscopy(SEM).Rutherford backscattering spectrometry(RBS)and elastic recoil detection analysis(ERDA)provided a detailed compositional depth profile of the films during ***-solid reaction kinetics theory applied to ERDA data revealed a H absorption mechanism controlled by H *** rate-limiting step was also confirmed by XRD *** diffusion coefficient(D)was also determined via RBS and ERDA,with a value of(1.1±0.1)·10^(−13)cm^(2)/s at 140℃.Results confirm the validity of IBA to monitor the hydrogenation process and to extract the control mechanism of the *** H kinetic information given by optical methods is strongly influenced by the optical absorption of the magnesium layer,revealing that thinner films are needed to extract further and reliable information from that technique.

关键词： magnesium hydride Hydrogen absorption Ion beam techniques Optical tracing Absorption mechanism

management of pancreatic cancer in the elderly

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World Journal of Gastroenterology 2016年第2期22卷 764-775页

作者： Oliver Higuera Ismael Ghanem Rula Nasimi Isabel prieto Laura Koren Jaime Feliu Department of Medical Oncology La Paz University Hospital28046 MadridSpain Department of General Surgery La Paz University Hospital28046 MadridSpain Department of Radiology 12 de Octubre University Hospital28041 MadridSpain

Currently, pancreatic adenocarcinoma mainly occurs after 60 years of age, and its prognosis remains poor despite modest improvements in recent decades. The aging of the population will result in a rise in the incidence of pancreatic adenocarcinoma within the next years. Thus, the management of pancreatic cancer in the elderly population is gaining increasing relevance. Older cancer patients represent a heterogeneous group with different biological, functional and psychosocial characteristics that can modify the usual management of this disease, including pharmacokinetic and pharmacodynamic changes, polypharmacy, performance status, comorbidities and organ dysfunction. However, the biological age, not the chronological age, of the patient should be the limiting factor in determining the most appropriate treatment for these patients. Unfortunately, despite the increased incidence of this pathology in older patients, there is an underrepresentation of these patients in clinical trials, and the management of older patients is thus determined by extrapolation from the results of studies performed in younger patients. In this review, the special characteristics of the elderly, the multidisciplinary management of localized and advanced ductal adenocarcinoma of the pancreas and the most recent advances in the management of this condition will be discussed, focusing on surgery, chemotherapy, radiation and palliative care.

关键词： Pancreatic ductal adenocarcinoma Elderly management Treatment Pancreatic cancer