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Navigating the dynamic landscape of alpha-synuclein morphology: a review of the physiologically relevant tetrameric conformation

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Neural Regeneration Research 2020年第3期15卷 407-415页

作者： Heather R.Lucas Ricardo d.fernández department of Chemistry Virginia Commonwealth University

N-acetylatedα-synuclein(αSyn)has long been established as an intrinsically disordered protein associated with a dysfunctional role in Parkinson’s *** recent years,a physiologically relevant,higher order conformation has been identified as a helical tetramer that is tailored by buried hydrophobic interactions and is distinctively aggregation *** canonical mechanism by which the tetramer assembles remains *** novel biochemical approaches,computational methods,pioneering purification platforms,and powerful imaging techniques continue to develop,puzzling information that once sparked debate as to the veracity of the tetramer has now shed light upon this new counterpart inαSyn *** magnetic resonance and computational studies on multimericαSyn structure have revealed that the protein folding propensity is controlled by small energy barriers that enable large scale ***,familial mutations ablate tetramerization and reconfigure polymorphic *** this review,we will discuss the dynamic landscape ofαSyn quaternary structure with a focus on the tetrameric conformation.

关键词： alpha-synuclein amyloid fibrils intrinsically disordered protein multimer N-acetylation oligomer Parkinson’s disease protein folding protein structure tetramer

design,fabrication,characterization and reliability study of CMOS-MEMS Lorentz-force magnetometers

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Microsystems & Nanoengineering 2022年第5期8卷 17-41页

作者： J.J.Valle J.M.Sánchez-Chiva d.fernández J.Madrenas department of Electronic Engineering Universitat Politècnica de CatalunyaJordi Girona 1 i 3Edifici C408034 BarcelonaSpain Sorbonne Université CNRSLaboratoire de Recherche en Informatique(LIP6)UMR76064 place Jussieu75005 ParisFrance Institut de Física d’Altes Energies(IFAE) The Barcelona Institute of Science and Technology(BIST)Edifici Cn.Facultat Ciències NordUniversitat Autónoma de Barcelona08193 Bellaterra(Barcelona)Spain

This article presents several design techniques to fabricate micro-electro-mechanical systems(MEMS)using standard complementary metal-oxide semiconductor(CMOS)*** were applied to fabricate high yield CMOS-MEMS shielded Lorentz-force magnetometers(LFM).The multilayered metals and oxides of the back-end-of-line(BEOL),normally used for electronic routing,comprise the structural part of the *** most important fabrication challenges,modeling approaches and design solutions are *** that predict the Q factor,sensitivity,Brownian noise and resonant frequency as a function of temperature,gas pressure and design parameters are presented and validated in characterization tests.A number of the fabricated magnetometers were packaged into Quad Flat No-leads(QFN)*** show this process can achieve yields above 95%when the proper design techniques are *** CMOS not being a process for MEMS manufacturing,estimated performance(sensitivity and noise level)is similar or superior to current commercial magnetometers and others built with MEMS ***,typical offsets present in Lorentz-force magnetometers were prevented with a shielding electrode,whose efficiency is ***,several reliability test results are presented,which demonstrate the robustness against high temperatures,magnetic fields and acceleration shocks.

关键词： Lorentz magnetometer characterization

Topical Calendula officinalis *** inflammatory pain through antioxidant,anti-inflammatory and peripheral opioid mechanisms

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Journal of Integrative Medicine 2023年第1期21卷 34-46页

作者： Bárbara B.Garrido-Suárez Gabino Garrido Addis Bellma Menéndez Nelson Merino Odalys Valdés Nilia de la Paz Aylema Romero Livan delgado Miguel d.fernández Octavio Piñeros Renédelgado-Hernández Pharmacology and Toxicology Chemical Analytic and Pharmaceutical Technology LaboratoriesCenter for Pharmaceutical Research and Development(CIDEM)Havana 10600Cuba department of Pharmacology Institute of Marine Science(ICIMAR)Havana 10300Cuba department of Pharmaceutical Sciences Faculty of SciencesCatholic University of the NorthAntofagasta 1240000Chile Research department University of Santiago de CaliCali 760032Colombia Center for Research and Biological Evaluations Institute of Pharmacy and FoodUniversity of HavanaHavana 17100Cuba

Objective The present study evaluated the antinociceptive activity of Calendula officinalis L.(Ca)cream on inflammatory *** Creams with different Ca concentrations were tested for their ability to ameliorate pain-related behavior and edema in rats using formalin test,carrageenan(Cg)-induced acute inflammation model,bradykinin(BK)-induced acute inflammation model,and complete Freund’s adjuvant(CFA)-induced chronic inflammation *** the formalin test,we also examined the implication of peripheral opioid receptors in the antinociceptive mechanisms of Ca cream,by means of Q-naloxone,a peripherally acting nonselective opioid ***,the effects of Ca cream compared with diclofenac on BK-induced edema were examined when the kininase II in tissue was preserved or inhibited by *** local production of redox biomarkers in formalin model,tumor necrosis factor-α(TNF-α)in Cg model and histopathological changes in CFA model were also *** A single application of Ca cream at a dose of 10%or 30%(w/w)decreased the formalin-induced licking/biting behavior during both phases of this test in a Q-naloxone-sensitive *** effect was associated with the reduction of oxidative stress in the injured paw and the edema associated with the later phase of formalin-induced pain.A single application of Ca cream(10%or 30%)reduced paw edema and thermal hypernociception in Cg-induced acute inflammation,corresponding with a local decrease in TNF-α.Ca cream also inhibited BK-induced spontaneous nociceptive behavior and paw inflammation in both paradigms *** applications of Ca cream also decreased CFA-induced chronic inflammation,mechanical hypernociception and histopathological changes in the *** These results reveal the topical antinociceptive and antiedematogenic effects of Ca cream.A modulatory action on peripheral opioid receptors associated with its antioxidant mechanism may be involved,at least in par

关键词： Calendulaofficinalis L. Formalintest Pain Hyperalgesia Inflammation

data-driven drug repositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

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Neural Regeneration Research 2025年第7期20卷 1997-1998页

作者： Paz Cartas-Cejudo Adriana Cortés Mercedes Lachén-Montes Elena Anaya-Cubero Joaquín fernández-Irigoyen Enrique Santamaría Clinical Neuroproteomics Unit Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:Neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous *** diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual *** the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining *** last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.

关键词： diseases drug amyloid

Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

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Neural Regeneration Research 2025年第9期20卷 2454-2463页

作者： Victoria Jiménez Carretero IrisÁlvarez-Merz Jorge Hernández-Campano Sergei A.Kirov Jesús M.Hernández-Guijo department of Pharmacology and Therapeutic School of MedicineUniv.Autónoma de MadridMadridSpain Ramón y Cajal Institute for Health Research(IRYCIS) Neurobiology-Research ServiceHospital Ramón y CajalMadridSpain Institute of Neurobiology Faculty of Mathematics and Natural SciencesHeinrich Heine University DüsseldorfDüsseldorfGermany department of Neuroscience and Regenerative Medicine&department of Neurosurgery Medical College of Georgia at Augusta UniversityAugustaGAUSA

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is ***,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely *** release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the *** findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma *** amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-d-aspartate *** N-methyl-d-aspartate receptors prevented neuronal damage in the presence of these amino acids during *** is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-d-aspartate receptor ***,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain *** these pathways co uld highlight new therapeutic targets to mitigate brain injury.

关键词： cell swelling N-methyl-d-aspartate receptor non-excitatory amino acids stroke synaptic transmission

dendritic spine degeneration:a primary mechanism in the aging process

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Neural Regeneration Research 2025年第6期20卷 1696-1698页

作者： Gonzalo Flores Leonardo Aguilar-Hernández fernado García-dolores Humberto Nicolini Andrea Judith Vázquez-Hernández Hiram Tendilla-Beltrán Instituto de Fisiología Benemérita Universidad Autónoma de Puebla(BUAP)PueblaMexico Instituto de Ciencias Forenses(INCIFO) Tribunal Superior de Justicia de la Ciudad de México(TSJCDMX).Mexico CityMexico Instituto Nacional de Medicina Genómica(INMEGEN) Mexico CityMexico

Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a wide range of factors, spanning from genetic to environmental factors, and even includes the gut microbiome(GM)(Mayer et al., 2022). All these processes coincide at some point in the inflammatory process, oxidative stress, and apoptosis, at different degrees in various organs and systems that constitute a living organism(Mayer et al., 2022;AguilarHernández et al., 2023).

关键词： aging process stress

A demand side management approach to increase self-consumption in buildings

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Building Simulation 2023年第2期16卷 317-335页

作者： Carlos fernández Bandera Gabriela Bastos Porsani María fernández-Vigil Iglesias School of Architecture University of Navarra31009 PamplonaSpain

There is a growing interest in increasing the presence of renewable energy in the electric *** production from grid-connected systems is leading this growth in terms of *** this development,concern about network security has emerged,because excesses of intermittent renewable energy on the grid could exceed voltage ***-consumption,understood as the capacity of the producer to consume his or her own production,can partially solve these *** controllable loads,such as heating and cooling,represent 50%of the total amount of energy consumed by buildings;the proper allocation of these loads could be a driving force for *** this study,a demand side management strategy is proposed based on a building energy model equipped with an inverter heat pump coupled with a photovoltaic *** goal is to maximize the use of local energy from the photovoltaic plant(self-consumption),reducing the export and import of energy to and from the *** goal is achieved by optimizing the set-points in each *** array of optimal set-points over six years is *** results show the capacity of the methodology to match similar values of self-consumption(70%in winter and 50%in summer)obtained by strategies based on chemical *** findings are shown in an energy matching chart at different levels of detail(yearly and monthly).Color bubbles are added to the matching chart to help visualize the unmatched energy of the system *** comparison with actual model predictive control technologies,this study’s strategy offers great simplicity and a large saving in computational time.

关键词： sensor data internal thermal mass energy simulation EnergyPlus inverse model

Superficial Color Patches as a Visual diagnostic Criterion for Agricultural Management

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Pedosphere 2013年第6期23卷 740-751页

作者： C.CASTANEdA d.MORET-fernndez Estacio'n Experimental de Aula dei CSIC

Soil management matters in semiarid lands are key to have acceptable yields and to preserve diversity. After the major agricultural intensification underwent in the semiarid lands of Monegros, NE Spain, custom tailored tools are needed to reconcile agriculture with habitats conservation. The objectives of this study were to quantify the effect of soil properties of two distinctly colored soils, white patches （WP） and dark patches （dP）, dominant in the arid landscape of the central Ebro Basin, Spain on winter cereal grain yield and to prove that superficial soil color could be used as a visual diagnostic criterion for evaluation of agricultural practices in arid lands. Significant differences between WP and dP soils were found in gypsum, carbonate contents, available water holding capacity and infiltration rate. The grain yield ranged from 51 to 5 713 kg ha-1. Significantly lower yields （P 〈 0.01） and precipitation-use efficiency （P 〈 0.05） were attained in the WP soils for the three seasons studied. This difference increased with the average rainfall due to the significantly lower soil water infiltration （P 〈 0.01） and water holding capacity （P 〈 0.05） found in the gypseous soils. Our results show that mapping the soil surface color at farm scale can be a low=cost tool for optimizing agricultural practices and recovering the natural vegetation. This approach can be advantageous in similar arid or semiarid environments around the world.

关键词： arid zones dryland cropping gypsum hydraulic conductivity soil mapping

Tandem pore TWIK-related potassium channels and neuroprotection

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Neural Regeneration Research 2019年第8期14卷 1293-1308页

作者： J.Antonio Lamas diego fernández-fernández Laboratory of Neuroscience Biomedical Research Center (CINBIO) University of Vigo

TWIK-related potassium channels (TREK) belong to a subfamily of the two-pore domain potassium channels family with three members, TREK1, TREK2 and TWIK-related arachidonic acid-activated potassium channels. The two-pore domain potassium channels is the last big family of channels being discovered, therefore it is not surprising that most of the information we know about TREK channels predominantly comes from the study of heterologously expressed channels. Notw让hstanding, in this review we pay special attention to the limited amount of information available on native TREK-like channels and real neurons in relation to neuroprotection. Mainly we focus on the role of free fatty acids, lysophospholipids and other neuroprotective agents like riluzole in the modulation of TREK channels, emphasizing on how important this modulation may be for the development of new therapies against neuropathic pain, depression, schizophrenia, epilepsy, ischemia and cardiac complications.

关键词： TREK channels TREK-1 TREK-2 TRAAK neuroprotection free fatty acids lysophospholipids riluzole