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

中国植物病理学会2005年学术年会暨植物病理学报创刊50周年纪念会

作者： Jurez,S. Hartweck,L. Alamillo,J.m. Simón-mateo,C. Pérez,J.J. fernndez-fernndez,m.r. Olszewski,N.E. García,J.A. Department of Plant molecular Genetics Centro Nacional de Biotecnología(CSIC)Campus Universidad Autónoma de Madrid28049 MadridSpain.Now working in Zhongshan Import & Export Inspection and Quarantine Bureau Department of Plant Biology and Plant molecular Genetics Institute University of MinnesotaSaint PaulMinnesota 55108USA

Serine and threonine of many nuclear and cytoplasmic proteins are post-translationally modified with O-linked N-acetylglucosamine (O-GlcNAc). This modification is made by O-linked Nacetylglucosamine transferases (OGTs). Genetic and biochemical data have demonstrated the existence of two OGTs of Arabidopsis thaliana, SECrET AGENT (SEC) and SPINDLY (SPY), with at least partly overlapping functions, but there is little information on their target proteins. The N-terminus of the capsid protein (CP) of Plum pox virus (PPV) isolated from Nicotiana clevelandii is O-GlcNAc modified. We show here that O-GlcNAc modification of PPV CP also takes place in other plant hosts, N. benthamiana and Arabidopsis. PPV was able to infect the Arabidopsis OGT mutants sec-1, sec-2 and spy-3 but, at early times of the infection, both rate of virus spread and accumulation were reduced in sec-1 and sec-2 relative to spy-3 and wild-type plants. By mALDI-TOF mass spectrometry, we determined that a 39 residue tryptic peptide from the N-terminus of CP of PPV purified from the spy-3 mutant, but not sec-1 or sec-2, was OGlcNAc modified, suggesting that SEC but not SPY modifies the capsid. While our results indicate that O-GlcNAc modification of PPV CP by SEC is not essential for infection, they show that the modification has a role(s) in the process.

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Neural regeneration research 2025年第7期20卷 1997-1998页

作者： Paz Cartas-Cejudo Adriana Cortés m.r.edes Lachén-montes Elena Anaya-Cubero Joaquín fernández-Irigoyen Enrique Santam.r.a 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 prim.r.ly 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 monom.r.c 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-m.r. 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 em.r.encies 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 prim.r. 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(Am.r.m 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

robust interface and excellent as-built mechanical properties of Ti–6Al–4V fabricated through laser-aided additive manufacturing with powder and wire

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International Journal of minerals,metallurgy and materials 2025年第1期32卷 154-168页

作者： Fei Weng Guijun Bi Youxiang Chew Shang Sui Chaolin Tan Zhenglin Du Jinlong Su fern Lan Ng Key Laboratory for Liquid-Solid Structural Evolution and Processing of materials Ministry of EducationShandong Engineering&Technology Research Center for Superhard MaterialSchool of Materials Science and EngineeringShandong UniversityJinan 250061China Institute of Intelligent manufacturing Guangdong Academy of SciencesGuangzhou 510095China Singapore Institute of manufacturing Technology 5 Cleantech Loop636732Singapore

The feasibility of manufacturing Ti-6Al-4V samples through a combination of laser-aided additive manufacturing with powder(LAAm_(p))and wire(LAAm_(w))was explored.A process study was first conducted to successfully circumvent defects in Ti-6Al-4V deposits for LAAm_(p) and LAAm_(w),*** the optimized process parameters,robust interfaces were achieved between powder/wire deposits and the forged substrate,as well as between powder and wire *** characterization results revealed the epitaxial prior β grains in the deposited Ti-6Al-4V,wherein the powder deposit was dominated by a finerα′microstructure and the wire deposit was characterized by lamellar α *** mechanisms of microstructure formation and correlation with mechanical behavior were analyzed and *** mechanical properties of the interfacial samples can meet the requirements of the relevant Aerospace material Specifications(AmS 6932)even without post heat *** fracture occurred within the interfacial area,further suggesting the robust *** findings of this study highlighted the feasibility of combining LAAm_(p) and LAAm_(w) in the direct manufacturing of Ti-6Al-4V parts in accordance with the required dimensional resolution and deposition rate,together with sound strength and ductility balance in the as-built condition.

关键词： laser-aided additive manufacturing powder deposition wire deposition interfacial characteristic mechanical behavior

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 m.r.a 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 em.r.ed,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 summ.r.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

A higher-order porous thermoelastic problem with microtemperatures

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Applied mathematics and mechanics(English Edition) 2023年第11期44卷 1911-1926页

作者： J.r.fernández r.QUINTANILLA Department of Applied mathematics I University of VigoETSI de Telecomunicacion Campus As Lagoas Marcosende s/nVigo 36310Spain Department of mathematics Polytechnical University of CatalunyaTerrassa 08222BarcelonaSpain

In this paper,we study a porous thermoelastic problem with microtemperatures assuming parabolic higher order in time derivatives for the thermal *** model is derived and written as a coupled linear ***,a uniqueness result is proved by using the logarithmic convexity method in the case that we do not assume that the mechanical energy is positive ***,the existence of the solution is obtained by introducing an energy function and applying the theory of linear semigroups.

关键词： higher order thermoelasticity microtemperature logarithmic convexity method existence and uniqueness

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

The power of“touch”and early enriched stimulation:neuroplasticity effects in rodents and preterm infants

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Neural regeneration research 2022年第6期17卷 1248-1250页

作者： Alberto fernández-Teruel Department of Psychiatry and Forensic medicine&Institute of Neurosciences School of MedicineAutonomous University of BarcelonaBellaterraBarcelonaSpain

Early postnatal stimulation,e.g.,neonatal handling(NH)in its most frequent form,and environmental enrichment(EE,the exposure of juvenile animals,usually during several weeks,to environments involving rich and variable sensory stimulation)produce profound and long-lasting behavioral and neurobiological *** treatments reduce anxiety and stress sensitivity,and im.r.ve neurodevelopment and learning/mem.r. in unconditioned and conditioned tasks in laboratory rodents.

关键词： stimulation neonatal enriched