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New insights into Wnt signaling alterations in amyotrophic lateral sclerosis: a potential therapeutic target?

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Neural Regeneration Research 2020年第9期15卷 1580-1589页

作者： Carlos González-fernández Pau González francisco Javier rodríguez Laboratory of Molecular Neurology Hospital Nacional de Parapléjicos (HNP)

Amyotrophic lateral sclerosis is a fatal neurodegenerative disorder characterized by upper and lower motor neuron degeneration, which leads to progressive paralysis of skeletal muscles and, ultimately, respiratory failure between 2–5 years after symptom onset. Unfortunately, currently accepted treatments for amyotrophic lateral sclerosis are extremely scarce and only provide modest benefit. As a consequence, a great effort is being done by the scientific community in order to achieve a better understanding of the different molecular and cellular processes that influence the progression and/or outcome of this neuropathological condition and, therefore, unravel new potential targets for therapeutic intervention. Interestingly, a growing number of experimental evidences have recently shown that, besides its well-known physiological roles in the developing and adult central nervous system, the Wnt family of proteins is involved in different neuropathologica conditions, including amyotrophic lateral sclerosis. These proteins are able to modulate, at least, three different signaling pathways, usually known as canonical(β-catenin dependent) and non-canonical(β-catenin independent) signaling pathways. In the present review, we aim to provide a general overview of the current knowledge that supports the relationship between the Wnt family of proteins and its associated signaling pathways and amyotrophic lateral sclerosis pathology, as well as their possible mechanisms of action. Altogether, the currently available knowledge suggests that Wnt signaling modulation might be a promising therapeutic approach to ameliorate the histopathological and functional deficits associated to amyotrophic lateral sclerosis, and thus improve the progression and outcome of this neuropathology.

关键词： ALS astrocytes Frizzled human microglia motor neuron neurodegeneration neuroinflammation spinal cord Wnt

Alcoholism: A systemic proinflammatory condition

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World Journal of Gastroenterology 2014年第40期20卷 14660-14671页

作者： Emilio González-Reimers francisco Santolaria-fernández María Candelaria Martín-González Camino María fernández-rodríguez Geraldine Quintero-Platt Servicio de Medicina Interna Hospital Universitario de Canarias Universidad de La Laguna Tenerife 38320 Canary Islands Spain

Excessive ethanol consumption affects virtually any organ,both by indirect and direct *** research in the last two decades has widened the knowledge about the paramount importance of proinflammatory cytokines and oxidative damage in the pathogenesis of many of the systemic manifestations of *** cytokines derive primarily from activated Kupffer cells exposed to Gram-negative intestinal bacteria,which reach the liver in supra-physiological amounts due to ethanol-mediated increased gut *** oxygen species(ROS)that enhance the inflammatory response are generated both by activation of Kupffer cells and by the direct metabolic effects of *** effects of this increased cytokine secretion and ROS generation lie far beyond liver *** addition to the classic consequences of endotoxemia associated with liver cirrhosis that weredescribed several decades ago,important research in the last ten years has shown that cytokines may also induce damage in remote organs such as brain,bone,muscle,heart,lung,gonads,peripheral nerve,and *** effects are even seen in alcoholics without significant liver ***,alcoholism can be viewed as an inflammatory condition,a concept which opens the possibility of using new therapeutic weapons to treat some of the complications of this devastating and frequent *** this review we examine some of the most outstanding consequences of the altered cytokine regulation that occurs in alcoholics in organs other than the liver.

关键词： Alcoholism Cytokines Brain Bone Muscle Oxidative damage Atherosclerosis Sepsis Lung Chronic pancreatitis Alcoholic liver disease

Tax avoidance and earnings management:a neural network approach for the largest European economies

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Financial Innovation 2023年第1期9卷 558-582页

作者： francisco J.Delgado Elena fernández‑rodríguez Roberto García‑fernández Manuel Landajo Antonio Martínez‑Arias Department of Economics Faculty of Economics and BusinessUniversity of OviedoAvda.del CristoS/N33071 OviedoSpain Department of Accounting Faculty of Economics and BusinessUniversity of OviedoAvda.del CristoS/N33071 OviedoSpain Department of Applied Economics Faculty of Economics and BusinessUniversity of OviedoAvda.del CristoS/N33071 OviedoSpain

In this study,we investigate the relationship between tax avoidance and earnings management in the largest five European Union economies by using artificial neural network *** methodology allows us to deal with nonlinearities detected in the data,which is the principal contribution to the previous *** ana-lyzed Compustat data for Germany,the United Kingdom,France,Italy,and Spain for the 2006–2015 period,focusing on discretionary *** considered three tax avoidance measures,two based on the effective tax rate(ETR)and one on book-tax differences(BTD).Our results indicate the presence of nonlinear patterns and a posi-tive,statistically significant relationship between discretionary accruals and both ETR indicators implying that when companies resort to earnings management,a larger tax-able income—and thus higher ETR and lesser tax avoidance–would ***,as also highlighted by the fact that discretionary accruals do not appear to affect BTD,our evidence does not suggest that companies are exploiting tax manipulation to reduce their tax payments;thus,the gap between accounting and taxation seems largely unaf-fected by earnings management.

关键词： Tax avoidance Earnings management Artificial neural networks European Union

Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

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Neural Regeneration Research 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro Martín-Belmonte Sergi Ferré francisco Ciruela Synaptic Structure Laboratory Instituto de Biomedicina de la UCLM(IB-UCLM)Departamento de Ciencias MédicasInstituto de Investigación en Salud de Castilla-La Mancha(IDISCAM)Facultad de MedicinaUniversidad Castilla-La ManchaCampus BiosanitarioC/AlmansaAlbaceteSpain Integrative Neurobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaNeuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic *** has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

关键词： Alzheimer pathology

Diplopoda in the world fossil record

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Zoological Systematics 2024年第3期49卷 185-245页

作者： Michelle Álvarez-rodríguez francisco Riquelme Miguel Hernández-Patricio Fabio Cupul-Magaña Laboratorio de Sistemática Molecular Escuela de Estudios Superiores del JicareroUniversidad Autónoma del Estado de MorelosC.P.62909JojutlaMorelosMexico MMRN Centro de Investigaciones BiológicasUniversidad Autónoma del Estado de MorelosC.P.62209CuernavacaMorelosMexico Unafíliate Centro Universitario de la Costa Universidad de GuadalajaraC.P.48280Puerto VallartaJaliscoMexico

We present a comprehensive catalog with an updated database of the fossil record of Diplopoda in the *** data was collected from descriptions and reports published from 1854 to the *** also include new records from Mexican amber(Upper Oligocene-Lower Miocene),counting 83 unknown fossil inclusions,with the first records of the orders Polyxenida,Platydesmida,and Julida,as well as the families Sphaeriodesmidae and Trichopolydesmidae within *** to our results,Diplopoda counts 413 records featuring 299 distinct taxa ranging from the Middle Silurian to the Upper Pleistocene,representing three subclasses,two subterclasses,six superorders,25 orders,15 superfamilies,55 families,93 genera,and 161 fossil *** date,no fossils of the order Siphonocryptida have been *** fossil record extends over three geological eras:the Paleozoic,with 161 taxa,including 97 species;the Mesozoic,with 53 taxa and 22 species;and the Cenozoic,with 85 taxa and 42 *** referred material shows different forms of fossil *** comprises 123 impressions,99 compressions,26 ichnites,predominantly from Paleozoic and Mesozoic sediments,and 165 amber inclusions from late Mesozoic and Cenozoic ***,this catalog allows us to estimate the size and taxonomic composition of Diplopoda in the fossil record worldwide.

关键词： Millipedes Paleozoic Mesozoic Cenozoic new records catalog

Bone changes in alcoholic liver disease

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World Journal of Hepatology 2015年第9期7卷 1258-1264页

作者： Emilio González-Reimers Geraldine Quintero-Platt Eva rodríguez-rodríguez Antonio Martínez-Riera Julio Alvisa-Negrín francisco Santolaria-fernández Servicio de Medicina Interna Hospital Universitario de Canarias Universidad de La Laguna

Alcoholism has been associated with growth impairment, osteomalacia, delayed fracture healing, and aseptic necrosis(primarily necrosis of the femoral head), but the main alterations observed in the bones of alcoholic patients are osteoporosis and an increased risk of fractures. Decreased bone mass is a hallmark of osteoporosis, and it may be due either to decreased bone synthesis and/or to increased bone breakdown. Ethanol may affect both mechanisms. It is generally accepted that ethanol decreases bone synthesis, and most authors have reported decreased osteocalcin levels(a "marker" of bone synthesis), but some controversy exists regarding the effect of alcohol on bone breakdown, and, indeed, disparate results have been reported for telopeptide and other biochemical markers of bone resorption. In addition to the direct effect of ethanol, systemic alterations such as malnutrition, malabsorption, liver disease, increased levels of proinflammatory cytokines, alcoholic myopathy and neuropathy, low testosterone levels, and an increased risk of trauma, play contributory roles. The treatment of alcoholic bone disease should be aimed towards increasing bone formation and decreasing bone degradation. In this sense, vitamin D and calcium supplementation, together with biphosphonates are essential, but alcohol abstinence and nutritional improvement are equally important. In this review we study the pathogenesis of bone changes in alcoholic liver disease and discuss potential therapies.

关键词： Alcoholism Liver disease Osteoporosis Vitamin D Bone fractures

Repulsion of polarised particles from anisotropic materials with a near-zero permittivity component

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Light(Science & Applications) 2016年第1期5卷 752-759页

作者： francisco J rodríguez-Fortuño Anatoly V Zayats Department of Physics King’s College LondonStrandLondon WC2R 2LSUK

Reduction of adhesion and stiction is crucial for robust operation on nanomechanical and optofluidic devices as well as atom and molecule behaviour near *** can be achieved using electric charging,magnetic materials or light pressure and optical *** we show that a particle scattering or emitting in close proximity to an anisotropic substrate can experience a repulsive force if one of the diagonal components of the permittivity tensor is close to *** derive an analytic condition for the existence of such repulsive force depending on the optical properties of the *** also demonstrate the effect using realistic anisotropic metamaterial implementations of a *** anisotropic metamaterial approach using metal–dielectric and graphene–dielectric multilayers provides a tuneable spectral range and a very broad bandwidth of electromagnetic repulsion forces,in contrast to isotropic substrates.

关键词： anisotropy metamaterials optical force repulsion

Highly graphitized carbon nanosheets with embedded Ni nanocrystals as anode for Li-ion batteries

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Nano Research 2020年第1期13卷 86-94页

作者： francisco Javier Soler-Piña Celia Hernández-Rentero Alvaro Caballero Julián Morales Enrique rodríguez-Castellón Jesús Canales-Vázquez Dpto.Química Inorgánica e Ingeniería Química Instituto de Química Fina y NanoquímicaUniversidad de Córdoba14071CórdobaSpain Dpto.Química Inorgánica Cristalografía y MineralogíaFacultad de CienciasUniversidad de Málaga29071MálagaSpain Instituto de Energías Renovables Universidad de Castilla-La ManchaPaseo de La Investigación 102071AlbaceteSpain

A C/Ni composite was prepared via thermal decomposition of a nickel oleate complex at 700℃,yielding disperse Ni nanocrystals with an average size of 20 nm,encapsulated by carbon nanosheets as deduced from transmission electron microscopy(TEM)images and confirmed from X-ray photoelectron spectroscopy(XPS).Furthermore,the X-ray diffraction pattern revealed a good ordering of the carbon layers,forced by the Ni encapsulation to adopt a bending *** the close interaction between the graphitized framework and the metallic nanoparticles we have studied the properties of the composite as an anode for Li-ion *** with other nanostructured synthetic carbons,this carbon composite has a low voltage hysteresis and a modest irreversible capacity value,properties that play a significant role in its behaviour as electrodes in full cell *** moderate rate values,0.25 C,the electrode delivers an average capacity value around 723 mAh·g^−1 on cycling,among the highest values so far reported for this carbon *** higher rate values,1 C,the average capacity values delivered by the cell on cycling decrease,around 205 mAh·g^−1,but it maintains good capacity retention,a coulombic efficiency close to 100%after the first cycles and recovery of the capacity values when the rate is restored from 3 to 0.1 C.

关键词： carbon nanosheets nickel nanoparticles anode lithium batteries

Adenosine A2A-dopamine D2 receptor heteromers operate striatal function:impact on Parkinson's disease pharmacotherapeutics

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Neural Regeneration Research 2018年第2期13卷 241-243页

作者： víctor fernández-duenas sergi ferré francisco ciruela unitat de farmacologia departament patologia i terapèutica experimentalfacultat de medicinaidibelluniversitat de barcelonal’hospitalet de llobregatBarcelonaSpain institut de neurociències universitat de barcelonaBarcelonaSpain integrative neurobiology section national institute on drug abuseintramural research programnational institutes of healthBaltimoreMDUSA

The basal ganglia （BG） assemble a series of deep gray matter structures forming recurrent loops that include the cortex and thalamus, and that participate in the regulation of a plethora of brain functions, including elicitation and learning of reward-and aversive stimuli-associated behaviors, motor activity control and sensorimotor gating （Brom- berg-Martin et al., 2010）.

关键词： AR Adenosine A impact on Parkinson’s disease pharmacotherapeutics Figure