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Implications of Klotho in vascular health and disease

World Journal of Cardiology 2014年第12期6卷 1262-1269页

作者： Ernesto Martín-Núez javier donate-correa Mercedes Muros-de-Fuentes Carmen Mora-Fernández Juan F Navarro-González Research Unit University Hospital Nuestra Se?ora de Candelaria 38010 Santa Cruz de Tenerife Spain Clinical Analysis Service and Research Unit University Hospital Nuestra Se ora de Candelaria 38010 Santa Cruz de Tenerife Spain Nephrology Service and Research Unit University Hospital Nuestra Se ora de Candelaria 38010 Santa Cruz de Tenerife Spain

Cardiovascular disease(CVD) is a prevalent condition in general population and the first cause of death overall. Klotho, a pleiotropic protein related to longevity that acts as a co-receptor of the fibroblast growth factor 23, has been proposed as a key regulator of the development of CVD. In the few clinical studies made, it has been observed a relationship between low levels of soluble Klotho and the occurrence and severity of CVD, as well as a reduction of cardiovascular risk when they are high. Also, different polymorphisms of human Klotho gene have been related to the incidence of cardiovascular events. Moreover, several experimental studies indicate that this protein acts in the maintenance of vascular homeostasis. Klotho improves endothelial dysfunction through promotion of NO production and mediates antiinflammatory and anti-aging effects such as suppression of adhesion molecules expression, attenuation of nuclear factor-kappa B or inhibition of Wnt signaling. Furthermore,this protein is related to the attenuation of vascular calcification as well as prevention of cardiac hypertrophy. The expression of this protein in the vascular wall implies a new scenario for the treatment of vascular disorders. The purpose of this review is to provide an overview of the relationship between the Klotho protein and CVD, in addition to its role in the maintenance of functional vascular integrity.

关键词： maintenance cardiovascular hypertrophy homeostasis suppression severity prevalent overview attenuation scenario

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Molecular Microbial Diagnostic in Lung Transplant Recipients

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Journal of Cancer Therapy 2012年第5期3卷 511-520页

作者： Sebastián Méndez-álvarez Gerardo Pulido-Reyes javier donate-correa Arturo Soriano Benítez de Lugo General Surgery Service Hospital Universitario Ntra. Sra. de Candelaria Santa Cruz de Tenerife Spain. Research Unit Hospital Universitario Ntra. Sra. de Candelaria Santa Cruz de Tenerife Spain

The appearing of microbial lineages carrying multiple dangerous loci are results from the extensive use of antibiotics and has brought a huge increase in the infections-derived morbidity and mortality, which is critical in the hospital setting. Etiologic agents of these non easily tractable infections include bacteria, such as the genus Staphylococcus, but also fungi and virus. Alterations in the immune system allow these organisms to invade and affect the functionality of any tissue, organ or system of the human being. Pulmonary infection occurs as result of deficient lung systemic defence mechanisms which could be altered by medical treatments or by environmental factors. The infective agents commonly gain access to the lung by air, but also by blood or lymphatic system. Staphylococcus aureus strains that share antibiotic resistance and virulence factors represent the aetiological agent responsible of many cases of bacterial pneumonia, thoracic surgery postoperative infections, and diverse tissue infections, resulting in significant disease and morbidity in recipient patients after lung transplantation. The control and treatment of Staphylococcus infections, especially methicillin resistant strains, need for developing reliable and rapid methods of detection and characterization of these microorganisms. Nowadays, new insights into the diagnostic and epidemiology of MRSA and other pathogenic staphylococci have been developed employing molecular methods. This has meant an important advance in the diagnostic and treatment plans of such infective bacteria.

关键词： Molecular Microbial Diagnostic Lung Transplant Recipients

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Daptomycin,Methicillin Resistant Staphylococcus hominis Catheter-Related Bacteraemia in a Hemodialysis Patient

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Open Journal of Medical Microbiology 2013年第1期3卷 53-55页

作者： Manuel Macia-Heras javier donate-correa Julia Alcoba-Florez Gerardo Pulido-Reyes Ernesto Martin-Nunez Joel Martin-Padron Sebastian Mendez-Alvarez Research Unit University Hospital Nuestra Senora de CandelariaSanta Cruz de TenerifeSpain Nephrology Service University Hospital Nuestra Senora de CandelariaSanta Cruz de TenerifeSpain Microbiology Service University Hospital Nuestra Senora de CandelariaSanta Cruz de TenerifeSpain Department of Microbiology and Cell Biology University of La LagunaTenerifeSpain

We report a case of a haemodialysis patient that presented a catheter-related bacteraemia caused by a Coagulase negative Staphylococcus. With the utilization of molecular biology techniques the bacterial isolate recovered from catheter was surprisingly identified as S. hominis by sequencing of the 16S ribosomal gene. The S. hominis isolate, which is not often associated with infections in dialysis patients, was resistant to methicillin, being mecA positive, and to daptomycin. The patient was successfully treated with vancomycin together with the catheter retirement.

关键词： Bacteraemia Catheter Daptomycin Methicillin Staphylococcus hominis

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Klotho in cardiovascular disease:Current and future perspectives

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World Journal of Biological Chemistry 2015年第4期6卷 351-357页

作者： javier donate-correa Ernesto Martin-Nunez Carmen Mora-Fernandez Mercedes Muros-de-Fuentes Nayra Perez-Delgado Juan F Navarro-Gonzalez Research Unit University Hospital Nuestra Senora de Candelaria Clinical Biochemistry Service University Hospital Nuestra Senora de Candelaria Nephrology Service University Hospital Nuestr Senora de Candelaria

Protein Klotho,beyond its role as a regulator of the phosphatemia,is also involved in the maintaining of the cardiovascular health,being associated its alterations with the development of cardiovascular damage and increased morbi-mortality. For all this,nowadays Klotho is the subject of a thorough research which is focused on uncover its intimate mechanisms of action,and in analyzing the utility of its modulation as a potential strategy with clinical applicability. Molecular mechanisms of Klotho are not well understood but an emerging research area links Klotho deficiency with vascular pathology. Changes in this protein have been associated with cardiovascular-related complications like inflammation,vascular calcification,and endothelial dysfunction. All this is particularly relevant if considering the recent discovery of Klotho expression in vascular tissue.

关键词： Klotho Cardiovascular disease Chronic kidney disea

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Origin of nucleation and growth of extension twins in grains unsuitably oriented for twinning during deformation of Mg-1%Al

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Journal of Magnesium and Alloys 2024年第3期12卷 1186-1203页

作者： Biaobiao Yang javier LLorca IMDEA Materials Institute C/Eric Kandel 2GetafeMadrid 28906Spain Department of Materials Science Polytechnic University of Madrid/Universidad Politécnica de MadridE.T.S.de Ingenieros de CaminosMadrid 28040Spain

A large number of anomalous extension twins,with low or even negative twinning Schmid factors,were found to nucleate and grow in a strongly textured Mg-1Al alloy during tensile deformation along the extruded direction.The deformation mechanisms responsible for this behaviour were investigated through in-situ electron back-scattered diffraction,grain reference orientation deviation,and slip trace-modified lattice rotation.It was found that anomalous extension twins nucleated mainly at the onset of plastic deformation at or near grain boundary triple junctions.They were associated with the severe strain incompatibility between neighbour grains as a result from the differentbasal slip-induced lattice rotations.Moreover,the anomalous twins were able to grow with the applied strain due to the continuous activation ofbasal slip in different neighbour grains,which enhanced the strain incompatibility.These results reveal the complexity of the deformation mechanisms in Mg alloys at the local level when deformed along hard orientations.

关键词： Magnesium Extension twinning In-situ electron back-scattered diffraction basal slip Deformation mechanisms.

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Contributions to the knowledge of Antarctodon sobrali(Mammalia:Astrapotheria)from the Eocene of Antarctica

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Advances in Polar Science 2024年第1期35卷 48-62页

作者： javier N.GELFO Consejo Nacional de Investigaciones Científicasy Técnicas(CONICET) Buenos Aires C1425FQBArgentina División Paleontología Vertebrados Museo de La PlataFacultad de Ciencias Naturales y Museo de La PlataUniversidad Nacional de La PlataLa Plata B1900FWAArgentina

The Astrapotheria constitutes one of the five orders of extinct South American native ungulates,with a fossil record that also extends to the Eocene of the Antarctic Peninsula.In contrast to the abundant specimens known for litoptern Sparnotheriodontidae and metatherians,astrapotheres are represented by scant remains assigned to the endemic Antarctodon sobrali and indeterminate astrapotheres,restricted to levels 35C_(u0)and 35n of the Cucullaea I Allomember of the La Meseta Formation.The discovery of alower molar assignable to this species in the Eocene levels of Seymour(Marambio)Island,enables a revision of the diagnosis and the homologies of the dental characters used to describe this taxon.A reanalysis of its phylogenetic relationships reveals the nearly simultaneous presence of basal astrapotheres in the early Eocene of Itaboraí(Brazil),Patagonia,and West Antarctica.These taxa are characterized by lacking dental specializations usually associated with more abrasive diets like terminal forms of Uruguaytheriinae and Astrapotheriinae.Antarctodon appears to have thrived on the Antarctic continent during the Early Eocene Climatic Optimum within the paleoclimatic context of a hot-house world.Unlike present conditions in Antarctica where no terrestrial mammals inhabit,the early Eocene climate was characterized by warmer temperatures and a biologically diverse environment rich in primary producers,dominated by Nothofagus forests,encompassing both deciduous and evergreen forests,which supported a diverse assemblage of continental vertebrates.

关键词： Astrapotheria Antarctodon Eocene Seymour Island La Meseta Formation

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Radiative loss of coherence in free electrons:a long-range quantum phenomenon

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Light(Science & Applications) 2024年第2期13卷 294-301页

作者： Cruz I.Velasco Valerio Di Giulio F.javier García de Abajo ICFO-Institut de Ciencies Fotoniques The Barcelona Institute of Science and Technology08860Castelldefels(Barcelona)Spain ICREA-InstitucióCatalana de Recerca i Estudis Avançats Passeig Lluís Companys 2308010BarcelonaSpain

Quantum physics rules the dynamics of small objects as they interact over microscopic length scales.Nevertheless,quantum correlations involving macroscopic distances can be observed between entangled photons as well as in atomic gases and matter waves at low temperatures.The long-range nature of the electromagnetic coupling between charged particles and extended objects could also trigger quantum phenomena over large distances.Here,we reveal a manifestation of quantum mechanics that involves macroscopic distances and results in a nearly complete depletion of coherence associated with which-way free-electron interference produced by electron-radiation coupling in the presence of distant extended objects.This is a ubiquitous effect that we illustrate through a rigorous theoretical analysis of a two-path electron beam interacting with a semi-infinite metallic plate and find the inter-path coherence to vanish proportionally to the path separation at zero temperature and exponentially at finite temperature.The investigated regime of large distances originates in the coupling of the electron to radiative modes assisted by diffraction at material structures but without any involvement of material excitations.Besides the fundamental interest of this macroscopic quantum phenomenon,our results suggest an approach to measuring the vacuum temperature and nondestructively sensing the presence of distant objects.

关键词： temperature quantum macroscopic

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Reachability-Based Confidence-Aware Probabilistic Collision Detection in Highway Driving

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Engineering 2024年第2期33卷 90-107页

作者： Xinwei Wang Zirui Li javier Alonso-Mora Meng Wang School of Engineering and Materials Science Queen Mary University of LondonLondon E14NSUK Department of Cognitive Robotics Delft University of TechnologyDelft 2628 CDNetherlands School of Mechanical Engineering Beijing Institute of TechnologyBeijing 100081China Chair of Traffic Process Automation “Friedrich List”Faculty of Transport and Traffic SciencesTU DresdenDresden 01069Germany

Risk assessment is a crucial component of collision warning and avoidance systems for intelligent vehicles.Reachability-based formal approaches have been developed to ensure driving safety to accurately detect potential vehicle collisions.However,they suffer from over-conservatism,potentially resulting in false–positive risk events in complicated real-world applications.In this paper,we combine two reachability analysis techniques,a backward reachable set(BRS)and a stochastic forward reachable set(FRS),and propose an integrated probabilistic collision–detection framework for highway driving.Within this framework,we can first use a BRS to formally check whether a two-vehicle interaction is safe;otherwise,a prediction-based stochastic FRS is employed to estimate the collision probability at each future time step.Thus,the framework can not only identify non-risky events with guaranteed safety but also provide accurate collision risk estimation in safety-critical events.To construct the stochastic FRS,we develop a neural network-based acceleration model for surrounding vehicles and further incorporate a confidence-aware dynamic belief to improve the prediction accuracy.Extensive experiments were conducted to validate the performance of the acceleration prediction model based on naturalistic highway driving data.The efficiency and effectiveness of the framework with infused confidence beliefs were tested in both naturalistic and simulated highway scenarios.The proposed risk assessment framework is promising for real-world applications.

关键词： Probabilistic collision detection Confidence awareness Probabilistic acceleration prediction Reachability analysis Risk assessment

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The effect of slime accumulated in a long-term operating UASB using crude glycerol to treat S-rich wastewater

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Journal of Environmental Sciences 2024年第1期135卷 353-366页

作者： Xudong Zhou Eva Fernández-Palacios Antoni DDorado javier Lafuente Xavier Gamisans David Gabriel Key Laboratory of Urban Pollutant Conversion Institute of Urban EnvironmentChinese Academy of SciencesXiamen 361021China GENOCOV Research Group Department of ChemicalBiological and Environmental EngineeringEscola d’EnginyeriaUniversitat Autònoma de Barcelona08193 BellaterraSpain Department of Mining Industrial and ICT EngineeringUniversitat Politècnica de CatalunyaAvinguda de les Bases de Manresa 61-7308242 ManresaSpain

An up-flow anaerobic sludge blanket(UASB)reactor targeting sulfate reduction was operated under a constant TOC/S-SO2-4ratio of 1.5±0.3 g C/g S for 639 days using crude glycerol as carbon source.A filamentous and fluffy flocculant material,namely slime-like substances(SLS),was gradually accumulated in the bioreactor after the cease of methanogenic activity.The accumulation of SLS was followed by a decrease in the removal efficiencies and a deterioration in the performance.Selected characteristics of SLS were investigated to explore the causes of its formation and the effect of SLS on the UASB performance.Results showed that glycerol fermentation and sulfate reduction processes taking place in the reactor were mainly accomplished in the bottom part of the UASB reactor,as the sludge concentration in the bottom was higher.The accumulation of SLS in the UASB reactor caused sludge flotation that further led to biomass washout,which decreased the sulfate and glycerol removal efficiencies.Batch activity tests performed with granular sludge(GS),slime-covered granular sludge(SCGS)and SLS showed that there was no difference between GS and SLS in the mechanism of glycerol fermentation and sulfate reduction.However,the specific sulfate reduction rate of GS was higher than that of SLS,while SLS showed a higher glycerol fermentation rate than that of GS.The different rates in GS and SLS were attributed to the higher relative abundances of fermentative microorganisms found in SLS and higher relative abundances of sulfate reducing bacteria(SRB)found in GS.

关键词： Sludge flotation Granular sludge Slime-like substances Glycerol fermentation Sulfate reduction Removal efficiency

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Astrocytes, reactive astrogliosis, and glial scar formation in traumatic brain injury

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Neural Regeneration Research 2025年第4期20卷 973-989页

作者： María Belén Cieri Alberto javier Ramos Laboratorio de Neuropatología Molecular IBCN UBA-CONICETFacultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

Traumatic brain injury is a global health crisis,causing significant death and disability worldwide.Neuroinflammation that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this response.Following traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain regions.Homeostatic astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are overexpressed.This altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive recovery.In addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional recovery.Current therapeutic strategies for traumatic brain injury are focused on preventing acute complications.Statins,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of astrocytes.In this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRNAs or lncRNA,viral vectors,and repurposed drugs.

关键词： astrocyte glial scar innate immunity neuroinflammation stab injury Toll-like receptors

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