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Insights into the structural biology of G-protein coupled receptors impacts drug design for central nervous system neurodegenerative processes

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Neural Regeneration Research 2013年第24期8卷 2290-2302页

作者： Farfán-García Eunice Dalet Trujillo-Ferrara josé Guadalupe Castillo-Hernández María del Carmen Guerra-Araiza Christian Humberto Soriano-Ursúa Marvin antonio Escuela Superior de Medicina Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón s/n Col. Casco de Santo Tomas

In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selec- tivity of ligands for G-protein coupled receptors, and that signaling by these receptors involves both G-protein dependent and independent pathways. The present review outlines the physiological and pharmacological implications of this perspective for the design of new drugs to treat disorders of the central nervous system. Specifically, new possibilities are explored in relation to allosteric and or- thosteric binding sites on dopamine receptors for the treatment of Parkinson＇s disease, and on muscarinic receptors for Alzheimer＇s disease. Future research can seek to identify ligands that can bind to more than one site on the same receptor, or simultaneously bind to two receptors and form a dimer. For example, the design of bivalent drugs that can reach homo/hetero-dimers of D2 dopa- mine receptor holds promise as a relevant therapeutic strategy for Parkinson＇s disease. Regarding the treatment of Alzheimer＇s disease, the design of dualsteric ligands for mono-oligomeric mus- carinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway.

关键词： neural regeneration G-Protein coupled receptors structural biology drug design neurodegenera-tive disorders , oligomedzation biased signaling Parkinson's disease Alzheimer's disease dopa-mine receptors muscarinic receptors grants-supported paper neuroregeneration

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Antimicrobial Potential and Phytochemical Content of Six Diverse Sources of Quinoa Seeds (<i>Chenopodium quinoa</i>Willd.)

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Agricultural Sciences 2014年第11期5卷 1015-1024页

作者： Margarita Miranda josé Delatorre-Herrera antonio Vega-Gálvez Evelyn Jorquera Issis Quispe-Fuentes Enrique A. Martínez Department of Food Engineering Universidad de La Serena La Serena Chile Department of Agriculture of Desert and Biotechnology Facultad de Recursos Naturales Renovables Universidad Arturo Prat Iquique Chile Centro de Estudios Avanzados en Zonas áridas (CEAZA) Facultad de Ciencias del Mar Universidad Católica del Norte Coquimbo and La Serena Chile

Antimicrobial potential of quinoa seeds from six diverse seeds, grown in three distinctive geo-graphical zones of Chile, was correlated with their total phenolic content (TPC), total flavonoid content (TFC) and total saponin content (TSC). The six seeds were Ancovinto, Cancosa, Cahuil, Faro, Regalona and Villarrica. A significant influence of quinoa source on chemical composition of seeds was observed. Extracts of all quinoa samples showed antimicrobial activity in the range of 8.3 - 14.8 mm inhibition zone for E. coli and 8.5 - 15.0 mm inhibition zone for S. aureus. Cancosa seeds had the highest antimicrobial action. The TPC and TFC ranged from 3.71 to 16.55 mg GA/100 g d.m. and 7.77 to 14.37 mg QE/100 g d.m., respectively. TSC varied from 1.78 to 3.08 g/100 g d.m. A cor-relation between TFC and antimicrobial activity was found. In conclusion, the six types of quinoa seeds were identified as potential sources of antioxidant compounds and antimicrobial activity.

关键词： Quinoa Antimicrobial Activity Phenols Flavonoids Saponin

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Narcea—an unknown,ancient cultivated rose variety from northern Spain

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Horticulture Research 2020年第1期7卷 2217-2228页

作者： María-Carmen Martínez josé-Luis Santiago Susana Boso Pilar Gago InmaculadaÁlvarez-Acero María-Estela De Vega Miguel Martínez-Bartolomé RafaelÁlvarez-Nogal Pilar Molíst Matteo Caser Valentina Scariot Daniel Gómez-García Misión Biológica de Galicia(CSIC) Carballeira 8Salcedo 36143 PontevedraSpain Instituto de Ciencia y Tecnología de Alimentos y Nutrición(CSIC)(Spain) C/JoséAntonio Novais 1028040 MadridSpain Departamento de Biología Molecular-Área de Biología Celular Universidad de LeónCampus de Vegazana s/n24071 LeónSpain Grupo Neurolamb Biología funcional y Ciencias de la SaludUniversidad de Vigo(Spain)36310 As Lagoas-MarcosendeSpain Department of Agricultural Forest and Food SciencesUniversity of TorinoLargo Paolo Braccini 210095 GrugliascoTurinItaly Instituto Pirenaico de Ecología(CSIC) Dpto.Conservación de Ecosistemas NaturalesAvda.Montaña S/NZaragoza50016 ZaragozaSpain

The present work reports the discovery and the complete characterisation of an ancient cultivated rose variety found growing in a private garden in the southwest of the Principality of Asturias(northern Spain).The variety is here given the name *** majority of roses currently cultivated belong to the so-called group of‘Modern Roses’,all of which were obtained after 1867 via artificial crosses and improvement *** are destined for ornamental *** the 19th century,the great majority of the many ancient cultivated roses in Europe were used in perfumery and cosmetics,or had medicinal *** damascena and Rosa centifollia are still grown and used by the French and Bulgarian perfume *** Asturian Massif of the Cantabrian Mountain Range provides a natural habitat for some 75%of the wild members of the genus Rosa,but until now there was no evidence that this area was home to ancient cultivated roses.A complete botanical description is here provided for a discovered ancient *** is also characterised according to a series of sequence tagged microsatellite sites,and its agronomic features are *** addition,a histological description(optical and scanning electronic microscope studies)of the petals is offered,along with an analysis of the volatile compounds present in these organs as determined by solid phase microextraction and gas chromatography-mass *** results reveal the uniqueness of this ancient type of rose and suggest it may be of interest to the perfume industry.

关键词： ancient southwest majority

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Nonlinear Coefficient Determination of Au/Pd Bimetallic Nanoparticles Using Z-Scan

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Advances in Nanoparticles 2013年第3期2卷 223-228页

作者： josé Luis jiménez Pérez Rubén Gutiérrez-Fuentes josé Francisco Sánchez Ramírez Omar Uriel García Vidal Daniel Erick Téllez-Sánchez Zormy Nacary Correa Pacheco Alfredo Cruz Orea Jesús antonio Fuentes García Centro de Investigación en Ciencia Aplicada y Tecnología Avanzada México D.F. México Departamento de Física Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional México D.F. México Unidad Profesional Interdisciplinaria en Ingeniería y Tecnologías Avanzadas del IPN México D.F. México

In this paper we present the nonlinear optical characterization of Au/Pd nanoparticles in order to obtain the nonlinear refractive indices using the Z-scan technique. The experiments were performed using a 514 nm laser beam Ar+, with 14 Hz of modulation frequency, as excitation source. By using a lens the excitation beam was focused to a small spot and the sample was moved across the focal region along the z-axis by a motorized translation stage. Seven samples with different concentration ratio of Au/Pd nanoparticles were prepared by simultaneous reduction of gold and palladium ions in presence of poly (N-vinyl-2-pirrolidone) (PVP) using ethanol as a reducing agent. In this work, we report the application of the Z-scan technique, to generate optical transmission of laser light as a function of the z position for solutions containing bimetallic nanoparticles of Au (core)/Pd (shell) with average sizes ranging from 3 to 5 nm. The magnitude of the obtained nonlinear refractive index was in the order of 10?8 cm2/W. Our results show that the nonlinear refractive index has a nonlinear behavior when the (Au/Pd) ratio was increased.

关键词： Nanofluids Nanoparticles Nonlinear Refractive Indices Z-Scan

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A bibliometric review of cryptocurrencies:how have they grown?

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Financial Innovation 2022年第1期8卷 25-55页

作者： Francisco Javier García-Corral joséantonio Cordero-García Jaime de Pablo-Valenciano Juan Uribe-Toril Research Group:Almeria Group of Applied Economy(SEJ 147) University of AlmeriaCarretera Sacramento s/n04120La Cañada de San UrbanoAlmeríaSpain Department of Law Financial and Tax LawUniversity of AlmeriaCarretera Sacramento s/n04120La Cañada de San UrbanoAlmeríaSpain Department of Business and Economics Applied Economic AreaUniversity of AlmeríaCarretera Sacramento s/n04120La Cañada de San UrbanoAlmeríaSpain

With the development of new technologies,some concepts become relevant in the economic area,as is the case with cryptocurrencies,in general,or Bitcoin and Ethereum,in *** to the impact of these tools,a detailed bibliometric study that allows us to obtain all information about cryptocurrencies must be *** study will help scientific production by specifying the development and lines of related research that have been followed and are currently being *** have used Tableau,R(Bibliometrix R Package),and VOSviewer software to analyze the *** have been combined to create and review unified metadata from the Web of Science(WoS)and Scopus *** bibliometric analysis shows 771 articles on the WoS database and 648 articles on Scopus published between 2010 and early *** present the most relevant articles,research areas,countries,institu-tions,authors,journals,and trends during the last few *** conclusion,the number of publications has grown in the last 3 *** analysis shows the evolution of block-chain technology used in this type of *** review of this period marks a possible end to the historical part of cryptocurrencies,thereby opening the current topic to its multiple applications.

关键词： Cryptocurrency Bitcoin Ethereum Bibliometric analysis Business and economics

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Tale of two kinases:Protein kinase A and Ca^(2+)/calmodulin-dependent protein kinase Ⅱ in pre-diabetic cardiomyopathy

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World Journal of Diabetes 2021年第10期12卷 1704-1718页

作者： Pamela Gaitán-González Rommel Sánchez-Hernández josé-antonio Arias-Montaño Angélica Rueda Department of Biochemistry Centro de Investigación y de Estudios Avanzados del Instituto Politécnico NacionalCiudad de México 07360Mexico Department of Physiology Biophysics and NeurosciencesCentro de Investigación y de Estudios Avanzados del Instituto Politécnico NacionalCiudad de México 07360Mexico

Metabolic syndrome is a pre-diabetic state characterized by several biochemical and physiological alterations,including insulin resistance,visceral fat accumulation,and dyslipidemias,which increase the risk for developing cardiovascular *** syndrome is associated with augmented sympathetic tone,which could account for the etiology of pre-diabetic *** review summarizes the current knowledge of the pathophysiological consequences of enhanced and sustainedβ-adrenergic response in pre-diabetes,focusing on cardiac dysfunction reported in diet-induced experimental models of pre-diabetic *** research reviewed indicates that both protein kinase A and Ca^(2+)/calmodulin-dependent protein kinase Ⅱ play important roles in functional responses mediated byβ1-adrenoceptors;therefore,alterations in the expression or function of these kinases can be *** review also outlines recent information on the role of protein kinase A and Ca^(2+)/calmodulin-dependent protein kinase Ⅱ in abnormal Ca^(2+)handling by cardiomyocytes from diet-induced models of pre-diabetic cardiomyopathy.

关键词： Ca^(2+)/calmodulin-dependent protein kinase II Protein kinase A Metabolic syndrome Pre-diabetes Pre-diabetic cardiomyopathy β-Adrenoceptors

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Pro-oxidative and anti-oxidative imbalance in human semen and its relation with male fertility

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Asian Journal of Andrology 2004年第1期6卷 59-65页

作者： Nicolás Garrido Marcos Meseguer Carlos Simon antonio Pellicer josé Remohi Instituto Valenciano de Infertilidad Valencia Valencia 46015 Spain Fundación Instituto Valenciano de Infertilidad Valencia SpainInstituto Valenciano de Infertilidad Valencia Valencia 46015 Spain Fundación Instituto Valenciano de Infertilidad Valencia SpainInstituto Valenciano de Infertilidad Valencia Valencia 46015 Spain Department of Pediatrics Obstetrics and Gynecology Valencia University School of Medicine Valencia SpainInstituto Valenciano de Infertilidad Valencia Valencia 46015 SpainDepartment of Pediatrics Obstetrics and Gynecology Valencia University School of Medicine Valencia SpainDepartment of Obstetrics and Gynecology Hospital Dr. Peset Valencia SpainInstituto Valenciano de Infertilidad Valencia Valencia 46015 SpainDepartment of Obstetrics and Gynecology Hospital Dr. Peset Valencia Spain

Oxidative stress is a common condition suffered by biological systems in aerobic conditions. Human semen also has its own molecular guard against the free radicals created by normal respiratory process or from immune reactions. The equilibrium of the creation and scavenging of free radicals is mandatory in the spermatozoa to fertilize and initiate a full-term pregnancy. The paper is a systematic review of publications that evaluate oxidative stress in semen. The Cochrane Library, Medline (1966-2003), Embase (1988-2003), SciSearch (1981-2003) and the conference papers were searched. When sperm samples from fertile and infertile males were analyzed, some of the mechanisms that determine the oxidative stress level were found to be impaired while others were unaltered. In conclusion, the literature as a whole provides contradictory findings and it is necessary to carry out more work to identify all the enzymatic and non-enzymatic systems involved in oxidative stress in the ejaculate, in order to develop new diagnostic systems and therapeutic strategies for combating detrimental free radical imbalance in the semen.

关键词： oxidative stress antioxidants semen spermatozoa male fertility

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Influence of Gamma Irradiation on Seedless Citrus Production: Pollen Germination and Fruit Quality

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Food and Nutrition Sciences 2011年第3期2卷 169-180页

作者： Almudena Bermejo josé Pardo antonio Cano 不详

Seedlessness is a desirable characteristic in citrus fruits sold for fresh consumption. Gamma irradiation is widely used to obtain seedless citrus fruits. Here, different clones of the self-incompatible parthenocarpic ‘Moncada’ mandarin, obtained by gamma irradiation, were studied to assess seedlessness, pollen germination, fruit characteristics and qua- lity attributes. Findings indicate that irradiation altered aspects other than seedlessness, such as pollen germination, and some of the clones presented different weight, size, acidity and maturity index. Fruit quality and nutritional bio- components were affected differently;some clones presented no changes compared to the control ‘Moncada’ man-darin, while other clones showed significant differences. In general, all clones examined presented low seed numbers and re- duced pollen viability. Some of these clones, which ripen late in the season and whose fruit quality is maintained or improved, are in the process of registration.

关键词： Citrus Clones Nutritional Bio-Components Fruit Quality Gamma Irradiation Seedlessness Pollen Germination

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Optimal Coordinated Operation of Distributed Static Series Compensators for Wide-area Network Congestion Relief

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Journal of Modern Power Systems and Clean Energy 2022年第5期10卷 1374-1384页

作者： Camilo Andres Ordonez M antonio Gomez-Exposito Guillermo EVinasco M jose Maria Maza-Ortega IEEE Smart Wires Union CityUSA Department of Electrical Engineering University of SevilleSevillaSpain Interconexion Electrica SA Intercolombia Sevilla Spain

Relieving network congestions is a critical goal for the safe and flexible operation of modern power systems, especially in the presence of intermittent renewables or distributed generation. This paper deals with the real-time coordinated operation of distributed static series compensators(DSSCs) to remove network congestions by suitable modifications of the branch reactance. Several objective functions are considered and discussed to minimize the number of the devices involved in the control actions, the total losses or the total reactive power exchanged, leading to a non-convex mixed-integer non-linear programming problem. Then, a heuristic methodology combining the solution of a regular NLP with k-means clustering algorithm is proposed to get rid of the binary variables, in an attempt to reduce the computational cost. The proposed coordinated operation strategy of the DSSCs is tested on several benchmark systems, providing feasible and sufficiently optimal solutions in a reasonable time frame for practical systems.

关键词： Distributed static series compensation(DSSC) flexible AC transmission system(FACTS) mixed-integer non-linear programming(MINLP) wide-area network control

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Effects of normobaric cyclic hypoxia exposure on mesenchymal stem-cell differentiation–pilot study on bone parameters in elderly

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World Journal of Stem Cells 2020年第12期12卷 1667-1690页

作者： Marta Camacho-Cardenosa joséManuel Quesada-Gómez Alba Camacho-Cardenosa Alejo Leal GabrielDorado Bárbara Torrecillas-Baena antonio Casado-Díaz Facultad Ciencias del Deporte Universidad De ExtremaduraCáceres 10003Spain CIBER De Fragilidad Y Envejecimiento Saludable(CIBERFES) Unidad De Gestión Clínica De Endocrinología Y NutriciónInstituto Maimónides De Investigación Biomédica De CórdobaHospital Universitario Reina SofíaCórdoba 14004Spain Servicio de Traumatología Hospital de CáceresCáceres 10004Spain Departamento Bioquímica y Biología Molecular Campus Rabanales C6-1-E17Campus de Excelencia Internacional Agroalimentario(ceiA3)Universidad de Córdoba-CIBERFES14071 CórdobaSpain

BACKGROUND Mesenchymal stem cells(MSC)of bone marrow are the progenitor of osteoblasts and *** tend to differentiate into adipocytes,instead of osteoblasts,with *** favors the loss of bone mass and development of *** induces hypoxia inducible factor 1αgene encoding transcription factor,which regulates the expression of genes related to energy metabolism and *** allows a better adaptation to low O2 *** hypoxia has negative effects on bone metabolism,favoring bone ***,surprisingly,cyclic hypoxia(CH),short times of hypoxia followed by long times in normoxia,can modulate MSC differentiation and improve bone health in *** To evaluate the CH effect on MSC differentiation,and whether it improves bone mineral density in *** MSC cultures were induced to differentiate into osteoblasts or adipocytes,in CH(3%O2 for 1,2 or 4 h,4 d a week).Extracellular-matrix mineralization and lipid-droplet formation were studied in MSC induced to differentiate into osteoblast or adipocytes,*** addition,gene expression of marker genes,for osteogenesis or adipogenesis,have been quantified by quantitative real time polymerase chain *** in vivo studies with elderly(>75 years old;n=10)were carried out in a hypoxia chamber,simulating an altitude of 2500 m above sea level,or in normoxia,for 18 wk(36 CH sessions of 16 min each).Percentages of fat mass and bone mineral density from whole body,trunk and right proximal femur(femoral,femoral neck and trochanter)were assessed,using dual-energy X-ray *** CH(4 h of hypoxic exposure)inhibited extracellular matrix mineralization and lipid-droplet formation in MSC induced to differentiate into osteoblasts or adipocytes,***,both parameters were not significantly affected by the other shorter hypoxia times *** longest periods of hypoxia downregulated the expression of genes related to extracellular matrix

关键词： Normobaric cyclic hypoxia Mesenchymal stem cells Cellular differentiation Osteoblasts Adipocytes Bone health

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