Citrate Stabilizes Hydroxylapatite Precursors: Implications for Bone Mineralization

Mineralization of hydroxylapatite (HAp), the main inorganic phase in bone, follows nonclassical crystallization routes involving metastable precursors and is strongly influenced by organic macromolecules. However, the effect of small organic molecules such as citrate on the formation of HAp is not well constrained. Using potentiometric titration experiments and titration calorimetry, in combination with a multianalytical approach, we show that citrate stabilizes prenucleation species as well as a liquid-like calcium phosphate precursor formed before any solid phase nucleates in the system. The stabilization of a liquid-like precursor phase could facilitate infiltration into the cavities of the collagen fibrils during bone mineralization, explaining the enhancement of collagen-mediated mineralization by citrate reported in previous studies. Hence, citrate can influence bone mineralization way before any solid phase (amorphous or crystalline) is formed. We also show that HAp formation after amorphous calcium phosphate (ACP) in the absence and presence of citrate results in nanoplates of about 5-12 nm thick, elongated along the c axis. Such nanoplates are made up of HAp nanocrystallites with a preferred c axis orientation and with interspersed ACP. The nanoplatelet morphology, size, and preferred crystallographic orientation, remarkably similar to those of bone HAp nanocrystals, appear to be an intrinsic feature of HAp formed from an amorphous precursor. Our results challenge current models for HAp mineralization in bone and the role of citrate, offering new clues to help answer the long-standing question as to why natural evolution favored HAp as the mineral phase in bone

Citrate Stabilizes Hydroxylapatite Precursors: Implications for Bone Mineralization

This research was funded by the Spanish Government (grant nos. RTI2018.099565.B.I00 and CGL2015-64683-P), the European Commission (ERDF funds), the University of Granada ("Unidad Cientifica de Excelencia" UCE-PP201605), and the Junta de Andalucia (no. P11-RNM-7550 and research group RNM-179). The authors thank M. Abad and Haidour Benamin from CIC-UGR for their assistance during microscopy and NMR studies. C.R.A. thanks project A7 from SFB1214 (DFG-Deutsche Forschungsgemeinschaf) and Zukunftstkolleg (University of Konstanz).Mineralization of hydroxylapatite (HAp), the main inorganic phase in bone, follows nonclassical crystallization routes involving metastable precursors and is strongly influenced by organic macromolecules. However, the effect of small organic molecules such as citrate on the formation of HAp is not well constrained. Using potentiometric titration experiments and titration calorimetry, in combination with a multianalytical approach, we show that citrate stabilizes prenucleation species as well as a liquid-like calcium phosphate precursor formed before any solid phase nucleates in the system. The stabilization of a liquid-like precursor phase could facilitate infiltration into the cavities of the collagen fibrils during bone mineralization, explaining the enhancement of collagen-mediated mineralization by citrate reported in previous studies. Hence, citrate can influence bone mineralization way before any solid phase (amorphous or crystalline) is formed. We also show that HAp formation after amorphous calcium phosphate (ACP) in the absence and presence of citrate results in nanoplates of about 5−12 nm thick, elongated along the c axis. Such nanoplates are made up of HAp nanocrystallites with a preferred c axis orientation and with interspersed ACP. The nanoplatelet morphology, size, and preferred crystallographic orientation, remarkably similar to those of bone HAp nanocrystals, appear to be an intrinsic feature of HAp formed from an amorphous precursor. Our results challenge current models for HAp mineralization in bone and the role of citrate, offering new clues to help answer the long-standing question as to why natural evolution favored HAp as the mineral phase in bone.Spanish Government European Commission RTI2018.099565.B.I00 CGL2015-64683-PEuropean Commission European Commission Joint Research CentreUniversity of Granada ("Unidad Cientifica de Excelencia") UCE-PP2016-05Junta de Andalucia P11-RNM-7550 RNM-179DFG-Deutsche Forschungsgemeinschaf SFB1214Zukunftstkolleg (University of Konstanz

Interacción con la Música Flamenca: Análisis y Generación

One main concern in Europe is the preservation and promotion of cultural heritage. Music is a main component of such heritage and flamenco is a main part of Andalusian musical culture. Focusing on flamenco music, in this paper, we describe steps on the analysis and generation of flamenco music oriented towards the diffusion and promotion of this musical style. Specifically, the separation of meaningful musical audio elements from flamenco excerpts by means of the scheme that will be described provides a novel an interactive way of listening to flamenco music by enabling the user to select or emphasize audio elements at will. Also, the scheme for the interactive generation of flamenco music that will be presented allows the user to play and interact with flamenco music by means of a user friendly interface implemented for iOS devices.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Ese trabajo ha sido parcialmente financiado por Campus de Excelencia Internacional en Patrimonio, PATRIMONIUN-10, para programas de generación de investigación de referencia internacional en materia de Patrimonio Cultural y Natural, convocatoria realizada en el ámbito del proyecto PATRIMONIUN-10, Jaén, Marzo de 2014, y por el Ministerio de Economía y Competitividad del Gobierno de España, Proyecto TIN2013-47276-C6-2-R

Evaluación de los peligros naturales y antrópicos para el turismo en Playas del Este, Cuba

Coloquio de Geografía del Turismo, Ocio y Recreación de la Asociación de Geógrafos Españoles. Colmenarejo (Madrid), del 17 al 19 de junio de 2010.Esta investigación forma parte de los resultados del proyecto "El sistema de embalses como forma de regulación y aprovechamiento del agua en la cuenca del río Guanabo, Cuba. Indicadores de sostenibilidad" (Código: A/023914/09), financiado por la Agencia Española de Cooperación Internacional para el Desarrollo y cuyo investigador principal es José Damián Ruiz SinogaPublicad

Ozone Eliminates SARS-CoV-2 from Difficult-to-Clean Office Supplies and Clinical Equipment.

Background: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to cause profound health, economic, and social problems worldwide. The management and disinfection of materials used daily in health centers and common working environments have prompted concerns about the control of coronavirus disease 2019 (COVID-19) infection risk. Ozone is a powerful oxidizing agent that has been widely used in disinfection processes for decades. The aim of this study was to assess the optimal conditions of ozone treatment for the elimination of heat-inactivated SARS-CoV-2 from office supplies (personal computer monitors, keyboards, and computer mice) and clinical equipment (continuous positive airway pressure tubes and personal protective equipment) that are difficult to clean. (2) Methods: The office supplies and clinical equipment were contaminated in an area of 1 cm2 with 1 × 104 viral units of a heat-inactivated SARS-CoV-2 strain, then treated with ozone using two different ozone devices: a specifically designed ozonation chamber (for low–medium ozone concentrations over large volumes) and a clinical ozone generator (for high ozone concentrations over small volumes). SARS-CoV-2 gene detection was carried out using quantitative real-time polymerase chain reaction (RT-qPCR). (3) Results: At high ozone concentrations over small surfaces, the ozone eliminated SARS-CoV-2 RNA in short time periods—i.e., 10 min (at 4000 ppm) or less. The optimum ozone concentration over large volumes was 90 ppm for 120 min in ambient conditions (24 °C and 60–75% relative humidity). (4) Conclusions: This study showed that the appropriate ozone concentration and exposure time eliminated heat-inactivated SARS-CoV-2 RNA from the surfaces of different widely used clinical and office supplies, decreasing their risk of transmission, and improving their reutilization. Ozone may provide an additional tool to control the spread of the COVID-19 pandemic.TRUEInstituto de Salud Carlos III, Madrid, Spain, and by the European Regional Development Funds (FEDER)Fundación Canaria del Instituto de Investigación Sanitaria de Canarias (FIISC), Las PalmasFundación Mapfre Guanarteme, Las PalmasGobierno de Canarias, Las Palmaspu

EVOLUCIÓN DE LAS ENTIDADES ANGIOSTRONGILOSIS Y FASCIOLOSIS DURANTE LOS AÑOS 2015 Y 2016 EN LA PROVINCIA VILLA CLARA, CUBA

Los moluscos constituyen el filo animal de mayor número de especies, solo superado por los artrópodos. El objetivo de la investigación estuvo dirigido a determinar el comportamiento de las entidades angiostrongilosis y fasciolosis en la provincia Villa Clara, Cuba durante los años 2015 y 2016. Se realizaron seis muestreos por cada año (bimestral) en 329 ecosistemas fluviales de los 13 municipios que conforman la provincia. Para la colecta se emplearon, el colador de bronce corto y el colador de mango largo. El método empleado fue el de captura por unidad de esfuerzo durante 15 min sin reposición. Los moluscos vivos recolectados fueron trasladados al Laboratorio de Malacología Médica de Villa Clara, para su identificación. Se identificaron 21 especies de moluscos; de las cuales, dos se clasificaron como endémica, 12 como locales y siete como introducidas. Las familias mejor representadas y distribuidas resultaron ser Thiaridae, Lymnaeidae y Ampullariidae. Las especies más abundantes y mejor representadas fueron Tarebia granifera Lamarck, 1816, Physella acuta (Dreparnaud, 1805), Galba cubensis Pfeiffer, 1839 and Melanoides tuberculata Müller, 1774. Si tenemos en cuenta la elevada riqueza de especies de moluscos de interés sanitario existente en la provincia y los altos valores de abundancia, pues es evidente el riesgo potencial que representa para la salud humana y animal de esta provincia la existencia de especies de moluscos con potencialidades para cerrar el ciclo biológico de numerosas especies de tremátodos y nemátodos

Collaborative blog as a multidisciplinary and interuniversity transversal learning tool

Llevamos décadas usando el blog como herramienta en docencia universitaria, fomentando el trabajo colaborativo en un entorno virtual familiar para el alumnado. Habitualmente, estas experiencias se realizan en asignaturas/ materias concretas de algún Grado. En el campo de la Arquitectura y la Edificación es imprescindible fomentar la transversalidad entre: Proyectos, Estructuras, Construcción e Instalaciones; y la colaboración y diálogo entre profesionales, garantizando la calidad de la obra construida. El Grado en Arquitectura y de Ingeniería de Edificación de la UCAM Universidad Católica de Murcia y el Grado en Fundamentos de la Arquitectura de la Universitat Politècnica de València, pusieron en marcha el curso 21/22 un proyecto de innovación docente, que utiliza el blog con una nueva y amplia perspectiva, implicando al profesorado y alumnado de varias asignaturas/materias de ambos grados y universidades. La participación activa del estudiantado nutrió el blog con 5 publicaciones por participante y semestre. Se ampliaron los conocimientos específicos y se trabajaron competencias básicas y trasnversales: la iniciación a la investigación, el aprendizaje autónomo, etc.; en un entorno colaborativo que despertó su razonamiento crítico y capacidad de gestión de información. Los buenos resultados motivan la continuidad del proyecto en este curso académico, estableciendo sinergias interuniversitarias muy enriquecedoras.It is been a while we have been using the blog as a tool for university teaching, aiming promoting collaborative work, in a daily virtual environment for students. These experiences are carried out in specific subjects/courses of a specific university degree. In the field of Architecture and Building, it is essential to promote transversality between: Project Design, Structures, Construction and Installations; as well as encourage collaboration and dialogue between professionals, guaranteeing the quality of the built work. The Degree in Architecture and the Degree in Building Engineering at UCAM Universidad Católica de Murcia, together with the Degree in the Fundamentals of Architecture of the Universitat Politècnica de València, launched together in the 21/22 academic year, a Teaching Innovation Project, which uses the blog with a new and broad perspective, involving teachers and students of various subjects/courses of both degrees and universities. The students’ active participation provided this blog with five publications per participant and semester. Specific knowledge was expanded and basic and transversal skills were worked on: initiation to research, autonomous learning, etc.; in a collaborative environment that awakened their critical thinking and information management skills

SGLT2 is not expressed in pancreatic α- and β-cells, and its inhibition does not directly affect glucagon and insulin secretion in rodents and humans.

OBJECTIVE: Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i), or gliflozins, are anti-diabetic drugs that lower glycemia by promoting glucosuria, but they also stimulate endogenous glucose and ketone body production. The likely causes of these metabolic responses are increased blood glucagon levels, and decreased blood insulin levels, but the mechanisms involved are hotly debated. This study verified whether or not SGLT2i affect glucagon and insulin secretion by a direct action on islet cells in three species, using multiple approaches. METHODS: We tested the in vivo effects of two selective SGLT2i (dapagliflozin, empagliflozin) and a SGLT1/2i (sotagliflozin) on various biological parameters (glucosuria, glycemia, glucagonemia, insulinemia) in mice. mRNA expression of SGLT2 and other glucose transporters was assessed in rat, mouse, and human FACS-purified α- and β-cells, and by analysis of two human islet cell transcriptomic datasets. Immunodetection of SGLT2 in pancreatic tissues was performed with a validated antibody. The effects of dapagliflozin, empagliflozin, and sotagliflozin on glucagon and insulin secretion were assessed using isolated rat, mouse and human islets and the in situ perfused mouse pancreas. Finally, we tested the long-term effect of SGLT2i on glucagon gene expression. RESULTS: SGLT2 inhibition in mice increased the plasma glucagon/insulin ratio in the fasted state, an effect correlated with a decline in glycemia. Gene expression analyses and immunodetections showed no SGLT2 mRNA or protein expression in rodent and human islet cells, but moderate SGLT1 mRNA expression in human α-cells. However, functional experiments on rat, mouse, and human (29 donors) islets and the in situ perfused mouse pancreas did not identify any direct effect of dapagliflozin, empagliflozin or sotagliflozin on glucagon and insulin secretion. SGLT2i did not affect glucagon gene expression in rat and human islets. CONCLUSIONS: The data indicate that the SGLT2i-induced increase of the plasma glucagon/insulin ratio in vivo does not result from a direct action of the gliflozins on islet cells

Measurement of the inclusive and differential Higgs boson production cross sections in the leptonic WW decay mode at p √ s=13 TeV

Measurements of the fiducial inclusive and differential production cross sections of the Higgs boson in proton-proton collisions at √ 8 = 13TeV are performed using events where the Higgs boson decays into a pair of W bosons that subsequently decay into a final state with an electron, a muon, and a pair of neutrinos. The analysis is based on data collected with the CMS detector at the LHC during 2016-2018, corresponding to an integrated luminosity of 137 fb-1. Production cross sections are measured as a function of the transverse momentum of the Higgs boson and the associated jet multiplicity. The Higgs boson signal is extracted and simultaneously unfolded to correct for selection efficiency and resolution effects using maximum-likelihood fits to the observed distributions in data. The integrated fiducial cross section is measured to be 86.5 ± 9.5 fb, consistent with the Standard Model expectation of 82.5 ± 4.2 fb. No significant deviation from the Standard Model expectations is observed in the differential measurements.We congratulate our colleagues in the CERN accelerator departments for the excellent performance of the LHC and thank the technical and administrative staffs at CERN and at other CMS institutes for their contributions to the success of the CMS effort. In addition, we gratefully acknowledge the computing centers and personnel of the Worldwide LHC Computing Grid for delivering so effectively the computing infrastructure essential to our analyses. Finally, we acknowledge the enduring support for the construction and operation of the LHC and the CMS detector provided by the following funding agencies: BMBWF and FWF (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, FAPERGS, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES and CSF (Croatia); RIF (Cyprus); SENESCYT (Ecuador); MoER, ERC IUT, PUT and ERDF (Estonia); Academy of Finland, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); NKFIA (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); MSIP and NRF (Republic of Korea); MES (Latvia); LAS (Lithuania); MOE and UM (Malaysia); BUAP, CINVESTAV, CONACYT, LNS, SEP, and UASLP-FAI (Mexico); MOS (Montenegro); MBIE (New Zealand); PAEC (Pakistan); MSHE and NSC (Poland); FCT (Portugal); JINR (Dubna); MON, RosAtom, RAS, RFBR, and NRC KI (Russia); MESTD (Serbia); SEIDI, CPAN, PCTI, and FEDER (Spain); MOSTR (Sri Lanka); Swiss Funding Agencies (Switzerland); MST (Taipei); ThEPCenter, IPST, STAR, and NSTDA (Thailand); TUBITAK and TAEK (Turkey); NASU (Ukraine); STFC (United Kingdom); DOE and NSF (U.S.A.). Individuals have received support from the Marie-Curie program and the European Research Council and Horizon 2020 Grant, contract Nos. 675440, 752730, and 765710 (European Union); the Leventis Foundation; the A.P. Sloan Foundation; the Alexander von Humboldt Foundation; the Belgian Federal Science Policy Office; the Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture (FRIA-Belgium); the Agentschap voor Innovatie door Wetenschap en Technologie (IWT-Belgium); the F.R.S.-FNRS and FWO (Belgium) under the “Excellence of Science — EOS” — be.h project n. 30820817; the Beijing Municipal Science & Technology Commission, No. Z191100007219010; the Ministry of Education, Youth and Sports (MEYS) of the Czech Republic; the Deutsche Forschungsgemeinschaft (DFG) under Germany’s Excellence Strategy — EXC 2121 “Quan tum Universe” — 390833306; the Lendület (“Momentum”) Program and the János Bolyai Research Scholarship of the Hungarian Academy of Sciences, the New National Excellence Program ÚNKP, the NKFIA research grants 123842, 123959, 124845, 124850, 125105, 128713, 128786, and 129058 (Hungary); the Council of Science and Industrial Research, India; the HOMING PLUS program of the Foundation for Polish Science, cofinanced from European Union, Regional Development Fund, the Mobility Plus program of the Ministry of Science and Higher Education, the National Science Center (Poland), contracts Harmonia 2014/14/M/ST2/00428, Opus 2014/13/B/ST2/02543, 2014/15/B/ST2/03998, and 2015/19/B/ST2/02861, Sonata-bis 2012/07/E/ST2/01406; the National Priorities Research Program by Qatar National Research Fund; the Ministry of Science and Higher Education, project no. 02.a03.21.0005 (Russia); the Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia María de Maeztu, grant MDM-2015- 0509 and the Programa Severo Ochoa del Principado de Asturias; the Thalis and Aristeia programs cofinanced by EU-ESF and the Greek NSRF; the Rachadapisek Sompot Fund for Postdoctoral Fellowship, Chulalongkorn University and the Chulalongkorn Academic into Its 2nd Century Project Advancement Project (Thailand); the Kavli Foundation; the Nvidia Corporation; the SuperMicro Corporation; the Welch Foundation, contract C-1845; and the Weston Havens Foundation (U.S.A.)