5,645 research outputs found

    Metal coordination and peripheral substitution modulate the activity of cyclic tetrapyrroles on αS aggregation: A structural and cell-based study.

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    The discovery of aggregation inhibitors and the elucidation of their mechanism of action are key in the quest to mitigate the toxic consequences of amyloid formation. We have previously characterized the antiamyloidogenic mechanism of action of sodium phtalocyanine tetrasulfonate ([Na4(H2PcTS)]) on α-Synuclein (αS), demonstrating that specific aromatic interactions are fundamental for the inhibition of amyloid assembly. Here we studied the influence that metal preferential affinity and peripheral substituents may have on the activity of tetrapyrrolic compounds on αS aggregation. For the first time, our laboratory has extended the studies in the field of the bioinorganic chemistry and biophysics to cellular biology, using a well-established cell-based model to study αS aggregation. The interaction scenario described in our work revealed that both N- and C-terminal regions of αS represent binding interfaces for the studied compounds, a behavior that is mainly driven by the presence of negatively or positively charged substituents located at the periphery of the macrocycle. Binding modes of the tetrapyrrole ligands to αS are determined by the planarity and hydrophobicity of the aromatic ring system in the tetrapyrrolic molecule and/or the preferential affinity of the metal ion conjugated at the center of the macrocyclic ring. The different capability of phthalocyanines and meso-tetra (N-methyl-4-pyridyl) porphine tetrachloride ([H2PrTPCl4]) to modulate αS aggregation in vitro was reproduced in cell-based models of αS aggregation, demonstrating unequivocally that the modulation exerted by these compounds on amyloid assembly is a direct consequence of their interaction with the target protein

    Biogeomorphological processes in an arid transgressive dunefield as indicators of human impact by urbanization

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    This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. This author accepted manuscript is made available following 24 month embargo from date of publication (August 2018) in accordance with the publisher’s archiving policyUrban and tourist developments can have long-lasting impacts on coastal environments and fundamentally alter the evolution of coastal dune systems. This is the case of the Maspalomas dunefield (Gran Canaria, Canary Islands), hosting one of the largest tourist resorts in Spain. The resort was built on top of a sedimentary terrace at 25 m above sea level (El Inglés) in the 1960s, and has subsequently affected local winds and therefore aeolian sediment transport patterns. Buildings on the terrace deflect the winds to the south of the dunefield, where the rate of sediment transport accelerated. A shadow zone appeared to the lee side of the resort with a consequent decrease in wind speed and aeolian sediment transport and an increase in vegetation cover. In this paper, first we characterize the environmental changes around El Inglés terrace in recent decades, and describe the changes in the shadow zone through an analysis of the evolution of sedimentary volumes and vegetation characteristics (density, spatial patterns, and plants communities). A series of historical aerial photographs, recent orthophotos and digital elevation models obtained by digital photogrammetry and LiDAR, as well as fieldwork were used to characterize plant communities and spatial-temporal changes in erosive landforms. Results show changes in the pattern and migration rates of dunes located at the southern edge of the urbanization, as well as the formation of blowouts and large deflation areas, where the vegetation increases in density and number of plant communities. We discuss eco-anthropogenic factors that have produced these environmental changes.This work is a contribution of projects CSO2013-43256-R and CSO2016-79673-R (National R & D & I Plan) co-financed with ERDF funds and a PhD contract of the Canary Islands Agency for Research, Innovation and Information Society and by the European Social Fund (ESF)

    Greedy Parabolics: Wind flow direction within the deflation basin of parabolic dunes is governed by deflation basin width and depth

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    Parabolic dunes are ‘U’ or ‘V’-shaped aeolian landforms that form on pre-existing sand deposits. Their morphology consists of an upwind deflation basin, bordered by often vegetated trailing arms and a downwind depositional lobe. The orientation of parabolic dunes is commonly attributed to the prevailing or resultant wind direction. Consequently, the orientation of parabolic dunes stabilised by vegetation growth has been used as a proxy for wind direction during past climates in several studies. However, the ability or extent of parabolic dune morphology to steer incident wind flow parallel to the orientation of the landform, and thus migrate in the direction of the current landform orientation rather than prevailing wind direction, is unknown. By numerically modelling wind flow within the deflation basin of eight parabolic dunes, we demonstrate for the first time that wind flow direction within the deflation basin of a parabolic dune is highly controlled by the depth and width of the deflation basin. The greater the depth–width ratio of the landform (i.e. the deeper and narrower the deflation basin), the greater the degree of flow steering relative to the axis orientation of the landform. These results demonstrate that future studies must exercise caution when using parabolic dune orientation as a direct proxy for prevailing wind direction, especially where parabolic dunes have a relatively high deflation basin depth–width ratio, as the deflation basin of these landforms may continue to migrate in an antecedent wind direction

    Enfermedad de Hirschsprung, a propósito de un caso

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    Introduction: Hirschsprung's disease (HD) is within theclinical context one of Pediatric diseases that lowerIncidencehas, representing barely 2.7% of all of them, according todata from the American College of Pediatrics (ACP). However, its pathophysiologyand clinical behavior governed by the age of the patient are the main variablesthat complicate the diagnosis and give errors of up to 35%(ACP). The mortality of patients can amount up to 65% whenthe EH is complicated with a picture of Necrotizingenterocolitis, in a patient who has notbeen theeliminationof meconium within the first 12 hours of life must suspecteh, always takinginto account the patient's age and recallingthat preterm the same delay can be considered normal, while in the case oflarger aged patients the incidence of thedisease is lower, however the diagnostic probability should not be disregarded. Sepsis in abdominal origin andnecrotising enterocolitis are two of the major complicationsof which the physician should be prevented, even when, asreported in the present case, even patients who are opposedto the main factors of risk described in literature, such asage, can develop a HD box and a latent risk of complicationlikethe rest of patients that if shared these risk factors. Objective: To describe a case of Hirschsprung's disease. Material and methods: a descriptive, retrospective studyabout Hirschsprung's disease clinical case presenta-tion. Results: Describes a case of Hirschsprung's disease inpediatric patient with complications and resolution satisfactory quirurgica. Conclusions: The proper implementation of the clinicalmethod allows an accurate diagnosis and timely treatmentof Hirschsprung's disease.Introducción: La Enfermedad deHirschsprung (EH) es dentro del contexto clínico-quirúrgico una de las patologías pediátricas que menor incidencia posee, representando a penas el 2,7% de todas ellas según datos del Colegio Americano de Pediatría (ACP). Sin embargo, su fisiopatología y su comportamiento clínico regido por la edad del paciente son las principales variables que complican el diagnóstico y dan errores de hasta un 35% (ACP). La mortalidad de los pacientes puede ascender hasta un 65% cuando la EHse complica con un cuadro de enterocolitis necrotizante, en un paciente que no se ha conseguido la eliminación de meconio dentro de las 12 primeras horas de vida deberá sospecharse de EH, siempre tomando en cuenta la edad del pacientey recordando que en pretérminos el retraso del mismopuede considerarse normal, mientras que en el caso de pacientes más grandes de edadla incidencia de la patología es menor, sin embargo la probabilidad diagnóstica no debe de ser menospreciada. La sepsis de origen abdominal y enterocolitis necrotizante son dos de las grandes complicaciones de las cuales el médico debe estar prevenido, más aún, cuando, como se relata en el presente caso clínico, incluso pacientes que se contraponen a los principales factores de riesgo descritos por la literatura, como la edad, pueden desarrollar un cuadro de EH y tener un riesgo latente de complicación al igual que el resto de pacientes que si comparten dichos factores de riesgos. Objetivo: Describir un caso clínico de Enfermedad de Hirschsprung. Material y métodos: Se realizó un estudio descriptivo, retrospectivo, presentación de caso clínico sobre Enfermedad de Hirschsprung. Resultados: Se describe un caso de Enfermedad de Hirschsprung en paciente pediátrico con complicaciones y resolución quirpurgica satisfactoria. Conclusiones: La adecuada aplicación del método clínico permite un diagnóstico preciso y tratamiento oportuno de la Enfermedad de Hirschsprung

    A Hubble Space Telescope ACS Search for Brown Dwarf Binaries in the Pleiades Open Cluster

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    We present the results of a high-resolution imaging survey for brown dwarf binaries in the Pleiades open cluster. The observations were carried out with the Advance Camera for Surveys onboard the Hubble Space Telescope. Our sample consists of 15 bona-fide brown dwarfs. We confirm 2 binaries and detect their orbital motion, but we did not resolve any new binary candidates in the separation range between 5.4AU and 1700AU and masses in the range 0.035--0.065~Msun. Together with the results of our previous study (Martin et al., 2003), we can derive a visual binary frequency of 13.3−4.3+13.7^{+13.7}_{-4.3}\% for separations greater than 7~AU masses between 0.055--0.065~M_{\sun} and mass ratios between 0.45--0.9<q<<q<1.0. The other observed properties of Pleiades brown dwarf binaries (distributions of separation and mass ratio) appear to be similar to their older counterparts in the field.Comment: 29 pages, 7 figures, 6 tables, accepted for publication in Ap

    Enfermedad de Hirschsprung, a propósito de un caso

    Get PDF
    Introduction: Hirschsprung's disease (HD) is within theclinical context one of Pediatric diseases that lowerIncidencehas, representing barely 2.7% of all of them, according todata from the American College of Pediatrics (ACP). However, its pathophysiologyand clinical behavior governed by the age of the patient are&nbsp;the main variablesthat complicate the diagnosis and give errors of up to 35%(ACP). The mortality of patients can amount up to 65% whenthe EH is complicated with a picture of Necrotizingenterocolitis, in a patient who has notbeen theeliminationof meconium within the first 12 hours of life must suspecteh, always takinginto account the patient's age and recallingthat preterm the same delay can be considered normal, while in the case oflarger aged patients the incidence of thedisease is lower, however the diagnostic probability should not be disregarded. Sepsis in abdominal origin andnecrotising enterocolitis are two of the major complicationsof which the physician should be prevented, even when, asreported in the present case, even patients who are opposedto the main factors of risk described in literature, such asage, can develop a HD box and a latent risk of complicationlikethe rest of patients that if shared these risk factors. Objective: To describe a case of Hirschsprung's disease. Material and methods: a descriptive, retrospective studyabout Hirschsprung's disease clinical case presenta-tion. Results: Describes a case of Hirschsprung's disease inpediatric patient with complications and resolution satisfactory quirurgica. Conclusions: The proper implementation of the clinicalmethod allows an accurate diagnosis and timely treatmentof Hirschsprung's disease.Introducción: La Enfermedad deHirschsprung (EH) es dentro del contexto clínico-quirúrgico una de las patologías pediátricas que menor incidencia posee, representando a penas el 2,7% de todas ellas según datos del Colegio Americano de Pediatría (ACP). Sin embargo, su fisiopatología y su comportamiento clínico regido por la edad del paciente son las principales variables que complican el diagnóstico y dan errores de hasta un 35% (ACP). La mortalidad de los pacientes puede ascender hasta un 65% cuando la EHse complica con un cuadro de enterocolitis necrotizante, en un paciente que no se ha conseguido la eliminación de meconio dentro de las 12 primeras horas de vida deberá sospecharse de EH, siempre tomando en cuenta la edad del pacientey recordando que en pretérminos el retraso del mismopuede considerarse normal, mientras que en el caso de pacientes más grandes de edadla incidencia de la patología es menor, sin embargo la probabilidad diagnóstica no debe de ser menospreciada. La sepsis de origen abdominal y enterocolitis necrotizante son dos de las grandes complicaciones de las cuales el médico debe estar prevenido, más aún, cuando, como se relata en el presente caso clínico, incluso pacientes que se contraponen a los principales factores de riesgo descritos por la literatura, como la edad, pueden desarrollar un cuadro de EH y tener un riesgo latente de complicación al igual que el resto de pacientes que si comparten dichos factores de riesgos. Objetivo: Describir un caso clínico de Enfermedad de Hirschsprung. Material y métodos: Se realizó un estudio descriptivo, retrospectivo, presentación de caso clínico sobre Enfermedad de Hirschsprung. Resultados: Se describe un caso de Enfermedad de Hirschsprung en paciente pediátrico con complicaciones y resolución quirpurgica satisfactoria. Conclusiones: La adecuada aplicación del método clínico permite un diagnóstico preciso y tratamiento oportuno de la Enfermedad de Hirschsprung

    Deployment and performance of a Low-Energy-Threshold Skipper-CCD inside a nuclear reactor

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    Charge Coupled Devices (CCD) are used for reactor neutrino experiments and already shown their potential in constraining new physics models. The prospect of a Skipper-CCD experiment looking for standard and beyond standard model physics (BSM) in a nuclear reactor has been recently evaluated for different benchmark scenarios. Here we report the installation of the first 2 g Skipper-CCD inside the containment building of a 2 GWth_{th} nuclear power plant, positioned 12 meters from the center of the reactor core. We discuss the challenges involved in the commissioning of the detector and present data acquired during reactor ON and reactor OFF periods, with the detector operating with a sub-electron readout noise of 0.17 e-. The ongoing efforts to improve sensitivities to CEvNS and BSM interaction are also discussed.Comment: 12 pages, 7 figures, 1 tabl
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