65 research outputs found

    Unveiling the spatial distribution of aflatoxin B1 and plant defense metabolites in maize using AP‐SMALDI mass spectrometry imaging

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    SUMMARYIn order to cope with the presence of unfavorable compounds, plants can biotransform xenobiotics, translocate both parent compounds and metabolites, and perform compartmentation and segregation at the cellular or tissue level. Such a scenario also applies to mycotoxins, fungal secondary metabolites with a pre‐eminent role in plant infection. In this work, we aimed to describe the effect of the interplay between Zea mays (maize) and aflatoxin B1 (AFB1) at the tissue and organ level. To address this challenge, we used atmospheric pressure scanning microprobe matrix‐assisted laser desorption/ionization mass spectrometry imaging (AP‐SMALDI MSI) to investigate the biotransformation, localization and subsequent effects of AFB1 on primary and secondary metabolism of healthy maize plants, both in situ and from a metabolomics standpoint. High spatial resolution (5 µm) provided fine localization of AFB1, which was located within the root intercellular spaces, and co‐localized with its phase‐I metabolite aflatoxin M2. We provided a parallel visualization of maize metabolic changes, induced in different organs and tissues by an accumulation of AFB1. According to our untargeted metabolomics investigation, anthocyanin biosynthesis and chlorophyll metabolism in roots are most affected. The biosynthesis of these metabolites appears to be inhibited by AFB1 accumulation. On the other hand, metabolites found in above‐ground organs suggest that the presence of AFB1 may also activate the biochemical response in the absence of an actual fungal infection; indeed, several plant secondary metabolites known for their antimicrobial or antioxidant activities were localized in the outer tissues, such as phenylpropanoids, benzoxazinoids, phytohormones and lipids

    Mechanistic models of α\alpha-synuclein homeostasis for Parkinson's disease: A blueprint for therapeutic intervention

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    Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide, yet there is no disease-modifying therapy up to this date. The biological complexity underlying PD hampers the investigation of the principal contributors to its pathogenesis. In this context, mechanistic models grounded in molecular-level knowledge provide virtual labs to uncover the primary events triggering PD onset and progression and suggest promising therapeutic targets. Multiple modeling efforts in PD research have focused on the pathological role of α\alpha-synuclein (α\alphasyn), a presynaptic protein that emerges from the intricate molecular network as a crucial driver of neurodegeneration. Here, we collect the advances in mathematical modeling of α\alphasyn homeostasis, focusing on aggregation and degradation pathways, and discussing potential modeling improvements and possible implications in PD therapeutic strategy design

    Mechanistic models of α-synuclein homeostasis for Parkinson's disease: A blueprint for therapeutic intervention

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    Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide, yet there is no disease-modifying therapy up to this date. The biological complexity underlying PD hampers the investigation of the principal contributors to its pathogenesis. In this context, mechanistic models grounded in molecular-level knowledge provide virtual labs to uncover the primary events triggering PD onset and progression and suggest promising therapeutic targets. Multiple modeling efforts in PD research have focused on the pathological role of α-synuclein (αsyn), a presynaptic protein that emerges from the intricate molecular network as a crucial driver of neurodegeneration. Here, we collect the advances in mathematical modeling of αsyn homeostasis, focusing on aggregation and degradation pathways, and discussing potential modeling improvements and possible implications in PD therapeutic strategy design

    Different Measures for Assessing Stroke Outcome

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    Background and Purpose — We sought to assess the relationship between 2 simple questions on recovery (question 1: do you feel that you have made a complete recovery from your stroke?) and dependency (question 2: do you require help from another person for everyday activities?) and the Barthel Index (BI) and Oxford Handicap Scale (OHS), as well as the relationship between BI and OHS, in a large number of Italian stroke survivors who participated in the International Stroke Trial (IST). Methods — We used data from 2423 patients interviewed by telephone at 6 months after the event. The κ statistic, sensitivity, and specificity were calculated for several comparisons. Internal consistency for BI was calculated. Results — The reliability of the dependency question compared with BI=20 (κ=0.93) and the reliability of the recovery question compared with OHS=0 (κ=0.89) were good. Sensitivity of the dependency question in predicting whether patients scored BI >18 was 0.98; sensitivity of the recovery question in predicting whether patients scored OHS=0 was 0.99. The reliability of BI=20 compared with OHS <3 was good (κ=0.87). Internal consistency of BI was very high (Cronbach's α=0.96). Conclusions — The 2 simple questions are a good means of evaluating outcome from a patient's view and of dichotomizing the stroke survivor in a time-effective and reliable way

    Services surround you:physical-virtual linkage with contextual bookmarks

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    Our daily life is pervaded by digital information and devices, not least the common mobile phone. However, a seamless connection between our physical world, such as a movie trailer on a screen in the main rail station and its digital counterparts, such as an online ticket service, remains difficult. In this paper, we present contextual bookmarks that enable users to capture information of interest with a mobile camera phone. Depending on the user’s context, the snapshot is mapped to a digital service such as ordering tickets for a movie theater close by or a link to the upcoming movie’s Web page

    Resonancia magnética versus tomografía computada para la detección de lesiones vasculares agudas en pacientes que consultan por síntomas de accidente cerebrovascular

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    ResumenAntecedentesLa resonancia magnética (RM) se utiliza cada vez con mayor frecuencia para el diagnóstico del accidente cerebrovascular isquémico agudo aunque ha sido debatida su sensibilidad para la detección precoz de la hemorragia intracerebral. La tomografía computada (TC) se usa ampliamente en el tratamiento clínico del accidente cerebrovascular agudo, especialmente para la exclusión rápida de la hemorragia intracerebral.ObjetivosComparar la precisión diagnóstica de la RM de difusión (RMD) y la CT para el accidente cerebrovascular isquémico agudo, y estimar la precisión diagnóstica de la RMD para el accidente cerebrovascular hemorrágico agudo.Estrategia de búsquedaSe efectuaron búsquedas en MEDLINE y EMBASE (enero de 1995 hasta marzo de 2009) y se examinó la bibliografía de los estudios pertinentes en busca de otras referencias.Criterios de selecciónSe seleccionaron los estudios que compararon RMD y TC en los mismos pacientes para la detección del accidente cerebrovascular isquémico o examinaron la utilidad de la RM para la detección del accidente cerebrovascular hemorrágico, que realizaron la imaginología dentro de las 12 horas de la aparición de los síntomas de accidente cerebrovascular y presentaron datos suficientes como para construir tablas de contingencia.Obtención y análisis de los datosTres autores de forma independiente extrajeron los datos de las características del estudio y las medidas de precisión. Los datos sobre el accidente cerebrovascular isquémico se evaluaron mediante metanálisis de efectos aleatorios y de efectos fijos.Resultados principalesOcho estudios, con un total de 308 participantes, cumplieron los criterios de inclusión. Siete estudios contribuyeron a la evaluación del accidente cerebrovascular isquémico y dos estudios a la evaluación del accidente cerebrovascular hemorrágico. El espectro de pacientes fue relativamente limitado en todos los estudios, los tamaños de las muestras fueron pequeños, hubo un significativo sesgo de incorporación y los procedimientos de cegamiento fueron a menudo incompletos. Entre los pacientes en quienes posteriormente se confirmó el diagnóstico de accidente cerebrovascular isquémico agudo (161/226), las estimaciones de resumen para la RMD fueron: sensibilidad 0,99 (IC del 95%: 0,23 a 1,00), especificidad 0,92 (IC del 95%: 0,83 a 0,97). Las estimaciones de resumen para la TC fueron: sensibilidad 0,39 (IC del 95%: 0,16 a 0,69), especificidad 1,00 (IC del 95%: 0,94 a 1,00).Los dos estudios sobre accidente cerebrovascular hemorrágico informaron estimaciones altas para las secuencias de difusión y ecogradiente pero tenían estándares de referencia inconsistentes. No se calcularon las estimaciones generales para estos dos estudios. No fue posible evaluar la practicidad o los temas relativos a la relación entre costo y efectividad.Conclusiones de los autoresLa RMD parece ser más sensible que la TC para la detección precoz del accidente cerebrovascular isquémico en pacientes sumamente seleccionados. Sin embargo, la variabilidad en la calidad de los estudios incluidos y la presencia de los sesgos de espectro e incorporación tornan dudosa la confiabilidad y la posibilidad de generalizar los resultados observados. Se requieren estudios adicionales bien diseñados, sin sesgos metodológicos, con muestras de pacientes más representativas y estimaciones de la practicidad y los costos, a fin de determinar qué pacientes deben ser sometidos a RM y qué pacientes a TC en el caso de presunto accidente cerebrovascular agudo
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