19 research outputs found

    Extracellular serine empowers epidermal proliferation and psoriasis-like symptoms

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    The contribution of nutrient availability to control epidermal cell proliferation, inflammation, and hyperproliferative diseases remains unknown. Here, we studied extracellular serine and serine/glycine metabolism using human keratinocytes, human skin biopsies, and a mouse model of psoriasis-like disease. We focused on a metabolic enzyme, serine hydroxymethyltransferase (SHMT), that converts serine into glycine and tetrahydrofolate-bound one‑carbon units to support cell growth. We found that keratinocytes are both serine and glycine auxotrophs. Metabolomic profiling and hypoxanthine supplementation indicated that SHMT silencing/inhibition reduced cell growth through purine depletion, leading to nucleotide loss. In addition, topical application of an SHMT inhibitor suppressed both keratinocyte proliferation and inflammation in the imiquimod model and resulted in a decrease in psoriasis-associated gene expression. In conclusion, our study highlights SHMT2 activity and serine/glycine availability as an important metabolic hub controlling both keratinocyte proliferation and inflammatory cell expansion in psoriasis and holds promise for additional approaches to treat skin diseases

    Identification of Gait Events Combining Bayesian Hidden Markov Models and Linear Regression

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    The Hidden Markov Model is a probabilistic time- series model that has recently found application in human motion analysis. HMMs are usually fit directly to time-series data obtained from motion capture systems, using Gaussian ob- servation models and the Expectation Maximization algorithm. The boundaries of the segmentation induced by the HMM are somewhat arbitrary, because the motion capture data usually consists of smooth trajectories. When a-priori segmentation is available, like in the case of clinically defined events in human gait, biasing the HMM parameters towards this prior knowledge is crucial to obtain a segmentation that is clinically relevant. To achieve this goal, we propose the combination of a fully Bayesian HMM with a sliding-window polynomial fit pre-processing step. In the context of automatic segmentation of gait time-series, we show how the proposed approach allows to better exploit a-priori segmentation, and to learn a set of motion primitives that improve the segmentation performances over classical HMMs.status: publishe

    Bayesian Hidden Markov Models for Segmentation of Gait Motion Capture Data

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    The interpretation of 3DGA data often requires the segmentation of joint angle time­series (e.g. the identification of rockers in the ankle sagittal plane kinematics). We introduce a novel method for the automatic segmentation of joint angle time­series based on a Bayesian time­series model called Hierachical Dirichlet Process Hidden Markov Model (HDP­HMM) [1]. The goal of the method is to segment a joint angle time­series in a set of piecewise polynomial curves, while at the same time estimating the curve parameters and the time­correlation between the segments. The proposed method is suited for segmention of a set of time­series, (e.g. , a set of gait cycles exhibiting a specific pattern identified by a clinician) and to learn a probabilistic shape signature that can be used for classification of gait trials. Due to its Bayesian nature, the proposed method is able to incorporate clinical prior knowledge to produce a clinically meaningful segmentation.status: publishe

    Changes in morphology, cell wall composition and soluble proteome in Rhodobacter sphaeroides cells exposed to chromate

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    The response of the carotenoidless Rhodobacter sphaeroides mutant R26 to chromate stress under photosynthetic conditions is investigated by biochemical and spectroscopic measurements, proteomic analysis and cell imaging. Cell cultures were found able to reduce chromate within 3-4 days. Chromate induces marked changes in the cellular dimension and morphology, as revealed by atomic force microscopy, along with compositional changes in the cell wall revealed by infrared spectroscopy. These effects are accompanied by significant changes in the level of several proteins: 15 proteins were found up-regulated and 15 down-regulated. The protein content found in chromate exposed cells is in good agreement with the biochemical, spectroscopic and microscopic results. Moreover at the present stage no specific chromate-reductase could be found in the soluble proteome, indicating that detoxification of the pollutant proceeds via aspecific reductants

    Effect of Moringa oleifera Leaf Powder on Postprandial Blood Glucose Response: In Vivo Study on Saharawi People Living in Refugee Camps

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    The hypoglycemic effect in humans of Moringa oleifera (MO) leaf powder has, to date, been poorly investigated. We assessed the chemical composition of MO leaf powder produced at Saharawi refugee camps, its in vitro ability to inhibit α-amylase activity, and its sensory acceptability in food. We then evaluated its effect on postprandial glucose response by randomly administering, on 2 different days, a traditional meal supplemented with 20 g of MO leaf powder (MOR20), or not (control meal, CNT), to 17 Saharawi diabetics and 10 healthy subjects. Capillary glycaemia was measured immediately before the meal and then at 30 min intervals for 3 h. In the diabetic subjects the postprandial glucose response peaked earlier with MOR20 compared to CNT and with lower increments at 90, 120, and 150 min. The mean glycemic meal response with MOR20 was lower than with CNT. The healthy subjects showed no differences. Thus, MO leaf powder could be a hypoglycemic herbal drug. However, given the poor taste acceptability of the 20 g MO meal, lower doses should be evaluated. Moreover, the hypoglycemic effects of MO leaf powder should also be demonstrated by trials evaluating its long-term effects on glycaemia

    (S)comunicazione e pandemia. Ricategorizzazioni e contrapposizioni di un'emergenza infinita

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    Nei due anni di pandemia da Sars-Cov-2 i media hanno rivestito un ruolo centrale nel fornire informazioni a una popolazione spaventata e confinata in casa a causa del cosiddetto “lockdown”. Essi non sono però canali neutri, non si limitano a veicolare le informazioni, ma interagiscono con le medesime e con gli individui. La costruzione mediale di un corpus di notizie reiterate nel tempo su un certo argomento alimenta alcuni “schemi di interpretazione”, categorie attraverso le quali gli attori sociali elaborano le proprie esperienze. Diventa dunque urgente interrogarsi con spirito critico rispetto alle narrazioni mediali di ciò che costituisce e costruisce il frame della crisi sanitaria da Covid-19. Spirito critico inteso non come atteggiamento critico o polemico verso la comunicazione dei media, ma come posizione che vuole riflettere su, e problematizzare, i contenuti e i soggetti delle comunicazioni mediali, interrogandosi anche sui differenti punti di vista presi o meno in considerazione. Il presente volume raccoglie una serie di contributi che, sotto diverse angolazioni, indagano alcune comunicazioni, talvolta parziali o polarizzanti, gli ossimori e le contrapposizioni create dalle narrazioni mediali e le ricategorizzazioni sociali profonde di concetti e attori

    A model to predict the response to therapy against hepatitis C virus (HCV) including low-density lipoprotein receptor genotype in HIV/HCV-coinfected patients

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    Accurate prediction of sustained virological response (SVR) to pegylated interferon-a (Peg-IFN) plus ribavirin in HIV/hepatitis C virus (HCV)-coinfected patients could improve the management of these patients. We aimed to develop a model to predict SVR to Peg-IFN/ribavirin in HIV/HCV-coinfected individuals combining HCV genotype and baseline HCV RNA load with interleukin 28B and low-density lipoprotein receptor genetic variations.Fil: Neukam, Karin. Hospital Universitario de Valme; EspañaFil: Almeida, Carmen. Hospital Universitario de Valme; EspañaFil: Caruz, Antonio. Universidad de Jaén; España;Fil: Rivero Juarez, Antonio. Hospital Universitario Reina Sofía. Instituto Maimónides de Investigación Biomédica de Córdoba. Unidad de Enfermedades Infecciosas; EspañaFil: Rallon, Norma. Hospital Carlos III. Departamento de Enfermedades Infecciosas; EspañaFil: Di Lello, Federico Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Herrero, Rocío. Universidad de Jaén; España;Fil: Camacho, Angela. Hospital Universitario Reina Sofía. Instituto Maimónides de Investigación Biomédica de Córdoba. Unidad de Enfermedades Infecciosas; EspañaFil: Benito, José. Hospital Carlos III. Departamento de Enfermedades Infecciosas; EspañaFil: Macias, Juan. Hospital Universitario de Valme; EspañaFil: Rivero, Antonio. Hospital Universitario Reina Sofía. Instituto Maimónides de Investigación Biomédica de Córdoba. Unidad de Enfermedades Infecciosas; EspañaFil: Soriano, Vicente. Hospital Carlos III. Departamento de Enfermedades Infecciosas; EspañaFil: Pineda, Juan Antonio. Hospital Universitario de Valme; Españ

    Variations at multiple genes improve interleukin 28B genotype predictive capacity for response to therapy against hepatitis C infection

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    To identify genetic factors that predict sustained virological response (SVR) to pegylated interferon (Peg-IFN)/ribavirin (RBV) in HIV/hepatitis C virus (HCV) genotype 1 or 4-coinfected patients and that enhance the predictive capacity of IL28B genotype in this population.Fil: Neukam, Karin. Hospital Universitario de Valme. Unidad de Enfermedades Infecciosas y Microbiología; España; Instituto de Biomedicina de Sevilla; España;Fil: Caruz, Antonio. Universidad de Jaén; España;Fil: Rivero Juarez, Antonio. Instituto Maimónides de Investigación Biomédica de Córdoba. Hospital Universitario Reina Sofía. Unidad de Enfermedades Infecciosas; España;Fil: Barreiro, Pablo. Hospital Carlos III. Departamento de Enfermedades Infecciosas; España;Fil: Merino, Dolores. Hospital Juan Ramón Jiménez. Unidad de Enfermedades Infecciosas; España;Fil: Real, Luis M.. Hospital Universitario de Valme. Unidad de Enfermedades Infecciosas y Microbiología; España; Instituto de Biomedicina de Sevilla; España;Fil: Herrero, Rocío. Universidad de Jaén; España;Fil: Camacho, Angela. Instituto Maimónides de Investigación Biomédica de Córdoba. Hospital Universitario Reina Sofía. Unidad de Enfermedades Infecciosas; España;Fil: Soriano, Vicente. Hospital Carlos III. Departamento de Enfermedades Infecciosas; España;Fil: Di Lello, Federico Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina; Hospital Universitario de Valme. Unidad de Enfermedades Infecciosas y Microbiología; España;Fil: Macias, Juan. Hospital Universitario de Valme. Unidad de Enfermedades Infecciosas y Microbiología; España; Instituto de Biomedicina de Sevilla; España;Fil: Rivero, Antonio. Instituto Maimónides de Investigación Biomédica de Córdoba. Hospital Universitario Reina Sofía. Unidad de Enfermedades Infecciosas; España;Fil: Pineda, Juan A.. Hospital Universitario de Valme. Unidad de Enfermedades Infecciosas y Microbiología; España; Instituto de Biomedicina de Sevilla; España
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