Nintedanib decreases muscle fibrosis and improves muscle function in a murine model of dystrophinopathy

Duchenne muscle dystrophy (DMD) is a genetic disorder characterized by progressive skeletal muscle weakness. Dystrophin deficiency induces instability of the sarcolemma during muscle contraction that leads to muscle necrosis and replacement of muscle by fibro-adipose tissue. Several therapies have been developed to counteract the fibrotic process. We report the effects of nintedanib, a tyrosine kinase inhibitor, in the mdx murine model of DMD. Nintedanib reduced proliferation and migration of human fibroblasts in vitro and decreased the expression of fibrotic genes such as COL1A1, COL3A1, FN1, TGFB1, and PDGFA. We treated seven mdx mice with 60 mg/kg/day nintedanib for 1 month. Electrophysiological studies showed an increase in the amplitude of the motor action potentials and an improvement of the morphology of motor unit potentials in the animals treated. Histological studies demonstrated a significant reduction of the fibrotic areas present in the skeletal muscles. Analysis of mRNA expression from muscles of treated mice showed a reduction in Col1a1, Col3a1, Tgfb1, and Pdgfa. Western blot showed a reduction in the expression of collagen I in skeletal muscles. In conclusion, nintedanib reduced the fibrotic process in a murine model of dystrophinopathy after 1 month of treatment, suggesting its potential use as a therapeutic drug in DMD patients.España, Ministerio de Economía y Competitividad BFU2016-74975-PEspaña, Instituto Ramón y Cajal PI13/0134

Aprendizaje cooperativo: rendimiento y satisfacción de los alumnos de inglés de 2º de ESO de Bell-lloc del Pla a corto plazo

In this research the practice of cooperative learning is introduced along four sessions in a second of ESO homogeneous English class, in a male single-sex school. Pupils’ satisfaction and their academic performance are analysed before and after introducing these mentioned methodological changes, using satisfaction surveys, objective tests about what has been worked in class from an academic point of view, and level B1 objective tests (Cambridge Preliminary English Test). The idea of pupils’ satisfaction is also analysed. The purpose of this investigation is to show that the difficulty of introducing cooperative learning in the classroom is compensated by the pupils’ satisfaction, and the fact that the academic performance might decrease in short term, that is also compensated by the attention the pupil is going to be able to pay, as he goes on with cooperative learning, whose initial results are already very positive.En el presente estudio se introduce la práctica del aprendizaje cooperativo durante cuatro sesiones en un aula de inglés de tipo homogéneo en segundo de la ESO, en una escuela diferenciada masculina. Se analizan la satisfacción de los alumnos y su rendimiento académico antes y después de haber introducido dichos cambios metodológicos, a través de encuestas de satisfacción, pruebas objetivas sobre lo que se ha trabajado desde un punto de vista académico, y pruebas objetivas de nivel B1 de inglés (Cambridge Preliminary English Test). Se analiza también la idea de satisfacción del alumno. El objetivo de este estudio es poner de manifiesto que la dificultad que conlleva la introducción del aprendizaje cooperativo en el aula se ve compensada por la satisfacción de los alumnos, y que si bien el rendimiento académico puede disminuir a corto plazo, ello se ve también compensado por el interés que podrá mostrar el alumno a medida que vaya avanzando en el aprendizaje cooperativo, cuyos resultados iniciales ya son muy positivos

Wear Mechanisms in Press Hardening: An Analysis through Comparison of Tribological Tests and Industrial Tools

Press hardened components have become widespread in the automotive industry in structural and crash-resistant applications, thanks to the combination of the complex shapes and high mechanical properties obtained. However, the press hardening of coated boron steel results in severe adhesive-based wear, with tool maintenance being required in as few as 3000 cycles. The current industrial implementation of press hardening is defined to work around this phenomenon. While this aspect has been studied by different authors, most of the literature deals with laboratory-scale tribosimulators, leaving an open question into how this knowledge transfers to macroscopic effects on the industrial process. In this work, wear in press hardening is studied by comparing the results obtained in laboratory conditions with a pilot-scale line, and finally, with wear mechanisms observed on industrial tools. The aim of this study is to consolidate the current knowledge about the micro-mechanisms involved, and to understand to what extent the existing tests reproduce the actual mechanisms observed in the press floor. The results show how material transfer mainly happens as an accumulation of dust compacted into initial defects on the tool surface. Moreover, this mechanism is effectively reproduced in laboratory tribosimulators and pilot environments, showing a similar morphology to wear on industrial tools. The work sheds light on the underlying causes of wear, and its potential mitigation strategies.Validerad;2023;Nivå 2;2023-06-07 (hanlid);Funder: European Commission Research Fund for Coal and Steel (RFCS-CT-2011-00023); Spanish Ministry of Science, Innovation and UniversityRetos-Colaboración 2017 Project RTC-2017-6448-4 INNOESTAMPTestToo

Estudio químico y actividad antimicrobiana, antiinflamatoria y cardiovascular de algunas especies de esponjas pertenecientes al género x estospongia en el caribe colombiano

IP 1107-09-241-98PONENCIA(S) EN CONGRESO: Estudio quimico del extracto en hexanode la esponja marina Xestospongia proxima /;C.M. Ospina ... [et.al]. -- En: Congreso Colombiano de CienciasFarmaceuticas (2 : 2001 oct 12-14 : Cartagena;de Indias) -- Estudio quimico del extracto en acetona de la esponja marinadel Caribe Colombiano Xestospongia;muta / Eduard L. Negrete M. ... [et.al]. -- En: Congreso Colombiano de Ciencias Farmaceuticas (2 : 2001 oct;12-14 : Cartagena de Indias) -- Evaluacion antibacterianade cinco especies de esponjas del genero;Xestospongia del Caribe Colombiano / Erika Rodriguez C., Bernarda CuadradoC., Ricardo Gaitan. -- En: Congreso;Nacional de Ciencias Biologicas (36 : 2001 oct. 10-13 : Cartagena de Indias) -- Esteroles minoritarios de las;esponjas marinas Xestospongia carbonaria y Xestospongia proxima/ Erika Rodriguez C., Dario Mendez C., Ricardo;Gaitan I. -- En: Congreso Nacional de Fitoquimica (7 : 2002 abr.30-may. 3: Bogotá) -- Estudio quimico y;antibacteriano de cuatro esteroles mayoritarios aislados de dosesponjas marinas del genero xestospongia /;Dario Mendez C. ... [et.al]. -- En: Congreso Nacional de Fitoquimica (7 :2002 abr. 30-may. 3 : Bogotá

Purification and structural stability of white Spanish broom (Cytisus multiflorus) peroxidase

New plant peroxidase has been isolated to homogeneity from the white Spanish broom Cytisus multiflorus. The enzyme purification steps included homogenization, NH4SO4 precipitation, extraction of broom colored compounds and consecutive chromatography on Phenyl-Sepharose, HiTrap™ SP HP and Superdex-75 and 200. The novel peroxidase was characterized as having a molecular weight of 50 ± 3 kDa. Steady-state tryptophan fluorescence and far-UV circular dichroism (CD) studies, together with enzymatic assays, were carried out to monitor the structural stability of C. multiflorus peroxidase (CMP) at pH 7.0. Thus changes in far-UV CD corresponded to changes in the overall secondary structure of enzyme, while changes in intrinsic tryptophan fluorescence emission corresponded to changes in the tertiary structure of the enzyme. It is shown that the process of CMP denaturation can be interpreted with sufficient accuracy in terms of the simple kinetic scheme, N->D , where k is a first-order kinetic constant that changes with temperature following the Arrhenius equation; N is the native state, and D is the denatured state. On the basis of this model, the parameters of the Arrhenius equation were calculated.This work was partially supported by Projects SA-06-00-0 ITACYL-Universidad de Salamanca, SA 129A07, and SA052A10-2 funded by the Instituto Tecnológico Agrario de Castilla y León and the Consejeria de Educación de la Junta de Castilla y León (Spain).Peer reviewe

Crystal structure analysis of peroxidase from the palm tree Chamaerops excelsa

Palm tree peroxidases are known to be very stable enzymes and the peroxidase from the Chamaerops excelsa (CEP), which has a high pH and thermal stability, is no exception. To date, the structural and molecular events underscoring such biochemical behavior have not been explored in depth. In order to identify the structural characteristics accounting for the high stability of palm tree peroxidases, we solved and refined the X-ray structure of native CEP at a resolution of 2.6 Å. The CEP structure has an overall fold typical of plant peroxidases and confirmed the conservation of characteristic structural elements such as the heme group and calcium ions. At the same time the structure revealed important modifications in the amino acid residues in the vicinity of the exposed heme edge region, involved in substrate binding, that could account for the morphological variations among palm tree peroxidases through the disruption of molecular interactions at the second binding site. These modifications could alleviate the inhibition of enzymatic activity caused by molecular interactions at the latter binding site. Comparing the CEP crystallographic model described here with other publicly available peroxidase structures allowed the identification of a noncovalent homodimer assembly held together by a number of ionic and hydrophobic interactions. We demonstrate, that this dimeric arrangement results in a more stable protein quaternary structure through stabilization of the regions that are highly dynamic in other peroxidases. In addition, we resolved five N-glycosylation sites, which might also contribute to enzyme stability and resistance against proteolytic cleavage

Down syndrome as risk factor for respiratory syncytial virus hospitalization : A prospective multicenter epidemiological study

Respiratory syncytial virus (RSV) infection in childhood, particularly in premature infants, is associated with significant morbidity and mortality. To compare the hospitalization rates due to RSV infection and severity of disease between infants with and without Down syndrome (DS) born at term and without other associated risk factors for severe RSV infection. In a prospective multicentre epidemiological study, 93 infants were included in the DS cohort and 68 matched by sex and data of birth (±1 week) and were followed up to 1 year of age and during a complete RSV season. The hospitalization rate for all acute respiratory infection was significantly higher in the DS cohort than in the non-DS cohort (44.1% vs 7.7%, P<.0001). Hospitalizations due to RSV were significantly more frequent in the DH cohort than in the non-DS cohort (9.7% vs 1.5%, P=.03). RSV prophylaxis was recorded in 33 (35.5%) infants with DS. The rate of hospitalization according to presence or absence of RSV immunoprophylaxis was 3.0% vs 15%, respectively. Infants with DS showed a higher rate of hospitalization due to acute lower respiratory tract infection and RSV infection compared to non-DS infants. Including DS infants in recommendations for immunoprophylaxis of RSV disease should be considered