Caracterización de un modelo de colitis en ratones knockout inducibles para adrenomedulina

Introducción: La adrenomedulina (AM) es un péptido biológicamente activo que es capaz de mejorar el pronóstico y progresión de las enfermedades inflamatorias intestinales (IBD), tanto en modelos animales, como en estudios piloto en pacientes con colitis ulcerosa severa. Recientemente se ha descubierto un polimorfismo en el gen de la AM que conduce a niveles plasmáticos más bajos de esta hormona en individuos portadores, lo que podría tener como consecuencia una mayor predisposición a padecer IBD, así como una mayor severidad clínica y/o una peor respuesta al tratamiento de estas enfermedades. Para conseguir una demostración formal de los efectos que los niveles endógenos de AM puedan tener en las IBD se necesita un abordaje genético, en el que se delecione este gen de todo el organismo. Objetivo: Pretendemos generar el primer modelo knock-out (KO) para AM viable, que permita establecer si existe o no relación entre la expresión de AM y el desarrollo y grado de patogénesis de las IBD. La hipótesis de la que partimos es que la ausencia de AM conducirá a una mayor severidad de la enfermedad. (…) Conclusiones: Todos los resultados de este trabajo apoyan el papel protector de la AM endógena frente al desarrollo de la colitis aguda inducida en ratón, siendo su efecto especialmente beneficioso en las hembrasMáster Universitario en Investigación en Ciencias de la SaludUnibertsitate Masterra Osasun Zientzietako Ikerketa

Prevention of Bone Loss in a Model of Postmenopausal Osteoporosis through Adrenomedullin Inhibition

Despite recent advances in the understanding and treatment options for osteoporosis, this condition remains a serious public health issue. Adrenomedullin (AM) is a regulatory peptide with reported activity on bone remodeling. To better understand this relationship we built an inducible knockout for AM. An outstanding feature of knockout mice is their heavier weight due, in part, to the presence of denser bones. The femur of knockout animals was denser, had more trabeculae, and a thicker growth plate than wild type littermates. The endocrine influence of AM on bone seems to be elicited through an indirect mechanism involving, at least, the regulation of insulin, glucose, ghrelin, and calcitonin gene-related peptide (CGRP). To confirm the data we performed a pharmacological approach using the AM inhibitor 16311 in a mouse model of osteoporosis. Ovariectomized females showed significant bone mass loss, whereas ovariectomized females treated with 16311 had similar bone density to sham operated females. In conclusion, we propose the use of AM inhibitors for the treatment of osteoporosis and other conditions leading to the loss of bone mass

Diurnal source apportionment of organic and inorganic atmospheric particulate matter at a high-altitude mountain site under summer conditions (Sierra Nevada; Spain)

This work was supported by the CuanTox (CTM2015-71832-P), Intempol (PGC2018-102288-B-I00) and BioCloud project (RTI2018.101154.A.I00) funded by MCIN/AEI/10.13039/501100011033 and FEDER "ERDF a way of making Europe" and NUCLEUS project (PID2021-128757OB-I00) funded by MCIN/AEI/10.13039/501100011033 and the "European Union NextGenerationEU/PRTR". The study was partially funded by the European Union's Horizon 2020 research and innovation program through project ACTRIS.IMP (grant agreement No 871115) and ATMO_ACCESS (grant agreement No 101008004), by the Spanish Ministry of Science and Innovation through projects ELPIS (PID2020-120015RB-I00), and ACTRIS-Espana (RED2022-134824-E), by the Junta de Andalucia Excellence project ADAPNE (P20-00136) and AEROPRE (P-18-RT -3820). This research was partially supported by University of Granada Plan Propio through Singular Laboratory AGORA (LS2022-1) and Scientific Units of Excellence Program (grant no. UCE-PP2017-02). IDAEA-CSIC is a Severo Ochoa Centre of Research Excellence (Spanish Ministry of Science and Innovation, CEX2018-000794-S). Funding from Generalitat de Catalunya, Research Group 2021SGR00986, is acknowledged. C.J. thanks the financial support from a Training of University Teachers (FPU 19/06826) grant from the Ministry of Science and Innovation (Spain).High-altitude mountain areas are sentinel ecosystems for global environmental changes such as anthropogenic pollution. In this study, we report a source apportionment of particulate material with an aerodynamic diameter smaller than 10 μm (PM10) in a high-altitude site in southern Europe (Sierra Nevada Station; SNS (2500 m a.s.l.)) during summer 2021. The emission sources and atmospheric secondary processes that determine the composition of aerosol particles in Sierra Nevada National Park (Spain) are identified from the concentrations of organic carbon (OC), elemental carbon (EC), 12 major inorganic compounds, 18 trace elements and 44 organic molecular tracer compounds in PM10 filter samples collected during day- and nighttime. The multivariate analysis of the joint dataset resolved five main PM10 sources: 1) Saharan dust, 2) advection from the urbanized valley, 3) local combustion, 4) smoke from a fire-event, and 5) aerosol from regional recirculation with high contribution of particles from secondary inorganic and organic aerosol formation processes. PM sources were clearly associated with synoptic meteorological conditions, and day- and nighttime circulation patterns typical of mountainous areas. Although a local pollution source was identified, the contribution of this source to PM10, OC and EC was small. Our results evidence the strong influence of middle- and long-range transport of aerosols, mainly from anthropogenic origin, on the aerosol chemical composition at this remote site.CuanTox CTM2015-71832-PIntempol PGC2018-102288-B-I00MCIN/AEI RTI2018.101154.A.I00, PID2021-128757OB-I00Marie Curie ActionsEuropean Union (EU)European Union's Horizon 2020 research and innovation program through project ACTRIS.IMP 871115ATMO_ACCESS 101008004Spanish Government PID2020-120015RB-I00ACTRIS-España RED2022-134824-EJunta de Andalucia P20-00136AEROPRE P-18-RT -3820University of Granada Plan Propio LS2022-1Scientific Units of Excellence Program UCE-PP2017-02Severo Ochoa Centre of Research Excellence (Spanish Ministry of Science and Innovation) CEX2018-000794-SGeneralitat de Catalunya 2021SGR00986Spanish Government FPU 19/0682

Diferencias en el perfil de derivación recibido en los centros de rehabilitación psicosocial en función del género.

Introducción: La percepción de los profesionales que trabajan en recursos de atención social a personas con trastorno mental grave apunta a la existencia de diferencias en las características de los hombres y mujeres que llegan a estos dispositivos. Material y Método: Este trabajo pretende ser una aproximación al análisis de dichas diferencias, para lo cual se ha comparado el perfil sociodemográfico y clínico-psiquiátrico de los hombres y mujeres derivados a los Centros de Rehabilitación Psicosocial de San Fernando de Henares, Alcalá de Henares y La Elipa, pertenecientes a la Red de recursos de atención social a personas con enfermedad mental grave y duradera de la Comunidad de Madrid, durante un período de cinco años. Durante esos años u total de 302 personas fueron derivadas a estos recursos, 188 varones y 114 mujeres. La muestra total se dividió en dos grupos: hombres-mujeres y se realizaron las tablas de contingencia y los análisis estadísticos pertinentes de las variables referidas. Resultados: Los análisis realizados indican que las mujeres que son derivadas a estos recursos son más mayores que los hombres, tienen en mayor medida certificado de minusvalía, cobran más a menudo pensiones no contributivas, no tienen una profesión definida y llegan tras un periodo de evolución mayor del trastorno

Análisis de los resultados de la encuesta sobre innovación en los festivales de música antigua de REMA

En este trabajo se pretende identificar las innovaciones que tienen lugar en los festivales de música antigua y averiguar en qué medida los diversos tipos de interesados, especialmente los patrocinadores, influyen en su consecución

Architectural Fire Protection Learning: the ETSAUN Case

Fire protection is a main parameter in the design of buildings, although it is often neglected in the Schools of Architecture because is being considered an “engineering thing”. In Spain, the education system provides a minimum dedication for this matter, but in the case that will be presented in the paper, it has been taken to a higher level. This is because fire protection is provided in three courses as we described in the article. This article will show the teaching itinerary in Architecture Studies Degrees explaining the dynamics of each of the three courses in which students are trained in fire protection, illustrated with real examples of work from the students themselves. We anticipate here that in the first year, students learn the theory, its impact on the Project; in the second year of learning, they relate it to the project at hand; and in the third, this time independently, consolidate learning in a complex project that takes place over two semesters. This teaching experience includes also the description from developing apps for smartphones, to the students practices of fire protection in the Laboratory. Far away from the opportunity of research and specialization that Fire Safety provides for future architects and construction engineers, it must be taken into account that Fire Safety it is not a limitation, Fire Safety becomes more real the architectural project

The transcribed pseudogene RPSAP52 enhances the oncofetal HMGA2-IGF2BP2-RAS axis through LIN28B-dependent and independent let-7 inhibition

Altres ajuts: We thank CERCA Program/Generalitat de Catalunya for their institutional support. This work was also supported by the Fundació La Marató de TV3, grant number #20131610 (S.G.), the AECC-Junta de Barcelona (S.G.), the Fundación Científica de la AECC under grant GCB13131578DEÁ (O.M.T.), the Health and Science Departments of the Catalan Government (Gen-eralitat de Catalunya). C.O.-M. is a pre-doctoral fellow funded by the Basque Government (PRE_2013_1_1009).One largely unknown question in cell biology is the discrimination between inconsequential and functional transcriptional events with relevant regulatory functions. Here, we find that the oncofetal HMGA2 gene is aberrantly reexpressed in many tumor types together with its antisense transcribed pseudogene RPSAP52. RPSAP52 is abundantly present in the cytoplasm, where it interacts with the RNA binding protein IGF2BP2/IMP2, facilitating its binding to mRNA targets, promoting their translation by mediating their recruitment on polysomes and enhancing proliferative and self-renewal pathways. Notably, downregulation of RPSAP52 impairs the balance between the oncogene LIN28B and the tumor suppressor let-7 family of miRNAs, inhibits cellular proliferation and migration in vitro and slows down tumor growth in vivo. In addition, high levels of RPSAP52 in patient samples associate with a worse prognosis in sarcomas. Overall, we reveal the roles of a transcribed pseudogene that may display properties of an oncofetal master regulator in human cancers

Hepatic galectin-3 is associated with lipid droplet area in non-alcoholic steatohepatitis in a new swine model

Non-alcoholic fatty liver disease (NAFLD) is currently a growing epidemic disease that can lead to cirrhosis and hepatic cancer when it evolves into non-alcoholic steatohepatitis (NASH), a gap not well understood. To characterize this disease, pigs, considered to be one of the most similar to human experimental animal models, were used. To date, all swine-based settings have been carried out using rare predisposed breeds or long-term experiments. Herein, we fully describe a new experimental swine model for initial and reversible NASH using cross-bred animals fed on a high saturated fat, fructose, cholesterol, cholate, choline and methionine-deficient diet. To gain insight into the hepatic transcriptome that undergoes steatosis and steatohepatitis, we used RNA sequencing. This process significantly up-regulated 976 and down-regulated 209 genes mainly involved in cellular processes. Gene expression changes of 22 selected transcripts were verified by RT-qPCR. Lipid droplet area was positively associated with CD68, GPNMB, LGALS3, SLC51B and SPP1, and negatively with SQLE expressions. When these genes were tested in a second experiment of NASH reversion, LGALS3, SLC51B and SPP1 significantly decreased their expression. However, only LGALS3 was associated with lipid droplet areas. Our results suggest a role for LGALS3 in the transition of NAFLD to NASH

Cumulative exposure to tacrolimus and incidence of cancer after liver transplantation

Cancer is the leading cause of death after liver transplantation (LT). This multicenter case–control nested study aimed to evaluate the effect of maintenance immunosuppression on post-LT malignancy. The eligible cohort included 2495 LT patients who received tacrolimus-based immunosuppression. After 13 922 person/years follow-up, 425 patients (19.7%) developed malignancy (cases) and were matched with 425 controls by propensity score based on age, gender, smoking habit, etiology of liver disease, and hepatocellular carcinoma (HCC) before LT. The independent predictors of post-LT malignancy were older age (HR = 1.06 [95% CI 1.05–1.07]; p < .001), male sex (HR = 1.50 [95% CI 1.14–1.99]), smoking habit (HR = 1.96 [95% CI 1.42–2.66]), and alcoholic liver disease (HR = 1.53 [95% CI 1.19–1.97]). In selected cases and controls (n = 850), the immunosuppression protocol was similar (p = .51). An increased cumulative exposure to tacrolimus (CET), calculated by the area under curve of trough concentrations, was the only immunosuppression-related predictor of post-LT malignancy after controlling for clinical features and baseline HCC (CET at 3 months p = .001 and CET at 12 months p = .004). This effect was consistent for de novo malignancy (after excluding HCC recurrence) and for internal neoplasms (after excluding non-melanoma skin cancer). Therefore, tacrolimus minimization, as monitored by CET, is the key to modulate immunosuppression in order to prevent cancer after LT