Macroecology and ecoinformatics: evaluating the accuracy of the ecological niche models calibrated with species occurrence data with biases and/or errors

Hoy en día es común estudiar los patrones globales de biodiversidad a partir de las predicciones generadas por diferentes modelos de nicho ecológico. Habitualmente, estos modelos se calibran con datos procedentes de bases de datos de libre acceso (e.g. GBIF). Sin embargo, a pesar de la facilidad de descarga y de la accesibilidad de los datos, la información almacenada sobre las localidades donde están presentes las especies suele tener sesgos y errores. Estos problemas en los datos de calibración pueden modificar drásticamente las predicciones de los modelos y con ello pueden enmascarar los patrones macroecológicos reales. El objetivo de este trabajo es investigar qué métodos producen resultados más precisos cuando los datos de calibración incluyen sesgos y cuáles producen mejores resultados cuando los datos de calibración tienen, además de sesgos, errores. Para ello creado una especie virtual, hemos proyectado su distribución en la península ibérica, hemos muestreado su distribución de manera sesgada y hemos calibrado dos tipos de modelos de distribución (Bioclim y Maxent) con muestras de distintos tamaños. Nuestros resultados indican que cuando los datos sólo están sesgados, los resultados de Bioclim son mejores que los de Maxent. Sin embargo, Bioclim es extremadamente sensible a la presencia de errores en los datos de calibración. En estas situaciones, el comportamiento de Maxent es mucho más robusto y las predicciones que proporciona son más ajustadas.In spite of the biases and errors of the open access biodiversity databases we need to take advantage of the occurrences stored in those databases for analyzing the global patterns of biodiversity. Here, we aimed to test which modelling method produces better predictions when calibrated with data samples that have biases and errors. We tested two different methods, a complex one, Maxent, and a simple one, Bioclim. We created a virtual species, sampled its distribution with both, bias and errors, and calibrated the models with those samples. Results indicated that Bioclim produces better predictions than Maxent when calibrated with biased data sets. Bioclim did not overestimate the species’ range and it was able to produce accurate predictions even when calibrated with small and biased data samples (25-50 points). However, when wrong occurrences were included in the calibration samples, Bioclim over-predicted the species’ range. Our experiments indicated that in that case, Maxent predictions remained robust and provided accurate maps. Thus, if the calibration data samples have just biases, Bioclim provided better maps than Maxent. However, when samples have both, biases and wrong occurrences, Maxent model provided better results than Bioclim.Este trabajo se enmarca dentro de los proyectos: “Support of establishment, development and mobility of quality research teams at the Charles University” CZ.1.07/2.3.00/30.0022, financiado por la European Science Foundation y la República Checa (S.Varela); y “Potential effects of climate change on Natura 2000 conservation targets in Castilla-La Mancha (CLICHE)” (Ref. no.: POIC10-0311-0585), financiado por el gobierno de Castilla La-Mancha, España (S. Varela, R. G. Mateos, R. García-Valdés, and F. Fernández-González)

Design, development, and characterization of an idebenone-loaded poly-ε-caprolactone intravitreal implant as a new therapeutic approach for LHON treatment

Leber's Hereditary Optic Neuropathy (LHON) is a hereditary mitochondrial neurodegenerative disease of unclear etiology and lack of available therapeutic alternatives. The main goal of the current pilot study was based on the evaluation of the feasibility and characteristics of prolonged and controlled idebenone release from a PCL intravitreal implant. The design, development, and characterization of idebenone-loaded PCL implants prepared by an homogenization/extrusion/solvent evaporation method allowed the obtention of high PY, EE and LC values. In vitro characterization was completed by the assessment of mechanical and instrumental properties. The in vitro release of idebenone from the PCL implants was assessed and the implant erosion was monitored by the mass loss and surface morphology changes. DSC was used to estimate stability and interaction among implant’s components. The present work demonstrated the controlled and prolonged idebenone delivery from the PCL implants in an in vitro model. A consistent preclinical base was established, supporting the idea of idebenone-loaded PCL implants as a new strategy of long-term sustained intraocular delivery for the LHON treatmentRVF acknowledges the financial support of the FIDIS (Health Research Institute of Santiago de Compostela Foundation). This work was supported by the Spanish Ministry of Science, Innovation and Universities (RTI2018-099597-B-100)S

La calidad de vida relacionada con la salud en fumadores que han recaído

Background: Previous studies have shown that smoking is associated with health-related quality of life (HRQoL) impairment. In order to evaluate HRQoL in a sample of Spanish relapsers, a cross-sectional study was conducted. Method: The sample was made up of 775 smokers who had relapsed after a period of abstinence. HRQoL was evaluated using the Euro-Qol questionnaire (EQ-5D); through the descriptive profi le, the EQ-5D index and the visual analogue scale (EQ-VAS). Results: Higher nicotine dependence was related to worse HRQL. According to the EQ-VAS, higher daily cigarette consumption and more years smoking were related to worse perceived health. In the EQ-5D those who had quit smoking in the previous year perceived worse health. Mobility and anxiety / depression are the dimensions affected by smoking. Those who are more nicotine dependent (OR = 2.29) and have been smoking for longer (OR = 4.12) are more likely to have mobility problems; and those who are nicotine dependent (OR = 1.85) and relapsed more than a year ago (OR = 0.63), are more likely to experience anxiety / depression. Conclusions: Nicotine dependence demonstrated a determining effect on HRQOL deterioration in smokers who have relapsedAntecedentes: estudios previos demuestran que fumar produce un deterioro de la calidad de vida relacionada con la salud (CVRS). Para evaluar la CVRS en fumadores españoles que han recaído se realizó un estudio transversal. Método: la muestra estaba formada por 775 fumadores que habían recaído tras un período de abstinencia. La CVRS se evaluó mediante el cuestionario Euro-Qol 5D (EQ-5D), utilizando el perfi l descriptivo, el índice EQ-5D y la escala visual-analógica (EQ-EVA). Resultados: a mayor dependencia de la nicotina peor CVRS. En la EQEVA, a mayor consumo diario de cigarrillos y más años consumiendo, peor estado de salud percibido. En el EQ-5D los que dejaron de fumar en el último año son los que perciben peor estado de salud. Movilidad y ansiedad/depresión son las dimensiones afectadas en esta muestra de fumadores que han recaído. Es más probable que tengan problemas en movilidad los que tienen dependencia (OR = 2,29) y llevan más años fumando (OR = 4,12), y es más probable que presenten ansiedad/depresión los dependientes (OR = 1,85) y los que recayeron hace más de un año (OR = 0,63). Conclusiones: la dependencia de la nicotina mostró un efecto determinante en el deterioro de la CVRS en fumadores que han recaídoThis research was supported by Spanish Ministerio de Economía y Competitividad (References: PSI2012-31196) and FEDER (European Regional Development Fund)S

Identification of Potential Kinase Inhibitors within the PI3K/AKT Pathway of Leishmania Species

Leishmaniasis is a public health disease that requires the development of more effective treatments and the identification of novel molecular targets. Since blocking the PI3K/AKT pathway has been successfully studied as an effective anticancer strategy for decades, we examined whether the same approach would also be feasible in Leishmania due to their high amount and diverse set of annotated proteins. Here, we used a best reciprocal hits protocol to identify potential protein kinase homologues in an annotated human PI3K/AKT pathway. We calculated their ligandibility based on available bioactivity data of the reported homologues and modelled their 3D structures to estimate the druggability of their binding pockets. The models were used to run a virtual screening method with molecular docking. We found and studied five protein kinases in five different Leishmania species, which are AKT, CDK, AMPK, mTOR and GSK3 homologues from the studied pathways. The compounds found for different enzymes and species were analysed and suggested as starting point scaffolds for the design of inhibitors. We studied the kinases’ participation in protein–protein interaction networks, and the potential deleterious effects, if inhibited, were supported with the literature. In the case of Leishmania GSK3, an inhibitor of its human counterpart, prioritized by our method, was validated in vitro to test its anti-Leishmania activity and indirectly infer the presence of the enzyme in the parasite. The analysis contributes to improving the knowledge about the presence of similar signalling pathways in Leishmania, as well as the discovery of compounds acting against any of these kinases as potential molecular targets in the parasite.Fil: Ochoa, Rodrigo. Universidad de Antioquia; ColombiaFil: Ortega Pajares, Amaya. University of Melbourne; AustraliaFil: Castello, Florencia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; ArgentinaFil: Serral, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; ArgentinaFil: Fernández Do Porto, Darío Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Villa Pulgarin, Janny A.. Coorporación Universitaria Remington; ColombiaFil: Varela M., Rubén E.. Universidad Santiago de Cali; ColombiaFil: Muskus, Carlos. Universidad de Antioquia; Colombi

Análisis comparativo de los condicionantes extra-escolares del desempeño de los alumnos de 3º y 6º año en Matemática y en Lengua de la Educación Primaria (ONE/2007). Modelos multinivel bivariados

Este trabajo realiza un análisis comparativo de los factores externos (factores extra-escolares) de los resultados en las pruebas de 3º y 6º de primaria del ONE/2007. Tal comparación contempla solamente dos variables individuales del alumno -sexo y edad– y un conjunto de indicadores de la ‘composición’ del alumnado de la escuela, construidos con datos provenientes del Cuestionario del Alumno de 6º. Para el análisis de los datos se utilizan modelos ‘multinivel bivariados’, a través de los cuales es posible analizar, de forma conjunta, el efecto de diversos factores sobre los resultados en las pruebas de Matemática y de Lengua

Operativo Nacional de Evaluación 2007.Análisis comparativo de los condicionantes extra-escolares del desempeño de los alumnos de 3º y 6º año en Matemática y en Lengua de la Educación Primaria (ONE/2007). Modelos multinivel bivariados

Este trabajo realiza un análisis comparativo de los factores externos (factores extra-escolares) de los resultados en las pruebas de 3º y 6º de primaria del ONE/2007. Tal comparación contempla solamente dos variables individuales del alumno -sexo y edad– y un conjunto de indicadores de la ‘composición’ del alumnado de la escuela, construidos con datos provenientes del Cuestionario del Alumno de 6º. Para el análisis de los datos se utilizan modelos ‘multinivel bivariados’, a través de los cuales es posible analizar, de forma conjunta, el efecto de diversos factores sobre los resultados en las pruebas de Matemática y de Lengua

Advances in Parkinson’s Disease: 200 Years Later

When James Parkinson described the classical symptoms of the disease he could hardly foresee the evolution of our understanding over the next two hundred years. Nowadays, Parkinson’s disease is considered a complex multifactorial disease in which genetic factors, either causative or susceptibility variants, unknown environmental cues, and the potential interaction of both could ultimately trigger the pathology. Noteworthy advances have been made in different fields from the clinical phenotype to the decoding of some potential neuropathological features, among which are the fields of genetics, drug discovery or biomaterials for drug delivery, which, though recent in origin, have evolved swiftly to become the basis of research into the disease today. In this review, we highlight some of the key advances in the field over the past two centuries and discuss the current challenges focusing on exciting new research developments likely to come in the next few years. Also, the importance of pre-motor symptoms and early diagnosis in the search for more effective therapeutic options is discussed

miR-873-5p targets mitochondrialGNMT-Complex II interface contributing tonon-alcoholic fatty liver disease

Objective:Non-alcoholic fatty liver disease (NAFLD) is a complex pathology in which several dysfunctions, including alterations in metabolicpathways, mitochondrial functionality and unbalanced lipid import/export, lead to lipid accumulation and progression to inflammation andfibrosis.The enzyme glycine N-methyltransferase (GNMT), the most important enzyme implicated in S-adenosylmethionine catabolism in the liver, isdownregulated during NAFLD progression. We have studied the mechanism involved in GNMT downregulation by its repressor microRNA miR-873-5p and the metabolic pathways affected in NAFLD as well as the benefit of recovery GNMT expression.Methods:miR-873-5p and GNMT expression were evaluated in liver biopsies of NAFLD/NASH patients. Differentin vitroandin vivoNAFLD murinemodels were used to assess miR-873-5p/GNMT involvement in fatty liver progression through targeting of the miR-873-5p as NAFLD therapy.Results:We describe a new function of GNMT as an essential regulator of Complex II activity in the electron transport chain in the mitochondria.In NAFLD, GNMT expression is controlled by miR-873-5p in the hepatocytes, leading to disruptions in mitochondrial functionality in a preclinicalmurine non-alcoholic steatohepatitis (NASH) model. Upregulation of miR-873-5p is shown in the liver of NAFLD/NASH patients, correlating withhepatic GNMT depletion. Importantly, NASH therapies based on anti-miR-873-5p resolve lipid accumulation, inflammation andfibrosis byenhancing fatty acidb-oxidation in the mitochondria. Therefore, miR-873-5p inhibitor emerges as a potential tool for NASH treatment.Conclusion:GNMT participates in the regulation of metabolic pathways and mitochondrial functionality through the regulation of Complex II activityin the electron transport chain. In NAFLD, GNMT is repressed by miR-873-5p and its targeting arises as a valuable therapeutic option for treatment

Magnesium accumulation upon cyclin M4 silencing activates microsomal triglyceride transfer protein improving NASH

Background & Aims: Perturbations of intracellular magnesium (Mg) homeostasis have implications for cell physiology. The cyclin M family, CNNM, perform key functions in the transport of Mg across cell membranes. Herein, we aimed to elucidate the role of CNNM4 in the development of non-alcoholic steatohepatitis (NASH). Methods: Serum Mg levels and hepatic CNNM4 expression were characterised in clinical samples. Primary hepatocytes were cultured under methionine and choline deprivation. A 0.1% methionine and choline-deficient diet, or a choline-deficient high-fat diet were used to induce NASH in our in vivo rodent models. Cnnm4 was silenced using siRNA, in vitro with DharmaFECT and in vivo with Invivofectamine® or conjugated to N-acetylgalactosamine. Results: Patients with NASH showed hepatic CNNM4 overexpression and dysregulated Mg levels in the serum. Cnnm4 silencing ameliorated hepatic lipid accumulation, inflammation and fibrosis in the rodent NASH models. Mechanistically, CNNM4 knockdown in hepatocytes induced cellular Mg accumulation, reduced endoplasmic reticulum stress, and increased microsomal triglyceride transfer activity, which promoted hepatic lipid clearance by increasing the secretion of VLDLs. Conclusions: CNNM4 is overexpressed in patients with NASH and is responsible for dysregulated Mg transport. Hepatic CNNM4 is a promising therapeutic target for the treatment of NASH. Lay summary: Cyclin M4 (CNNM4) is overexpressed in non-alcoholic steatohepatitis (NASH) and promotes the export of magnesium from the liver. The liver-specific silencing of Cnnm4 ameliorates NASH by reducing endoplasmic reticulum stress and promoting the activity of microsomal triglyceride transfer protein.Ministerio de Ciencia e Innovación, Programa Retos-Colaboración RTC2019-007125-1 (for JS and MLM-C); Instituto de Salud Carlos III, Proyectos de Investigación en Salud DTS20/00138 (for JS and MLM-C); Departamento de Industria del Gobierno Vasco (for MLM-C); Ministerio de Ciencia, Innovación y Universidades MICINN: SAF2017-87301-R and RTI2018-096759-A-100 integrado en el Plan Estatal de Investigación Cientifica y Técnica y Innovación, cofinanciado con Fondos FEDER (for MLM-C and TCD, respectively); BIOEF (Basque Foundation for Innovation and Health Research); EITB Maratoia BIO15/CA/014; Asociación Española contra el Cáncer (MLM-C, TCD); Fundación Científica de la Asociación Española Contra el Cancer (AECC Scientific Foundation) Rare Tumor Calls 2017 (for MLM); La Caixa Foundation Program (for MLM); Fundacion BBVA UMBRELLA project (for MLM); BFU2015-70067-REDC, BFU2016-77408-R, and BES-2017- 080435 (MINECO / FEDER, UE) and the FIGHT-CNNM2 project from the EJP RD Joint Transnational Call (JTC2019) (Ref. AC19/ 00073) (for LAM-C); RTI2018-095134-B-100 and Grupos de Investigación del Sistema Universitario Vasco (IT971-16) (for PA); National Institutes of Health under grant CA217817 (for DB); AGL2014-54585-R, AGL-2017-86927-R and EQC2018-004897-P from MINECO; PC0148-2016-0149 and PAI-BIO311 from Junta de Andalucía (for FM). Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III. We thank Silence Therapeutics plc. for the financial support provided. We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV- 2016-0644)