In vivo testing of gold nanoparticles using the Caenorhabditis elegans model organism

Gold nanoparticles (AuNPs) are present in many man-made products and cosmetics, and are also used by the food and medical industries. Tight regulations regarding the use of mammalian animals for product testing can hamper the study of the specific interactions between engineered nanoparticles and biological systems. Invertebrate models, such as the nematode Caenorhabditis elegans (C. elegans), can offer alternative approaches during the early phases of nanoparticle discovery. Here, we thoroughly evaluated the biodistribution of 11-nm and 150-nm citrate-capped AuNPs in the model organism C. elegans at multiple scales, moving from micrometric to nanometric resolution and from the organismal to cellular level. We confirmed that the nanoparticles were not able to cross the intestinal and dermal barriers. We investigated the effect of AuNPs on the survival and reproductive performance of C. elegans, and correlated these effects with the uptake of AuNPs in terms of their number, surface area, and metal mass. In general, exposure to 11-nm AuNPs resulted in a higher toxicity than the larger 150-nm AuNPs. NP aggregation inside C. elegans was determined using absorbance microspectroscopy, which allowed the plasmonic properties of AuNPs to be correlated with their confinement inside the intestinal lumen, where anatomical traits, acidic pH and the presence of biomolecules play an essential role on NP aggregation. Finally, quantitative PCR of selected molecular markers indicated that exposure to AuNPs did not significantly affect endocytosis and intestinal barrier integrity. Statement of significance This work highlights how the simple, yet information-rich, animal model C. elegans is ideally suited for preliminary screening of nanoparticles or chemicals mitigating most of the difficulties associated with mammalian animal models, namely the ethical issues, the high cost, and time constraints. This is of particular relevance to the cosmetic, food, and pharmaceutical industries, which all have to justify the use of animals, especially during the discovery, development and initial screening phases. This work provides a detailed and thorough analysis of 11-nm and 150-nm AuNPs at multiple levels of organization (the whole organism, organs, tissues, cells and molecules).Peer ReviewedPostprint (author's final draft

A actual crise planetária. Uma dimensão esquecida na educação em ciência

Afinalidade da presente investigação foi analisar qual o possível contributo da Educação em Ciência na clarificação e compreensão pública dos problemas e desafios relacionados com o futuro do nosso planeta. Iniciámos o trabalho procurando o contributo de diferentes estudos elaborados numa perspectiva holística, tendo como objectivo principal elaborar uma visão global do estado do planeta Terra e estudar as possíveis causas e soluções para os problemas identificados. Posteriormente analisámos as percepções de professores de ciências, 327 'em serviço' e 521 'em formação' de Espanha, Portugal e América Latina. Analisámos, ainda, o conteúdo de 127 manuais escolares referentes ao ensino secundário e 3485 artigos publicados entre 1992 e 1998 em Espanha e em revistas internacionais de educação em ciência. Podemos dizer que todos os resultados obtidos mostram semelhanças e, também, indicam, que o estado do Planeta é, ainda, uma dimensão em falta na Educação em Ciência (Biologia, Física, Geologia, Química, ...), devendo ser incorporada com urgência no currículo

Recensión de la obra dirigida por el Prof. Dr. D. Javier Boix Reig, Catedrático de Derecho penal de la Universidad de Valencia: Derecho penal. Parte especial. Volumen I. La protección penal de los intereses jurídicos personales (Adaptado a las reformas de

Bibliography commentComentario bibliografí

Acciones docentes prácticas en Derecho penal, Derecho penitenciario y Criminología: experiencias didácticas fuera del aula

Con la implantación del Espacio Europeo de Educación Superior se han venido operando cambios importantes en los métodos y técnicas aplicados en la docencia del Derecho y, más concretamente, en las disciplinas jurídicas que conforman las Ciencias penales. Así, se ha ido avanzando en la dirección de promover una participación más activa del estudiante, mediante el empleo de herramientas y métodos innovadores que han contribuido a proporcionar una formación más integral, comprensiva de competencias genéricas, transversales y específicas. En esta línea de cambio del modelo educativo, la Red de Investigación sobre acciones docentes prácticas en Derecho penal, Derecho penitenciario y Criminología ha desarrollado nuevos recursos que giran en torno a la realización de salidas didácticas de los alumnos a instituciones y organizaciones directamente relacionadas con el sistema penal, fundamentalmente las que componen la judicatura, el aparato policial y el sistema penitenciario

Digenic inheritance in cystinuria mouse model

Cystinuria is an aminoaciduria caused by mutations in the genes that encode the two subunits of the amino acid transport system b0,+, responsible for the renal reabsorption of cystine and dibasic amino acids. The clinical symptoms of cystinuria relate to nephrolithiasis, due to the precipitation of cystine in urine. Mutations in SLC3A1, which codes for the heavy subunit rBAT, cause cystinuria type A, whereas mutations in SLC7A9, which encodes the light subunit b0,+AT, cause cystinuria type B. By crossing Slc3a1-/- with Slc7a9-/- mice we generated a type AB cystinuria mouse model to test digenic inheritance of cystinuria. The 9 genotypes obtained have been analyzed at early (2- and 5-months) and late stage (8-months) of the disease. Monitoring the lithiasic phenotype by X-ray, urine amino acid content analysis and protein expression studies have shown that double heterozygous mice (Slc7a9+/-Slc3a1+/-) present lower expression of system b0,+ and higher hyperexcretion of cystine than single heterozygotes (Slc7a9+/-Slc3a1+/+ and Slc7a9+/+Slc3a1+/-) and give rise to lithiasis in 4% of the mice, demonstrating that cystinuria has a digenic inheritance in this mouse model. Moreover in this study it has been demonstrated a genotype/phenotype correlation in type AB cystinuria mouse model providing new insights for further molecular and genetic studies of cystinuria patients

Disrupting MLC1 and GlialCAM and ClC-2interactions in leukodystrophy entails glial chloridechannel dysfunction

Defects in the astrocytic membrane protein MLC1, the adhesion molecule GlialCAM or the chloride channel ClC-2 underlie human leukoencephalopathies. Whereas GlialCAM binds ClC-2 and MLC1, and modifies ClC-2 currents in vitro, no functional connections between MLC1 and ClC-2 are known. Here we investigate this by generating loss-of-function Glialcam and Mlc1 mouse models manifesting myelin vacuolization. We find that ClC-2 is unnecessary for MLC1 and GlialCAM localization in brain, whereas GlialCAM is important for targeting MLC1 and ClC-2 to specialized glial domains in vivo and for modifying ClC-2's biophysical properties specifically in oligodendrocytes (OLs), the cells chiefly affected by vacuolization. Unexpectedly, MLC1 is crucial for proper localization of GlialCAM and ClC-2, and for changing ClC-2 currents. Our data unmask an unforeseen functional relationship between MLC1 and ClC-2 in vivo, which is probably mediated by GlialCAM, and suggest that ClC-2 participates in the pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts

Dysfunctional LAT2 amino acid transporter is associated with cataract in mouse and humans

Cataract, the loss of ocular lens transparency, accounts for ∼50% of worldwide blindness and has been associated with water and solute transport dysfunction across lens cellular barriers. We show that neutral amino acid antiporter LAT2 (Slc7a8) and uniporter TAT1 (Slc16a10) are expressed on mouse ciliary epithelium and LAT2 also in lens epithelium. Correspondingly, deletion of LAT2 induced a dramatic decrease in lens essential amino acid levels that was modulated by TAT1 defect. Interestingly, the absence of LAT2 led to increased incidence of cataract in mice, in particular in older females, and a synergistic effect was observed with simultaneous lack of TAT1. Screening SLC7A8 in patients diagnosed with congenital or age-related cataract yielded one homozygous single nucleotide deletion segregating in a family with congenital cataract. Expressed in HeLa cells, this LAT2 mutation did not support amino acid uptake. Heterozygous LAT2 variants were also found in patients with cataract some of which showed a reduced transport function when expressed in HeLa cells. Whether heterozygous LAT2 variants may contribute to the pathology of cataract needs to be further investigated. Overall, our results suggest that defects of amino acid transporter LAT2 are implicated in cataract formation, a situation that may be aggravated by TAT1 defects

UVagile 5.0.

Esta colección de documentos proporciona un resumen de los resultados obtenidos en el proyecto UVagile durante el curso 2022-2023: - Presentación general del proyecto “UVagile 5.0”, en el marco del Laboratorio de Innovación Docente de la Universidad de Valladolid (LIDUVa) - Artículo y presentación del trabajo “Una metodología basada en prácticas ágiles para la realización de Trabajos Fin de Grado”, publicado en las Actas de las Jornadas sobre Enseñanza Universitaria de la Informática (JENUI): https://aenui.org/actas/. - Póster “Hacia el examen como instrumento de aprendizaje y evaluación”, presentado en la VII Jornada de Innovación Docente de la Universidad de Valladolid - #JIDUVa.Departamento de Informática (Arquitectura y Tecnología de Computadores, Ciencias de la Computación e Inteligencia Artificial, Lenguajes y Sistemas Informáticos

Presence of histological risk factors in radical cystectomy pieces with tumor and its association with mortality by age

Introducción: La probabilidad de padecer un tumor vesical a lo largo de la vida es de más del 4% en hombres y de alrededor del 1,2% en mujeres, incidencia que aumenta con la edad, lo que supone más de 100000 nuevos casos anuales de cáncer vesical en Europa, de los cuales un 30% tendrán invasión muscular. En 2006 provocó el 4,1 % y 1,8 % del total de muertes por cáncer en los varones y las mujeres europeos, por lo que el cálculo del pronóstico es fundamental para optimizar el tratamiento adecuado a cada paciente. Son marcadores de riesgo establecidos la estirpe y el subtipo histológico junto con el grado y el estadio tumoral, al igual que la invasión linfovascular. Hemos realizado un estudio para valorar la relación existente entre la edad y dichos marcadores de riesgo con la mortalidad. Material y Métodos: Se ha realizado un estudio retrospectivo observacional, incluyendo los pacientes que se realizaron cistectomía por tumor infiltrante en el Hospital Universitario San Cecilio de Granada (España) desde enero de 2000 hasta diciembre de 2011. Se recogieron datos sobre características histológicas de la pieza quirúrgica. Resultados: De las 172 cistectomías realizadas durante ese periodo, el 75% se incluyeron en el estudio (129 pacientes) por encontrar en la pieza tumor transicional. La edad media a la cistectomía fue de 66.69 años (35 a 85 años). Prácticamente todos los tumores fueron de alto grado, en un 73% de los casos no existía diferenciación, y la diferenciación escamosa apareció en un 19%. Se observó la presencia de carcinoma in situ en el 7.1%, invasión vascular en 34.6%, linfática en 21.4% y perineural en 19.5%. El patrón de crecimiento fue papilar en 9.3% y sólido en 29.5%. Tras dividir la muestra en grupos: - grupo 1: pacientes con 65 años o menores, y - grupo 2: pacientes mayores de 65 años. Apreciamos que el grupo 1 tenía mayor incidencia de invasión vascular sin diferencias en otros marcadores. La mortalidad fue similar en ambos grupos y no se influyó por la diferencia en la invasión vascular. En los pacientes del grupo 1 en cuya pieza de cistectomía se especifica diferenciación escamosa tienen más riesgo de morir por tumor. En el grupo 2, la invasión vascular se asocia significativamente con el riesgo de mortalidad por tumor y global; la invasión perineural también se asocia con la mortalidad cáncer específica. Conclusiones: Los pacientes con 65 años o menos tienen mayor incidencia de permeación vascular, aunque ésta no influye en la mortalidad. Sin embargo, en pacientes mayores de 65 años, donde la invasión vascular es menos frecuente, ésta afecta más claramente a la mortalidad tanto global como cáncer específica. Otros factores, como la diferenciación escamosa en jóvenes y la permeación perineural en mayores, también influyen sobre la mortalidad específica por tumor.Introduction: The probability of having a bladder cancer over the lifetime is more than 4% in men and about 1.2% in women. This proportion increases with age, representing more than 100,000 new cases of bladder cancer annually in Europe, 30 % of which have muscle invasion. In 2006 caused 4.1% and 1.8% of all cancer deaths in men and women in Europe, so prognosis calculation is essential to optimize the appropriate treatment for each patient. The lineage and the histological subtype along with the tumor stage and grade, as lymphovascular invasion are established like risk markers. We conducted a study to assess the relationship between age and these risk markers with mortality. Material and Methods: We performed a retrospective observational study, including patients who underwent cystectomy for invasive tumor at the University Hospital San Cecilio of Granada (Spain) from January 2000 to December 2011. Data were collected on histology from the surgical specimen. Results: Of the 172 patients who were performed a cystectomy during that period, 75% were included in the study (129 patients) because of finding transitional tumor in the surgical piece. The average age at cystectomy was 66.69 years (35-85 years). Virtually all were high grade tumors, in 73% of cases there was no differentiation, and squamous differentiation appeared by 19%. We observed the presence of carcinoma in situ in 7.1%, vascular invasion by 34.6%, lymphatic by 21.4% and perineural by 19.5%. The pattern of growth was papillary by 9.3% and solid by 29.5%. After dividing the sample into groups: - Group 1: patients 65 years or younger, and - Group 2: patients over 65 years We appreciate that group 1 had a higher incidence of vascular invasion without differences in other markers. Mortality was similar in both groups and was not influenced by the difference in vascular invasion. In patients from group 1 whose cystectomy piece were specified squamous differentiation are more likely to die from tumor. In group 2, vascular invasion was significantly associated with the risk of overall and tumor-specific mortality; also perineural invasion is also associated with cancer-specific mortality. Conclusions: Patients aged 65 years or less have a higher incidence of vascular permeation, although this does not affect mortality. However, in patients over 65 years, where vascular invasion is less common, vascular permeation affects to global and specific cancer mortality more clearly. Other factors, such as squamous differentiation in young patients and perineural permeation in older patients also influence tumor-specific mortality