Dianas implicadas en la enfermedad renal: síntesis y evaluación de nuevos inhibidores de PTP-1B y FABP

Premio Extraordinario de Doctorado de la UAH en el año académico 2013-2014Vaquero López, Juan José, codir.Diabetes mellitus is a chronic multifactorial metabolic disease caused by insulin deficiency or insuline resistance. Diabetes is often associated with cardiovascular risk factors, and may lead to severe secondary complications, including atherosclerosis, microangiopathy, renal dysfunction and failure, cardiac abnormalities, diabetic retinopathy and ocular disorders. Insuline resistance is a major pathophysiological factor in the development of type 2 diabetes and it is associated not only with hyperinsulinemia and hyperglycemia but also with other disorders such as atherosclerosis, hypertension and abnormal lipid profile, which are known collectively referred to as Metabolic Syndrome or Insuline Resistance Associated Disorders. This work focused on the synthesis and biological activity of new compounds designed as inhibitors of Protein Tyrosine Phosphatase 1B (PTP-1B) and Fatty Acid Binding Proteins (FABPs). These two therapeutic targets, are involved in diseases such as obesity, diabetes or atherosclerosis. Series of dihydropyrrolo-quinoxalines, pyrrolo-quinoxalinium salts and pyridazino-pyrrolo-quinoxalinium salts were obtained and evaluated for in vitro inhibition of PTP1B. Structure-activity relationships (SAR) where established. Dihydropyrrolo-quinoxaline serie showed inhibition in micromolar range. Molecular modeling by docking studies of pyridazino-pyrrolo-quinoxalinium salts showed binding at the allosteric site. Series of [alfa]-, [beta]-, [gamma]- and [delta]-carboline alkanoic acids and carboxyalkyl [alfa]-, [beta]-, [gamma]- and [delta]--carbolinium salts were synthesized and evaluated for in vitro inhibition of TNF-[alfa] synthesis in THP-1 cells. [alfa]- and [gamma]-carbolinium derivatives were the most active and the carboxy moiety was further modified. Best inhibition results were obtained for N-(15-carboxypentadecyl)-[gamma]-carbolinium. Inhibition of FABP4 binding was also evaluated for the [alfa]-carbolinium serie resulting in inhibitions in the same magnitude order than the reference. A methodology to synthesize dihydroderivatives of [beta]- and [gamma]-carbolines from the corresponding indol-2- and indol-3-ylmethyl TosMIC derivatives was explored. 2,3-dihydroindenimines and indole-2- and indole-3-carbonitrile derivatives were obtained through a isocyanide-nitrile long distance rearrangement

Dianas implicadas en la enfermedad renal: síntesis y evaluación de nuevos inhibidores de PTP-1B y FABP

Premio Extraordinario de Doctorado de la UAH en el año académico 2013-2014Vaquero López, Juan José, codir.Diabetes mellitus is a chronic multifactorial metabolic disease caused by insulin deficiency or insuline resistance. Diabetes is often associated with cardiovascular risk factors, and may lead to severe secondary complications, including atherosclerosis, microangiopathy, renal dysfunction and failure, cardiac abnormalities, diabetic retinopathy and ocular disorders. Insuline resistance is a major pathophysiological factor in the development of type 2 diabetes and it is associated not only with hyperinsulinemia and hyperglycemia but also with other disorders such as atherosclerosis, hypertension and abnormal lipid profile, which are known collectively referred to as Metabolic Syndrome or Insuline Resistance Associated Disorders. This work focused on the synthesis and biological activity of new compounds designed as inhibitors of Protein Tyrosine Phosphatase 1B (PTP-1B) and Fatty Acid Binding Proteins (FABPs). These two therapeutic targets, are involved in diseases such as obesity, diabetes or atherosclerosis. Series of dihydropyrrolo-quinoxalines, pyrrolo-quinoxalinium salts and pyridazino-pyrrolo-quinoxalinium salts were obtained and evaluated for in vitro inhibition of PTP1B. Structure-activity relationships (SAR) where established. Dihydropyrrolo-quinoxaline serie showed inhibition in micromolar range. Molecular modeling by docking studies of pyridazino-pyrrolo-quinoxalinium salts showed binding at the allosteric site. Series of [alfa]-, [beta]-, [gamma]- and [delta]-carboline alkanoic acids and carboxyalkyl [alfa]-, [beta]-, [gamma]- and [delta]--carbolinium salts were synthesized and evaluated for in vitro inhibition of TNF-[alfa] synthesis in THP-1 cells. [alfa]- and [gamma]-carbolinium derivatives were the most active and the carboxy moiety was further modified. Best inhibition results were obtained for N-(15-carboxypentadecyl)-[gamma]-carbolinium. Inhibition of FABP4 binding was also evaluated for the [alfa]-carbolinium serie resulting in inhibitions in the same magnitude order than the reference. A methodology to synthesize dihydroderivatives of [beta]- and [gamma]-carbolines from the corresponding indol-2- and indol-3-ylmethyl TosMIC derivatives was explored. 2,3-dihydroindenimines and indole-2- and indole-3-carbonitrile derivatives were obtained through a isocyanide-nitrile long distance rearrangement

A Simple, Reliable, and Inexpensive Solution for Contact Color Measurement in Small Plant Samples

Correct color measurement by contact-type color measuring devices requires that the sample surface fully covers the head of the device, so their use on small samples remains a challenge. Here, we propose to use cardboard adaptors on the two aperture masks (3 and 8 mm diameter measuring area) of a broadly used portable spectrophotometer. Adaptors in black and white to reduce the measuring area by 50% and 70% were applied in this study. Representatives of the family Campanulaceae have been used to test the methodology, given the occurrence of small leaves. Our results show that, following colorimetric criteria, the only setting providing indistinguishable colors according to the perception of the human eye is the use of a 50%-reducing adaptor on the 3-mm aperture. In addition, statistical analysis suggests the use of the white adaptor. Our contribution offers a sound measurement technique to gather ecological information from the color of leaves, petals, and other small samplesPatricia Sanmartín and Miguel Serrano thank the financial support of Xunta de Galicia grants ED431C 2018/32 and ED431B 2018/36. Elsa Fuentes acknowledges receipt of the PhD Fellowship-Contract MICINN-FPI (BES-2017-079927)S

Cracks in consolidants containing TiO2 as a habitat for biological colonization: A case of quaternary bioreceptivity

The recently proposed concept of quaternary bioreceptivity applies to substrates treated with coating materials and it is considered in the present study with the alga Bracteacoccus minor and the cyanobacterium Nostoc sp. onto granite specimens treated with ethyl silicate and nano-sized silica doped with different amounts of TiO2 (0, 0.5, 1 and 3 wt%). The findings showed a lack of correlation between the amount of TiO2 and the level of colonization (main bioreceptivity estimator) to the presence of cracks on the surface, which annul the biocidal power of TiO2. Crack formation, which depends on the mechanical properties, greatly influences the bioreceptivity of the material. Thus, the cracks provided anchor points where water is retained, in turn strongly influencing the early stages of colonization kinetics, to a greater extent than the biocidal power of TiO2, which will probably increase as the biofilm develops over the entire surface. In addition, although the cracks were more abundant and wider in the ethyl silicate-based consolidant, the nano-sized silica provided better anchoring points, making the material treated with the corresponding consolidant more bioreceptiveS

Síndrome de Burnout en el personal de enfermería en UVI

Introduction: The burnout syndrome occurs when a supportive relationship is maintained with a strong interpersonal relationship with the beneficiaries of that work. Several studies have considered the nursing staff as a fragile group. Some studies revealed that units that generate greater stress are those that meet critical or terminal patients: the environment, physical and emotional continuing demands to the nurses who are subjected by patients, and role ambiguity are characteristics that predispose the development of this syndrome.Objectives: The main objective is to determine the degree of burnout in the team ICU nursing Hospital Medical Ramón y Cajal.Material and methods: Sample of 68 nurses and assistants working in the ICU. As an instrument, we used Maslach Burnout Inventory in its Spanish version, self administered.Results: Low scores on the three dimensions of the syndrome (emotional exhaustion, depersonalization and personal accomplishment), and most sample with a 45.6%, tendency to suffer.Conclusions: Profile of workers suffering burnout is: nurse, 35 to 44 years, with contract fixed, experience over 16 years and an age of 1-5 years in that job.Introducción: El síndrome de Burnout aparece cuando se mantiene una relación de ayuda con una relación interpersonal intensa con los beneficiarios del trabajo. En numerosos estudios se ha considerado al personal de enfermería como grupo vulnerable. Algunos estudios revelan que las unidades que generan mayor estrés son aquellas que reúnen pacientes críticos o terminales. El ambiente laboral de estas unidades, las continuas demandas físicas y emocionales a las que las enfermeras se ven sometidas por parte de los pacientes y la ambigüedad en su rol son características que predisponen al desarrollo de dicho síndrome.  Objetivos: El objetivo principal es determinar el grado de Burnout en el equipo de enfermería de la UVI médica del hospital Ramón y Cajal.  Material y métodos: Muestra de 68 enfermeros y auxiliares que trabajan en la UVI. Como instrumento, se utiliza el cuestionario Maslach Burnout Inventory en su versión en español, de manera autoadministrada.  Resultados: Bajas puntuaciones en las tres dimensiones del síndrome (cansancio emocional, despersonalización y realización personal), y la mayoría de la población, un 45,6%, tendencia a padecerlo.  Conclusiones: El perfil del trabajador que padece síndrome de Burnout sería: enfermera, de 35 a 44 años, con contrato fijo, experiencia laboral mayor de 16 años y una antigüedad de 1 a 5 años en el puesto de trabajo

Evaluación de la calidad de vida en personas drogodopendientes mediante el modelo de Rasch

La Escala GENCAT aparece como el único instrumento que permite evaluar la calidad de vida individual de personas con drogodependencias desde una perspectiva diferente a la de calidad de vida relacionada con la salud (CVRS). Dado que las propiedades psicométricas de la mencionada escala sólo se han estudiado para la muestra general de usuarios de servicios sociales, este estudio tiene como objetivo analizar su fiabilidad y validez en un grupo específico de personas con drogodependencias. Para ello, se aplicó a 75 drogodependientes usuarios de servicios sociales en Cataluña. Los datos obtenidos permiten concluir que la escala, para este colectivo, presenta una adecuada consistencia interna (que supera en algunos casos la obtenida para la muestra general) según la Teoría Clásica de los Tests. Además, se observó que el ajuste medio de los ítems al modelo y la fiabilidad promedio de las estimaciones de los ítems fueron altos según el modelo de Rasch, aunque los índices de fiabilidad de las personas resultaron más moderados en la mayoría de las subescalas y deficiente en el caso de la dimensión bienestar físico. Se concluye que, aunque la escala es válida y fiable en términos generales, es aconsejable una revisión de la dimensión mencionada

Phytochemical Compounds as Cleaning Agents on Granite Colonized by Phototrophic Subaerial Biofilms

The society has become increasingly interested in using natural products over chemicals for cleaning activities. In this study, the cleaning potential of formulations embedded in a hydrogel matrix and composed respectively of essential oils (EOs) of Origanum vulgare, Thymus vulgaris, and Calamintha nepeta, and their respective main active components (EO-ACs), viz., Carvacrol, Thymol, and Pulegone, on a phototropic biofilm growing on granite was investigated. In addition, and for comparative purposes, analysis with the combination of the three EOs, the combination of the three EO-ACs, and Preventol RI-80® (one of the most effective commercial cleaning agents based on quaternary ammonium salts) in all three cases embedded in a hydrogel matrix, as well as only the hydrogel matrix, distilled water, and Preventol RI-80®, in both latter cases applied with brush, were also studied. The cleaning effect of the treatments was assessed immediately after the treatment and after one and two weeks by color spectrophotometry, a reliable tool to evaluate the presence and vitality of the phototrophs and the cleaning effectiveness in granite. C. nepeta and its active component Pulegone proved to be the most effective and yielded similar results, comparable to those of uncolonized granite, and better than those obtained with Preventol RI-80® applied with brush (most common way), especially at the end of the experiment. These promising first results support the suitable use of the phytochemical compounds used on phototrophs field where there are still few published studies and encourage further investigation toward the evaluation of their exhibited biocidal activityThis study was partly funded by projects ED431C 2018/32 and CGL2016-79778-R AEI/FEDER, UE. E. Fuentes is supported by a PhD Fellowship-Contract MICINN-FPI (BES-2017-079927)S

Entrepreneurship learning in doctoral programs: an online collaborative methodology

[EN] The European Commission's Entrepreneurship 2020 Action Plan, adopted in 2013, states that EU economies need more entrepreneurs with higher levels of technical education to be more competitive and innovative. Besides, it identifies education as one of the three pillars for facilitating entrepreneurship and recognizes that universities must become more effective in supporting entrepreneurial activity. H2020 project prodPhD’s main objective is the design and evaluation of a social network online methodology for teaching and learning entrepreneurship in Ph.D. programs. This communication shows the main intermediate results of ProdPhD, which started in January of 2021and will last until December 2022. The next steps will try the methods developed during the first year through the use of demonstration actions.[ES] El Plan de Acción sobre el Espíritu Empresarial 2020 de la Comisión Europea, adoptado en 2013, afirma que las economías de la UE necesitan más emprendedores con un mayor nivel de formación técnica para ser más competitivas e innovadoras. Además, identifica la educación como uno de los tres pilares para facilitar el emprendimiento, y reconoce que las universidades deben ser más eficaces en el apoyo a la actividad emprendedora. El proyecto H2020 prodPhD tiene como objetivo principal el diseño y la evaluación de una metodología colaborativa en línea para la enseñanza y el aprendizaje de emprendimiento en los programas de doctorado. Esta comunicación muestra los principales resultados intermedios de ProdPhD, que comenzó en enero de 2021 y terminará en diciembre de 2022. En la fase siguiente se probarán los métodos desarrollados durante el primer año mediante acciones piloto.Alonso Álvarez, P.; Serrano López, A.; Lascurain Sánchez, M. (2022). Enseñanza de emprendimiento en los programas de doctorado: diseño y puesta en marcha de una metodología online colaborativa. Editorial Universitat Politècnica de València. 1028-1039. https://doi.org/10.4995/INRED2022.2022.158731028103

Differential antiviral activity of European sea bass interferon-stimulated 15 protein (ISG15) against RGNNV and SJNNV betanodaviruses.

ISG15 is an antiviral protein acting intracellularly, by conjugation to viral or cellular proteins, or extracellularly, as cytokine. In this work, an in vitro system, consisting of E-11 cells over-expressing European sea bass ISG15 (Dl_ISG15_E11 cells), has been developed to evaluate the European sea bass ISG15 protein activity against RGNNV and SJNNV isolates. Regarding RGNNV, RNA2 copy number and viral titres were similar in E-11 and Dl_ISG15_E11 cells, and the cellular survival analyses demonstrated that Dl_ISG15_E11 cells were not protected against this virus. In contrast, ISG15 compromises SJNNV replication, since a reduction of the SJNNV genome synthesis has been recorded. The ISG15 anti-SJNNV activity was confirmed by viral titration and survival assays. In addition, a role of the intracellular ISG15 in modulating the transcription of endogenous genes has being recorded, with tlr3 gene being knocked out and e3 gene being up-regulated in RGNNV-inoculated Dl_ISG15_E11 cells. Sea bass ISG15 has also been detected extracellularly, and its activity has been evaluated by co-culture. The survival rate of RGNNV-inoculated E-11 cells increased from 25% to 46% when they were co-cultured with ISG15-producing cells. Similarly, the survival rate of SJNNV-inoculated E-11 cells increased from 27% to 51% in co-culture with ISG15-producing cells. To our knowledge, this is the first description of a differential antiviral activity of an ISG15 protein against two betanodavirus species, and the first evaluation of the cytokine-like activity of a fish ISG15 protein on non-immune cells.This study has been supported by the project AGL2017-84644-R (MINECO/AEI/FEDER, UE). P. Moreno was supported by a fellowship from Ministerio de Educación, Cultura y Deporte (FPU12/00265, Spanish Government)

Norway rat (Rattus norvegicus) ectoparasites in livestock production systems from central Argentina: influencing factors on parasitism

Haematophagous ectoparasites are worldwide vectors of many zoonotic bacterial diseases, both emerging and re-emerging, whose incidences are rising. Livestock development alters different environmental characteristics such as the microclimate of a site, changing the availability, density and susceptibility of the hosts to pathogens and vectors, indirectly influencing the spread and persistence of a disease within an ecosystem. The Norway rat (Rattus norvegicus), the most abundant vertebrate pest species found on livestock farms from Argentina, is a reservoir for several important zoonotic bacteria and may harbor ectoparasite species, which act as their vectors. Even though the Norway rat is widely known for its role as an ectoparasite host, the ecological characteristics of their ectoparasite communities and the related factors with parasitism on livestock farms have never been described. In the present study, we describe the ectoparasite community in Norway rats from central Argentina livestock farms, while also depicting the influencing factors on both ectoparasite occurrence and abundance. Ectoparasites were collected from rats captured in 20 sites from Buenos Aires province, between the winter of 2016 and the summer of 2018. A total of 1441 ectoparasite individuals were collected from 159 Norway rat individuals [Total ectoparasite prevalence = 69.2%; Mean ectoparasite specimen abundance (± CI) = 9.06 ± 2.32 ectoparasite individuals per rat; Mean ectoparasite specimen intensity (±CI) = 13.10 ± 3.08 ectoparasite individuals per infested rat found]. Ectoparasite assemblage consisted of four cosmopolitan species, recognized for their sanitary relevance: mites (Laelapidae: Laelaps nuttalli and Laelaps echidninus), lice (Polyplacidae: Polyplax spinulosa) and fleas (Pulicidae: Xenopsylla cheopis). We observed higher Norway rat abundance in sites related to higher ectoparasite occurrence and abundance frequencies on the rats. Additionally, ectoparasites were more abundant on rats in warm seasons and on male individuals, over female rats. Moreover, the geographical location of the studied sites influenced the ectoparasite assemblage structure observed on the rats. This study broadens the knowledge on the role of Norway rats as zoonotic ectoparasites hosts and analyzes the drivers influencing ectoparasite occurrence and abundance on the most populated region of Argentina, which is also the region with the most intensive livestock farming. Therefore, this survey may assist in evaluating potential risks for humans and generate effective sanitary control strategies for ectoparasite-borne infectious diseases.Fil: Alonso, Rodrigo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Ruiz, Melanie. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Lovera, Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Montes de Oca, Daniela Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Cavia, Regino. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Sánchez, Juliana Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentin