Stakeholder governance and private benefits: The case of politicians in Spanish cajas

Our research focuses on the private benefits of politicians as board directors of Spanish savings banks (cajas). We use hand-collected data on the political affiliation and personal loans of 1,578 directors to investigate whether political directors used private benefits through excessive personal loans, loans granted to their political parties, or the institutions they represented. Our results show that a higher proportion of political directors on a board is associated with larger personal loans and with better terms than those granted to non-political directors. Furthermore, this higher proportion is also linked to larger loans granted to the public administrations that the political directors represented on the cajas’ governing board. Finally, we also find in-group favouritism based on the social identity theory and directors’ party identification. Therefore, political directors make greater use of private benefits when allocated to their political party and its membersThis study was supported by the Spanish Ministry of Economy and Competitiveness (Grant ECO2017-85356), the UAM - Comunidad de Madrid Research Project for Young Researchers (SI3-PJI-2021-00276) and it benefited from the Professorship Excellence Program in accordance with the multi-year agreement signed by the Government of Madrid and the Autonomous University of Madri

Photomutagenicity of chlorpromazine and its N-demethylated metabolites assessed by NGS

[EN] The human genome is constantly attacked by endogenous and exogenous agents (ultraviolet light, xenobiotics, reactive oxygen species), which can induce chemical transformations leading to DNA lesions. To combat DNA damage, cells have developed several repair mechanisms; however, if the repair is defective, DNA lesions lead to permanent mutations. Single-cell gel electrophoresis (COMET assay) is a sensitive and well-established technique for quantifying DNA damage in individual cells. Nevertheless, this tool lacks relationship with mutagenesis. Therefore, to identify errors that give rise to mutations it would be convenient to test an alternative known procedure, such as next generation sequencing (NGS). Thus, the present work aims to evaluate the photomutagenicity of neuroleptic drug chlorpromazine (CPZ), and its N-demethylated metabolites using COMET assay and to test NGS as an alternative method to assess photomutagenesis. In this context, upon exposure to UVA radiation, COMET assay reveals CPZ-photosensitized DNA damage partially repaired by cells. Conversely with this result, metabolites demethylchlorpromazine (DMCPZ) and didemethylchlorpromazine (DDMCPZ) promote extensive DNA-photodamage, hardly repaired under the same conditions. Parallel assessment of mutagenesis by NGS is consistent with these results with minor discrepancies for DDMCPZ. To our knowledge, this is the first example demonstrating the utility of NGS for evaluating drug-induced photomutagenicity.This study was funded by the Carlos III Institute (ISCIII) of Health (Grants: PI15/00303, PI18/00540, PI16/01877, CPII16/00052, the Thematic Networks and Co-operative Research Centres: ARADyAL RD16/0006/0004 and RD16/0006/0030), IB16170, GR18145 from Junta de Extremadura, Spain, co-funded by European Regional Development Fund and Generalitat Valenciana Prometeo/2017/075. We would also like to thank M. Dolores Coloma for technical assistance in the preliminary experiments.Agúndez, JA.; García-Martín, E.; Garcia-Lainez, G.; Miranda Alonso, MÁ.; Andreu Ros, MI. (2020). Photomutagenicity of chlorpromazine and its N-demethylated metabolites assessed by NGS. Scientific Reports. 10(1):1-6. https://doi.org/10.1038/s41598-020-63651-yS16101Bjelland, S. & Seeberg, E. Mutagenicity, toxicity and repair of DNA base damage induced by oxidation. Mutat. Res. 531, 37–80 (2003).Friedberg, E. C. A brief history of the DNA repair field. Cell Res. 18, 3–7 (2008).Cadet, J. & Wagner, J. R. DNA base damage by reactive oxygen species, oxidizing agents, and UV radiation. Cold Spring Harb. Perspect. Biol. 5, (2013).Bauer, N. C., Corbett, A. H. & Doetsch, P. W. The current state of eukaryotic DNA base damage and repair. Nucleic Acids Res. 43, 10083–10101 (2015).Cadet, J. & Davies, K. J. A. Oxidative DNA damage & repair: An introduction. Free Radic. Biol. Med. 107, 2–12 (2017).Sancar, A., Lindsey-Boltz, L. A., Unsal-Kaçmaz, K. & Linn, S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu. Rev. Biochem. 73, 39–85 (2004).Roos, W. P., Thomas, A. D. & Kaina, B. DNA damage and the balance between survival and death in cancer biology. Nat. Rev. Cancer 16, 20–33 (2016).Møller, P. Assessment of reference values for DNA damage detected by the comet assay in human blood cell DNA. Mutat. Res. 612, 84–104 (2006).Azqueta, A. & Collins, A. R. The essential comet assay: a comprehensive guide to measuring DNA damage and repair. Arch. Toxicol. 87, 949–968 (2013).Collins, A. R. et al. Controlling variation in the comet assay. Front. Genet. 5, 359 (2014).Møller, P. The comet assay: ready for 30 more years. Mutagenesis 33, 1–7 (2018).Shendure, J. & Ji, H. Next-generation DNA sequencing. Nat. Biotechnol. 26, 1135–1145 (2008).Metzker, M. L. Sequencing technologies—the next generation. Nat. Rev. Genet. 11, 31 (2010).Gawad, C., Koh, W. & Quake, S. R. Single-cell genome sequencing: current state of the science. Nat. Rev. Genet. 17, 175–188 (2016).Schwarz, U. I., Gulilat, M. & Kim, R. B. The Role of Next-Generation Sequencing in Pharmacogenetics and Pharmacogenomics. Cold Spring Harb. Perspect. Med. 9, (2019).Epstein, J. H., Brunsting, L. A., Petersen, M. C. & Schwarz, B. E. A study of photosensitivity occurring with chlorpromazine therapy. J. Invest. Dermatol. 28, 329–338 (1957).Kochevar, I. E., Chung, F. L. & Jeffrey, A. M. Photoaddition of chlorpromazine to DNA. Chem. Biol. Interact. 51, 273–284 (1984).Palumbo, F. et al. Enhanced photo(geno)toxicity of demethylated chlorpromazine metabolites. Toxicol. Appl. Pharmacol. 313, 131–137 (2016).Miki, Y. et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266, 66–71 (1994).Wooster, R. et al. Identification of the breast cancer susceptibility gene BRCA2. Nature 378, 789–792 (1995)

Models d'anàlisi de l'arquitectura ibèrica. Espai públic i construccions religioses en medis urbans

[spa] Este articulo analiza la distribución de los espacios públicos y construcciones religiosas en los recintos fortificados ibéricos en el nordeste de España. En primer lugar, explicamos què es un espacio público y cómo se articula en la planta de la ciudad ibérica. En segundo lugar, analizamos las actividades de culto que tienen lugar en algunos espacios públicos y aclaramos luego las estructuras monumentales religiosas. El significado de estos espacios es explicado a partir de su forma y sus contenidos. Para completar los datos disponibles tenemos necesidad de modelos teóricos que nos permitan obtener un mejor conocimiento de la organización social de los que construyeron estas estructuras. Esta es la razón por la cual, finalmente, diseñamos un modelo que muestra cómo reconstruir recintos públicos que han servido para actividades religiosas.[eng] This article analizes the distribution of public spaces and religious buildings in North-Eastern Spain Iberian fortified places. First of all, we explain what a public space is and how it is articulated in the Iberian town plan. Secondly, we describe the cult activities that take place in some public spaces and we will then clarify the monumental religious structures. The meaning of this spaces is explained by their form and contents. In order to complement the existing data we need the help of theoretical models that allow us a better knowledge of the social organization of the people that built these structures. Therefore we outline a model which shows how to rebuild public precints that have religious purpose

In silico and functional analyses of immunomodulatory peptides encrypted in the human gut metaproteome

This work supports the massive presence of potential immunomodulatory peptides in the human gut metaproteome. These peptides were identified through the MAHMI database as potentially anti-inflammatory, and sixteen of them synthesized for characterize their mechanism of action. From them, peptide HM14 was encrypted in an extracellular protein produced by Bifidobacterium longum, a common member of the human microbiota, and displayed the highest anti-inflammatory capability. Molecular mechanism of action of HM14 pointed to a specific interaction between this immunomodulatory peptide and antigen presenting cells, which resulted in a higher formation of iTreg cells. Moreover, HM14 was effective in decreasing pro-inflammatory parameters in PBMCs isolated from a cohort of Crohn's patients. Finally, non-targeted metabolomics confirmed the ability of HM14 to modulate the metabolic activity of PBMCs to fulfil its energy and biosynthetic requirements. Overall, our combined in silico/multiomics approach supports the human gut metaproteome as a source for immunomodulatory peptides.Ministerio de Economía y Competitividad | Ref. AGL2013-44761-PAgencia Estatal de Investigación | Ref. AGL2016-78311-

3D numerical simulation of slope-flexible system interaction using a mixed FEM-SPH model

Flexible membranes are light structures anchored to the ground that protect infrastructures or dwellings from rock or soil sliding. One alternative to design these structures is by using numerical simulations. However, very few models were found until date and most of them are in 2D and do not include all their components. This paper presents the development of a numerical model combining Finite Element Modelling (FEM) with Smooth Particle Hydrodynamics (SPH) formulation. Both cylindrical and spherical failure of the slope were simulated. One reference geometry of the slope was designed and a total of 21 slip circles were calculated considering different soil parameters, phreatic level position and drainage solutions. Four case studies were extracted from these scenarios and simulated using different dimensions of the components of the system. As a validation model, an experimental test that imitates the soil detachment and its retention by the steel membrane was successfully reproduced

3D numerical simulation of slope-flexible system interaction using a mixed FEM-SPH model

Flexible membranes are light structures anchored to the ground that protect infrastructures or dwellings from rock or soil sliding. One alternative to design these structures is by using numerical simulations. However, very few models were found until date and most of them are in 2D and do not include all their components. This paper presents the development of a numerical model combining Finite Element Modelling (FEM) with Smooth Particle Hydrodynamics (SPH) formulation. Both cylindrical and spherical failure of the slope were simulated. One reference geometry of the slope was designed and a total of 21 slip circles were calculated considering different soil parameters, phreatic level position and drainage solutions. Four case studies were extracted from these scenarios and simulated using different dimensions of the components of the system. As a validation model, an experimental test that imitates the soil detachment and its retention by the steel membrane was successfully reproduced.The FORESEE project has received funding from the EuropeanUnion’s Horizon 2020 research and innovation program undergrant agreement No 769373

Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) is related to smoking as the main etiological agent although there are other risk factors that can interact influencing the development of the disease. The definition of COPD is based on three points: the presence of persistent respiratory symptoms, exposure to risk agents, and a non-reversible obstructive spirometric ratio. Forced spirometry with a bronchodilator test is necessary to confirm the diagnosis of COPD, however, attempts are being made to develop alternative methods for screening given the current significant underdiagnosis of this pathology. In order to advance in a more personalized medicine for the patient, classification tools have been adopted such as clinical phenotypes and treatable traits, allowing treatments to be adapted according to the characteristics of the patients. Non-pharmacological treatment (smoking cessation, vaccination, physical exercise…) are essential for the management of the disease, as well as pharmacological treatment based on clinical phenotypes. Eosinophils have become a key marker when establishing treatment with inhaled glucocorticoids. In the follow-up of the disease, it is very relevant to evaluate the degree of control being a fundamental element the absence of exacerbations given their implications in mortality, morbidity and quality of life of patients. More studies are needed to better define the phenotypes of exacerbations and their biomarkersLa enfermedad pulmonar obstructiva crónica (EPOC) se relaciona con el tabaquismo como principal agente etiológico, si bien existen otros factores de riesgo que pueden interactuar influyendo en el desarrollo de la enfermedad. La definición de EPOC se asienta en tres puntos: la presencia de síntomas respiratorios persistentes, la exposición a agentes etiológicos y un cociente espirométrico obstructivo no reversible. La espirometría forzada con prueba broncodilatadora es la prueba de elección para confirmar el diagnóstico de EPOC, no obstante, se están intentando desarrollar métodos alternativos para el cribado de la enfermedad, dado el importante infradiagnóstico actual de esta patología. Con el fin de avanzar en una medicina más personalizada, en el paciente se han adoptado herramientas de clasificación como son los fenotipos clínicos y los rasgos tratables, permitiendo adecuar los tratamientos en función de las características de los pacientes. El tratamiento no farmacológico, como la deshabituación tabáquica, la vacunación, el ejercicio físico. . . es fundamental en el manejo de la enfermedad, así como el tratamiento farmacológico basado en los fenotipos clínicos. Los eosinófilos se han convertido en un marcador clave a la hora de instaurar el tratamiento con glucocorticoides inhalados. En el seguimiento de la enfermedad, es de especial relevancia evaluar el grado de control de esta, siendo un elemento fundamental para establecer un adecuado control la ausencia de agudizaciones. Estas conllevan importantes implicaciones en la mortalidad, morbilidad y calidad de vida de los pacientes, siendo necesarios más estudios para definir mejor los fenotipos de las agudizaciones y sus biomarcadore