Oso pardo ibérico : conflictos derivados de su conservación

Treball presentat a l'assignatura d'Ètica i Legislació. Gestió empresarial (102680)¿Qué prevalece en los montes? ¿La seguridad de un animal protegido o la de los seres humanos? ¿Es ético el gasto de recursos públicos y personal en la conservación del oso pardo ibérico a costa de las pérdidas económicas y los conflictos sociales que se derivan? Esta cuestión ha sido planteada en muchas ocasiones ante los intentos de conservación de diversas especies en peligro de extinción, y también ha sucedido en esta ocasión con el programa del oso pardo en la península ibérica. Este trabajo busca analizar y comprender los distintos puntos de vista de las colectividades afectadas por esta situación, así como tratar de llegar a una conclusión acerca de la viabilidad del proyecto y la posibilidad de que exista un punto de encuentro y entendimiento entre ambas partes del conflicto

Transcriptional response to metal starvation in the emerging pathogen Mycoplasma genitalium is mediated by Fur-dependent and -independent regulatory pathways

Transition metals participate in numerous enzymatic reactions and they are essential for survival in all living organisms. For this reason, bacterial pathogens have evolved dedicated machineries to effectively compete with their hosts and scavenge metals at the site of infection. In this study, we investigated the mechanisms controlling metal acquisition in the emerging human pathogen Mycoplasma genitalium. We observed a robust transcriptional response to metal starvation, and many genes coding for predicted lipoproteins and ABC-transporters were significantly up-regulated. Transcriptional analysis of a mutant strain lacking a metalloregulator of the Fur family revealed the activation of a full operon encoding a putative metal transporter system and a gene coding for a Histidine-rich lipoprotein (Hrl). We recognized a conserved sequence with dyad symmetry within the promoter region of the Fur-regulated genes. Mutagenesis of the predicted Fur operator within the hrl promoter abrogated Fur- and metal-dependent expression of a reporter gene. Metal starvation still impelled a strong transcriptional response in the fur mutant, demonstrating the existence of Fur-independent regulatory pathways controlling metal homeostasis. Finally, analysis of metal accumulation in the wild-type strain and the fur mutant by ICP-MS revealed an important role of Fur in nickel acquisition

Transcriptional response to metal starvation in the emerging pathogen Mycoplasma genitalium is mediated by Fur-dependent and -independent regulatory pathways

Transition metals participate in numerous enzymatic reactions and they are essential for survival in all living organisms. For this reason, bacterial pathogens have evolved dedicated machineries to effectively compete with their hosts and scavenge metals at the site of infection. In this study, we investigated the mechanisms controlling metal acquisition in the emerging human pathogen Mycoplasma genitalium. We observed a robust transcriptional response to metal starvation, and many genes coding for predicted lipoproteins and ABC-transporters were significantly up-regulated. Transcriptional analysis of a mutant strain lacking a metalloregulator of the Fur family revealed the activation of a full operon encoding a putative metal transporter system and a gene coding for a Histidine-rich lipoprotein (Hrl). We recognized a conserved sequence with dyad symmetry within the promoter region of the Fur-regulated genes. Mutagenesis of the predicted Fur operator within the hrl promoter abrogated Fur- and metal-dependent expression of a reporter gene. Metal starvation still impelled a strong transcriptional response in the fur mutant, demonstrating the existence of Fur-independent regulatory pathways controlling metal homeostasis. Finally, analysis of metal accumulation in the wild-type strain and the fur mutant by ICP-MS revealed an important role of Fur in nickel acquisition. Keywords: Ferric uptake regulator; Histidine-rich proteins; Mycoplasma genitalium; emerging STI pathogen; metal acquisition systems; metallome; novel therapeutic targets

Reference Data for Attentional, Executive, Linguistic, and Visual Processing Tests Obtained from Cognitively Healthy Individuals with Normal Alzheimer's Disease Cerebrospinal Fluid Biomarker Levels

BACKGROUND: Conventional neuropsychological norms likely include cognitively unimpaired (CU) individuals with preclinical Alzheimer's disease (AD) pathology (amyloid-β, tau, and neurodegeneration) since they are based on cohorts without AD biomarkers data. Due to this limitation, population-based norms would lack sensitivity for detecting subtle cognitive decline due to AD, the transitional stage between healthy cognition and mild cognitive impairment. We have recently published norms for memory tests in individuals with normal cerebrospinal fluid (CSF) AD biomarker levels. OBJECTIVE: The aim of the present study was to provide further AD biomarker-based cognitive references covering attentional, executive function, linguistic, and visual processing tests. METHODS: We analyzed 248 CU individuals aged between 50-70 years old with normal CSF Aβ, p-tau, and neurodegeneration (t-tau) biomarker levels. The tests included were the Trail Making Test (TMT), Semantic Fluency Test, Digit and Symbol Span, Coding, Matrix Reasoning, Judgement of Line Orientation and Visual Puzzles. Normative data were developed based on regression models adjusted for age, education, and sex when needed. We present equations to calculate z-scores, the corresponding normative percentile tables, and online calculators. RESULTS: Age, education, and sex were associated with performance in all tests, except education for the TMT-A, and sex for the TMT-B, Coding, and Semantic Fluency. Cut-offs derived from the current biomarker-based reference data were higher and more sensitive than standard norms. CONCLUSION: We developed reference data obtained from individuals with evidence of non-pathologic AD biomarker levels that may improve the objective characterization of subtle cognitive decline in preclinical AD

Helios modulates the maturation of a CA1 neuronal subpopulation required for spatial memory formation

Currently, molecular, electrophysiological and structural studies delineate several neural subtypes in the hippocampus. However, the precise developmental mechanisms that lead to this diversity are still unknown. Here we show that alterations in a concrete hippocampal neuronal subpopulation during development specifically affect hippocampal-dependent spatial memory. We observed that the genetic deletion of the transcription factor Helios in mice, which is specifically expressed in developing hippocampal calbindin-positive CA1 pyramidal neurons (CB-CA1-PNs), induces adult alterations affecting spatial memory. In the same mice, CA3-CA1 synaptic plasticity and spine density and morphology in adult CB-CA1-PNs were severely compromised. RNAseq experiments in developing hippocampus identified an aberrant increase on the Visinin-like protein 1 (VSNL1) expression in the hippocampi devoid of Helios. This aberrant increase on VSNL1 levels was localized in the CB-CA1-PNs. Normalization of VSNL1 levels in CB-CA1-PNs devoid of Helios rescued their spine loss in vitro. Our study identifies a novel and specific developmental molecular pathway involved in the maturation and function of a CA1 pyramidal neuronal subtype

Swarms of Enzyme-Powered Nanomotors Enhance the Diffusion of Macromolecules in Viscous Media

Over the past decades, the development of nanoparticles (NPs) to increase the efficiency of clinical treatments has been subject of intense research. Yet, most NPs have been reported to possess low efficacy as their actuation is hindered by biological barriers. For instance, synovial fluid (SF) present in the joints is mainly composed of hyaluronic acid (HA). These viscous media pose a challenge for many applications in nanomedicine, as passive NPs tend to become trapped in complex networks, which reduces their ability to reach the target location. This problem can be addressed by using active NPs (nanomotors, NMs) that are self-propelled by enzymatic reactions, although the development of enzyme-powered NMs, capable of navigating these viscous environments, remains a considerable challenge. Here, the synergistic effects of two NMs troops, namely hyaluronidase NMs (HyaNMs, Troop 1) and urease NMs (UrNMs, Troop 2) are demonstrated. Troop 1 interacts with the SF by reducing its viscosity, thus allowing Troop 2 to swim more easily through the SF. Through their collective motion, Troop 2 increases the diffusion of macromolecules. These results pave the way for more widespread use of enzyme-powered NMs, e.g., for treating joint injuries and improving therapeutic effectiveness compared with traditional methods. The conceptual idea of the novel approach using hyaluronidase NMs (HyaNMs) to interact with and reduce the viscosity of the synovial fluid (SF) and urease NMs (UrNMs) for a more efficient transport of therapeutic agents in joints.imag

Therapeutic targeting of HER2–CB2R heteromers in HER2-positive breast cancer

There is a subtype of breast cancer characterized by the overexpression of the oncogene HER2. Although most patients with this diagnosis benefit from HER2-targeted treatments, some do not respond to these therapies and others develop resistance with time. New tools are therefore warranted for the treatment of this patient population, and for early identification of those individuals at a higher risk of developing innate or acquired resistance to current treatments. Here, we show that HER2 forms heteromer complexes with the cannabinoid receptor CB2R, the expression of these structures correlates with poor patient prognosis, and their disruption promotes antitumor responses. Collectively, our results support HER2–CB2R heteromers as new therapeutic targets and prognostic tools in HER2+ breast cancer

Charming and bewitching : considering the Harry Potter series

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ICO-ICS Praxis para el tratamiento médico y con irradiación del adenocarcinoma del páncreas

Tractament mèdic; Tractament amb irradiació; Adenocarcinoma; Pàncrees; CàncerTratamiento médico; Tratamiento con irradiación; Adenocarcinoma; Páncreas; CáncerMedical treatment; Irradiation treatment; Adenocarcinoma; Pancreas; CancerEl càncer de pàncrees se situa com la tercera causa més freqüent de càncer en la forma d'adenocarcinoma ductal pancreàtic. És un dels càncers més agressius i amb un percentatge més baix de curació. Els objectius d'aquesta guia són: -Desenvolupar, difondre, implementar i avaluar resultats de la ICO-ICSPraxi de càncer de pàncrees. -Disminuir la variabilitat terapèutica entre els pacients tractats als diferents centres d'aquesta institució. -Implementar els resultats de la terapèutica en els pacients amb adenocarcinoma de pàncrees tractats d'acord amb les recomanacions d'aquesta guia

ICO-ICS Praxi per al tractament mèdic i amb irradiació de càncer gàstric i d'unió esofagogàstrica

Tractament mèdic; Tractament amb irradiació; Càncer de la unió esofagogàstricaTratamiento médico; Tratamiento con irradiación; Cáncer de la unión esofagogástricaMedical treatment; Irradiation treatment; Esophagogastric union cancerEl càncer gàstric (CG) és actualment el vuitè tipus de càncer més prevalent a la Unió Europea on, segons les estimacions, el 2018 es calculen 80.211 casos diagnosticats en ambdós sexes amb una taxa estimada d'incidència estandarditzada per edat de 6,4 casos per cada 100.000 habitants. En el cas d'Espanya, segons dades d'incidència i mortalitat del projecte GLOBOCAN i de l'Observatori Europeu del Càncer, se situa en novè lloc, després del càncer de bufeta i el càncer uterí, pel que fa a freqüència. Els objectius d'aquesta guia són: Desenvolupar, difondre, implementar i avaluar resultats de l'ICO-ICSPraxi de càncer gàstric i d'unió esofagogàstrica. Disminuir la variabilitat terapèutica entre els pacients tractats als diferents centres d'aquesta institució. Implementar els resultats de la terapèutica en els pacients amb càncer gàstric i d'unió esofagogàstrica tractats d'acord amb les recomanacions d'aquesta guia.El cáncer gástrico (CG) es actualmente el octavo tipo de cáncer más prevalente en la Unión Europea donde, según las estimaciones, el 2018 se calculan 80.211 casos diagnosticados en ambos sexos con una tasa estimada de incidencia estandarizada por edad de 6,4 casos por cada 100.000 habitantes. En el caso de España, según datos de incidencia y mortalidad del proyecto GLOBOCAN y del Observatorio Europeo del Cáncer, se sitúa en noveno lugar, después del cáncer de vejiga y el cáncer uterino, en cuanto a frecuencia. Los objetivos de esta guía son: Desarrollar, difundir, implementar y evaluar resultados del ICO-ICSPraxi de cáncer gástrico y de unión esofagogástrica. Disminuir la variabilidad terapéutica entre los pacientes tratados en los diferentes centros de esta institución. Implementar los resultados de la terapéutica en los pacientes con cáncer gástrico y de unión esofagogástrica tratados de acuerdo con las recomendaciones de esta guía.Gastric cancer (GC) is currently the eighth most prevalent type of cancer in the European Union where, according to estimates, 80,211 cases diagnosed in both sexes are estimated at an estimated rate of incidence standardized by age of 6.4 cases per 100,000 people. In the case of Spain, according to the incidence and mortality data of the GLOBOCAN project and the European Cancer Observatory, it is placed ninth, after bladder cancer and uterine cancer, as it happens frequently. The objectives of this guide are: Developing, disseminating, implementing and evaluating the results of the ICO-ICSPraxi of gastric cancer and esophagogastric binding. Decrease the therapeutic variability between patients treated at the different centers of this institution. Implement the results of therapeutic treatment in patients with gastric cancer and esphagogastric binding treated in accordance with the recommendations of this guide