La ética informativa y el derecho de la información, ¿necesitan una nueva regulación?

Los cambios producidos por la globalización han generado un escenario cambiante, complejo y ambiguo, en el que los principios éticos han sufrido una merma importante, más allá de los estilos de gobierno, y que se instala particularmente en la problemática del derecho de la información. Dicho cambio traspone la necesidad de establecer distinciones éticas y legales, las cuales debencolocarse dentro de las nuevas dinámicas e interacciones, a la defensa de los periodistas para informar de los ciudadanos para acceder a dicha información. En este ensayo se ofrecen principios para el fortalecimiento de los principios ya establecidos frente a la idea de una nueva regulación sobre estos tópicos

Salt glands in Maledictosuchus riclaensis (Metriorhynchidae, Thalattosuchia) from the Callovian of the Iberian Peninsula

Maledictosuchus riclaensis is a Callovian metriorhynchid from the Iberian Peninsula. Metriorhynchids are marine crocodylomorphs that evolved numerous adaptations to a pelagic life-style. As well as morphological adaptations, they evolved hypertrophied salt glands, which imply a high degree of specialization. These glands were described in two metriorhynchid species. The salt glands control the ionic concentration balance in the organism. As they are soft tissue, they hardly fossilize. In the last years, computerized tomography has achieved great importance in palaeontological research, since it allows the visualization and study of the internal bone structures and the 3D digitalization in a non-invasive way and without putting the specimen at risk. The holotype of Maledictosuchus riclaensis consists on a very well preserved skull and three vertebrae. A computerized tomography of the skull shows the presence of hypertrophied salt glands in this taxonMaledictosuchus riclaensis es un metriorrínquido del Calloviense de la Península Ibérica. Los metriorrinquidos son un grupo de crocodilomorfos marinos que desarrollaron numerosas adaptaciones al medio marino pelágico. Además de adaptaciones morfológicas, desarrollaron glándulas de la sal hipertrofiadas, lo cual implica un alto grado de especialización. Estas glándulas se han descrito en dos especies de metriorrínquidos. Las glándulas de la sal se encargan de controlar el balance de la concentración de sales en el organismo. Al tratarse de tejidos blandos su preservación es muy poco frecuente. La tomografía computarizada ha alcanzado en los últimos años gran importancia en la investigación paleontológica, ya que permite la visualización y estudio de las estructuras internas de los huesos y su digitalización en 3D, de una forma no invasiva y sin poner en riesgo al ejemplar. El holotipo de Maledictosuchus riclaensis consiste en un cráneo muy bien preservado y tres vértebras. Una tomografía computarizada del cráneo reveló la presencia de glándulas de la sal hipertrofiadas en este taxó

Estudio de serie de casos de trombofilia primaria en Pediatría

Objetivo: Estudio descriptivo de niños con trombofilia primaria, analizando en los niños con trombosis las formas de presentación, análisis de factores de trombofilia adquirida en el periodo neonatal y fuera de él. Estudio evolutivo de los pacientes diagnosticados. Pacientes y métodos: Revisión retrospectiva de todos los pacientes que fueron diagnosticados trombofilia primaria en el periodo 1998-2017 en la consulta de hematología Infantil del Hospital Clínico de Valladolid. Se describen la edad, el sexo, los motivos de derivación y el tipo de trombofilia detectada y se analizan los factores de trombofilia adquirida en los casos de trombosis. Resultados: Fueron diagnosticados de trombofilia primaria 47 niños, 29 mujeres (61,7%) y 18 varones (38,3%), con una mediana de edad decimal al diagnóstico de 5,5 años. Diez de los pacientes presentaron trombosis (21,3%), siendo el estudio familiar por trombofilia en la familia el motivo más frecuente de estudio (35 casos, 75,5%). Durante el periodo de estudio se diagnosticaron 21 niños con trombosis y de ellos en 10 pacientes se encontró trombofilia primaria (47,6%). En los 35 niños sin trombosis como motivo de estudio predominó el Factor V de Leiden 21 casos (60%), seguidos de mutación de la protrombina G20210A en 5 casos (14,3%) y de déficit de proteína C en 5 casos (14,3%). Ninguno de los niños presentó episodios trombóticos evolutivos en los que no habían tenido ni nuevos episodios en los que presentaron trombosis. De los 10 casos de trombosis sólo 3 fueron Factor V Leiden (30%). En los casos de trombosis se describen y analizan, además de la trombofilia primaria encontrada, los factores de trombofilia adquirida y las patologías de base encontradas, siendo en el periodo neonatal las más frecuentes la hipoxia neonatal, prematuridad, sepsis y catéter central y fuera del periodo neonatal patologías de base significativas como el cáncer y su tratamiento, catéter central, infección, autoinmunidad, cardiopatía y anticoagulante lúpico. Conclusiones: En nuestro Hospital se diagnostica una media de un caso al año de trombosis en población pediátrica (1/30.000). La trombofilia primaria está presente en el 47,6% de los niños que presentan trombosis. La trombofilia primaria aislada no es suficiente para que un niño presente trombosis, siendo muy frecuente en la infancia que se sumen varios factores de trombofilia adquirida y patología de base importante.Grado en Medicin

Inhibitors against Fungal Cell Wall Remodeling Enzymes

Fungal β-1,3-glucan glucanosyltransferases are glucan-remodeling enzymes that play important roles in cell wall integrity, and are essential for the viability of pathogenic fungi and yeasts. As such, they are considered possible drug targets, although inhibitors of this class of enzymes have not yet been reported. Herein we report a multidisciplinary approach based on a structure-guided design using a highly conserved transglycosylase from Sacharomyces cerevisiae, that leads to carbohydrate derivatives with high affinity for Aspergillus fumigatus Gel4. We demonstrate by X-ray crystallography that the compounds bind in the active site of Gas2/Gel4 and interact with the catalytic machinery. The topological analysis of noncovalent interactions demonstrates that the combination of a triazole with positively charged aromatic moieties are important for optimal interactions with Gas2/Gel4 through unusual pyridinium cation–π and face-to-face π–π interactions. The lead compound is capable of inhibiting AfGel4 with an IC value of 42 μm.This work was supported by Spanish MINECO Contracts (CTQ2016‐76155‐R to P.M., and BFU2016‐75633‐P to R.H.‐G.), and an MRC Programme Grant (M004139) to D.M.F.v.A. We also acknowledge the Government of Aragón (Spain) (Bioorganic Chemistry group E‐10 and Protein Targets group B‐89) for financial support. The European Commission is gratefully acknowledged (BioStruct‐X grant agreement no. 283570 and BIOSTRUCTX_5186).Peer Reviewe

The south of Pozuelos (Jujuy, Argentina) before 1000 A.D. : first archaeological evidences

Este artículo tiene como objetivo dar a conocer las evidencias arqueológicas anteriores al 1.000 d.C. registradas en el sector sur de Pozuelos, las primeras de tal antigüedad reportadas para el área. Estas son escasas en relación a las de épocas posteriores, y consisten en representaciones rupestres, fragmentos cerámicos y material lítico hallado en superficie. No se han detectado hasta el momento ocupaciones en cuevas o aleros, ni arquitectura que puedan asignarse a este período temporal. En base a la información presentada se plantea que la ocupación arcaica de la región habría sido más intensa y extendida que la de época formativa temprana, y que la paulatina disminución en la cantidad de evidencias arqueológicas a medida que avanzamos en el tiempo, se habría acentuado notablemente para el primer milenio de nuestra era. Esto reflejaría un relativo despoblamiento del sur de Pozuelos hasta que, luego del 1.200 d.C., el número de habitantes del área de estudio se habría incrementado exponencialmente.This article aims to present the archaeological evidences prior to 1.000 AD recorded in the area of the South of Pozuelos, the oldest reported until this moment for the region. These are less abundant compared to those of recent times, and include rock art, pottery fragments and lithic materials found on the surface. We have not detected so far neither human occupations in caves or rockshelters, nor architecture that can be assigned to this temporary period. Based on the information presented it is suggested that the archaic occupation of the region would have been more intense and widespread than the early formative presence, and that the gradual decrease in the amount of archaeological evidence as we move forward in time, would have considerably accelerated in the first millennium AD. This would reflect a relative depopulation of the South of Pozuelos until 1.200 AD, when the number of inhabitants in the area of study would have exponentially increased.Fil: Angiorama, Carlos Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto Superior de Estudios Sociales. Universidad Nacional de Tucuman. Instituto Superior de Estudios Sociales; ArgentinaFil: Argañaraz Fochi, Diego. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Becerra, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto Superior de Estudios Sociales. Universidad Nacional de Tucuman. Instituto Superior de Estudios Sociales; ArgentinaFil: del Bel, Ezequiel. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto de Arqueología y Museo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Diaz, Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto Superior de Estudios Sociales. Universidad Nacional de Tucuman. Instituto Superior de Estudios Sociales; ArgentinaFil: Giusta, Marco Nicolás. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Leiton, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto Superior de Estudios Sociales. Universidad Nacional de Tucuman. Instituto Superior de Estudios Sociales; ArgentinaFil: Perez Pieroni, María Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto Superior de Estudios Sociales. Universidad Nacional de Tucuman. Instituto Superior de Estudios Sociales; ArgentinaFil: Rodriguez Curletto, Silvina Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto Superior de Estudios Sociales. Universidad Nacional de Tucuman. Instituto Superior de Estudios Sociales; ArgentinaFil: Torres Vega, Lucrecia Marina Raquel. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentin

Effect of a Very-Low-Calorie Ketogenic Diet on Circulating Myokine Levels Compared with the Effect of Bariatric Surgery or a Low-Calorie Diet in Patients with Obesity

: The preservation of muscle mass and muscle function after weight loss therapy is currently a considerable challenge in the fight against obesity. Muscle mass secretes proteins called myokines that have relevant functions in the regulation of metabolism and health. This study was aimed to evaluate whether a very low-calorie ketogenic (VLCK) diet may modulate myokine levels, in addition to changes in body composition, compared to a standard, balanced low-calorie (LC) diet or bariatric surgery in patients with obesity. Body composition, ketosis, insulin sensitivity and myokines were evaluated in 79 patients with overweight/obesity after a therapy to lose weight with a VLCK diet, a LC diet or bariatric surgery. The follow-up was 6 months. The weight loss therapies induced changes in myokine levels in association with changes in body composition and biochemical parameters. The effects on circulating myokine levels compared to those at baseline were stronger after the VLCK diet than LC diet or bariatric surgery. Differences reached statistical significance for IL-8, MMP2 and irisin. In conclusion, nutritional interventions or bariatric surgery to lose weight induces changes in circulating myokine levels, being this effect potentially most notable after following a VLCK diet

Genetic diversity in two variants of Orobanche gracilis Sm. [var. gracilis and var. deludens (Beck) A. Pujadas] (Orobanchaceae) from different regions of Spain

The pattern of genetic variation among populations of two Orobanche gracilis Sm. taxa (var. gracilis and var. deludens (Beck) A. Pujadas) from Northern and Southern Spain growing on different hosts was analysed using RAPD markers. The diversity analysis within populations revealed a higher level of diversity in the populations from the North when compared to the Southern ones. The results of principal co-ordinate analysis (PCoA) based on Dice distances among samples clearly established the separation of samples according to the taxonomical variety and the geographical origin of each population. The Southern populations of both var. gracilis and var. deludens were more differentiated among them than those of var. gracilis from the North. The analysis of molecular variance (AMOVA) indicated that the lowest level of population differentiation was found in O. gracilis var. gracilis from the North, whereas in the case of O.gracilis var. deludens from the South most of the genetic diversity was attributable to differences among populations. Possible explanations for the distribution of variation in these populations are discussed

Biomarkers of tumor-reactive CD4+ and CD8+ TILs associate with improved prognosis in endometrial cancer

Background: Despite the growing interest in immunotherapeutic interventions for endometrial cancer (EC), the prevalence, phenotype, specificity and prognostic value of tumor infiltrating lymphocytes (TILs) in this tumor type remains unclear. Methods: To better understand the role of TILs in EC, we analyzed the phenotypic traits of CD8+ and CD4+ EC-resident T cells from 47 primary tumors by high-dimensional flow cytometry. In addition, CD8+ and CD4+ TIL subpopulations were isolated based on the differential expression of programmed cell death protein-1 (PD-1) (negative, dim and high) and CD39 (positive or negative) by fluorescence activated cell sorting (FACS), expanded in vitro, and screened for autologous tumor recognition. We further investigated whether phenotypic markers preferentially expressed on CD8+ and CD4+ tumor-reactive TIL subsets were associated with the four distinct molecular subtypes of EC, tumor mutational burden and patient survival. Results: We found that CD8+TILs expressing high levels of PD-1 (PD-1hi) co-expressed CD39, TIM-3, HLA-DR and CXCL13, as compared with TILs lacking or displaying intermediate levels of PD-1 expression (PD-1- and PD-1dim, respectively). Autologous tumor reactivity of sorted and in vitro expanded CD8+ TILs demonstrated that the CD8+PD-1dimCD39+ and PD-1hiCD39+ T cell subsets both contained tumor-reactive TILs and that a higher level of PD-1 expression was associated with increased CD39 and a superior frequency of tumor reactivity. With respect to CD4+ T conventional (Tconv) TILs, co-expression of inhibitory and activation markers was more apparent on PD-1hi compared with PD-1- or PD-1dim T cells, and in fact, it was the CD4+PD-1hi subpopulation that accumulated the antitumor T cells irrespective of CD39 expression. Most importantly, detection of CD8+PD-1hiCD39+ and CD4+PD-1hi tumor-reactive T-cell subsets, but also markers specifically expressed by these subpopulations of TILs, that is, PD-1hi, CD39, CXCL13 and CD103 by CD8+ TILs and PD-1hi and CXCL13 by CD4+ Tconv TILs, correlated with prolonged survival of patients with EC. Conclusions: Our results demonstrate that EC are frequently infiltrated by tumor-reactive TILs, and that expression of PD-1hi and CD39 or PD-1hi can be used to select and expand CD8+ and CD4+ tumor-reactive TILs, respectively. In addition, biomarkers preferentially expressed on tumor-reactive TILs, rather than the frequency of CD3+, CD8+ and CD4+ lymphocytes, hold prognostic value suggesting their protective role in antitumor immunity

Comprehensive establishment and characterization of orthoxenograft mouse models of malignant peripheral nerve sheath tumors for personalized medicine

Malignant peripheral nerve sheath tumors (MPNSTs) are soft-tissue sarcomas that can arise either sporadically or in association with neurofibromatosis type 1 (NF1). These aggressive malignancies confer poor survival, with no effective therapy available. We present the generation and characterization of five distinct MPNST orthoxenograft models for preclinical testing and personalized medicine. Four of the models are patient-derived tumor xenografts (PDTX), two independent MPNSTs from the same NF1 patient and two from different sporadic patients. The fifth model is an orthoxenograft derived from an NF1-related MPNST cell line. All MPNST orthoxenografts were generated by tumor implantation, or cell line injection, next to the sciatic nerve of nude mice, and were perpetuated by 7-10 mouse-to-mouse passages. The models reliably recapitulate the histopathological properties of their parental primary tumors. They also mimic distal dissemination properties in mice. Human stroma was rapidly lost after MPNST engraftment and replaced by murine stroma, which facilitated genomic tumor characterization. Compatible with an origin in a catastrophic event and subsequent genome stabilization, MPNST contained highly altered genomes that remained remarkably stable in orthoxenograft establishment and along passages. Mutational frequency and type of somatic point mutations were highly variable among the different MPNSTs modeled, but very consistent when comparing primary tumors with matched orthoxenografts generated. Unsupervised cluster analysis and principal component analysis (PCA) using an MPNST expression signature of ~1,000 genes grouped together all primary tumor-orthoxenograft pairs. Our work points to differences in the engraftment process of primary tumors compared with the engraftment of established cell lines. Following standardization and extensive characterization and validation, the orthoxenograft models were used for initial preclinical drug testing. Sorafenib (a BRAF inhibitor), in combination with doxorubicin or rapamycin, was found to be the most effective treatment for reducing MPNST growth. The development of genomically well-characterized preclinical models for MPNST allowed the evaluation of novel therapeutic strategies for personalized medicine

The Arabidopsis condensin CAP‐D subunits arrange interphase chromatin

Condensins are best known for their role in shaping chromosomes. Other functions such as organizing interphase chromatin and transcriptional control have been reported in yeasts and animals, but little is known about their function in plants. To elucidate the specific composition of condensin complexes and the expression of CAP-D2 (condensin I) and CAP-D3 (condensin II), we performed biochemical analyses in Arabidopsis. The role of CAP-D3 in interphase chromatin organization and function was evaluated using cytogenetic and transcriptome analysis in cap-d3 T-DNA insertion mutants. CAP-D2 and CAP-D3 are highly expressed in mitotically active tissues. In silico and pull-down experiments indicate that both CAP-D proteins interact with the other condensin I and II subunits. In cap-d3 mutants, an association of heterochromatic sequences occurs, but the nuclear size and the general histone and DNA methylation patterns remain unchanged. Also, CAP-D3 influences the expression of genes affecting the response to water, chemicals, and stress. The expression and composition of the condensin complexes in Arabidopsis are similar to those in other higher eukaryotes. We propose a model for the CAP-D3 function during interphase in which CAP-D3 localizes in euchromatin loops to stiffen them and consequently separates centromeric regions and 45S rDNA repeats