The Tordera Delta, a hotspot to storm impacts in the coast northwards ofBarcelona (NW Mediterranean)

The Catalan coast, as most of the developed Mediterranean coastal zone, can be characterized as a high-risk area to the impact of storms due to the large concentrationof values together with the dominance of eroding shorelines. In consequence, any long-term coastal management scheme must include a risk analysis to permitdecision makers to better allocate resources. This can be done in a nested approach in which hotspots are first identified along the coast at a regional scale andsecondly, they are further analysed to produce dedicated risk reduction strategies. In this work, we apply the methodology developed within the RISC-KIT project foridentifying and analysing coastal hotspots in the Catalan coast as a test for applying it to Mediterranean conditions. Obtained results show that this methodology isvery efficient in identifying hotspots of storm-induced flooding and erosion at a regional scale. The adoption of the response approach resulted in the direct assessmentof the hazards' probability distributions, which allowed for the selection of the severity of the hotspots to be identified. When a given coastal stretch behaves as ahotspot for both hazards, it is identified as a very highly-sensitive area to storm impacts. In the study area, the Tordera Delta possesses this condition of very high“hotspotness.” This has been demonstrated by the large and frequent damages suffered by the site during the past decades. The paper analyses different aspects related to the risk management of this area, including stakeholder actions

CoQ10 reduces glioblastoma growth and infiltration through proteome remodeling and inhibition of angiogenesis and inflammation

Purpose: Most monotherapies available against glioblastoma multiforme (GBM) target individual hallmarks of this aggressive brain tumor with minimal success. In this article, we propose a therapeutic strategy using coenzyme Q10 (CoQ10) as a pleiotropic factor that crosses the blood-brain barrier and accumulates in cell membranes acting as an antioxidant, and in mitochondrial membranes as a regulator of cell bioenergetics and gene expression. Methods: Xenografts of U251 cells in nu/nu mice were used to assay tumor growth, hypoxia, angiogenesis, and inflammation. An orthotopic model was used to explore microglial infiltration, tumor growth, and invasion into the brain parenchyma. Cell proliferation, migration, invasion, proteome remodeling, and secretome were assayed in vitro. Conditioned media were used to assay angiogenesis, monocyte chemoattraction, and differentiation into macrophages in vitro. Results: CoQ10 treatment decreased tumor volume in xenografts and orthotopic models, although its effect on tumor cell proliferation was not direct. Tumors from mice treated with CoQ10 were less hypoxic and vascularized, having less infiltration from inflammatory cells. Treatment-induced downregulation of HIF-1α and NF-kB led to a complete remodeling of the tumor cells proteome and secretome, impacting angiogenesis, monocyte infiltration, and their differentiation into macrophages. Besides, tumor cell migration and invasion were drastically restricted by mechanisms involving modulation of the actin cytoskeleton and downregulation of matrix metalloproteases (MMPs). Conclusions: CoQ10 has a pleiotropic effect on GBM growth, targeting several hallmarks simultaneously. Thus, its integration into current treatments of this fatal disease should be considered. Keywords: Angiogenesis; Coenzyme Q10; Glioblastoma; Inflammation; Invasion.Propósito: La mayoría de las monoterapias disponibles contra el glioblastoma multiforme (GBM) se dirigen a las características individuales de este tumor cerebral agresivo con un éxito mínimo. En este artículo proponemos una estrategia terapéutica utilizando la coenzima Q 10 (CoQ 10 ) como factor pleiotrópico que atraviesa la barrera hematoencefálica y se acumula en las membranas celulares actuando como antioxidante, y en las membranas mitocondriales como regulador de la bioenergética celular y gen expresión. Métodos: Se utilizaron xenoinjertos de células U251 en ratones nu/nu para analizar el crecimiento tumoral, la hipoxia, la angiogénesis y la inflamación. Se utilizó un modelo ortotópico para explorar la infiltración microglial, el crecimiento tumoral y la invasión del parénquima cerebral. Se ensayaron in vitro la proliferación celular, la migración, la invasión, la remodelación del proteoma y el secretoma. Se usaron medios acondicionados para analizar la angiogénesis, la quimioatracción de monocitos y la diferenciación en macrófagos in vitro. Resultados: el tratamiento con CoQ 10 disminuyó el volumen tumoral en xenoinjertos y modelos ortotópicos, aunque su efecto sobre la proliferación de células tumorales no fue directo. Los tumores de ratones tratados con CoQ 10 eran menos hipóxicos y vascularizados, con menos infiltración de células inflamatorias. La regulación a la baja inducida por el tratamiento de HIF-1α y NF-kB condujo a una remodelación completa del proteoma y el secretoma de las células tumorales, lo que impactó en la angiogénesis, la infiltración de monocitos y su diferenciación en macrófagos. Además, la migración e invasión de células tumorales se vieron drásticamente restringidas por mecanismos que involucran la modulación del citoesqueleto de actina y la regulación a la baja de las metaloproteasas de matriz (MMP). Conclusiones: CoQ 10 tiene un efecto pleiotrópico en el crecimiento de GBM, apuntando a varios sellos simultáneamente. Por lo tanto, se debe considerar su integración en los tratamientos actuales de esta enfermedad mortal

Different rates of spontaneous mutation of chloroplastic and nuclear viroids as determined by high-fidelity ultra-deep sequencing

[EN] Mutation rates vary by orders of magnitude across biological systems, being higher for simpler genomes. The simplest known genomes correspond to viroids, subviral plant replicons constituted by circular non-coding RNAs of few hundred bases. Previous work has revealed an extremely high mutation rate for chrysanthemum chlorotic mottle viroid, a chloroplastreplicating viroid. However, whether this is a general feature of viroids remains unclear. Here, we have used high-fidelity ultra-deep sequencing to determine the mutation rate in a common host (eggplant) of two viroids, each representative of one family: the chloroplastic eggplant latent viroid (ELVd, Avsunviroidae) and the nuclear potato spindle tuber viroid (PSTVd, Pospiviroidae). This revealed higher mutation frequencies in ELVd than in PSTVd, as well as marked differences in the types of mutations produced. Rates of spontaneous mutation, quantified in vivo using the lethal mutation method, ranged from 1/1000 to 1/800 for ELVd and from 1/7000 to 1/3800 for PSTVd depending on sequencing run. These results suggest that extremely high mutability is a common feature of chloroplastic viroids, whereas the mutation rates of PSTVd and potentially other nuclear viroids appear significantly lower and closer to those of some RNA viruses.This work was supported by the European Research Council (erc.europa.eu; ERC-2011-StG-281191-VIRMUT to RS), the Spanish Ministerio de Economia y Competitividad (www.mineco.gob.es; BFU2013-41329 grant to RS, BFU2014-56812-P grant to RF, and a predoctoral fellowship to ALC), and the Spanish Junta de Comunidades de Castilla-La Mancha (www.castillalamancha.es;postdoctoral fellowship to CB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.López-Carrasco, MA.; Ballesteros Martínez, C.; Sentandreu, V.; Delgado Villar, SG.; Gago Zachert, SP.; Flores Pedauye, R.; Sanjuan Verdeguer, R. (2017). Different rates of spontaneous mutation of chloroplastic and nuclear viroids as determined by high-fidelity ultra-deep sequencing. PLoS Pathogens. 13(9):1-17. https://doi.org/10.1371/journal.ppat.1006547S117139Ganai, R. A., & Johansson, E. (2016). DNA Replication—A Matter of Fidelity. Molecular Cell, 62(5), 745-755. doi:10.1016/j.molcel.2016.05.003Lynch, M. (2010). Evolution of the mutation rate. Trends in Genetics, 26(8), 345-352. doi:10.1016/j.tig.2010.05.003Sanjuán, R., & Domingo-Calap, P. (2016). Mechanisms of viral mutation. Cellular and Molecular Life Sciences, 73(23), 4433-4448. doi:10.1007/s00018-016-2299-6Gago, S., Elena, S. F., Flores, R., & Sanjuan, R. (2009). 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Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Ahora / Ara

La cinquena edició del microrelatari per l’eradicació de la violència contra les dones de l’Institut Universitari d’Estudis Feministes i de Gènere «Purificación Escribano» de la Universitat Jaume I vol ser una declaració d’esperança. Aquest és el moment en el qual les dones (i els homes) hem de fer un pas endavant i eliminar la violència sistèmica contra les dones. Ara és el moment de denunciar el masclisme i els micromasclismes començant a construir una societat més igualitària. Cadascun dels relats del llibre és una denúncia i una declaració que ens encamina cap a un món millor

Efficacy and safety evaluation of nilotinib and dasatinib (2G -TKI) on first line treatment in 73 patients with CML-CP outside of clinical trials. Andalusian CML registry (RALMC)

Even though they were approved last June 2011 to be used on first line, it is not a common procedure to begin treatment of CML-CP with 2GTKI, despite it has been demonstrated its efficacy and safety against imatinib on ENESTnd and Dasision clinical trials.N