A Stiff Extracellular Matrix Favors the Mechanical Cell Competition that Leads to Extrusion of Bacterially-Infected Epithelial Cells

Cell competition refers to the mechanism whereby less fit cells (“losers”) are sensed and eliminated by more fit neighboring cells (“winners”) and arises during many processes including intracellular bacterial infection. Extracellular matrix (ECM) stiffness can regulate important cellular functions, such as motility, by modulating the physical forces that cells transduce and could thus modulate the output of cellular competitions. Herein, we employ a computational model to investigate the previously overlooked role of ECM stiffness in modulating the forceful extrusion of infected “loser” cells by uninfected “winner” cells. We find that increasing ECM stiffness promotes the collective squeezing and subsequent extrusion of infected cells due to differential cell displacements and cellular force generation. Moreover, we discover that an increase in the ratio of uninfected to infected cell stiffness as well as a smaller infection focus size, independently promote squeezing of infected cells, and this phenomenon is more prominent on stiffer compared to softer matrices. Our experimental findings validate the computational predictions by demonstrating increased collective cell extrusion on stiff matrices and glass as opposed to softer matrices, which is associated with decreased bacterial spread in the basal cell monolayer in vitro. Collectively, our results suggest that ECM stiffness plays a major role in modulating the competition between infected and uninfected cells, with stiffer matrices promoting this battle through differential modulation of cell mechanics between the two cell populations

Glucocorticoid receptor changes its cellular location with breast cancer development.

Glucocorticoids play a major role in attenuation of the inflammatory response and they are useful in the primary combination chemotherapy of breast cancer, since in vitro studies have demonstrated an antiproliferative effect in human breast cancer cells. In contrast, it was recently shown that glucocorticoids protect against apoptotic signals evoked by cytokines, cAMP, tumour suppressors, and death genes in mammary gland epithelia. Their actions are mediated by intracellular receptor (GR) that functions as a hormone-dependent transcription factor; however, no previous studies have been focused on GR expression in different pathologies of the human breast, and the possible relationship with that of mineralocorticoid receptor (MR) and COX-2. Also, the role of these proteins on tumoral breast epithelial cells remains unclear. Therefore, we examined GR, MR and COX-2 expression by immunohistochemistry and Western blot techniques in 142 samples of human breast obtained by total or partial mastectomy. We found that the percentage of positive patients presenting nuclear immunoreaction to GR decreased with tumor development, while all samples analyzed showed cytoplasmic immunoreactions to MR. All positive samples to COX-2 antibody showed cytoplasmic location, a higher immunoreaction being observed in benign breast diseases than in carcinomatous lesions. Thus, breast cancer progression is associated with the accumulation of GR in the cytoplasm of tumoral cells and the decrease of COX-2 expression

Main crustal seismic sources in El Salvador

We present a map and a data set containing information about intra-plate seismic sources in El Salvador. These are the results of the field campaigns and data analysis carried out by the research group of Planetary Geodinamics, Active Tectonics and Related Risks from Complutense University of Madrid during the last 12 years. We include two maps, the first map contains 1405 fault traces with evidences of Quaternary activity derived form morphometric, paleoseismological and geomorphological analysis together with field data mapping carried in El Salvador. The second map is a synthesis of the 29 intra-plate seismic sources selected from the quaternary faults map. The geometry of these sources was simplified and we also include a table where some available data of the proposed sources are included, such as their name, orientation, length and slip-rate. For further interpretation and discussion of these sources see (Alonso-Henar et al., 2018) [1, doi.org/10.1016/j.enggeo.2018.06.015]This research was supported by the project“ QUAKESTEP”(CGL2017–83931-C3-1-P) founded by the Spanish Ministry of Science, Innovation and Universities. We are grateful to our colleagues atDGOA-MARN (Observatorio Ambiental del Ministerio de Medio Ambiente y Recursos Naturales de ElSalvador): Manuel Díaz, Walter Hernandez and Douglas Hernández for their assistance. Figures were produced using GMT softwar

Geochemistry of the Quaternary alkali basalts of Garrotxa (NE Volcanic Province, Spain): a case of double enrichment of the mantle lithosphere

The area of Garrotxa (also known as the Olot area) represents the most recent (700,000–11,500 y) and better preserved area of magmatic activity in the NE Volcanic Province of Spain (NEVP). This region comprises a suite of intracontinental leucite basanites, nepheline basanites and alkali olivine basalts, which in most cases represent primary or nearly primary liquids. The geochemical characteristics of these lavas are very similar to the analogous petrologic types of other Cenozoic volcanics of Europe, which are intermediate between HIMU, DM and EM1. Quantitative trace element modeling, suggests derivation from an enriched mantle source by degrees of melting that progressively increased from the leucite basanites (,4%) to the olivine basalts (,16%). However, the relatively more variable Sr–Nd–Pb isotope signature of the magmas suggests the participation of at least two distinct components in the mantle source: (1) a sublithospheric one with a geochemical signature similar to the magmas of Calatrava (Central Spain) and other basalts of Europe; and (2) an enriched lithospheric component with a K-bearing phase present. The geochemical model proposed here involves the generation of a hybrid mantle lithosphere source produced by the infiltration of the sublithospheric liquids into enriched domains of the mantle lithosphere, shortly before the melting event that generated the Garrotxa lavas. The available geological data suggest that the first enrichment event of the mantle lithosphere under the NEVP could be the result of Late Variscan mantle upwelling triggered by the extensional collapse of the Variscan orogen during the Permo-Carboniferous. By Jurassic/Cretaceous time, large-scale NNE-directed sublithospheric mantle channeling of thermally and chemically anomalous plume material was placed under the Iberian Peninsula and Central Europe. However, the geodynamic conditions in the NEVP did not favor magmatism, which could not take place until the Cenozoic after extension started. This favored the second enrichment event of the mantle lithosphere by entrainment and storage of liquids generated in the sublithospheric plume material. After a relatively short period of time, as extension progressed, it triggered melting in the enriched portions of the mantle lithosphere during the Quaternary, generating the Garrotxa volcanism.Depto. de Mineralogía y PetrologíaFac. de Ciencias GeológicasTRUEpu

CVD-MET: an image difference metric designed for analysis of color vision deficiency aids

Color vision deficiency (CVD) has gained in relevance in the last decade, with a surge of proposals for aid systems that aim to improve the color discrimination capabilities of CVD subjects. This paper focuses on the proposal of a new metric called CVD-MET, that can evaluate the efficiency and naturalness of these systems through a set of images using a simulation of the subject’s vision. In the simulation, the effect of chromatic adaptation is introduced via CIECAM02, which is relevant for the evaluation of passive aids (color filters). To demonstrate the potential of the CVD-MET, an evaluation of a representative set of passive and active aids is carried out both with conventional image quality metrics and with CVD-MET. The results suggest that the active aids (recoloration algorithms) are in general more efficient and produce more natural images, although the changes that are introduced do not shift the CVD’s perception of the scene towards the normal observer’s perception.Junta de Andalucia A-TIC-050-UGR18Spanish Government FIS2017-89258-PMinisterio de Ciencia, Innovación y Universidades RTI2018-094738-B-I0

Human pregnane X receptor is expressed in breast carcinomas, potential heterodimers formation between hPXR and RXR-alpha.

The human pregnane X receptor (hPXR) is an orphan nuclear receptor that induces transcription of response elements present in steroid-inducible cytochrome P 450 gene promoters. This activation requires the participation of retinoid X receptors (RXRs), needed partners of hPXR to form heterodimers. We have investigated the expression of hPXR and RXRs in normal, premalignant, and malignant breast tissues, in order to det. whether their expression profile in localized infiltrative breast cancer is assocd. with an increased risk of recurrent disease. Methods: Breast samples from 99 patients including benign breast diseases, in situ and infiltrative carcinomas were processed for immunohistochem. and Western-blot anal. Results: Cancer cells from patients that developed recurrent disease showed a high cytoplasmic location of both hPXR isoforms. Only the infiltrative carcinomas that relapsed before 48 mo showed nuclear location of hPXR isoform 2. This location was assocd. with the nuclear immunoexpression of RXR-alpha. Conclusion: Breast cancer cells can express both variants 1 and 2 of hPXR. Infiltrative carcinomas that recurred showed a nuclear location of both hPXR and RXR-alpha; therefore, the overexpression and the subcellular location changes of hPXR could be considered as a potential new prognostic indicator

Borrelia burgdorferi modulates the physical forces and immunity signaling in endothelial cells

Borrelia burgdorferi (Bb), a vector-borne bacterial pathogen and the causative agent of Lyme disease, can spread to distant tissues in the human host by traveling in and through monolayers of endothelial cells (ECs) lining the vasculature. To examine whether Bb alters the physical forces of ECs to promote its dissemination, we exposed ECs to Bb and observed a sharp and transient increase in EC traction and intercellular forces, followed by a prolonged decrease in EC motility and physical forces. All variables returned to baseline at 24 h after exposure. RNA sequencing analysis revealed an upregulation of innate immune signaling pathways during early but not late Bb exposure. Exposure of ECs to heat-inactivated Bb recapitulated only the early weakening of EC mechanotransduction. The differential responses to live versus heat-inactivated Bb indicate a tight interplay between innate immune signaling and physical forces in host ECs and suggest their active modulation by Bb

The Spanish Network on Environmental DMAs: introduction and main activities

Comunicación presentada en: V Reunión Española de Ciencia y Tecnología de Aerosoles – RECTA 2011 celebrada del 27 al 29 de junio de 2011 en CIEMAT, Madrid

Robust Resolution-Enhanced Prostate Segmentation in Magnetic Resonance and Ultrasound Images through Convolutional Neural Networks

[EN] Prostate segmentations are required for an ever-increasing number of medical applications, such as image-based lesion detection, fusion-guided biopsy and focal therapies. However, obtaining accurate segmentations is laborious, requires expertise and, even then, the inter-observer variability remains high. In this paper, a robust, accurate and generalizable model for Magnetic Resonance (MR) and three-dimensional (3D) Ultrasound (US) prostate image segmentation is proposed. It uses a densenet-resnet-based Convolutional Neural Network (CNN) combined with techniques such as deep supervision, checkpoint ensembling and Neural Resolution Enhancement. The MR prostate segmentation model was trained with five challenging and heterogeneous MR prostate datasets (and two US datasets), with segmentations from many different experts with varying segmentation criteria. The model achieves a consistently strong performance in all datasets independently (mean Dice Similarity Coefficient -DSC- above 0.91 for all datasets except for one), outperforming the inter-expert variability significantly in MR (mean DSC of 0.9099 vs. 0.8794). When evaluated on the publicly available Promise12 challenge dataset, it attains a similar performance to the best entries. In summary, the model has the potential of having a significant impact on current prostate procedures, undercutting, and even eliminating, the need of manual segmentations through improvements in terms of robustness, generalizability and output resolutionThis work has been partially supported by a doctoral grant of the Spanish Ministry of Innovation and Science, with reference FPU17/01993Pellicer-Valero, OJ.; González-Pérez, V.; Casanova Ramón-Borja, JL.; Martín García, I.; Barrios Benito, M.; Pelechano Gómez, P.; Rubio-Briones, J.... (2021). 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