Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease

R-Ras2 is a transforming GTPase that shares downstream effectors with Ras subfamily proteins. However, little information exists about the function of this protein in tumorigenesis and its signalling overlap with classical Ras GTPases. Here we show, by combining loss- and gain-of-function studies in breast cancer cells, mammary epithelial cells and mouse models, that endogenous R-Ras2 has a role in both primary breast tumorigenesis and the late metastatic steps of cancer cells in the lung parenchyma. R-Ras2 drives tumorigenesis in a phosphatidylinostiol-3 kinase (PI3K)-dependent and signalling autonomous manner. By contrast, its prometastatic role requires other priming oncogenic signals and the engagement of several downstream elements. R-Ras2 function is required even in cancer cells exhibiting constitutive activation of classical Ras proteins, indicating that these GTPases are not functionally redundant. Our results also suggest that application of long-term R-Ras2 therapies will result in the development of compensatory mechanisms in breast tumoursFil: Larive, Ramon. Universidad de Salamanca; España. University of Montpellier I and II; FranciaFil: Moriggi, Giulia. Universidad de Salamanca; EspañaFil: Menacho Márquez, Mauricio Ariel. Universidad de Salamanca; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Cañamero, Marta. Centro Nacional de Investigaciones Oncológicas; EspañaFil: de Alava, Enrique. Universidad de Salamanca; España. Hospital Universitario Virgen del Rocío. Sevilla; EspañaFil: Alarcón, Balbino. Centro de Biología Molecular ‘‘Severo Ochoa’. Madrid; EspañaFil: Dosil, Mercedes. Universidad de Salamanca; EspañaFil: Bustelo, Xosé R.. Universidad de Salamanca; Españ

Endoscopic ultrasound-guided transvascular needle biopsy of thoracic and abdominal lesions: a multicenter experience

Background and study aims Traditionally in the case of a vascular interposition, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been contraindicated. A transvascular route (TV) is feasible and probably a safe alternative approach in selected patients, but data are scarce. The primary aim of this study was to analyze the diagnostic yield and safety of EUS-TV-FNA in thoracic and abdominal lesions. Secondary aims included evaluation of the clinical impact and technical aspects. Patients and methods A retrospective multicenter study was conducted with inclusion of all consecutive patients that underwent EUS-TV-FNA from July 2007 to January 2020. Feasibility, cytopathology, procedure details, and safety were evaluated. Univariate analysis was performed to identify variables associated with incidents, cytopathological diagnosis, and clinical impact. Results Data were collected from a total of 49 cases and 50 EUS-TV-FNAs. The aorta (n = 19) and portal system (n = 17) were the most frequently punctured. The most frequent lesions were mediastinal lymph nodes (n = 13) and pancreatic tumors (n = 11). The diagnostic yield was 86 %, and there were nondiagnostic samples in seven cases. Overall sensitivity, specificity, and accuracy were 88% (95 % CI, 0.74-0.96), 100% (95 % CI, 0.59-1), and 90% (95 % CI, 0.78-0.96), respectively. Only three incidents were detected: two mural hematomas and a self-limited bleeding of gastroduodenal artery. In most patients, there was a significant impact on clinical management (88%). Arterial vessel and ASA-III had a trend with incidents (both, P < 0.08). Rapid on-site evlauation was found to be an independent predictor for obtaining a conclusive sample (OR 6.2; 95%CI, 1.06-36.73, P < 0.04). Conclusions EUS-TV-FNA is feasible, seems to be safe, and can be recommended when no other targets are available, and the information obtained would impact on the clinical plan

SEOM clinical guideline thyroid cancer (2019)

Thyroid carcinoma is the most frequent endocrine malignancy and accounts for around 3% of global cancer incidence. Different histologies and clinical scenarios make necessary a multidisciplinary approach that includes new diagnostic methods and surgical, radiopharmaceutical and systemic therapies. This guideline updates several aspects of management of thyroid cancer

The PAU survey: Estimating galaxy photometry with deep learning

With the dramatic rise in high-quality galaxy data expected from Euclid and Vera C. Rubin Observatory, there will be increasing demand for fast high-precision methods for measuring galaxy fluxes. These will be essential for inferring the redshifts of the galaxies. In this paper, we introduce Lumos, a deep learning method to measure photometry from galaxy images. Lumos builds on BKGnet, an algorithm to predict the background and its associated error, and predicts the background-subtracted flux probability density function. We have developed Lumos for data from the Physics of the Accelerating Universe Survey (PAUS), an imaging survey using 40 narrow-band filter camera (PAUCam). PAUCam images are affected by scattered light, displaying a background noise pattern that can be predicted and corrected for. On average, Lumos increases the SNR of the observations by a factor of 2 compared to an aperture photometry algorithm. It also incorporates other advantages like robustness towards distorting artifacts, e.g. cosmic rays or scattered light, the ability of deblending and less sensitivity to uncertainties in the galaxy profile parameters used to infer the photometry. Indeed, the number of flagged photometry outlier observations is reduced from 10% to 2%, comparing to aperture photometry. Furthermore, with Lumos photometry, the photo-z scatter is reduced by ~10% with the Deepz machine learning photo-z code and the photo-z outlier rate by 20%. The photo-z improvement is lower than expected from the SNR increment, however currently the photometric calibration and outliers in the photometry seem to be its limiting factor.Comment: 20 pages, 22 figure

On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm

N-Acetyl-L-Glutamate Kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence→structure→dynamics→function © 2010 Marcos et al

Characterizing the Invasive Tumor Front of Aggressive Uterine Adenocarcinoma and Leiomyosarcoma

The invasive tumor front (the tumor-host interface) is vitally important in malignant cell progression and metastasis. Tumor cell interactions with resident and infiltrating host cells and with the surrounding extracellular matrix and secreted factors ultimately determine the fate of the tumor. Herein we focus on the invasive tumor front, making an in-depth characterization of reticular fiber scaffolding, infiltrating immune cells, gene expression, and epigenetic profiles of classified aggressive primary uterine adenocarcinomas (24 patients) and leiomyosarcomas (11 patients). Sections of formalin-fixed samples before and after microdissection were scanned and studied. Reticular fiber architecture and immune cell infiltration were analyzed by automatized algorithms in colocalized regions of interest. Despite morphometric resemblance between reticular fibers and high presence of macrophages, we found some variance in other immune cell populations and distinctive gene expression and cell adhesion-related methylation signatures. Although no evident overall differences in immune response were detected at the gene expression and methylation level, impaired antimicrobial humoral response might be involved in uterine leiomyosarcoma spread. Similarities found at the invasive tumor front of uterine adenocarcinomas and leiomyosarcomas could facilitate the use of common biomarkers and therapies. Furthermore, molecular and architectural characterization of the invasive front of uterine malignancies may provide additional prognostic information beyond established prognostic factors

The PAU Survey: A Forward Modeling Approach for Narrow-band Imaging

Weak gravitational lensing is a powerful probe of the dark sector, once measurement systematic errors can be controlled. In Refregier & Amara (2014), a calibration method based on forward modeling, called MCCL, was proposed. This relies on fast image simulations (e.g., UFig; Berge et al. 2013) that capture the key features of galaxy populations and measurement effects. The MCCL approach has been used in Herbel et al. (2017) to determine the redshift distribution of cosmological galaxy samples and, in the process, the authors derived a model for the galaxy population mainly based on broad-band photometry. Here, we test this model by forward modeling the 40 narrow-band photometry given by the novel PAU Survey (PAUS). For this purpose, we apply the same forced photometric pipeline on data and simulations using Source Extractor (Bertin & Arnouts 1996). The image simulation scheme performance is assessed at the image and at the catalogues level. We find good agreement for the distribution of pixel values, the magnitudes, in the magnitude-size relation and the interband correlations. A principal component analysis is then performed, in order to derive a global comparison of the narrow-band photometry between the data and the simulations. We use a `mixing' matrix to quantify the agreement between the observed and simulated sets of Principal Components (PCs). We find good agreement, especially for the first three most significant PCs. We also compare the coefficients of the PCs decomposition. While there are slight differences for some coefficients, we find that the distributions are in good agreement. Together, our results show that the galaxy population model derived from broad-band photometry is in good overall agreement with the PAUS data. This offers good prospect for incorporating spectral information to the galaxy model by adjusting it to the PAUS narrow-band data using forward modeling.Comment: Submitted to JCAP, 28 pages, 15 figures, 3 appendice

Redes internacionales de la arquitectura española : 1r Seminario AEMCI : Barcelona, 9 de julio de 2019, Escuela Técnica Superior de Arquitectura de Barcelona, ETSAB-UPC

Descripció del recurs: 24 gener 2020Contribucions del primer Seminario AEMCI, celebrat a l'Escola Tècnica Superior d'Arquitectura de Barcelona, el 9 de juliol de 2019, en el marc del projecte competitiu "La arquitectura española en los medios de comunicación internacionales: publicaciones, exposiciones, congresos (primera parte: 1940-1975)". Els textos recullen els avenços de les investigacions en curs que formen part del projecte HAR2017-85205-PPrimera edició