Oncogenic Role of Secreted Engrailed Homeobox 2 (EN2) in Prostate Cancer

Engrailed variant-2 (EN2) has been suggested as a potential diagnostic biomarker; however, its presence and functional role in prostate cancer (PCa) cells is still controversial or unknown. Here, we analyzed 1) the expression/secretion profile of EN2 in five independent samples cohorts from PCa patients and controls (prostate tissues and/or urine) to determine its utility as a PCa biomarker; and 2) the functional role of EN2 in normal (RWPE1) and tumor (LNCaP/22Rv1/PC3) prostate cells to explore its potential value as therapeutic target. EN2 was overexpressed in our two cohorts of PCa tissues compared to control and in tumor cell lines compared with normal-like prostate cells. This profile was corroborated in silico in three independent data sets [The Cancer Genome Atlas(TCGA)/Memorial Sloan Kettering Cancer Center (MSKCC)/Grasso]. Consistently, urine EN2 levels were elevated and enabled discrimination between PCa and control patients. EN2 treatment increased cell proliferation in LNCaP/22Rv1/PC3 cells, migration in RWPE1/PC3 cells, and PSA secretion in LNCaP cells. These effects were associated, at least in the androgen-sensitive LNCaP cells, with increased AKT and androgen-receptor phosphorylation levels and with modulation of key cancer-associated genes. Consistently, EN2 treatment also regulated androgen-receptor activity (full-length and splicing variants) in androgen-sensitive 22Rv1 cells. Altogether, this study demonstrates the potential utility of EN2 as a non-invasive diagnostic biomarker for PCa and provides novel and valuable information to further investigate its putative utility to develop new therapeutic tools in PCa

The ALMA Spectroscopic Survey in the Hubble Ultra Deep Field: The Nature of the Faintest Dusty Star-forming Galaxies

We present a characterization of the physical properties of a sample of 35 securely detected, dusty galaxies in the deep ALMA 1.2 mm image obtained as part of the ALMA Spectroscopic Survey in the Hubble Ultra Deep Field (ASPECS) Large Program. This sample is complemented by 26 additional sources identified via an optical/ infrared source positional prior. Using their well-characterized spectral energy distributions, we derive median stellar masses and star formation rates (SFR) of 4.8 10 ´ 10 M☉ and 30 M☉ yr−1 , respectively, and interquartile ranges of (2.4–11.7) × 1010 M☉ and 20–50 M☉ yr−1 . We derive a median spectroscopic redshift of 1.8 with an interquartile range 1.1–2.6, significantly lower than submillimeter galaxies detected in shallower, wide-field surveys. We find that 59% ± 13%, 6% ± 4%, and 34% ± 9% of our sources are within, above, and below±0.4 dex from the SFR–stellar-mass relation or main sequence (MS), respectively. The ASPECS galaxies closely follow the SFR–molecular gas mass relation and other previously established scaling relations, confirming a factor of five increase of the gas-to-stellar-mass ratio from z = 0.5 to 2.5 and a mild evolution of the gas depletion timescales with a typical value of 0.7 Gyr at z = 1–3. ASPECS galaxies located significantly below the MS, a poorly exploited parameter space, have low gas-to-stellar-mass ratios of ∼0.1–0.2 and long depletion timescales >1 Gyr. Galaxies along the MS dominate the cosmic density of molecular gas at all redshifts. Systems above the MS have an increasing contribution to the total gas reservoirs from z < 1 to z = 2.5, while the opposite is found for galaxies below the MS

Communication, development, and social change in Spain: A field between institutionalization and implosion

This paper renders an account of the rapid institutionalization of the academic field of Communication for Development and Social Change (CDCS) in Spain in recent years following a period of neglect and marginalization. The ongoing expansion of the field of CDSC in the Spanish context is understood as a process of implosion, i.e. a collapse inwards, which results from the inconsistencies and weaknesses of fast and late institutionalization. The methodological approach for this inquiry is a documental review of both academic literature and research and institutional reports produced in Spain between 1980 and 2010. Based on this review, the paper contrasts the trajectory of the field in Spain with the debates at the international level, establishing relevant continuities and differences.This article is part of the Research Project (Ministry of Economy and Competitiveness, Spain) CSO2014-52005-R titled ‘Evaluation and Monitoring of Communication for Development and Social Change in Spain: design of indicators to measure its social impact’ (2015–2017)17 página

The ALMA Spectroscopic Survey in the Hubble Ultra Deep Field: Evolution of the Molecular Gas in CO-selected Galaxies

We analyze the interstellar medium properties of a sample of 16 bright CO line emitting galaxies identified in the ALMA Spectroscopic Survey in the Hubble Ultra Deep Field (ASPECS) Large Program. This CO−selected galaxy sample is complemented by two additional CO line emitters in the UDF that are identified based on their MultiUnit Spectroscopic Explorer (MUSE) optical spectroscopic redshifts. The ASPECS CO−selected galaxies cover a larger range of star formation rates (SFRs) and stellar masses compared to literature CO emitting galaxies at z > 1 for which scaling relations have been established previously. Most of ASPECS CO-selected galaxies follow these established relations in terms of gas depletion timescales and gas fractions as a function of redshift, as well as the SFR–stellar mass relation (“galaxy main sequence”). However, we find that ∼30% of the galaxies (5 out of 16) are offset from the galaxy main sequence at their respective redshift, with ∼12% (2 out of 16) falling below this relationship. Some CO-rich galaxies exhibit low SFRs, and yet show substantial molecular gas reservoirs, yielding long gas depletion timescales. Capitalizing on the well-defined cosmic volume probed by our observations, we measure the contribution of galaxies above, below, and on the galaxy main sequence to the total cosmic molecular gas density at different lookback times. We conclude that main-sequence galaxies are the largest contributors to the molecular gas density at any redshift probed by our observations (z ∼ 1−3). The respective contribution by starburst galaxies above the main sequence decreases from z ∼ 2.5 to z ∼ 1, whereas we find tentative evidence for an increased contribution to the cosmic molecular gas density from the passive galaxies below the main sequenc

The ALMA Spectroscopic Survey in the HUDF: CO Luminosity Functions and the Molecular Gas Content of Galaxies through Cosmic History

We use the results from the ALMA large program ASPECS, the spectroscopic survey in the Hubble Ultra Deep Field (HUDF), to constrain CO luminosity functions of galaxies and the resulting redshift evolution of ρ(H2). The broad frequency range covered enables us to identify CO emission lines of different rotational transitions in the HUDF at z > 1. We find strong evidence that the CO luminosity function evolves with redshift, with the knee of the CO luminosity function decreasing in luminosity by an order of magnitude from ~2 to the local universe. Based on Schechter fits, we estimate that our observations recover the majority (up to ~90%, depending on the assumptions on the faint end) of the total cosmic CO luminosity at z = 1.0–3.1. After correcting for CO excitation, and adopting a Galactic CO-to-H2 conversion factor, we constrain the evolution of the cosmic molecular gas density ρ(H2): this cosmic gas density peaks at z ~ 1.5 and drops by a factor of ${6.5}_{-1.4}^{+1.8}$ to the value measured locally. The observed evolution in ρ(H2), therefore, closely matches the evolution of the cosmic star formation rate density ρ SFR. We verify the robustness of our result with respect to assumptions on source inclusion and/or CO excitation. As the cosmic star formation history can be expressed as the product of the star formation efficiency and the cosmic density of molecular gas, the similar evolution of ρ(H2) and ρ SFR leaves only little room for a significant evolution of the average star formation efficiency in galaxies since z ~ 3 (85% of cosmic history)

Prevention, assessment, diagnosis and management of diabetic foot based on clinical practice guidelines: A systematic review.

Diabetic foot complications are the main reason for hospitalization and amputation in people with diabetes and have a prevalence of up to 25%. Clinical practice guidelines are recommendations based on evidence with the aim of improving health care. The main aim of this study was to carry out a systematic review of the levels of the evaluation and treatment strategies that appear in the clinical practice guidelines focus on diabetic foot or diabetes with diabetic foot section. Another objective of this study was to perform an analysis of the levels of evidence in support of the recommendations made by the selected clinical practice guidelines. A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and a quality assessment by the Appraisal of Guidelines for Research and Evaluation (AGREE II) were performed. The databases checked were "NICE", "Cinahl", "Health Guide", "RNAO", "Sign", "PubMed", "Scopus" and "NCG". The search terms included were "diabetic foot", "guideline(s)", "practice guideline(s)" and "diabetes." Twelve articles were selected after checked inclusion criteria and quality assessment. A summary and classification of the recommendations was completed. The heterogeneity of levels of evidence and grades of recommendation of the CPGs included regarding the management, approach and treatment of DF makes it difficult to interpret and assume them in clinical practice in order to select the most correct procedures. Despite this and according to the detailed study of the guidelines included in this work, it can be concluded that the highly recommendable interventions for DF management are debridement (very high level of evidence and strongly recommended), foot evaluation (moderate level of evidence and fairly recommended) and therapeutic footwear (moderate level of evidence and fairly recommended)

A distancia

Compendio de artículos que tratan de acercar a la comunidad universitaria algunos de los aspectos básicos para conocer la problemática del medio ambiente desde la perspectiva económica. La sensibilidad medioambiental y la actuación de los ciudadanos, de las empresas y del sector público; las políticas económicas ambientales -en su triple perspectiva: nacional, comunitaria e internacional- y la teoría de juegos, como modelo explicativo de la estrategia de los agentes de mercado, constituyen los temas analizados.MadridBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5 - 3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

The ALMA Spectroscopic Survey in the HUDF: The Cosmic Dust and Gas Mass Densities in Galaxies up to z ∼ 3

Using the deepest 1.2 mm continuum map to date in the Hubble Ultra Deep Field, which was obtained as part of the ALMA Spectroscopic Survey (ASPECS) large program, we measure the cosmic density of dust and implied gas (H2+H I) mass in galaxies as a function of look-back time. We do so by stacking the contribution from all H-band selected galaxies above a given stellar mass in distinct redshift bins, r M Mz > , dust * ( ) and r M Mz > , gas * ( ). At all redshifts, r M Mz > , dust * ( ) and r M Mz > , gas * ( ) grow rapidly as M decreases down to 1010 Me, but this growth slows down toward lower stellar masses. This flattening implies that at our stellar mass-completeness limits (108 Me and 108.9 Me at z ∼ 0.4 and z ∼ 3), both quantities converge toward the total cosmic dust and gas mass densities in galaxies. The cosmic dust and gas mass densities increase at early cosmic time, peak around z ∼ 2, and decrease by a factor ∼4 and 7, when compared to the density of dust and molecular gas in the local universe, respectively. The contribution of quiescent galaxies (i.e., with little on-going star formation) to the cosmic dust and gas mass densities is minor (10%). The redshift evolution of the cosmic gas mass density resembles that of the SFR density, as previously found by CO-based measurements. This confirms that galaxies have relatively constant star formation efficiencies (within a factor ∼2) across cosmic time. Our results also imply that by z ∼ 0, a large fraction (∼90%) of dust formed in galaxies across cosmic time has either been destroyed or ejected to the intergalactic medium

Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis

Cholangiocarcinoma (CCA) comprises a group of heterogeneous biliary cancers with dismal prognosis. The etiologies of most CCAs are unknown, but primary sclerosing cholangitis (PSC) is a risk factor. Non-invasive diagnosis of CCA is challenging and accurate biomarkers are lacking. We aimed to characterize the transcriptomic profile of serum and urine extracellular vesicles (EVs) from patients with CCA, PSC, ulcerative colitis (UC), and healthy individuals. Serum and urine EVs were isolated by serial ultracentrifugations and characterized by nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting. EVs transcriptome was determined by Illumina gene expression array [messenger RNAs (mRNA) and non-coding RNAs (ncRNAs)]. Differential RNA profiles were found in serum and urine EVs from patients with CCA compared to control groups (disease and healthy), showing high diagnostic capacity. The comparison of the mRNA profiles of serum or urine EVs from patients with CCA with the transcriptome of tumor tissues from two cohorts of patients, CCA cells in vitro, and CCA cells-derived EVs, identified 105 and 39 commonly-altered transcripts, respectively. Gene ontology analysis indicated that most commonly-altered mRNAs participate in carcinogenic steps. Overall, patients with CCA present specific RNA profiles in EVs mirroring the tumor, and constituting novel promising liquid biopsy biomarkers.This research was funded by Spanish Carlos III Health Institute (ISCIII) [J.M. Banales (FIS PI15/01132, PI18/01075 and Miguel Servet Program CON14/00129; M.J. Perugorria: PI14/00399, PI17/00022; J.J.G. Marin: FIS PI16/00598 and PI19/00819; P.M. Rodrigues: Sara Borrell CD19/00254] cofinanced by “Fondo Europeo de Desarrollo Regional” (FEDER); CIBERehd (ISCIII): J.M. Banales, M.J. Perugorria, L. Bujanda and J.J.G. Marin; Spanish Ministry of Economy and Competitiveness (M.J. Perugorria: Ramon y Cajal Programme RYC-2015-17755); AMMF (J.M. Banales and P.M. Rodrigues 2019/202); PSC Partners US (J.M. Banales); PSC Supports UK (J.M. Banales: 06119JB); Horizon 2020 (J.M. Banales: H2020 ESCALON project: H2020-SC1-BHC-2018-2020); IKERBASQUE, Basque foundation for Science (M.J. Perugorria and J.M. Banales), Spain; “Junta de Castilla y Leon” (J.J.G. Marin: SA06P17); “Diputación Foral Gipuzkoa” (J.M. Banales: DFG15/010, DFG16/004; M.J. Perugorria: DFG18/114, DFG19/081), BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/BD to J.M. Banales), Department of Health of the Basque Country (L. Bujanda: 2013111173; J.M. Banales: 2017111010) and Euskadi RIS3 (J.M. Banales: 2016222001, 2017222014, 2018222029; 2019222054). La Caixa Scientific Foundation (J.M. Banales: HR17-00601). “Fundación Científica de la Asociación Española Contra el Cáncer” (AECC Scientific Foundation, to J.M. Banales and J.J.G. Marin). “Centro Internacional sobre el Envejecimiento”, Spain (R.I.R. Macias: OLD-HEPAMARKER, 0348-CIE-6-E). A. Lapitz and A Santos-Laso were funded by the Basque Government (PRE_2018_2_0195 and PRE_2015_1_0126, respectively). J.B. Andersen is supported by the Danish Medical Research Council, Danish Cancer Society, Novo Nordisk Foundation, and A.P. Møller Foundation. C.J. O’Rourke is supported by Marie Skłodowska -Curie Program