Ensayo de simulaciones numéricas para la prevención de desastres en la laguna 513 (cordillera blanca, Perú)

En muchas áreas de montaña alrededor del mundo, como consecuencia del impacto del cambio climático actual, el riesgo de Glacier Lake Outburst Floods (GLOFs) se ha incrementado debido a la formación de nuevas lagunas a causa de la retracción de los glaciares. Ese proceso está siendo especialmente relevante en la Cordillera Blanca, la alineación de montañas con glaciares actuales más grande de la zona tropical de la Tierra, donde se localiza el área de estudio de este trabajo. Se ha ensayado una modelización de los eventos en cascada que serían causa y efecto de un GLOF en la laguna 513, al suroeste del Nevado Hualcán. El modelo consta de tres fases, en las que se han simulado: 1) Una avalancha de hielo y rocas que impacta en la laguna (en el módulo RAMMS AVALANCHE). 2) El tránsito hidráulico del caudal que la avalancha genera en la laguna (en HEC-RAS). 3) El flujo de detritos generado por el desbordamiento de la laguna, que arranca desde la salida del vaso y alcanza los centros poblados localizados vertiente abajo de la laguna, terminando en la ciudad de Carhuaz. Las simulaciones han permitido cartografiar las áreas que podrían ser afectadas por el GLOF, diferenciando peligrosidades media y alta. También se ha desarrollado una aplicación en ArcGIS online como instrumento para facilitar la transferencia de resultados, en relación con la prevención de desastres, a la sociedad local: tomadores de decisiones y población en riesgo

Simultaneous purifying selection on the ancestral MC1R allele and positive selection on the melanoma-risk allele V60L in South Europeans

In humans, the geographical apportionment of the coding diversity of the pigmentary locus melanocortin-1 receptor (MC1R) is, unusually, higher in Eurasians than in Africans. This atypical observation has been interpreted as the result of purifying selection due to functional constraint on MC1R in high UV-B radiation environments. By analyzing 3,142 human MC1R alleles from different regions of Spain in the context of additional haplotypic information from the 1000 Genomes (1000G) Project data, we show that purifying selection is also strong in southern Europe, but not so in northern Europe. Furthermore, we show that purifying and positive selection act simultaneously on MC1R. Thus, at least in Spain, regions at opposite ends of the incident UV-B radiation distribution show significantly different frequencies for the melanoma-risk allele V60L (a mutation also associated to red hair and fair skin and even blonde hair), with higher frequency of V60L at those regions of lower incident UV-B radiation. Besides, using the 1000G south European data, we show that the V60L haplogroup is also characterized by an extended haplotype homozygosity (EHH) pattern indicative of positive selection. We, thus, provide evidence for an adaptive value of human skin depigmentation in Europe and illustrate how an adaptive process can simultaneously help to maintain a disease-risk allele. In addition, our data support the hypothesis proposed by Jablonski and Chaplin (Human skin pigmentation as an adaptation to UVB radiation. Proc Natl Acad Sci U S A. 2010;107:8962-8968), which posits that habitation of middle latitudes involved the evolution of partially depigmented phenotypes that are still capable of suitable tanning.This works was supported by the former Spanish Ministerio de Ciencia e Innovación, project CGL2008-04066/BOS to S.A.; by the Dpt. Educacion, Universidades e Investigación of the Basque Government, project IT542-10; by program UFI11/09 by the University of the Basque Country, by "Programa de Investigacion Cientifica de la Universidad de La Laguna" (boc-a- 2010-255-7177), and by grants from the Health Institute “Carlos III” (FIS PI08/1383, FIS PI11/00623) to C.F. and co-financed by the European Regional Development Funds, “A way of making Europe” from the European Union. M.P.Y. was supported by a postdoctoral fellowship from Fundación Ramón Areces. We thank the Spanish Banco Nacional de AND (BNADN) (http://www.bancoadn.org/) for providing us with DNA samples from all over Spain. We also thank the Spanish Agencia Estatal de Meteorología (AEMET) (http://www.aemet.es/) for kindly providing us with the UV-B radiation data

Virtualizing university teaching through Open Educational Resources by means of ArcGIS Online (REARGOL)

La pandemia provocada por el virus SARS-CoV-2 (COVID19) ha demostrado la necesidad de acelerar la digitalización de la docencia universitaria. Las herramientas digitales para la transferencia ciencia-educación, que ya eran esenciales para asegurar la calidad de la docencia presencial, se han transformado en imprescindibles cuando las circunstancias han impuesto la docencia virtual. El proyecto REARGOL ha desarrollado y ensayado en ArcGIS online instrumentos para la virtualización de contenidos en asignaturas de grado y máster, sobre geomorfología, gestión de desastres, patrimonio natural y patrimonio cultural. Ha sido un ensayo piloto, replicable en todas las titulaciones y temáticas susceptibles de generar información geoespacial (prácticamente todos los títulos y áreas de conocimiento). El único límite es la imaginación. El proyecto ha priorizado la participación de estudiantes de grado, máster y doctorado, que han desarrollado 4 tipos de aplicaciones: Mapas Web y Web AppBuilder (visores cartográficos interactivos), encuestas Survey 123 (formularios recogida de datos), Cuadros de Mandos (plataformas online que permiten combinar varias aplicaciones) y Story Maps (presentaciones para mostrar conjuntamente información y aplicaciones ArcGIS online). Las aplicaciones que se ensayaron con éxito durante el curso 2020-2021, en asignaturas de grado y máster, así como en TFMs y TFGs, continúan utilizándose en el curso 2021-2022.The SARS-CoV-2 (COVID19) pandemic has shown the urgent need to improve university teaching. Digital resources for Science-Education transfer, which already were crucial for ensuring the quality of face-to-face teaching, turned to be indispensable when the health crisis forced virtual teaching. The REARGOL project has developed and tested ArcGIS Online tools for the virtualization of Bachelor’s and Master’s courses focused on geomorphology, natural disaster management, and natural and cultural heritage. This has been a preliminary test that could be applied to all undergraduate and postgraduate degrees, that can produce geospatial information in all knowledge areas. Imagination is the only constraint. The project has prioritized the participation of undergraduate and postgraduate students (Master and PhD). The project has priorized the participation of undergraduate and postgraduate (Master’s and PhD) students. They have developed four types of applications: Web Maps and Web AppBuilder (interactive cartographical viewers), Survey 123 (data collection forms), Dashboards (online platforms allowing to combine several applications) and Story Maps (presentations for displaying information and ArcGIS online applications). The tools successfully tested during the 2020-2021 academic year are still being used in the current one, in Bachelor’s and Master’s degrees, as well as in Bachelor’s and Master’s final dissertations.Depto. de GeografíaFac. de Geografía e HistoriaFALSEsubmitte

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Internal backbone dynamics of PCNA in solution measured by ¹⁵N relaxation.

<p>The order parameter S² for backbone HN bonds are plotted for those residues whose ¹⁵N T₁, T₂, and ¹⁵N{¹H} NOE values could be measured and analyzed. The location of the secondary structure elements along the PCNA sequence is indicated by red and blue boxes for α-helices and β-strands, respectively. The last five residues at the C-terminal end are not seen in the crystal structure and therefore an order parameter was not calculated, but these residues have the smallest heteronuclear NOEs and the largest T₂ times, indicating that they are the most flexible residues in the protein (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048390#pone.0048390.s001" target="_blank">Figure S1</a>). The regions of the graph corresponding to the IDCL (residues 117–134), the βD2−βE2 loop (184–195), and the C-terminus (252–261) are shaded in yellow. Inset: Representation of the PCNA backbone structure as a coil whose thickness is proportional to the order parameter S² of the backbone NH bond of the corresponding residue. For simplicity only one of the protomers is shown, but the data correspond to measurements done on the homotrimer. For the residues whose order parameter could not be calculated the thickness was interpolated based on the solid line joining the available values plotted in the graph. Helices and strands are colored in red and blue, and the three most flexible regions are colored in yellow (as in the graph). The loops with high relative disorder are labeled using the same nomenclature as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048390#pone-0048390-g001" target="_blank">Figure 1</a>.</p

Chemical shift perturbations of PCNA backbone amide resonances caused by PIP-box peptides.

<p>The top and middle panels show the CSP values for each PCNA residue in the presence of a 1.2 or 1.6 excess (on a monomer basis) of p21²⁰ or p21¹² peptides, respectively. Under the experimental conditions used PCNA is saturated with the peptides (we calculate that 99.9 and 99.8% of the PCNA molecules are bound to the p21²⁰ or the p21¹² peptide, respectively). The bottom panel represents the CSP values in the presence of a 7.8 excess of the ING1²² peptide. The inset shows the CSP experienced by PCNA residue H44 at increasing concentrations of the peptide with error bars spanning twice the estimated uncertainty in the CSP values (±0.005 ppm), which is the average CSP value. The line is the best fit to a model of one set of identical binding sites.</p

Proliferating Cell Nuclear Antigen (PCNA) Interactions in Solution Studied by NMR

PCNA is an essential factor for DNA replication and repair. It forms a ring shaped structure of 86 kDa by the symmetric association of three identical protomers. The ring encircles the DNA and acts as a docking platform for other proteins, most of them containing the PCNA Interaction Protein sequence (PIP-box). We have used NMR to characterize the interactions of PCNA with several other proteins and fragments in solution. The binding of the PIP-box peptide of the cell cycle inhibitor p21 to PCNA is consistent with the crystal structure of the complex. A shorter p21 peptide binds with reduced affinity but retains most of the molecular recognition determinants. However the binding of the corresponding peptide of the tumor suppressor ING1 is extremely weak, indicating that slight deviations from the consensus PIP-box sequence dramatically reduce the affinity for PCNA, in contrast with a proposed less stringent PIP-box sequence requirement. We could not detect any binding between PCNA and the MCL-1 or the CDK2 protein, reported to interact with PCNA in biochemical assays. This suggests that they do not bind directly to PCNA, or they do but very weakly, with additional unidentified factors stabilizing the interactions in the cell. Backbone dynamics measurements show three PCNA regions with high relative flexibility, including the interdomain connector loop (IDCL) and the C-terminus, both of them involved in the interaction with the PIP-box. Our work provides the basis for high resolution studies of direct ligand binding to PCNA in solution.This work was supported by the Spanish Ministry of Economic Affairs and Competitiveness (www.mineco.gob.es)grants CTQ2011-28680 to FJB and BIO2009-13265-CO2-01 to IL, and by the grant BIPEDD-CM (P-BIO-0214-2006) from Comunidad Autónoma de Madrid (www.madrid.org) to RCO. ADB was supported by a Juan de la Cierva contract from the Spanish Ministry of Economic Affairs and Competitiveness

Discovering HIV related information by means of association rules and machine learning

Acquired immunodeficiency syndrome (AIDS) is still one of the main health problems worldwide. It is therefore essential to keep making progress in improving the prognosis and quality of life of affected patients. One way to advance along this pathway is to uncover connections between other disorders associated with HIV/AIDS-so that they can be anticipated and possibly mitigated. We propose to achieve this by using Association Rules (ARs). They allow us to represent the dependencies between a number of diseases and other specific diseases. However, classical techniques systematically generate every AR meeting some minimal conditions on data frequency, hence generating a vast amount of uninteresting ARs, which need to be filtered out. The lack of manually annotated ARs has favored unsupervised filtering, even though they produce limited results. In this paper, we propose a semi-supervised system, able to identify relevant ARs among HIV-related diseases with a minimal amount of annotated training data. Our system has been able to extract a good number of relationships between HIV-related diseases that have been previously detected in the literature but are scattered and are often little known. Furthermore, a number of plausible new relationships have shown up which deserve further investigation by qualified medical experts

Pseudomonas aeruginosa antibiotic susceptibility profiles, genomic epidemiology and resistance mechanisms: a nation-wide five-year time lapse analysisResearch in context

Summary: Background: Pseudomonas aeruginosa healthcare-associated infections are one of the top antimicrobial resistance threats world-wide. In order to analyze the current trends, we performed a Spanish nation-wide high-resolution analysis of the susceptibility profiles, the genomic epidemiology and the resistome of P. aeruginosa over a five-year time lapse. Methods: A total of 3.180 nonduplicated P. aeruginosa clinical isolates from two Spanish nation-wide surveys performed in October 2017 and 2022 were analyzed. MICs of 13 antipseudomonals were determined by ISO-EUCAST. Multidrug resistance (MDR)/extensively drug resistance (XDR)/difficult to treat resistance (DTR)/pandrug resistance (PDR) profiles were defined following established criteria. All XDR/DTR isolates were subjected to whole genome sequencing (WGS). Findings: A decrease in resistance to all tested antibiotics, including older and newer antimicrobials, was observed in 2022 vs 2017. Likewise, a major reduction of XDR (15.2% vs 5.9%) and DTR (4.2 vs 2.1%) profiles was evidenced, and even more patent among ICU isolates [XDR (26.0% vs 6.0%) and DTR (8.9% vs 2.6%)] (p < 0.001). The prevalence of Extended-spectrum β-lactamase/carbapenemase production was slightly lower in 2022 (2.1%. vs 3.1%, p = 0.064). However, there was a significant increase in the proportion of carbapenemase production among carbapenem-resistant strains (29.4% vs 18.1%, p = 0.0246). While ST175 was still the most frequent clone among XDR, a slight reduction in its prevalence was noted (35.9% vs 45.5%, p = 0.106) as opposed to ST235 which increased significantly (24.3% vs 12.3%, p = 0.0062). Interpretation: While the generalized decrease in P. aeruginosa resistance, linked to a major reduction in the prevalence of XDR strains, is encouraging, the negative counterpart is the increase in the proportion of XDR strains producing carbapenemases, associated to the significant advance of the concerning world-wide disseminated hypervirulent high-risk clone ST235. Continued high-resolution surveillance, integrating phenotypic and genomic data, is necessary for understanding resistance trends and analyzing the impact of national plans on antimicrobial resistance. Funding: MSD and the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea—NextGenerationEU