Linear models of activation cascades: analytical solutions and coarse-graining of delayed signal transduction

Cellular signal transduction usually involves activation cascades, the sequential activation of a series of proteins following the reception of an input signal. Here we study the classic model of weakly activated cascades and obtain analytical solutions for a variety of inputs. We show that in the special but important case of optimal-gain cascades (i.e., when the deactivation rates are identical) the downstream output of the cascade can be represented exactly as a lumped nonlinear module containing an incomplete gamma function with real parameters that depend on the rates and length of the cascade, as well as parameters of the input signal. The expressions obtained can be applied to the non-identical case when the deactivation rates are random to capture the variability in the cascade outputs. We also show that cascades can be rearranged so that blocks with similar rates can be lumped and represented through our nonlinear modules. Our results can be used both to represent cascades in computational models of differential equations and to fit data efficiently, by reducing the number of equations and parameters involved. In particular, the length of the cascade appears as a real-valued parameter and can thus be fitted in the same manner as Hill coefficients. Finally, we show how the obtained nonlinear modules can be used instead of delay differential equations to model delays in signal transduction.Comment: 18 pages, 7 figure

Correlation between the surface chemistry and the atmospheric corrosion of AZ31, AZ80 and AZ91D magnesium alloys

X-ray photoelectron spectroscopy (XPS) was used in order to investigate the correlation between the surface chemistry and the atmospheric corrosion of AZ31, AZ80 and AZ91D magnesium alloys exposed to 98% relative humidity at 50 °C. Commercially pure magnesium, used as the reference material, revealed MgO, Mg(OH)2 and tracers of magnesium carbonate in the air-formed film. For the AZ80 and AZ91D alloys, the amount of magnesium carbonate formed on the surface reached similar values to those of MgO and Mg(OH)2. A linear relation between the amount of magnesium carbonate formed on the surface and the subsequent corrosion behaviour in the humid environment was found. The AZ80 alloy revealed the highest amount of magnesium carbonate in the air-formed film and the highest atmospheric corrosion resistance, even higher than the AZ91D alloy, indicating that aluminium distribution in the alloy microstructure influenced the amount of magnesium carbonate formedThanks to the MCYT for the financial support given to this work (Project MAT2006-13179-C02-01-02)Peer reviewe

Caracterización de un vidrio rojo medieval procedente de las vidrieras del Monasterio de las Huelgas de Burgos

En el año 2007 se culminó el proceso de restauración integral de las vidrieras que cierran los ventanales de la Sala Capitular del Claustro de S. Fernando del Real Monasterio de Santa María la Real de las Huelgas de Burgos. Un vidrio rojo, de características peculiares, extraído durante el proceso de conservación-restauración de una de las vidrieras, se ha caracterizado mediante las técnicas de Microscopía óptica de luz reflejada (MOLR), Microscopía electrónica de emisión de campo (MEEC), Fluorescencia de rayos X (FRX), Emisión de rayos X inducidos por partículas (PIXE) y Microscopía electrónica de transmisión (MET) para conocer su composición química y su estructura. Los análisis realizados por las técnicas de FRX y PIXE permiten comprobar la buena concordancia que existe entre los resultados. El vidrio analizado presenta una sección transversal muy original, formada por un vidrio soporte ligeramente verdoso y múltiples capas de color rojo, característico de los siglos XIII y XIV. El análisis mediante micro-PIXE en cámara de vacío ha permitido obtener información sobre la distribución en profundidad de los elementos que lo componen.In the year 2007 the process of conservation-restoration of the windows of the apostles that close the windows of the Chapter Hall of Cloister of S. Fernando del Real Monasterio de Santa María la Real de las Huelgas de Burgos was completed the process. A red glass obtained from the process of conservation and restoration has been characterized by Optical microscopy by light reflected (OMLR), Field emission scanning electron microscopy (FE-SEM), X ray fluorescence espectrpmetry (XRF), Particle induced X ray emission (PIXE), Transmission electron microscopy (TEM) to identify the chemical composition and structure. Chemical analys by XRF and PIXE are in the good agreement. The studied glass has a very original cross section, consisting of a lightly greenish glass holder and multilayers of red glass, characteristic of the thirteenth and fourteenth centuries. A elemental mapping of the cross-section showing the distribution of elements in the glass has been obtained by micro PIXE analysis in a vacuum chamber

Clinical relevance of the transcriptional signature regulated by CDC42 in colorectal cancer.

CDC42 is an oncogenic Rho GTPase overexpressed in colorectal cancer (CRC). Although CDC42 has been shown to regulate gene transcription, the specific molecular mechanisms regulating the oncogenic ability of CDC42 remain unknown. Here, we have characterized the transcriptional networks governed by CDC42 in the CRC SW620 cell line using gene expression analysis. Our results establish that several cancer-related signaling pathways, including cell migration and cell proliferation, are regulated by CDC42. This transcriptional signature was validated in two large cohorts of CRC patients and its clinical relevance was also studied. We demonstrate that three CDC42-regulated genes offered a better prognostic value when combined with CDC42 compared to CDC42 alone. In particular, the concordant overexpression of CDC42 and silencing of the putative tumor suppressor gene CACNA2D2 dramatically improved the prognostic value. The CACNA2D2/CDC42 prognostic classifier was further validated in a third CRC cohort as well as in vitro and in vivo CRC models. Altogether, we show that CDC42 has an active oncogenic role in CRC via the transcriptional regulation of multiple cancer-related pathways and that CDC42-mediated silencing of CACNA2D2 is clinically relevant. Our results further support the use of CDC42 specific inhibitors for the treatment of the most aggressive types of CRC

Multimorbidity clusters in patients with chronic obstructive airway diseases in the EpiChron Cohort

Chronic obstructive airway diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis, and obstructive sleep apnea (OSA) are amongst the most common treatable and preventable chronic conditions with high morbidity burden and mortality risk. We aimed to explore the existence of multimorbidity clusters in patients with such diseases and to estimate their prevalence and impact on mortality. We conducted an observational retrospective study in the EpiChron Cohort (Aragon, Spain), selecting all patients with a diagnosis of allergic rhinitis, asthma, COPD, and/or OSA. The study population was stratified by age (i.e., 15–44, 45–64, and = 65 years) and gender. We performed cluster analysis, including all chronic conditions recorded in primary care electronic health records and hospital discharge reports. More than 75% of the patients had multimorbidity (co-existence of two or more chronic conditions). We identified associations of dermatologic diseases with musculoskeletal disorders and anxiety, cardiometabolic diseases with mental health problems, and substance use disorders with neurologic diseases and neoplasms, amongst others. The number and complexity of the multimorbidity clusters increased with age in both genders. The cluster with the highest likelihood of mortality was identified in men aged 45 to 64 years and included associations between substance use disorder, neurologic conditions, and cancer. Large-scale epidemiological studies like ours could be useful when planning healthcare interventions targeting patients with chronic obstructive airway diseases and multimorbidity

Cohort Profile: The epidemiology of chronic diseases and multimorbidity. The EpiChron cohort study

Why was the cohort set up? Greater life expectancy in Europe over the past few decades has been translated into an increasing burden of chronic diseases that accumulate as the population ages, whereas acute infectious diseases have been progressively pushed into the background. The incidence of conditions such as hypertension, obesity and asthma has increased dramatically worldwide, and cancer, diabetes and respiratory and cardiovascular diseases are responsible for almost 70% of global deaths. Concurrently, the prevalence of multimorbidity (as of people affected by more than one chronic disorder) is also increasing and appears as the most common chronic condition at present. Multimorbidity affects almost 3 in 4 individuals aged 65 years and older, although it represents a problem not only for the elderly but also for adult and even young populations, at whom prevention strategies should aim. People affected by multimorbidity often experience fragmentation of care, greater and inadequate use of health services and polypharmacy, which in turn may increase the risk of low adherence and adverse drug reactions. All of this leads to individuals’ quality of life deterioration and higher risk of mortality. Besides, handling patients with multimorbidity represents a daily challenge for physicians and health systems..

Accelerator-based research activities at "Centro Nacional de Aceleradores", Seville (Spain)

5 páginas.-- PACS nrs.: 29.17.+w; 29.20.−c; 82.80.−d; 07.30.Kf.In February 1998, almost 10 years ago, the set-up of the first IBA (ion beam analysis) facility in Spain took place with the arrival of a 3 MV tandem accelerator [J. García-López, F.J. Ager, M. Barbadillo-Rank, F.J. Madrigal, M.A. Ontalba, M.A. Respaldiza, M.D. Ynsa, Nucl. Instr. and Meth. B 161–163 (2000) 1137]. Since then, an intensive research program using IBA techniques has been carried out. Subsequently, a cyclotron for 18 MeV protons has been also installed at the “Centro Nacional de Aceleradores” (CNA), devoted mainly to isotope production for PET (positron emission tomography) techniques, but possibly applied to material analysis and damage studies on a dedicated beam line. Moreover, a 1 MV tandem has been recently installed for AMS (accelerator mass spectrometry) 14C dating and environmental research with other isotopes.In the present paper we describe the new facilities and the developments of the 3 MV tandem beam lines occurred during the past years, as well as some examples of the most recent research activities in our Center in the fields of Material Science, Archaeometry, Biomedicine and Environment.Thanks are due to the three host Institutions, Universidad de Sevilla, Junta de Andalucía and CSIC, for the continuous support given to our Centre.Peer reviewe

Baseline chronic comorbidity and mortality in laboratory-confirmed COVID-19 cases: Results from the PRECOVID study in Spain

We aimed to analyze baseline socio-demographic and clinical factors associated with an increased likelihood of mortality in men and women with coronavirus disease (COVID-19). We conducted a retrospective cohort study (PRECOVID Study) on all 4412 individuals with laboratory-confirmed COVID-19 in Aragon, Spain, and followed them for at least 30 days from cohort entry. We described the socio-demographic and clinical characteristics of all patients of the cohort. Age-adjusted logistic regressions models were performed to analyze the likelihood of mortality based on demographic and clinical variables. All analyses were stratified by sex. Old age, specific diseases such as diabetes, acute myocardial infarction, or congestive heart failure, and dispensation of drugs like vasodilators, antipsychotics, and potassium-sparing agents were associated with an increased likelihood of mortality. Our findings suggest that specific comorbidities, mainly of cardiovascular nature, and medications at the time of infection could explain around one quarter of the mortality in COVID-19 disease, and that women and men probably share similar but not identical risk factors. Nonetheless, the great part of mortality seems to be explained by other patient-and/or health-system-related factors. More research is needed in this field to provide the necessary evidence for the development of early identification strategies for patients at higher risk of adverse outcomes

Doñana. Acta vertebrata. vol 21 (2)

Requerimientos ambientales de Microtus arvalis asturianus Miller, 1908 (Rodentia, Arvicolidae) en la Península Ibérica.Dinámica anual de la comunidad de paseriformes en un salador litoral del sudeste Ibérico.Helminthfauna of canidae and felidae in the Montseny massif (Catalonia, Spain)Métodos de sujección utilizados por dos especies de alcaudones (Lanius excubitor y L. collurio) para almacenar alimentoSelección del microhábitat en una población de Podarcis bocagei del noroeste ibéricoConducta de puesta, de eclosión y de los recién nacidos en Podarciis bocagei.Nota sobre alimentación de mochuelo (Athene noctua, L. Aves: Strigiformes).Micromamíferos utilizando nidos abandonados de aves como almacenes de alimento y lugares comedorAcerca de la dieta primaveral de perros asilvestrados (Canis familiaris) en una localidad del sureste ibérico.Localización del fartet, Aphanius iberus, en la cuenca del rio Adra (Almeria, sudeste ibérico).Estimación de la dieta de la garcilla bueyera a partir del análisis de regurgitaciones de pollos: problemas debidos a la digestión diferencial de las presas.Peer reviewe