Metabolomic profile of cancer stem cell-derived exosomes from patients with malignant melanoma

Malignant melanoma (MM) is the most aggressive and life-threatening form of skin cancer. It is characterized by an extraordinary metastasis capacity and chemotherapy resistance, mainly due to melanoma cancer stem cells (CSCs). To date, there are no suitable clinical diagnostic, prognostic or predictive biomarkers for this neoplasia. Therefore, there is an urgent need for new MM biomarkers that enable early diagnosis and effective disease monitoring. Exosomes represent a novel source of biomarkers since they can be easily isolated from different body fluids. In this work, a primary patient-derived MM cell line enriched in CSCs was characterized by assessing the expression of specific markers and their stem-like properties. Exosomes derived from CSCs and serums from patients with MM were characterized, and their metabolomic profile was analysed by highresolution mass spectrometry (HRMS) following an untargeted approach and applying univariate and multivariate statistical analyses. The aim of this study was to search potential biomarkers for the diagnosis of this disease. Our results showed significant metabolomic differences in exosomes derived from MM CSCs compared with those from differentiated tumour cells and also in serum-derived exosomes from patients with MM compared to those from healthy controls. Interestingly, we identified similarities between structural lipids differentially expressed in CSC-derived exosomes and those derived from patients with MM such as the glycerophosphocholine PC 16:0/0:0. To our knowledge, this is the first metabolomic-based study aimed at characterizing exosomes derived from melanoma CSCs and patients’ serum in order to identify potential biomarkers for MM diagnosis. We conclude that metabolomic characterization of CSC-derived exosomes sets an open door to the discovery of clinically useful biomarkers in this neoplasia.MICIU FPU15/03682 FPU15/02350Ministerio de Ciencia, Innovación y Universidades (MICIU) MAT2015-62644.C2.2.R RTI2018-101309-BC2Instituto de Salud Carlos III PIE16-00045Junta de Andalucía SOMM17/6109/UGR (UCE-PP2017-3)European Union (EU) SOMM17/6109/UGR (UCE-PP2017-3)Chair 'Doctors Galera-Requena in cancer stem cell research' CMC-CTS963Fundación MEDIN

Article Interferon-Alpha Decreases Cancer Stem Cell Properties and Modulates Exosomes in Malignant Melanoma

Malignant melanoma (MM) can spread to other organs and is resistant in part due to the presence of cancer stem cell subpopulations (CSCs). While a controversial high dose of interferon-alpha (IFN-α) has been used to treat non-metastatic high-risk melanoma, it comes with undesirable side effects. In this study, we evaluated the effect of low and high doses of IFN-α on CSCs by analyzing ALDH activity, side population and specific surface markers in established and patient-derived primary cell lines. We also assessed the clonogenicity, migration and tumor initiation capacities of IFN-α treated CSCs. Additionally, we investigated genomic modulations related to stemness properties using microRNA sequencing and microarrays. The effect of IFN-α on CSCs-derived exosomes was also analyzed using NanoSight and liquid chromatography (LC-HRMS)-based metabolomic analysis, among others. Our results showed that even low doses of IFN-α reduced CSC formation and stemness properties, and led to a significant decrease in the ability to form tumors in mice xenotransplants. IFN-α also modulated the expression of genes and microRNAs involved in several cancer processes and metabolomics of released exosomes. Our work suggests the utility of low doses of interferon, combined with the analysis of metabolic biomarkers, as a potential clinical approach against the aggressiveness of CSCs in melanoma.Ministerio de Ciencia, Innovación y Universidades (MICIU, projects noº MAT2015-62644.C2.2.RRTI2018-101309-B-C2, FEDER Funds), by the Instituto de Salud Carlos III (PIE16-00045), by Consejería de Economía, Conocimiento, Empresas y Universidad de la Junta de Andalucía and European Regional Development Fund (ERDF)ref. SOMM17/6109/UGR (UCE-PP2017-3)Consejería de Salud y Familias de la Junta de Andalucía (projects noº PEMP- 0205-2020 FEDER funds)The Chair “Doctors Galera-Requena in cancer stem cell research” (CMC-CTS963

Revista de Vertebrados de la Estación Biológica de Doñana

Contribución al estudio de la bermejuela Rutilus arcasi, Steindachner, 1866 de la cuenca del Júcar (Osteichthyes: Cyprinidae)II. Edad y crecimientoSobre la taxonomía de Barbus comiza Steindachner, 1865 (Ostariophysi: Cyprinidae)Fenología de una comunidad de anfibios asociada a cursos fluviales temporales.Nueva especie para la ciencia de Anolis (Lacertilia: Iguanidae) de Cuba pertenecient eal complejo argillaceusSegregación ecológica en una comunidad de ofidios.El Aguila Imperial (Aquila adalberti): dispersión de los jóvenes, estructura de edades y mortalidaSobre diferencias individuales en la alimentación de Tyto albaInfluencia de las condiciones ambientales sobre la organización de la comunidad de aves invernantes en un bosque subalpino mediterráneoVariaciones en la agregación y distribución de la cabra montés (Capra pyrenaica Schinz,1838) detectadas con un muestreo de excrementosAlimentación del conejo (Oryctolagus cuniculus L. 1758) en Doñana. SO, EspañaSobre la distribución de Barbus meridionales Risso, 1826 (Ostariophysi: Cyprinidae) en la Península IbéricaSobre la distribución de Barbus meridionales Risso, 1826 (Ostariophysi: Cyprinidae) en la Península IbéricaNueva cita de Barbus microcephalus Almaça (Pisces, Cyprinidae) en España.Revisión taxonómica y distribución de Cobitis maroccana Pellegrin, 1929 (Osteichthyes, Cobitidae)Datos sobre una población de Lacerta viviparaSobre la presencia de Emys orbicularis en la provincia de León.Algunas observaciones sobre la captura de quirópteros por Falco subbuteo y Falco tinunculusNyctalus leisleri (Kuhk, 1818) (Mammalia: Chiroptera). Una nueva especie para las islas CanariaNuevos datos acerca de la distribución del topillo campesino Microtus arvalis, PALLAS 1778, en la Península IbéricaPeer reviewe

MicroRNA-dependent regulation of transcription in non-small cell lung cancer

Squamous cell lung cancer (SCC) and adenocarcinoma are the most common histological subtypes of non-small cell lung cancer (NSCLC), and have been traditionally managed in the clinic as a single entity. Increasing evidence, however, illustrates the biological diversity of these two histological subgroups of lung cancer, and supports the need to improve our understanding of the molecular basis beyond the different phenotypes if we aim to develop more specific and individualized targeted therapy. The purpose of this study was to identify microRNA (miRNA)-dependent transcriptional regulation differences between SCC and adenocarcinoma histological lung cancer subtypes. In this work, paired miRNA (667 miRNAs by TaqMan Low Density Arrays (TLDA)) and mRNA profiling (Whole Genome 44 K array G112A, Agilent) was performed in tumor samples of 44 NSCLC patients. Nine miRNAs and 56 mRNAs were found to be differentially expressed in SCC versus adenocarcinoma samples. Eleven of these 56 mRNA were predicted as targets of the miRNAs identified to be differently expressed in these two histological conditions. Of them, 6 miRNAs (miR-149, miR-205, miR-375, miR-378, miR- 422a and miR-708) and 9 target genes (CEACAM6, CGN, CLDN3, ABCC3, MLPH, ACSL5, TMEM45B, MUC1) were validated by quantitative PCR in an independent cohort of 41 lung cancer patients. Furthermore, the inverse correlation between mRNAs and microRNAs expression was also validated. These results suggest miRNA-dependent transcriptional regulation differences play an important role in determining key hallmarks of NSCLC, and may provide new biomarkers for personalized treatment strategies

Doñana, diversidad y ciencia

144 páginasLa biodiversidad es más que la suma de los elementos que componen el mundo vivo; también son biodiversidad las relaciones entre esos elementos, los procesos ecológicos que hacen posible su existencia y los procesos evolutivos que los han originado. […] Los seres humanos necesitamos a la biodiversidad más que ella a nosotros, ya que es la responsable de que la Tierra funcione de una manera satisfactoria. […] El entramado de la vida se ocupa de regular la composición de la atmósfera (y con ella, el clima), de depurar el aire y el agua, de hacer fértil al suelo, de evitar riadas y avalanchas, de polinizar las cosechas, de reducir las plagas, etc. Por todo ello es indispensable conservar la biodiversidad, hoy amenazada.” (Miguel Delibes) Doñana, diversidad y ciencia es un paseo conceptual por el espacio natural más emblemático de Europa. La esencia de un mito a través de decenas de fotografías… Un acercamiento respetuoso a la diversidad de sus conceptos, un paseo por la esencia de su historia y una curiosa aproximación a la ciencia que genera hoy en día. En este recorrido descubriremos el carácter distintivo de algunos de los parajes de la reserva, sus matices más interesantes, las texturas y las formas más sorprendentes de la naturaleza, sus colores y conjuntos, sus transformaciones en las últimas décadas y la influencia de la presencia humana en el privilegiado ecosistema de la Reserva Biológica de Doñana

Monitoring grape ripeness using a voltammetric electronic tongue

The use of a voltammetric electronic tongue as a tool to monitor grape ripeness is proposed herein. The electronic tongue consists of eight metallic electrodes housed inside a stainless steel cylinder. The study was carried out over a period of ca. 1 month (August 2012) on different grape varieties (Macabeo, Chardonnay, Pinot Noir, Cabernet Sauvignon, Shyrah, Merlot and Bobal) from various vineyards near Requena and Utiel (Valencia, Spain). Apart from the electrochemical studies, the physico-chemical parameters, such as, Total Acidity, pH and °Brix, were also determined in grapes. The PCA models, obtained using the physico-chemical or electrochemical data, showed variation of ripenesswith time.Moreover the studywas completed by using partial least squares (PLS) regression in an attempt to establish a correlation between the data collected from the electronic tongue and Total Acidity, pH and °Brix values. A good predictive modelwas obtained for the prediction of Total Acidity and °Brix. These results suggest the possibility of employing electronic tongues to monitor grape ripeness and of, therefore, evaluating the right time for harvesting.The financial support from the Spanish Government (project MAT2012-38429-C04-01) and the Generalitat Valenciana (Valencian Regional Government; project PROMETEO/2009/016) is gratefully acknowledged.Campos Sánchez, I.; Bataller Prats, R.; Armero, R.; Gandía Romero, JM.; Soto Camino, J.; Martínez Mañez, R.; Gil Sánchez, L. (2013). Monitoring grape ripeness using a voltammetric electronic tongue. Food Research International. 54(2):1369-1375. https://doi.org/10.1016/j.foodres.2013.10.011S1369137554

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Altres ajuts: Spanish AIDS Research Network; European Funding for Regional Development (FEDER).Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad

Acta de congresoLa conmemoración de los cien años de la Reforma Universitaria de 1918 se presentó como una ocasión propicia para debatir el rol de la historia, la teoría y la crítica en la formación y en la práctica profesional de diseñadores, arquitectos y urbanistas. En ese marco el VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad constituyó un espacio de intercambio y reflexión cuya realización ha sido posible gracias a la colaboración entre Facultades de Arquitectura, Urbanismo y Diseño de la Universidad Nacional y la Facultad de Arquitectura de la Universidad Católica de Córdoba, contando además con la activa participación de mayoría de las Facultades, Centros e Institutos de Historia de la Arquitectura del país y la región. Orientado en su convocatoria tanto a docentes como a estudiantes de Arquitectura y Diseño Industrial de todos los niveles de la FAUD-UNC promovió el debate de ideas a partir de experiencias concretas en instancias tales como mesas temáticas de carácter interdisciplinario, que adoptaron la modalidad de presentación de ponencias, entre otras actividades. En el ámbito de VIII Encuentro, desarrollado en la sede Ciudad Universitaria de Córdoba, se desplegaron numerosas posiciones sobre la enseñanza, la investigación y la formación en historia, teoría y crítica del diseño, la arquitectura y la ciudad; sumándose el aporte realizado a través de sus respectivas conferencias de Ana Clarisa Agüero, Bibiana Cicutti, Fernando Aliata y Alberto Petrina. El conjunto de ponencias que se publican en este Repositorio de la UNC son el resultado de dos intensas jornadas de exposiciones, cuyos contenidos han posibilitado actualizar viejos dilemas y promover nuevos debates. El evento recibió el apoyo de las autoridades de la FAUD-UNC, en especial de la Secretaría de Investigación y de la Biblioteca de nuestra casa, como así también de la Facultad de Arquitectura de la UCC; va para todos ellos un especial agradecimiento