Improving the understanding of cancer in a descriptive way: An emerging pattern mining-based approach

This paper presents an approach based on emerging pattern mining to analyse cancer through genomic data. Unlike existing approaches, mainly focused on predictive purposes, the proposal aims to improve the understanding of cancer descriptively, not requiring either any prior knowledge or hypothesis to be validated. Additionally, it enables to consider high-order relationships, so not only essential genes related to the disease are considered, but also the combined effect of various secondary genes that can influence different pathways directly or indirectly related to the disease. The prime hypothesis is that splitting genomic cancer data into two subsets, that is, cases and controls, will allow us to determine which genes, and their expressions, are associated with different cancer types. The possibilities of the proposal are demonstrated by analyzing RNA-Seq data for six different types of cancer: breast, colon, lung, thyroid, prostate, and kidney. Some of the extracted insights were already described in the related literature as good cancer bio-markers, while others have not been described yet mainly due to existing techniques are biased by prior knowledge provided by biological databases

Antileishmanial activity and evaluation of the mechanism of action of strychnobiflavone flavonoid isolated from Strychnos pseudoquina against Leishmania infantum

© 2015, Springer-Verlag Berlin Heidelberg. The present study aimed to investigate the in vitro antileishmanial activity of strychnobiflavone flavonoid against Leishmania infantum, as well as its mechanism of action, and evaluate the ex vivo biodistribution profile of the flavonoid in naive BALB/c mice. The antileishmanial activity (IC50 value) of strychnobiflavone against stationary promastigote and amastigote-like stages of the parasites was of 5.4 and 18.9 μM, respectively; with a 50% cytotoxic concentration (CC50) value of 125.0 μM on murine macrophages, resulting in selectivity index (SI) of 23.2 and 6.6, respectively. Amphotericin B, used as a positive control, presented SI values of 7.6 and 3.3 for promastigote and amastigote-like stages of L. infantum, respectively. The strychnobiflavone was also effective in reducing in significant levels the percentage of infected macrophages, as well as the number of amastigotes per macrophage, after the treatment of infected macrophages using the flavonoid. By using different fluorescent probes, we investigated the bioenergetics metabolism of L. infantum promastigotes and demonstrated that the flavonoid caused the depolarization of the mitochondrial membrane potential, without affecting the production of reactive oxygen species. In addition, using SYTOX® green as a fluorescent probe, the strychnobiflavone demonstrated no interference in plasma membrane permeability. For the ex vivo biodistribution assays, the flavonoid was labeled with technetium-99m and studied in a mouse model by intraperitoneal route. After a single dose administration, the scintigraphic images demonstrated a highest uptake by the liver and spleen of the animals within 60 min, resulting in low concentrations after 24 h. The present study therefore demonstrated, for the first time, the antileishmanial activity of the strychnobiflavone against L. infantum, and suggests that the mitochondria of the parasites may be the possible target organelle. The preferential distribution of this compound into the liver and spleen of the animals could warrant its employ in the treatment of visceral leishmaniasis.This work was supported by grants from Instituto Nacional de Ciência e Tecnologia em Nanobiofarmacêutica (INCT-Nanobiofar), FAPEMIG (CBB-APQ-00819-12), CNPq (APQ-472090/2011-9, APQ- 482976/2012-8, and APQ-488237/2013-0) and São Paulo State Research Fundation (FAPESP 2012/18756-1). MACF is a grant recipient of FAPEMIG/CAPES. EAFC, VNC and AGT are grant recipient of CNPqPeer Reviewe

Functional role of endothelial adhesion molecules in the early stages of brain metastasis

BACKGROUND: Cellular adhesion molecules (CAMs), which are normally associated with leukocyte trafficking, have also been shown to play an essential role in tumor metastasis to non-CNS sites. However, the role played by CAMs in brain metastasis is largely unexplored. It is known that leukocyte recruitment to the brain is very atypical and that mechanisms of disease in peripheral tissues cannot be extrapolated to the brain. Here, we have established the spatiotemporal expression of 12 key CAMs in the initial phases of tumor seeding in 2 different models of brain metastasis. METHODS: BALB/c or SCID mice were injected intracardially (10(5) cells/100 μL phosphate-buffered saline with either 4T1-GFP or MDA231BR-GFP cells, respectively (n = 4–6/group), and expression of the CAMs was determined by immunohistochemistry and immunofluorescence colocalisation. RESULTS: Endothelial expression of E-selectin, VCAM-1, ALCAM, ICAM-1, VLA-4, and β(4) integrin was markedly increased early in tumor seeding. At the same time, the natural ligands to these adhesion molecules were highly expressed on the metastatic tumor cells both in vitro and in vivo. Two of these ligands showed particularly high tumor cell expression (ALCAM and VLA-4), and consequently their functional role in tumor seeding was determined. Antibody neutralization of either ALCAM or VLA-4 significantly reduced tumor seeding within the brain (>60% decrease in tumor number/mm(2) brain; P < .05–0.01). CONCLUSIONS: These findings suggest that ALCAM/ALCAM and VLA-4/VCAM-1 interactions play an important functional role in the early stages of metastasis seeding in the brain. Moreover, this work identifies a specific subset of ligand-receptor interactions that may yield new therapeutic and diagnostic targets for brain metastasis

Influence of Nutrients and pH on the Efficiency of Vertical Flow Constructed Wetlands Treating Winery Wastewater

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] Winery wastewater is characterized by high organic content, low nutrient content and low pH at least during vintage periods. The effect of nutrient shortage and low pH on constructed wetlands (CWs) operation was scarcely studied, but early field studies indicate that some operational problems can arise. This work aims to determine the effect of nutrient shortage and acidic pH during the treatment of high organic load wastewater in one-step vertical subsurface flow (VF) CWs. Two lab scale VF units at hydraulic loading rates over 70 L/m2·d and surface loading rate in the range of 110−170 g COD/m2·d were operated for periods with and without nutrients in the influent as well as with influent pH of 7.0 and 4.5. The results showed that neither low nutrient nor low pH impair organic matter removal whilst low pH decreased nitrogen removal rates. At low pH, the effluent concentration of ammonia and nitrate increased, indicating deterioration in both nitrification and denitrification processes. The paper discuss the implications of these findings for a better strategy in the treatment of winery process wastewater, such as options for separate treatment or its combination with other nutrient-containing streams

Should we use closed or open infusion containers for prevention of bloodstream infections?

<p>Abstract</p> <p>Background</p> <p>Hospitalized patients in critical care settings are at risk for bloodstream infections (BSI). Most BSIs originate from a central line (CL), and they increase length of stay, cost, and mortality. Open infusion containers may increase the risk of contamination and administration-related (CLAB) because they allow the entry of air into the system, thereby also providing an opportunity for microbial entry. Closed infusion containers were designed to overcome this flaw. However, open infusion containers are still widely used throughout the world.</p> <p>The objective of the study was to determine the effect of switching from open (glass, burettes, and semi-rigid) infusion containers to closed, fully collapsible, plastic infusion containers (Viaflex^®) on the rate and time to onset of central line-associated bloodstream infections CLABs.</p> <p>Methods</p> <p>An open label, prospective cohort, active healthcare-associated infection surveillance, sequential study was conducted in four ICUs in Mexico. Centers for Disease Control National Nosocomial Infections Surveillance Systems definitions were used to define device-associated infections.</p> <p>Results</p> <p>A total of 1,096 adult patients who had a central line in place for >24 hours were enrolled. The CLAB rate was significantly higher during the open versus the closed container period (16.1 versus 3.2 CLAB/1000 central line days; RR = 0.20, 95% CI = 0.11-0.36, P < 0.0001). The probability of developing CLAB remained relatively constant in the closed container period (1.4% Days 2-4 to 0.5% Days 8-10), but increased in the open container period (4.9% Days 2-4 to 5.4% Days 8-10). The chance of acquiring a CLAB was significantly decreased (81%) in the closed container period (Cox proportional hazard ratio 0.19, P < 0.0001). Mortality was statistically significantly lower during the closed versus the open container period (23.4% versus 16.1%; RR = 0.69, 95% CI = 0.54-0.88, P < 0.01).</p> <p>Conclusions</p> <p>Closed infusion containers significantly reduced CLAB rate, the probability of acquiring CLAB, and mortality.</p

Experiencias comparadas en autoevaluación y formación en competencias a través de la WebCT en Física

El EEES fomenta el uso por parte del estudiante de ejercicios de autoevaluación como complemento en el proceso de enseñanza-aprendizaje, y ejercitando de esta forma las distintas competencias asociadas a la asignatura y facilitando a la vez su evaluación final por parte del profesorado. Con este objetivo se implementaron en dos cursos sucesivos de la asignatura de Física en el grado de Ciencias Ambientales, 2009-2010 y 2010-2011, la autoevaluación formativa a través de exámenes virtuales utilizando la plataforma WebCT como retroalimentación por parte del alumno del propio proceso. El análisis de los resultados obtenidos tras la implantación vislumbra una alta participación y valoración de los alumnos del sistema de evaluación.Artículo revisado por pare

Research at the medical imaging laboratory, CIBERSAM CB07/09/0031

The Medical Imaging Laboratory is a research group within the Hospital General Universitario Gregorio Marañón. The main research line of the group is focused towards the development and exploitation of medical imaging techniques, including the development of new processing tools for image analysis in clinical and preclinical research. The group has a multi-disciplinary profile and a priority for translational research topics, derived from real problems faced by the clinical specialists. One of the main research areas is the development of technologies for molecular imaging, some of which have been transferred to the industry and are now among the top products of the market. These systems include high-resolution PET, CT and PET-CT. Over the last years the group has developed several software tools to enable quantification of multimodal brain images using morphometric and functional data. Some research applications of these hardware and software tools are illustrated in the paper“Ministerio de Sanidad y Consumo”, CDTEAM Programa CÉNIT, Ministerio de Industria. FIS PI052271 “Ministerio de Sanidad y Consumo”. CIBER Salud Mental (CIBERSAM) “Ministerio de Sanidad y Consumo” and Fundación Mutua MadrileñaPublicad

Melatonin-doped polymeric nanoparticles induce high crystalline apatite formation in root dentin

This work was funded by the Ministry of Economy and Competitiveness and European Regional Development Fund( MINECO/AEI/FEDER/UE) Project number PID2020-114694RBI00. Funding for open access charge: University of Granada / CBUA.Objective. To investigate the effect of novel polymeric nanoparticles (NPs) doped with melatonin (ML) on nano-hardness, crystallinity and ultrastructure of the formed hydroxyapatite after endodontic treatment. Methods. Undoped-NPs and ML-doped NPs (ML-NPs) were tested at radicular dentin, after 24 h and 6 m. A control group without NPs was included. Radicular cervical and apical dentin surfaces were studied by nano-hardness measurements, X-ray diffraction and transmission electron microscopy. Mean and standard deviation were analyzed by ANOVA and StudentNewman-Keuls multiple comparisons (p < 0.05). Results. Cervical dentin treated with undoped NPs maintained its nano-hardness values after 6 m of storage being [24 h: 0.29 (0.01); 6 m: 0.30 (0.02) GPa], but it decreased at apical dentin [24 h: 0.36 (0.01); 6 m: 0.28 (0.02) GPa]. When ML-NPs were used, nano-hardness was similar over time [24h: 0.31 (0.02); 6 m: 0.28 (0.03) GPa], at apical dentin. Root dentin treated with ML-NPs produced, in general, high crystallinity of new minerals and thicker crystals than those produced in the rest of the groups. After 6 m, crystals became organized in randomly oriented polyhedral, square polygonal block-like apatite or drop-like apatite polycrystalline lattices when ML-NPs were used. Undoped NPs generated poor crystallinity, with preferred orientation of small crystallite and increased microstrain. Significance. New polycrystalline formations encountered in dentin treated with ML-NPs may produce structural dentin stability and high mechanical performance at the root. The decrease of mechanical properties over time in dentin treated without NPs indicates scarce remineralization potential, dentin demineralization and further potential degradation. The amorphous stage may provide high hydroxyapatite solubility and remineralizing activity.Ministry of Economy and Competitiveness and European Regional Development Fund( MINECO/AEI/FEDER/UE) PID2020-114694RB-I00University of Granada/CBU

Selective pressure against horizontally acquired prokaryotic genes as a driving force of plastid evolution

Altres ajuts: del Consejo Nacional de Investigaciones Científicas y Técnicas- Argentina (CONICET) i del Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo (IBERCAROT).The plastid organelle comprises a high proportion of nucleus-encoded proteins that were acquired from different prokaryotic donors via independent horizontal gene transfers following its primary endosymbiotic origin. What forces drove the targeting of these alien proteins to the plastid remains an unresolved evolutionary question. To better understand this process we screened for suitable candidate proteins to recapitulate their prokaryote-to-eukaryote transition. Here we identify the ancient horizontal transfer of a bacterial polyphenol oxidase (PPO) gene to the nuclear genome of an early land plant ancestor and infer the possible mechanism behind the plastidial localization of the encoded enzyme. Arabidopsis plants expressing PPO versions either lacking or harbouring a plastid-targeting signal allowed examining fitness consequences associated with its subcellular localization. Markedly, a deleterious effect on plant growth was highly correlated with PPO activity only when producing the non-targeted enzyme, suggesting that selection favoured the fixation of plastid-targeted protein versions. Our results reveal a possible evolutionary mechanism of how selection against heterologous genes encoding cytosolic proteins contributed in incrementing plastid proteome complexity from non-endosymbiotic gene sources, a process that may also impact mitochondrial evolution

ANALYSIS OF UNCERTAINTY IN THE STANDARIZATION OF CPUE INDEXES

Catch per unit effort (CPUE) indices are considered as one of the main information sources used in fish stock assessment models (Zou et al., 2019). There are many ways for the standardization of these indices: • Generalized lineal models (GLMs) • Generalized additive models (GAMs) • Geostatistical models. To evaluate the accuracy and uncertainty associated with CPUE indices derived from datasets with different spatial information. • How? With the standardization of CPUE indices using geostatistical models in different sampling scenarios, comparing them with GLMs and GAMs models