Emergent Properties of Tumor Microenvironment in a Real-life Model of Multicell Tumor Spheroids

Multicellular tumor spheroids are an important {\it in vitro} model of the pre-vascular phase of solid tumors, for sizes well below the diagnostic limit: therefore a biophysical model of spheroids has the ability to shed light on the internal workings and organization of tumors at a critical phase of their development. To this end, we have developed a computer program that integrates the behavior of individual cells and their interactions with other cells and the surrounding environment. It is based on a quantitative description of metabolism, growth, proliferation and death of single tumor cells, and on equations that model biochemical and mechanical cell-cell and cell-environment interactions. The program reproduces existing experimental data on spheroids, and yields unique views of their microenvironment. Simulations show complex internal flows and motions of nutrients, metabolites and cells, that are otherwise unobservable with current experimental techniques, and give novel clues on tumor development and strong hints for future therapies.Comment: 20 pages, 10 figures. Accepted for publication in PLOS One. The published version contains links to a supplementary text and three video file

Actividad antioxidante de los alcaloides de Bocconia arborea. Estudio sobre seis métodos de análisis

Antioxidative activity-guided fractionation together with chemical analysis led to the isolation of three benzophenanthridinealkaloids from methanol extract of the bark of Bocconia arborea. Identification was based on spectroscopic methods.The isolated alkaloids 6-acetonyldihydrochelerythrine, chelerythrine and dihydrochelerythrine were tested for antioxidativeactivity on thiocyanate assays, free radical scavenging activity, b-carotene bleaching method, and deoxyribose assay. Allalkaloids exhibited significant antioxidant activities in linoleic acid and b-carotene. Although afforded protection againstthe damage of deoxyribose, liposome peroxidation and microsomial lipid from peroxidation, also exhibited scavengingeffects on the 1,1-diphenyl-2-picrylhydrazyl radicals.El fraccionamiento de la actividad antioxidante dirigida por actividad, junto con el análisis químico, llevaron alaislamiento de tres alcaloides de benzofenantridina del extracto de metanol de la corteza de Bocconia arborea. Laidentificación se basó en métodos espectroscópicos. Se analizó la actividad antioxidante de los alcaloides aislados 6-acetonildihidroqueleritrina, queleritrina y dihidroqueleritrina en ensayos de tiocianato, la actividad de barrido delos radicales libres, el método de decoloración del b-caroteno y el ensayo de la desoxirribosa. Todos los alcaloidesmostraron actividad antioxidante significativa en ácido linoleico y b-caroteno. Además de conceder protección frentea la desoxirribosa, la peroxidación liposómica y los lípidos microsomiales de la peroxidación, también presentaronefectos de barrido en los radicales de 1,1-difenil-2-picrilhidrazi

Robots That Do Not Avoid Obstacles

The motion planning problem is a fundamental problem in robotics, so that every autonomous robot should be able to deal with it. A number of solutions have been proposed and a probabilistic one seems to be quite reasonable. However, here we propose a more adoptive solution that uses fuzzy set theory and we expose this solution next to a sort survey on the recent theory of soft robots, for a future qualitative comparison between the two.Comment: To appear in the Handbook of Nonlinear Analysis, Edt Th. Rassias, Springe

Towards an Energy-Aware Framework for Application Development and Execution in Heterogeneous Parallel Architectures

The Transparent heterogeneous hardware Architecture deployment for eNergy Gain in Operation (TANGO) project’s goal is to characterise factors which affect power consumption in software development and operation for Heterogeneous Parallel Hardware (HPA) environments. Its main contribution is the combination of requirements engineering and design modelling for self-adaptive software systems, with power consumption awareness in relation to these environments. The energy efficiency and application quality factors are integrated into the application lifecycle (design, implementation and operation). To support this, the key novelty of the project is a reference architecture and its implementation. Moreover, a programming model with built-in support for various hardware architectures including heterogeneous clusters, heterogeneous chips and programmable logic devices is provided. This leads to a new cross-layer programming approach for heterogeneous parallel hardware architectures featuring software and hardware modelling. Application power consumption and performance, data location and time-criticality optimization, as well as security and dependability requirements on the target hardware architecture are supported by the architecture

Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention

Information transmission in oscillatory neural activity

Periodic neural activity not locked to the stimulus or to motor responses is usually ignored. Here, we present new tools for modeling and quantifying the information transmission based on periodic neural activity that occurs with quasi-random phase relative to the stimulus. We propose a model to reproduce characteristic features of oscillatory spike trains, such as histograms of inter-spike intervals and phase locking of spikes to an oscillatory influence. The proposed model is based on an inhomogeneous Gamma process governed by a density function that is a product of the usual stimulus-dependent rate and a quasi-periodic function. Further, we present an analysis method generalizing the direct method (Rieke et al, 1999; Brenner et al, 2000) to assess the information content in such data. We demonstrate these tools on recordings from relay cells in the lateral geniculate nucleus of the cat.Comment: 18 pages, 8 figures, to appear in Biological Cybernetic

Molecular Cytogenetic Analysis of the European Hake Merluccius merluccius (Merlucciidae, Gadiformes): U1 and U2 snRNA Gene Clusters Map to the Same Location

The European hake (Merluccius merluccius) is a highly valuable and intensely fished species in which a long-term alive stock has been established in captivity for aquaculture purposes. Due to their huge economic importance, genetic studies on hakes were mostly focused on phylogenetic and phylogeographic aspects; however chromosome numbers are still not described for any of the fifteen species in the genus Merluccius. In this work we report a chromosome number of 2n = 42 and a karyotype composed of three meta/submetacentric and 18 subtelo/telocentric chromosome pairs. Telomeric sequences appear exclusively at both ends of every single chromosome. Concerning rRNA genes, this species show a single 45S rDNA cluster at an intercalary location on the long arm of subtelocentric chromosome pair 12; the single 5S rDNA cluster is also intercalary to the long arm of chromosome pair 4. While U2 snRNA gene clusters map to a single subcentromeric position on chromosome pair 13, U1 snRNA gene clusters seem to appear on almost all chromosome pairs, but showing bigger clusters on pairs 5, 13, 16, 17 and 19. The brightest signals on pair 13 are coincident with the single U2 snRNA gene cluster signals. Therefore, the use of these probes allows the unequivocal identification of at least 7 of the chromosome pairs that compose the karyotype of Merluccius merluccius thus opening the way to integrate molecular genetics and cytological data on the study of the genome of this important species.Versión del editor4,411

The Antioxidant Potential of the Mediterranean Diet in Patients at High Cardiovascular Risk: An In-Depth Review of the PREDIMED

Cardiovascular disease (CVD) is the leading global cause of death. Diet is known to be important in the prevention of CVD. The PREDIMED trial tested a relatively low-fat diet versus a high-fat Mediterranean diet (MedDiet) for the primary prevention of CVD. The resulting reduction of the CV composite outcome resulted in a paradigm shift in CV nutrition. Though many dietary factors likely contributed to this effect, this review focuses on the influence of the MedDiet on endogenous antioxidant systems and the effect of dietary polyphenols. Subgroup analysis of the PREDIMED trial revealed increased endogenous antioxidant and decreased pro-oxidant activity in the MedDiet groups. Moreover, higher polyphenol intake was associated with lower incidence of the primary outcome, overall mortality, blood pressure, inflammatory biomarkers, onset of new-onset type 2 diabetes mellitus (T2DM), and obesity. This suggests that polyphenols likely contributed to the lower incidence of the primary event in the MedDiet groups. In this article, we summarize the potential benefits of polyphenols found in the MedDiet, specifically the PREDIMED cohort. We also discuss the need for further research to confirm and expand the findings of the PREDIMED in a non-Mediterranean population and to determine the exact mechanisms of action of polyphenols

The Goal Programming as a Tool for Measuring the Sustainability of Agricultural Production Chains of Rice

Agricultural activity is characterized by an intensive use of capital and a considerable dependence on external financing. Access to credit is often limited by the scarcity of resources and lack of guarantees, seriously affecting the productivity and economic performance of agricultural exploitations. The objective of this paper is to assess the sustainability of agricultural production chain of rice in Latin America using multi-criteria analysis tools to facilitate decision-making through a benchmarking process to contribute to their economic sustainability. The implementation of the model in an exploitation typy depending on financing sources (conservative, intermediate, and innovative) has revealed the conflict between the goals, being the intermediate exploitation, which gets the best results. The conclusions show that the flexibilization of financing options positively affects the economic performance