Using hybrid concurrent constraint programming to model dynamic biological systems

Rapport interne.Systems biology is a new area in biology that aims at achieving a systems-level understanding of biological systems. While current genome projects provide a huge amount of data on genes or proteins, lots of research is still necessary to understand how the different parts of a biological system interact in order to perform complex biological functions. Computational models that help to analyze, explain or predict the behavior of biological systems play a crucial role in systems biology. The goal of this paper is to show that hybrid concurrent constraint programming (Gupta/Jagadeesan/Saraswat 98) may be a promising alternative to existing modeling approaches in systems biology. Hybrid cc is a declarative compositional programming language with a well-defined semantics. It allows one to model and simulate the dynamics of hybrid systems, which exhibit both discrete and continuous change. We show that Hybrid cc can be used naturally to model a variety of biological phenomena, such as reaching thresholds, kinetics, gene interaction or biological pathways

Encapsulation of epsilon-Viniferin into Multi-Lamellar Liposomes: Development of a Rapid, Easy and Cost-Efficient Separation Method to Determine the Encapsulation Efficiency

Onion-type multi-lamellar liposomes (MLLs), composed of a mixture of phosphatidylcholine and Tween 80, were analyzed for their ability to encapsulate epsilon-Viniferin (epsilon Vin), a resveratrol dimer. Their encapsulation efficiency (EE) was measured by UV-VIS spectroscopy using three different separation methods-ultracentrifugation, size exclusion chromatography, and a more original and advantageous one, based on adsorption filtration. The adsorption filtration method consists indeed of using syringe filters to retain the molecule of interest, and not the liposomes as usually performed. The process is rapid (less than 10 min), easy to handle, and inexpensive in terms of sample amount (around 2 mg of liposomes) and equipment (one syringe filter is required). Whatever the separation method, a similar EE value was determined, validating the proposed method. A total of 80% +/- 4% of epsilon Vin was found to be encapsulated leading to a 6.1% payload, roughly twice those reported for resveratrol-loaded liposomes. Finally, the release kinetics of epsilon Vin from MLLs was followed for a 77 day period, demonstrating a slow release of the polyphenol

Beneficial Effects of ε-Viniferin on Obesity and Related Health Alterations

Viniferin is a phenolic compound belonging to the group of stilbenoids. In particular, ε-viniferin is a dimer of resveratrol, found in many plant genders, among which grapes (Vitis vinifera) are a primary source. Due to the fact that ε-viniferin is mainly present in the woody parts of plants, their use as a source of this bioactive compound is a very interesting issue in a circular economy. Both, in vitro studies carried out in pre-adipocytes and mature adipocytes and in vivo studies addressed in mice show that ε-viniferin is able to reduce fat accumulation. Moreover, it prevents the development of some obesity co-morbidities, such as type 2 diabetes, dyslipidemias, hypertension and fatty liver. ε-viniferin can be absorbed orally, but it shows a very low bioavailability. In this scenario, further research on animal models is needed to confirm the effects reported in a great number of studies; to determine which metabolites are involved, including the main one responsible for the biological effects observed and the mechanisms that justify these effects. In a further phase, human studies should be addressed in order to use ε-viniferin as a new tool for obesity management, as a nutraceutical or to be included in functional foods.This research was funded by CIBEROBN under Grant CB12/03/30007 and the Government of the Basque Country (IT1482-22)

Chronic hypoxia aggravates monocrotaline-induced pulmonary arterial hypertension: a rodent relevant model to the human severe form of the disease

International audienc

J. Agric. Food Chem.

Stilbene metabolites are attracting great interest because many of them exhibit similar or even stronger biological effects than their parent compounds. Furthermore, the metabolized forms are predominant in biological fluids; therefore, their study is highly relevant. After hemisynthesis production, isolation, and structural elucidation, three glucuronide metabolites for oxyresveratrol (ORV) were formed: trans-ORV-4′-O-glucuronide, trans-ORV-3-O-glucuronide, and trans-ORV-2′-O-glucuronide. In addition, two glucuronide metabolites were obtained for gnetol (GN): trans-GN-2′-O-glucuronide and trans-GN-3-O-glucuronide. When the metabolism of ORV and GN is studied in vitro by human and rat hepatic enzymes, four of the five hemisynthesized compounds were identified and quantified. Human enzymes glucuronidated preferably at the C-2′ position, whereas rat enzymes do so at the C-3 position. In view of these kinetic findings, rat enzymes have a stronger metabolic capacity than human enzymes. Finally, ORV, GN, and their glucuronide metabolites (mainly at the C-3 position) decreased nitric oxide, reactive oxygen species, interleukin 1β, and tumor necrosis factor α production in lipopolysaccharide-stimulated macrophages

Impairment of NO-Dependent Relaxation in Intralobar Pulmonary Arteries: Comparison of Urban Particulate Matter and Manufactured Nanoparticles

International audienceBACKGROUND AND OBJECTIVES: Because pulmonary circulation is the primary vascular target of inhaled particulate matter (PM), and nitric oxide is a major vasculoprotective agent, in this study we investigated the effect of various particles on the NO-cyclic guanosine monophosphate (cGMP) pathway in pulmonary arteries. METHODS: We used intrapulmonary arteries and/or endothelial cells, either exposed in vitro to particles or removed from PM-instilled animals for assessment of vasomotricity, cGMP and reactive oxygen species (ROS) levels, and cytokine/chemokine release. RESULTS: Endothelial NO-dependent relaxation and cGMP accumulation induced by acetylcholine (ACh) were both decreased after 24 hr exposure of rat intrapulmonary arteries to standard reference material 1648 (SRM1648; urban PM). Relaxation due to NO donors was also decreased by SRM1648, whereas responsiveness to cGMP analogue remained unaffected. Unlike SRM1648, ultrafine carbon black and ultrafine and fine titanium dioxide (TiO2) manufactured particles did not impair NO-mediated relaxation. SRM1648-induced decrease in relaxation response to ACh was prevented by dexamethasone (an anti-inflammatory agent) but not by antioxidants. Accordingly, SRM1648 increased the release of proinflammatory mediators (tumor necrosis factor-alpha, interleukin-8) from intrapulmonary arteries or pulmonary artery endothelial cells, but did not elevate ROS levels within intrapulmonary arteries. Decreased relaxation in response to ACh was also evidenced in intrapulmonary arteries removed from rats intratracheally instilled with SRM1648, but not with fine TiO2. CONCLUSION: In contrast to manufactured particles (including nanoparticles), urban PM impairs NO but not cGMP responsiveness in intrapulmonary arteries. We attribute this effect to oxidative-stress-independent inflammatory response, resulting in decreased guanylyl cyclase activation by NO. Such impairment of the NO pathway may contribute to urban-PM-induced cardiovascular dysfunction

Recent Asian origin of chytrid fungi causing global amphibian declines

Globalized infectious diseases are causing species declines worldwide, but their source often remains elusive. We used whole-genome sequencing to solve the spatiotemporal origins of the most devastating panzootic to date, caused by the fungus Batrachochytrium dendrobatidis, a proximate driver of global amphibian declines. We traced the source of B. dendrobatidis to the Korean peninsula, where one lineage, BdASIA-1, exhibits the genetic hallmarks of an ancestral population that seeded the panzootic. We date the emergence of this pathogen to the early 20th century, coinciding with the global expansion of commercial trade in amphibians, and we show that intercontinental transmission is ongoing. Our findings point to East Asia as a geographic hotspot for B. dendrobatidis biodiversity and the original source of these lineages that now parasitize amphibians worldwide