Large oncosomes contain distinct protein cargo and represent a separate functional class of tumor-derived extracellular vesicles

Large oncosomes (LO) are atypically large (1-10 mu m diameter) cancer-derived extracellular vesicles (EVs), originating from the shedding of membrane blebs and associated with advanced disease. We report that 25% of the proteins, identified by a quantitative proteomics analysis, are differentially represented in large and nano-sized EVs from prostate cancer cells. Proteins enriched in large EVs included enzymes involved in glucose, glutamine and amino acid metabolism, all metabolic processes relevant to cancer. Glutamine metabolism was altered in cancer cells exposed to large EVs, an effect that was not observed upon treatment with exosomes. Large EVs exhibited discrete buoyant densities in iodixanol (OptiPrep (TM)) gradients. Fluorescent microscopy of large EVs revealed an appearance consistent with LO morphology, indicating that these structures can be categorized as LO. Among the proteins enriched in LO, cytokeratin 18 (CK18) was one of the most abundant (within the top 5th percentile) and was used to develop an assay to detect LO in the circulation and tissues of mice and patients with prostate cancer. These observations indicate that LO represent a discrete EV type that may play a distinct role in tumor progression and that may be a source of cancer-specific markers.1182Ysciescopu

P2 receptors in atherosclerosis and postangioplasty restenosis

Atherosclerosis is an immunoinflammatory process that involves complex interactions between the vessel wall and blood components and is thought to be initiated by endothelial dysfunction [Ross (Nature 362:801–09, 1993); Fuster et al. (N Engl J Med 326:242–50, 1992); Davies and Woolf (Br Heart J 69:S3–S11, 1993)]. Extracellular nucleotides that are released from a variety of arterial and blood cells [Di Virgilio and Solini (Br J Pharmacol 135:831–42, 2002)] can bind to P2 receptors and modulate proliferation and migration of smooth muscle cells (SMC), which are known to be involved in intimal hyperplasia that accompanies atherosclerosis and postangioplasty restenosis [Lafont et al. (Circ Res 76:996–002, 1995)]. In addition, P2 receptors mediate many other functions including platelet aggregation, leukocyte adherence, and arterial vasomotricity. A direct pathological role of P2 receptors is reinforced by recent evidence showing that upregulation and activation of P2Y2 receptors in rabbit arteries mediates intimal hyperplasia [Seye et al. (Circulation 106:2720–726, 2002)]. In addition, upregulation of functional P2Y receptors also has been demonstrated in the basilar artery of the rat double-hemorrhage model [Carpenter et al. (Stroke 32:516–22, 2001)] and in coronary artery of diabetic dyslipidemic pigs [Hill et al. (J Vasc Res 38:432–43, 2001)]. It has been proposed that upregulation of P2Y receptors may be a potential diagnostic indicator for the early stages of atherosclerosis [Elmaleh et al. (Proc Natl Acad Sci U S A 95:691–95, 1998)]. Therefore, particular effort must be made to understand the consequences of nucleotide release from cells in the cardiovascular system and the subsequent effects of P2 nucleotide receptor activation in blood vessels, which may reveal novel therapeutic strategies for atherosclerosis and restenosis after angioplasty

Modeling in MiningZinc

MiningZinc offers a framework for modeling and solving constraint-based mining problems. The language used is MiniZinc, a high-level declarative language for modeling combinatorial (optimisation) problems. This language is augmented with a library of functions and predicates that help modeling data mining problems and facilities for interfacing with databases. We show how MiningZinc can be used to model constraint-based itemset mining problems, for which it was originally designed, as well as sequence mining, Bayesian pattern mining, linear regression, clustering data factorization and ranked tiling. The underlying framework can use any existing MiniZinc solver. We also showcase how the framework and modeling capabilities can be integrated into an imperative language, for example as part of a greedy algorithm

Effects of the Erika oil spill on the common starfish Asterias rubens, evaluated by field and laboratory studies.

Impacts of the Erika oil spill on the common starfish Asterias rubens were investigated in the field and using laboratory experiments based on contamination via food at different stages of the starfish reproductive cycle. Two months after the shipwreck, levels of hydrocarbons characteristic of Erika fuel were significantly higher in pyloric ceca and body wall of A. rubens from a contaminated site, compared with control animals from an unpolluted reference area. Concomitant immunological responses and detoxification enzyme activity (CYP1A) were enhanced in the impacted starfish, suggesting rapid biotransformation processes. This was confirmed by laboratory experiments which showed a fast PAH uptake during the 10 first days of contamination and the start of biotransformation processes from the third day. Our study confirms benzo(a)pyrene hydroxylase activity (BPH) in A. rubens and demonstrates the influence of CYP1A in the conversion of insoluble PAHs into soluble derivatives in this species for the first time. The rapidity of decontamination could explain why starfish growth, level of motile activity, reproductive investment, energy storage, and larval development were not significantly affected by these contaminants.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe