Basement membrane-rich Organoids with functional human blood vessels are permissive niches for human breast cancer metastasis

Metastasic breast cancer is the leading cause of death by malignancy in women worldwide. Tumor metastasis is a multistep process encompassing local invasion of cancer cells at primary tumor site, intravasation into the blood vessel, survival in systemic circulation, and extravasation across the endothelium to metastasize at a secondary site. However, only a small percentage of circulating cancer cells initiate metastatic colonies. This fact, together with the inaccessibility and structural complexity of target tissues has hampered the study of the later steps in cancer metastasis. In addition, most data are derived from in vivo models where critical steps such as intravasation/extravasation of human cancer cells are mediated by murine endothelial cells. Here, we developed a new mouse model to study the molecular and cellular mechanisms underlying late steps of the metastatic cascade. We have shown that a network of functional human blood vessels can be formed by co-implantation of human endothelial cells and mesenchymal cells, embedded within a reconstituted basement membrane-like matrix and inoculated subcutaneously into immunodeficient mice. The ability of circulating cancer cells to colonize these human vascularized organoids was next assessed in an orthotopic model of human breast cancer by bioluminescent imaging, molecular techniques and immunohistological analysis. We demonstrate that disseminated human breast cancer cells efficiently colonize organoids containing a functional microvessel network composed of human endothelial cells, connected to the mouse circulatory system. Human breast cancer cells could be clearly detected at different stages of the metastatic process: initial arrest in the human microvasculature, extravasation, and growth into avascular micrometastases. This new mouse model may help us to map the extravasation process with unprecedented detail, opening the way for the identification of relevant targets for therapeutic intervention

Un panista opina sobre su partido

Entrevista hecha por Ana María Silva a Felipe Vicencio Álvarez, senador por el estado de Jalisco de la LIX Legislatura del Congreso de la Unión, por el Partido Acción Nacional (PAN). En ella plantea las estrategias que tendría que llevar a cabo su partido para realizar su proyecto social, económico y político.ITESO, A.C

Lipid-free Antigen B subunits from echinococcus granulosus: oligomerization, ligand binding, and membrane interaction properties

Background: The hydatid disease parasite Echinococcus granulosus has a restricted lipid metabolism, and needs to harvest essential lipids from the host. Antigen B (EgAgB), an abundant lipoprotein of the larval stage (hydatid cyst), is thought to be important in lipid storage and transport. It contains a wide variety of lipid classes, from highly hydrophobic compounds to phospholipids. Its protein component belongs to the cestode-specific Hydrophobic Ligand Binding Protein family, which includes five 8-kDa isoforms encoded by a multigene family (EgAgB1-EgAgB5). How lipid and protein components are assembled into EgAgB particles remains unknown. EgAgB apolipoproteins self-associate into large oligomers, but the functional contribution of lipids to oligomerization is uncertain. Furthermore, binding of fatty acids to some EgAgB subunits has been reported, but their ability to bind other lipids and transfer them to acceptor membranes has not been studied.<p></p> Methodology/Principal Findings: Lipid-free EgAgB subunits obtained by reverse-phase HPLC were used to analyse their oligomerization, ligand binding and membrane interaction properties. Size exclusion chromatography and cross-linking experiments showed that EgAgB8/2 and EgAgB8/3 can self-associate, suggesting that lipids are not required for oligomerization. Furthermore, using fluorescent probes, both subunits were found to bind fatty acids, but not cholesterol analogues. Analysis of fatty acid transfer to phospholipid vesicles demonstrated that EgAgB8/2 and EgAgB8/3 are potentially capable of transferring fatty acids to membranes, and that the efficiency of transfer is dependent on the surface charge of the vesicles.<p></p> Conclusions/Significance: We show that EgAgB apolipoproteins can oligomerize in the absence of lipids, and can bind and transfer fatty acids to phospholipid membranes. Since imported fatty acids are essential for Echinococcus granulosus, these findings provide a mechanism whereby EgAgB could engage in lipid acquisition and/or transport between parasite tissues. These results may therefore indicate vulnerabilities open to targeting by new types of drugs for hydatidosis therapy.<p></p&gt

Toxicity of ZnO nanoparticles, ZnO bulk and ZnCl2 on earthworms in a spiked natural soil and toxicological effects of leachates on aquatic organisms

The present study assessed the uptake and toxicity of ZnO nanoparticles (NPs), ZnO bulk, and ZnCl2 salt in earthworms in spiked agricultural soils. In addition, the toxicity of aqueous extracts to Daphnia magna and Chlorella vulgaris was analyzed to determine the risk of these soils to the aquatic compartment. We then investigated the distribution of Zn in soil fractions to interpret the nature of toxicity. Neither mortality nor differences in earthworm body weight were observed compared with the control. The most sensitive end point was reproduction. ZnCl2 was notably toxic in eliminating the production of cocoons. The effects induced by ZnO-NPs and bulk ZnO on fecundity were similar and lower than those of the salt. In contrast to ZnO bulk, ZnO-NPs adversely affected fertility. The internal concentrations of Zn in earthworms in the NP group were greater than those in the salt and bulk groups, although bioconcentration factors were consistently <1. No relationship was found between toxicity and internal Zn amounts in earthworms. The results from the sequential extraction of soil showed that ZnCl2 displayed the highest availability compared with both ZnO. Zn distribution was consistent with the greatest toxicity showed by the salt but not with Zn body concentrations. The soil extracts from both ZnO-NPs and bulk ZnO did not show effects on aquatic organisms (Daphnia and algae) after short-term exposure. However, ZnCl2 extracts (total and 0.45-μm filtered) were toxic to Daphnia

Gromov hyperbolicity of Denjoy domains

25 pages, no figures.-- MSC2000 codes: 41A10, 46E35, 46G10.MR#: MR2276245 (2007i:30069)Zbl#: Zbl 1115.53030In this paper we characterize the Gromov hyperbolicity of the double of a metric space. This result allows to give a characterization of the hyperbolic Denjoy domains, in terms of the distance to $\Bbb{R}$ of the points in some geodesics. In the particular case of trains (a kind of Riemann surfaces which includes the flute surfaces), we obtain more explicit criteria which depend just on the lengths of what we have called fundamental geodesics.Research partially supported by three grants from M.E.C. (MTM 2006-11976, MTM 2006-13000-C03-02 and MTM 2004-21420-E), Spain.Publicad

Kinetics of Thermal Degradation of Cellulose: Analysis Based on Isothermal and Linear Heating Data

[Abstarct]: In spite of the many studies performed, there is not yet a kinetic model to predict the thermal degradation of cellulose in isothermal and non-isothermal conditions for the full extent of conversion. A model proposed by the authors was tested on non-oxidising thermogravimetric data. The method consisted of initially fitting several isothermal and non-isothermal curves, then obtaining a critical temperature and an energy barrier from the set of fittings that resulted from different experimental conditions. While the critical temperature, approximately 226 °C, represented the minimum temperature for the degradation process, the degradation rate at a given temperature was related to both the critical temperature and the energy barrier. These results were compared with those observed in other materials. The quality of fittings obtained was superior to any other reported to date, and the results obtained from each single curve were in line with each other.This work was partially funded by the Spanish Ministerio de Educación y Ciencia (MTM2011-22393 and MTM2014-52876-R

Microwave-assisted parallel synthesis of a 2-aryl-1H-isoindole-1,3-dione library

An efficient parallel synthesis of a representative 28-member library of phthalimides is described. Parallel chromatography afforded the library members in suitable purity and with high yields

Synthesis and characterization of new membranes based on sulfonated polysulfone/Zn,Al-heptamolibdate LDH

New proton conducting organic/inorganic nano-hybrid polymer electrolyte membranes were synthesized by solving casting method. Inorganic nanopowders were a layered double hydroxides (LDH) with Zn,Al cations in which heptamolybdate were inserted. These nanopowders were prepared by anion exchange method from hydrotalcite (LDH) with interlayer anions (NO₃). The sulfonated polymers were prepared by an electrophilic aromatic substitution reaction between the polymer and trimethylsylil cholorosulfonate (TMSCS). The composites membranes were characterized by FTIR and TGA and water uptake was determined. Electrochemical impedance spectroscopy (EIS) was used to study the proton conductivity of the membranes. EIS measurements were performed facing the membrane to different HCl concentrations (103 ≤ c ≤101 M). It was concluded that these new composite membranes present good thermal properties and proton conductivity slightly higher than SPSU.This work has been supported by the Projects from the regional government (Comunidad de Madrid through MATERYENER3CM S2013/MIT2753) and Spanish Government, MINECO (MAT2013 46452C43R)

Porous Titanium Cylinders Obtained by the Freeze-Casting Technique: Influence of Process Parameters on Porosity and Mechanical Behavior

 The discrepancy between the stiffness of commercially pure titanium and cortical bone  tissue compromises its success as a biomaterial. The use of porous titanium has been widely studied,  however, it is still challenging to obtain materials able to replicate the porous structure of the bones  (content, size, morphology and distribution). In this work, the freeze‐casting technique is used to  manufacture cylinders with elongated porosity, using a home‐made and economical device. The  relationship between the processing parameters (diameter and material of the mold, temperature  gradient), microstructural features and mechanical properties is established and discussed, in terms  of ensuring biomechanical and biofunctional balance. The cylinders have a gradient porosity  suitable for use in dentistry, presenting higher Young’s modulus at the bottom, near the cold spot  and, therefore better mechanical resistance (it would be in contact with a prosthetic crown), while  the opposite side, the hot spot, has bigger, elongated pores and walls.  Ministry of Economy and Competitiveness of Spain  grant  MAT2015‐71284‐P  FEDER‐Junta de Andalucía Research  Project (Modeling and implementation of the freeze casting technique: gradients of porosity with a tribomechanical equilibrium and electro‐stimulated cellular behavior).