Influence of IFN-gamma and its receptors in human breast cancer

<p>Abstract</p> <p>Background</p> <p>Interferons are a group of proteins that trigger multiple responses including prevention of viral replication, inhibition of cell growth, and modulation of cell differentiation. In different mammary carcinoma cell lines IFNγ induces growth arrest at mid-G1. At the present there are no <it>in vivo </it>studies in human breast. The aim of this study was to investigate the expression patterns of IFNγ and its two receptors (IFNγ-Rα and IFNγ-Rβ) by Western blot and immunohistochemistry, in order to elucidate its role in the different types of human breast cancer (<it>in situ </it>and infiltrative).</p> <p>Methods</p> <p>Immunohistochemical and semiquantitative study of IFNγ, its receptors types (IFNγ-Rα and IFNγ-Rβ), cell proliferation (proliferating cell nuclear antigen, also named PCNA), and apoptosis (TUNEL method) was carried between the three breast groups (fibrocystic lesions, <it>in situ</it> tumors and infiltrating tumors).</p> <p>Results</p> <p>In the three groups of patients, IFNγ and IFNγ-Rα immunoreactions appeared in the cytoplasm while IFNγ-Rβ also was found in the nucleus. The optical density to IFNγ was higher in <it>in situ </it>carcinoma than in benign and infiltrating tumors. When we observed IFNγ-Rα, the optical density was lower in infiltrating carcinoma than in benign and <it>in situ </it>tumors (the higher density). To IFNγ-Rβ, the optical density was similar in the three group samples. In tumor samples PCNA and TUNEL index was significantly higher; than in benign diseases. PCNA index increased with the malignance. No significant differences were found between cancer types to TUNEL. IFNγ could be a potential therapeutic tool in breast cancer. However, tumor cells are able to escape from the control of this cytokine in the early tumor stages; this is probably due to a decreased expression of IFNγ, or also to an alteration of either its receptors or some transduction elements.</p> <p>Conclusion</p> <p>We conclude that the decrease in the % positive samples that expressed IFNγ and IFNγ-Rα together with the nuclear localization of IFNγ-Rβ, could be a tumoral cell response, although perhaps insufficient to inhibit the uncontrolled cell proliferation. Perhaps, IFNγ might be unable to activate p21 to stop the cell cycle, suggesting a possible participation in breast cancer development.</p

Comparison of Physical-chemical and Mechanical Properties of Chlorapatite and Hydroxyapatite Plasma Sprayed Coatings

Chlorapatite can be considered a potential biomaterial for orthopaedic applications. Its use as plasma-sprayed coating could be of interest considering its thermal properties and particularly its ability to melt without decomposition unlike hydroxyapatite. Chlorapatite (ClA) was synthesized by a high-temperature ion exchange reaction starting from commercial stoichiometric hydroxyapatites (HA). The ClA powder showed similar characteristics as the original industrial HA powder, and was obtained in the monoclinic form. The HA and ClA powders were plasma-sprayed using a low-energy plasma spraying system with identical processing parameters. The coatings were characterized by physical-chemical methods, i.e. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy, including distribution mapping of the main phases detected such as amorphous calcium phosphate (ACP), oxyapatite (OA), and HA or ClA. The unexpected formation of oxyapatite in ClA coatings was assigned to a side reaction with contaminating oxygenated species (O2, H2O). ClA coatings exhibited characteristics different from HA, showing a lower content of oxyapatite and amorphous phase. Although their adhesion strength was found to be lower than that of HA coatings, their application could be an interesting alternative, offering, in particular, a larger range of spraying conditions without formation of massive impurities.This study was carried out under a MNT ERA-Net Project named NANOMED. The authors gratefully thank the Midi-Pyrénées region (MNT ERA Net Midi-Pyrénées Région, NANOMED2 project) and the Institute National Polytechnique de Toulouse (BQR INPT 2011, BIOREVE project) for supporting this research work, especially the financial support for research carried out in the CIRIMAT and the LGP laboratories (France), and the Basque government and Tratamientos Superficiales Iontech, S.A. for their financial and technical support under the IG-2007/0000381 grant for the development of the LEPS device and deposition of the coatings carried out in Inasmet-Tecnalia. The French industrial collaborators (TEKNIMED SA and 2PS SA) were financed by the OSEO programs

The Rise and Fall of "Respectable" Spanish Liberalism, 1808-1923: An Explanatory Framework

The article focuses on the reasons behind both the consolidation of what I have termed “respectable” liberalism between the 1830s and the 1840s and its subsequent decline and fall between 1900 and 1923. In understanding both processes I study the links established between “respectable” liberals and propertied elites, the monarchy, and the Church. In the first phase these links served to consolidate the liberal polity. However, they also meant that many tenets of liberal ideology were compromised. Free elections were undermined by the operation of caciquismo, monarchs established a powerful position, and despite the Church hierarchy working with liberalism, the doctrine espoused by much of the Church was still shaped by the Counter-Reformation. Hence, “respectable” liberalism failed to achieve a popular social base. And the liberal order was increasingly denigrated as part of the corrupt “oligarchy” that ruled Spain. Worse still, between 1916 and 1923 the Church, monarch, and the propertied elite increasingly abandoned the liberal Monarchist Restoration. Hence when General Primo de Rivera launched his coup the rug was pulled from under the liberals’ feet and there was no one to cushion the fall

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

MEGARA, the R=6000-20000 IFU and MOS of GTC

MEGARA is the new generation IFU and MOS optical spectrograph built for the 10.4m Gran Telescopio CANARIAS (GTC). The project was developed by a consortium led by UCM (Spain) that also includes INAOE (Mexico), IAA-CSIC (Spain) and UPM (Spain). The instrument arrived to GTC on March 28th 2017 and was successfully integrated and commissioned at the telescope from May to August 2017. During the on-sky commissioning we demonstrated that MEGARA is a powerful and robust instrument that provides on-sky intermediate-to-high spectral resolutions RFWHM ~ 6,000, 12,000 and 20,000 at an unprecedented efficiency for these resolving powers in both its IFU and MOS modes. The IFU covers 12.5 x 11.3 arcsec 2 while the MOS mode allows observing up to 92 objects in a region of 3.5 x 3.5 arcmin 2 . In this paper we describe the instrument main subsystems, including the Folded-Cassegrain unit, the fiber link, the spectrograph, the cryostat, the detector and the control subsystems, and its performance numbers obtained during commissioning where the fulfillment of the instrument requirements is demonstrated. © 2018 SPIE

Linking electrostatic effects and protein motions in enzymatic catalysis. A theoretical analysis of catechol o-methyltransferase

The role of protein motions in enzymatic catalysis is the subject of a hot scientific debate. We here propose the use of an explicit solvent coordinate to analyze the impact of environmental motions during the reaction process. The example analyzed here is the reaction catalyzed by catechol O-methyltransferase, a methyl transfer reaction from S-adenosylmethionine (SAM) to the nucleophilic oxygen atom of catecholate. This reaction proceeds from a charged reactant to a neutral product, and then a large electrostatic coupling with the environment could be expected. By means of a two-dimensional free energy surface, we show that a large fraction of the environmental motions needed to attain the transition state happens during the first stages of the reaction because most of the environmental motions are slower than changes in the substrate. The incorporation of the solvent coordinate in the definition of the transition state improves the transmission coefficient and the committor histogram in solution, while the changes are much less significant in the enzyme. The equilibrium solvation approach seems then to work better in the enzyme than in aqueous solution because the enzyme provides a preorganized environment where the reaction takes place

A Novel Strategy to Study Electrostatic Effects in Chemical Reactions: Differences between the Role of Solvent and the Active Site of Chalcone Isomerase in a Michael Addition

The electrostatic behavior of active site residues in enzyme catalysis is quite different from that of water molecules in solution. To highlight the electrostatic differences between both environments, we propose a QM/MM strategy to study the role of the environment in chemical reactions. The novelty of the present communication is that free energy surfaces are generated by means of two distinguished reaction coordinates: a solute coordinate and the electrostatic potential created by the environment. This is applied to analyze the origin of catalysis in the transformation of a chalcone into a flavanone, a Michael addition that requires the desolvation of the nucleophile