Phospho-mTOR expression in human glioblastoma microglia-macrophage cells

The glioblastoma (GBM) immune microenvironment is highly heterogeneous, and microglia may represent 30–70% of the entire tumor. However, the role of microglia and other specific immune populations is poorly characterized. Activation of mTOR signaling occurs in numerous human cancers and has roles in microglia-glioma cell interactions. We now show in human tumor specimens (42 patients), that 39% of tumor-associated microglial (TAM) cells express mTOR phosphorylated at Ser-2448; and similar mTOR activation is observed using a human microglia-glioma interaction paradigm. In addition, we confirm previous studies that microglia express urea and ARG1 (taken as M2 marker) in the presence of glioma cells, and this phenotype is down-regulated in the presence of a mTOR inhibitor. These results suggest that mTOR suppression in GBM patients might induce a reduction of the M2 phenotype expression in up to 40% of all TAMs. Since the M2 profile of microglial activation is believed to be associated with tumor progression, reductions in that phenotype may represent an additional anti-tumor mechanism of action of mTOR inhibitors, along with direct anti-proliferative activities

Pdia3 expression in glioblastoma modulates macrophage/microglia pro-tumor activation

The glioblastoma (GB) microenvironment includes cells of the innate immune system identified as glioma-associated microglia/macrophages (GAMs) that are still poorly characterized. A potential role on the mechanisms regulating GAM activity might be played by the endoplasmic reticulum protein ERp57/PDIA3 (protein disulfide-isomerase A3), the modulation of which has been reported in a variety of cancers. Moreover, by using The Cancer Genome Atlas database, we found that overexpression of PDIA3 correlated with about 55% reduction of overall survival of glioma patients. Therefore, we analyzed the expression of ERp57/PDIA3 using specimens obtained after surgery from 18 GB patients. Immunohistochemical analysis of tumor samples revealed ERp57/PDIA3 expression in GB cells as well as in GAMs. The ERp57/PDIA3 levels were higher in GAMs than in the microglia present in the surrounding parenchyma. Therefore, we studied the role of PDIA3 modulation in microglia\u2013glioma interaction, based on the ability of conditioned media collected from human GB cells to induce the activation of microglial cells. The results indicated that reduced PDIA3 expression/activity in GB cells significantly limited the microglia pro-tumor polarization towards the M2 phenotype and the production of pro-inflammatory factors. Our data support a role of PDIA3 expression in GB-mediated protumor activation of microglia

Screening of Iberian Coinage in the 2(th)-1(th) BCE Period Using the Voltammetry of Immobilized Particles

This is the peer reviewed version of the following article: A. Doménech-Carbó, M. T. Doménech-Carbó, C. Álvarez-Romero, T. Pasíes, M. Buendía, Electroanalysis 2019, 31, 1164, which has been published in final form at https://doi.org/10.1002/elan.201900090. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.[EN] The voltammetry of immobilized particles (VIMP) was applied for grouping a series of 86 Iberian coins nominally minted in the cities of Iltirta, Castulo and Obulco in the 2(th)-1(th) BCE period for which there are no chronological data. Using characteristic signatures for the reduction of cuprite, tenorite and lead corrosion products in the patina of the coins, voltammetric grouping of coins was proposed. Voltammetric data were found to be consistent with textural and compositional properties of the surface and subsurface of selected coins using FIB-FESEM-EDX. The obtained data confirmed a clear separation between the productions of Iltirta on one side, and those of Castulo and Obulco on the other side, indicating the possibility to establish a rough chronology for these productions.Project CTQ2017-85317-C2-1-P, supported with Ministerio de Economia, Industria y Competitividad (MINECO), Fondo Europeo de Desarrollo Regional (ERDF) and Agencia Estatal de Investigacion (AEI), is gratefully acknowledged. The authors wish also to thank Mr. Manuel Planes and Dr. Jose Luis Moya, technical supervisors of the Electron Microscopy Service of the Universitat Politecnica de Valencia. Thanks to Manuel Gozalbes for his technical assistance in the numismatic domain and Gonzalo Cores and the Museu de Prehistrica de Valencia for facilitating the access to its collections.Doménech-Carbó, A.; Domenech Carbo, MT.; Álvarez-Romero, C.; Pasíes, T.; Buendía, M. (2019). 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The analysis of European lacquer : optimization of thermochemolysis temperature of natural resins

In order to optimize chromatographic analysis of European lacquer, thermochemolysis temperature was evaluated for the analysis of natural resins. Five main ingredients of lacquer were studied: sandarac, mastic, colophony, Manila copal and Congo copal. For each, five temperature programs were tested: four fixed temperatures (350, 480, 550, 650 degrees C) and one ultrafast thermal desorption (UFD), in which the temperature rises from 350 to 660 degrees C in 1 min. In total, the integrated signals of 27 molecules, partially characterizing the five resins, were monitored to compare the different methods. A compromise between detection of compounds released at low temperatures and compounds formed at high temperatures was searched. 650 degrees C is too high for both groups, 350 degrees C is best for the first, and 550 degrees C for the second. Fixed temperatures of 480 degrees C or UFD proved to be a consensus in order to detect most marker molecules. UFD was slightly better for the molecules released at low temperatures, while 480 degrees C showed best compounds formed at high temperatures

XPS characterization of (copper-based) coloured stains formed on limestone surfaces of outdoor Roman monuments

Limestone basements holding bronzes or other copper alloys artefacts such as sculptures, decorations and dedicatory inscriptions are frequently met both in modern and ancient monuments. In outdoor conditions, such a combination implies the corrosion products of the copper based alloy, directly exposed to rainwater, will be drained off and migrate through the porous surfaces, forming stains of different colours and intensities, finally causing the limestone structures to deteriorate

Avaliação e perspectivas da abordagem à conservação do patrimônio organístico no Brasil

Órgãos de tubos são construídos no Brasil, ou importados do exterior, desde as primeiras décadas do período colonial. Estes instrumentos, apesar de constituírem um conjunto relativamente exíguo, representam um testemunho histórico e musical de valor inestimável. No entanto, de um modo geral, encontram-se em condições precárias de funcionamento e, em parte, mais ou menos descaracterizados profundamente, quanto à sua estrutura e configuração original, às vezes em estado de abandono e, por incrível que pareça, ainda sujeitos ao risco de intervenções arbitrárias e desprovidas de bases técnicas e de preocupação histórica e musicológica. Neste artigo, busca-se percorrer o caminho que levou à atual situação e discutem-se os princípios e os critérios de processos de recuperação, manutenção e conservação preventiva desse patrimônio, partindo dos pressupostos do respeito à sua originalidade e do direito a restauros segundo os rigorosos cânones já definidos para objetos com plena condição de bem cultural, cujo reconhecimento para os órgãos de qualquer época deve ser urgentemente garantido.Pipe organs have been built in Brazil or imported from elsewhere since the very first decades of the colonial period. Albeit relatively small in number, such instruments have inestimable historical and musical value. Notwithstanding, they are generally in very poor working condition and some have lost much of their original structure and configuration; they are often found in a state of abandonment and, incredible as it may seem, still under the threat of arbitrary interventions performed with no technical expertise or any concern for their historical and musicological significance. This article is an effort to understand how this state of affairs came to be, and discusses principles and criteria for the restoration, maintenance and preventive conservation of this legacy, based on assumptions regarding its original conditions and entitlement to restoration in accordance with the stringent standards already set for artifacts that enjoy the full status of cultural assets, which should also be urgently granted to pipe organs of any time and age

Effect of jenny milk addition on the inhibition of late blowing in semihard cheese

The occurrence of late blowing defects in cheese produces negative effects on the quality and commercial value of the product. In this work, we verified whether the addition of raw jenny milk to bulk cow milk reduced the late blowing defects in semihard cheeses. During cheesemaking, different aliquots of jenny milk were poured into 2 groups of 4 vats, each containing a fixed amount of cow milk. A group of cheeses was created by deliberately contaminating the 4 vats with approximately 3 log10 cfu/mL milk of Clostridium tyrobutyricum CLST01. The other 4 vats, which were not contaminated, were used for a second group of cheeses. After 120 d of ripening, some physical, chemical, and microbiological parameters were evaluated on the obtained semihard cheeses. Differences in sensory properties among cheeses belonging to the uncontaminated group were evaluated by 80 regular consumers of cheese. Our results showed that the increasing addition of jenny milk to cow milk led to a reduction of pH and total bacterial count in both cheese groups, as well as C. tyrobutyricum spores that either grew naturally or artificially inoculated. We observed a progressive reduction of the occurrence of late blowing defects in cheese as consequence of the increasing addition of jenny milk during cheese making. Moreover, the addition of jenny milk did not affect the acceptability of the product, as consumers found no difference among cheeses concerning sensorial aspects. In conclusion, the important antimicrobial activity of lysozyme contained in jenny milk has been confirmed in the current research. It is recommend for use as a possible and viable alternative to egg lysozyme for controlling late blowing defects in cheese