Gastric cancer extracellular vesicles tune the migration and invasion of epithelial and mesenchymal cells in a histotype-dependent manner

Extracellular vesicles (EVs) secreted by tumor cells modulate recipient cells’ behavior, but their effects in normal cells from the tumor microenvironment remain poorly known. In this study, we dissected the functional impact of gastric cancer cell-derived EVs (GC-EVs), representative of distinct GC histotypes, on the behavior of normal isogenic epithelial and mesenchymal cells. GC-EVs were isolated by differential centrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, and imaging flow-cytometry. Epithelial and mesenchymal cells were challenged with GC-EVs and submitted to proliferation, migration, and invasion assays. Expression of epithelial and mesenchymal markers was followed by immunofluorescence and flow-cytometry. Our results indicated that GC-EVs secreted by diffuse-type cancer cells decrease the migration of recipient cells. This effect was more prominent and persistent for mesenchymal recipient cells, which also increased Fibronectin expression in response to EVs. GC-EVs secreted by cancer cells derived from tumors with an intestinal component increased invasion of recipient epithelial cells, without changes in EMT markers. In summary, this study demonstrated that GC-EVs modulate the migration and invasion of epithelial and mesenchymal cells from the tumor microenvironment, in a histotype-dependent manner, highlighting new features of intestinal and diffuse-type GC cells, which may help explaining differential metastasis patterns and aggressiveness of GC histotypes.Ipatimup integrate the i3S Research Unit, which is partially supported by FCT, the Portuguese Foundation for Science and Technology. This work was supported by (1) FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through Portuguese Science and Technology Foundation (FCT)/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274); (2) the project NORTE-01-0145-FEDER-000029, supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); (3) Portuguese FCT with the Grant Reference PTDC/BBB-ECT/2518/2014; (4) FCT PhD Programmes and by Programa Operacional Potencial Humano (POCH), specifically by the BiotechHealth Programe (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences); (5) Ipatimup Board of Directors: Project “The role of gastric cancer cell-derived extracellular vesicles”; and (6) FCT fellowships PD/BD/128406/2017 to SR, SFRH/BPD/86543/2012 to JC, and SFRH/BPD/89764/2012 to PO

Deletion of BmoR affects the expression of genes related to thiol/disulfide balance in Bacteroides fragilis

Bacteroides fragilis, an opportunistic pathogen and commensal bacterium in the gut, is one the most aerotolerant species among strict anaerobes. However, the mechanisms that control gene regulation in response to oxidative stress are not completely understood. In this study, we show that the MarR type regulator, BmoR, regulates the expression of genes involved in the homeostasis of intracellular redox state. Transcriptome analysis showed that absence of BmoR leads to altered expression in total of 167 genes. Sixteen of these genes had a 2-fold or greater change in their expression. Most of these genes are related to LPS biosynthesis and carbohydrates metabolism, but there was a signifcant increase in the expression of genes related to the redox balance inside the cell. A pyridine nucleotide-disulfde oxidoreductase located directly upstream of bmoR was shown to be repressed by direct binding of BmoR to the promoter region. The expression of two other genes, coding for a thiosulphate:quinoneoxidoreductase and a thioredoxin, are indirectly afected by bmoR mutation during oxygen exposure. Phenotypic assays showed that BmoR is important to maintain the thiol/disulfde balance in the cell, confrming its relevance to B. fragilis response to oxidative stress

Human breast cancer cells demonstrate electrical excitability

Breast cancer is one of the most prevalent types of cancers worldwide and yet, its pathophysiology is poorly understood. Single-cell electrophysiological studies have provided evidence that membrane depolarization is implicated in the proliferation and metastasis of breast cancer. However, metastatic breast cancer cells are highly dynamic microscopic systems with complexities beyond a single-cell level. There is an urgent need for electrophysiological studies and technologies capable of decoding the intercellular signaling pathways and networks that control proliferation and metastasis, particularly at a population level. Hence, we present for the first time non-invasive in vitro electrical recordings of strongly metastatic MDA-MB-231 and weakly/non-metastatic MCF-7 breast cancer cell lines. To accomplish this, we fabricated an ultra-low noise sensor that exploits large-area electrodes, of 2 mm2, which maximizes the double-layer capacitance and concomitant detection sensitivity. We show that the current recorded after adherence of the cells is dominated by the opening of voltage-gated sodium channels (VGSCs), confirmed by application of the highly specific inhibitor, tetrodotoxin (TTX). The electrical activity of MDA-MB-231 cells surpasses that of the MCF-7 cells, suggesting a link between the cells’ bioelectricity and invasiveness. We also recorded an activity pattern with characteristics similar to that of Random Telegraph Signal (RTS) noise. RTS patterns were less frequent than the asynchronous VGSC signals. The RTS noise power spectral density showed a Lorentzian shape, which revealed the presence of a low-frequency signal across MDA-MB-231 cell populations with propagation speeds of the same order as those reported for intercellular Ca2+ waves. Our recording platform paves the way for real-time investigations of the bioelectricity of cancer cells, their ionic/pharmacological properties and relationship to metastatic potential

What traits are carried on mobile genetic elements, and why?

Although similar to any other organism, prokaryotes can transfer genes vertically from mother cell to daughter cell, they can also exchange certain genes horizontally. Genes can move within and between genomes at fast rates because of mobile genetic elements (MGEs). Although mobile elements are fundamentally self-interested entities, and thus replicate for their own gain, they frequently carry genes beneficial for their hosts and/or the neighbours of their hosts. Many genes that are carried by mobile elements code for traits that are expressed outside of the cell. Such traits are involved in bacterial sociality, such as the production of public goods, which benefit a cell's neighbours, or the production of bacteriocins, which harm a cell's neighbours. In this study we review the patterns that are emerging in the types of genes carried by mobile elements, and discuss the evolutionary and ecological conditions under which mobile elements evolve to carry their peculiar mix of parasitic, beneficial and cooperative genes

Base of the Toarcian Stage of the Lower Jurassic defined by the Global Boundary Stratotype Section and Point (GSSP) at the Peniche section (Portugal)

This is the final version of the article. Available from the publisher via the DOI in this record.The Global Stratotype Section and Point (GSSP) for the base of Toarcian Stage, Lower Jurassic, is placed at the base of micritic limestone bed 15e at Ponta do Trovão (Peniche, Lusitanian Basin, Portugal; coordinates: 39°22'15''N, 9°23'07''W), 80km north of Lisbon, and coincides with the mass occurrence of the ammonite Dactylioceras (Eodactylites). The Pliensbachian/ Toarcian boundary (PLB/TOA) is contained in a continuous section forming over 450m of carbonate-rich sediments. Tectonics, syn-sedimentary disturbance, metamorphism or significant diagenesis do not significantly affect this area. At the PLB/TOA, no vertical facies changes, stratigraphical gaps or hiatuses have been recorded. The base of the Toarcian Stage is marked in the bed 15e by the first occurrence of D. (E.) simplex, co-occurring with D. (E.) pseudocommune and D. (E.) polymorphum. The ammonite association of D. (Eodactylites) ssp. and other species e.g. Protogrammoceras (Paltarpites) cf. paltum, Lioceratoides aff. ballinense and Tiltoniceras aff. capillatum is particularly significant for the boundary definition and correlation with sections in different basins. Ammonites of the PLB/ TOA are taxa characteristic of both the Mediterranean and Northwest European provinces that allow reliable, global correlations. The PLB/TOA is also characterized by other biostratigraphical markers (brachiopods, calcareous nannofossils, ostracods and benthic foraminifers) and by high-resolution stable carbon and oxygen isotopes, and 87Sr/86Sr ratios that show distinctive changes just above the PLB/TOA, thus providing additional, powerful tools for global correlations. The PBL-TOA lies at the end of a second (and third) order cycle of sea-level change, and the top of bed 15e is interpreted as a sequence boundary. Cyclostratigraphy analysis is available for the Lower Toarcian of Ponta do Trovão. Detailed correlations with the Almonacid de la Cuba section (Iberian Range, Spain) provide complementary data of the ammonite succession in the Northwest European Hawskerense and Paltum Subzones, and magnetostratigraphical data that allow supraregional correlations. The proposal was voted on by the Toarcian Working Group in June, 2012, and by the International Subcommission on Jurassic Stratigraphy in September, 2012, approved by the ICS in November, 2014, and ratified by the IUGS in December, 2014. With this Toarcian GSSP, all international stages of the Lower Jurassic have been officially defined.Several scientists have been members of the Toarcian Working Group. We would like to acknowledge all of them. We are also grateful to the ISJS and ICS members who have made valuable comments on a previous version of this manuscript. We warmly thank Marc Philippe for his help with the literature on Pliensbachian/Toarcian continental successions. We warmly thank Christian Meister and Jim Ogg for their helpful review. Constructive remarks by Jim Ogg on an early version of the paper were greatly appreciated. We also acknowledge the precious help of David Besson for providing the ammonite specimens from the Mouterde collection (Musée des Confluences, Lyon). Ammonite photographs were taken by Emmanuel Robert (Collections de Géologie de Lyon). This paper is dedicated to the memory of Abbé René Mouterde and Serge Elmi, who died in 2007 after having been for years the main supporters of the Peniche section as GSSP of Toarcian Stage. Calcareous nannofossil slides are curated at the Collections de Géologie de Lyon (No. FSL 766535-766617). This work has been supported by the BIOSCALES Project (POCTI/ 36438/PAL/2000), coordinated by the Universidade NOVA de Lisboa; R. B. Rocha thanks the support of A. F. Soares, J. C. Kullberg, P. S. Caetano and P. H. Verdial. Financial support was provided to L. V. Duarte, S. Pinto and M. C. Cabral by Projects PDCTE/CTA/44907/2002 and PTDC/CTE-GIX/098968/2008

Constructal blade shape in nanofluids

Blade configuration of nanofluids has been proven to perform much better than dispersed configuration for some heat conduction systems. The analytical analysis and numerical calculation are made for the cylinder--shaped and regular-rectangular-prism--shaped building blocks of the blade-configured heat conduction systems (using nanofluids as the heat conduction media) to find the optimal cross-sectional shape for the nanoparticle blade under the same composing materials, composition ratio, volumetric heat generation rate, and total building block volume. The regular-triangular-prism--shaped blade has been proven to perform better than all the other three kinds of blades, namely, the regular-rectangular-prism--shaped blade, the regular-hexagonal-prism--shaped blade, and the cylinder--shaped blade. Thus, the regular-triangular-prism--shaped blade is selected as the optimally shaped blade for the two kinds of building blocks that are considered in this study. It is also proven that the constructal cylinder--regular-triangular-prism building block performs better than the constructal regular-rectangular-prism--regular-triangular-prism building block

Cognitive impairment and magnetic resonance imaging correlates in primary progressive multiple sclerosis

Objectives: To characterize cognitive impairment in primary progressive multiple sclerosis (PPMS) and to correlate the pattern of cognitive deficits with brain magnetic resonance imaging (MRI) volumetric data. Materials and methods: In a multicenter cross-sectional study, we recruited consecutive patients with PPMS as well as age, sex, and education level-matched healthy controls (HC). All participants underwent neuropsychological (NP) assessment, and brain MRI was performed in patients with PPMS for analysis of lesion load, subcortical GM volumes, and regional cortical volumes. Results: We recruited 55 patients with PPMS and 36 HC. Thirty-six patients were included in the MRI analysis. Patients with PPMS performed significantly worse than HC in all NP tests. Subcortical GM volume was significantly correlated with all NP tests, except for Stroop Test, with the largest effect for the thalamus (r=−.516 [BVMT-R DR, P=.016 FDR-corrected] to r=.664 [SDMT, P<.001 FDR-corrected]). In the stepwise linear regression model, thalamic volume was the only predictor of performance in all NP tests. Conclusion: Cognitive impairment is common in PPMS and affects all evaluated cognitive domains. Subcortical GM volume, particularly of the thalamus, is a strong predictor of cognitive performance, suggesting it has a central role in the pathophysiology of PPMS-related cognitive dysfunction