Computational modelling of epithelial cell monolayers during infection with Listeria monocytogenes

Intracellular bacterial infections alter the normal functionality of human host cells and tissues. Infection can also modify the mechanical properties of host cells, altering the mechanical equilibrium of tissues. In order to advance our understanding of host–pathogen interactions, simplified in vitro models are normally used. However, in vitro studies present certain limitations that can be alleviated by the use of computer-based models. As complementary tools these computational models, in conjunction with in vitro experiments, can enhance our understanding of the mechanisms of action underlying infection processes. In this work, we extend our previous computer-based model to simulate infection of epithelial cells with the intracellular bacterial pathogen Listeria monocytogenes. We found that forces generated by host cells play a regulatory role in the mechanobiological response to infection. After infection, in silico cells alter their mechanical properties in order to achieve a new mechanical equilibrium. The model pointed the key role of cell–cell and cell–extracellular matrix interactions in the mechanical competition of bacterial infection. The obtained results provide a more detailed description of cell and tissue responses to infection, and could help inform future studies focused on controlling bacterial dissemination and the outcome of infection processes. © 2022 The Author(s

Patients- and physicians- priorities for improvement: The case of rheumatic diseases

OBJECTIVES: To compare the health priorities elected by patients with rheumatic diseases and by their attending rheumatologists. PATIENTS AND METHODS: We undertook a cross-sectional study among patients and rheumatologists in Portuguese rheumatology outpatient clinics. 75% of all Portuguese Rheumatology Departments agreed to participate. Rheumatologists from non-participating hospital departments were asked to collaborate through their private practices. All patients were eligible for inclusion except if they were under 18 years of age or had a mental disorder that would affect their participation. Data were collected through dedicated questionnaires. Patients were asked to indicate 3 priorities for improvement out of 12 health domains (Arthritis Impact Measurement Scale 2) regarding their rheumatic disease. Rheumatologists were asked similar questions focused around rheumatoid arthritis (RA) and osteoarthritis (OA). RESULTS: 1,868 patients and 56 rheumatologists entered the study. The most commonly selected priorities by patients with rheumatic diseases were: "Rheumatic pain" (70%), "Walking and bending" (45%), and "Hand and Finger Function" (40%). The main priority for improvement among patients with RA was "Rheumatic Pain" (69%), while rheumatologists more commonly elected "Work" (55%) as their main priority for these patients. Among patients with OA, "Rheumatic Pain" was the first priority for both patients and doctors (elected by 75%, and 55% of respondents, respectively). CONCLUSIONS: Our study showed discordance between the priorities for improvement elected by patients and by their respective physicians. This was more pronounced in RA than in OA. Studying and addressing such differences may support physicians and institutions to better achieve the prime goal of incorporating and responding to patients' needs and preferences

Resolving galaxies in time and space: II: Uncertainties in the spectral synthesis of datacubes

In a companion paper we have presented many products derived from the application of the spectral synthesis code STARLIGHT to datacubes from the CALIFA survey, including 2D maps of stellar population properties and 1D averages in the temporal and spatial dimensions. Here we evaluate the uncertainties in these products. Uncertainties due to noise and spectral shape calibration errors and to the synthesis method are investigated by means of a suite of simulations based on 1638 CALIFA spectra for NGC 2916, with perturbations amplitudes gauged in terms of the expected errors. A separate study was conducted to assess uncertainties related to the choice of evolutionary synthesis models. We compare results obtained with the Bruzual & Charlot models, a preliminary update of them, and a combination of spectra derived from the Granada and MILES models. About 100k CALIFA spectra are used in this comparison. Noise and shape-related errors at the level expected for CALIFA propagate to 0.10-0.15 dex uncertainties in stellar masses, mean ages and metallicities. Uncertainties in A_V increase from 0.06 mag in the case of random noise to 0.16 mag for shape errors. Higher order products such as SFHs are more uncertain, but still relatively stable. Due to the large number statistics of datacubes, spatial averaging reduces uncertainties while preserving information on the history and structure of stellar populations. Radial profiles of global properties, as well as SFHs averaged over different regions are much more stable than for individual spaxels. Uncertainties related to the choice of base models are larger than those associated with data and method. Differences in mean age, mass and metallicity are ~ 0.15 to 0.25 dex, and 0.1 mag in A_V. Spectral residuals are ~ 1% on average, but with systematic features of up to 4%. The origin of these features is discussed. (Abridged)Comment: A&A, accepte

Statin pretreatment diminishes the levels of myocardial ischemia markers not only in CABG

A response to Ege E, Dereli Y, Kurban S, Sarigul A: Atorvastatin pretreatment diminishes the levels of myocardial ischemia markers early after CABG operation: an observational study. J Cardiothorac Surg 2010, 5:60

Star formation histories in mergers: the spatially resolved properties of the early-stage merger luminous infrared galaxies IC 1623 and NGC 6090

The role of major mergers in galaxy evolution is investigated through a detailed characterization of the stellar populations, ionized gas properties and star formation rates (SFR) in the early-stage merger luminous infrared galaxies (LIRGs) IC 1623 W and NGC 6090, by analysing optical integral field spectroscopy and high-resolution Hubble Space Telescope imaging. The spectra were processed with the starlight full spectral fitting code, and the emission lines measured in the residual spectra. The results are compared with non-interacting control spiral galaxies from the Calar Alto Legacy Integral Field Area survey. Merger-induced star formation is extended and recent, as revealed by the young ages (50–80 Myr) and high contributions to light of young stellar populations (50–90 per cent), in agreement with merger simulations in the literature. These early-stage mergers have positive central gradients of the stellar metallicity, with an average ∼0.6 Z⊙. Compared to non-interacting spirals, they have lower central nebular metallicity, and flatter profiles, in agreement with the gas inflow scenario. We find that they are dominated by star formation, although shock excitation cannot be discarded in some regions, where high velocity dispersion is found (170–200 km s−1). The average SFR in these early-stage mergers (∼23–32 M⊙ yr−1) is enhanced with respect to main-sequence Sbc galaxies by factors of 6–9, slightly above the predictions from classical merger simulations, but still possible in about 15 per cent of major galaxy mergers, where U/LIRGs belong

Viruses Previously Identified in Brazil as Belonging to HIV-1 CRF72_BF1 Represent Two Closely Related Circulating Recombinant Forms, One of Which, Designated CRF122_BF1, Is Also Circulating in Spain

Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Those derived from recombination between subtype B and subsubtype F1, with 18 reported, most of them of South American origin, are among the most diverse. In this study, we identified a HIV-1 BF1 recombinant cluster that is expanding in Spain, transmitted mainly via heterosexual contact, which, analyzed in near full-length genomes in four viruses, exhibited a coincident BF1 mosaic structure, with 12 breakpoints, that fully coincided with that of two viruses (10BR_MG003 and 10BR_MG005) from Brazil, previously classified as CRF72_BF1. The three remaining Brazilian viruses (10BR_MG002, 10BR_MG004, and 10BR_MG008) previously identified as CRF72_BF1 exhibited mosaic structures highly similar, but not identical, to that of the Spanish viruses and to 10BR_MG003 and 10BR_MG005, with discrepant subtypes in two short genome segments, located in pol and gp120env. Based on these results, we propose that the five viruses from Brazil previously identified as CRF72_BF1 actually belong to two closely related CRFs, one comprising 10BR_MG002, 10BR_MG004, and 10BR_MG008, which keep their CRF72_BF1 designation, and the other, designated CRF122_BF1, comprising 10BR_MG003, 10BR_MG005, and the viruses of the identified Spanish cluster. Three other BF1 recombinant genomes, two from Brazil and one from Italy, previously identified as unique recombinant forms, were classified as CRF72_BF1. CRF122_BF1, but not CRF72_BF1, was associated with protease L89M substitution, which was reported to contribute to antiretroviral drug resistance. Phylodynamic analyses estimate the emergence of CRF122_BF1 in Brazil around 1987. Given their close phylogenetic relationship and similar structures, the grouping of CRF72_BF1 and CRF122_BF1 in a CRF family is proposed.This work was funded through Acción Estratégica en Salud Intramural (AESI), Instituto de Salud Carlos III, projects “Estudios Sobre Vigilancia Epidemiológica Molecular del VIH-1 en España”, PI16CIII/00033, and “Epidemiología Molecular del VIH-1 en España y su Utilidad Para Investigaciones Biológicas y en Vacunas“, PI19CIII/00042, and through scientific agreement with Consellería de Sanidade, Government of Galicia (MVI 1004/16).S

Resolving galaxies in time and space: I: Applying STARLIGHT to CALIFA data cubes

Fossil record methods based on spectral synthesis techniques have matured over the past decade, and their application to integrated galaxy spectra fostered substantial advances on the understanding of galaxies and their evolution. Yet, because of the lack of spatial resolution, these studies are limited to a global view, providing no information about the internal physics of galaxies. Motivated by the CALIFA survey, which is gathering Integral Field Spectroscopy over the full optical extent of 600 galaxies, we have developed an end-to-end pipeline which: (i) partitions the observed data cube into Voronoi zones in order to, when necessary and taking due account of correlated errors, increase the S/N, (ii) extracts spectra, including propagated errors and bad-pixel flags, (iii) feeds the spectra into the STARLIGHT spectral synthesis code, (iv) packs the results for all galaxy zones into a single file, (v) performs a series of post-processing operations, including zone-to-pixel image reconstruction and unpacking the spectral and stellar population properties into multi-dimensional time, metallicity, and spatial coordinates. This paper provides an illustrated description of this whole pipeline and its products. Using data for the nearby spiral NGC 2916 as a show case, we go through each of the steps involved, presenting ways of visualizing and analyzing this manifold. These include 2D maps of properties such as the v-field, stellar extinction, mean ages and metallicities, mass surface densities, star formation rates on different time scales and normalized in different ways, 1D averages in the temporal and spatial dimensions, projections of the stellar light and mass growth (x,y,t) cubes onto radius-age diagrams, etc. The results illustrate the richness of the combination of IFS data with spectral synthesis, providing a glimpse of what is to come from CALIFA and future surveys. (Abridged)Comment: A&A, accepte

Tumour growth: An approach to calibrate parameters of a multiphase porous media model based on in vitro observations of Neuroblastoma spheroid growth in a hydrogel microenvironment

To unravel processes that lead to the growth of solid tumours, it is necessary to link knowledge of cancer biology with the physical properties of the tumour and its interaction with the surrounding microenvironment. Our understanding of the underlying mechanisms is however still imprecise. We therefore developed computational physics-based models, which incorporate the interaction of the tumour with its surroundings based on the theory of porous media. However, the experimental validation of such models represents a challenge to its clinical use as a prognostic tool. This study combines a physics-based model with in vitro experiments based on microfluidic devices used to mimic a three-dimensional tumour microenvironment. By conducting a global sensitivity analysis, we identify the most influential input parameters and infer their posterior distribution based on Bayesian calibration. The resulting probability density is in agreement with the scattering of the experimental data and thus validates the proposed workflow. This study demonstrates the huge challenges associated with determining precise parameters with usually only limited data for such complex processes and models, but also demonstrates in general how to indirectly characterise the mechanical properties of neuroblastoma spheroids that cannot feasibly be measured experimentally