Multiple Disguises for the Same Party: The Concepts of Morphogenesis and Phenotypic Variations in Cryptococcus neoformans†

Although morphological transitions (such as hyphae and pseudohyphae formation) are a common feature among fungi, the encapsulated pathogenic yeast Cryptococcus neoformans is found during infection as blastoconidia. However, this fungus exhibits striking variations in cellular structure and size, which have important consequences during infection. This review will summarize the main aspects related with phenotypic and morphological variations in C. neoformans, which can be divided in three classes. Two of them are related to changes in the capsule, while the third one involves changes in the whole cell. The three morphological and phenotypic variations in C. neoformans can be classified as: (1) changes in capsule structure, (2) changes in capsule size, and (3) changes in the total size of the cell, which can be achieved by the formation of cryptococcal giant/titan cells or microforms. These changes have profound consequences on the interaction with the host, involving survival, phagocytosis escape and immune evasion and dissemination. This article will summarize the main features of these changes, and highlight their importance during the interaction with the host and how they contribute to the development of the disease

Filosofía y filosofar en Platón

230 mm x 165 mm; 150 págQué es la filosofía? Qué es el filosofar? Encontrar las respuestas, en la obra de Platón, es la motivación del presente libro. Sin duda, puede pensarse que se trata de dos preguntas inocentes. Sin embargo, cuando se cuestiona no existe la inocencia. Preguntamos por el qué en el más puro sentido platónico. Con las misma intención y con iguales características. Le preguntamos directamente, tal como él lo hace al interrogar sobre sus actividades al rapsoda o al sofista. Debe entonces, para responder a esta exigencia, contestarnos el ateniense. El resultado de este diálogo lo ponemos ahora a disposición de los lectores para continuar efectuando la filosofía como diálogo.Facultad de Humanidades, Universidad Autónoma del Estado de Méxic

Coded Modulation for Satellite Broadcasting

In this paper, three-level block coded 8-PSK modulations, suitable for satellite broadcasting of digital TV signals, are presented. A design principle to achieve unequal error protection is introduced. The coding scheme is designed in such a way that the information bits carrying the basic definition TV signal have a lower error rate than the high definition information bits. The large error coefficients, formally associated with standard mapping by set partitioning, are reduced by considering a nonstandard partition of an 8-PSK signal set. The bits-to-signal mapping induced by this partition allows the use of suboptimal low-complexity soft-decision decoding of binary block codes. Parallel operation of the first and second stage decoders is possible, for high data rate transmission. Furthermore, there is no error propagation from the first-stage decoder to the second-stage decoder

Acceleration strategies for large-scale sequential simulations using parallel neighbour search: Non-LVA and LVA scenarios

This paper describes the application of acceleration techniques into existing implementations of Sequential Gaussian Simulation and Sequential Indicator Simulation. These implementations might incorporate Locally Varying Anisotropy (LVA) to capture non-linear features of the underlying physical phenomena. The imple- mentation focuses on a novel parallel neighbour search algorithm, which can be used on both non-LVA and LVA codes. Additionally, parallel shortest path executions and optimized linear algebra libraries are applied with focus on LVA codes. Execution time, speedup and accuracy results are presented. Non-LVA codes are benchmarked using two scenarios with approximately 50 million domain points each. Speedup results of 2× and 4× were obtained on SGS and SISIM respectively, where each scenario is compared against a baseline code published in Peredo et al. (2018). The aggregated contribution to speedup of both works results in 12× and 50× respectively. LVA codes are benchmarked using two scenarios with approximately 1.7 million domain points each. Speedup results of 56× and 1822× were obtained on SGS and SISIM respectively, where each scenario is compared against the original baseline sequential codes.The authors acknowledge the donated resources from project PID2019-107255GB of the Spanish Ministerio de Economía y Competitividad, and project 2017-SGR-1414 from the Generalitat de Catalunya, Spain.Peer ReviewedPostprint (published version

Visualization of Lipid Droplets in the Alveolar Macrophage Cell Line MH-S with Live-cell Imaging by 3D Holotomographic Microscopy (Nanolive)

Lipid droplets (LD), triglycerides and sterol esters among them, are well known for their capacity as lipid storage organelles. Recently, they have emerged as critical cytoplasmic structures involved in numerous biological functions. LD storage is generated de novo by the cell and provides an energy reserve, lipid precursors, and cell protection. Moreover, LD accumulation can be observed in some pathologies as obesity, atherosclerosis, or lung diseases. Fluorescence imaging techniques are the most widely used techniques to visualize cellular compartments in live cells, including LD. Nevertheless, presence of fluorophores can damage subcellular components and induce cytotoxicity, or even alter the dynamics of the organelles. As an alternative to fluorescence microscopy, label-free techniques such as stimulated Raman scattering and coherent anti-stokes Raman scattering microscopy offer a solution to avoid the undesirable effects caused by dyes and fluorescent proteins, but are expensive and complex. Here, we describe a label-free method using live-cell imaging by 3D holotomographic microscopy (Nanolive) to visualize LD accumulation in the MH-S alveolar macrophage cell line after treatment with oleic acid, a monounsaturated fatty acid that promotes lipid accumulation.We are grateful to Instituto de Salud Carlos III for financial support to S.H.(PI20CIII/00018). A. Pérez-Montero is supported by Comunidad de Madrid (PEJ-2020-AI/BMD-17651).S

A path-level exact parallelization strategy for sequential simulation

Sequential Simulation is a well known method in geostatistical modelling. Following the Bayesian approach for simulation of conditionally dependent random events, Sequential Indicator Simulation (SIS) method draws simulated values for K categories (categorical case) or classes defined by K different thresholds (continuous case). Similarly, Sequential Gaussian Simulation (SGS) method draws simulated values from a multivariate Gaussian field. In this work, a path-level approach to parallelize SIS and SGS methods is presented. A first stage of re-arrangement of the simulation path is performed, followed by a second stage of parallel simulation for non-conflicting nodes. A key advantage of the proposed parallelization method is to generate identical realizations as with the original non-parallelized methods. Case studies are presented using two sequential simulation codes from GSLIB: SISIM and SGSIM. Execution time and speedup results are shown for large-scale domains, with many categories and maximum kriging neighbours in each case, achieving high speedup results in the best scenarios using 16 threads of execution in a single machine.Peer ReviewedPostprint (author's final draft

Role of IL-17 in Morphogenesis and Dissemination of Cryptococcus neoformans during Murine Infection

Cryptococcus neoformans is a pathogenic yeast that can form Titan cells in the lungs, which are fungal cells of abnormally large size. The factors that regulate Titan cell formation in vivo are still unknown, although an increased proportion of these fungal cells of infected mice correlates with induction of Th2-type responses. Here, we focused on the role played by the cytokine IL-17 in the formation of cryptococcal Titan cells using Il17a-/- knockout mice. We found that after 9 days of infection, there was a lower proportion of Titan cells in Il17a-/- mice compared to the fungal cells found in wild-type animals. Dissemination to the brain occurred earlier in Il17a-/- mice, which correlated with the lower proportion of Titan cells in the lungs. Furthermore, knockout-infected mice increased brain size more than WT mice. We also determined the profile of cytokines accumulated in the brain, and we found significant differences between both mouse strains. We found that in Il17a-/-, there was a modest increase in the concentrations of the Th1 cytokine TNF-α. To validate if the increase in this cytokine had any role in cryptococcal morphogenesis, we injected wild-type mice with TNF-α t and observed that fungal cell size was significantly reduced in mice treated with this cytokine. Our results suggest a compensatory production of cytokines in Il17a-/- mice that influences both cryptococcal morphology and dissemination.This work was supported by Grant SAF2017-86912-R and PID 2020-114546RB-100 from the Spanish Ministry for Science and Innovation. Roselletti E. is funded by an international collaboration with the company Lesaffre International Sarl. Garcia-Rodas R. is funded by a “Juan de la Cierva” contract from the Spanish Ministry for Economics, Industry, and Competitivity (Reference: IJCI-2015-25683). Trevijano-Contador N. is funded by an “Ayudas de Atracción de Talento Investigador” contract of the Community of Madrid (Reference: 2019-T2/BMD-14926).S

Affinity of cefotiam for the alternative penicillin binding protein PBP3SAL used by Salmonella inside host eukaryotic cells

Background: Following the invasion of eukaryotic cells, Salmonella enterica serovar Typhimurium replaces PBP2/PBP3, main targets of β-lactam antibiotics, with PBP2SAL/PBP3SAL, two homologue peptidoglycan synthases absent in Escherichia coli. PBP3SAL promotes pathogen cell division in acidic environments independently of PBP3 and shows low affinity for β-lactams that bind to PBP3 such as aztreonam, cefepime, cefotaxime, ceftazidime, ceftriaxone, cefuroxime and cefalotin. Objectives: To find compounds with high affinity for PBP3SAL to control Salmonella intracellular infections. Methods: An S. Typhimurium ΔPBP3 mutant that divides using PBP3SAL and its parental wild-type strain, were exposed to a library of 1520 approved drugs in acidified (pH 4.6) nutrient-rich LB medium. Changes in optical density associated with cell filamentation, a read-out of blockage in cell division, were monitored. Compounds causing filamentation in the ΔPBP3 mutant but not in wild-type strain-the latter strain expressing both PBP3 and PBP3SAL in LB pH 4.6-were selected for further study. The bactericidal effect due to PBP3SAL inhibition was evaluated in vitro using a bacterial infection model of cultured fibroblasts. Results: The cephalosporin cefotiam exhibited higher affinity for PBP3SAL than for PBP3 in bacteria growing in acidified LB pH 4.6 medium. Cefotiam also proved to be effective against intracellular Salmonella in a PBP3SAL-dependent manner. Conversely, cefuroxime, which has higher affinity for PBP3, showed decreased effectiveness in killing intracellular Salmonella. Conclusions: Antibiotics with affinity for PBP3SAL, like the cephalosporin cefotiam, have therapeutic value for treating Salmonella intracellular infections.This work was supported by grants PDC2021-121094-I00/10.13039/501100011033 (to F.G-d.P.) from the Spanish Ministry of Science and Innovation and the Next Generation European Union EU/PRTR Program, and PID2020-114546RB (to O.Z.) from the Spanish Ministry of Science and Innovation.S