Croup and COVID‐19

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A toggle-switch and a feed-forward loop engage in the control of the Drosophila retinal determination gene network

Dipterans show a striking range of eye sizes, shapes, and functional specializations. Their eye is of the compound type, the most frequent eye architecture in nature. The development of this compound eye has been most studied in Drosophila melanogaster. The early development of the Drosophila eye is under the control of a gene regulatory network of transcription factors and signaling molecules called the retinal determination gene network (RDGN). Nodes in this network have been found to be involved not only in the development of different eye types in invertebrates and vertebrates, but also of other organs. Here we have analyzed the network properties in detail. First, we have generated quantitative expression profiles for a number of the key RDGN transcription factors, at a single-cell resolution. With these profiles, and applying a correlation analysis, we revisited several of the links in the RDGN. Our study uncovers a new link, that we confirm experimentally, between the transcription factors Hth/Meis1 and Optix/Six3 and indicates that, at least during the period of eye differentiation, positive feedback regulation from Eya and Dac on the Pax6 gene Ey is not operating. From this revised RDGN we derive a simplified gene network that we model mathematically. This network integrates three basic motifs: a coherent feedforward loop, a toggle-switch and a positive autoregulation which, together with the input from the Dpp/BMP2 signaling molecule, recapitulate the gene expression profiles obtained experimentally, while ensuring a robust transition from progenitor cells into retinal precursors.This work was funded by MINECO and the Agencia Estatal de Investigacion (AEI) of Spain, co-financed by FEDER funds (EU) through grants BFU2012-34324 and BFU2015-66040-P to FC, MDM-2016-0687 in which FC is participant researcher, and TIN2017-89842 P in which MCL is participant researcher

Biological and immunological characterization of recombinant Yellow Fever 17D Viruses expressing a Trypanosoma cruzi Amastigote Surface Protein-2 CD8+ T cell epitope at two distinct regions of the genome

<p>Abstract</p> <p>Background</p> <p>The attenuated Yellow fever (YF) 17D vaccine virus is one of the safest and most effective viral vaccines administered to humans, in which it elicits a polyvalent immune response. Herein, we used the YF 17D backbone to express a <it>Trypanosoma cruzi </it>CD8⁺T cell epitope from the Amastigote Surface Protein 2 (ASP-2) to provide further evidence for the potential of this virus to express foreign epitopes. The TEWETGQI CD8⁺T cell epitope was cloned and expressed based on two different genomic insertion sites: in the <it>fg </it>loop of the viral Envelope protein and the protease cleavage site between the NS2B and NS3. We investigated whether the site of expression had any influence on immunogenicity of this model epitope.</p> <p>Results</p> <p>Recombinant viruses replicated similarly to vaccine virus YF 17D in cell culture and remained genetically stable after several serial passages in Vero cells. Immunogenicity studies revealed that both recombinant viruses elicited neutralizing antibodies to the YF virus as well as generated an antigen-specific gamma interferon mediated T-cell response in immunized mice. The recombinant viruses displayed a more attenuated phenotype than the YF 17DD vaccine counterpart in mice. Vaccination of a mouse lineage highly susceptible to infection by <it>T. cruzi </it>with a homologous prime-boost regimen of recombinant YF viruses elicited TEWETGQI specific CD8⁺T cells which might be correlated with a delay in mouse mortality after a challenge with a lethal dose of <it>T. cruzi</it>.</p> <p>Conclusions</p> <p>We conclude that the YF 17D platform is useful to express <it>T. cruzi </it>(Protozoan) antigens at different functional regions of its genome with minimal reduction of vector fitness. In addition, the model <it>T. cruzi </it>epitope expressed at different regions of the YF 17D genome elicited a similar T cell-based immune response, suggesting that both expression sites are useful. However, the epitope as such is not protective and it remains to be seen whether expression of larger domains of ASP-2, which include the TEWETGQI epitope, will elicit better T-CD8+ responses to the latter. It is likely that additional antigens and recombinant virus formulations will be necessary to generate a protective response.</p

Stroke-based splatting: an efficient multi-resolution point cloud visualization technique

Current state-of-the-art point cloud visualization techniques have shortcomings when dealing with sparse and less accurate data or close-up interactions. In this paper, we present a visualization technique called stroke-based splatting, which applies concepts of stroke-based rendering to surface-aligned splatting, allowing for better shape perception at lower resolutions and close-ups. We create a painterly depiction of the data with an impressionistic aesthetic, which is a metaphor the user is culturally trained to recognize, thus attributing higher quality to the visualization. This is achieved by shaping each object-aligned splat as a brush stroke, and orienting it according to globally coherent tangent vectors from the Householder formula, creating a painterly depiction of the scanned cloud. Each splat is sized according to a color-based clustering analysis of the data, ensuring the consistency of brush strokes within neighborhood areas. By controlling brush shape generation parameters and blending factors between neighboring splats, the user is able to simulate different painting styles in real time. We have tested our method with data sets captured by commodity laser scanners as well as publicly available high-resolution point clouds, both having highly interactive frame rates in all cases. In addition, a user study was conducted comparing our approach to state-of-the-art point cloud visualization techniques. Users considered stroke-based splatting a valuable technique as it provides a higher or similar visual quality to current approaches

Gene by environment QTL mapping through multiple trait analyses in blood pressure salt-sensitivity: identification of a novel QTL in rat chromosome 5

BACKGROUND: The genetic mechanisms underlying interindividual blood pressure variation reflect the complex interplay of both genetic and environmental variables. The current standard statistical methods for detecting genes involved in the regulation mechanisms of complex traits are based on univariate analysis. Few studies have focused on the search for and understanding of quantitative trait loci responsible for gene × environmental interactions or multiple trait analysis. Composite interval mapping has been extended to multiple traits and may be an interesting approach to such a problem. METHODS: We used multiple-trait analysis for quantitative trait locus mapping of loci having different effects on systolic blood pressure with NaCl exposure. Animals studied were 188 rats, the progenies of an F2 rat intercross between the hypertensive and normotensive strain, genotyped in 179 polymorphic markers across the rat genome. To accommodate the correlational structure from measurements taken in the same animals, we applied univariate and multivariate strategies for analyzing the data. RESULTS: We detected a new quantitative train locus on a region close to marker R589 in chromosome 5 of the rat genome, not previously identified through serial analysis of individual traits. In addition, we were able to justify analytically the parametric restrictions in terms of regression coefficients responsible for the gain in precision with the adopted analytical approach. CONCLUSION: Future work should focus on fine mapping and the identification of the causative variant responsible for this quantitative trait locus signal. The multivariable strategy might be valuable in the study of genetic determinants of interindividual variation of antihypertensive drug effectiveness

Effects of the functional HOTAIR rs920778 and rs12826786 genetic variants in glioma susceptibility and patient prognosis

Abnormal expression of the long non-coding RNA HOX transcript antisense intergenic RNA (HOTAIR) is oncogenic in several human cancers, including gliomas. The HOTAIR single nucleotide polymorphisms (SNPs) rs920778 (C > T) and rs12826786 (C > T) present in the intronic enhancer and promoter regions of HOTAIR, respectively, are associated with expression, cancer susceptibility, and patient prognosis in some tumor types. However, the relevance of these HOTAIR SNPs has not been studied in glioma. Here, we report a case-control study comprising 177 Portuguese glioma patients and 199 cancer-free controls. All subjects were genotyped by PCR and restriction fragment length polymorphism (RFLP). No statistically significant differences were found in the genotype or allele distributions of either rs920778 or rs12826786 between glioma patients and controls, suggesting these SNPs are not associated with glioma risk. No significant associations were found between rs920778 variants and HOTAIR expression levels, while rs12826786 CT genotype was associated with increased intratumoral HOTAIR RNA levels when compared to TT genotype (p-value = 0.04). Univariate (Log-rank) and multivariate (Cox proportional) analyses showed both rs920778 CT and rs12826786 CT genotypes were significantly associated with longer overall survival of WHO grade III anaplastic oligodendroglioma patients. Our results suggest that HOTAIR SNPs rs920778 and rs12826786 do not play a significant role in glioma susceptibility, but may be important prognostic factors in anaplastic oligodendroglioma patients. Future studies are warranted to validate and expand these findings, and to further dissect the importance of these SNPs in glioma.info:eu-repo/semantics/publishedVersio