Search results for "Cellular Types"
showing 10 items of 150 documents
Establishment of a pulmonary epithelial barrier on biodegradable poly-L-lactic-acid membranes
2019
Development of biocompatible and functional scaffolds for tissue engineering is a major challenge, especially for development of polarised epithelia that are critical structures in tissue homeostasis. Different in vitro models of the lung epithelial barrier have been characterized using non-degradable polyethylene terephthalate membranes which limits their uses for tissue engineering. Although poly-L-lactic acid (PLLA) membranes are biodegradable, those prepared via conventional Diffusion Induced Phase Separation (DIPS) lack open-porous geometry and show limited permeability compromising their use for epithelial barrier studies. Here we used PLLA membranes prepared via a modification of the…
TLR4 abrogates the Th1 immune response through IRF1 and IFN-β to prevent immunopathology during L. infantum infection
2020
A striking feature of human visceral leishmaniasis (VL) is chronic inflammation in the spleen and liver, and VL patients present increased production levels of multiple inflammatory mediators, which contribute to tissue damage and disease severity. Here, we combined an experimental model with the transcriptional profile of human VL to demonstrate that the TLR4-IFN-β pathway regulates the chronic inflammatory process and is associated with the asymptomatic form of the disease. Tlr4-deficient mice harbored fewer parasites in their spleen and liver than wild-type mice. TLR4 deficiency enhanced the Th1 immune response against the parasite, which was correlated with an increased activation of de…
Platelet function testing in pigs using the Multiplate® Analyzer.
2019
PLOS ONE 14(8), e0222010 (2019). doi:10.1371/journal.pone.0222010
CiliaCarta: An integrated and validated compendium of ciliary genes
2019
The cilium is an essential organelle at the surface of mammalian cells whose dysfunction causes a wide range of genetic diseases collectively called ciliopathies. The current rate at which new ciliopathy genes are identified suggests that many ciliary components remain undiscovered. We generated and rigorously analyzed genomic, proteomic, transcriptomic and evolutionary data and systematically integrated these using Bayesian statistics into a predictive score for ciliary function. This resulted in 285 candidate ciliary genes. We generated independent experimental evidence of ciliary associations for 24 out of 36 analyzed candidate proteins using multiple cell and animal model systems (mouse…
Pterostilbene-induced tumor cytotoxicity: a lysosomal membrane permeabilization-dependent mechanism.
2012
The phenolic phytoalexin resveratrol is well known for its health-promoting and anticancer properties. Its potential benefits are, however, limited due to its low bioavailability. Pterostilbene, a natural dimethoxylated analog of resveratrol, presents higher anticancer activity than resveratrol. The mechanisms by which this polyphenol acts against cancer cells are, however, unclear. Here, we show that pterostilbene effectively inhibits cancer cell growth and stimulates apoptosis and autophagosome accumulation in cancer cells of various origins. However, these mechanisms are not determinant in cell demise. Pterostilbene promotes cancer cell death via a mechanism involving lysosomal membrane …
The role of PNI to predict survival in advanced hepatocellular carcinoma treated with Sorafenib
2020
Background and aims The present study aims to investigate the role of the prognostic nutritional index (PNI) on survival in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. Methods This multicentric study included a training cohort of 194 HCC patients and three external validation cohorts of 129, 76 and 265 HCC patients treated with Sorafenib, respectively. The PNI was calculated as follows: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). Univariate and multivariate analyses were performed to investigate the association between the covariates and the overall survival (OS). Results A PNI cut-off value of 31.3 was established using the ROC an…
Large-scale analysis of SARS-CoV-2 spike-glycoprotein mutants demonstrates the need for continuous screening of virus isolates
2021
Due to the widespread of the COVID-19 pandemic, the SARS-CoV-2 genome is evolving in diverse human populations. Several studies already reported different strains and an increase in the mutation rate. Particularly, mutations in SARS-CoV-2 spike-glycoprotein are of great interest as it mediates infection in human and recently approved mRNA vaccines are designed to induce immune responses against it. We analyzed 1,036,030 SARS-CoV-2 genome assemblies and 30,806 NGS datasets from GISAID and European Nucleotide Archive (ENA) focusing on non-synonymous mutations in the spike protein. Only around 2.5% of the samples contained the wild-type spike protein with no variation from the reference. Among…
Evolutionary plasticity of SH3 domain binding by Nef proteins of the HIV-1/SIVcpz lentiviral lineage
2021
The accessory protein Nef of human and simian immunodeficiency viruses (HIV and SIV) is an important pathogenicity factor known to interact with cellular protein kinases and other signaling proteins. A canonical SH3 domain binding motif in Nef is required for most of these interactions. For example, HIV-1 Nef activates the tyrosine kinase Hck by tightly binding to its SH3 domain. An archetypal contact between a negatively charged SH3 residue and a highly conserved arginine in Nef (Arg77) plays a key role here. Combining structural analyses with functional assays, we here show that Nef proteins have also developed a distinct structural strategy—termed the "R-clamp”—that favors the formation …
Incidence of DAA failure and the clinical impact of retreatment in real-life patients treated in the advanced stage of liver disease: Interim evaluat…
2017
Background: Few data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure. Aim: To evaluate DAA failure incidence and the retreatment clinical impact in patients treated in the advanced liver disease stage. Methods: Data on HCV genotype, liver disease severity, and first and second line DAA regimens were prospectively collected in consecutive patients who reached the 12-week post-treatment and retreatment evaluations from January 2015 to December 2016 in 23 of the PITER network centers. Results: Among 3,830 patients with advanced fibrosis (F3) or cirrhosis, 139 (3.6%) failed to achieve SVR. Genotype 3, bilirubin lev…
Reservoir computing model of prefrontal cortex creates novel combinations of previous navigation sequences from hippocampal place-cell replay with sp…
2019
As rats learn to search for multiple sources of food or water in a complex environment, they generate increasingly efficient trajectories between reward sites. Such spatial navigation capacity involves the replay of hippocampal place-cells during awake states, generating small sequences of spatially related place-cell activity that we call “snippets”. These snippets occur primarily during sharp-wave-ripples (SWRs). Here we focus on the role of such replay events, as the animal is learning a traveling salesperson task (TSP) across multiple trials. We hypothesize that snippet replay generates synthetic data that can substantially expand and restructure the experience available and make learni…