The Journey of SCAPs (Stem Cells from Apical Papilla), from Their Native Tissue to Grafting: Impact of Oxygen Concentration

Tissue engineering strategies aim at characterizing and at optimizing the cellular component that is combined with biomaterials, for improved tissue regeneration. Here, we present the immunoMap of apical papilla, the native tissue from which SCAPs are derived. We characterized stem cell niches that correspond to a minority population of cells expressing Mesenchymal stromal/Stem Cell (CD90, CD105, CD146) and stemness (SSEA4 and CD49f) markers as well as endothelial cell markers (VWF, CD31). Based on the colocalization of TKS5 and cortactin markers, we detected migration-associated organelles, podosomes-like structures, in specific regions and, for the first time, in association with stem cell niches in normal tissue. From six healthy teenager volunteers, each with two teeth, we derived twelve cell banks, isolated and amplified under 21 or 3% O2. We confirmed a proliferative advantage of all banks when cultured under 3% versus 21% O2. Interestingly, telomerase activity was similar to that of the highly proliferative hiPSC cell line, but unrelated to O2 concentration. Finally, SCAPs embedded in a thixotropic hydrogel and implanted subcutaneously in immunodeficient mice were protected from cell death with a slightly greater advantage for cells preconditioned at 3% O2

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

Scalability upper limit estimation of silicon microring based configurable optical switches

International audienceScalability of a Silicon Micro-Ring switch in a Benes architecture is investigated, modelling waveguide non linearity using experimental data and intra/inter-channel crosstalk. The benefits of double ring configuration is demonstrated both regarding stability and scalability. © 2019 The Author(s

Scalability upper limit estimation of silicon microring based configurable optical switches

International audienceScalability of a Silicon Micro-Ring switch in a Benes architecture is investigated, modelling waveguide non linearity using experimental data and intra/inter-channel crosstalk. The benefits of double ring configuration is demonstrated both regarding stability and scalability. © 2019 The Author(s

Co-integration of TSV mid process and optical devices for Silicon photonics interposers

International audienceIn the framework of High Performance Computing and Datacom, silicon photonics interposers propose an interesting approach, while providing new challenges. This paper demonstrates such an integration and focuses on TSV Mid integration impact on sensitive photonic structures such as ring modulators, focusing on two specific technological aspects: substrate thinning and TSV integration. It is shown that thinning down to 100 microns and integrating TSV do not impact photonic performances more than wafer level process variability. Finally, thanks to these results, 3D Si photonics design opportunities will be discussed

Proteomic analysis of three Borrelia burgdorferi sensu lato native species and disseminating clones

Lyme borreliosis is the most important vector-borne disease in the Northern hemisphere. It is caused by Borrelia burgdorferi sensu lato bacteria transmitted to humans by the bite of hard ticks, Ixodes spp. Although antibiotic treatments are efficient in the early stage of the infection, a significant number of patients develop disseminated manifestations (articular, neurological and cutaneous) due to unnoticed or absence of erythema migrans, or to inappropriate treatment. Vaccine could be an efficient approach to decrease Lyme disease incidence. We have developed a proteomic approach based on a Ge-LC-MS/MS strategy to identify new vaccine candidates. We analyzed a disseminating clone and the associated wild type strain for each major pathogenic Borrelia species: B. burgdorferi sensu stricto, B. garinii and B. afzelii. We identified specific proteins and common proteins to the disseminating clones of the three main species. In parallel, we used a spectral counting strategy to identify up-regulated proteins common to the clones. Finally, 40 proteins were found that could potentially be involved in bacterial virulence and of interest in the development of a new vaccine. We selected the three proteins specifically detected in the disseminating clones of the three Borrelia species and checked by RT-PCR whether they are expressed in mouse skin upon B. burgdorferi ss inoculation. Interestingly, BB0566 appears as a potential vaccine candidate. This article is protected by copyright. All rights reserved

Spatiotemporally distinct responses to mechanical forces shape the developing seed of Arabidopsis

International audienceOrgan morphogenesis depends on mechanical interactions between cells and tissues. These interactions generate forces that can be sensed by cells and affect key cellular processes. However, how mechanical forces contribute, together with biochemical signals, to the shaping of complex organs is still unclear. We address this question using the seed of Arabidopsis as a model system. We show that seeds first experience a phase of high anisotropic growth that is dependent on the response of cortical microtubule (CMT) to forces, which guide cellulose deposition according to shape-driven stresses in the outermost layer of the seed coat. However, at later stages of development, we show that seed growth is isotropic and depend on the properties of an inner layer of the seed coat that stiffens its walls in response to tension but has isotropic material properties. Finally, we show that the transition from anisotropic to isotropic growth is due to dampening of CMT responses to shape-driven stresses. Altogether, our work supports that spatiotemporally distinct mechanical responses control the shape of developing seeds in Arabidopsis

Dissociating effect of salivary gland extract from Ixodes ricinus on human fibroblasts: Potential impact on Borrelia transmission

International audienceUnderstanding the mechanism of pathogen transmission is essential for the development of strategies to reduce arthropod-borne diseases. The pharmaco- and immunomodulatory properties of insect and acarine saliva play an essential role in the efficiency of pathogen transmission. The skin as the site where arthropod saliva and pathogens are inoculated - represents the key interface in vector-borne diseases. We identified tick molecules potentially involved in pathogen transmission, using micro-HPLC and mass spectrometry, followed by in vitro assays on human skin cells. Histone H4 isolated from Ixodes ricinus salivary gland extract was identified as a molecule with a dissociating effect on human primary fibroblasts. This histone might be involved in the formation of the feeding pool formed around the tick mouthparts and responsible of tissue necrosis in the vertebrate host. Thanks to its selective antimicrobial activity, it may also sterilize the feeding pool and facilitate transmission of pathogens such as Borrelia burgdorferi sensu lato