Stress-Induced Sphingolipid Signaling: Role of Type-2 Neutral Sphingomyelinase in Murine Cell Apoptosis and Proliferation

International audienceBACKGROUND: Sphingomyelin hydrolysis in response to stress-inducing agents, and subsequent ceramide generation, are implicated in various cellular responses, including apoptosis, inflammation and proliferation, depending on the nature of the different acidic or neutral sphingomyelinases. This study was carried out to investigate whether the neutral Mg(2+)-dependent neutral sphingomyelinase-2 (nSMase2) plays a role in the cellular signaling evoked by TNFalpha and oxidized LDLs, two stress-inducing agents, which are mitogenic at low concentrations and proapoptotic at higher concentrations. METHODOLOGY AND PRINCIPAL FINDINGS: For this purpose, we used nSMase2-deficient cells from homozygous fro/fro (fragilitas ossium) mice and nSMase2-deficient cells reconstituted with a V5-tagged nSMase2. We report that the genetic defect of nSMase2 (in fibroblasts from fro/fro mice) does not alter the TNFalpha and oxidized LDLs-mediated apoptotic response. Likewise, the hepatic toxicity of TNFalpha is similar in wild type and fro mice, thus is independent of nSMase2 activation. In contrast, the mitogenic response elicited by low concentrations of TNFalpha and oxidized LDLs (but not fetal calf serum) requires nSMase2 activation. CONCLUSION AND SIGNIFICANCE: nSMase2 activation is not involved in apoptosis mediated by TNFalpha and oxidized LDLs in murine fibroblasts, and in the hepatotoxicity of TNFalpha in mice, but is required for the mitogenic response to stress-inducing agents

COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms.

Funder: Bundesministerium für Bildung und ForschungFunder: Bundesministerium für Bildung und Forschung (BMBF)We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective

Tunable graded cavity resonator integrated grating filters

International audienceWe demonstrated Graded Cavity Resonator Integrated Grating Filters (G-CRIGFs) that are narrowband spectral reflectors, spectrally tunable over more than 40 nm around 850 nm using a spatial gradient. A simple analytical model is introduced and validated experimentally to determine spectral performance of G-CRIGFs from the spectral properties of a standard Cavity Resonator Integrated Grating Filter (CRIGF)

Cavity Resonator Integrated Grating Filters fabricated by soft-mold nanoimprint lithography

International audienceCavity Resonator Integrated Filers are a novel generation of free space filters that rely on efficient coupling of a free space beam to a localized mode. We introduce the physical principles underlying their optical properties, and show that soft mold nanoimprint lithography is particularly adapted for their fabrication. We experimentally demonstrate high efficiency (50%) narrow band (300 pm) filters at 850 nm wavelength

Laser diode stabilisation and tuning using Cavity Resonator Integrated Guided-mode resonance Filters

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Graded CRIGF filters for tunable external cavity lasers

International audienceGraded CRIGF filters were fabricated and characterized. When inserted in a three elements cat’s eyes laser diode external cavity, they allow continuous tuning of the emission wavelength over 20 nm in the 850 nm range

Nanoimprint lithography as a new tool for cavity-resonator-integrated guided-mode resonance fabrication

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Tunable external-cavity lasers with graded CRIGF filters

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CRIGF as external cavity mirror for laser stabilisation

International audienceCavity Resonantor Integrated Grating Filters are anew generation of optical filters deriving fromguided mode resonant filters. We demonstrateexternal cavity lasers using such filters as outputcouplers and show that tunable graded filters canbe fabricated and successfully exploited to createtunable external cavity lasers

Vestibular Schwann cells are a distinct subpopulation of peripheral glia with specific sensitivity to growth factors and extracellular matrix components

International audienceVestibular nerve Schwann cells are predisposed to develop schwannoma. While knowledge concerning this condition has greatly improved, little is known about properties of normal vestibular Schwann cells. In an attempt to understand this predisposition, we evaluated cell density regulation and proliferative features of these cells taken from 6-day-old rats. Data were compared to those obtained with sciatic Schwann cells. In both vestibular and sciatic 7-day-old cultures, Schwann cells appear as bipolar or flattened cells. However , sciatic and vestibular cells greatly differ in other aspects: on poly-L-lysine coating, sciatic cells specifically synthesize myelin basic protein, while expression of P0 mRNAs is restricted to some vestibular cells. Laminin increases sciatic cell density but not that of vestibular cells. Fibronectin selectively enhances the proliferation of vestibular Schwann cells and lacks an effect on sciatic ones. Comparison of cell density changes between sciatic and vestibular cells shows that they are sensitive to two different sets of growth factors. Progesterone and FGF-2 combined with forskolin selectively enhance the cell density of sciatic glia, while IGF-1 and GDNF specifically increase vestibular cell density. Furthermore, BrdU incorporation assays indicate that GDNF is also a mitogen for vestibular cells. Altogether, vestibular Schwann cells display phenotypic features and responsiveness to exog-enous signals that are significantly different from sciatic Schwann cells, suggesting that vestibular glia form a subpopulation of Schwann cells