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Lyon, France

Michallet M.C.,University of Lyon
Current opinion in microbiology | Year: 2013

Pattern recognition receptors (PRRs) are commonly known as sensor proteins crucial for the early detection of microbial or host-derived stress signals by innate immune cells. Interestingly, some PRRs are also expressed and functional in cells of the adaptive immune system. These receptors provide lymphocytes with innate sensing abilities; for example, B cells express Toll-like receptors, which are important for the humoral response. Strikingly, certain other NOD-like receptors are not only highly expressed in adaptive immune cells, but also exert functions related specifically to adaptive immune system pathways, such as regulating antigen presentation. In this review, we will focus particularly on the current understanding of PRR functions intrinsic to B and T lymphocytes; a developing aspect of PRR biology. Copyright © 2013 Elsevier Ltd. All rights reserved. Source

Buchert T.,University of Lyon
Classical and Quantum Gravity | Year: 2011

We outline the key steps toward the construction of a physical, fully relativistic cosmology. The influence of inhomogeneities on the effective evolution history of the Universe is encoded in backreaction terms and expressed through spatially averaged geometrical invariants. These are absent and potential candidates for the missing dark sources in the standard model. Since they can be interpreted as energies of an emerging scalar field (the morphon), we are in a position to propose a strategy of how phenomenological scalar field models for dark energy, dark matter and inflation, that are usually added as fundamental sources to a homogeneous-geometry (FLRW) cosmology, can be potentially traced back to the inhomogeneous geometrical properties of space and its embedding into spacetime. We lay down a line of arguments that is - thus far only qualitatively - conclusive, and we address open problems of quantitative nature, related to the interpretation of observations. We discuss within a covariant framework (i) the foliation problem and invariant definitions of backreaction effects; (ii) the background problem and the notion of an effective cosmology; (iii) generalizations of the cosmological principle and generalizations of the cosmological equations; (iv) dark energies as energies of an effective scalar field; (v) the global gravitational instability of the standard model and basins of attraction for effective states; (vi) multiscale cosmological models and volume acceleration; (vii) effective metrics and strategies for effective distance measurements on the light cone, including observational predictions; (viii) examples of non-perturbative models, including explicit backreaction models for the LTB solution, extrapolations of the relativistic Lagrangian perturbation theory and scalar metric inhomogeneities. The role of scalar metric perturbations is critically examined and embedded into the non-perturbative framework. © 2011 IOP Publishing Ltd. Source

Ricard-Blum S.,University of Lyon
Cold Spring Harbor perspectives in biology | Year: 2011

Collagens are the most abundant proteins in mammals. The collagen family comprises 28 members that contain at least one triple-helical domain. Collagens are deposited in the extracellular matrix where most of them form supramolecular assemblies. Four collagens are type II membrane proteins that also exist in a soluble form released from the cell surface by shedding. Collagens play structural roles and contribute to mechanical properties, organization, and shape of tissues. They interact with cells via several receptor families and regulate their proliferation, migration, and differentiation. Some collagens have a restricted tissue distribution and hence specific biological functions. Source

Bachelard-Cascales E.,University of Lyon
Stem cells (Dayton, Ohio) | Year: 2010

The major components of the mammary ductal tree are an inner layer of luminal cells, an outer layer of myoepithelial cells, and a basement membrane that separates the ducts from the underlying stroma. Cells in the outer layer express CD10, a zinc-dependent metalloprotease that regulates the growth of the ductal tree during mammary gland development. To define the steps in the human mammary lineage at which CD10 acts, we have developed an in vitro assay for human mammary lineage progression. We show that sorting for CD10 and EpCAM cleanly separates progenitors from differentiated luminal cells and that the CD10-high EpCAM-low population is enriched for early common progenitor and mammosphere-forming cells. We also show that sorting for CD10 enriches sphere-forming cells from other tissue types, suggesting that it may provide a simple tool to identify stem or progenitor populations in tissues for which lineage studies are not currently possible. We demonstrate that the protease activity of CD10 and the adhesion function of beta1-integrin are required to prevent differentiation of mammary progenitors. Taken together, our data suggest that integrin-mediated contact with the basement membrane and cleavage of signaling factors by CD10 are key elements in the niche that maintains the progenitor and stem cell pools in the mammary lineage. Source

Salles G.A.,University of Lyon
Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2013

The phase II part of the phase I/II GAUGUIN study evaluated the efficacy and safety of two different doses of obinutuzumab (GA101), a type II, glycoengineered, humanized anti-CD20 monoclonal antibody, in patients with relapsed/refractory indolent non-Hodgkin lymphoma. Patients were randomly assigned to receive eight cycles of obinutuzumab (GA101) as a flat dose of 400 mg on days 1 and 8 of cycle 1 and also on day 1 of cycles 2 to 8 (400/400 mg) or 1,600 mg on days 1 and 8 of cycle 1 and 800 mg on day 1 of cycles 2 to 8 (1,600/800 mg). Forty patients were enrolled, including 34 with follicular lymphoma; 38 of 40 patients had previously received rituximab and 22 of 40 were rituximab refractory. The overall response rate at the end of treatment was 55% (95% CI, 32% to 76%) in the 1,600/800-mg group (9% complete responders) and 17% (95% CI, 4% to 41%) in the 400/400-mg group (no complete responders). Five of 10 rituximab-refractory patients had an end-of-treatment response in the 1,600/800-mg group versus one of 12 in the 400/400-mg group. Median progression-free survival was 11.9 months in the 1,600/800-mg group (range, 1.8 to 33.9+ months) and 6.0 months in the 400/400-mg group (range, 1.0 to 33.9+ months). The most common adverse events were infusion-related reactions (IRRs) seen in 73% of patients, but only two patients had grade 3 to 4 IRRs (both in the 1,600/800-mg group). No IRRs were considered serious, and no patients withdrew for IRRs. The 1,600/800-mg dose schedule of obinutuzumab (GA101) has encouraging activity with an acceptable safety profile in relapsed/refractory indolent non-Hodgkin lymphoma. Source

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