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In addition to their hemostatic role, platelets play a significant role in immunity. Once activated, platelets release extracellular vesicles (EVs) formed by the budding of their cytoplasmic membranes. Because of their heterogeneity, platelet EVs (PEVs) are thought to perform diverse functions. It is unknown, however, whether the proteasome is transferred from platelets to PEVs or whether its function is retained. We hypothesized that functional protein processing and antigen presentation machinery are transferred to PEVs by activated platelets. Using molecular and functional assays, we found that the active 20S proteasome was enriched in PEVs, along with major histocompatibility complex class I (MHC-I) and lymphocyte costimulatory molecules (CD40L and OX40L). Proteasome-containing PEVs were identified in healthy donor blood, but did not increase in platelet concentrates that caused adverse transfusion reactions. They were augmented, however, after immune complex injections in mice. The complete biodistribution of murine PEVs after injection into mice revealed that they principally reached lymphoid organs, such as spleen and lymph nodes, in addition to the bone marrow, and to a lesser extent, liver and lungs. The PEV proteasome processed exogenous ovalbumin (OVA) and loaded its antigenic peptide onto MHC-I molecules, which promoted OVA-specific CD8+ T-lymphocyte proliferation. These results suggest that PEVs contribute to adaptive immunity through cross-presentation of antigens and have privileged access to immune cells through the lymphatic system, a tissue location that is inaccessible to platelets.

Tertiary lymphoid structures (TLS) accumulate at sites of chronic injury where they function as an ectopic germinal center, fostering local autoimmune responses. Vascular injury leads to the release of endothelial‐derived apoptotic exosome‐like vesicles (ApoExo) that contribute to rejection in transplanted organs. The purpose of the study was to evaluate the impact of ApoExo on TLS formation in a model of vascular allograft rejection. Mice transplanted with an allogeneic aortic transplant were injected with ApoExo. The formation of TLS was significantly increased by ApoExo injection along with vascular remodeling and increased levels of antinuclear antibodies and anti‐perlecan/LG3 autoantibodies. ApoExo also enhanced allograft infiltration by γδT17 cells. Recipients deficient in γδT cells showed reduced TLS formation and lower autoantibodies levels following ApoExo injection. ApoExo are characterized by proteasome activity, which can be blocked by bortezomib. Bortezomib treated ApoExo reduced the recruitment of γδT17 cells to the allograft, lowered TLS formation, and reduced autoantibody production. This study identifies vascular injury‐derived extracellular vesicles (ApoExo), as initiators of TLS formation and demonstrates the pivotal role of γδT17 in coordinating TLS formation and autoantibody production. Finally, our results suggest proteasome inhibition with bortezomib as a potential option for controlling TLS formation in rejected allografts. In this study, Dieudé et al identify vascular injury–derived extracellular vesicles as initiators of tertiary lymphoid structure formation and autoantibody production, demonstrate the pivotal role of γδT17 in coordinating formation of these structures, and suggest proteasome inhibition with bortezomib to control tertiary structure formation in rejected allografts.

Autoantibodies against perlecan/LG3 (anti‐LG3) have been associated with increased risks of delayed graft function, acute rejection, and reduced long‐term survival. High titers of anti‐LG3 antibodies have been found in de novo renal transplants recipients in the absence of allosensitizing or autoimmune conditions. Here, we seek to understand the pathways controlling anti‐LG3 production prior to transplantation. Mice immunized with recombinant LG3 produce concomitantly IgM and IgG anti‐LG3 antibodies suggesting a memory response. ELISpot confirmed the presence of LG3‐specific memory B cells in nonimmunized mice. Purification of B1 and B2 subtypes identified peritoneal B1 cells as the major source of memory B cells reactive to LG3. Although nonimmunized CD4‐deficient mice were found to express LG3‐specific memory B cells, depletion of CD4+T cells in wild type mice during immunization significantly decreased anti‐LG3 production. These results demonstrate that B cell memory to LG3 is T cell independent but that production of anti‐LG3 antibodies requires T cell help. Further supporting an important role for T cells in controlling anti‐LG3 levels, we found that human renal transplant recipients show a significant decrease in anti‐LG3 titers upon the initiation of CNI‐based immunosuppression. Collectively, these results identify T cell targeting interventions as a means of reducing anti‐LG3 levels in renal transplant patients. Perlecan/LG3‐specific memory B cells are present within the normal immune repertoire and require T cell help to initiate production of anti‐LG3 antibodies.

The consumption of poor-quality protein increases the risk of essential amino acid (EAA) deficiency, particularly for lysine and threonine. Thus, it is necessary to be able to detect easily EAA deficiency.

The fibre–fed echelle spectrograph of Observatoire de Haute–Provence, ELODIE, is presented. This instrument has been in operation since the end of 1993 on the 1.93 m telescope. ELODIE is designed as an updated version of the cross–correlation spectrometer CORAVEL, to perform very accurate radial velocity measurements such as needed in the search, by Doppler shift, for brown–dwarfs or giant planets orbiting around nearby stars. In one single exposure a spectrum at a resolution of 42000 ($\lambda/\Delta\lambda$) ranging from 3906 Å  to 6811 Å  is recorded on a 1024×1024 CCD. This performance is achieved by using a $\tan\theta=4$echelle grating and a combination of a prism and a grism as cross–disperser. An automatic on–line data treatment reduces all the ELODIE echelle spectra and computes cross–correlation functions. The instrument design and the data reduction algorithms are described in this paper. The efficiency and accuracy of the instrument and its long term instrumental stability allow us to measure radial velocities with an accuracy better than 15-1for stars up to 9th magnitude in less than 30 minutes exposure time. Observations of 16th magnitude stars are also possible to measure velocities at about 1-1accuracy. For classic spectroscopic studies ($S/N$>100) 9th magnitude stars can be observed in one hour exposure time.

Primates exhibit unusual quadrupedal features (e.g. diagonal gaits, compliant walk) compared with other quadrupedal mammals. Their origin and diversification in arboreal habitats have certainly shaped the mechanics of their walking pattern to meet the functional requirements necessary for balance control in unstable and discontinuous environments. In turn, the requirements for mechanical stability probably conflict with mechanical energy exchange. In order to investigate these aspects, we conducted an integrative study on quadrupedal walking in the olive baboon (Papio anubis) at the Primatology station of the CNRS in France. Based on kinematics, we describe the centre of mass mechanics of the normal quadrupedal gait performed on the ground, as well as in different gait and substrate contexts. In addition, we studied the muscular activity of six hindlimb muscles using non-invasive surface probes. Our results show that baboons can rely on an inverted pendulum-like exchange of energy (57% on average, with a maximal observed value of 84%) when walking slowly (<0.9 m s-1) with a tight limb phase (~55%) on the ground using diagonal sequence gaits. In this context, the muscular activity is similar to that of other quadrupedal mammals, thus reflecting the primary functions of the muscles for limb movement and support. In contrast, walking on a suspended branch generates kinematic and muscular adjustments to ensure better control and to maintain stability. Finally, walking using the lateral sequence gait increases muscular effort and reduces the potential for high recovery rates. The present exploratory study thus supports the assumption that primates are able to make use of an inverted pendulum mechanism on the ground using a diagonal walking gait, yet a different footfall pattern and substrate appear to influence muscular effort and efficiency.

In addition to their hemostatic role, platelets play a significant role in immunity. Once activated, platelets release extracellular vesicles (EVs) formed by budding of their cytoplasmic membranes. Because of their heterogeneity, platelet EVs (PEVs) are thought to perform diverse functions. It is unknown, however, whether the proteasome is transferred from platelets to PEVs or whether its function is retained.We hypothesized that functional protein processing and antigen presentation machinery is transferred to PEVs by activated platelets.Using molecular and functional assays, we showthat the active 20S proteasomeis enriched in PEVs along with MHC-I and lymphocyte costimulatory molecules (CD40L and OX40L). Proteasome-containing PEVs were identified in healthy donor blood, butdid not increase in platelet concentrates that caused adverse transfusion reactions. They were, however, augmented after immune complex injections in mice.The complete biodistribution ofmurine PEVs following injection into mice revealed that they could principally reach lymphoid organs such as spleen and lymph nodes, in addition to the bone marrow, and to a lesser extent liverand lungs. The PEV proteasome processed exogenous ovalbumin (OVA) and loaded its antigenic peptideonto MHC-I molecules which promotedOVA-specific CD8+T lymphocyte proliferation. These results suggest that PEVs contribute to adaptive immunity through cross-presentation of antigens and have privileged access to immune cells through the lymphatic system, a tissue location that is inaccessible to platelets.

Presents the poem "Les Corbeaux," by Arthur Rimbaud, translated from the French by John Kinsella.