B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction.

Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6C(hi) monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell-selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction.This work was supported by Inserm, British Heart Foundation (Z.M.), European Research Council (Z.M.), Fondation Coeur et Recherche (Z.M., T.S., N.D.), Fondation pour la Recherche Medicale (J.S.S.), European Union Seven Framework programme TOLERAGE (Z.M.), Fondation Leducq transatlantic network (C.J.B., D.T., A.T., J.S.S., Z.M.), National Institutes of Health grants AI56363 and AI057157, and a grant from The Lymphoma Research Foundation (T.F.T).This is the author accepted manuscript. The final version is available from Nature Publishing Group at http://dx.doi.org/10.1038/nm.3284

In situ evolution of Ni environment in magnesium aluminosilicate glasses and glass–ceramics–Influence of ZrO2 and TiO2 nucleating agents

International audienceThe evolutionofNi2þ environmenthasbeensystematicallyinvestigatedusingopticaland in situ X-rayabsorption spectroscopy(XAS)todeterminetheinfluence ofnucleatingagents(TiO2 and/or ZrO2) duringthe formationofspinelinmagnesiumaluminosilicateglass–ceramics.Theresultswerecomplementedby in situ X-raydiffractiondata.AccordingtoXASandopticalspectroscopy,thenatureofnucleatingagents doesnotmodifysignificantly theNienvironmentininitialglasses.However,ithasarelativelystrong influence intheobservedcrystallizationsequence.Ni2þ ions donotentertheZr-containingcrystalline phaseofZrO2 or ZrTiO4 but aNi2þ coordinationchangefromthe fivefold coordinatedsites,with asmallamountoftetrahedralsitesinparentglasses,to [6]Ni2þ and [4]Ni2þ sites inspinel(inglassesnucleated byZrO2 and/or TiO2) orin β-quartzsolidsolutions(inglassesnucleatedbyZrO2) hasbeenfound

Bromine speciation in hydrous silicate melts at high pressure

International audienceBr speciation in hydrous silicate melts at high pressure has been investigated up to 7.6 GPa using X-ray Absorption Spectroscopy (XAS) at the Br K-edge in a Paris-Edinburgh press. Br in silicate melts is surrounded by an average of 6 Na cations, a number slightly increasing with pressure (5.8 to 6.6), with a Br-Na distance increasing from 3.49 to 3.72 Å. Two oxygens, either from a water, an –OH molecule or from the tetrahedral silicate network, with an average Br-O distance of 1.80 Å, form the closest coordination shell around Br ions. The persistence of an alkali shell around Br, in a structure similar to crystalline NaBr, throughout the pressure range investigated shows that Br can be retained in the melt structure at relatively high pressure and supports the idea of its deep recycling. Finally, our results confirm that Br could be efficiently degassed with water at low pressures and that Br may also have been efficiently degassed along with water during the early stages of an oxidized magma ocean

In situ characterization of liquid network structures at high pressure and temperature using X-ray absorption spectroscopy coupled with the Paris-Edinburgh press

International audienceWe review recent progress in studying structural properties of liquids using X-ray absorption spectroscopy coupled with the Paris-Edinburgh press at third-generation synchrotron facilities. This experimental method allows for detecting subtle changes in atomic arrangements of melts over a wide pressure-temperature range. It has been also employed to monitor variations of the local coordination environment of diluted species contained in glasses, liquids and crystalline phases as a function of the pressure and temperature. Such information is of great importance for gaining deeper insights into the physico-chemical properties of liquids at extreme condition, including the understanding of such phenomena as liquid-liquid phase transitions, viscosity drops and various transport properties of geological melts. Here, we describe the experimental approach and discuss its potential in structural characterization on selected scientific highlights. Finally, the current ongoing instrumental developments and future scientific opportunities are discussed

D026 Catecholamines regulate vascular progenitor cells mobilization from bone marrow

Endogenous catecholamine stimulation of adrenergic receptors contributes to artery growth and remodeling in pathological and adaptive physiological settings. Recently, it has been shown that enforced stem/progenitor cells egress from bone marrow (BM) niches depends critically on the nervous system. In particular, pharmacological or genetic ablation of adrenergic neurotransmission indicates that noradrenalin (NA) signaling controls bone SDF-1 downregulation, and hematopoietic stem cells mobilization. We hypothesized that catecholamines may control vascular progenitor cells mobilization from bone marrow and subsequently trigger post-ischemic neovascularization.Ischemia was induced by right femoral artery ligation in C57Bl6 mice (n=7 per group) treated with or without 6-hydroxydopamin (6-OHDA, 100mg/kg, i.p., 2 days), clenbuterol (2mg/kg, i.p., 5 days), dopamine (DA, 50mg/kg, i.p., 5 days), NA (2.5mg/kg, i.p., 5 days) and eticlopride (10mg/kg, i.p., 5 days). Sympathectomy induced by 6-OHDA led to a decrease in foot perfusion, angiographic score and capillary density by 41.4 % (p<0.001), 20.2 % (p<0.01) and 21.6 % (p<0.05) respectively, compared to controls, 21 days after ischemia. In contrast, administration of DA and NA increased angiographic score by 57.4 % (p=0.05) and 80.3 % (p<0.05), respectively and raised capillary density by around 15 % (p<0.01). Treatment with the β2-receptor agonist, clenbuterol, increased vessel and capillary densities by 30 % and 13 %, respectively (p<0.01 versus untreated control). Injection of eticlopride, a specific DA D2 receptor antagonist, also raised vessel density compared to controls. We next assessed the mobilization of stem/progenitor cells from bone marrow and their recruitment to ischemic tissue using chimeric mice lethally irradiated and transplanted with BM mononuclear cells isolated from GFP mice. Three days after ischemia, the number of GFP/ BS-1 lectin positive cells was reduced by 53.7 % (p<0.05) in the ischemic muscle of mice treated with 6-OHDA compared with controls. In contrast, clenbuterol increased by 46.4 % (p<0.05) the number of double positive cells suggesting that β2-receptor activation mediates BM stem cells mobilization and incorporation into vascular structure.Therefore, activation of the β2-receptor promotes postnatal vessel growth in response to ischemia. This effect is likely mediated by activation of stem/progenitor cells migration out of the bone marrow

Behaviour of niobium during early Earth's differentiation: insights from its local structure and oxidation state in silicate melts at high pressure

International audienceNiobium (Nb) is one of the key trace elements used to understand Earth's formation and differentiation, and is remarkable for its deficiency relative to tantalum in terrestrial rocks compared to the building chondritic blocks. In this context, the local environment of Nb in silica-rich melts and glasses is studied by in situ X-ray absorption spectroscopy (XAS) at high pressure (P) up to 9.3 GPa and 1350 K using resistive-heating diamond-anvil cells. Nb is slightly less oxidized in the melt (intermediate valence between +4 and +5) than in the glass (+5), an effect evidenced from the shift of the Nb-edge towards lower energies. Changes in the pre-edge features are also observed between melt and glass states, consistently with the observed changes in oxidation state although likely enhanced by temperature (T) effects. The oxidation state of Nb is not affected by pressure neither in the molten nor glassy states, and remains constant in the investigated P-range. The Nb-O coordination number is constant and equal to 6.3 ± 0.4 below 5 GPa, and only progressively increases up to 7.1 ± 0.4 at 9.3 GPa, the maximum P investigated. If these findings were to similarly apply to basaltic melts, that would rule out the hypothesis of Nb/Ta fractionation during early silicate Earth's differentiation, thus reinforcing the alternative hypothesis of fractionation during core formation on reduced pre-planetary bodies