Acceleration predicts energy expenditure in a fat, flightless, diving bird

Funding The project was supported logistically by the French Polar Institute and funded by the PEW fellowship to Y.R.-C., the WWF-UK, and the Zone Atelier Antarctique et Terres Australes from the CNRS. D.M.W. received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska‐Curie Individual Fellowship Grant Agreement No. 748026.Peer reviewedPublisher PD

Trypanosoma cruzi Adjuvants Potentiate T Cell-Mediated Immunity Induced by a NY-ESO-1 Based Antitumor Vaccine

Immunological adjuvants that induce T cell-mediate immunity (TCMI) with the least side effects are needed for the development of human vaccines. Glycoinositolphospholipids (GIPL) and CpGs oligodeoxynucleotides (CpG ODNs) derived from the protozoa parasite Trypanosoma cruzi induce potent pro-inflammatory reaction through activation of Toll-Like Receptor (TLR)4 and TLR9, respectively. Here, using mouse models, we tested the T. cruzi derived TLR agonists as immunological adjuvants in an antitumor vaccine. For comparison, we used well-established TLR agonists, such as the bacterial derived monophosphoryl lipid A (MPL), lipopeptide (Pam3Cys), and CpG ODN. All tested TLR agonists were comparable to induce antibody responses, whereas significant differences were noticed in their ability to elicit CD4+ T and CD8+ T cell responses. In particular, both GIPLs (GTH, and GY) and CpG ODNs (B344, B297 and B128) derived from T. cruzi elicited interferon-gamma (IFN-γ) production by CD4+ T cells. On the other hand, the parasite derived CpG ODNs, but not GIPLs, elicited a potent IFN-γ response by CD8+ T lymphocytes. The side effects were also evaluated by local pain (hypernociception). The intensity of hypernociception induced by vaccination was alleviated by administration of an analgesic drug without affecting protective immunity. Finally, the level of protective immunity against the NY-ESO-1 expressing melanoma was associated with the magnitude of both CD4+ T and CD8+ T cell responses elicited by a specific immunological adjuvant

Atlas de sensibilité du littoral aux pollutions marines. Création d’un site dédié Sextant. Atlas Polmar Réunion.

Dans le cadre de l’élaboration de l’Atlas de sensibilité du littoral aux pollutions marines, L’IFREMER a souhaité mettre à disposition des institutions un outil permettant d’accéder à l’ensemble des informations cartographiques ayant permis l’élaboration de cette annexe technique du dispositif spécifique POLMAR/TERRE. Le portail Sextant, infrastructure de données géoréférencées marines et littorales, permettant la mise en commun et le partage de l‘information géographique, permet de répondre à ces exigences

Molecular mechanisms of cardiac electromechanical remodeling during Chagas disease: Role of TNF and TGF-beta

Chagas disease is caused by the trypanosomatid Trypanosoma cruzi, which chronically causes heart problems in up to 30% of infected patients. Chagas disease was initially restricted to Latin America. However, due to migratory events, this disease may become a serious worldwide health problem. During Chagas disease, many patients die of cardiac arrhythmia despite the apparent benefits of anti arrhythmic therapy (e.g., amiodarone). Here, we assimilate the cardiac form of Chagas disease to an inflammatory cardiac disease. Evidence from the literature, mostly provided using experimental models, supports this view and argues in favor of new strategies for treating cardiac arrhythmias in Chagas disease by modulating cytokine production and/or action. But the complex nature of myocardial inflammation underlies the need to better understand the molecular mechanisms of the inflammatory response during Chagas disease. Here, particular attention has been paid to tumor necrosis factor alpha (TNF) and transforming growth factor beta (TGF-beta) although other cytokines may be involved in the chagasic cardiomyopathy.CNPq, BrazilFAPESP, BrazilFAPEMIG, BrazilUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Pampulha, MG, BrazilUniv Fed Sao Paulo, Dept Biofis, Lab Biofis, Rua Botucatu,862 Edificio Ciencias Biomed, BR-04023062 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Biofis, Lab Biofis, Rua Botucatu,862 Edificio Ciencias Biomed, BR-04023062 Sao Paulo, SP, BrazilCNPq: 404353/2012-6FAPESP: 2014/09861-1FAPEMIG: APQ-02410-10FAPEMIG: APQ-00460-12Web of Scienc

Differential Use of TLR2 and TLR9 in the Regulation of Immune Responses during the Infection with Trypanosoma cruzi

Submitted by Nuzia Santos ([email protected]) on 2018-12-05T18:14:36Z No. of bitstreams: 1 Differential Use of TLR2 and TLR9 .pdf: 5776313 bytes, checksum: 3206b5a0f2e440a9c95d8318a58fc1f8 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2018-12-05T18:20:21Z (GMT) No. of bitstreams: 1 Differential Use of TLR2 and TLR9 .pdf: 5776313 bytes, checksum: 3206b5a0f2e440a9c95d8318a58fc1f8 (MD5)Made available in DSpace on 2018-12-05T18:20:21Z (GMT). No. of bitstreams: 1 Differential Use of TLR2 and TLR9 .pdf: 5776313 bytes, checksum: 3206b5a0f2e440a9c95d8318a58fc1f8 (MD5) Previous issue date: 2013Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil/Division of Infectious Diseases and Immunology. University of Massachusetts Medical School. Worcester, MA, Untied States of America.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrazilPathogens express ligands for several TLRs that may play a role in the induction or control of the inflammatory response during infection. Concerning Trypanosoma cruzi, the agent of Chagas disease, we have previously characterized glycosylphosphatidylinositol (GPI) anchored mucin-like glycoproteins (tGPI-mucin) and unmethylated CpG DNA sequences as TLR2 and TLR9 agonists, respectively. Here we sought to determine how these TLRs may modulate the inflammatory response in the following cell populations: F4/80+CD11b+ (macrophages), F4/80lowCD11b+ (monocytes) and MHCII+CD11chigh (dendritic cells). For this purpose, TLR2−/− and TLR9−/− mice were infected with Y strain of T. cruzi and different immunological parameters were evaluated. According to our previous data, a crucial role of TLR9 was evidenced in the establishment of Th1 response, whereas TLR2 appeared to act as immunoregulator in the early stage of infection. More precisely, we demonstrated here that TLR2 was mainly used by F4/80+CD11b+ cells for the production of TNF-α. In the absence of TLR2, an increased production of IL-12/IL-23p40 and IFN-γ was noted suggesting that TLR2 negatively controls the Th1 response. In contrast, TLR9 was committed to IL-12/IL-23p40 production by MHCII+CD11chigh cells that constitute the main source of IL-12/IL-23p40 during infection. Importantly, a down-regulation of TLR9 response was observed in F4/80+CD11b+ and F4/80lowCD11b+ populations that correlated with the decreased TLR9 expression level in these cells. Interestingly, these cells recovered their capacity to respond to TLR9 agonist when MHCII+CD11chigh cells were impeded from producing IL-12/IL-23p40, thereby indicating possible cross-talk between these populations. The differential use of TLR2 and TLR9 by the immune cells during the acute phase of the infection explains why TLR9- but not TLR2-deficient mice are susceptible to T. cruzi infection

Early effects of erythropoietin on serum hepcidin and serum iron bioavailability in healthy volunteers.

International audienceHepcidin regulates plasma iron bioavailability and subsequently iron availability for erythropoiesis. rHuEPO has been reported to decrease hepcidin expression in case of repeated subcutaneous injections. Thus, hepcidin level measurement could be a candidate marker for detection of rHuEPO abuse. However, when used for doping, rHuEPO can be injected intravenously and the scheme of injection is unknown. Our aim was to evaluate the early effects of a single intravenous rHuEPO injection on serum hepcidin levels. Fourteen male healthy volunteers received one intravenous injection of 50 U/Kg of rHuEPO during a placebo-controlled, randomized, double-blind, cross-over study. Serum hepcidin, quantified by a competitive ELISA method and iron parameters was then evaluated for 24 h. Serum levels of hepcidin were significantly increased 4 h after rHuEPO injection when compared with placebo injection (78.3 ± 55.5 vs. 57.5 ± 34.6 ng/ml, respectively; +36%, p < 0.05), whereas iron and transferrin saturation dramatically decreased 12 h after rHuEPO injection when compared with placebo injection (9.2 ± 3.5 vs. 15.8 ± 4.2 μg/l, respectively; -42%, p < 0.05 and 14.8 ± 5.0 vs. 26.3 ± 6.4%, respectively; -44%, p < 0.05). In addition, 12 and 24 h after rHuEPO injection serum hepcidin levels were lower compared with placebo injection (41.6 ± 27.4 vs. 56.6 ± 28.1 ng/ml after 12 h; -27%, p < 0.05 and 26.0 ± 29.6 vs. 81.2 ± 29.4 ng/ml after 24 h; -68%, p < 0.05). Intravenous injection of recombinant EPO induces a precocious and transient increase of serum hepcidin leading to a transient decrease of iron bioavailability. The transitory increase and dynamics of its concentration make difficult the practical use of hepcidin to detect rHuEPO doping

Comparison of the proinflammatory response in TLR2- and TLR9-deficient mice during the acute phase of <i>T.cruzi</i> infection.

<p>Cytokine levels in spleen cell culture (A) and serum (B) from either control (NI) or infected (I) C57BL/6 WT, TLR2^−/−, TLR9^−/− mice evaluated seven days post-infection. The data represent the mean of two experiments. *p<0.05 and **p<0.01 indicate statistical significance when comparing cytokine level in serum or in splenocyte culture from knockout versus C57BL/6 WT infected mice.</p

Schematic representation of the complementary effect of TLR2 and TLR9 activation during <i>T.cruzi</i> infection.

<p>A) The early release of IFN-γ induces an increase of TLR9 expression in DC and primes cells to TLR9 response (1). The high levels of IL-12/IL-23p40 secreted by DCs down-regulate the TLR9 responses of monocytes/macrophages by modulating the TLR9 expression (2). On the other hand, TLR2 is used by macrophage population to produce TNF-α (3). B) In DCs, TLR2 regulates negatively TLR9-dependent IL-12/IL-23p40 production by modulating signaling pathway.</p