Simulating impacts of climate and management on timothy growth in Northern countries

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Economic geology: Volatile destruction

International audienceDirect evidence for the role of volatiles in magmatic ore formation has been elusive. Magma degassing at Merapi volcano in Indonesia is found to be directly linked to the selective leaching of metals from sulphide melts that ultimately form ore deposits

Estimation des taux de recombinaison entre les locus Phi et Pgd et le complexe SLA chez le porc

International audienc

IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

Funding: This work was funded by a Career Development Fellowship (1028634) and a project grant (GRNT1028641) awarded to AHa by the Australian National Health & Medical Research Council (NHMRC). IS was supported by The University of Queensland Centennial and IPRS Scholarships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

An empirical approach towards the efficient and optimal production of influenza-neutralizing ovine polyclonal antibodies demonstrates that the novel adjuvant CoVaccine HT(TM) is functionally superior to Freund's adjuvant

Passive immunotherapies utilising polyclonal antibodies could have a valuable role in preventing and treating infectious diseases such as influenza, particularly in pandemic situations but also in immunocompromised populations such as the elderly, the chronically immunosuppressed, pregnant women, infants and those with chronic diseases. The aim of this study was to optimise current methods used to generate ovine polyclonal antibodies. Polyclonal antibodies to baculovirus-expressed recombinant influenza haemagglutinin from A/Puerto Rico/8/1934 H1N1 (PR8) were elicited in sheep using various immunisation regimens designed to investigate the priming immunisation route, adjuvant formulation, sheep age, and antigen dose, and to empirically ascertain which combination maximised antibody output. The novel adjuvant CoVaccine HT™ was compared to Freund’s adjuvant which is currently the adjuvant of choice for commercial production of ovine polyclonal Fab therapies. CoVaccine HT™ induced significantly higher titres of functional ovine anti-haemagglutinin IgG than Freund’s adjuvant but with fewer side effects, including reduced site reactions. Polyclonal hyperimmune sheep sera effectively neutralised influenza virus in vitro and, when given before or after influenza virus challenge, prevented the death of infected mice. Neither the age of the sheep nor the route of antigen administration appeared to influence antibody titre. Moreover, reducing the administrated dose of haemagglutinin antigen minimally affected antibody titre. Together, these results suggest a cost effective way of producing high and sustained yields of functional ovine polyclonal antibodies specifically for the prevention and treatment of globally significant diseases.Natalie E. Stevens, Cara K. Fraser, Mohammed Alsharifi, Michael P. Brown, Kerrilyn R. Diener, John D. Haybal

Light chain deposition disease presenting as paroxysmal atrial fibrillation: a case report

<p>Abstract</p> <p>Introduction</p> <p>Light chain deposition disease (LCDD) can involve the heart and cause severe heart failure. Cardiac involvement is usually described in the advanced stages of the disease. We report the case of a woman in whom restrictive cardiomyopathy due to LCDD presented with paroxysmal atrial fibrillation.</p> <p>Case presentation</p> <p>A 55-year-old woman was admitted to our emergency department because of palpitations. In a recent blood test, serum creatinine was 1.4 mg/dl. She was found to have high blood pressure, left ventricular hypertrophy and paroxysmal atrial fibrillation. An ACE-inhibitor was prescribed but her renal function rapidly worsened and she was admitted to our nephrology unit. On admission serum creatinine was 9.4 mg/dl, potassium 6.8 mmol/l, haemoglobin 7.7 g/dl, N-terminal pro-brain natriuretic peptide 29894 pg/ml. A central venous catheter was inserted and haemodialysis was started. She underwent a renal biopsy which showed kappa LCDD. Bone marrow aspiration and bone biopsy demonstrated kappa light chain multiple myeloma. Echocardiographic findings were consistent with restrictive cardiomyopathy. Thalidomide and dexamethasone were prescribed, and a peritoneal catheter was inserted. Peritoneal dialysis has now been performed for 15 months without complications.</p> <p>Discussion</p> <p>Despite the predominant tubular deposition of kappa light chain, in our patient the first clinical manifestation of LCDD was cardiac disease manifesting as atrial fibrillation and the correct diagnosis was delayed. The clinical management initially addressed the cardiovascular symptoms without paying sufficient attention to the pre-existing slight increase in our patient's serum creatinine. However cardiac involvement is a quite uncommon presentation of LCDD, and this unusual case suggests that the onset of acute arrhythmias associated with restrictive cardiomyopathy and impaired renal function might be related to LCDD.</p

IL-21 and IL-6 Are Critical for Different Aspects of B Cell Immunity and Redundantly Induce Optimal Follicular Helper CD4 T Cell (Tfh) Differentiation

Cytokines are important modulators of lymphocytes, and both interleukin-21 (IL-21) and IL-6 have proposed roles in T follicular helper (Tfh) differentiation, and directly act on B cells. Here we investigated the absence of IL-6 alone, IL-21 alone, or the combined lack of IL-6 and IL-21 on Tfh differentiation and the development of B cell immunity in vivo. C57BL/6 or IL-21−/− mice were treated with a neutralizing monoclonal antibody against IL-6 throughout the course of an acute viral infection (lymphocytic choriomeningitis virus, LCMV). The combined absence of IL-6 and IL-21 resulted in reduced Tfh differentiation and reduced Bcl6 protein expression. In addition, we observed that these cytokines had a large impact on antigen-specific B cell responses. IL-6 and IL-21 collaborate in the acute T-dependent antiviral antibody response (90% loss of circulating antiviral IgG in the absence of both cytokines). In contrast, we observed reduced germinal center formation only in the absence of IL-21. Absence of IL-6 had no impact on germinal centers, and combined absence of both IL-21 and IL-6 revealed no synergistic effect on germinal center B cell development. Studying CD4 T cells in vitro, we found that high IL-21 production was not associated with high Bcl6 or CXCR5 expression. TCR stimulation of purified naïve CD4 T cells in the presence of IL-6 also did not result in Tfh differentiation, as determined by Bcl6 or CXCR5 protein expression. Cumulatively, our data indicates that optimal Tfh formation requires IL-21 and IL-6, and that cytokines alone are insufficient to drive Tfh differentiation

Process-based modelling of the nutritive value of forages: a review

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Significance of Toll-like Receptors Expression in Tumor Growth and Spreading: A Short Review

Toll-like receptors (TLRs) are considered now as crucial sensors of innate immunity. Their role in the recognition of pathogens and the initiation of adaptive immune responses against them is well known. However, in last years TLRs have been identified on several tumor cells, including human malignancies. Their expression in cancer was found to be twofold: either promoting or inhibiting tumor progression. It was also demonstrated that several TLRs agonists, either natural or synthetic ones, may have beneficial effect on tumor-mediated disease, leading to potentiation of immune response to tumor-associated antigens. TLR-agonist linked tumor immunotherapy is still in nascent state, but growing rapidly, also in the area of common human malignancies. To date, the most promising and the most frequently studied interaction in tumor immunotherapy trials seems to be TLR9 and its synthetic agonists