Time-dependent photoionization of azulene: Competition between ionization and relaxation in highly excited states

Pump-probe photoionization has been used to map the relaxation processes taking place from highly vibrationally excited levels of the S2 state of azulene, populated directly or via internal conversion from the S4 state. Photoelectron spectra obtained by 1+2’ two-color time-resolved photoelectron imaging are invariant (apart from in intensity) to the pump-probe time delay and to pump wavelength. This reveals a photoionization process which is driven by an unstable electronic state (e.g. doubly excited state) lying below the ionization potential. This state is postulated to be populated by a probe transition from S2 and to rapidly relax via an Auger like process onto highly vibrationally excited Rydberg states. This accounts for the time invariance of the photoelectron spectrum. The intensity of the photoelectron spectrum is proportional to the population in S2. An exponential energy gap law is used to describe the internal conversion rate from S2 to S0. The vibronic coupling strength is found to be larger than 60±5 μeV

Evaluation of options for harvest of a recombinant E. coli fermentation producing a domain antibody using ultra scale-down techniques and pilot-scale verification

Ultra scale-down (USD) methods operating at the millilitre scale were used to characterise full-scale processing of E. coli fermentation broths autolysed to different extents for release of a domain antibody. The focus was on the primary clarification stages involving continuous centrifugation followed by depth filtration. The performance of this sequence was predicted by USD studies to decrease significantly with increased extents of cell lysis. The use of polyethyleneimine (PEI) reagent was studied to treat the lysed cell broth by precipitation of soluble contaminants such as DNA and flocculation of cell debris material. The USD studies were used to predict the impact of this treatment on the performance and here it was found that the fermentation could be run to maximum productivity using an acceptable clarification process (e.g a centrifugation stage operating at 0.11 L per m(2) equivalent gravity settling area per h followed by a resultant required depth filter area of 0.07 m(2) per L supernatant). A range of USD predictions was verified at the pilot scale for centrifugation followed by depth filtration. This article is protected by copyright. All rights reserved

Current review of genetically modified lactic acid bacteria for the prevention and treatment of colitis using murine models

Inflammatory Bowel Diseases (IBD) are disorders of the gastrointestinal tract characterized by recurrent inflammation that requires lifelong treatments. Probiotic microorganisms appear as an alternative for these patients; however, probiotic characteristics are strain dependent and each probiotic needs to be tested to understand the underlining mechanisms involved in their beneficial properties. Genetic modification of lactic acid bacteria (LAB) was also described as a tool for new IBD treatments.The first part of this review shows different genetically modified LAB (GM-LAB) described for IBD treatment since 2000.Then, the two principally studied strategies are discussed (i) GM-LAB producing antioxidant enzymes and (ii) GM-LAB producing the anti-inflammatory cytokine IL-10. Different delivery systems, including protein delivery and DNA delivery, will also be discussed. Studies show the efficacy of GM-LAB (using different expression systems) for the prevention and treatment of IBD, highlighting the importance of the bacterial strain selection (with anti-inflammatory innate properties) as a promising alternative. These microorganisms could be used in the near future for the development of therapeutic products with anti-inflammatory properties that can improve the quality of life of IBD patients.Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: del Carmen, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Chatel, Jean Marc. Institut National de la Recherche Agronomique; FranciaFil: Miyoshi, Anderson. Universidade Federal do Minas Gerais; BrasilFil: Azevedo, Vasco. Universidade Federal do Minas Gerais; BrasilFil: Langella, Philippe. Institut National de la Recherche Agronomique; FranciaFil: Bermudez Humaran, Luis G.. Institut National de la Recherche Agronomique; FranciaFil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin

Neutralization of IFN-γ reverts clinical and laboratory features in a mouse model of macrophage activation syndrome.

BACKGROUND: The pathogenesis of macrophage activation syndrome (MAS) is not clearly understood: a large body of evidence supports the involvement of mechanisms similar to those implicated in the setting of primary hemophagocytic lymphohistiocytosis. OBJECTIVE: We sought to investigate the pathogenic role of IFN-γ and the therapeutic efficacy of IFN-γ neutralization in an animal model of MAS. METHODS: We used an MAS model established in mice transgenic for human IL-6 (IL-6TG mice) challenged with LPS (MAS mice). Levels of IFN-γ and IFN-γ-inducible chemokines were evaluated by using real-time PCR in the liver and spleen and by means of ELISA in plasma. IFN-γ neutralization was achieved by using the anti-IFN-γ antibody XMG1.2 in vivo. RESULTS: Mice with MAS showed a significant upregulation of the IFN-γ pathway, as demonstrated by increased mRNA levels of Ifng and higher levels of phospho-signal transducer and activator of transcription 1 in the liver and spleen and increased expression of the IFN-γ-inducible chemokines Cxcl9 and Cxcl10 in the liver and spleen, as well as in plasma. A marked increase in Il12a and Il12b expression was also found in livers and spleens of mice with MAS. In addition, mice with MAS had a significant increase in numbers of liver CD68+ macrophages. Mice with MAS treated with an anti-IFN-γ antibody showed a significant improvement in survival and body weight recovery associated with a significant amelioration of ferritin, fibrinogen, and alanine aminotransferase levels. In mice with MAS, treatment with the anti-IFN-γ antibody significantly decreased circulating levels of CXCL9, CXCL10, and downstream proinflammatory cytokines. The decrease in CXCL9 and CXCL10 levels paralleled the decrease in serum levels of proinflammatory cytokines and ferritin. CONCLUSION: These results provide evidence for a pathogenic role of IFN-γ in the setting of MAS

The Non--Ergodicity Threshold: Time Scale for Magnetic Reversal

We prove the existence of a non-ergodicity threshold for an anisotropic classical Heisenberg model with all-to-all couplings. Below the threshold, the energy surface is disconnected in two components with positive and negative magnetizations respectively. Above, in a fully chaotic regime, magnetization changes sign in a stochastic way and its behavior can be fully characterized by an average magnetization reversal time. We show that statistical mechanics predicts a phase--transition at an energy higher than the non-ergodicity threshold. We assess the dynamical relevance of the latter for finite systems through numerical simulations and analytical calculations. In particular, the time scale for magnetic reversal diverges as a power law at the ergodicity threshold with a size-dependent exponent, which could be a signature of the phenomenon.Comment: 4 pages 4 figure

The Credit ratings Game and Its Effect on Firm Investment

The spectacular collapse of structured financial products, which were given top ratings by the Credit Rating Agencies in the last financial crisis, brought back the debate regarding the importance and relevance of these agencies and their so-called “issuer pays” business model. This paper shows, from a game theoretical perspective, the influence of Credit Rating Agencies on firm investment. This is done through a signalling game involving cheap talk. The model outlines three key variables that affect firm investment: (1) the bias of the firm regarding its value, (2) the bias of the Credit Rating Agency regarding a firm’s value, and (3) the cost of credit rating. These variables have a significant effect on communication between the players in this game and thus, by extensions, on firm investment

Novel insights into host-fungal pathogen interactions derived from live-cell imaging

Acknowledgments The authors acknowledge funding from the Wellcome Trust (080088, 086827, 075470 and 099215) including a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377 and FP7-2007–2013 grant agreement HEALTH-F2-2010-260338–ALLFUN to NARG.Peer reviewedPublisher PD

Novel Staufen1 ribonucleoproteins prevent formation of stress granules but favour encapsidation of HIV-1 genomic RNA

Human immunodeficiency virus type 1 (HIV-1) Gag selects for and mediates genomic RNA (vRNA) encapsidation into progeny virus particles. The host protein, Staufen1 interacts directly with Gag and is found in ribonucleoprotein (RNP) complexes containing vRNA, which provides evidence that Staufen1 plays a role in vRNA selection and encapsidation. In this work, we show that Staufen1, vRNA and Gag are found in the same RNP complex. These cellular and viral factors also colocalize in cells and constitute novel Staufen1 RNPs (SHRNPs) whose assembly is strictly dependent on HIV-1 expression. SHRNPs are distinct from stress granules and processing bodies, are preferentially formed during oxidative stress and are found to be in equilibrium with translating polysomes. Moreover, SHRNPs are stable, and the association between Staufen1 and vRNA was found to be evident in these and other types of RNPs. We demonstrate that following Staufen1 depletion, apparent supraphysiologic-sized SHRNP foci are formed in the cytoplasm and in which Gag, vRNA and the residual Staufen1 accumulate. The depletion of Staufen1 resulted in reduced Gag levels and deregulated the assembly of newly synthesized virions, which were found to contain several-fold increases in vRNA, Staufen1 and other cellular proteins. This work provides new evidence that Staufen1-containing HIV-1 RNPs preferentially form over other cellular silencing foci and are involved in assembly, localization and encapsidation of vRNA.Fil: Abrahamyan, Levon G.. Davis Jewish General Hospital; CanadáFil: Chatel Chaix, Laurent. Davis Jewish General Hospital; CanadáFil: Ajamian, Lara. Mc Gill University; Canadá. Davis Jewish General Hospital; CanadáFil: Milev, Miroslav P.. Mc Gill University; Canadá. Davis Jewish General Hospital; CanadáFil: Monette, Anne. Mc Gill University; Canadá. Davis Jewish General Hospital; CanadáFil: Clément, Jean François. Davis Jewish General Hospital; CanadáFil: Song, Rujun. Mc Gill University; Canadá. Davis Jewish General Hospital; CanadáFil: Lehmann, Martin. Davis Jewish General Hospital; CanadáFil: DesGroseillers, Luc. University Of Montreal; CanadáFil: Laughrea, Michael. Mc Gill University; Canadá. Davis Jewish General Hospital; CanadáFil: Boccaccio, Graciela Lidia. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: Mouland, Andrew J.. Mc Gill University; Canadá. Davis Jewish General Hospital; Canad

Lactococcus lactis carrying the pValac DNA expression vector coding for IL-10 reduces inflammation in a murine model of experimental colitis

Background: Inflammatory bowel diseases (IBD) are intestinal disorders characterized by inflammation in the gastrointestinal tract. Interleukin-10 is one of the most important anti-inflammatory cytokines involved in the intestinal immune system and because of its role in downregulating inflammatory cascades, its potential for IBD therapy is under study. We previously presented the development of an invasive strain of Lactococcus lactis (L. lactis) producing Fibronectin Binding Protein A (FnBPA) which was capable of delivering, directly to host cells, a eukaryotic DNA expression vector coding for IL-10 of Mus musculus (pValac:il-10) and diminish inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced mouse model of intestinal inflammation. As a new therapeutic strategy against IBD, the aim of this work was to evaluate the therapeutic effect of two L. lactis strains (the same invasive strain evaluated previously and the wild-type strain) carrying the therapeutic pValac:il-10 plasmid in the prevention of inflammation in a dextran sodium sulphate (DSS)-induced mouse model. Results: Results obtained showed that not only delivery of the pValac:il-10 plasmid by the invasive strain L. lactis MG1363 FnBPA+, but also by the wild-type strain L. lactis MG1363, was effective at diminishing intestinal inflammation (lower inflammation scores and higher IL-10 levels in the intestinal tissues, accompanied by decrease of IL-6) in the DSS-induced IBD mouse model. Conclusions: Administration of both L. lactis strains carrying the pValac:il-10 plasmid was effective at diminishing inflammation in this murine model of experimental colitis, showing their potential for therapeutic intervention of IBD.Fil: Zurita Turk, Meritxell. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; BrasilFil: del Carmen, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Santos, Ana C. G.. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; BrasilFil: Pereira, Vanessa Bastos. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; BrasilFil: Cara, Denise C.. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; BrasilFil: Leclercq, Sophie Y.. Fundaçao Ezequiel Dias. Laboratório de Inovaçao Biotecnológica; BrasilFil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Azevedo, Vasco. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; BrasilFil: Chatel, Jean-Marc. Universidade Federal do Minas Gerais; BrasilFil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Miyoshi, Anderson. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; Brasi