Urea production and turnover following the addition of AMP, CMP, RNA and a protein mixture to a marine sediment

The potential of adenosine 5′-monophosphate (AMP), cytidine 5′-monophosphate (CMP), 16S ribosomal RNA, and a protein (bovine serum albumin) to serve as substrates for bacterial urea production was evaluated in a defaunated, anoxic marine sediment. AMP, CMP and RNA stimulated urea production and urea turnover, but CMP to a lesser degree than AMP and RNA. The increase in urea production and turnover rates took place immediately after AMP, CMP, and RNA were added to the sediment. The rapid response in urea production and turnover rates suggests that the necessary uptake mechanisms and enzymes to utilize the substrates were present constitutively. Addition of the protein mixture did not result in any measurable changes in the urea pool size, urea turnover rate, or urea production rate during the 165 h of incubation. However, an increased and continuous net NH4+ production in the protein-amended sediment relative to the control sediment indicated that the added protein mixture was accessible for bacterial degradation. The results showed that purines and pyrimidines were substrates for the bacterial urea production in the marine sediment, whereas protein was not important for urea production

La messe est dite

Auteur d’une thèse remarquable et remarquée sur La conversion des intellectuels au catholicisme en France, 1885-1935 (Paris, CNRS Éditions, 1998, réédition en 2010), Frédéric Gugelot s’est intéressé plus particulièrement depuis à la figure de l’écrivain catholique. Il a dirigé notamment, avec Alain Dierkens, Fabrice Preyat et Cécile Vanderpelen-Diagre, le précieux ouvrage collectif La Croix et la bannière. L’écrivain catholique en francophonie (xviie-xxie siècles), paru en 2007 aux Éditions d..

Multi-source analysis reveals latitudinal and altitudinal shifts in range of Ixodes ricinus at its northern distribution limit

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence for a latitudinal and altitudinal shift in the distribution range of <it>Ixodes ricinus</it>. The reported incidence of tick-borne disease in humans is on the rise in many European countries and has raised political concern and attracted media attention. It is disputed which factors are responsible for these trends, though many ascribe shifts in distribution range to climate changes. Any possible climate effect would be most easily noticeable close to the tick's geographical distribution limits. In Norway- being the northern limit of this species in Europe- no documentation of changes in range has been published. The objectives of this study were to describe the distribution of <it>I. ricinus </it>in Norway and to evaluate if any range shifts have occurred relative to historical descriptions.</p> <p>Methods</p> <p>Multiple data sources - such as tick-sighting reports from veterinarians, hunters, and the general public - and surveillance of human and animal tick-borne diseases were compared to describe the present distribution of <it>I. ricinus </it>in Norway. Correlation between data sources and visual comparison of maps revealed spatial consistency. In order to identify the main spatial pattern of tick abundance, a principal component analysis (PCA) was used to obtain a weighted mean of four data sources. The weighted mean explained 67% of the variation of the data sources covering Norway's 430 municipalities and was used to depict the present distribution of <it>I. ricinus</it>. To evaluate if any geographical range shift has occurred in recent decades, the present distribution was compared to historical data from 1943 and 1983.</p> <p>Results</p> <p>Tick-borne disease and/or observations of <it>I. ricinus </it>was reported in municipalities up to an altitude of 583 metres above sea level (MASL) and is now present in coastal municipalities north to approximately 69°N.</p> <p>Conclusion</p> <p><it>I. ricinus </it>is currently found further north and at higher altitudes than described in historical records. The approach used in this study, a multi-source analysis, proved useful to assess alterations in tick distribution.</p

Lethal Antibody Enhancement of Dengue Disease in Mice Is Prevented by Fc Modification

Immunity to one of the four dengue virus (DV) serotypes can increase disease severity in humans upon subsequent infection with another DV serotype. Serotype cross-reactive antibodies facilitate DV infection of myeloid cells in vitro by promoting virus entry via Fcγ receptors (FcγR), a process known as antibody-dependent enhancement (ADE). However, despite decades of investigation, no in vivo model for antibody enhancement of dengue disease severity has been described. Analogous to human infants who receive anti-DV antibodies by transplacental transfer and develop severe dengue disease during primary infection, we show here that passive administration of anti-DV antibodies is sufficient to enhance DV infection and disease in mice using both mouse-adapted and clinical DV isolates. Antibody-enhanced lethal disease featured many of the hallmarks of severe dengue disease in humans, including thrombocytopenia, vascular leakage, elevated serum cytokine levels, and increased systemic viral burden in serum and tissue phagocytes. Passive transfer of a high dose of serotype-specific antibodies eliminated viremia, but lower doses of these antibodies or cross-reactive polyclonal or monoclonal antibodies all enhanced disease in vivo even when antibody levels were neutralizing in vitro. In contrast, a genetically engineered antibody variant (E60-N297Q) that cannot bind FcγR exhibited prophylactic and therapeutic efficacy against ADE-induced lethal challenge. These observations provide insight into the pathogenesis of antibody-enhanced dengue disease and identify a novel strategy for the design of therapeutic antibodies against dengue

P53 in human melanoma fails to regulate target genes associated with apoptosis and the cell cycle and may contribute to proliferation

<p>Abstract</p> <p>Background</p> <p>Metastatic melanoma represents a major clinical problem. Its incidence continues to rise in western countries and there are currently no curative treatments. While mutation of the <it>P53 </it>tumour suppressor gene is a common feature of many types of cancer, mutational inactivation of <it>P53 </it>in melanoma is uncommon; however, its function often appears abnormal.</p> <p>Methods</p> <p>In this study whole genome bead arrays were used to examine the transcript expression of P53 target genes in extracts from 82 melanoma metastases and 6 melanoma cell lines, to provide a global assessment of aberrant P53 function. The expression of these genes was also examined in extracts derived from diploid human melanocytes and fibroblasts.</p> <p>Results</p> <p>The results indicated that P53 target transcripts involved in apoptosis were under-expressed in melanoma metastases and melanoma cell lines, while those involved in the cell cycle were over-expressed in melanoma cell lines. There was little difference in the transcript expression of P53 target genes between cell lines with null/mutant <it>P53 </it>compared to those with wild-type <it>P53</it>, suggesting that altered expression in melanoma was not related to <it>P53 </it>status. Similarly, down-regulation of P53 by short-hairpin RNA (shRNA) had limited effect on P53 target gene expression in melanoma cells, whereas there were a large number of P53 target genes whose mRNA expression was significantly altered by P53 inhibition in melanocytes. Analysis of whole genome gene expression profiles indicated that the ability of P53 to regulate genes involved in the cell cycle was significantly reduced in melanoma cells. Moreover, inhibition of P53 in melanocytes induced changes in gene expression profiles that were characteristic of melanoma cells and resulted in increased proliferation. Conversely, knockdown of P53 in melanoma cells resulted in decreased proliferation.</p> <p>Conclusions</p> <p>These results indicate that P53 target genes involved in apoptosis and cell cycle regulation are aberrantly expressed in melanoma and that this aberrant functional activity of P53 may contribute to the proliferation of melanoma.</p

Intracranial injection of dengue virus induces interferon stimulated genes and CD8(+) T cell infiltration by sphingosine kinase 1 independent pathways

We have previously reported that the absence of sphingosine kinase 1 (SK1) affects both dengue virus (DENV) infection and innate immune responses in vitro. Here we aimed to define SK1-dependancy of DENV-induced disease and the associated innate responses in vivo. The lack of a reliable mouse model with a fully competent interferon response for DENV infection is a challenge, and here we use an experimental model of DENV infection in the brain of immunocompetent mice. Intracranial injection of DENV-2 into C57BL/6 mice induced body weight loss and neurological symptoms which was associated with a high level of DENV RNA in the brain. Body weight loss and DENV RNA level tended to be greater in SK1-/- compared with wildtype (WT) mice. Brain infection with DENV-2 is associated with the induction of interferon-β (IFN-β) and IFN-stimulated gene (ISG) expression including viperin, Ifi27l2a, IRF7, and CXCL10 without any significant differences between WT and SK1-/- mice. The SK2 and sphingosine-1-phosphate (S1P) levels in the brain were unchanged by DENV infection or the lack of SK1. Histological analysis demonstrated the presence of a cellular infiltrate in DENV-infected brain with a significant increase in mRNA for CD8 but not CD4 suggesting this infiltrate is likely CD8+ but not CD4+ T-lymphocytes. This increase in T-cell infiltration was not affected by the lack of SK1. Overall, DENV-infection in the brain induces IFN and T-cell responses but does not influence the SK/S1P axis. In contrast to our observations in vitro, SK1 has no major influence on these responses following DENV-infection in the mouse brain.Wisam H. Al-Shujairi, Jennifer N. Clarke, Lorena T. Davies, Mohammed Alsharifi, Stuart M. Pitson, Jillian M. Car