Wild type and mutant 2009 pandemic influenza A (H1N1) viruses cause more severe disease and higher mortality in pregnant BALB/c mice

Background: Pregnant women infected by the pandemic influenza A (H1N1) 2009 virus had more severe disease and higher mortality but its pathogenesis is still unclear. Principal Findings: We showed that higher mortality, more severe pneumonitis, higher pulmonary viral load, lower peripheral blood T lymphocytes and antibody responses, higher levels of proinflammatory cytokines and chemokines, and worse fetal development occurred in pregnant mice than non-pregnant controls infected by either wild type (clinical isolate) or mouse-adapted mutant virus with D222G substitution in hemagglutinin. These disease-associated changes and the lower respiratory tract involvement were worse in pregnant mice challenged by mutant virus. Though human placental origin JEG-3 cell line could be infected and proinflammatory cytokines or chemokines were elevated in amniotic fluid of some mice, no placental or fetal involvement by virus were detected by culture, real-time reverse transcription polymerase chain reaction or histopathological changes. Dual immunofluorescent staining of viral nucleoprotein and type II alveolar cell marker SP-C protein suggested that the majority of infected alveolar epithelial cells were type II pneumocytes. Conclusion: The adverse effect of this pandemic virus on maternal and fetal outcome is largely related to the severe pulmonary disease and the indirect effect of inflammatory cytokine spillover into the systemic circulation. © 2010 Chan et al.published_or_final_versio

Gas storage

International audienceThe continuous increase of energy demands based on fossil fuels in the last years have lead to an increase of greenhouse gases (GHG) emission which strongly contribute to global warming. The main strategies to limit this phenomenon are related to the efficient capture of these gases and to the development of renewable energies sources with limited environmental impact. Particularly, carbon dioxide (CO2) and methane (CH4) are the main constituents of greenhouse gases while hydrogen (H2) is considered an alternative clean energy source to fossil fuels. Therefore, tremendous research to store these gases has been reported by several approaches and among them the physisorption on activated carbons (AC) have received significant attention. Their abundance, low cost and tunable porous structure and chemical functionalities with an existing wide range of precursors that includes bio-wastes make them ideal candidates for gas applications. This chapter presents the recent developments on CH4, CO2 and H2 storage by activated carbons with focus on biomass as precursor materials. An analysis of the main carbon properties affecting the AC's adsorption capacity (i.e. specific surface area, pore size and surface chemistry) is discussed in detail herein

Science and the stock market: Investors' recognition of unburnable carbon

This paper documents the stock market's reaction to a 2009 paper in the Nature journal of science, which concluded that only a fraction of the world's existing oil, gas, and coal reserves could be emitted if global warming by 2050 were not to exceed 2 °C above pre-industrial levels. This Nature article is now one of the most cited environmental science studies in recent years. Our analysis indicates that this publication prompted an average stock price drop of 1.5% to 2% for our sample of the 63 largest U.S. oil and gas firms. Later, in 2012-2013, the press "discovered" this article, writing hundreds of stories on the grim consequences of unburnable carbon for fossil fuel companies. We show only a small negative reaction to these later stories, mostly in the two weeks following their publication. This limited market response contrasts with the predictions of some analysts and commentators of a substantial decline in the shareholder value of fossil fuel companies from a carbon bubble. Our paper discusses possible reasons for this discrepancy

Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa

In MRI scans of patients with anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknown whether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlying AN. Here, we used a battery of methods (LD score regression, genetic risk scores, sign test, SNP effect concordance analysis, and Mendelian randomization) to investigate the genetic covariation between subcortical brain volumes and risk for AN based on summary measures retrieved from genome-wide association studies of regional brain volumes (ENIGMA consortium, n = 13,170) and genetic risk for AN (PGC-ED consortium, n = 14,477). Genetic correlations ranged from − 0.10 to 0.23 (all p > 0.05). There were some signs of an inverse concordance between greater thalamus volume and risk for AN (permuted p = 0.009, 95% CI: [0.005, 0.017]). A genetic variant in the vicinity of ZW10, a gene involved in cell division, and neurotransmitter and immune system relevant genes, in particular DRD2, was significantly associated with AN only after conditioning on its association with caudate volume (pFDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDR = 0.021). In this comprehensive set of analyses and based on the largest available sample sizes to date, there was weak evidence for associations between risk for AN and risk for abnormal subcortical brain volumes at a global level (that is, common variant genetic architecture), but suggestive evidence for effects of single genetic markers. Highly powered multimodal brain- and disorder-related genome-wide studies are needed to further dissect the shared genetic influences on brain structure and risk for AN

Functional dissection of an IFN-α/β receptor 1 promoter variant that confers higher risk to chronic hepatitis B virus infection

Background/Aims: We previously demonstrated that two linked single nucleotide polymorphisms (SNPs) at -408 and -3 of type I interferon receptor 1 (IFNAR1) promoter are associated with susceptibility to chronic HBV infection. We aimed to elucidate the mechanism by which -3 and/or -408 C/T SNPs had such profound effects. Methods: A functional SNP in IFNAR1 promoter was defined by reporter gene assay, mutational analysis, flow cytometry analysis and gel shift assay. The nuclear protein binding to the essential polymorphic site was identified and its effect on transcriptional regulation of IFNAR1 was further demonstrated in a series of ex vivo and in vivo experiments. Results: We found C > T change at the -3 locus reduced the transcriptional activity of IFNAR1 promoter. High mobility group B protein 1 (HMGB1) and PARP-1 were co-recruited to the IFNAR1 promoter to regulate its transcription. We demonstrated HMGB1-binding affinity to IFNAR1 promoter was reduced in the -3T variant. Additionally, PARP-1, a cofactor for IFNAR1 transcription activation, was significantly suppressed by HBV. Conclusion: Upon HBV infection, decreased binding affinity of HMGB1 to the IFNAR1 promoter -3T variant is aggravated by the suppressed PARP-1 expression caused by HBV, resulting in a further attenuated IFNAR1 expression. This compromises the antiviral and immuno-regulatory effects of IFN-α/β, which may in turn affect the clinical outcome of HBV infection. © 2009 European Association for the Study of the Liver.link_to_subscribed_fulltex

Recombinant receptor-binding domain of SARS-CoV spike protein expressed in mammalian, insect and E. coli cells elicits potent neutralizing antibody and protective immunity

Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease. The potential recurrence of the disease from animal reservoirs highlights the significance of development of safe and efficient vaccines to prevent a future SARS epidemic. In this study, we expressed the recombinant receptor-binding domain (rRBD) in mammalian (293T) cells, insect (Sf9) cells, and E. coli, respectively, and compared their immunogenicity and protection against SARS-CoV infection in an established mouse model. Our results show that all rRBD proteins expressed in the above systems maintained intact conformation, being able to induce highly potent neutralizing antibody responses and complete protective immunity against SARS-CoV challenge in mice, albeit the rRBD expressed in 293T cells elicited stronger humoral immune responses with significantly higher neutralizing activity (P < 0.05) than those expressed in Sf9 and E. coli cells. These results suggest that all three rRBDs are effective in eliciting immune responses and protection against SARS-CoV and any of the above expression systems can be used for production of rRBD-based SARS subunit vaccines. Preference will be given to rRBD expressed in mammalian cells for future evaluation of the vaccine efficacy in a non-human primate model of SARS because of its ability to refold into a native conformation more readily and to induce higher level of neutralizing antibody responses than those expressed in E. coli and insect cells. © 2009 Elsevier Inc. All rights reserved.link_to_OA_fulltex