Evaluation of the Influenza A Replicon for Transient Expression of Recombinant Proteins in Mammalian Cells

Recombinant protein expression in mammalian cells has become a very important technique over the last twenty years. It is mainly used for production of complex proteins for biopharmaceutical applications. Transient recombinant protein expression is a possible strategy to produce high quality material for preclinical trials within days. Viral replicon based expression systems have been established over the years and are ideal for transient protein expression. In this study we describe the evaluation of an influenza A replicon for the expression of recombinant proteins. We investigated transfection and expression levels in HEK-293 cells with EGFP and firefly luciferase as reporter proteins. Furthermore, we studied the influence of different influenza non-coding regions and temperature optima for protein expression as well. Additionally, we exploited the viral replication machinery for the expression of an antiviral protein, the human monoclonal anti-HIV-gp41 antibody 3D6. Finally we could demonstrate that the expression of a single secreted protein, an antibody light chain, by the influenza replicon, resulted in fivefold higher expression levels compared to the usually used CMV promoter based expression. We emphasize that the influenza A replicon system is feasible for high level expression of complex proteins in mammalian cells

A national-scale assessment of climate change impacts on species: assessing the balance of risks and opportunities for multiple taxa

It is important for conservationists to be able to assess the risks that climate change poses to species, in order to inform decision making. Using standardised and repeatable methods, we present a national-scale assessment of the risks of range loss and opportunities for range expansion, that climate change could pose for over 3,000 plants and animals that occur in England. A basic risk assessment that compared projected future changes in potential range with recently observed changes classified 21% of species as being at high risk and 6% at medium risk of range loss under a B1 climate change scenario. A greater number of species were classified as having a medium (16%) or high (38%) opportunity to potentially expand their distribution. A more comprehensive assessment, incorporating additional ecological information, including potentially confounding and exacerbating factors, was applied to 402 species, of which 35 % were at risk of range loss and 42 % may expand their range extent. This study covers a temperate region with a significant proportion of species at their poleward range limit. The balance of risks and opportunities from climate change may be different elsewhere. The outcome of both risk assessments varied between taxonomic groups, with bryophytes and vascular plants containing the greatest proportion of species at risk from climate change. Upland habitats contained more species at risk than other habitats. Whilst the overall pattern was clear, confidence was generally low for individual assessments, with the exception of well-studied taxa such as birds. In response to climate change, nature conservation needs to plan for changing species distributions and increasing uncertainty of the future

Metabolic fate of the heart agent [18F]6-fluorometaraminol

Studies were performed to determine whether [18F]6-fluorometaraminol (18F-FMR), a new neuronal heart radiopharmaceutical, is metabolized in vivo and if the metabolites are taken up in heart. Rat, dog, baboon and guinea pig were injected with 18F-FMR and tissue samples were analyzed for metabolites by HPLC. Liver contained the most metabolites of the tissues studied with 25-90% of the radioactivity present as metabolites at 1 h in all the species studied. While metabolites of 18F-FMR are found in blood, no significant accumulation of these metabolites is found in heart ([les]0.3%) 1 h after i.v. administration in any species except rat. These studies suggest that 18F-FMR is a suitable agent for quantitative imaging of the heart by positron emission tomography.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28226/1/0000679.pd

Rapport du Groupe Biodiversité : partie III

[Departement_IRSTEA]Territoires [TR1_IRSTEA]SEDYVINDes signes de modifications de la biodiversité terrestre, aquatique et marine, attribuables aux changements graduels induits par le changement climatique, sont d'ores et déjà observables. La biodiversité est affectée directement par la modification de la température et de la pluviométrie, à laquelle s'ajoute l'acidification des eaux en domaine marin. Protéger les espèces et les écosystèmes impose de réduire les pressions qui diminuent leur résilience : fragmentation des milieux naturels, artificialisation des sols, etc. Le groupe insiste sur le rôle des effets indirects à moyen terme, qui pourraient être au moins aussi importants (par exemple, la reconstruction des infrastructures littorales sur les espaces naturels en arrière des côtes). Il est donc essentiel d'analyser systématiquement les effets croisés des impacts du changement climatique d'une part et des adaptations spontanées ou planifiées d'autre part, afin de prévenir les conséquences négatives pour la biodiversité. L'évaluation des services rendus par la biodiversité pour certains types d'occupation du territoire les estime à 900¤/ha/an pour les forêts et 300¤/ha/an pour les prairies, dans un récent rapport du Centre d'Analyse Stratégique, ce qui permet de cerner les enjeux économiques. Des impacts négatifs sont révélés par cette approche, appliquée aux écosystèmes coralliens et aux services non-marchands fournis par la forêt. Plus globalement, des pertes économiques significatives liées à la diminution voire la disparition de services de production (forêts de hêtre du Sud et de l'Ouest par exemple) et de régulation (tels que le stockage du carbone, la prévention des crues et des inondations, la régulation de l'érosion) sont à envisager à des niveaux accrus à la fin du siècle. L'Outre-mer est particulièrement fragile du fait des impacts sur les récifs coralliens, les forêts tropicales et les nombreuses espèces endémiques. Grâce à une gouvernance des politiques d'adaptation conduites à des échelles spatiales pertinentes avec le plus grand nombre d'acteurs et à une politique intégrée pour favoriser les approches transversales et systémiques, ces pertes pourront être limitées. Enfin, la préservation d'écosystèmes naturels choisis peut constituer une action d'adaptation en tant que telle pour un maximum d'espèces et de milieux