Temperature affects the size-structure of phytoplankton communities in the ocean

The strong inverse correlation between resource availability and temperature in the ocean poses a challenge to determine the relative effect of these two variables on the size-structure of natural phytoplankton communities. Marañón et al (2012) compiled a dataset of concurrent temperature and resource level proxies that they claim disentangled the effect of temperature from that of resource supply. They concluded that the hypothesis that temperature per se plays a direct role in controlling phytoplankton size structure should be rejected. But our reanalysis of their data reaches a very different conclusion and suggests that they failed to separate the effects of temperature from the effects of resources. Although we obviously concur with Marañón et al (2012) in the long-known predominance of small phytoplankton cells under oligotrophic conditions, from our point of view this should not deter us from considering temperature as an important explanatory variable at a global scale since we show that, for the vast oligotrophic areas of the world's oceans where chlorophyll concentrations are below <1 μg L-1 temperature explains a high proportion of the variability in the size distribution of phytoplankton communities, a variability that can not be explained on the basis of the resource level proxies advocated by Marañón et al. (2012).Versión del editor3,385

CAF01 Potentiates Immune Responses and Efficacy of an Inactivated Influenza Vaccine in Ferrets

Trivalent inactivated vaccines (TIV) against influenza are given to 350 million people every year. Most of these are non-adjuvanted vaccines whose immunogenicity and protective efficacy are considered suboptimal. Commercially available non-adjuvanted TIV are known to elicit mainly a humoral immune response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6′-dibehenate, CAF01) was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different experimental vaccine candidates. In this study, we compared the immune responses in ferrets to a commercially available TIV with the responses to the same vaccine mixed with the CAF01 adjuvant. Two recently circulating H1N1 viruses were used as challenge to test the vaccine efficacy. CAF01 improved the immunogenicity of the vaccine, with increased influenza-specific IgA and IgG levels. Additionally, CAF01 promoted cellular-mediated immunity as indicated by interferon-gamma expressing lymphocytes, measured by flow cytometry. CAF01 also enhanced the protection conferred by the vaccine by reducing the viral load measured in nasal washes by RT-PCR. Finally, CAF01 allowed for dose-reduction and led to higher levels of protection compared to TIV adjuvanted with a squalene emulsion. The data obtained in this human-relevant challenge model supports the potential of CAF01 in future influenza vaccines

De-Novo Transcriptome Sequencing of a Normalized cDNA Pool from Influenza Infected Ferrets

The ferret is commonly used as a model for studies of infectious diseases. The genomic sequence of this animal model is not yet characterized, and only a limited number of fully annotated cDNAs are currently available in GenBank. The majority of genes involved in innate or adaptive immune response are still lacking, restricting molecular genetic analysis of host response in the ferret model. To enable de novo identification of transcriptionally active ferret genes in response to infection, we performed de-novo transcriptome sequencing of animals infected with H1N1 A/California/07/2009. We also included splenocytes induced with bacterial lipopolysaccharide to allow for identification of transcripts specifically induced by Gram-negative bacteria. We pooled and normalized the cDNA library in order to delimit the risk of sequencing only highly expressed genes. While normalization of the cDNA library removes the possibility of assessing expression changes between individual animals, it has been shown to increase identification of low abundant transcripts. In this study, we identified more than 19000 partial ferret transcripts, including more than 1000 gene orthologs known to be involved in the innate and the adaptive immune response

A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis

Objective. To evaluate the safety and efficacy of infliximab in the treatment of juvenile rheumatoid arthritis (JRA). Methods. This was an international, multicenter, randomized, placebo-controlled, double-blind study. One hundred twenty-two children with persistent polyarticular JRA despite prior, methotrexate (MTX) therapy were randomized to receive infliximab or placebofor 14 weeks, after which all children received infliximab through week 44. Patients received MTX plus infliximab 3 mg/kg through week 44, or MTX plus placebo for 14 weeks followed by MTX plus infliximab 6 mg/kg through week 44. Results. Although a higher proportion of patients in the 3 mg/kg infliximab group than in the placebo group had achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) criteria for improvement at week 14 (63.8% and 49.2%, respectively), the between-group difference in this primary efficacy end point was not statistically significant (P = 0.12). By week 16, after the crossover from placebo to infliximab 6 mg/kg when all patients were receiving infliximab, an ACR Pedi 30 response was achieved in 73.2% of all patients. By week 52, ACR Pedi 50 and ACR Pedi 70 responses had been reached in 69.6% and 51.8%, respectively, of patients. Infliximab was generally well tolerated, but the safety profile of infliximab 3 mg/kg appeared less favorable than that of infliximab 6 mg/kg, with more frequent occurrences of serious adverse events, infusion reactions, antibodies to infliximab, and newly induced antinuclear antibodies and antibodies to double-stranded DNA observed with the 3 mg/kg dose. Conclusion. While infliximab at 3 mg/kg and 6 mg/kg showed durable efficacy at I year, achievement of the primary efficacy end point at 3 months did not differ significantly between infliximab-treated and placebo-treated patients. Safety data indicated that the 6-mg/kg dose may provide a more favorable risk/benefit profile. These results warrant further investigation in children with JRA