Adjuvant-free immunization with hemagglutinin-Fc fusion proteins as an approach to influenza vaccines

The hemagglutinins (HAs) of human H1 and H3 influenza viruses and avian H5 influenza virus were produced as recombinant fusion proteins with the human immunoglobulin Fc domain. Recombinant HA-human immunoglobulin Fc domain (HA-HuFc) proteins were secreted from baculovirus-infected insect cells as glycosylated oligomer HAs of the anticipated molecular mass, agglutinated red blood cells, were purified on protein A, and were used to immunize mice in the absence of adjuvant. Immunogenicity was demonstrated for all subtypes, with the serum samples demonstrating subtype-specific hemagglutination inhibition, epitope specificity similar to that seen with virus infection, and neutralization. HuFc-tagged HAs are potential candidates for gene-to-vaccine approaches to influenza vaccination.

The economic theory of international business: a supply chain perspective

This paper proposes a way of addressing unresolved issues in international business theory by modelling the multinational enterprise as a coordinator of supply chains. It identifies a new market seeking strategy that is an alternative to conventional strategies such as exporting, licensing and FDI, and analyses the conditions under which it will be adopted by firms. The new strategy involves the off-shoring of production and the out-sourcing of R&D, and is implemented through co-operation between a source country firm and a host country firm.

A proposal for a new scenario framework to support research and assessment in different climate research communities

In this paper, we propose a scenario framework that could provide a scenario “thread” through the different climate research communities (climate change – vulnerability, impact, and adaptation (VIA) and mitigation) in order to provide assessment of mitigation and adaptation strategies and other VIA challenges. The scenario framework is organised around a matrix with two main axes: radiative forcing levels and socio-economic conditions. The radiative forcing levels (and the associated climate signal) are described by the new Representative Concentration Pathways. The second axis, socio-economic developments, comprises elements that affect the capacity for mitigation and adaptation, as well as the exposure to climate impacts. The proposed scenarios derived from this framework are limited in number, allow for comparison across various mitigation and adaptation levels, address a range of vulnerability characteristics, provide information across climate forcing and vulnerability states and span a full century time scale. Assessments based on the proposed scenario framework would strengthen cooperation between integrated-assessment modelers, climate modelers and vulnerability, impact and adaptation researchers, and most importantly, facilitate the development of more consistent and comparable research within and across communities.

The effect of environmental change on human migration

The influence of the environment and environmental change is largely unrepresented in standard theories of migration, whilst recent debates on climate change and migration focus almost entirely on displacement and perceive migration to be a problem. Drawing on an increasing evidence base that has assessed elements of the influence of the environment on migration, this paper presents a new framework for understanding the effect of environmental change on migration. The framework identifies five families of drivers which affect migration decisions: economic, political, social, demographic and environmental drivers. The environment drives migration through mechanisms characterised as the availability and reliability of ecosystem services and exposure to hazard. Individual migration decisions and flows are affected by these drivers operating in combination, and the effect of the environment is therefore highly dependent on economic, political, social and demographic context. Environmental change has the potential to affect directly the hazardousness of place. Environmental change also affects migration indirectly, in particular through economic drivers, by changing livelihoods for example, and political drivers, through affecting conflicts over resources, for example. The proposed framework, applicable to both international and internal migration, emphasises the role of human agency in migration decisions, in particular the linked role of family and household characteristics on the one hand, and barriers and facilitators to movement on the other in translating drivers into actions. The framework can be used to guide new research, assist with the evaluation of policy options, and provide a context for the development of scenarios representing a range of plausible migration futures.

Migration and global environmental change

Introduction to a special issue on migration and global environmental change

Policy: the perils of doing nothing

A lack of buy-in by the United States arguably represents the greatest obstacle to tackling climate change. A major new report urges America to take action to cut emissions and begin adapting to climate change.

Genetic predisposition to type 2 diabetes is associated with impaired insulin secretion but does not modify insulin resistance or secretion in response to an intervention to lower dietary saturated fat

Genome-wide association studies have identified SNPs reproducibly associated with type 2 diabetes (T2D). We examined the effect of genetic predisposition to T2D on insulin sensitivity and secretion using detailed phenotyping in overweight individuals with no diagnosis of T2D. Furthermore, we investigated whether this genetic predisposition modifies the responses in beta-cell function and insulin sensitivity to a 24-week dietary intervention. We genotyped 25 T2D-associated SNPs in 377 white participants from the RISCK study. Participants underwent an IVGTT prior to and following a dietary intervention that aimed to lower saturated fat intake by replacement with monounsaturated fat or carbohydrate. We composed a genetic predisposition score (T2D-GPS) by summing the T2D risk-increasing alleles of the 25 SNPs and tested for association with insulin secretion and sensitivity at baseline, and with the change in response to the dietary intervention. At baseline, a higher T2D-GPS was associated with lower acute insulin secretion (AIRg 4% lower/risk allele, P = 0.006) and lower insulin secretion for a given level of insulin sensitivity, assessed by the disposition index (DI 5% lower/risk allele, P = 0.002), but not with insulin sensitivity (Si). T2D-GPS did not modify changes in insulin secretion, insulin sensitivity or the disposition index in response to the dietary interventions to lower saturated fat. Participants genetically predisposed to T2D have an impaired ability to compensate for peripheral insulin resistance with insulin secretion at baseline, but this does not modify the response to a reduction in dietary saturated fat through iso-energetic replacement with carbohydrate or monounsaturated fat.

The type and quantity of dietary fat and carbohydrate alter faecal microbiome and short-chain fatty acid excretion in a metabolic syndrome ‘at-risk’ population syndrome.

An obese-type human microbiota with an increased Firmicutes:Bacteroidetes ratio has been described that may link the gut microbiome with obesity and metabolic syndrome (MetS) development. Dietary fat and carbohydrate are modifiable risk factors that may impact on MetS by altering the human microbiome composition. We determined the effect of the amount and type of dietary fat and carbohydrate on faecal bacteria and short chain fatty acid (SCFA) concentrations in people ‘at risk’ of MetS.

PPARγ2 gene Pro12Ala and PPARα gene Leu162Val single nucleotide polymorphisms interact with dietary intake of fat in determination of plasma lipid concentrations

Background/Aims: The peroxisome proliferator-activated receptors (PPARs) are transcriptional regulators of lipid metabolism, activated by unsaturated fatty acids. We investigated independent and interactive effects of PPARγ2 gene PPARG Pro12Ala (rs1801282) andPPARαgene PPARA Leu162Val (rs1800206) genotypes with dietary intake of fatty acids on concentrations of plasma lipids in subjects of whom 47.5% had metabolic syndrome. Methods: The RISCK study is a parallel design, randomised controlled trial. Plasma lipids were quantified at baseline after a 4-week high saturated fatty acids diet and after three parallel 24-week interventions with reference (high saturated fatty acids), high monounsaturated fatty acids and low-fat diets. Single nucleotide polymorphisms were genotyped in 466 subjects. Results: At baseline, the PPARG Ala12allele was associated with increased plasma total cholesterol (n = 378; p = 0.04), LDL cholesterol (p = 0.05) and apoB (p =0.05) after adjustment for age, gender and ethnicity. At baseline, PPARA Leu162Val × PPARG Pro12Ala genotype interaction did not significantly influence plasma lipid concentrations. After dietary intervention, gene-gene interaction significantly influenced LDL cholesterol (p =0.0002) and small dense LDL as a proportion of LDL (p = 0.005) after adjustments. Conclusions: Interaction between PPARG Pro12Ala and PPARA Leu162Valgenotypes may influence plasma LDL cholesterol concentration and the proportion as small dense LDL after a high monounsaturated fatty acids diet.