Angiotensin receptors and β-catenin regulate brain endothelial integrity in malaria

Cerebral malaria is characterized by cytoadhesion of Plasmodium falciparum–infected red blood cells (Pf-iRBCs) to endothelial cells in the brain, disruption of the blood-brain barrier, and cerebral microhemorrhages. No available antimalarial drugs specifically target the endothelial disruptions underlying this complication, which is responsible for the majority of malaria-associated deaths. Here, we have demonstrated that ruptured Pf-iRBCs induce activation of β-catenin, leading to disruption of inter–endothelial cell junctions in human brain microvascular endothelial cells (HBMECs). Inhibition of β-catenin–induced TCF/LEF transcription in the nucleus of HBMECs prevented the disruption of endothelial junctions, confirming that β-catenin is a key mediator of P. falciparum adverse effects on endothelial integrity. Blockade of the angiotensin II type 1 receptor (AT1) or stimulation of the type 2 receptor (AT2) abrogated Pf-iRBC–induced activation of β-catenin and prevented the disruption of HBMEC monolayers. In a mouse model of cerebral malaria, modulation of angiotensin II receptors produced similar effects, leading to protection against cerebral malaria, reduced cerebral hemorrhages, and increased survival. In contrast, AT2-deficient mice were more susceptible to cerebral malaria. The interrelation of the β-catenin and the angiotensin II signaling pathways opens immediate host-targeted therapeutic possibilities for cerebral malaria and other diseases in which brain endothelial integrity is compromised.

Toxoplasma gondii seropositive rates of animals living on Svalbard

Samples (blood or tissue fluid) from 594 arctic foxes (Alopex lagopus), 390 Svalbard reindeer (Rangifer tarandus platyrhynchus), 361 sibling voles (Microtus rossiaemeridionalis), 17 walruses (Odobenus rosmarus), 149 barnacle geese (Branta leucopsis), 58 kittiwakes (Rissa tridactyla), and 27 glaucous gulls (Larus hyperboreus) from Svalbard and nearby waters were assayed for antibodies against Toxoplasma gondii using a direct agglutination test. The proportion of seropositive animals was 43% in arctic foxes, 7% in barnacle geese, and 6% (1 of 17) in walruses. There were no seropositive Svalbard reindeer, sibling voles, glaucous gulls, or kittiwakes. The prevalence in the arctic fox was relatively high compared to previous reports from canid populations. There are no wild felids in Svalbard and domestic cats are prohibited, and the absence of antibodies against T gondii among the herbivorous Svalbard reindeer and voles indicates that transmission of the parasite by oocysts is not likely to be an important mechanism in the Svalbard ecosystem. Our results suggest that migratory birds, such as the barnacle goose, may be the most important vectors bringing the parasite to Svalbard. In addition to transmission through infected prey and carrion, the age-seroprevalence profile in the fox population suggests that their infection levels are enhanced by vertical transmission.

Fatty acid composition of tissue samples from Arctic walruses (Odobenus rosmarus rosmarus) and their prey

Blubber biopsies were collected from 18 adult male walruses from Svalbard, Norway. The biopsies were taken vertically through the skin and the entire blubber layer down to, but not including, the muscle layer. Fatty acid (FA) compositions of inner blubber, outer blubber and dermis of the walruses and of potential prey organisms were determined. The three layers differed significantly from one another in FA composition. Generally, the inner blubber contained more long-chained monounsaturated, saturated and polyunsaturated FAs, while the outer blubber and dermis contained more short-chained monounsaturated FAs. This stratification is similar to what has been observed in other marine mammal species. However, differences between layers were less pronounced than in most other species, possibly because the extremely thick overlying dermis of walruses provides an insulating shield, which affects the FA composition of the outer blubber. The FA composition of the potential prey organisms was different from that of the blubber of the walruses, although more similar to the inner blubber than to the outer blubber or dermis. FA composition in the inner blubber was not significantly correlated with age (assessed by tusk volume), while the FA composition of the outer blubber and dermis were significantly correlated with age.

(Table 2) Age determination of harp seals (Pagophilus groenlandicus) from the Barents Sea - comparison of methods

Lower jaws (containing the teeth), eyes, and skin samples were collected from harp seals (Pagophilus groenlandicus) in the southeastern Barents Sea for the purpose of comparing age estimates obtained by 3 different methods, the traditional technique of counting growth layer groups (GLGs) in teeth and 2 novel approaches, aspartic acid racemization (AAR) in eye lens nuclei and telomere sequence analyses as a proxy for telomere length. A significant correlation between age estimates obtained using GLGs and AAR was found, whereas no correlation was found between GLGs and telomere length. An AAR rate (k Asp) of 0.00130/year ± 0.00005 SE and a D-enantiomer to L-enantiomer ratio at birth (D/L 0 value) of 0.01933 ± 0.00048 SE were estimated by regression of D/L ratios against GLG ages from 25 animals (12 selected teeth that had high readability and 13 known-aged animals). AAR could prove to be useful, particularly for ageing older animals in species such as harp seals where difficulties in counting GLGs tend to increase with age. Age estimation by telomere length did not show any correlation with GLG ages and is not recommended for harp seals.

Stable isotope record, calcium carbonate conentrations, and sea surface temperture reconstructions of sediment cores from the North Atlantic

We analyze five high-resolution time series spanning the last 1.65 m.y.: benthic foraminiferal delta18O and delta13O, percent CaCO3, and estimated sea surface temperature (SST) at North Atlantic Deep Sea Drilling Project site 607 and percent CaCO3 at site 609. Each record is a multicore composite verified for continuity by splicing among multiple holes. These climatic indices portray changes in northern hemisphere ice sheet size and in North Atlantic surface and deep circulation. By tuning obliquity and precession components in the delta18O record to orbital variations, we have devised a time scale (TP607) for the entire Pleistocene that agrees in age with all K/Ar-dated magnetic reversals to within 1.5%. The Brunhes time scale is taken from Imbrie et al. [1984], except for differences near the stage 17/16 transition (0.70 to 0.64 Ma). All indicators show a similar evolution from the Matuyama to the Brunhes chrons: orbital eccentricity and precession responses increased in amplitude; those at orbital obliquity decreased. The change in dominance from obliquity to eccentricity occurred over several hundred thousand years, with fastest changes around 0.7 to 0.6 Ma. The coherent, in-phase responses of delta18O, delta13O, CaCO3 and SST at these rhythms indicate that northern hemisphere ice volume changes have controlled most of the North Atlantic surface-ocean and deep-ocean responses for the last 1.6 m.y. The delta13O, percent CaCO3, and SST records at site 607 also show prominent changes at low frequencies, including a prominent long-wavelength oscillation toward glacial conditions that is centered between 0.9 and 0.6 Ma. These changes appear to be associated neither with orbital forcing nor with changes in ice volume.

(Table 1) Age, sex, length, girth and blubber thickness and content of ringed seals (Pusa hispida) in Kongsfjorden in 2000

This study of vertical fatty acid profiles, based on analysis of 58 fatty acids sampled at 3-mm intervals throughout the blubber column of a model marine mammal, the ringed seal (Pusa hispida), revealed three chemically distinct layers. The average depths of the outer and inner layers were quite consistent (~1.5 and ~1 cm, respectively). Consequently, the middle layer varied greatly in thickness, from being virtually absent in the thinnest animals to 2.5 cm thick in the fattest. The relative consistencies of the thickness and composition of the layers as well as the nature of the fatty acids making up each layer support the generally assumed function of the various layers: (1) the outer layer is primarily structural and thermoregulatory, (2) the inner layer is metabolically active with a fatty acid composition that is strongly affected by recent/ongoing lipid mobilization/deposition, and (3) the middle layer is a storage site that contracts and expands with food availability/consumption. The remarkable dynamics of the middle layer along with the discrete pattern of stratification found in the vertical fatty acid profiles have important implications for methodological sampling design for studies of foraging ecology and toxicology based on analyses of blubber of marine mammals.

Rethinking Care Through Social Reproduction: Articulating Circuits of Migration

Care has come to dominate much feminist research on globalized migrations and the transfer of labor from the South to the North, while the older concept of reproduction had been pushed into the background but is now becoming the subject of debates on the commodification of care in the household and changes in welfare state policies. This article argues that we could achieve a better understanding of the different modalities and trajectories of care in the reproduction of individuals, families, and communities, both of migrant and nonmigrant populations by articulating the diverse circuits of migration, in particular that of labor and the family. In doing this, I go back to the earlier North American writing on racialized minorities and migrants and stratified social reproduction. I also explore insights from current Asian studies of gendered circuits of migration connecting labor and marriage migrations as well as the notion of global householding that highlights the gender politics of social reproduction operating within and beyond households in institutional and welfare architectures. In contrast to Asia, there has relatively been little exploration in European studies of the articulation of labor and family migrations through the lens of social reproduction. However, connecting the different types of migration enables us to achieve a more complex understanding of care trajectories and their contribution to social reproduction.

A change in behaviour — getting the balance right for research and policy.

Behaviour change interventions offer clinical pharmacists many opportunities to optimise the use of medicines. ‘MINDSPACE’ is a framework used by a Government-affiliated organisation in the United Kingdom to communicate an approach to changing behaviour through policy. The Theoretical Domains Framework (TDF) organises constructs of psychological theories that are most relevant to behaviour change into 14 domains. Both frameworks offer a way of identifying what drives a change in behaviour, providing a target for an intervention. This article aims to compare and contrast MINDSPACE and the TDF, and serves to inform pharmacy practitioners about the potential strengths and weaknesses of using either framework in a clinical pharmacy context. It appears that neither framework can deliver evidence-based interventions that can be developed and implemented with the pace demanded by policy and practice-based settings. A collaborative approach would ensure timely development of acceptable behaviour change interventions that are grounded in evidence.

D5.1 – Scenario Arrangement Document – round 1

This deliverable is a confirmation and update of 'D5.5 - First Version Scenario Arrangement Document – round 1' after a revisions with game developers. It outlines the implementation plan for each of the first-round studies of the RAGE pilots. The main goal of these pilots is to perform a small-scale test of the RAGE games with end-users and intermediary stakeholders in five different non-leisure domains to guide the further development of the games for the final validation studies.

The Copenhagen Consensus Conference 2016: children, youth, and physical activity in schools and during leisure time

From 4 to 7 April 2016, 24 researchers from 8 countries and from a variety of academic disciplines gathered in Snekkersten, Denmark, to reach evidence-based consensus about physical activity in children and youth, that is, individuals between 6 and 18 years. Physical activity is an overarching term that consists of many structured and unstructured forms within school and out-of-school-time contexts, including organised sport, physical education, outdoor recreation, motor skill development programmes, recess, and active transportation such as biking and walking. This consensus statement presents the accord on the effects of physical activity on children's and youth's fitness, health, cognitive functioning, engagement, motivation, psychological well-being and social inclusion, as well as presenting educational and physical activity implementation strategies. The consensus was obtained through an iterative process that began with presentation of the state-of-the art in each domain followed by plenary and group discussions. Ultimately, Consensus Conference participants reached agreement on the 21-item consensus statement.

Monitoring Infection Risk for Air and Soil Borne Fungal Plant Pathogens using Antibody and DNA Techniques and Mathematical Models describing Environmental Parameters

Economic losses resulting from disease development can be reduced by accurate and early detection of plant pathogens. Early detection can provide the grower with useful information on optimal crop rotation patterns, varietal selections, appropriate control measures, harvest date and post harvest handling. Classical methods for the isolation of pathogens are commonly used only after disease symptoms. This frequently results in a delay in application of control measures at potentially important periods in crop production. This paper describes the application of both antibody and DNA based systems to monitor infection risk of air and soil borne fungal pathogens and the use of this information with mathematical models describing risk of disease associated with environmental parameters.