Interactive effects of social environment, age and sex on immune responses in Drosophila melanogaster

Social environments have been shown to have multiple effects on individual immune responses. For example, increased social contact might signal greater infection risk and prompt a prophylactic upregulation of immunity. This differential investment of resources may in part explain why social environments affect ageing and lifespan. Our previous work using Drosophila melanogaster showed that single-sex social contact reduced lifespan for both sexes. Here, we assess how social interactions (isolation or contact) affect susceptibility to infection, phagocytotic activity and expression of a subset of immune and stress related genes in young and old flies of both sexes. Social contact had a neutral, or even improved, effect on post-infection lifespan in older flies and reduced the expression of stress response genes in females, however it reduced phagocytotic activity. Overall the effects of social environment were complex and largely subtle, and do not indicate a consistent effect. Together, these findings indicate that social contact in D. melanogaster does not have a predictable impact on immune responses and does not simply trade-off immune investment with lifespan

Sex-specific effects of social isolation on ageing in Drosophila melanogaster

Social environments can have a major impact on ageing profiles in many animals. However, such patterns in variation in ageing and their underlying mechanisms are not well understood, particularly because both social contact and isolation can be stressful. Here, we use Drosophila melanogaster fruitflies to examine sex-specific effects of social contact. We kept flies in isolation versus same-sex pairing throughout life, and measured actuarial (lifespan) and functional senescence (declines in climbing ability). To investigate underlying mechanisms, we determined whether an immune stress (wounding) interacted with effects of social contact, and assessed behaviours that could contribute to differences in ageing rates. Pairing reduced lifespan for both sexes, but the effect was greater for males. In contrast, for females pairing reduced the rate of decline in climbing ability, whereas for males, pairing caused more rapid declines with age. Wounding reduced lifespan for both sexes, but doubled the negative effect of pairing on male lifespan. We found no evidence that these effects are driven by behavioural interactions. These findings suggest that males and females are differentially sensitive to social contact, that environmental stressors can impact actuarial and functional senescence differently, and that these effects can interact with environmental stressors, such as immune challenges

TLR-4 ligation of dendritic cells is sufficient to drive pathogenic T cell function in experimental autoimmune encephalomyelitis

<p>Abstract</p> <p>Background</p> <p>Experimental autoimmune encephalomyelitis (EAE) depends on the initial activation of CD4⁺ T cells responsive to myelin autoantigens. The key antigen presenting cell (APC) population that drives the activation of naïve T cells most efficiently is the dendritic cell (DC). As such, we should be able to trigger EAE by transfer of DC that can present the relevant autoantigen(s). Despite some sporadic reports, however, models of DC-driven EAE have not been widely adopted. We sought to test the feasibility of this approach and whether activation of the DC by toll-like receptor (TLR)-4 ligation was a sufficient stimulus to drive EAE.</p> <p>Findings</p> <p>Host mice were seeded with myelin basic protein (MBP)-reactive CD4+ T cells and then were injected with DC that could present the relevant MBP peptide which had been exposed to lipopolysaccharide as a TLR-4 agonist. We found that this approach induced robust clinical signs of EAE.</p> <p>Conclusions</p> <p>DC are sufficient as APC to effectively drive the differentiation of naïve myelin-responsive T cells into autoaggressive effector T cells. TLR-4-stimulation can activate the DC sufficiently to deliver the signals required to drive the pathogenic function of the T cell. These models will allow the dissection of the molecular requirements of the initial DC-T cell interaction in the lymphoid organs that ultimately leads to autoimmune pathology in the central nervous system.</p

Get Organised: The 'Do's' Preceding Successful Field Research

There is no shortage in the political science literature on field research regarding issues of research design, methodology, and data evaluation. Yet, the practical and organisational intricacies that precede successful fieldwork are frequently overlooked. This lack of methodical advice may be due to the impression that field research is highly contextual, and so case-specific that general guidelines, which apply to all field research endeavours alike, are inconceivable. While we acknowledge the organisational complexity of field research, we disagree with the notion that the preparatory dimension of fieldwork is by necessity unique for every undertaking. Rather, recommendations for common challenges that occur during the preparation and organisation phase of a field trip can be identified and formulated. Consequently, we present and discuss ten organisational ?do's? preceding successful field research. Current graduate students and future field researchers will regard these ten pointers as useful hints in the organisation of their own endeavour. While the list is by no means exhaustive, the ten recommendations will lower the organisational entry costs of aspiring field researchers, and enable them to hit the ground running when arriving in the field

Effect of Groundwater Pumping on Seawater Intrusion in Coastal Aquifers

Many aquifers around the globe are located in coastal areas and are thus subjected to the seawater intrusion phenomenon. The growth of population in coastal areas and the conjugate increase in human, agricultural, and industrial activities have imposed an increasing demand for freshwater. This increase in water demand is often covered by extensive pumping of fresh groundwater, causing subsequent lowering of the water table (or piezometric head) and upsetting the dynamic balance between freshwater and saline water bodies. The classical result of such a development is seawater intrusion. This paper presents a review for the seawater intrusion phenomenon in coastal aquifers. The effect of pumping activities on the seawater intrusion in the Nile Delta aquifer of Egypt is investigated. It was concluded that any additional pumping should be located in the middle Delta and avoided in the eastern and western sides of the Delta

Acquisition of naturally occurring antibody responses to recombinant protein domains of Plasmodium falciparum erythrocyte membrane protein 1

Background: Antibodies targeting variant antigens expressed on the surface of Plasmodium falciparum infected erythrocytes have been associated with protection from clinical malaria. The precise target for these antibodies is unknown. The best characterized and most likely target is the erythrocyte surface-expressed variant protein family Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). Methods: Using recombinant proteins corresponding to five domains of the expressed A4 var gene, A4 PfEMP1, the naturally occurring antibody response was assessed, by ELISA, to each domain in serum samples obtained from individuals resident in two communities of differing malaria transmission intensity on the Kenyan coast. Using flow cytometry, the correlation in individual responses to each domain with responses to intact A4-infected erythrocytes expressing A4 PfEMP1 on their surface as well as responses to two alternative parasite clones and one clinical isolate was assessed. Results: Marked variability in the prevalence of responses between each domain and between each transmission area was observed, as wasa strong correlation between age and reactivity with some but not all domains. Individual responses to each domain varied strikingly, with some individuals showing reactivity to all domains and others with no reactivity to any, this was apparent at all age groups. Evidence for possible cross-reactivity in responses to the domain DBL4γ was found. Conclusion: Individuals acquire antibodies to surface expressed domains of a highly variant protein. The finding of potential cross-reactivity in responses to one of these domains is an important initial finding in the consideration of potential vaccine targets

Equitable representation in councils: theory and an application to the United Nations Security Council

We analyze democratic equity in council voting games (CVGs). In a CVG, a voting body containing all members delegates decision-making to a (time-varying) subset of its members, as describes, e.g., the relationship between the United Nations General Assembly and the United Nations Security Council (UNSC). We develop a theoretical framework for analyzing democratic equitability in CVGs at both the country and region levels, and for different assumptions regarding preference correlation. We apply the framework to evaluate the equitability of the UNSC, and the claims of those who seek to reform it. We find that the individual permanent members are overrepresented by between 21.3 times (United Kingdom) and 3.8 times (China) from a country-level perspective, while from a region perspective Eastern Europe is the most heavily overrepresented region with more than twice its equitable representation, and Africa the most heavily underrepresented. Our equity measures do not preclude some UNSC members from exercising veto rights, however

The effects of a partitioned var gene repertoire of Plasmodium falciparum on antigenic diversity and the acquisition of clinical immunity

<p>Abstract</p> <p>Background</p> <p>The human malaria parasite <it>Plasmodium falciparum </it>exploits antigenic diversity and within-host antigenic variation to evade the host's immune system. Of particular importance are the highly polymorphic <it>var </it>genes that encode the family of cell surface antigens PfEMP1 (<it>Plasmodium falciparum </it>Erythrocyte Membrane Protein 1). It has recently been shown that in spite of their extreme diversity, however, these genes fall into distinct groups according to chromosomal location or sequence similarity, and that recombination may be confined within these groups.</p> <p>Methods</p> <p>This study presents a mathematical analysis of how recombination hierarchies affect diversity, and, by using simple stochastic simulations, investigates how intra- and inter-genic diversity influence the rate at which individuals acquire clinical immunity.</p> <p>Results</p> <p>The analysis demonstrates that the partitioning of the <it>var </it>gene repertoire has a limiting effect on the total diversity attainable through recombination and that the limiting effect is strongly influenced by the respective sizes of each of the partitions. Furthermore, by associating expression of one of the groups with severe malaria it is demonstrated how a small number of infections can be sufficient to protect against disease despite a seemingly limitless number of possible non-identical repertoires.</p> <p>Conclusion</p> <p>Recombination hierarchies within the <it>var </it>gene repertoire of <it>P. falciparum </it>have a severe effect on strain diversity and the process of acquiring immunity against clinical malaria. Future studies will show how the existence of these recombining groups can offer an evolutionary advantage in spite of their restriction on diversity.</p

Prevention of Birch Pollen-Related Food Allergy by Mucosal Treatment with Multi-Allergen-Chimers in Mice

Among birch pollen allergic patients up to 70% develop allergic reactions to Bet v 1-homologue food allergens such as Api g 1 (celery) or Dau c 1 (carrot), termed as birch pollen-related food allergy. In most cases, specific immunotherapy with birch pollen extracts does not reduce allergic symptoms to the homologue food allergens. We therefore genetically engineered a multi-allergen chimer and tested if mucosal treatment with this construct could represent a novel approach for prevention of birch pollen-related food allergy.BALB/c mice were poly-sensitized with a mixture of Bet v 1, Api g 1 and Dau c 1 followed by a sublingual challenge with carrot, celery and birch pollen extracts. For prevention of allergy sensitization an allergen chimer composed of immunodominant T cell epitopes of Api g 1 and Dau c 1 linked to the whole Bet v 1 allergen, was intranasally applied prior to sensitization.Intranasal pretreatment with the allergen chimer led to significantly decreased antigen-specific IgE-dependent β-hexosaminidase release, but enhanced allergen-specific IgG2a and IgA antibodies. Accordingly, IL-4 levels in spleen cell cultures and IL-5 levels in restimulated spleen and cervical lymph node cell cultures were markedly reduced, while IFN-γ levels were increased. Immunomodulation was associated with increased IL-10, TGF-β and Foxp3 mRNA levels in NALT and Foxp3 in oral mucosal tissues. Treatment with anti-TGF-β, anti-IL10R or anti-CD25 antibodies abrogated the suppression of allergic responses induced by the chimer.Our results indicate that mucosal application of the allergen chimer led to decreased Th2 immune responses against Bet v 1 and its homologue food allergens Api g 1 and Dau c 1 by regulatory and Th1-biased immune responses. These data suggest that mucosal treatment with a multi-allergen vaccine could be a promising treatment strategy to prevent birch pollen-related food allergy