Schistosome-induced portacaval haemodynamic changes in Rattus rattus are associated with translocation of adult worms to the lungs

The presence of naturally portacaval shunts has been investigated in the vasculature of normal and Schistosoma mansoni-infected Rattus rattus. Using the technique of injecting Polystyrene microspheres in the superior mesenteric vein, we demonstrated that the presence of adult schistosomes in the lungs of R. rattus was not due to an innate anomaly of the rat vasculature but resulted from the formation of portacaval shunts during infection. In rats harbouring a bisexual infection, microspheres were only detected in the lungs from week 7. The development and increasing size of the shunts were maximal between weeks 7 and 10 and coincident with the translocation of adult worms from the portal tract to the lungs. At weeks 20–25, only 1–2% of the microspheres were recovered from the lungs, suggesting that the portacaval anastomoses have regressed due to reduction in portal hypertension after worm translocation. R. rattus with a male-only schistosome infection harboured adult worms in the lungs, indicating that the development of shunts does not solely depend upon egg deposition in the liver to generate hypertension. The relationships between the presence of the schistosomes in the lungs, the portacaval shunting and the resistance to reinfection is discussed

Characterization, cloning and immunogenicity of antigens released by transforming cercariae of Schistosoma mansoni

A schistosome infection is initiated when the parasite penetrates the skin of a susceptible host. Relatively large quantities of protein are released by transforming cercariae compared to later larval stages. This represents the first parasite material to which the host's immune system is exposed, yet little is known about the proteins which are released during the first few hours post-transformation. We have shown that antiserum raised against such molecules was capable of imparting protection against a schistosome challenge infection upon passive transfer to naïve mice. By screening a cercarial cDNA library with this serum, 38 positive clones were identified. Sequence analysis showed these to represent 8 different molecules which included Schistosoma mansoni 21·7 kDa antigen, calcium-binding-protein and the vaccine candidate glutathione S-transferase (Sm28GST). In addition, 5 clones were isolated, 1 of which had significant homology to many cytochrome C proteins, another with leukocyte elastase inhibitors and 3 which represented novel molecules. Four clones were expressed in a prokaryotic high-level expression vector, sera produced against each purified recombinant protein and used subsequently to probe Western blots and parasite sections. The leukocyte elastase inhibitor homologue and 2 unknowns induced significant proliferation by lymph node cells recovered from mice vaccinated with irradiated cercariae. More strikingly, the 2 novel proteins stimulated very high levels of interferon [gamma] (IFN[gamma]) secretion both by lymph node cells and those recovered by broncho-alveolar lavage from the lungs of vaccinated mice. Such results will be discussed in the context of vaccine development

Antibodies to glycans dominate the host response to schistosome larvae and eggs: Is their role protective or subversive?

Multiple exposures of chimpanzees to the radiation-attenuated schistosome vaccine provoked a strong parasite-specific cellular and humoral immune response. Specific IgM and IgG were directed mainly against glycans on antigens released by cercariae; these were also cross-reactive with soluble antigens from larvae, adult worms, and eggs. Egg deposition was the major antigenic stimulus after challenge of vaccinated and control chimpanzees with normal parasites, eliciting strong antiglycan responses to egg secretions. Glycan epitopes recognized included LacdiNAc, fucosylated LacdiNAc, LewisX (weakly), and those on keyhole limpet hemocyanin. Antibodies to peptide epitopes became prominent only during the chronic phase of infection, as glycan-specific IgM and IgG decreased. Because of their intensity and cross-reactivity, the antiglycan responses resulting from infection could be a smoke screen to subvert the immune system away from more vulnerable larval peptide epitopes. Their occurrence in humans might explain the long time required for antischistosome immunity to build up after infection

Chitinase and Fizz family members are a generalized feature of nematode infection with selective Upregulation of Ym1 and F10.1 by antigen-presenting cells

Ym1 and Fizz1 are secreted proteins that have been identified in a variety of Th2-mediated inflammatory settings. We originally found Ym1 and Fizz1 as highly expressed macrophage genes in a Brugia malayi infection model. Here, we show that their expression is a generalized feature of nematode infection and that they are induced at the site of infection with both the tissue nematode Litomosoides sigmodontis and the gastrointestinal nematode Nippostrongylus brasiliensis. At the sites of infection with N. brasiliensis, we also observed induction of other chitinase and Fizz family members (ChaFFs): acidic mammalian chitinase (AMCase) and Fizz2. The high expression of both Ym1 and AMCase in the lungs of infected mice suggests that abundant chitinase production is an important feature of Th2 immune responses in the lung. In addition to expression of ChaFFs in the tissues, Ym1 and Fizz1 expression was observed in the lymph nodes. Expression both in vitro and in vivo was restricted to antigen-presenting cells, with the highest expression in B cells and macrophages. ChaFFs may therefore be important effector or wound-repair molecules at the site of nematode infection, with potential regulatory roles for Ym1 and Fizz1 in the draining lymph nodes

Parameters of the attenuated schistosome vaccine evaluated in the olive baboon

Five exposures of baboons to the attenuated schistosome vaccine gave greater protection than three exposures, but this attenuation was not sustained when challenge was delayed. Within the scope of the data collected, fecal egg counts and circulating antigen levels did not accurately predict the observed worm burdens. Levels of immunoglobulin G at challenge correlated best with protection, but there was little evidence of a recall response

Universality and Critical Phenomena in String Defect Statistics

The idea of biased symmetries to avoid or alleviate cosmological problems caused by the appearance of some topological defects is familiar in the context of domain walls, where the defect statistics lend themselves naturally to a percolation theory description, and for cosmic strings, where the proportion of infinite strings can be varied or disappear entirely depending on the bias in the symmetry. In this paper we measure the initial configurational statistics of a network of string defects after a symmetry-breaking phase transition with initial bias in the symmetry of the ground state. Using an improved algorithm, which is useful for a more general class of self-interacting walks on an infinite lattice, we extend the work in \cite{MHKS} to better statistics and a different ground state manifold, namely $\R P^2$, and explore various different discretisations. Within the statistical errors, the critical exponents of the Hagedorn transition are found to be quite possibly universal and identical to the critical exponents of three-dimensional bond or site percolation. This improves our understanding of the percolation theory description of defect statistics after a biased phase transition, as proposed in \cite{MHKS}. We also find strong evidence that the existence of infinite strings in the Vachaspati Vilenkin algorithm is generic to all (string-bearing) vacuum manifolds, all discretisations thereof, and all regular three-dimensional lattices.Comment: 62 pages, plain LaTeX, macro mathsymb.sty included, figures included. also available on http://starsky.pcss.maps.susx.ac.uk/groups/pt/preprints/96/96011.ps.g

EchidnaCSI: engaging the public in research and conservation of the short-beaked echidna

The short-beaked echidna is an iconic Australian animal and the most-widespread native mammal, inhabiting diverse environments. The cryptic nature of echidnas has limited research into their ecology in most areas; however, from the well-researched and endangered Kangaroo Island echidna population, we understand that the threats include habitat loss, roads, and invasive species. To obtain more information about echidnas Australia-wide, we established the Echidna Conservation Science Initiative (EchidnaCSI) citizen science project. EchidnaCSI calls on members of the public to submit photographs of wild echidnas and learn to identify and collect echidna scats for molecular analysis. To facilitate participation, we developed a smartphone application as well as ongoing social and traditional media activities and community events. In 3 y, more than 9,000 members of the public have downloaded the EchidnaCSI app, collecting 400 scats and submitting over 8,000 sightings of echidnas from across Australia. A subset of submitted scat samples were subjected to DNA extraction and PCR, which validated the approach of using citizen science for scat collection and viability for molecular analysis. To assess the impact of the project through public participation, we surveyed our participants (n = 944) to understand their demographics and motivations for engagement. Survey results also revealed that EchidnaCSI served as a gateway into citizen science more generally for many participants. EchidnaCSI demonstrates the potential for using citizen science approaches to collect high-quality data and material from a cryptic species over a very large geographic area and the considerable engagement value of citizen science research.Tahlia Perry, Alan Stenhouse, Isabella Wilson, Imma Perfetto, Michael W. McKelvey, Michelle Coulson, Rachel A. Ankeny, Peggy D. Rismiller, and Frank Grützne

Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6,809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA

The ecogenetic link between demography and evolution : can we bridge the gap between theory and data?

Calls to understand the links between ecology and evolution have been common for decades. Population dynamics, i.e. the demographic changes in populations, arise from life history decisions of individuals and thus are a product of selection, and selection, on the contrary, can be modified by such dynamical properties of the population as density and stability. It follows that generating predictions and testing them correctly requires considering this ecogenetic feedback loop whenever traits have demographic consequences, mediated via density dependence (or frequency dependence). This is not an easy challenge, and arguably theory has advanced at a greater pace than empirical research. However, theory would benefit from more interaction between related fields, as is evident in the many near-synonymous names that the ecogenetic loop has attracted. We also list encouraging examples where empiricists have shown feasible ways of addressing the question, ranging from advanced data analysis to experiments and comparative analyses of phylogenetic data