Proteomic Identification of IPSE/alpha-1 as a Major Hepatotoxin Secreted by Schistosoma mansoni Eggs

The flatworm disease, schistosomiasis, is a major public health problem in sub-Saharan Africa, South America and East Asia. A hallmark of infection with Schistosoma mansoni is the immune response to parasite eggs trapped in the liver and other organs. This response involves an infiltration of cells that surround the parasite egg forming a “granuloma.” In mice deprived of T-cells, this granulomatous response is lacking, and toxic products released by eggs quickly cause liver damage and death. Thus the granulomata protect the host from toxic egg products. Only one hepatotoxic molecule, omega-1, has been described to date. We set out to identify other S. mansoni egg hepatotoxins using liver cells grown in culture. We first showed that live eggs, their secretions, and pure omega-1 are toxic. Using a physical separation technique to prepare fractions from whole egg secretions, we identified the presence of IPSE/alpha-1, a protein that is known to strongly influence the immune system. We showed that IPSE/alpha-1 is also hepatotoxic, and that toxicity of both omega-1 and IPSE/alpha-1 can be prevented by first mixing the proteins with specific neutralizing antibodies. Both proteins constitute the majority of hepatotoxicity released by eggs

Investigating FPIC: Can Peace-Culture Complement the Absence of Meaningful Consent? : An analysis of Indigenous Rights and Resource Extraction in Canada and Sweden

Despite the increase of policies, guidelines, and developments in international law, the actual recognition of Indigenous peoples’ rights remains at odds in the collaborative management of Indigenous territories. Numerous studies demonstrate that mining companies have been slow to adopt international legal developments, particularly regarding Free, Prior, and Informed Consent (FPIC). States and natural resource companies often fail to adequately consult with affected Indigenous communities and rarely seek their consent before exploiting natural resources. Sweden and Canada have, despite making generalized claims about ethical behavior, respect for human rights and recognition of historical injustices, legislations that promote resource companies’ to extractivism. The purpose of this study is to examine the interpretation and implementation of FPIC in a Swedish and Canadian context, using a comparative qualitative content analysis, based on purposive sampling.  In order to investigate conflicts between the Indigenous communities, local non-communities, the state itself, and commercial mining interests in Nunavut (Canada) and Laponia (Sweden), we aim to explore what interpretations and implementations of FPIC that exist between stakeholders and what mechanisms that are used for advocating interests. By doing this, we compare the contexts with focus on how corporate policies, practices and state narratives frequently diverge from FPIC principles. The study explores the possibility of integrating the concept of ‘the culture of Peace’ or ‘Peace-Culture’ with FPIC, which emphasizes peaceful approaches to conflict resolution. The themes are presented as ‘Indigenous knowledge’, ‘Asymmetric Power relations and Triangular conflict’, as well as ‘Persisting Post-Colonial Structures’. The study indicates that both Canada and Sweden lack effective mechanisms for obtaining consent from Indigenous communities and that the conflicts emerge from a combination of structural, cultural, and extractive violence. We further propose that fostering a Peace-Culture approach could enhance the implementation of Free, Prior, and Informed Consent (FPIC).

The susceptibility of adult schistosomes to immune attrition

Mouse infection models are described that demonstrate reduction of egg production in Schistosoma haematobium infections and both worm loss and reduced fecundity in S. bovis infections. Neither phenomenum could be shown in S. mansoni infected mice. The immunological basis for these anti-adult responses was inferred by comparison with infections in T-cell deprived mice and by the serum transfer of the ability to reduce a S. bovis worm burden into immunocompromised hosts. Vaccination with irradiation attenuated parasites was also shown to have consequences for the adults of a challenge infections of S. haematobium and S. bovis specifically. Prior vaccination resulted in an abrogation of the anti-fecundity and adult worm elimination that occurred in non-vaccinated similary infected mice. hese models are being used to define the targets and mechanisms involved in anti-adult attrition. A serological assay, quantitation of a circulating antigen (CAA) has been assessed for its ability to measure worm burdens of different species of schistosome in mice. This assay will be used to question whether anti-adult immunity contributes to the pattern of infection with S. mansoni and S. haematobium in man